The post EM@3AM: Penile Fracture appeared first on emDOCs.net - Emergency Medicine Education.

Originally published at EM Cases. Reposted with permission. Listen to accompany podcast HERE

Follow Dr. Anton Helman on twitter at @EMCases

For such a large organ, EM physicians spend proportionally little time thinking about the liver. Sure, we’re often in the neighborhood (whether it be doing a FAST or diagnosing biliary disease), but the liver really doesn’t get the credit it’s due. Nonetheless, from time to time, whether it be the acute liver failure patient gushing from a varix whose INR is greater than his shoe size, or the confused hepatic encephalopathy patient levitating off the bed using nothing but asterixis, there are definitely times where the middle child of the abdomen steals the show.

In this podcast on liver emergencies and acute liver failure with Dr.Walter Himmel and Dr.Brian Steinhart, we answer questions such as: What are the most important causes of acute liver failure that we need to identify in the ED so we can initiate timely treatment? What are some of the common medications we use in the ED that we should avoid in the liver patient? How should we approach the interpretation of liver enzymes and liver function tests? What are the key management steps in treating acute liver and hepatorenal syndrome? Why do liver failure patients become hypoglycemic and how should hypoglycemia in these patients be treated in the ED? How do we diagnose hepatorenal syndrome in the ED? How can the MELD score help us manage liver patients? What are the indications for IV albumin? What is the role of an ammonia level in the diagnosis of hepatic encephalopathy? Is polyethylene glycol a better alternative to lactulose for treating hepatic encephalopathy? and much more…

Acute Liver Failure

Patients with acute liver failure in the ED may progress to multiorgan failure unless treatment is initiated early. The cytokine release in liver failure and necrosis kicks off a systemic inflammatory response, causing vasodilation and hypoperfusion.

Patients with liver cirrhosis have an increased susceptibility to bacterial infections due to a compromised immune system, portal hypertension due increased portal venous flow and hepatic resistance, thrombosis due to complex alterations in the coagulation factors and hypoalbuminemia, and bleeding due to portal hypertension as well as complex alterations in the coagulation factors . Liver patients may have decreased gluconeogenesis (leading to hypoglycemia), decreased lactate clearance (leading to metabolic acidosis) and decreased ammonia clearance (leading to hyperammonemia). All of these need to be considered in the ED management of patients with acute liver failure.

Triggers for decompensation in patients with liver disease: Search carefully for infections

Infections are a common high risk trigger for acute liver failure in patients with chronic liver disease and may present in a subtle manner, similar to the immunocompromised patient. It is therefore incumbent upon the emergency physician to conduct a thorough search for underlying infection in the sick liver patient. Pneumonia, ARDS and sepsis are the most common diagnoses of ESLD patients admitted to ICU. These patients are also at high risk for urinary tract infections, C. Diff and spontaneous bacterial peritonitis. Have a low threshold to treat for sepsis on speculation.

Other common triggers include ongoing alcohol use, acetaminophen overdose, adverse drug effects, trauma, GI bleed and electrolyte disturbances. Common vague triggers include constipation (decreased gut transit time increases ammonia levels) and malnutrition.

Causes of acute liver failure in the absence of known liver disease

Hepatic ischemia from any shock state (“shock liver”) is a common cause of acute liver failure in the ED where treatment is aimed at the underlying cause of shock.

Common disease states that cause fulminant acute liver failure that should be considered in the ED:

• Acetaminophen toxicity
• Drug induced liver injury
• Viral hepatic diseases
• Autoimmune diseases
• Mushroom toxicity
• Wilson’s disease

Pearl: As recommended by The Association for the Study of Liver Diseases, draw an acetaminophen level on all patients with acute liver failure (recognizing that a “therapeutic” level does not rule out acetaminophen toxicity) and have low threshold for starting NAC in those suspected of acetaminophen toxicity

Misconception: a common misconception is that patients with acute liver failure will be jaundiced. Jaundice may not be present despite severe decompensated acute liver failure.

Treatment of Acute Liver Failure in the ED

Hypoperfusion/vasodilatation – our experts recommend blood products for the bleeding patient in shock, fluid resuscitation with normal saline for the non-bleeding liver failure patient, and to consider IV albumin in patients with hepatorenal syndrome, hepatic encephalopathy and low albumin, post-paracentesis >5L and bacterial peritonitis.

Bacterial infections – have a low threshold for initiating antibiotics in patients with acute liver failure suspected of infection as a trigger.

Hypoglycemia – a common pitfall in managing acute liver failure patients in the ED is the inadequate treatment of hypoglycemia. Maintaining normal glucose levels can help prevent starvation ketosis, ketoacidosis and lactic acidosis. One bolus of 50% dextrose may not be adequate therapy because of depleted glycogen stores; maintenance infusions of D10W or D25W should be administered after the D50W bolus.

Hyperammonemia – ammonia levels are unreliable and may be misleading; patients with acute liver failure and hepatic encephalopathy should be presumed to have elevated ammonia levels and be treated with lactulose and/or PEG and rifaximin accordingly

Demystifying Liver Enzymes and Liver Function Tests in Liver Emergencies

Liver enzymes (AST, ALT, ALP, GGT) and liver function tests – LFTs (INR, PTT, albumin, bilirubin) are terms that are often mistakenly used interchangeably. Simply put, the main difference between liver enzymes and LFTs is that the former are a measure of the degree of cell death/damage to the liver, whereas the latter involves the synthetic capability of liver – liver metabolism.

Liver enzymes

Insults to hepatocytes lead to necrosis and cause elevated transaminases. ALT is most specific for liver disease. ALP is found in bone and liver and is usually elevated in obstructive biliary disease. An elevated GGT that is proportional to an elevated ALP can help distinguish liver disease from bone disease.

The degree of elevation of liver enzymes can help guide the differential diagnosis:

• Mild elevation: up to 5 x of normal – fatty liver, end-stage liver cirrhosis, infiltrative liver disease
• Moderate elevation: 5-10 x of normal – alcohol related liver disease, chronic hepatocellular and cholestatic disease
• Severe elevation: >15 x of normal – acute liver failure including viral hepatitis, acetaminophen toxicity, shock liver, HELLP

The commonly known ratio of 2:1 AST:ALT is suggestive of alcoholic liver disease, with the caveat that other conditions such as NASH, hepatitis C and rhabdomyolysis may have a similar liver enzyme ratio.

Pearl: in cholestasis, the first enzyme to increase is often ALT, which occurs prior to the elevation of ALP.

Adapted from: Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014;98(1):1-16.

LFTs

Albumin – hypoalbuminemia is found not only in patients with liver disease, but also in those with nephrotic syndrome, protein losing enteropathy, heart failure and malnutrition.

INR – while the INR is elevated in many patients with liver disease and may help to predict prognosis, a liver patient with an elevated INR is not necessarily at increased risk for bleeding, and an elevated INR in a liver patient does not rule out the possibility of thrombosis

Bilirubin – serum conjugated bilirubin level does not become elevated until the liver has lost 50% of its excretory capacity; while an elevated bilirubin may suggest poor liver function it cannot distinguish between hepatocellular, cholestatic, or infiltrative liver disease and may be normal or elevated in each

MELD score stratifies severity of end-stage liver disease for transplant planning and includes Creatinine, INR, bilirubin, sodium and renal replacement therapy. It has poor sensitivity, but its constituents are useful in the ED to get a general sense of severity of disease.

ED Medications to Adjust or Avoid in Liver Patients and Liver Emergencies

Susceptibility to adverse effects from medications increases with worsening liver function. In general, try to avoid sedative drugs (benzodiazepines, opioids, antihistamines, antiemetics) in patients with severe liver disease.

Opioids

No opioid is ideal in the liver patient. Morphine has toxic metabolites that may accumulate in liver patients; hydromorphone has impaired elimination. If opioids are required, our experts recommend IV fentanyl in the ED and oral hydromorphone at lower doses with longer time in between doses (e.g. hydromorpohone 0.5mg po q8h) after discharge. Consider IV ketamine as an alternative to opioids for analgesia in the liver patient in the ED.

Acetaminophen

A common misperception is that acetaminophen is strictly contraindicated in all liver patients. In those with mild liver disease, it is generally safe to prescribe acetaminophen at a lower dose (500mg q6h, max 2g daily). Acetaminophen should be avoided in patients with severe liver disease and those with active alcohol use.

NSAIDs

• NSAIDs can cause renal impairment and even lead to hepatorenal syndrome in liver patients in addition to triggering GI bleeding
• NSAIDs should be avoided in patients with cirrhosis and in patients with acute liver failure, but can be considered in low doses/short courses in patients with mild liver disease

Benzodiazepines

Benzodiazepines should generally be avoided in patients with severe liver disease and dosages should be lowered in those with mild liver disease. Patients with even mild hepatic encephalopathy are very sensitive to GABAergic medications. The exception, of course, is alcohol withdrawal. Lorazepam is the benzodiazepine of choice for alcohol withdrawal in patients with severe liver disease – see Episode 87 Alcohol Withdrawal & Delirium Tremens for details.

Antiepileptic medications

Carbamazepine and valproate are contraindicated in patients with severe liver disease and phenytoin should be used with caution. Expert opinion dictates that if ALT values exceeding 5x the upper limit of normal (or lesser elevations associated with any rise in bilirubin or any associated symptoms of hepatitis), phenytoin should be discontinued. The antiepileptic medication of choice in patients with liver disease is levetiracetam.

Antiemetics

Sedating antiemetics should should be avoided in patients with severe liver disease. Metoclopramide and ondansetron require significant dose reduction in patients with cirrhosis.

Antibiotics

While most antibiotics are safe in liver patients, macrolides, ciprofloxacin, nitrofurantoin, trimethoprim-sulfamethoxazole should be avoided in liver patients, and amoxicillin/clavulanic acid can cause liver failure even when taken at therapeutic doses.

Cardiac medications

Medications such as beta-blockers, diltiazem and amiodarone are metabolized through first-pass metabolism. If starting these medications, start low, go slow.

Pearl: if prescribing a drug that may be constipating, consider starting a laxative empirically to decrease transit time in the GI tract and minimizing the risk of hepatic encephalopathy

Antibiotics to avoid in liver patients

• Patients with hepatic encephalopathy have excess GABA stimulation, so they are very sensitive to GABAergic medications (e.g. benzodiazepines or barbiturates).
• Administration of benzodiazepines or barbiturates to a patient with hepatic encephalopathy risks inducing a prolonged stuporous/comatose state.

Hepatic Encephalopathy: A Diagnosis of Exclusion

Step 1: Rule out other causes of altered level of awareness (LOA) including sepsis, renal failure, alcohol withdrawal and subdural hematoma.

Step 2: Assess for and address common precipitants of hepatic encephalopathy which include:

• Medications – noncompliance/use of diuretics/benzodiazepines
• GI bleeding
• Hypokalemia
• Alkalosis
• Volume depletion
• Sepsis

Step 3: Make the diagnosis

• After excluding other causes of altered LOA look for asterixis (nonspecific – also seen in renal failure) and signs of cirrhosis
• Diurnal sleep pattern reversal may help support a diagnosis of hepatic encephalopathy
• In general, the more altered the patient is, the more severe the disease

Step 4: Correct presumed hyperammonemia (without the need for a serum ammonia level)

• Lactulose 20 g (30mL) po, titrated to 3 to 4 soft stools per day (reduces mortality, serious complications)
• If patient is NPO, Polyethylene glycol (PEG) via NG tube 4L over 4 hours (more rapid resolution of hepatic encephalopathy compared to lactulose in 2 small RCTs) or lactulose enema with 1–3 L of 20% solution

Step 5: Replace fluid and glucose deficits

• NS is our experts’ crystalloid of choice for fluid replacement in hepatic encephalopathy
• Consider albumin in patients with low serum albumin given some weak RCT evidence that it may improve outcomes in hepatic encephalopathy
• One bolus of 50% dextrose may not be adequate therapy for hypoglycemia because of depleted glycogen stores; maintenance infusions of D10W or D25W should be administered after the D50W bolus

Step 6: Treat even the mildest hypokalemia

• Hypokalemia contributes to hyperammonemia by decreasing ammonia excretion; correcting hypokalemia is thought to decrease ammonia levels in patients with hepatic encephalopathy

Step 7: Assess for and treat cerebral edema

• Cerebral edema is the most common cause of death in patients with hepatic encephalopathy due to the rapid accumulation of ammonia
• Cerebral edema may be clinically subtle; if suspected, keep the head of the bed elevated at 45 degrees and consider hypertonic saline (20 ml of 30% NaCl targeting a serum Na level between 145-150 mmol/L)

Step 8: Consider refaximin

• Rifaximin 400-550 mg po daily – this antibiotic is not absorbed through the gut, eradicates E. Coli which produces ammonia, and is used for long term maintenance of patients with recurrent hepatic encephalopathy

Pearl: Diurnal Sleep Pattern Reversal: Could it be Hepatic Encephalopathy? This can present with a patient who may be up all night and sleeping during the day. It is not 100% sensitive or specific for the diagnosis but may help support a diagnosis of hepatic encephalopathy.

The myth of ammonia

The #1 recommendation by Choosing Wisely Canada – Hepatology is “don’t order serum ammonia to diagnose or manage hepatic encephalopathy”. Elevated ammonia levels do not add diagnostic or prognostic value in liver patients suspected of hepatic encephalopathy. Encephalopathy can precede the rise in ammonia levels.

Pitfall: a common pitfall is ruling out hepatic encphalopathy with a normal ammonia level; ammonia levels can be normal or near-normal in hepatic encephalopathy; as such they can be misleading

Pearl: a trick to eliciting asterixis in a patient who is unable to follow commands involves placing their forearm on the stretcher and forcibly dorsiflexing the wrist to bring out asterixis

Hepatorenal Syndrome: Another Diagnosis of Exclusion

Hepatorenal Syndrome carries a mortality rate of >50% in the absence of liver transplant. It is a diagnosis of exclusion.

It is difficult to diagnose Hepatorenal Syndrome in the ED because the diagnostic criteria include:

1. Cirrhosis with ascites
2. Creatinine > 132 umol/L
3. No improvement in serum Creatinine after 2 days of diuretic withdrawal and albumin volume expansion
4. Absence of shock
5. Absence of nephrotoxic medications
6. No parenchymal renal disease (no proteinuria > 500 mg/day, microhematuria, or renal US abnormality)

Patients typically have decreased urine output, elevated creatinine, low urine sodium, and no/little urine sediment/protein (“bland urine”), and no improvement in renal function with correction of hypovolemia.

Many liver patients are on diuretics which may alter sodium excretion. While low urine sodium is typical in hepatorenal syndrome, it can only be interpreted accurately after several days of discontinuation of diuretics, long after the patient has left the ED.

Clinical clue: suspect Hepatorenal Syndrome in a patient with liver disease in whom volume status does not improve with fluids or albumin

Beware: the excessive use of diuresis, underuse of albumin and underperformance of paracentesis increase the risk of Hepatorenal Syndrome

ED Management of Hepatorenal Syndrome

• This is a complex disease – get help from your ICU and GI colleagues
• Avoid give diuretics and benzodiazepines
• Replace low serum albumin with IV albumin 1.5 g/kg
• Manage hypotension aggressively as these patients are significantly vasodilated; consider norepinephrine
• Discuss giving octreotide and/or midodrine with admitting physician
• Consider if patient is a liver transplant candidate based on the MELD score

 

Take home points for Liver Emergencies: Acute Liver Failure, Hepatic Encephalopathy, Hepatorenal Syndrome, Liver Test Interpretation & Drugs to Avoid

• Have a low threshold to order acetaminophen levels in the sick liver patient
• Sepsis is a common trigger of acute liver failure and may be subtle – when in doubt, treat on speculation
• ED medications requiring dose adjustment or avoidance in the liver patient: NSAIDs, opioids, acetaminophen, benzodiazepines, antiepileptics (except levetiracetam), macrolides, B-blockers, amiodarone
• Watch out for hypoglycemia in sick liver patients and start an infusion of D10W after you have corrected the hypoglycemia
• Serum ammonia levels are unreliable and can be misleading; assume high ammonia levels in the patient suspected of hepatic encephalopathy and treat with lactulose and/or polyethylene glycol and rifaximin
• IV albumin needs to be considered in the patient with acute liver failure, hepatorenal syndrome and hepatic encephalopathy
• Have a low threshold to treat for hepatic encephalopathy and hepatorenal syndrome on speculation as they are both diagnoses of exclusion
• Some patients with hepatic encephalopathy will develop cerebral edema and this may be subtle; keep the head of bed at 45 degrees and give hypertonic saline if there are any clinical signs of cerebral edema

For part 2 of this series on Liver Emergencies go to Episode 149 Liver Emergencies: Thrombosis and Bleeding, Portal Vein Thrombosis, SBP, Paracentesis Tips and Tricks

References

 

Expand to view reference list

 

1. Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med. 2019;37(2):329-337.
2. Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369(26):2525-34.
3. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55(3):965-7.
4. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55(3):965-7.
5. Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med. 2019;37(2):329-337.
6. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis – a practical guide. Aliment Pharmacol Ther. 2013;37(12):1132-56.
7. Lewis JH. The rational use of potentially hepatotoxic medications in patients with underlying liver disease. Expert Opin Drug Saf. 2002;1(2):159-72.
8. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis – a practical guide. Aliment Pharmacol Ther. 2013;37(12):1132-56.
9. Mazoit JX, Sandouk P, Zetlaoui P, Scherrmann JM. Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects. Anesth Analg. 1987;66(4):293-8.
10. Soleimanpour H, Safari S, Shahsavari nia K, Sanaie S, Alavian SM. Opioid Drugs in Patients With Liver Disease: A Systematic Review. Hepat Mon. 2016;16(4):e32636.
11. Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451-8.
12. Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014;98(1):1-16.
13. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367-79.
14. Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014;98(1):1-16.
15. Shakil AO, Kramer D, Mazariegos GV, Fung JJ, Rakela J. Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria. Liver Transpl. 2000;6(2):163-9.
16. Fouad YM, Yehia R. Hepato-cardiac disorders. World J Hepatol. 2014;6(1):41-54.
17. Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med. 2019;37(2):329-337.
18. Lockwood AH. Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis. 2004 Dec;19(3-4):345-9.
19. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35.
20. Nassar Junior AP, Farias AQ, D’ Albuquerque LA, et al. Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis. PLoS One 2014;9(9):e107466.
21. Salerno F, Navickis RJ, Wilkes MM. Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis. BMC Gastroenterol 2015;15: 167.
22. Bohra A, Worland T, Hui S, Terbah R, Farrell A, Robertson M. Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care. World J Gastroenterol. 2020;26(18):2221-2231.
23. Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev 2016;(5):CD003044.
24. Kimer N, Krag A, Møller S, et al. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther 2014;40(2): 123–32.
25. Long B, Koyfman A. The emergency medicine evaluation and management of the patient with cirrhosis. Am J Emerg Med. 2018;36(4):689-698.
26. Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology. 2004;39(2):464-70.
27. Sharma BC, Singh J, Srivastava S, et al. Randomized controlled trial comparing lactulose plus albumin versus lactulose alone for treatment of hepatic encephalopathy. J Gastroenterol Hepatol 2017;32(6):1234–9.

Drs. Helman, Himmel and Steinhart have no conflicts of interest to declare

The post EM Cases: Liver Emergencies – Acute Liver Failure, Hepatic Encephalopathy, Hepatorenal Syndrome, Liver Test Interpretation & Drugs to Avoid appeared first on emDOCs.net - Emergency Medicine Education.

Here’s another case from Medical Malpractice Insights – Learning from Lawsuits, a monthly email newsletter for ED physicians. The goal of MMI-LFL is to improve patient safety, educate physicians and reduce the cost and stress of medical malpractice lawsuits. To opt in to the free subscriber list, click here.

Chuck Pilcher MD FACEP

Editor, Med Mal Insights

Teens can have strokes too.

16-year-old female with sudden unilateral paralysis is partially paralyzed for life. Was cervical artery dissection considered?

Facts: A 16-year-old female presents to the ED only 30 minutes after noticing sudden loss of left sided motor function with “numbness.” Past medical history is remarkable only for occasional headaches and “numbness” in her L arm over the past few weeks. She has an appointment with her PCP in 4 days to address her earlier headaches and numbness. The physical exam states only that “the L arm is tucked to her chest with the hand clenched.” Gait is not documented. A head CT is normal. The patient improves during the visit and is discharged to see her PCP as planned in 4 days. Discharge dx is “”numbness” and “weakness” L side. She suffers a stroke a few hours after discharge due to a carotid artery dissection. She is left with a L hemiplegia and is unable to perform many basic ADL’s. An attorney is consulted and a lawsuit filed against the ED physician. Plaintiff: I was having a major TIA. You didn’t do anything except tell me I did not have a stroke. A normal CT scan does not rule out a stroke OR a TIA, both of which can be caused by a cervical artery dissection. Even a brief paralysis of one side of my body is serious, and you just brushed it off. You didn’t even tell me or my parents that a stroke was anything you were concerned about. You never even considered a TIA in your differential. If you had, you would have realized I needed more tests and should see a neurologist immediately, especially when I’m only 16-year-old. Defense: I thought of a stroke and ruled it out by getting the CT scan. You didn’t complain of neck pain. You had no risk factors. Because you weren’t having a stroke, I didn’t need to consider a dissection. You got better in the ED.

Result: Settled pre-trial for an undisclosed (but likely at least 7 figures) amount.

Takeaways:

• Even teenagers can have a stroke or TIA.
• Sudden onset of unilateral neuro symptoms deserve one’s utmost concern, regardless of age.
• The cost of missing this diagnosis increases the younger the patient because of the “Quality of Life Years” ahead of them.
• Include cervical artery dissection in the differential when considering stroke/TIA.
• A normal CT scan does not rule out a stroke OR TIA (duh).
• Could an assumption that this was a histrionic female teenage have played a role?
• If you can only do ONE neurological test, gait is the simplest and most comprehensive. Walk (“Road Test”) your neuro patients before discharge.

References:

1. emDocs Cervical Vessel Dissection
2. EM Educator Series

The post Medical Malpractice Insights: Teens can have strokes too. appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Forrest Turner, MD and Ann-Jeannette Geib, MD (Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC) // Reviewed by: Cynthia Santos, MD (@CynthiaSantosMD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 3-year-old (15kg) boy presents to the emergency department by EMS with frequent vomiting. The family had immigrated from India 2 years prior, but the patient has no prior past medical history and is fully immunized. Family states the patient was in normal state of health earlier when he was playing around the garage.  A few minutes later patient was noted to have frequent emesis and retching with associated ataxia and altered mental status. In his hand were some pellets that the parents identified as a rodenticide.  Upon arrival, patient has an episode of dark emesis that is notable for a foul garlicky odor. He is clutching his abdomen and moaning, GCS of 10. Initial vital signs are heart rate 170, BP 60/palp, respirations 40, O₂ saturation 90%.

Question:

Which of the following rodenticide ingestions would be associated with the highest potential for death in this patient and is associated with garlicky breath?

1. Cholecalciferol
2. Aluminum phosphide
3. Brodifacoum
4. Bromethalin

Answer: B, the rodenticide with garlic breath.

Background:

• Commonly available metal phosphides include Zinc phosphide, Aluminum phosphide, and Magnesium phosphide.
• Cheap and frequently used insecticide and rodenticide. Typically tablet, pellet, or powder forms. Often added to grain supplies in enclosed spaces to act as a fumigant.
• High concentration formulations are readily available to the public in India, Iran, Sri Lanka, Morocco, and other locales. It is a frequent agent for intentional ingestion/suicide in these countries, also seen in accidental ingestions and occupational exposure.
• Metal phosphides are also available to the public in the US. Phosphine gas exposure is sometimes seen related to methamphetamine production.
• Toxicity after ingestion is related to the liberation of phosphine gas when metal phosphides are exposed to water or acid. Phosphine gas is then absorbed through the GI mucosa and into the bloodstream.¹

Al P + 3H₂O → Al (OH)₃ + PH₃

Al P + 3H⁺ → Al⁺³ + PH₃

• Phosphine gas can also be inhaled and absorbed across the respiratory mucosa in settings of an occupational or chemical agent of opportunity exposure,² with minimal risk of dermal exposure leading to toxicity.
• The volume of distribution is unknown. Excreted as hypophosphite by the kidneys or exhaled as unmetabolized phosphine gas.
• Phosphine is odorless; side reactions create compounds that lead to the characteristic garlicky/fishy odor.¹
• Mechanism of action is unknown although hypotheses include poisoning mitochondria and inhibition of oxidative respiration, increase in free radicals and depletion of glutathione, caustic effects especially in the GI tract, oxidation of hemoglobin, and methemoglobinemia. There is uncertainty as to the toxic dose, estimates from 150-500mg for AlP, 500-1000mg for ZnP. Rodent studies have shown 40mg/kg for both.
• There is uncertainty regarding mortality, various estimates from 40-77%, with the majority of deaths in the first 12-24 hours. Death is usually attributed to multisystem organ failure, common features include cardiogenic shock, pulmonary edema, renal failure, and metabolic acidosis^1,3,4,5.

Presentation:

• Low dose inhaled toxicity which may be seen in agricultural occupational exposure is characterized by respiratory irritation, dyspnea, chest pain, nausea, vomiting, headache, and neurological findings (tremor, diplopia, weakness, etc.).
• Symptoms from ingestion are rapid (10-15 minutes) and characterized by nausea, vomiting, hematemesis, abdominal pain, chest pain, shortness of breath, irritability, and garlicky breath. Predominant features of GI, cardiac, pulmonary, and electrolyte derangements, although almost any organ system can be affected.
• GI – gastritis, ulcers, erosions, later can form strictures or fistulae, hepatitis, rarely pancreatitis.
• Cardiac – hypotension, arrhythmias, acute heart failure.
• Pulmonary – pulmonary edema, ARDS.
• Electrolytes – high or low potassium, magnesium, sodium, glucose. Metabolic acidosis.
• CNS – agitation, dizziness, ataxia, tremor, numbness, tremor, later seizure, and coma.
• Hematologic – hemolysis, DIC, methemoglobinemia, although these are less common. Methemoglobinemia may reach levels that require treatment and correlate with survival.^6,7
• Renal – AKI and ATN, less common.⁸

Diagnosis:

• History and the presence of garlic or fishy breath are helpful in determining a diagnosis. Readily available definitive testing is limited and unlikely to result in a time frame that would affect management. Paper infused with silver nitrate will turn black if exposed to phosphine, can be used on breath or gastric fluid to make ⁸
• It is important to inquire about the exposure type (accidental or intentional), route of exposure, the concentration of the product, time of occurrence, and estimated amount ingested.

Laboratory Testing:

Broad workup to determine derangements from toxicity: CBC, CMP, lipase, magnesium, coagulation studies, lactate. VBG or ABG with co-oximetry to examine for methemoglobin should be obtained.⁸

Imaging:

• ECG may demonstrate sinus tachycardia early on, can see QRS, PR widening, heart blocks, or STEMI mimics, after 6 hours one may see supraventricular tachycardias, ventricular tachycardia, or ventricular fibrillation.
• Bedside echo may demonstrate systolic dysfunction, wall motion abnormalities, or pericardial effusion.
• Chest x-ray may demonstrate evidence of pulmonary edema or ARDS.^5,8

Clinical Management:

• Don’t forget PPE and eye protection for the healthcare team. Be mindful that standard ED respiratory protection (eg, N-95) will not prevent phosphine exposure. Patients should be fully unclothed and decontaminated.
• ABC’s with good supportive care is the mainstay of treatment; no antidote exists. There is no proven role of hemodialysis to remove phosphine.
• GI decontamination is performed frequently in these cases around the world although data showing benefit is scarce. A variety of agents have been described to reduce the systemic absorption of phosphine including potassium permanganate, bicarbonate, lipids such as coconut oil, vegetable oil, or liquid paraffin, and activated charcoal. Several case reports and small studies demonstrate survival with the administration of some cocktail of these, although controlled studies do not exist.^3,4,5,8,9 While the evidence is not well-established, it would be reasonable to deploy GI decontamination with activated charcoal as it is readily available in the ED environment.
• Antidotal therapies: The antioxidants vitamin E and N-acetylcysteine have shown some promising preliminary data.
• NAC – There is data from 3 controlled studies, with 2 showing mortality benefit and 1 not. Studies used a variety of regimens; it would be reasonable to select an IV regimen routinely used at your facility.^4,10
• Vitamin E – A controlled study of 36 critically ill patients in Turkey saw significant improvements in mortality and the need for mechanical ventilation with 400mg IM vitamin E BID for 3 days.¹¹
• Continuous magnesium infusions have shown differing results in the 2 controlled studies, one showed mortality benefit and the other did not.¹
• Several other adjuncts show promise, but data does not extend beyond in vitro or animal studies including melatonin, sodium selenite, triiodothyronine, acetyl-L-carnitine, pralidoxime, and others.
• Rescue maneuvers
• High-dose insulin can be considered. 88 patients in a controlled study showed significant mortality benefit (72% vs 50%).¹²
• Case reports document successful deployment of intra-aortic balloon pumps and ECMO.⁸

Case Conclusion:

The emergency department physician was astute in suspecting toxic ingestion with special concern for metal phosphide poisoning. Intravenous access was obtained, and a broad set of labs were drawn. The patient was placed on oxygen, although due to waning mental status and O₂ saturation, as well as ongoing dark emesis, the decision was made to proceed with endotracheal intubation. With airway secured and suspected recent ingestion, a nasogastric tube was placed, the patient’s gastric contents were aspirated, and a dose of activated charcoal was administered. Labs were significant for hypokalemia to 3.0, hypomagnesemia to 1.1, mild elevations in LFTs, normal renal function, and anion gap acidosis pH 7.18, bicarb 14, AG 18 attributed to elevated lactate of 5.6. Chest x-ray showed bilateral opacifications concerning for ARDS or infectious process. Bedside point of care echocardiogram demonstrated a moderate degree of systolic dysfunction. An IV fluid bolus was given, empiric antibiotics were initiated, and electrolyte replacement was started.

Upon arrival to the PICU, NAC was started. A central line and norepinephrine infusion were started for down trending blood pressure. The family confirmed the presence of an aluminum phosphide containing rat poison stored in their garage. Over the course of the night, the patient had increasing vasopressor requirements despite the addition of epinephrine infusion. ECMO was considered but the team opted to trial high dose insulin therapy. Over the next 24 hours, the patient was able to be weaned from vasopressors and he was extubated on hospital day 3. Ultimately, he was discharged without sequelae.

Key Points:     

• Metal phosphides are potent pesticides with disproportionate numbers of poisonings in countries such as India and Iran.
• Toxicity stems from the production of phosphine gas when a metal phosphide contacts water or acids, particularly in the stomach when ingested, with rapid onset of symptoms by this route.
• Predominant symptoms involve garlicky or fishy breath or vomitus, GI irritation often with dark emesis, hepatopathy, acute heart failure, shock, arrhythmias, ARDS, and electrolyte derangements, although any organ system can be affected.
• Obtain a full panel of labs, ECG, CXR, and bedside echo if able.
• Management is focused on ABCs and good supportive care. GI decontamination with a variety of agents including bicarb, potassium permanganate, lipids, and charcoal are given frequently around the world although data supporting their use is scarce. Some small studies show benefits with NAC, vitamin E, and high-dose insulin.

References:

1. Proudfoot AT. Aluminium and zinc phosphide poisoning. Clin Toxicol (Phila). 2009 Feb;47(2):89-100. doi: 10.1080/15563650802520675. PMID: 19280425.
2. Bogle RG, Theron P, Brooks P, Dargan PI, Redhead J. Aluminium phosphide poisoning. Emerg Med J. 2006 Jan;23(1):e3. doi: 10.1136/emj.2004.015941. PMID: 16373788; PMCID: PMC2564148.
3. Shadnia S, Soltaninejad K. Fumigants. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed January 25, 2021. https://accessemergencymedicine-mhmedical-com.libproxy.lib.unc.edu/content.aspx?bookid=2569&sectionid=210275622
4. Karimani A, Mohammadpour AH, Zirak MR, et al. Antidotes for aluminum phosphide poisoning – An update. Toxicol Rep. 2018;5:1053-1059. Published 2018 Oct 28. doi:10.1016/j.toxrep.2018.10.009
5. Moghadamnia AA. An update on toxicology of aluminum phosphide. Daru. 2012 Sep 3;20(1):25. doi: 10.1186/2008-2231-20-25. PMID: 23351193; PMCID: PMC3555759.
6. Soltaninejad K, Nelson LS, Khodakarim N, Dadvar Z, Shadnia S. Unusual complication of aluminum phosphide poisoning: Development of hemolysis and methemoglobinemia and its successful treatment. Indian J Crit Care Med. 2011 Apr;15(2):117-9. doi: 10.4103/0972-5229.83021. PMID: 21814377; PMCID: PMC3145296.
7. Mostafazadeh B, Pajoumand A, Farzaneh E, Aghabiklooei A, Rasouli MR. Blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome. J Med Toxicol. 2011 Mar;7(1):40-3. doi: 10.1007/s13181-010-0121-7. PMID: 21057909; PMCID: PMC3614104.
8. Hashemi-Domeneh B, Zamani N, Hassanian-Moghaddam H, Rahimi M, Shadnia S, Erfantalab P, Ostadi A. A review of aluminium phosphide poisoning and a flowchart to treat it. Arh Hig Rada Toksikol. 2016 Sep 1;67(3):183-193. doi: 10.1515/aiht-2016-67-2784. PMID: 27749266.
9. Trakulsrichai S, Kosanyawat N, Atiksawedparit P, et al. Clinical characteristics of zinc phosphide poisoning in Thailand. Ther Clin Risk Manag. 2017;13:335-340. Published 2017 Mar 14. doi:10.2147/TCRM.S129610
10. Agarwal A, Robo R, Jain N, Gutch M, Consil S, Kumar S. Oxidative stress determined through the levels of antioxidant enzymes and the effect of N-acetylcysteine in aluminum phosphide poisoning. Indian J Crit Care Med. 2014 Oct;18(10):666-71. doi: 10.4103/0972-5229.142176. PMID: 25316977; PMCID: PMC4195197.
11. Halvaei Z, Tehrani H, Soltaninejad K, Abdollahi M, Shadnia S. Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning. Turk J Med Sci. 2017 Jun 12;47(3):795-800. doi: 10.3906/sag-1512-6. PMID: 28618724.
12. Hassanian-Moghaddam H, Zamani N. Therapeutic role of hyperinsulinemia/euglycemia in aluminum phosphide poisoning. Medicine (Baltimore). 2016 Aug;95(31):e4349. doi: 10.1097/MD.0000000000004349. PMID: 27495040; PMCID: PMC4979794.

The post ToxCard: Metal Phosphides appeared first on emDOCs.net - Emergency Medicine Education.

The post Journal Feed Weekly Wrap-Up appeared first on emDOCs.net - Emergency Medicine Education.

Originally published at Pediatric EM Morsels on January 4, 2019. Reposted with permission.

Follow Dr. Sean M. Fox on twitter @PedEMMorsels

A New Year begins. With it, personal resolutions are being made throughout the lands. If you have yet to select a worthwhile New Year’s Resolution, join me in striving toward an improvement goal that can benefit ourselves as well as may actually help others. What’s this noble goal? Unambiguous Commincation. Certainly, this is a skill we all can improve and one that has direct, and sometimes dire, consequences in our professional lives.  One of the most vital attributes of clear communication is ensuring that you are speaking the same “language” as the other party. This is intuitive, but on occasion we underestimate its importance. Certainly, I need an interpreter for patients who don’t speak my language (sometimes I even need help with the English language), but let’s not overlook the various languages our other medical specialist and colleagues use. Medical languages have many dialects and regional variances. When we speak to our Orthopods, we should know what terms are meaningful to them when describing a Supracondular fracture. Recently, I learned a new phrase that can help me clearly communicate with our Urology colleagues when dealing with children presenting with acute scrotal pain. Let’s make sure we speak clearly – Testicular Workup for Ischemic and Suspected Torsion (TWIST):

Testicular Torsion: Basics

• Testicular Torsion has 2 peaks of incidence: one peak during 1st year of life and another from 12-18 yrs.

• Classic presentation is of:
  • Acute, unilateral testicular pain with,
  • Nausea and vomiting
  • Absent cremasteric reflex on affected side
  • Swelling and tenderness
  • Abnormal testicular position

• Unfortunately, nothing is that simple, and classic is not common.
  • Cases of testicular torsion have occurred in which each finding has been violated, including having had torsion in the presence of normal cremasteric reflexes.
  • Intermittent Torsion (Torsion – Detorsion) does occur –
    • Can lead to confounding presentations and even “fool” ultrasound.
    • 50% of patients diagnosed with torsion have had a prior episode of intermittent torsion that had spontaneous resolution.

• Time is critical though (as with it with many of the conditions we mange in the ED).
  • Salvage rates are very good for Torsion lasting <6 hours (90-100%) [Frohlich, 2017]
    • Rates are not as good between 6-12 hours (20-50%) and …
    • Very low after 12 hours (<11%) [Frohlich, 2017]
  • Waiting for imaging can lead to further delay.

Testicular Torsion: The Dilemma

• There are several factors in this equation:
  • Time is critical.
  • Testicular torsion is less common than other causes of acute scrotal pain.
  • Urologist do not usually hang out in the ED waiting for boys with testicular pain to show up.
  • No single historic or exam feature can reliably rule in or rule out the condition.
  • Ultrasound is often requested to further assist with clarity.
  • Ultrasound takes time (although, another great reason to improve your use of bedside ultrasound – that can be another New Year’s Resolution).

• A possible way to improve clarity of communication has recently been advocated for – The TWIST Score

Testicular Torsion: TWIST Score

• Testicular Workup for Ischemic and Suspected Torsion (TWIST) Score was developed by Urologist, validated with non-physician triage, and recently tested in tertiary Pediatric ED with physician providers utilizing it. [Frohlich, 2017; Sheth, 2016; Brunhara, 2016]

• TWIST Score is a Summation of 5 Clinical Variable:
  • Presence of Testicular Swelling = 2 points
  • Presence of Hard Testicle = 2 points
  • Absence of Cremasteric Reflex = 1 point
  • Presence of High Riding Testicle = 1 point
  • Presence of Nausea/Vomiting = 1 point

• Scores, Risk, and Proposed Management [Frohlich, 2017; Sheth, 2016; Brunhara, 2016]
  • High Risk = Score of 6 or 7
    • NO imaging.
    • Consider imaging those children who are Tanner Stage 1-2 (who had more confounded exams) – some advocate for only using TWIST Score in pubertal males.
    • Convey this high risk score and help expedite surgical exploration with your Urology colleagues.
  • Intermediate Risk = Scores of 1-5
    • Obtain scrotal ultrasound 
    • Consider alternative diagnoses (ex, Epididymitis) and obtain additional testing as warranted (ex, U/A, STD screen)
  • “Low” Risk = Scores of 0
    • In original paper, “Low Risk” was not associated with Torsion and avoiding ultrasound in this group was advocated for…. but, as was mentioned above, Torsion can be deceptive and present atypically… so I would still have a low threshold for obtaining an ultrasound.
    • Alternative diagnosis is more likely, though, so consider the rest of the DDx as well (ex, Epididymitis, Varicoceles, UTI, Nephrolithiasis, Mumps, HSP).

Moral of the Morsel

• Communication is a 2 Way Street. Make sure we are speaking the right language.
• Don’t Get it TWISTed! Know the TWIST Score and communicate it clearly to your Urology colleagues, but know that it is not perfect and your H+P and clinical acumen need to be “calculated” as well.
• Coordinate with your Urology Colleagues Early. For time sensitive conditions, particularly ones that may lead to early activation of an OR, develop strategies and protocols even before the patient has arrived!

References

The post Testicular Workup for Ischemia and Suspected Torsion (TWIST) Score appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Brannon Inman, MD (EM resident, San Antonio, TX) and Lloyd Tannenbaum, MD (EM Attending Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case:

During a bustling emergency medicine shift, a mom presents to the ER via her pediatrician’s request with Bubba, a 4-month-old previously “healthy”, ex-term, fully immunized baby boy. Baby boy Bubba was referred to the ED with a chief complaint of worsening poor feeding, irritability, and failure to thrive according to his pediatrician. Mom also notes Bubba has been having recurrent episodes of wheezing, and has been having a week of “viral-like symptoms.” He was also diagnosed with asthma 1 week ago. During your initial evaluation, he appears listless but arousable. He is much less active than expected for a child of this age. He is tachycardic, with a HR in the 190’s. On exam, you note a mildly dehydrated, thin child, smaller than expected for the stated age, with rhinorrhea, wheezing, and hepatomegaly. You also note a diastolic murmur best appreciated at the cardiac apex.

You see the following ECG:

Figure 1: Adapted from Electrocardiogram of Anomalous Left Coronary Artery From the Pulmonary Artery in Infants ¹

Notice anything strange about this ECG?

Let’s zoom in on the various leads:

Figure 2: Adapted from The caveats in the diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)

Notice how there are very deep q waves in leads I, aVL, and V3-V6. You think to yourself: “Self, why does this baby have signs of anterolateral ischemia, poor feeding, wheezing, and failure to thrive? Could it be myocarditis?”. Maybe, but it could also an Alpaca!

Wait, ALCAPA!

Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous left coronary artery arising from the pulmonary artery (ALCAPA), AKA Bland-White-Garland syndrome is a relatively uncommon albeit life-threatening ideology that occurs in approximately one in 300,000 live births. Left untreated, the mortality rate of ALCAPA can approach 90%, with most children dying in the first year of life.^2–4 Early in infancy, the patient continues to have elevated pulmonary vascular resistance thus often having a lesser degree of symptoms.³ However, later in life, as vascular pressure decreases, blood flow via the left corner artery is effectively stolen and transmitted back to the pulmonary artery.  This steal phenomenon occurs because the pressure in the pulmonary artery is less than the pressure in the left coronary artery during systole.³ This results in chronic ischemia of the myocardium perfused by the left corner artery. Some children eventually develop collateral blood flow which can augment the degree of chronic ischemia and may lead to alterations in presentation, however to some degree chronic LCA distribution ischemia is a part of the natural history of ALCAPA. Ultimately this results in symptoms of congestive heart failure, left ventricular dysfunction, mitral regurgitation, arrhythmias, and death.³ Frequently the condition results in a dilated cardiomyopathy, which fortunately typically improves after surgical correction.⁵

The ECG findings of ALCAPA are those typical of anterolateral ischemia and often resemble old infarction. Deep q waves are often present in I, aVL, and V3-6 (Figure 2).^4–6 Q waves are not typically present in the inferior leads, though they may be seen in lead II. Q waves in lead III are not suggestive of ALCAPA.⁷ ST-segment elevations are often accompanied by deep q waves in the anterolateral leads.⁶ Other common ECG findings include loss of R waves height in precordial leads and poor R wave progression, often with accompanying ST/T wave changes.⁷

Diagnostics typically involve an echocardiogram and CT angiogram (Figures 3 and 4). Management is surgical.^2,3,5

The post ECG Pointers: Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) appeared first on emDOCs.net - Emergency Medicine Education.

Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover cerebral venous thrombosis.

Cerebral Venous Thrombosis

Introduction: CVT is an uncommon neurologic emergency that can lead to stroke, seizures, and death. CVT is defined by thrombosis of the intracranial veins and dural sinuses and has an estimated annual incidence of 0.3-1.5 cases/100,000 person-years, accounting for up to 1% of all strokes worldwide. This incidence approaches that of meningitis. Delays in diagnosis are associated with worse morbidity.

Pathophysiology: An obstruction within the dural venous system leads to increased venous pressure and reduced capillary perfusion pressure, which can result in ischemia, edema, elevated intracranial pressure (ICP), and even hemorrhagic infarction.

Epidemiology: There is a female predominance to CVT, and the typical age is less than 50 years old (commonly 33 years). Less than 10% are over age 60 years. Most patients with CVT will have at least one risk factor for thrombosis which includes peripartum states, hypercoagulability, inflammatory conditions, neurosurgery, and infections.

Table 1. Risk Factors Associated with CVT.

Presentation: Headache is the most common presenting complaint of CVT, occurring in 81-95% of patients, while focal neurologic deficits, seizures ,and altered mental status can be additional features of CVT.

Table 2. Clinical Presentations Suggestive of CVT.

While headache is common in ED patients, several distinguishing factors may suggest CVT. The headache of CVT is most often subacute, lasting for 4 days to 2 weeks prior to presentation. A combination of headache and seizure or headache and papilledema have a high sensitivity but low specificity for CVT.

Focal neurological deficits, including cranial nerve palsies and extremity weakness occur in 31-68% of cases. Seizures occur in 23-44% of patients with CVT. The location of the clot can be related to the symptoms that the patient will manifest.

Table 3. CVT Locations.

Laboratory Testing: Laboratory evaluation cannot be used to rule in or rule out CVT. D-dimer is classically thought to be elevated in CVT, but the false negative rate ranges from 24-40%. A recent prospective multicenter study proposes a predictive clinical score for the diagnosis of CVT.

Table 4. CVT Clinical Score.

Imaging: The most common initial imaging modality obtained in the emergency department in patients with suspected high-risk headaches is non-contrast head CT. Unfortunately, this test is poorly sensitive for CVT and can be normal in up to 30% of patients. CT venography has an overall sensitivity of 95% for CVT. MRI findings alone are dependent on the age of thrombus. MRV highly sensitive and should be considered in those with suspected involvement of the deep venous system (altered mental status).

Management:  The overall goals of treatment of CVT are to treat the sequela/complications of CVT, prevent propagation of the clot, recanalize the occluded vessel, and prevent thrombosis elsewhere in the body.

• Seizures: Patients actively seizing should be treated first with benzodiazepines. A retrospective study of seizures in CVT reported that lorazepam was the most commonly used medication to treat acute seizures from CVT
• ICP: There is no evidence to support the use of steroids or acetazolamide for increased ICP in CVT. Recommendations for elevating the head of bead to 30 degrees, hyperventilation to 30-35mmHg PaCO₂, and either hypertonic saline or mannitol to lower ICP are based on expert opinion. Decompressive surgery should be considered in patients with CVT and signs of impending herniation as small case series have shown that decompressive craniotomy can be life-saving, but there are little data to guide patient selection.
• Anticoagulation: Anticoagulation is the mainstay of ED treatment of CVT. Intracerebral hemorrhage is not a contraindication to starting anticoagulation. Initial anticoagulation with low molecular weight heparin is recommended. European guidelines currently do not recommend systemic thrombolysis. A recent RCT of endovascular therapy showed no difference in mortality when compared with standard of care.

Take Homes

• CVT is a rare and difficult diagnosis to make due to a wide variety of signs and symptoms.
• Patients are commonly under 50 years of age.
• Scenarios warranting CVT investigation include headache that is atypical and persistent, stroke with no typical risk factors or in the setting of seizure, intracranial hypertension with no explanation, multiple hemorrhagic infarcts, hemorrhagic infarcts not in a specific arterial distribution, or objective neurologic symptoms in a patient with risk factors for CVT.
• Patients can present with four major syndromes, the most common of which is headache from intracranial hypertension.
• Do not rely on labs such as D-dimer for ruling out or ruling in. Imaging is required, including CT with venography or MRI/MRV.
• Treatment includes stabilizing immediate condition, anticoagulation, and managing underlying condition.

The post emDOCs Podcast – Episode 37: Cerebral Venous Thrombosis appeared first on emDOCs.net - Emergency Medicine Education.

Author: Martin Yang, MD (EM Resident Physician, University of Kentucky) // Reviewed by: Courtney Cassella, MD (@corablacas); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit) 

The Case

A 35-year-old healthy young individual presents after an MVC. The patient had a prolonged extrication due to a pinned left leg under the steering column. Plain films demonstrate a left femur fracture. Fortunately, there are no other injuries on imaging. The trauma service was consulted for admission and orthopedics was consulted for management of his femur fracture. Repeated exams demonstrate an increasingly uncomfortable patient with an intact neurovascular exam. The patient complains of considerable thigh pain and is requiring escalating amounts of opioid pain medication. The admitting trauma service is aware, however is unable to evaluate the patient due to a complicated operative case. The bedside nurse approaches you for more pain medication orders. The easy thing to do would be to provide more pain medication with the assumption that the patient is under treated and defer further assessment to the primary team. However, that minor delay in care could result in lifelong consequences for this patient in the setting of acute compartment syndrome (ACS). In this review, we will discuss the etiology, general features, evaluation, and special considerations of this rather insidious and potentially devastating complication.

TL;DR (Too Long; Didn’t Read)

• In the setting of uncontrolled pain or increasing pain medications, the clinician should consider ACS.

Etiology

Trauma remains the most common setting for ACS, and fractures are the greatest single risk factor.[1] However, it is important to bear in mind that other etiologies can cause ACS. By definition, compartment syndrome arises from an increase in the compartment pressure which overcomes the diastolic pressure (as opposed to systolic pressure for which we would venture into the realm of limb ischemia).[1] This may result from increased volume within a compartment or reduced size of a compartment. An intracompartmental pressure (ICP) greater than the diastolic pressure initiates a potentially devastating snowballing effect of reduced capillary and lymphatic flow, venous outflow, and arterial inflow.[1] This leads to ischemic compromise which subsequently generates further edema all in a non-distensible compartment. With this in mind, ACS must be considered in patients who experience circumferential burns, snake bites, chronic anticoagulation, rhabdomyolysis, and Intravenous Drug Use (IVDU). However, this is hardly an exhaustive list.

Acute compartment syndrome is commonly associated with a fracture (up to 75%)[2] and 69% of cases occur secondary to a traumatic injury.[3] Prevalence favors lower extremities fractures with approximately 40% of ACS have an associated tibial fracture. Although tibial fractures demonstrate a significant association (positive predictive value ~ 11%)[2], this hardly excludes other areas, such as upper extremities, feet, and even lumbar spine. In fact, forearm fractures contributed to 18% of the population who ultimately received an ACS diagnosis.[2]

TL;DR

• Trauma is the most common setting for ACS, but this is not exclusive.
• Anything that can increase compartment pressure can lead to ACS.
• General etiology of increased compartment pressure: hemorrhage/extravasation, inflammation/infection, foreign object.
• Compartment pressure > diastolic pressure = Reduced capillary, lymphatic, venous flow = arterial compromise = tissue ischemia.

Once ACS is suspected, a thorough physical exam is needed. Compartment syndrome is a clinical diagnosis in the ED. If concerned for ACS based on history or exam, consultation with orthopedic surgery is recommended. Additionally, compartment pressures can be obtained if applicable. Pain with passive stretch of the isolated compartment is considered the most sensitive physical exam finding and should promptly be followed by surgical consultation.

For more information on the clinical findings see: http://www.emdocs.net/the-dreaded-acute-compartment-syndrome/

Compartment pressures can be measured directly with commercially available kits and can provide important diagnostic information. The utility of these pressures is, however, debatable. Normal compartment pressures are < 10 mmHg. Traditionally, an absolute pressure > 30 mmHg led to a fasciotomy.[1] However, this neglects the extremely varied patient specific tolerance of compartment pressures, systemic clinical contexts (i.e. hypotension), or other confounding patient specific cardiovascular/perfusion variances.

More recently, delta pressures have been utilized as a means of accounting for this in the decision to perform a fasciotomy. Delta pressures are calculated by subtracting the absolute compartment pressure from the diastolic blood pressure.

Delta Pressure = [Diastolic BP] – [Absolute Compartment Pressure] [4]

McQueen et al. attempted to provide some further clarity in the utility of delta pressures. They proposed a period of 24-hour monitoring with the threshold for fasciotomy being >2 sustained hours of >30 mmHg delta pressure. Ultimately, the study included 116 individuals with tibial fractures; only 3 of which received fasciotomies based on this criterion. Reportedly there were no overtreatments (unnecessary fasciotomies), no missed ACS diagnoses, and no sequelae noted on 15 month follow up.[5]

TL;DR

• Pain with passive stretch is most sensitive, but difficult to discern from pain secondary to primary trauma.
• Compartment pressures:
  • <10 mmHg normal
  • Absolute pressure >30 mmHg concerning for ACS, but not absolute in diagnostic criteria
• Delta pressures may provide better indication for the need for fasciotomy.

ACS is frequently mentioned in initial discussions. Indeed, many will remember it a repeatedly highlighted teaching point in our medical school lectures.  So why is it such an easily missed diagnosis? To start, the diagnosis is fairly uncommon with an incidence of 1 to 7.9 per 100,000 population per year.[2] The dynamisms of such cases set within the confines of a busy emergency department and a lack of standardized initial screening assessment tools tend to set emergency providers up for failure. Understanding some of these pitfalls could help the provider avoid them.

Let us refer back to our initial case. One contributor to missed diagnosis is our environment and cognitive burden. Rarely can the environment of the emergency department be considered an advantage in patient care. For such insidious pathologies as ACS, this environment creates a significant clinical blind-spot. The cycles of head-spinning chaos interspersed by tense calm rarely takes into consideration the needs of our patients. His disposition is clear and inevitable. The five to six minutes it may take the ED provider to fully reassess the patient will take the provider away from another patient without a clear disposition. In a crowded department, it is easy to understand why another disposition would be prioritized. Nary an excuse, but more so an explanation, this situation does highlight that even from a workflow perspective, the emergency provider can be subconsciously disadvantaged.

How do we improve?

• ACS is a dynamic diagnosis.
• Despite a busy ED and lots of patients, frequent reassessments are necessary to fully make this diagnosis.

Again referencing our case, as a seasoned resident, you reassess our patient and find that he is indeed in a great deal of pain. It is hard to argue that this is out of the ordinary, as this patient did suffer a femur fracture. Furthermore, after reviewing medical records available, the provider notes that the patient is on suboxone and has a strong history of opioid abuse, further complicating the patient’s pain management. Pain ubiquitously remains the first of the P’s that are frequented cited for ACS. Pain with passive stretch should increase suspicion. However, isolation of the affected compartment (although not in our specific case), especially in the smaller compartments of the hand and feet, may be difficult. Additionally as expected, pain itself is not reliable as a diagnostic tool with sensitivities ranging from 13% to 54%. In fact, clinical findings overall have sensitivities ranging from 13-64% as compared to ICP monitoring at 94%. [6] If a provider were to anchor onto increased tolerance to opioids or decreased pain tolerance as the cause for the patient’s increasing need for pain medication, this could create the cognitive bias that would lead to the correct ACS diagnosis and subsequently a delay in this patient’s care.

How do we improve?

• Early and aggressive pain control.
• Establish reliable baseline physical exam after pain control is achieved.
• Reassess your differential diagnosis for the etiology of pain.

The case obviously becomes even more skewed and problematic when patients are intubated and/or critically ill. A hypotensive trauma by definition will decrease the diastolic pressure which would adversely affect the threshold in which venous return becomes compromised leading to ACS.[1] In theory, appropriate resuscitation should leave hypotension as a transient complication. Identifying all injuries related to a trauma will help provide the needed context to consider ACS. If the patient is intubated, pain becomes an unmeasurable factor, removing a large tool in the ED physicians’ assessment of ACS. However, this can be overcome by a high index of suspicion after a thorough identification of all injuries as emphasized previously. Intracompartmental monitoring has been show to assist in the decision for fasciotomy as shown by a sensitivity of 94%.[6]

How do we improve?

• Thorough account of all injuries => really highlights the importance of the secondary and tertiary survey
• Intubated patients provide special challenges: unreliable exams, relative hypotension, patient unable to vocalize changes
• Rely on consideration of diagnosis and ICP monitoring

Even from these specific examples, a multitude of traps are apparent for the EM physician. Additionally, lack of useful screening tools, systems issues, and other cognitive biases increase the complexity of ACS. Although definitive diagnosis and management may be decided by consultants, our vigilance and advocacy are crucial.  The emergency physician should provide a reliable initial baseline exam, consider this diagnosis, reassess escalating pain, and more importantly pursue aggressive patient advocacy and management.

The management of ACS is less difficult than diagnosis. As discussed previously, absolute pressures >30 mmHg may be an indication for urgent fasciotomy. However, equivocal pressures can provide baseline information for the admitting team. Once the diagnosis is made or suspicion is high, an immediate surgical consultation will be necessary. If possible, place limb at the level of the heart or slightly dependent. In the setting of immobilization, immediately remove or bivalve the cast or splint to decompress the compartment.

Complications of ACS include rhabdomyolysis, hyperkalemia, and acute kidney injury. In the setting of suspected ACS, basic metabolic panel, creatinine kinase, urinalysis, and EKG are appropriate to screen for these complications. Larger compartments (lumbar, lower extremity) will proportionally contribute more to these complications by causing higher degrees of rhabdomyolysis. Have an increased index of suspicion in patients with pre-existing kidney disease or history of renal failure. Monitoring urine output may not be immediately beneficial, but could assist the inpatient team with fluid status monitoring.

Aggressive fluid resuscitation may be necessary for two reasons: treatment of rhabdomyolysis and subsequent acute kidney injury and augmentation of compartment vascular pressures of hypotensive patients to increase the threshold for ACS.

Finally, treat pain with opioid and non-opioid analgesics. Avoid ketorolac or NSAIDs given the possible impairment of renal function.

• 5 Ps = PAIN, pallor, paresthesia, paralysis, pulselessness
• Increasing pain despite analgesia should increase suspicion for ACS.
• Passive stretch of compartment thought to be most sensitive exam finding.
• Compartment pressures: <10 mmHg normal, >30 mmHg concerning for ACS
• Consider use of delta pressure for monitoring in equivocal exams.
• Special consideration with hypotensive patients, lower pressures required to overcome arterial pressures.
• Treat associated rhabdomyolysis, hyperkalemia, and acute kidney injury.

1. https://litfl.com/compartment-syndrome-ccc/
2. Ferri FF (2017).Ferri’s Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 317. ISBN 9780323529570.
3. McQueen MM, Gaston P, Court-Brown CM. Acute compartment syndrome: who’s at risk? J Bone Joint Surg [Br] 2000;82-B:200-3.
4. Elliott, KGB. Diagnosing acute compartment syndrome. J Bone Joint Surg Br. 2003 Jul;85(5):625-32.
5. McQueen et al. Compartment Monitoring in Tibial Fractures. J Bone Joint Surg. 1996;78-B:99-104
6. McQueen MM, Duckworth AD. The diagnosis of acute compartment syndrome: a review.Eur J Trauma Emerg Surg. 2014;40(5):521-528. doi:10.1007/s00068-014-0414-7

The post Acute Compartment Syndrome: Why do we miss it, and how do we improve? appeared first on emDOCs.net - Emergency Medicine Education.

Author: Richard J. Cunningham, MD (@HappyDays_EM, EM Resident Physician, Creighton/Maricopa Emergency Medicine Residency, Phoenix, AZ) // Reviewed by: Alex Koyfman, MD @EMHighAK) and Brit Long, MD (@long_brit)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

What is the diagnosis and management?

Answer: Laryngospasm

Epidemiology:

• Vagally-mediated involuntary closure of the vocal folds
• High incidence with extubation after general anesthesia (0.78-5%)¹, though most commonly associated with ketamine use in the Emergency Department (ED)
  • Large doses and rapid administration increase risk
  • Incidence of 4.2 per 1000 among patients undergoing procedural sedation in the emergency department²
• Risk higher with airway manipulation, recent upper respiratory infection, and pediatric patients³
• However, case-control series found no association of ketamine-induced laryngospasm with age, dose, oropharyngeal procedure, underlying physical illness, route, or co-administration with anticholinergics⁴
• Can lead to aspiration, hypoxia, post-obstructive pulmonary edema, and cardiac arrest¹

Clinical Presentation:

• Partial obstruction may present as stridor, tracheal tugging, and paradoxical chest movement
• Complete obstruction will present with apnea and no end-tidal CO2 waveform
• Up to 23% of laryngospasm may not be clinically obvious, and 61% can result in oxygen desaturation¹
• Pediatric patients are at particular risk of developing bradycardia as a result of hypoxia

Evaluation and Treatment:

• Laryngospasm is a clinical diagnosis that requires prompt recognition and treatment
• Use the following stepwise approach:
  • Perform jaw thrust with pressure applied posterior to the ramus of the mandible and anterior to the mastoid process at Larson’s notch⁵ (Figure 1)
  • Administer 100% FiO2 positive pressure ventilation via BVM with PEEP valve
  • If these do not correct laryngospasm, propofol can be administered, followed by succinylcholine if laryngospasm is not relieved, but be prepared for endotracheal intubation
    • Propofol 0.5 mg/kg IV can deepen sedation and result in muscle relaxation, breaking the laryngospasm
      • While this strategy is common in the OR, many emergency physicians would feel uncomfortable giving these agents to a patient with an unprotected airway; proceeding to RSI may be more prudent
    • Succinylcholine 0.5 mg/kg may break laryngospasm without causing full paralysis, thereby avoiding need for intubation.
      • Doses as low as 0.1 mg/kg may be successful³
      • This can be attempted if propofol not effective
      • If no IV access, can give 4mg/kg IM; will break laryngospasm in 45 seconds to 1 min and lead to full paralysis in 3-4 min, but this requires intubation⁶
    • If above measures fail, perform rapid sequence intubation (RSI)
  • One small study performed in the OR showed gentle chest compression to be more successful than positive pressure ventilation in breaking laryngospasm (73.9% vs 38.4%, p<0001)⁷

Disposition:

• Patients will likely require a several-hour period of observation in the ED before discharge to monitor for signs of aspiration or post-obstructive pulmonary edema
• If intubated, attempt extubation with anesthesia present as there is a risk of recurrence

Pearls:

• Laryngospasm is a clinical diagnosis that requires prompt recognition and treatment to avoid morbidity and mortality
• Laryngospasm is most commonly associated with ketamine use in the ED
• It can present as stridor and respiratory distress or apnea depending on degree of obstruction
• To treat, perform a jaw thrust while applying pressure at Larson’s point and administering positive pressure via BVM
• If above fails, RSI will likely be required

Further Reading:

emDOCs: 10 Procedural Sedation Errors in the Emergency Department

5 Minute Airway: Beating Laryngospasm

First 10 EM: Managing laryngospasm

References:

1. Visvanathan T, Kluger MT, Webb RK, Westhorpe RN. Crisis management during anaesthesia: laryngospasm. Qual Saf Health Care. 2005;14(3):e3. doi:10.1136/qshc.2002.004275
2. Bellolio MF, Gilani WI, Barrionuevo P, et al. Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med. 2016;23(2):119-134. doi:10.1111/acem.12875
3. Hobaika AB, Lorentz MN. Laryngospasm. Rev Bras Anestesiol. 2009 Jul-Aug;59(4):487-95. PMID: 19669024.
4. Green SM, Roback MG, Krauss B; Emergency Department Ketamine Meta-Analysis Study Group. Laryngospasm during emergency department ketamine sedation: a case-control study. Pediatr Emerg Care. 2010;26(11):798-802. doi:10.1097/PEC.0b013e3181fa8737
5. Larson CP Jr. Laryngospasm–the best treatment. Anesthesiology. 1998;89(5):1293-1294. doi:10.1097/00000542-199811000-00056
6. Gavel G, Walker RWM. Laryngospasm in anaesthesia. Contin Educ Anaesth Crit Care Pain. 2014; 14: 47–51.
7. Al-Metwalli RR, Mowafi HA, Ismail SA. Gentle chest compression relieves extubation laryngospasm in children. J Anesth. 2010;24(6):854-857. doi:10.1007/s00540-010-1036-9

The post EM@3AM: Laryngospasm appeared first on emDOCs.net - Emergency Medicine Education.

Originally published on Ultrasound G.E.L. on 5/10/21 – Visit HERE to listen to accompanying PODCAST! Reposted with permission.

Follow Dr. Michael Prats, MD (@PratsEM) from Ultrasound G.E.L. team!

The post Ultrasound G.E.L. – PEA Arrest appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Neha Ray, MD and Ann-Jeannette Geib, MD (Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC) // Reviewed by: Cynthia Santos, MD (@CynthiaSantosMD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 26-year-old female with a history of opioid-use disorder presents to the emergency room with nausea, anxiety, and myalgias. She is adamant that she has not taken narcotic pills, IV drugs, or other illicit substances for over a year. She does report however that she has been purchasing kratom on the internet for the last year, but she has not had access to it for the last two days.

Questions:

• What is kratom and is it safe?
• What considerations should the emergency physician have for patients who use Kratom?

Background:

• Kratom (Mitragyna speciosa) is a plant native to Southeast Asia. It has been used for centuries as an herbal remedy for a variety of ailments.
• In recent years, Kratom has been increasingly popular in the United States. While it has not been approved by the FDA for therapeutic use, there are an estimated 3-5 million Kratom users in the US. ¹
• Kratom has been shown to produce both stimulant and opioid-like analgesic effects and has been used for the treatment of opioid use disorder (OUD), pain, and anxiety.

Clinical Effects:

• Kratom has mitragynine-type indole alkaloids that can interact with opioid receptors and produce some opioid-like effects. The active substance in kratom is mitragynine, an indole alkaloid. It also has an active metabolite, 7-hydroxy mitragynine, that appears to have a greater affinity for mu-opioid receptors than mitragynine.^2,3 Kratom is thought to act at the mu-opioid receptor without activating the β-arrestin-2 signaling pathway that produces some of the side effects of classical opioids.^2,4
• At low to moderate doses, kratom has mild stimulating effects, likely due to multiple alkaloids in the herbal mix.^5,6 With typical dosing, there are opioid-like effects, including analgesia and euphoria, though the euphoric effects of kratom tend to be less intense than classical opioids.⁵
• Kratom is overall thought to be less likely to cause significant respiratory depression compared to classical opioids. In a review of poison center calls, only one death was noted which was in the setting of co-ingestants.⁷ A study of the UK, western European, and US deaths related to kratom found polysubstance use in nearly 83% of decedents, with the most common co-intoxicants being opioids, benzodiazepines, antidepressants, and/or other psychopharmaceuticals.⁸
• The most common adverse effects are agitation, tachycardia, and nausea and are usually mild overall.⁹
• More serious effects including cardiotoxicity [bradycardia, asystole], acute liver injury, and seizures have been reported.⁹ Alkaloid extracts from Kratom work on multiple receptors including calcium channel blockade, and intravenous lipid emulsion has been attempted for treatment in one overdose case.^10,11  Acute liver injury typically occurs within the first 8 weeks of use and can involve severe hyperbilirubinemia or prolonged cholestasis, and typically resolves with discontinuation of kratom.¹²  Multiple case reports indicate that kratom may be a pro-convulsant.¹³  In one case, changes on brain MRI were noted for a patient with recurrent seizures associated with Kratom use.¹⁴ Traditional anticonvulsants have been used with some success, as has detoxification.^{13, 14}
• There have been several deaths reported in the setting of Kratom use, but causality is unclear or associated with coingestants in most of these cases.^{7, 9}

Pearls:

• While kratom itself is much less likely to cause respiratory depression compared with classical opioids, lack of regulation makes contaminated samples more likely.⁶ Consider intentional or unintentional co-ingestions in patients who report Kratom use.
• There have not been any multi-center, controlled clinical trials regarding the therapeutic effects of Kratom, but there is significant anecdotal evidence suggesting a possible role in managing OUD and chronic pain.⁵ Kratom has been shown to lead to tolerance and dependence, however, this is typically milder than with classical opioids.¹ There are multiple case reports of buprenorphine used to treat kratom dependence.^15,16
• There is evidence, though limited, that kratom has attenuated euphoria and abuse potential when compared to classical opioids, indicating a possible therapeutic role for kratom.⁵
• While kratom itself appears relatively safe at therapeutic doses, be wary of potential drug-drug interactions. There is evidence that mitragynine inhibits cytochrome P450 2C9, 2D6, and 3A4.¹⁷ Potential interactions in humans have specifically been reported with amlodipine and quetiapine.¹ Providers should also be wary of interactions with any CNS-active substances.¹
• When treating patients with suspected or known OUD, clinicians should ask patients what they are using to prevent or treat withdrawal, including herbal substances.
• Kratom is considered a Drug of Concern by the United States DEA.¹⁰

Case Conclusion:

The ED physician identifies that the patient’s presentation is due to kratom withdrawal. They discuss both symptomatic treatments as well as initiation of buprenorphine. The patient is agreeable to buprenorphine administration and has improvement in her symptoms. She is discharged with a warm hand-off to substance use disorder treatment.

References:

1. Veltri C, Grundmann O. Current perspectives on the impact of Kratom use. Subst Abuse Rehabil. 2019;10:23-31. Published 2019 Jul 1.
2. Váradi, András, et al. “Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit β-arrestin-2.” Journal of medicinal chemistry 59.18 (2016): 8381-8397.
3. Eastlack SC, Cornett EM, Kaye AD. Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review. Pain Ther. 2020 Jun;9(1):55-69. doi: 10.1007/s40122-020-00151-x. Epub 2020 Jan 28. PMID: 31994019; PMCID: PMC7203303.
4. Raehal KM, Walker JK, Bohn LM. Morphine side effects in beta-arrestin 2 knockout mice. J Pharmacol Exp Ther. 2005 Sep;314(3):1195-201. doi: 10.1124/jpet.105.087254. Epub 2005 May 25. PMID: 15917400
5. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792-799.
6. Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. Kratom Use and Toxicities in the United States. Pharmacotherapy. 2019 Jul;39(7):775-777. doi: 10.1002/phar.2280. Epub 2019 Jun 13. PMID: 31099038.
7. Anwar M, Law R, Schier J. Notes from the Field. Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016;65:748–749.
8. Corkery JM, Streete P, Claridge H, Goodair C, Papanti D, Orsolini L, Schifano F, Sikka K, Körber S, Hendricks A. Characteristics of deaths associated with kratom use. J Psychopharmacol. 2019 Sep;33(9):1102-1123. doi: 10.1177/0269881119862530. Epub 2019 Aug 20. PMID: 31429622.
9. Post S, Spiller HA, Chounthirath T, Smith GA. Kratom exposures reported to United States poison control centers: 2011-2017. Clin Toxicol (Phila). 2019 Oct;57(10):847-854. doi: 10.1080/15563650.2019.1569236. Epub 2019 Feb 20. PMID: 30786220. Prozialeck WC, Avery BA, Boyer EW, et al. Kratom policy: The challenge of balancing therapeutic potential with public safety. Int J Drug Policy. 2019;70:70-77.
10. Hassan Z, Muzaimi M, Navaratnam V, Yusoff NH, Suhaimi FW, Vadivelu R, Vicknasingam BK, Amato D, von Hörsten S, Ismail NI, Jayabalan N, Hazim AI, Mansor SM, Müller CP. From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction. Neurosci Biobehav Rev. 2013 Feb;37(2):138-51. doi: 10.1016/j.neubiorev.2012.11.012. Epub 2012 Dec 1. PMID: 23206666.
11. Aggarwal G, Robertson E, McKinlay J, Walter E. Death from Kratom toxicity and the possible role of intralipid. J Intensive Care Soc. 2018;19(1):61-63. doi:10.1177/1751143717712652
12. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Kratom. [Updated 2020 Apr 3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548231/
13. Alsarraf, E., Myers, J., Culbreth, S. et al.Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities. Curr Emerg Hosp Med Rep 7, 141–168 (2019). https://doi.org/10.1007/s40138-019-00194-1
14. Tatum WO, Hasan TF, Coonan EE, Smelick CP. Recurrent seizures from chronic kratom use, an atypical herbal opioid. Epilepsy Behav Case Rep. 2018;10:18-20. Published 2018 Apr 17. doi:10.1016/j.ebcr.2018.04.002
15. Buresh M. Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance. J Addict Med. 2018 Nov/Dec;12(6):481-483. doi: 10.1097/ADM.0000000000000428. PMID: 29944481.
16. Khazaeli A, Jerry JM, Vazirian M. Treatment of Kratom Withdrawal and Addiction With Buprenorphine. J Addict Med. 2018 Nov/Dec;12(6):493-495. doi: 10.1097/ADM.0000000000000435. PMID: 30383616.
17. Hanapi NA, Ismail S, Mansor SM. Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy Res. 2013 Oct;5(4):241-6. doi: 10.4103/0974-8490.118806. PMID: 24174816; PMCID: PMC3807987.

The post ToxCard: Kratom appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Rachel Lynn Graves, MD (EM Resident Physician, University of Pennsylvania) and Gillian Bach, MD (Medical Education Scholarship Fellow, Interim Assistant Residency Program Director, University of Pennsylvania) // Reviewed by: Edward Lew, MD (@elewMD); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case:

A 36-year-old male with a past medical history of migraines, GERD, anxiety, depression, and alcohol use disorder presents to the ED with palpitations. He experienced sudden onset of palpitations about 12 hours ago while lying in bed watching a movie. He’s never had similar symptoms in the past. He endorses associated lightheadedness and shortness of breath but denies chest pain. He drinks about three 16-ounce cups of coffee and 8 beers per day. He denies recent travel and illicit drug use. On exam, the patient is a comfortable-appearing, well-developed male, wearing a suit and reclining in a stretcher. He has a temperature of 97.9°F, blood pressure of 135/90, heart rate of 119, respiratory rate of 13, and SpO2 99% on room air. He has no jugular venous distention, abnormal lung sounds, abdominal tenderness or distention, or lower extremity edema or asymmetry. His extremities are warm and well-perfused with 2+ bilateral radial and dorsalis pedis pulses.

An EKG shows the following:

After discussion of different management options, the decision is made to pursue cardioversion in the ED.

Is this patient low-risk or high-risk for electrical cardioversion? Why? What would be your approach to cardioverting this patient?

Electrical cardioversion (henceforth referred to simply as “cardioversion”) is the application of a synchronized electrical impulse to convert a perfusing tachydysrhythmia back to normal sinus rhythm.^1,2 It is indicated for hemodynamically unstable patients who present in ventricular tachycardia (VT), supraventricular tachycardia (SVT), atrial flutter, and atrial fibrillation (AF). Cardioversion may also be considered, along with pharmacologic cardioversion, for stable patients with these dysrhythmias.¹

While cardioversion is generally well-tolerated, complications can occur. Most of these complications are self-limiting (e.g. EKG changes, hypotension related to sedation delivered to perform the procedure) or relatively benign (e.g.superficial skin burns). However, cardioversion does have the potential to cause life-threatening complications, including thromboembolic events, dangerous dysrhythmias, and hemodynamic decompensation.

Understanding which patients are at highest risk for immediate, life-threatening complications following cardioversion—as well as how to manage those risks—is of critical importance for the emergency medicine physician.

High risk patients: who crashes?

Patients with pre-existing cardiovascular diseases, older patients

Older age and certain chronic cardiovascular diseases have been implicated in the development of acute onset, life-threatening complications following cardioversion.^3-9

Multiple studies have shown that patients with pre-existing structural heart disease are at risk for developing acute pulmonary edema following electrical cardioversion.^3,4,10,11

A 2017 retrospective study by Leitman et al. found that, among the subset of patients who underwent electrical cardioversion for AF and subsequently developed complications, the strongest independent predictor of any complication and death during hospitalization was severe mitral or aortic regurgitation, followed by pulmonary hypertension. Other cardiovascular diseases—including diabetes, left ventricular hypertrophy (LVH), left ventricular dysfunction, and recurrent AF—were also predictive of severe complications and/or in-hospital mortality, though not independently.Among the subset of patients who died in the acute period following electrical cardioversion, fatal complications included: respiratory failure, pulmonary edema, arrythmias, and pulmonary embolism, among others.³

Case reports have described the development of stress cardiomyopathy following electrical cardioversion.^12-16 In all of these cases, the patients were older, had chronic cardiovascular disease, or both. In most of these patients, stress cardiomyopathy led to the development of pulmonary edema and/or cardiogenic shock requiring intensive supportive management. The exact mechanism by which electrical cardioversion led to stress cardiomyopathy in these patients is not known, though catecholamine-induced cardiac injury and direct electrical injury have both been proposed as mechanisms.¹⁷

The presence of cardiovascular disease and age also have a bearing upon risk of thromboembolism. It is well-known that thromboembolism is a risk for patients who undergo any type of cardioversion for AF (even spontaneous), especially in the absence of anticoagulation or if AF has been present for 12 hours or more.^5-8,18 In certain subgroups—including older patients, female patients, and patients with heart failure or diabetes—the risk is particularly high.^5,7 Thromboembolism can occur due to dislodgement of left atrial thrombi present at the time of cardioversion or when a new thrombus forms during the period of post-cardioversion left atrial mechanical dysfunction.^2,19

Multiple studies have shown that a non-negligible proportion of individuals, despite being on appropriate anticoagulation therapy, still have left atrial thrombus visible on TEE prior to planned cardioversion. Structural heart disease also appears to be a risk factor in these cases.^19-24

Patients who undergo inappropriate unsynchronized cardioversion

Arrhythmias and conduction abnormalities are frequently observed after cardioversion. These arrhythmias are usually benign, but clinically or hemodynamically significant arrhythmias such as ventricular fibrillation (VF) and sustained VT occur as well.^2,25-32

If cardioversion is performed inappropriately, particularly during the relative refractory period of the cardiac cycle, it may induce VF. Shocks that are not correctly synchronized to the QRS complex can occur due to operator error (i.e. the operator does not engage the “sync” function on the defibrillator) or machine error (i.e. the defibrillator does not correctly identify the QRS complexes).

Numerous case reports describe the phenomenon of inappropriate synchronization with T waves leading to VF immediately after cardioversion. ^25-32  In all of these cases, the presenting rhythm was AF with a pre-excitation syndrome such as Wolff-Parkinson-White (WPW) syndrome.

In patients with WPW, the simultaneous occurrence of AF can cause rapid ventricular activation via the accessory pathway and lead to an irregular wide-complex tachycardia.³³  In these cases, there is usually variable QRS morphology, depending on how much conduction is through the AV node and how much is through the accessory pathway. If the refractory period of the accessory pathway is short, antegrade conduction to the ventricles occurs mostly via the accessory pathway, and the QRS complexes are relatively wide and bizarre in appearance. The ventricular rate might be very rapid (>300 beats per minute) due to 1:1 conduction from the atrium to the ventricles.³⁴ QRS complexes in these cases may also have small amplitude relative to the T wave, making them difficult to distinguish from T waves. Thus, a defibrillator may mistake the T waves for QRS complexes and deliver an unsynchronized shock during the vulnerable repolarization phase of the cardiac cycle.

Patients with AF and pre-excitation syndromes such as WPW may have bizarre QRS complexes that are difficult to distinguish from T waves. In these cases, a mechanical defibrillator may inappropriately identify a T wave as a QRS complexes and deliver an asynchronous shock. Patients who receive asynchronous shocks are at high risk of developing VF.

How can we improve?

Assess risk of electrical cardioversion using historical data, a targeted physical exam, data obtained on the day of presentation, and risk stratification tools

Minimizing complications associated with electrical cardioversion begins with careful patient selection. Ideally (that is, if the patient is stable and time allows), the emergency medicine physician should do the following:

1. Search the medical record for relevant historical information, with particular attention to prior EKGs, echocardiograms, and evidence of pre-existing cardiac disease (g. cardiac catheterization reports, stress tests, and cardiology office visits). Patient often do not know or do not communicate these crucial historical data.
2. Perform a targeted physical exam. Does the patient appear well, obese, or chronically ill? Do they have evidence of volume overload (g. rales on pulmonary auscultation, lower extremity edema)? Do they have sequelae of uncontrolled diabetes such as decreased sensation in the distal extremities, diabetic ulcers, or amputation?
3. Collect pertinent data on the data of the visit, including a complete metabolic panel (CMP), a complete blood count (CBC), and PT/PTT/INR for patients who are prescribed anticoagulation. Obtain an EKG and compare to prior EKGs if available. Does the patient have LVH, evidence of conduction abnormalities, or other abnormalities suggestive of structural heart disease? Has the patient presented with a dysrhythmia before, or have they historically been in sinus rhythm? If able, obtain a bedside echocardiogram to assess for the presence of systolic dysfunction, LVH, and other structural abnormalities.
4. Use risk stratification tools (g. CHA₂DS₂-VASc score for stroke risk in patients with AF), patient demographics, and details of the history can help emergency medicine physicians weigh the risks and benefits of cardioversion.

All of this information will inform the physician’s overall assessment of a patient’s risk, even for patients who provide vague or limited history, or for whom prior data is not available. While exact quantification of risk is difficult, it is critical to consider carefully and, when able, have an informed discussion with the patient about their particular risk factors.

Some risk factors are binary; for example, a patient does or does not have diabetes, or heart failure, etc. Other risk factors, particularly age, exist along a spectrum. Various studies have found different age cut offs at which the risk of a particular complication or complications in general becomes statistically significant. Leitman et al. found that patients older than 72 were at risk for a number of complications.³ Davarashvili et al. found that patients who were 79 (+/- 9) years old were at greater risk of pulmonary congestion (p < 0.001).⁴ Airaksinen et al. found that thromboembolic complications were statistically more likely in patient aged 69.9 (+/- 9.3) (p < 0.0001).⁵ From a practical perspective, use of the age cut offs in the CHA₂DS₂-VASc score is a reasonable approach to risk stratification by age, wherein patients aged 65-74 are considered at increased risk, and patients 75 or older are at especially increased risk.

If the decision is made to proceed with anticoagulation, be aware of—and prepared to manage—potential procedural complications, particularly in high risk patients.

Treat potentially modifiable conditions.

Treatment of potentially modifiable conditions that may be contributing to the presenting dysrhythmia should be considered prior to cardioversion if possible in high risk patients—to avoid the risks of electrical cardioversion, optimize the patient should cardioversion become necessary, and to facilitate maintenance of sinus rhythm if successful cardioversion is achieved.^7,35  Optimization might include the management of hypertension, treatment of volume overload with diuresis, volume repletion, respiratory support with BiPAP or high flow oxygen via nasal cannula, provision of antibiotics if there is concern for infection, and symptom management, depending on the patient.

Strongly consider anticoagulation in appropriate patients.

Appropriate anticoagulation reduces the risk of thromboembolism following cardioversion, particularly in higher risk patients.^5-8 Current guidelines recommend systemic anticoagulation for at least 3 weeks with a novel oral anticoagulant (NOAC) or vitamin K antagonist (VKA) prior to cardioversion for AF among patients with an unknown duration of AF, definite duration of AF greater than 48 hours, or an identified thrombus on TEE.⁷ Anticoagulation should also be continued for at least 4 weeks after elective electrical cardioversion in all but patients at lowest risk for stroke (i.e.CHA₂DS₂-VASc 0 in men, 1 in women, for whom it may be optional).^[7]  

Of course, there are emergent cases in which it is not possible to adhere to these guidelines regarding optimal anticoagulation status prior to pursuing electrical cardioversion. Following cardioversion in these cases, the entire care team should be vigilant for changes in neurologic status that might suggest CVA. If the patient experiences changes in vital signs—particularly hypotension, tachycardia, and hypoxia—pulmonary embolism should be considered on the differential. Anticoagulation with either a NOAC, low-molecular-weight heparin, or heparin should be strongly considered in all but the lowest risk patients and/or those with absolute contraindications to anticoagulation therapy.⁷

Know how to distinguish AF with pre-excitation syndrome from other dysrhythmias on EKG.

It may not be known, by the physician or the patient, whether a patient has a pre-excitation syndrome like WPW. Individuals with accessory pathways only display features characteristic of pre-excitation when impulses are actually conducted over the accessory pathway, which is usually intermittent.³³ Emergency medicine physicians may mistake AF with pre-excitation for other dysrhythmias, including VT, or AF with left bundle branch block (LBBB), which can lead to inappropriate, even dangerous, management of the patient. Knowing what EKG features distinguish AF with pre-excitation may help prevent these complications.

The ECG features of AF with WPW include a rapid (200-300 bpm), irregular rhythm with wide QRS complexes showing variable shape and morphology.^[3]

Further Reading: How can the rhythm in the EKG above be distinguished from AF with LBBB?

(See answer at https://litfl.com/pre-excitation-syndromes-ecg-library/.)

Further Reading: How can this EKG be distinguished from torsades de pointes?

(See answer at https://litfl.com/pre-excitation-syndromes-ecg-library/.)

 Case Conclusion:

After discussion of risks and benefits, the emergency medicine team and the patient decided to proceed with electrical cardioversion, primarily because the patient preferred the earliest possible resolution of his symptoms. He was successfully cardioverted to sinus rhythm after a single shock was administered under light procedural sedation without complication. Because the patient’s CHA₂DS₂-VASc score was zero, he was considered low risk and did not wish to initiate anticoagulation. He was discharged home in improved condition with a referral for expedited cardiology follow up.

Take Home Points:

• Patients with pre-existing cardiovascular disease, particularly structural heart disease and older patients (defined as age 65 and older, to error on the side of inclusion) are at risk for life-threatening complications following cardioversion. Be prepared to manage complications when cardioverting these patients.
• Patients with pre-excitation syndromes may have bizarre QRS complexes that are difficult to distinguish from T waves, which can lead to asynchronous shock delivery and the development of VF.
• All but the lowest risk patients should be anticoagulated prior to and following cardioversion unless they have a direct contraindication.

References:

1. Ong MEH, Leong BSH, Ng YY. Defibrillation and electrical cardioversion. In Tintinalli JE, ed. Tintinalli’s Emergency Medicine: A Comprehensive Study-Guide. 9^th United States of America: McGraw-Hill Education; 2020: 149-153.
2. Knight BP. Cardioversion for Specific Arrhythmias. UpToDate. https://www.uptodate.com/contents/cardioversion-for-specific-arrhythmias?search=cardioversion%20complications&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H2560757. Published May 1, 2019. Accessed March 6, 2021.
3. Leitman M, Tyomkin V, Peleg E, et al. When cardioversion may be complicated. Isr Med Assoc J. 2017;19(5):282-288.
4. Davarashvili I, Acha MR, Glikson M, et al. Pulmonary congestion complicating atrial fibrillation cardioversion. Am J Cardiol. 2018;122(10):1701-1706.
5. Airaksinen KEJ, Gronberg T, Nuotio I, et al. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol. 2013;62(13):1187-1192.
6. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2893-2962.
7. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;42(5):373-498.
8. Hansen ML, Jepsen RM, Olesen JB, et al. thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. 2015;17:18-23.
9. Khan MU, Khouzam RN, Khalid H, et al. Cardiogenic shock following electro-cardioversion of new onset atrial flutter. Heart Lung. 2013;42(6):462-464.
10. Gowda RM, Misra D, Khan IA, Schweitzer P. Acute pulmonary edema after cardioversion of cardiac arrhythmias. Int J Cardiol. 2003;92(2-3):271-274.
11. Wang RN, Khordipour E. Acute pulmonary edema: a rare cause of dyspnea after electrical cardioversion. J Emerg Med. 2020;58(3):497-499.
12. Pir MS, Saqib N, Oza F, Rao M. Iatrogenic heartbreak: stress cardiomyopathy after electrical cardioversion. J Am Coll Cardiol. 2019;73(9_Supplement_1): 2701
13. Landi A, De Servi S. Takotsubo syndrome and electrical storm following electrical cardioversion of atrial fibrillation: cause, consequence or both? J Cardiovasc Med (Hagerstown). 2021;22(2):139-142.
14. Zaghlol R, Hritani R, O’Donoghue S. Shock begets shock: a case of direct current cardioversion-induced takotsubo cardiomyopathy. HeartRhythm Case Rep. 2019;5(6):310-313.
15. McCutcheon K, Butler I, Vachiat A, Manga P. Takotsubo syndrome in an elderly woman due to electrical cardioversion. Int J Cardiol. 2016;224:69-71.
16. Siegfried JS, Bhusri S, Guttenplan N, Coplan NL. Takotsubo cardiomyopathy as a sequela of elective direct-current cardioversion for atrial fibrillation. Tex Heart Inst J. 2014;41(2):184-187.
17. Ghadri JR, Wittstein IS, Prasad A et al. International expert consensus document on takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018;39(2018):2032-2046.
18. Nuotio I, Hartikainen JE, Gronberg et al. Time to cardioversion for acute atrial fibrillation and thromboembolic complications. 2014;312:647-649.
19. Bursi F, Santangelo G, Ferrante G, et al. Prevalence of left atrial thrombus by real time three-dimensional echocardiography in patients undergoing electrical cardioversion of atrial fibrillation: A contemporary cohort study. Echocardiography. 2021;0. https://doi.org/10.1111/echo.15015. Accessed March 7, 2021.
20. Durmaz E, Karpuz MH, Bilgehan K, et al. Left atrial thrombus in patients with atrial fibrillation and under oral anticoagulant therapy; 3-D transesophageal echocardiographic study. Int J Cardiovasc Imaging. 2020;36(6):1097-1103.
21. Hwang J, Park HS, Jun SW, et al. The incidence of left atrial appendage thrombi on transesophageal echocardiography after pretreatment with apixaban for cardioversion in the real-world practice. PLoS One.2018;13(12):e0208734.
22. Niku AD, Shiota T, Siegel RJ, Rader F. Prevalence and resolution of left atrial thrombus in patients with nonvalvular atrial fibrillation and flutter with oral anticoagulation. Am J Cardiol. 2019;123(1):63-68.
23. Zylla MM, Pohlmeier M, Hess A, et al. Prevalence of intracardiac thrombi under phenprocoumon, direct oral anticoagulants (dabigatran and rivaroxaban), and bridging therapy in patients with atrial fibrillation and flutter. Am J Cardiol. 2015;115(5):635-640.
24. Fukuda S, Watanabe H, Shimada K, et al. Left atrial thrombus and prognosis after anticoagulation therapy in patients with atrial fibrillation. J Cardiol. 2011;58(3):266-277.
25. Danon A, Militianu A, Schliamser JE. Cardioversion of pre-excited atrial fibrillation leading to ventricular fibrillation-case report and review of literature. Am J Emerg Med. 2019;37(8):1539-1543.
26. Kaufmann MR, McKillop MS, Burkart TA, et al. Iatrogenic ventricular fibrillation after direct-current cardioversion of preexcited atrial fibrillation caused by inadvertent t-wave synchronization. Tex Heart Inst J. 2018;45(1):39-41.
27. Ikeda S, An Y, Yanagisawa M, et al. Iatrogenic ventricular fibrillation caused by inappropriately synchronized cardioversion in a patient with pre-excited atrial fibrillation: A case report. J Cardiol Cases. 2020;23(1):31-34.
28. Ebrahimi R, Rubin SA. Electrical cardioversion resulting in death from synchronization failure. Am J Cardiol.1994;74(1):100-102.
29. Adlam D, Azeem T. Ventricular fibrillation during electrical cardioversion of pre-excited atrial fibrillation. Postgrad Med J. 2003;79(931):297-299.
30. Taylor N. Direct current cardioversion causing ventricular fibrillation in Wolff-Parkinson-White syndrome. Emerg Med Australas. 2013;25(5):612-614.
31. Xavier LC, Memon A. Synchronized cardioversion of unstable supraventricular tachycardia resulting in ventricular fibrillation. Ann Emerg Med. 2004;44:178-180.
32. O’Connell M, Bernard A. A serious cause of panic attack. Case Rep Emerg Med. 2012; 2012:393275.
33. Burns E, Buttner R. Pre-excitation Syndromes. Life in the Fast Lane. https://litfl.com/pre-excitation-syndromes-ecg-library. Published Feb 8, 2021. Accessed March 7, 2021.
34. Prutkin JM. ECG Tutorial: Preexcitation Syndromes. UpToDate. https://www.uptodate.com/contents/ecg-tutorial-preexcitation-syndromes?search=ecg%20tutorial:%20preexcitation%20syndromes&source=search_result&selectedTitle=1~135&usage_type=default&display_rank=1. Published Dec 30, 2019. Accessed March 7, 2021.
35. Rienstra M, Hobbelt AH, Alings M, et al. Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: results of the RACE 3 trial. Eur Heart J. 2018;39:2987-2996.

The post Electrical cardioversion in the ED: who crashes and how to improve appeared first on emDOCs.net - Emergency Medicine Education.

The post Journal Feed Weekly Wrap-Up appeared first on emDOCs.net - Emergency Medicine Education.

Originally published at EM Cases. Reposted with permission. Listen to accompany podcast HERE

Follow Dr. Anton Helman on twitter at @EMCases

In this podcast, Part 2 of our diabetic emergencies series with Melanie Baimel, Bourke Tillmann and Leeor Sommer, we dive into the recognition and ED management of Hyperglycemic Hyperosmolar State (HHS). We answer questions such as: how does one differentiate DKA from HHS clinically? How do patients with HHS become hyperglycemic, dry and altered? Why is finding and treating the cause or trigger of HHS so important in the ED? How does fluid management differ in HHS from DKA? and many more…

For part 1 of this series on Diabetic Emergencies go to Episode 146 DKA Recognition and ED Management

DKA and HHS are two distinct entities that exist on the spectrum of diabetic emergencies. HHS is characterized by the triad of severe hyperglycemia (>33.3 mmol/L or >600 mg/dL), elevated serum osmolality (>320 Osm/kg), and altered level of awareness (LOA). HHS occurs without significant ketoacidosis, the anion gap is variable and patients often present with profound volume depletion. Importantly, HHS can occur concurrently with DKA making the ED diagnosis even more challenging.

Differentiating DKA from HHS

 

How do patients with HHS become severely hyperglycemic, dry and altered?

In HHS, there is relative insulin deficiency or resistance, leading to impaired glucose utilization, resulting in severe hyperglycemia and subsequent volume depletion from osmotic diuresis. However, there is sufficient insulin to suppress ketogenesis (thus minimal or no ketones), but not enough to control hyperglycemia. This insidious process permits ongoing osmotic diuresis and progressive volume depletion. Increased counter-regulatory hormones in HHS can also exacerbate this cycle of hyperglycemia and further volume depletion through decreased insulin sensitivity, increased glycogenolysis and gluconeogenesis. This is the reason why patients with HHS often present with a protracted course of illness.

In contrast, DKA is a state of absolute insulin deficiency. In order for the body to meet its basic metabolic demands, fatty acid metabolism/ketosis occurs. Patients in DKA often present much sooner in their course of illness as their body cannot tolerate the ketotic/acidotic state.

Finding the cause of HHS is of paramount importance

The mortality rate of HHS is considerably higher than DKA partly because it more often targets older people with concurrent illnesses.

HHS is often precipitated by similar conditions seen in DKA including: infection (pneumonia, UTI, intra-abdominal etc.), insulin deficiency (medication access/non-adherence, intercurrent illness (ACS, PE, stroke etc.) and inadequate hydration. Use the mnemonic 5 “I”s plus drugs if that helps you remember the triggers.

Pearl: Mortality in HHS is frequently due to an underlying cause rather than the complications of the condition itself; a thorough investigation for the cause should always be undertaken.

Filling the tank: HHS fluid resuscitation

Osmotic diuresis from profound hyperglycemia results in significant volume depletion. Fluid resuscitation will help restore intravascular volume and help normalize plasma hyperosmolality. Our experts recommend using POCUS to help guide fluid resuscitation and avoid fluid overload.

• Use NS or RL for initial fluid replacement
• American Diabetes Association (ADA): 1000-1500mL NS over 1 hr, then adjust to hemodynamic and electrolyte status, and maintain between 250 and 500 mL/hr
• ADA: Patients with a normal or high corrected sodium can be switched to 0.45% sodium chloride after the first hour of fluid replacement
• ADA: Add dextrose (D5W) when the blood glucose falls below 16.7 mmol/L (300 mg/dL)

 

Correcting the potassium deficit in HHS before starting insulin

Patients with HHS have large total body potassium deficits that must replaced after adequate renal function (urine output) is assessed. The initial potassium lab report is commonly normal or high due to intracellular shifts secondary to volume contraction.

• ADA: 20-30 mmol (20-30 mEq) potassium per liter of infusion fluid when serum potassium <5.2 mmol/L
• UK: 40 mmol (40 mEq) potassium per litre of infusion fluid when serum potassium <5.5 mmol/L
• Evidence is lacking to support either recommendation over the other
• Potassium must be replaced prior to initiation of insulin therapy as insulin further promotes an intracellular shift of potassium; it is recommended that insulin should not be started if the serum potassium is <3 mmol/L (<3 mEq/L) to avoid worsening of hypokalemia

 

Restoring metabolic homeostasis with insulin in HSS

In contrast to DKA where insulin therapy is used to close the gap, in HHS, the purpose of insulin is to restore metabolic homeostasis to allow for glucose utilization in a relative insulin deficient state.

The optimal time to start intravenous insulin in the management of HHS has not been determined.

• ADA: “Start intravenous insulin after initiation of fluid resuscitation and correction of any hypokalemia“

The optimal starting dose of intravenous insulin in the management of HHS has not been determined

• ADA: “Start intravenous insulin at either a fixed weight-based dose of 0.14 units/kg/h or at a fixed weight-based dose of 0.1 units/kg/h after a 0.1 units/kg bolus“

The rate of intravenous insulin should be adjusted to achieve an adequate drop in blood glucose

• ADA: “If plasma glucose does not decrease by 3-4 mmol/L/h (50-75 mg/dL/h) from the initial value in the first hour, the insulin infusion should be increased every hour until a steady glucose decline is achieved. When blood glucose is < 16 mmol/L (<300 mg/ dL), adjust dextrose or intravenous insulin rate to maintain concentrations in the 14-16 mmol/L (250-300 mg/dL) range until HHS has resolved.”

 

Key take home points for HHS recognition and ED management

1. Clues that point to the diagnosis of HHS are protracted illness with progressive altered LOA and a high serum osmolarity – there usually is not an anion gap metabolic acidosis
2. HHS and DKA can occur concurrently making the diagnosis challenging
3. Identify the underlying cause which is the most common cause of death in HHS patients – use the mnemonic 5 “I”s plus drugs if that helps you remember the triggers
4. HHS patients usually require aggressive fluid resuscitation but be careful not to fluid overload; use POCUS to help assess volume status
5. Correct the potassium deficit in HHS before starting insulin

2018 Canadian Guidelines DKA and HHS

2009 ADA Guidelines DKA and HHS

 

References for Episode 147 HHS Recognition and ED Management

Expand to view reference list

 

1. 1. Goguen J, et al. Hyperglycemic emergencies in adults: 2018 Clinical Practice Guidelines. Canadian Journal of Diabetes, 42: S109-S114.
   2. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343.
   3. Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19 Suppl 27:155-177.Fayfman M, Pasquel F, Umpierrez G. Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Med Clin North Am. 2017;101(3):587-606.
   4. Van Ness-Otunnu R, Hack JB. Hyperglycemic crisis. J Emerg Med 2013;45(5): 797–805.

    

Drs. Helman, Baimel, Sommer and Tillmann have no conflicts of interest to declare

The post EM Cases: HHS Recognition and ED Management appeared first on emDOCs.net - Emergency Medicine Education.

Welcome back to Small Talk; a new monthly section from emDOCs.  Every first Wednesday of the month we will release high yield PEM content written by PEM talent from around the country.  We hope you enjoy these reviews. Comments, questions, accolades or concerns: feel free to reach out to Joe Ravera, MD (pemgemspod@gmail.com).

Author: Raymen Rammy Assaf, MD, MPH, MA (Pediatric Emergency Medicine Fellow, Harbor UCLA Medical Center) // Reviewed by: Joe Ravera, MD (@pemuvm1, Director of Pediatric Emergency Medicine, UVM Medical Center, Assistant Professor of Surgery, UVM College of Medicine); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case

Paramedics bring in a 2-week-old girl weighing 3.8 kg after a 30-second-long episode of facial cyanosis, loss of tone, and decreased responsiveness. Her mother states she looked like she was struggling to breathe during that entire time. She had breastfed 2 ounces and then laid down supine for a nap about an hour prior. The baby is acting normally now according to her mother. She is comfortable, with soft and flat fontanelles, no increased work of breathing, no cardiac murmur with equal pulses in upper and lower extremities, abdomen soft with no masses, normal strength and tone, no obvious signs of trauma and no dysmorphic features. The patient’s mother anxiously asks “Is my baby going to be ok?”

Background

Clinical practice guidelines on the brief resolved unexplained event (BRUE) were introduced by the American Academy of Pediatrics (AAP) in 2016 which defined it as an event occurring in an infant younger than 12 months with one or more of the following features:¹

1) Cyanosis or pallor

2) Absent, decreased, or irregular breathing

3) Marked change in tone (hyper- or hypotonia)

4) Altered level of responsiveness

Those at lower risk for a repeat event or serious underlying condition must meet all of the following criteria:¹

• Age greater than 60 days
• Absent prematurity: gestational age ≥ 32 weeks and post-conceptual age ≥ 45 weeks
• First BRUE (no previous BRUE ever and no repeat events)
• Duration of event < 1 minute
• No CPR required by trained medical provider
• No concerning historical features (e.g. sudden death in first-degree relative)
• No concerning physical examination findings (e.g. unexplained bruising)

The BRUE Effect

BRUE did not simply replace the former term apparent life-threatening event (ALTE) – which itself had supplanted the term “near-miss sudden infant death syndrome (SIDS)” in 1986 – but offered a more precise definition of the transient and often benign event characteristics using clear criteria that help guide management.¹ Understanding the history of the nomenclature and its evolution is important as the term “life-threatening” was removed since a diagnosis of ALTE was never found to confer mortality risk.^1-4 In multiple retrospective reviews, only a minority of patients with ALTE met BRUE criteria.^2,5,6 The effect of this more standardized approach to management has translated into a significant reduction of diagnostic/invasive testing, ED length of stay, and admission rate of infants in both the 0 to 60 day and 61 to 365 day age group with no change in clinical outcome including readmissions or repeat ED visits.^7,8

BRUE Documentation Do’s and Don’ts

A BRUE is, by definition, unexplained after careful history and physical exam. For instance, in a patient with findings such as reflux (20 to 54% of patients), URI (8%), or seizure (4 to 7%), a diagnosis of BRUE should not be made and the patient be managed according to the presumed etiology.⁹ Consistent with guidelines, a thorough history and physical exam are the most important components of the patient assessment.¹ The clinician should be clear in their documentation of differentiating a patient with lower risk versus higher risk BRUE, as this will guide evaluation and management. It is critical to obtain a detailed recount of the event from the caregiver and/or transporting personnel, with description of the patient’s state immediately before, during, at the conclusion of, and after the event.⁹ Complete history-taking includes preceding or concurrent illness and thorough medical, family, social, and environmental history.⁹ A documented physical exam should note any vital sign abnormality, growth curve irregularity, altered infant responsiveness, craniofacial anomaly or dysmorphic features, respiratory impediment, abnormal auscultation findings, palpable masses, genital anomaly, complete neurologic exam (strength, sensation, tone), and skin exam (bruising, rash, swelling or any subtle signs of child maltreatment).¹ If there is any noted abnormality and/or concern for possible abuse, the event is not categorized as lower risk and requires further detailed investigation.⁹

Lower Risk BRUE

Apart from being pragmatic, fulfillment of the lower risk BRUE criteria has proven to be a reliable indicator of excellent prognosis based on patient long-term follow-up.¹⁰ These patients have decreased overall risk of adverse outcomes and do not warrant hospitalization nor broad clinical evaluation, assuming the clinician has screened for social risk factors including child abuse.⁹ Patients may undergo a screening 12-lead ECG and be observed on continuous pulse oximetry for a short (1 to 4 hour) period of time in the emergency department (ED). Current guidelines strongly recommend against obtaining any bloodwork (e.g. glucose, CBC, blood gas, blood culture, urine studies, viral respiratory tests) or imaging (e.g. chest XR, head CT).

Higher Risk BRUE

A myriad of causes from nearly every organ system may lead to presentation of a BRUE. For those that do not meet lower risk criteria, there is at this time a general lack of evidence to guide evaluation.¹¹ Therefore, the clinician, on a case-by-case basis among these patients, should consider wide differential diagnoses and pursue workup based on an index of clinical suspicion after reviewing pertinent history and clinical findings, all in the context of shared clinical decision making with the caregiver.⁹ While clinicians should err on the side of caution, routine hospitalization may not be warranted for all of the higher risk patients.^9,11 Initial evaluation and management to identify a condition with potentially serious adverse outcomes may include:¹¹

• Continuous pulse oximetry monitoring for at least 4 hours;
• Consultation with social worker (or other health care worker with similar experience and skills);
• Bedside feeding evaluation (by a feeding therapist, if available);
• Electrocardiogram to be read by a pediatric cardiologist or electrophysiologist;
• Rapid viral respiratory panel testing;
• Rapid pertussis polymerase chain reaction in endemic areas, during regional outbreaks, or in underimmunized patients;
• Complete blood count (CBC) with differential;
• Chest and/or abdominal radiographic imaging;
• Blood glucose, bicarbonate or venous blood gas, and lactate; and
• If concerned for child maltreatment, consultation with a child abuse expert, head imaging with computed tomography (CT) or MRI, and skeletal survey

If no cause is identified, a secondary tier of evaluations is performed either inpatient or outpatient and may include the following:¹¹

• Specialty consultation with a gastroenterologist, otolaryngologist, pulmonologist or sleep expert, child abuse expert, neurologist, cardiologist, and/or biochemical geneticist;
• Videofluoroscopic swallowing study (VFSS) for “silent” oropharyngeal dysphagia not seen in bedside evaluation;
• Continuous prolonged oximetry to characterize recurring events;
• Comprehensive polysomnography (PSG) to characterize and quantify central versus obstructive apnea;
• Prolonged (≥ 12–24 hours) EEG;
• Blood sodium, potassium, chloride, blood urea nitrogen, creatinine, calcium, and ammonia for metabolic disturbance;
• Upper gastrointestinal series (UGI);
• Esophageal multichannel intraluminal impedance–pH monitoring (MII-pH);
• Esophagogastroduodenoscopy with biopsy;
• Echocardiogram; and
• Urine organic acids, plasma amino acids, or plasma acylcarnitines

An individualized, family-centered multidisciplinary approach to management of the higher risk patient with BRUE is advocated. Below is a table of specific time-sensitive diagnoses arranged by organ system, which if missed, may have serious impact on patient morbidity or mortality:¹¹

Discussing a BRUE with parents

BRUE remains an imperfect label. It is less of a diagnosis and more a constellation of symptoms.¹² Parents of infants with BRUE – specifically those discharged who compose the majority – have expressed confusion, anxiety, unease, and fear around the unexplained nature BRUE, but more so the possibility of its unexpected recurrence.¹² Shared medical decision making with the family should guide evaluation, and the clinician should ensure timely follow-up with the infant’s pediatrician.⁹ In communicating with the caregiver at discharge, it is recommended that clinicians shift away focus “from what is unexplained to what is known”, addressing the benign nature of lower risk BRUE and extremely low likelihood of recurrence or serious underlying condition.^9,12 CPR training resources should also be offered. Of course, should an etiology such as reflux be identified, the patient should not be diagnosed with BRUE and the family should be counseled on “reflux precautions” including appropriately-sized feeds (e.g. avoid overfeeding), proper burping, and keeping the child upright immediately after a feed, as well as the commonality of gastroesophageal reflux in infants.

Case Continued

After a thorough history and exam, no apparent etiology of the BRUE is discovered. The neonate is appropriately categorized as a higher risk patient (based on age <60 days) and the decision is made to obtain basic labs, an ECG, and chest XR in the ED with admission to the general pediatric inpatient team. No repeat events are noted in the ED. Together with shared medical decision making involving the caregiver, the ED clinician discusses the lack of abnormal findings on initial workup and the importance of inpatient monitoring.

Pearls and Pitfalls

• Since 2016, a defined BRUE criteria among infants has had a profound impact on reducing invasive diagnostic testing, ED length of stay, and admission rate without negatively impacting any clinical outcomes.
• A detailed and complete clinical history and physical exam remain the most important aspects of early evaluation. A BRUE should be diagnosed only if there remains no explanation for the event. If there are any concerning features discovered, the patient is not lower risk and warrants further workup.
• Infants with lower risk BRUE exhibit a transient and benign event that has an extremely low risk of recurrence and/or underlying serious condition. In the ED, these patients may undergo a screening 12-lead ECG and/or observation of 1 to 4 hours, but no other interventions are warranted.
• Clinical guidelines among higher risk BRUE remain less clear, and thus the ED clinician should consider wide differential diagnoses, pursuing an initial workup based on clinical index of suspicion while erring on the side of caution.
• Whether lower or higher risk criteria are met, it is essential the clinician clearly communicate their findings and appropriately counsel caregivers, while remaining empathic to their concerns.

References/Further Reading

1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief unresolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants. Pediatrics. 2016;137(5):e20160590.
2. Gerber NL, Fawcett KJ, Weber EG, et al. Brief resolved unexplained event: not just a new name for apparent life-threatening event. Pediatric Emergency Care. 2020. 10.1097/pec.0000000000002069
3. Mittal MK, Sun G, Baren JM. A clinical decision rule to identify infants with apparent life-threatening event who can be safely discharged from the emergency department. Pediatric Emergency Care. 2012;28(7):599–605.
4. Kaji AH, Claudius I, Santillanes G, et al. Apparent life-threatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital. Annals of Emergency Medicine. 2013;61(4):379–387.
5. Ramgopal S, Soung J, Pitetti R. Brief resolved unexplained events: analysis of an apparent life threatening event database. Academic Pediatrics. 2019;19(8):963-968.
6. Meyer JS, Stensland EG, Murzycki J, et al. Retrospective application of BRUE criteria to patients presenting with ALTE. Hospital Pediatrics. 2018;8:740–745.
7. Ramgopal S, Noorbakhsh K, Callaway C, et al. Changes in the management of children with brief resolved unexplained events (BRUEs). Pediatrics. 2019;144(4):e20190375.
8. Sethi A, Baxi K, Cheng D, et al. Impact of guidelines regarding brief resolved unexplained events on care of patients in a pediatric emergency department. Pediatric Emergency Care. 2020. 10.1097/PEC.0000000000002081.
9. Behnam-Terneus M, Clemente M. SIDS, BRUE, and Safe Sleep Guidelines. Pediatrics in Review. 2019;40(9):443-455.
10. Ari A, Atias Y, Amir J. Long-term follow-up of infants after a brief resolved unexplained event-related hospitalization. Pediatric Emergency Care. 2019;35(11):765-768.
11. Merritt JL, Quinonez RA, Bonkowsky JL, et al. A framework for evaluation of the higher-risk infant after a brief resolved unexplained event. Pediatrics. 2019;144(2):e20184101.
12. DeLaroche AM, Mittal MK. But what was “it”? Talking to parents about BRUE. Hospital Pediatrics. 2019;9(7):566-568.

The post Small Talk – Finding the Right Clues to Manage BRUEs appeared first on emDOCs.net - Emergency Medicine Education.

Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover severe asthma and asthma mimics.

Severe Asthma and Asthma Mimics

Approach

The approach for asthma and asthma mimics is to first assess for life threats, provide emergent interventions, and then obtain history and focused exam. Rapid treatment with bronchodilator and corticosteroids is required.  Non-Invasive Positive Pressure Ventilation (NIPPV) should be considered.

Once treatment and initial stabilization have been completed, focused history and exam should be conducted to evaluate for mimics. As discussed, there are many causes of wheezing, and these conditions must be considered to prevent anchoring bias. Red flags for other conditions include absence of asthma history, prior history of mild asthma, or poor response to therapy.

Treatment:

– Assess the ABCs.

– Administer oxygen to relieve hypoxemia. If severe exacerbation present, provide IV fluids (address secondary losses).

-Deliver a short acting beta-agonist (SABA) with ipratropium (anticholinergic).

-Give systemic corticosteroids to decrease airway inflammation. Options include prednisone, methylprednisolone, and dexamethasone.

-If patients fail to respond to inhaled therapies and steroids, next steps include parenteral beta agonist, magnesium, heliox, ketamine, and/or NIPPV.

-Epinephrine is a non-selective beta agonist that causes bronchodilation, vasoconstriction, increased cardiac contractility and increased heart rate. Dose for IM is 300-500 mcg, while IV is recommended in hypotensive patients or those who fail to respond to IM dosing. Dose is 5mcg IV and titrate to effect.

-Magnesium is effective in those with severe exacerbation by relaxing bronchial smooth muscle. In adults, start with 2g, which can be repeated twice.

-Ketamine may have bronchodilator properties. It can also assist with delayed sequence intubation.

-Heliox is an option; it can improve laminar flow of inhaled has which may allow better airflow through the constricted airways; allows better gas exchange and transport of medications to flow down to distal airways and alveoli. Evidence suggests limited utility, and if hypoxic, an adequate amount of FiO₂ may not be reached.

-Non-invasive positive pressure ventilation should be considered for all patients who display: moderate to severe dyspnea or respiratory distress, hypercapnic acidosis, a respiratory rate > 25/min, accessory muscle use, or paradoxical breathing.  Bilevel settings are recommended to improve ventilation.

-Intubation is an inherently dangerous intervention in asthma because it does not fix the underlying problem (bronchoconstriction) and can cause dynamic hyperinflation, and rapid acidosis if respiration is not matched during RSI or post-intubation. The decision to intubate is based on a number of factors including the patients overall appearance, work of breathing, perceived ability to maintain their effort of breathing, mental status etc. Before intuition, preoxygenate and rehydrate with IV fluids. Ketamine 1-2 mg/kg IV can be used for induction. A paralytic such as rocuronium offers the advantage of longer paralysis which avoids vent asynchrony early in management.

-Mechanical ventilation: Must ensure that the patient has an adequate time to fully expire the delivered breath and avoid hyperinflation. Permissive hypercapnia involves decreasing the RR and allowing PaCO₂ to rise to supranormal levels, which avoids breath stacking. Ensure post-intubation analgesia and sedation, which will assist with vent synchrony.

The post emDOCs Podcast – Episode 36: Severe Asthma and Mimics appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Gabrielle Leonard, MD (EM Resident Physician, Vanderbilt University Medical Center) and Aaron Lacy, MD (@AaronLacyMD, EM Attending Physician, Vanderbilt University Medical Center) // Reviewed by: Alex Koyfman, MD (@EMHighA); Brit Long, MD (@long_brit)

Case:

A 70-year-old-female is brought to the ED for altered mental status. The patient has had decreased PO intake over the last 3-4 days and fever and confusion that worsened in the last 24 hours. Her past medical history is significant for hypertension and coronary artery disease.

Vitals are notable for a blood pressure of 82/44, HR of 118, temperature of 39.1C, RR of 14, and 96% on RA. The patient appears confused and dehydrated. Evaluation reveals a WBC of 24,000, lactate of 6.0, K of 5.8, and UTI on urinalysis. You have identified that the patient is in septic shock and requires fluid resuscitation.

What fluid will you use to resuscitate your patient? What evidence will support that decision? Does the patients’ elevated lactic acid and potassium play a role in your choice of fluid?

Background

Fluids are a standard treatment for various disease processes that present to the ED. Thought to increase intravascular and intracellular volume, fluids are critical in treatment of multiple disease processes that cause dehydration and loss of circulating fluid, leading to hypoperfusion and hypotension.¹  Historically, normal saline (NS) has been the fluid of choice for resuscitation with more than 200 million liters given annually.² There has been recent debate about which fluids are preferable based on composition, and multiple clinical trials have evaluated whether balanced crystalloids, such as lactated ringers (LR) or plasma-lyte, have less harmful associated reactions and are superior in treatment of various illnesses.

Fluid Composition

Table 1. Fluid composition of human plasma compared to 0.9% saline, LR, and plasma-lyte. Used with permission from Self et al.³

NS 0.9% has markedly more sodium and chloride than human plasma.^3,4 There is concern the high concentration of chloride in NS may lead to hyperchloremic metabolic acidosis, delaying recovery in some disease processes and contributing to worsening renal function during treatment.^{2, 5} It is theorized that elevated chloride causes renal vasoconstriction and may decrease renal perfusion via this mechanism.⁵ Balanced crystalloids such as LR and plasma-lyte more closely resemble the physiologic makeup of human plasma.^2,6 Decreasing risk of acidosis when compared to NS, as well as similar physiologic makeup more similar to human plasma, have led to studies investigating adverse reactions and patient outcomes in different presenting illnesses.

Two randomized clinical trials conducted in 2016 at a single center large academic hospital sought to compare NS and balanced crystalloids in both non-critically ill (SALT-ED trial) and critically ill (SMART) patients.^2,5 The SALT-ED trial randomized patients to either saline or balanced crystalloids and monitored the course of their hospitalization (if admitted to a unit outside of the intensive care areas). This trial evaluated hospital-free days as well as major adverse kidney events within 30 days (composite of death from any cause, new renal replacement therapy, persistent renal dysfunction with creatinine >200% from baseline) and found that while the primary outcome of hospital-free days did not have a significant difference between NS and crystalloid groups, there was a significantly lower rate of adverse major kidney events in 30 days (4.7% vs. 5.6%). Additionally, patients in the balanced crystalloid arm showed lower chloride and higher bicarbonate concentrations persisting for several days into hospitalization. Patients with underlying renal dysfunction or hypochloremia at presentation appeared to have the largest benefit from the crystalloid therapy by having reduced incidents of major adverse kidney events in 30 days.² The SMART trial randomized patients to receive NS or balanced crystalloids and monitored the course of their hospitalization if admitted to an intensive care unit, with the majority of patients continuing to receive the fluids they were initially randomized to in the ED. This trial showed a significant decrease in major adverse kidney events within 30 days for balanced crystalloids vs NS (14.3%% vs 15.4%, p=0.04). There was also an insignificant decrease in in-hospital mortality at 30 days for the balanced crystalloid vs. NS group (10.3% vs 11.1%, p=0.06). Similarly, the balanced crystalloid group showed lower incidence of hyperchloremia defined as Cl > 110 mmol/L (24.5% VS 35.6%) and lower incidence of plasma bicarbonate concentration < 20 mmol/L (35.2% vs. 42.1%) when compared to NS. Importantly, patients with a diagnosis of sepsis had lower incidence of 30-day mortality in the balanced crystalloid vs. NS groups (25.2% vs 29.4%, p=0.02). This is also important because fluids are a key treatment in sepsis and volume of fluid resuscitation is often higher. Based on these results, 1 patient in every 94 admitted to the ICU and treated with balanced crystalloid instead of NS may prevent the need for new renal replacement therapy, persistent renal dysfunction, or death when compared to NS.⁵

These two RCTs were groundbreaking and practice changing, leading many emergency departments and intensive care units to transition to more regularly using balanced crystalloids over NS. While conclusions of the trials often point to LR being superior to NS, it can also be reassuring that NS was given to so many patients without substantial harm.

More recently in August of 2021 a robust RCT, BaSICS was published. This was a double-blind, randomized clinical trial in 75 ICUs in Brazil with over 10,000 patients participating. The two intervention arms were looking at both fluid type (plasma-lyte vs NS) and fluid infusion speed (333ml/hr and 999ml/hr).  Of note, LR was not the balanced fluid evaluated in this study. Ultimately, 90-day mortality rate was 26.4% in the plasma-lyte group and 27.2% in the NS group (aHR 0.97, CI 0.90-1.05, P=.47),⁷ and 26.6% in the slower infusion rate vs 27.0% in the faster infusion rate group (aHR, 1.03; 95% CI, 0.96-1.11; P=.46).⁸ A secondary outcome from the BaSICS trial showed no significant difference in need for renal replacement therapy or doubled creatinine in balanced crystalloid group (27.8%) versus NS group (28.9%) (95% CI, 0.86-1.04). This study also sought to answer another important question about the volume and rate or volume given to patients during resuscitation. The idea of “you have to swell to get well” is no longer the standard of care, and permissive hypotension is preferred in several disease states.⁹ Currently a RCT, CLOVERS, comparing early transition from fluids to vasopressors in patients with septic shock is underway and set to finish sometime in 2021, which will add further data in this domain.¹⁰

Given the recent publication of BaSICS it becomes clear that there is not one fluid that is the end all, and certain populations and diseases will benefit from selected fluid choice.  We will discuss myths surrounding LR along with specific disease processes for choosing balanced crystalloids versus NS.

Pearls:  Two RCTs show that both non-critically ill and critically ill patients who received balanced crystalloids were less likely to have renal injury leading to need for renal replacement therapy or to have persistent renal dysfunction, but an additional large ICU based RCT did not show statistical difference in balanced crystalloid versus NS. Fluid therapy should be targeted to specific patient populations and presenting disease. 

One of the most significant issues from these studies is that the amount of IV fluid administered is likely more important that the specific type of fluid (i.e., worse outcomes with excess IV fluid).

Myths surrounding lactated ringers 

Despite these studies, there are still several concerns regarding the use of LR in the ED. Which of these concerns are myths, truths, or something in between?

Hyperkalemia

Myth – “Lactated Ringers should not be used in hyperkalemia because it contains potassium and may make the problem worse.”

Of all electrolyte abnormalities, hyperkalemia is the most likely to quickly kill a patient. Major causes of hyperkalemia include renal failure, acidosis, drug-effect (NSAIDs, Ace-I, TMP-SMX), rhabdomyolysis, or cell death.¹¹ If hyperkalemia is suspected, the K level should be repeated and an EKG obtained immediately.  The question then arises, knowing that LR and plasma-lyte contain a higher concentration of potassium (4-5mEq/L) when compared to NS (0 mEq/L), should these balanced crystalloids be avoided in patients with known or suspected hyperkalemia?

The potassium composition of LR is physiologically closest to human serum and is typically slightly lower.³ Due to this, there is negligible effect on overall serum potassium level as a result of LR infusion. Potassium’s volume of distribution is greater in extracellular fluid causing little to no change on the overall serum potassium level. It would take a significant amount of fluid to have any effect on raising overall serum potassium level since the potassium equilibrates between intracellular and extracellular fluid spaces. Additionally, the hyperchloremic metabolic acidosis which can result from NS infusion will increase cellular shifting and worsen extracellular potassium levels when compared to lactated ringers which has no effect on the K+/H+ gradient. In fact, the alkalinization that occurs as a result of lactated ringer infusion due to the 28 mEq/L of bicarbonate may even further drive potassium into the cell, lowering the overall serum potassium level.¹²

One subgroup analysis from the SALT-ED trial evaluated critically ill adults with hyperkalemia who received balanced crystalloids LR or plasma-lyte vs. NS. Overall, eight (8.5%) of the patients in the balanced crystalloid group vs. 13 (14.0%) patients in the NS group developed severe hyperkalemia (p=0.24). While this is not statistically significant, it does show that the higher level of potassium that is administered from LR or plasma-lyte (4-5) vs. NS (0) is closer to physiologic plasma and does not lead to worsening hyperkalemia.¹³

Pearl: LR is a safe fluid to use in resuscitation of patients with elevated potassium levels. The potassium/hydrogen shifts that occur as result of the acidic environment from normal saline infusion may worsen serum potassium levels.

Lactic Acidosis

Myth – “Lactated Ringers causes lactic acidosis, and therefore should be avoided.”

Lactic acidosis is a result of failed oxidative metabolism, leading to an anion-gap metabolic acidosis. This can be secondary to decreased metabolism of naturally generated lactate in the body (such as in liver disease) or increased production of lactate when there is decreased oxygen available for aerobic metabolism. The most common etiologies of lactic acidosis in the ED are from sepsis, trauma, and dehydration.¹⁴ While less common, there can also be iatrogenic causes of type B lactic acidosis secondary to beta agonist administration, such as epinephrine¹⁵ or albuterol.¹⁶

There is speculation that the lactate concentration in LR (28 mEq/L) compared to NS (0 mEq/L) and human plasma (1-2 mEq/L) may worsen lactic acidosis. In reality, this lactate is in the form of sodium lactate which our bodies metabolize to products that prevent cellular death. It is not the same lactate that is generated during anaerobic metabolism, which causes metabolic acidosis.⁶

One double-blind RCT evaluated the change in lactate between LR and NS groups while also looking at the overall change in pH, bicarbonate, sodium, and chloride levels. This study found that after an infusion of 30mL/kg IV LR, lactate increased by 0.93 mmol/L compared to 0.37 mmol/L in the NS group (p-0.2), but the NS group saw a larger decline in overall pH (0.06 vs. 0.03) and bicarbonate level (2.35 vs. 0.36).¹⁴ In an additional RCT published in 1997, 24 healthy adults received 1L infusions of LR, NS, dextrose, or D5W and showed no difference in lactate levels post-infusion.¹⁷

It is theorized that the lactate infused in the LR group may be metabolized under ischemic conditions and decrease overall cell death and is less likely to worsen an acidosis when compared to the hyperchloremic acidosis that results from NS.⁶

Pearl: Though LR contains sodium lactate, this is generally metabolized by the body and does not contribute to worsening lactic acidosis. In fact, the acidosis associated with NS likely has more clinically harmful effects.

Medication Reactions

Some Truth – “Because lactated ringers can have calcium precipitation with so many medications, it is easier and safer to use normal saline.”

Which fluids can be administered concomitantly with medications such as antibiotics or blood transfusions? The FDA warns against using LR with ceftriaxone in infants <28 days due to the risk of ceftriaxone-calcium salt precipitation which has previously been linked to death.¹⁸ In patients older than 28 days, a separate infusion line must be used for calcium-containing solutions such as LR and ceftriaxone to avoid precipitation. The precipitates were noted as early as 1999 when infusions of ceftriaxone were mixed with varying doses of LR in the IV lines. It was postulated that the sodium concentration within ceftriaxone contributes to the formation of calcium precipitates and therefore the mixture of these solutions in the same line should be avoided.¹⁹ It is safe to use LR in fluid resuscitation when infused through a separate line.

An additional study evaluated compatibility of LR with 94 medications by in vitro visual observation, particle counting testing, and light obscuration particle count testing. Eight drugs were considered incompatible with lactated ringers including ciprofloxacin, cyclosporine, diazepam, ketamine, lorazepam, nitroglycerin, phenytoin, and propofol and are recommended against administering through the same IV line as lactated ringers.²⁰

Two separate studies were performed to evaluate the incidence of clot formation when LR was transfused with pRBCs and Whole Blood. In both studies, there was on statistically significant difference in clot formation when NS or LR was infused or used as a diluent in emergent transfusions.^{21, 22} There is theoretical risk of coagulation when LR is administered together with preserved blood (with citrate anticoagulant) via the same infusion set. In order to avoid this, a separate line should be considered or alternative fluid should be chosen if limited access is available.⁶

Pearl: Though theoretical risk of clotting exists, LR can be administered simultaneously in patients >28 days with ceftriaxone, blood products and other calcium-containing medications. If possible, a separate line should be used to avoid potential precipitation.

Specific Indications

Diabetic Ketoacidosis (DKA)

In patients with DKA, the body responds to low insulin levels by burning fatty acids and producing ketone bodies, leading to an anion-gap metabolic acidosis. Often overall body potassium is low; however, it may appear to be falsely elevated due to hydrogen ions shifting intracellularly and potassium moving extracellularly. Fluids, in addition to insulin and potassium, are the main treatment for this disease process.¹

One subgroup analysis from the SALT-ED and SMART trial compared patients with a clinical diagnosis of DKA to look at time to resolution (glucose <200 mg/dL and 2 of the following: bicarb > 15, venous pH >7.3, anion gap < or equal to 12) as well as time to discontinuation of insulin infusion. Given the sheer volume of fluid required to treat this disease process, (on average, 4.5 liters) differences in fluid composition can be a key factor in recovery. This study found a significant decrease in both time to resolution of DKA (13 hours vs 16.9 hours) in the balanced crystalloid group as well as time to insulin discontinuation (9.8 hours vs 13.4 hours).¹ This equates to an absolute reduction of 4 hours and relative reduction of 20-30% in time to DKA resolution and discontinuation of insulin infusion, possibly decreasing overall hospital stay and associated morbidity. This is hypothesized to be due to the concentrations of sodium lactate in LR and acetate in plasma-lyte which metabolize into bicarbonate helping to close the anion gap metabolic acidosis.²³ Additionally, fewer patients in the balanced crystalloid group exhibited hypokalemia (K<3) compared with the NS group. However, this study was in contrast to prior work on the subject which failed to show any significant difference.^{3, 24-27}

Dehydration

In patients with dehydration (defined as dry mucous membranes, SBP <90, HR >100 or PO intolerance), one randomized controlled trial comparing normal saline balanced crystalloids showed significantly lower pH levels in patients who received NS (7.40 7.37 7.36) as well as a drop in bicarbonate levels (23.1, 22.2, 21.5) compared to an increase in the plasma-lyte group (23.4, 23.9, 24.4).²³ A similar study conducted in pediatric patients with acute diarrhea and severe dehydration showed no significant difference in pH between NS and LR, but the LR group required less fluids (310 vs 530mL) and had a shorter median hospital stay (38 vs 51).²⁸

Pancreatitis

One RCT compared LR with NS in patients with acute pancreatitis and found a significant reduction in SIRS after 24 hours in the LR group (84% vs 0%, p=0.035). There was also a reduction in CRP in the LR group (51.5 vs 104, p=0.02), a marker of systemic inflammation.²⁹ An additional study by Lee et al showed that there was a significantly shorter hospital length of stay and fewer ICU admissions in patients diagnosed with acute pancreatitis who were treated with aggressive fluid resuscitation via LR compared to NS.³⁰ Though the exact mechanism is unknown, there are animal studies showing decrease in enzymes involved in pancreatitis such as zymogen.³¹

Pearl: Several studies balanced crystalloids are associated with improved outcomes in patients with DKA, dehydration, and pancreatitis.

Considerations for Alternative Fluid to LR

Traumatic Brain Injury

It is theorized that due to hyperosmolarity of the solution and ability to decrease cerebral edema, NS is the preferred resuscitation fluid in patients with Traumatic Brain Injuries (TBI) when compared with LR. Additionally, LR is thought to increase neutrophil and inflammatory responses. One study comparing outcomes of patients with TBI who were treated with LR vs NS prior to hospital arrival found LR was associated with higher 30-day mortality than NS (HR = 1.78, CI 1.04 – 3.04).³² Subgroup analysis on this topic with the best RCT to date, BaSICS, showed that a balanced crystalloid (plasma-lyte) had higher 90-day mortality rate (31.3%) versus NS (21.1%) (HR 1.48, 95% CI 1.03-2.12, P=0.02).⁷

Hyponatremia

LR contains 130 mEq/L Na compared to 135-145mEq/L Na in plasma.¹ Because of this, there is concern that resuscitation with LR may worsen or lead to hyponatremia. There is limited data around LR causing hyponatremia or the use of LR in treating acute hypovolemic hyponatremia in the Emergency Department setting. One study evaluated post-operative hyponatremia and cited quantity of fluid resuscitation as the cause of hyponatremia versus use of LR itself. The theory is that increased extracellular volume leads to ADH release and worsens hyponatremia.³³ There is opportunity for further investigation into the use of LR for hypovolemic hyponatremia as well as the potential for LR to cause hyponatremia after ED resuscitation.

Burns

In acute burns, there is concern for both dehydration and electrolyte imbalances such as hyponatremia and hypoglycemia secondary to evaporative losses and changes in cellular permeability. One RCT evaluated the use of LR alone in burn resuscitation when compared to use of LR and dextrose NS in an attempt to correct electrolyte abnormalities. This study showed that due to low sodium (130mEq/L) and potassium (4mEq/L) levels in LR when compared to human plasma, dextrose containing NS should be used as an adjunct to assist in replenishing electrolytes. Burn patients treated with LR and DNS had statistically significant less evidence of hyponatremia and hypoglycemia.³⁴

Pearl: In patients presenting with hyponatremia and acute burns, LR is not necessarily the sole fluid choice for resuscitation, and NS is preferred in patients with concern for TBI.

Case Conclusion:

The 70-year-old female is febrile with signs of dehydration and hypotension in the setting of sepsis due to a urinary tract infection. She also has a lactic acidosis and hyperkalemia on her initial workup. Based on the data above, lactated ringers are a safe and appropriate approach to fluid resuscitation in combination with antibiotics. Broad spectrum antibiotics were started and the patient was admitted to the medical intensive care unit for further workup and care.

Pearls:

• LR composition is more similar to human plasma than NS.
• LR is preferred to NS in select ED presentations, such as DKA.
• LR will not worsen hyperkalemia and the acidosis from NS may in fact be more detrimental.
• LR does contain sodium lactate but will not contribute to clinically significant worsening lactic acidosis.
• NS is preferred to plasma-lyte in patients with TBI.
• Consider NS when mixed with certain medications such as ceftriaxone or blood transfusions to avoid precipitation when only a single IV access site it available.

References:

1.   Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, Coston TD, Felbinger M, Flemmons LN, Hellervik SM, Lindsell CJ, Liu D, McCoin NS, Niswender KD, Slovis CM, Stollings JL, Wang L, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open. 2020 Nov 2;3(11):e2024596.
2.   Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828.
3.   Self WH, Semler MW, Wanderer JP, et al. Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017;18(1):178.
4.   Tonog P, Lakhkar AD. Normal Saline. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.
5.   Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839.
6.   Singh S, Kerndt CC, Davis D. Ringer’s Lactate. [Updated 2021 Apr 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-
7. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA.Published online August 10, 2021.
8. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA.Published online August 10, 2021
9. Frazee E, Kashani K: Fluid Management for Critically Ill Patients: A Review of the Current State of Fluid Therapy in the Intensive Care Unit. Kidney Dis 2016;2:64-71.
10. National Library of Medicine (U.S). (2018, February – present). Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS). Identifier NCT03434028. https://clinicaltrials.gov/ct2/show/NCT03434028
11.   Simon LV, Hashmi MF, Farrell MW. Hyperkalemia. [Updated 2021 Feb 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-
12. 12.   Farkas, J. Myth-busting. Lactated ringers is safe in hyperkalemia, and superior to normal saline. Online Publication. www.EMcrit.org
13.   Toporek AH, Semler MW, Self WH, Bernard GR, Wang L, Siew ED, Stollings JL, Wanderer JP, Rice TW, Casey JD; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults with Hyperkalemia or Acute Kidney Injury: Secondary Analysis of a Clinical Trial. Am J Respir Crit Care Med.2021 May 15;203(10):1322-1325.
14. Zitek T, Skaggs ZD, Rahbar A, Patel J, Khan M. Does Intravenous Lactated Ringer’s Solution Raise Serum Lactate? J Emerg Med. 2018 Sep;55(3):313-318.
15. Totaro, Richard J. MBBS, FRACP; Raper, Raymond F. MBBS, BA, MD, FRACP Epinephrine-induced lactic acidosis following cardiopulmonary bypass, Critical Care Medicine: October 1997 – Volume 25 – Issue 10 – p 1693-1699
16. Sharif Z, Al-Alawi M. Beware of beta! A case of salbutamol-induced lactic acidosis in severe asthma. BMJ Case Rep. 2018 Jun 17;2018:bcr2017224090.
17. Didwania A et al. Effect of Intravenous Lactated Ringer’s Solution Infusion on the Circulating Lactate Concentration: Part 3. Results of a Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Crit Care Med. 1997 Nov;25(11):1851-4.
18. Gin A, Walker S. Notice to Hospitals Regarding Ceftriaxone-Calcium Incompatibility: What’s a Clinician to Do?. Can J Hosp Pharm. 2009;62(2):157-158.
19. Burkiewicz JS. Incompatibility of ceftriaxone sodium with lactated Ringer’s injection. Am J Health Syst Pharm. 1999 Feb 15;56(4):384.
20. Vallée M, Barthélémy I, Friciu M, et al. Compatibility of Lactated Ringer’s Injection With 94 Selected Intravenous Drugs During Simulated Y-site Administration. Hospital Pharmacy. 2021;56(4):228-234.
21. Lorenzo M, Davis JW, Negin S, Kaups K, Parks S, Brubaker D, Tyroch A. Can Ringer’s lactate be used safely with blood transfusions? Am J Surg. 1998 Apr;175(4):308-10.
22. Cull DL, Lally KP, Murphy KD. Compatibility of packed erythrocytes and Ringer’s lactate solution. Surg Gynecol Obstet. 1991 Jul;173(1):9-12.
23. Hasman H, Cinar O, Uzun A, Cevik E, Jay L, Comert B. A randomized clinical trial comparing the effect of rapidly infused crystalloids on acid-base status in dehydrated patients in the emergency department. Int J Med Sci. 2012;9(1):59-64.
24. Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med. 2011 Jul;29(6):670-4.
25. Van Zyl DG, Rheeder P, Delport E. Fluid management in diabetic-acidosis–Ringer’s lactate versus normal saline: a randomized controlled trial. QJM. 2012 Apr;105(4):337-43.
26. Yung, M., Letton, G. and Keeley, S. (2017), Controlled trial of Hartmann’s solution versus 0.9% saline for diabetic ketoacidosis. J Paediatr Child Health. 53: 12-17.
27. Jayashree M, Williams V, Iyer R. Fluid Therapy For Pediatric Patients With Diabetic Ketoacidosis: Current Perspectives. Diabetes Metab Syndr Obes. 2019 Nov 12;12:2355-2361.
28. Mahajan V, Sajan SS, Sharma A, Kaur J. Ringers lactate vs Normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial. Indian Pediatr. 2012 Dec;49(12):963-8.
29. Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011 Aug;9(8):710-717.e1.
30. Lee A, Ko C, Buitrago C, Hiramoto B, Hilson L, Buxbaum J; NS-LR Study Group. Lactated Ringers vs Normal Saline Resuscitation for Mild Acute Pancreatitis: A Randomized Trial. Gastroenterology. 2021 Feb;160(3):955-957.e4.
31. Khatua B, Yaron JR, El-Kurdi B, Kostenko S, Papachristou GI, Singh VP. Ringer’s Lactate Prevents Early Organ Failure by Providing Extracellular Calcium. J Clin Med. 2020;9(1):263. Published 2020 Jan 18. doi:10.3390/jcm9010263
32. Rowell SE, Fair KA, Barbosa RR, Watters JM, Bulger EM, Holcomb JB, Cohen MJ, Rahbar MH, Fox EE, Schreiber MA. The Impact of Pre-Hospital Administration of Lactated Ringer’s Solution versus Normal Saline in Patients with Traumatic Brain Injury. J Neurotrauma. 2016 Jun 1;33(11):1054-9.
33. Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML. Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of desalination. Ann Intern Med. 1997 Jan 1;126(1):20-5.
34. Bedi MK, Sarabahi S, Agrawal K. New fluid therapy protocol in acute burn from a tertiary burn care centre. Burns. 2019 Mar;45(2):335-340. doi: 10.1016/j.burns.2018.03.011

The post Lactated Ringers versus Normal Saline: Myths and Pearls in the ED appeared first on emDOCs.net - Emergency Medicine Education.

Author: Andrea Nillas, MD (EM Resident Physician, UTSW/Parkland Hospital) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

Answer: Nephrotic syndrome

Background:

-Epidemiology

• Annual incidence in adults is 3 per 100,000 individuals [1]
• Majority of causes (90%) are primary (idiopathic) while secondary causes are rarer [2]
• Primary causes:
  • Minimal change disease (MCD) – most common in children [3]
  • Membranous nephropathy – most common cause in Caucasian populations
    • Generally favorable prognosis where 1/3 are benign with high remission rate, 1/3 have chronic proteinuria/edema without renal dysfunction, and 1/3 progress to ESRD within 10yrs [1]
  • Focal segmental glomerulosclerosis (FSGS) – most common cause in African Americans
    • Tend to have poorer prognosis with degree of proteinuria being a significant prognostic factor [1]
• Secondary causes:

-Nephrotic syndrome is classically characterized by:

• Heavy proteinuria (urine protein >3-3.5g in 24hrs)
• Hypoalbuminemia (serum Albumin <2.5g/dL)
• Hyperlipidemia (serum cholesterol >200mg/dL)
• Edema [2]
• *Hyperlipidemia may not always be present and is not required for diagnosis [1,3]

Pathophysiology:

• Permeability of the renal glomerulus is increased when podocytes in the glomerular membrane are damaged by immune dysfunction or systemic disease
  • Proteinuria and hypoproteinemia – diagnostic hallmarks of nephrotic syndrome
    • Low intravascular oncotic pressure + Sodium and water retention leads to systemic edema
    • Reactive hepatic lipoprotein synthesis and decreased lipid catabolism leads to hyperlipidemia

• Renin-angiotensin-aldosterone system (RAAS) is stimulated by fluid shifts to extracellular space and intravascular volume depletion
  • Increased distal sodium absorption, worsening cycle and hypertension

• Thrombogenesis- multifactorial; venous and arterial
  • Increased platelet aggregation
  • Impaired fibrinolysis – fibrinogen levels are increased and plasminogen is decreased
  • Loss of coagulation factors (antithrombin III, protein C) in urine [4]

Clinical Presentation:

• Edema is the most common complaint [1]
  • Anasarca = significant peripheral edema, ascites, genitourinary and periorbital edema
• Respiratory- shortness of breath, orthopnea or cough could suggest pleural effusion or pulmonary edema
• Gastrointestinal- abdominal fullness, nausea/vomiting may result from ascites or bowel edema
  • Fever raises suspicion for spontaneous bacterial peritonitis (SBP)
• Foamy/frothy urine
• Hypertension – presence varies with underlying etiology (e.g. not common in minimal change disease)

Complications:

• Infections- loss of complement and antibodies in urine, in addition to steroid therapy leads to relative immunocompromised state [2,3]
• Thromboembolic risk is increased by up to 44%
  • Risk is greatest in the first 3 months, but remains for over 5 years
  • Serum albumin <2.5g/dL increases risk by 3-fold [5]
• Acute kidney injury
• Malnutrition

Evaluation:

• Careful history including medication review and family history may suggest underlying systemic diseases [2]
• Laboratory analysis
  • CBC- elevated Hgb may suggest hemoconcentration while anemia may indicate chronic kidney disease or secondary cause
  • CMP- assess albumin, electrolytes, renal and liver function
    • Hyponatremia may be secondary to hypertriglyceridemia
  • Coagulation studies
  • Lipid panel
  • Urinalysis
    • Nephrotic syndrome criteria = proteinuria >3.5g in 24hrs OR
    • Spot urine protein to creatinine ratio > 3-3.5
  • Serum complement (C3, C4)
  • ANA, anti-dsDNA Ab
  • Hepatitis panel
• Imaging- usually not indicated unless there is concern for thrombotic event or pleural effusion
  • CXR for pulmonary edema vs pleural effusion
  • Duplex ultrasound for deep vein thrombosis (DVT)
  • Renal US evaluating for renal vein thrombosis if hematuria and/or flank pain present
  • CT chest angiogram if clinically concerned about PE
  • MRI brain or venogram for stroke or cerebral venous thrombosis, respectively, if headache and/or neurologic deficit present

Differential diagnoses: 

• Congestive heart failure
• Hepatic failure
• Hypothyroidism
• Anaphylaxis
• DVT
• Cellulitis
• Venous insufficiency
• Lymphedema

Management:

–Steroids are the mainstay of treatment

• Prednisone 2mg/kg/d, max 60mg/d [2]
  • Duration varies, but may continue for weeks to months
  • If patient with steroid responsive disease presents in relapse, steroids may be restarted in the ED in consultation with nephrology
  • Steroid-dependent or resistant disease necessitates nephrology consult for initiation of treatment plan, as this may entail second-line therapy [3]
• Second-line options for refractory disease include cyclosporine, cyclophosphamide, mycophenolate, tacrolimus, and rituximab
• Minimal change disease and mesangial proliferative nephritis are usually steroid responsive
• Membranous nephropathy may be steroid responsive or resistant
• Focal segmental sclerosis is usually resistant

–Diuresis – treatment for edema if euvolemic or hypervolemic

• Oral furosemide 1-2 mg/kg/d, adding spironolactone 2-4 mg/kg/d will prevent hypokalemia if prolonged use of furosemide > 7 days
  • Maximize furosemide to 4mg/kg/d if refractory to above combination
  • Can then add Hydrochlorothiazide PO 1-2mg/kg/d or Metolazone 0.1-0.3mg/kg/d
• If failed PO treatment, initiate IV furosemide 1-3 mg/kg bolus or infusion at 0.1-1 mg/kg/h
  • Can add 20% albumin 0.5-1g/kg over 2-4hr IV followed by IV furosemide if severe hypoalbuminemia (albumin <1.5g/dL)
    • Ensure adequate urine output prior to albumin administration to avoid worsened hypertension resulting in pulmonary edema [2]

–Fluids– initiate resuscitation with isotonic fluid for hypovolemic or hypotensive patients regardless of edema severity as these patients are intra-vascularly depleted [5]

–Anticoagulation– despite risk of thrombosis, the benefit of routine prophylactic anticoagulation is unclear due to limited data available and lack of randomized control trials

• No guidelines exist on indications or duration of treatment [1]
• Decision should be on a case-by-case basis

–Antihypertensives– RAS inhibitors (ACEIs and ARBs) are indicated for persistent hypertension despite control of edema or decline in steroid use, and has been shown to reduce proteinuria [6]

Disposition:

-Admit if evidence of the following [3]:

• Severe edema and anasarca
• Pulmonary effusions or respiratory distress
• Infection or thrombotic complications

-Discharge with nephrology follow up for mild to moderate edema

• Recommend low salt diet to prevent worsening edema

Key points:

• Proteinuria and hypoalbuminemia are the hallmarks for nephrotic syndrome
• Nephrotic syndrome patients are at increased risk of infection and thrombotic events
• Mild disease will need nephrology follow up while severe disease warrants IV diuresis and admission

From Dr. Katy Hanson at Hanson’s Anatomy:

Further FOAMed Reading:

https://pedemmorsels.com/nephrotic-syndrome/

https://coreem.net/core/nephrotic-syndrome/

Resources

1. Kodner C. Diagnosis and management of nephrotic syndrome in adults. Am Fam Physician.3(6):479-485.
2. Sinha A and Bagga A. Nephrotic syndrome. Indian J Pediatr.79(8):1045-1055
3. Dixon A and Stauffer B. Renal emergencies in children. In:Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9e. McGraw Hill.
4. Liebeskind DS. Nephrotic syndrome. In: Biller J, Ferro FM eds. Handbook of Clinical Neurology Vol 119. 2014.
5. Kelddal S, Nykjaer KM, Gregersen JW, et al. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications. BMC Nephrology.20:139
6. Nishi S, et al. Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clin Exp Nephrol.20:342-370.

The post EM@3AM: Nephrotic Syndrome appeared first on emDOCs.net - Emergency Medicine Education.

Originally published at Pediatric EM Morsels on January 29, 2011. Reposted with permission.

Follow Dr. Sean M. Fox on twitter @PedEMMorsels

Neonatal Conjunctivitis

• As the name suggests, it is conjunctivitis that develops within the 1st 4 weeks of life.

• Traditionally teachings about etiologies:
  • Chemical – day #1, mild conjunctivitis; less common now (less silver nitrate use)
  • GC – days #2-7, SEVERE conjunctivitis; can become disseminated (problem)!
  • Chlamydia – days 5-14, mild conjunctivitis; may lead to pneumonia
  • Other bugs/viruses – days 5-14, mild conjunctivitis; most prevalent

Unfortunately, nothing is that simple, and the concern for disseminated GC often leads to full sepsis work-ups.

• The Red Book can be used to support this approach… and also a less aggressive approach.

• If GC is suspected, “cultures of blood, eye discharge, or other sites of infection, such as CSF, should be performed…” and “Infants with gonococcal ophthalmia should be hospitalized and evaluated for disseminated infection (sepsis, arthritis, meningitis).”

• Chlamydial infection, however, are much more common (GC accounts for <1% of neonatal conjunctivitis: even less disseminated complications of it).

• Chlamydial infection is managed with ORAL antibiotics as an outpatient.

Where’s that leave us?

• Well, here are two approaches that I think are justifiable.

1. Do the full sepsis work-up. Rationalize that, in the ED, there is not a clinical way to determine whether you are dealing with GC and because of the potential concerns, cover all of your bases. This is the most conservative certainly.
2. Send a blood culture and send a culture and PCR (for Chlamydia) of the ocular discharge. Send a gram stain of the ocular discharge and admit the child. If the Gram stain is suspicious for GC, then the decision to LP and start abx can be made.
   • The emergent administration of antibiotics is less of an issue and, as long as the child is doing well, this decision can be made in concert with the admission team.

• With either plan, the most important therapy needs to be started; eye irrigation.

Ophthalmia neonatorum in Red Book.
Much appreciation to Dr. Amina Ahmed for her rational insight.

The post Neonatal Conjunctivitis / Ophthalmia neonatorum appeared first on emDOCs.net - Emergency Medicine Education.