Case 3:

• 56-year-old female with history of seizures, actively seizing, EMS called. Patient seized for approximately 20 minutes prior to EMS arrival. They administer two doses of 10 mg midazolam IM. After second dose the tonic clonic movement stop; GCS is 3, and she’s unresponsive.
• On ED arrival GCS is 3, there are rapid eye movements to the right but no other apparent seizure activity. Concern for nonconvulsive status epilepticus (NCSE).
• Two forms of status epilepticus (SE): convulsive and nonconvulsive
• Nonconvulsive SE: Change in cognitive or mental processes with no cmajor/significant convulsive activity AND…
  • Electrographic abnormalities on EEG for at least 10 continuous minutes, or there’s intermittent seizure activity for over 20% of an hour on EEG OR
  • EEG abnormalities plus clinical manifestations
• NCSE is a difficult diagnosis:
  • Usually presents with AMS and no readily apparent motor activity
  • No complete agreement on diagnostic criteria
  • Official diagnosis requires EEG, which most of us do not have in the ED, and EEG is not 100% specific.
• NCSE accounts for almost 47% of all cases of status epilepticus.
• Causes: Inadequately treated convulsive status, acute brain injury or structural lesion, infection, encephalopathy, medications/toxins
• Underlying cause is the most important factor in morbidity and mortality.
• NCSE presents with subtle signs/symptoms: ocular abnormalities (gaze deviation, nystagmus, eyelid twitching), change in speech, lip smacking, motor twitches of face or distal extremities.
  • Negative findings: phasia, mutism, amnesia and catatonia
  • Positive findings: rhythmic twitching of one or more muscle groups, tonic eye deviation, hippus, or nystagmoid eye jerking
  • Ocular abnormalities have 85% specificity
• Think NCSE in patients with these signs/symptoms, those with a history of seizures/epilepsy, intracranial pathology and AMS, prolonged post ictal status, and AMS with no other explanation despite testing.
• Look for life threats, check a serum glucose, and obtain neuroimaging.
• Treatment includes benzodiazepines.
  • If patient improves with benzo’s, that can be diagnostic.
  • Have a low threshold to administer a second line ant-epileptic, and be ready for sedation with propofol/ketamine and intubation.
• Patient had received midazolam, but with concern for NCSE, decision made to administer ketamine and propofol.  Levetiracetam also administered.
• Challenging airway: BMI > 40, kyphotic, short neck.
• Airway: Must have an approach, be prepared, and have backups.
• Our plan: 1) Video with hyperangulated blade, 2) direct standard geometry blade with bougie, 3) cricothyrotomy. Video with standard blade and flexible intubating endoscope unavailable at location.
• Airway plan discussed with resuscitation team. Cric is progression of the airway plan; it is not a failure.
• First attempt with hyperangulated blade. While second attempt ongoing, neck prepped and marked for cric.
• Second attempt with DL and bougie successful; ETT position confirmed with US. Propofol utilized for sedation; patient admitted to ICU for EEG monitoring. CT demonstrated no acute, actionable findings.

Learning points:

• Have an approach to seizures/status epilepticus: first dose benzo, but while asking for the second dose and other agent, prepare for intubation with ketamine and/or propofol.
• NCSE is likely more common than we think.
  • Consider NCSE in patients with altered mental status and abnormal ocular movements, lip smacking or subtle twitches in the face or extremities, and those with a history of seizures/epilepsy or a medication history on an anti-epileptic. Also think about NCSE in patients with prior cerebral pathology (ie, ischemic stroke); a patient who was seizing, was treated, and is not coming out of their post ictal state; and in patients with unexplained altered mental status with no other cause.
  • Official diagnosis requires EEG, which is not something we can typically obtain in the ED.
  • Check glucose, obtain imaging, stop the seizure.
• Every airway requires a plan and backups. Cric is not a failure; it is an integral part of every airway plan.

Reference:

• emDOCs – NCSE
• Journal of Emergency Medicine – Review

Case 4:

• 52-year-0ld male brought in by EMS with “code STEMI”. ECG demonstrates ST depressions with rocket like T waves in V2-V4.
• American College of Cardiology released a new consensus statement, “Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department: A Report of the American College of Cardiology Solution Set Oversight Committee“. This document covers high sensitivity troponin, risk disposition pathways, and STEMI equivalents.
  • STEMI vs. NSTEMI dichotomy is not sensitive for true occlusion MI or acute coronary occlusion.
  • “The application of STEMI ECG criteria on a standard 12-lead ECG alone will miss a significant miry of patients who have acute coronary occlusion.”
•  “In the absence of ischemic ST-segment elevation, the ECG should be examined for other changes that have been associated with coronary artery occlusion; when present, these should prompt evaluation for emergent coronary angiography.”
  • LBBB or ventricular paced rhythm with Sgarbossa or Smith-modified Sgarbossa criteria
  • Posterior STEMI
  • Hyperacute T waves
  • DeWinter T waves
• LBBB/ventricular paced rhythm with Sgarbossa or Smith-modified Sgarbossa criteria

• Posterior STEMI 

• Hyperacute T waves

• De Winter T waves

• Cardiology consulted; patient taken to cath lab, 100% proximal LAD occlusion.

The post emDOCs Podcast – Episode 86 Tricky Cases Part 2 appeared first on emDOCs.net - Emergency Medicine Education.

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

Answer: Extensor tendon laceration

Epidemiology:

• Hand extensor injuries make up >25% of orthopedic soft tissue injuries^{2, 3}
• Common in young men in manual labor
• Dominant hand more likely to be injured⁴
  • 2012 study on 86 patients reported 83% men with a mean age of 34.2 years and the dominant hand involved 60% of the time⁴
• Most common finger injuries are thumb (25.7%), index (24.8%), middle (23.8%) fingers, respectively^{4, 5, 6}

Anatomy:

• Tendons are more superficial on the dorsal hand and are therefore more commonly injured⁸
• Extensor retinaculum overlays the wrist, which can make tendon repair difficult⁹
• Primary muscles of hand extension
  • Primary wrist extensors: Extensor carpi radialis longus/brevis, extensor carpi ulnaris
  • Primary thumb extensors: Extensor pollicis longus/brevis, abductor pollicis longus
  • Primary finger extension: Extensor digiti minimi, extensor digitorum, extensor indicis

Classic injuries: 

Mallet finger

• Forced flexion of the DIP while extended
• May include bony avulsion fracture^{10, 11}

Clinical Presentation:

• Extensor injuries typically from more superficial lacerations to the dorsal surface of the hand
• Loss of strength with extension effected digit(s)
• Deeper lacerations may have neurovascular injury with loss of sensation or motor control

Evaluation:

• History should include mechanism, occupation, handedness, time of injury, tetanus status, prior injuries¹⁰
• Examine prior to anesthesia to obtain accurate sensorimotor function¹⁰
• Isolate each joint to test strength against resistance
• Test for neurovascular deficits with light touch/pinprick sensation, doppler
• Evaluate for bruising, wounds, deformities
• Adequate anesthesia should be used for wound exploration and decontamination
  • Utilize finger, radial, ulnar nerve blocks or local anesthesia
  • Evaluate wounds by reducing blood flow and irrigation; consider use of finger tourniquets¹⁰
  • Note wounds involving joint spaces or open fractures
• Painful nodule may be seen with tendon retraction
• X-ray should be used to identify fractures or retained foreign bodies
  • Ultrasound is effective for identifying hand fractures and foreign bodies¹²
• Ultrasound may be useful to evaluate for tendon disruption¹³
• Evaluate the zone of injury

Zones of injury 

• Tendon zones will help identify structures injured and guide further treatment

• More relevant as treatment may vary depending on zone
• I: DIP joint – injuries are typically closed injuries^{14, 15}
• II: Middle phalanx
• III: PIP joint
• IV: Proximal phalanx
• V: Metacarpophalangeal (MCP) joint
• VI: Dorsum of the hand
• VII: Wrist
• VIII: Distal forearm
• TI: Interphalangeal (IP) joint of thumb
• TII: Proximal phalanx of thumb
• TIII: MCP of the thumb
• TIV: Carpometacarpal (CMC) joint

Treatment: 

• Treatment depends on the zone of injury
• All tendon injuries, open or closed, should be referred to a hand specialist
  • In general, patients with simple extensor tendon injuries should be followed up outpatient by a hand specialist, if one is not available in the area, transfer to a higher level of care should be considered
• Most patients get a short course of antibiotics in open tendon injuries, but not required
  • Several prospective, randomized control trials show no statistical significance in wound infection with hand lacerations^16,17,18
  • Cephalexin 500mg for 5-7 days would be appropriate for open tendon injuries
  • Consider extensive contamination, open fractures, which would warrant orthopedic consultation
    • Type I: open fracture with <1cm clean laceration, minimal soft tissue damage
      • Cefazolin 2g IV three times daily in adults
        • 30mg/kg three times daily in children
    •  Type II: open fracture with 1-10 cm clean laceration without extensive injury
      • Same as Type I
    • Type III: open fracture >10cm with extensive soft tissue damage or heavily contaminated/farm injury
      • Cefazoline 2G IV Three times daily
      • Gentamicin 5-7 mg/kg IV once daily in adults; 2.5 mg/kg IV three times daily in pediatrics¹⁹

• Zone I and II: For closed injuries, place DIP in hyperextension and immobilize finger with a splint for 6-8 weeks²¹
  • Patient compliance with splint will determine success of treatment²²
  • Open injuries should be repaired with a roll stitch (see image 6)²³
    • 4-0 or 5-0 non absorbable suture used to involve both skin and tendon
• Zone III: Tendon should not be repaired in the ED
  • Repair requires hand specialist to prevent Boutonniere deformity^{23, 24}
  • If in a community setting, suture overlying skin, splint wrist in 30° extension, MCP in 15° flexion and PIP in neutral²⁴

• Zone IV: Tendons are larger and more amenable for repair in ED²³
  • Use modified Kessler/Bunnell technique with low tissue reactivity and high strength suture such as 4-0 ethibond or mersilene (see image 7)²⁵
    • https://www.youtube.com/watch?v=yGJ5JzcFJYQ
    • https://www.youtube.com/watch?v=paXHJl_Hccc
  • Splint similar to zone III injuries
• Zone V: Have a high suspicion for fight bite injuries^{14, 22}
  • If physician suspects above, extensively irrigate and do not close skin
  • Tendon repair similar to zone IV, splint wrist 45° extension, MCP 20° flexion²²
  • Patient will need antibiotics i.e. Augmentin if fight bite suspected²²
    • Amoxicillin/clavulanate 875 mg/125 mg by mouth twice daily in adults
      • 25 mg/kg by mouth twice daily in children
  • Patient should follow up within 24 hours
•  Zone VI: Tendons are large and superficial on the dorsum, making for an easier repair
  • Modified Kessler/Bunnell technique with 4-0 non-absorbable sutures similar to above¹
  • Splint wrist in 30° of extension, MCP neutral with digits free
•  Zone VII and VIII: Beyond scope of ED repair
  • Junctions with muscle bodies become involved²⁴
  • Close overlying skin, place in volar splint, ortho consultation vs urgent referral
  • Consider consulting orthopedics or transfer to a center with hand specialist if extensor tendon injury is more proximal to wrist, as this eventually requires surgical repair
•  Ensure the patient is up to date with their tetanus vaccination
  • Past vaccination unknown or <3 total
    • Wound is clean: Td
    • Wound is dirty: Td + tetanus immunoglobulin
  • At least 3 prior Td vaccinations
    • Wound is clean: Td if last vaccine >10 years ago
    • Wound is dirty: Td if last vaccine >5 years ago²⁶

Disposition: 

• If there is no extensive injury to soft tissue, patients can be discharged
  • Ensure urgent follow-up with orthopedics if there is suspected flexor/extensor damage²⁷
  • Concern for open fractures/joints should prompt orthopedics consultation
  • Depending on extent of injury/local practice, orthopedics may need ED consultation

Pearls: 

• Complete a thorough physical exam, noting neurovascular status as well as isolated joint mobility and strength
• Extensor injuries should be repaired based on location of injury zone
• Use non-absorbable 4-0 suture with modified Kessler or Burnell technique when repairing extensor tendons
• Patients generally have tendon repair, splinting, and outpatient hand specialist follow-up, but consider hand consultation if damage is extensive or consider transferring if no hand specialist for follow up

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

Authors: Danae Massengill, MD (Medical Toxicology Fellowship Rocky Mountain Poison and Safety, Denver Health); Christine Murphy, MD (Atrium Health Emergency Department) // Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UT Southwestern Medical Center, Dallas, TX); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Historical Case:

Over a 2-week period in November 2008, 13 cases of unexplained acute renal failure occurred among children from a hospital in Lagos State, Nigeria. Upon review of the history, several of the patients had been exposed to a liquid acetaminophen-based teething medication.¹

Clinical Questions:

1. When should a clinician suspect diethylene glycol (DEG) toxicity?
2. What is the management of suspected or confirmed DEG toxicity?
3. What are the public health implications of DEG toxicity?

Background:  

• DEG is a clear, colorless, odorless liquid with a sweet taste.
• An industrial chemical used as a solvent, lubricant, or chemical intermediate, DEG is also found in automobile fluids, cleaning products, and canned heat cooking fuels.
• In mass poisoning cases, DEG has been substituted as a solvent in oral medications and in topical medicinal products.²
• Clinically significant toxicity has been reported from oral and topical exposures.²
• Patients with suspected or known DEG ingestions present a diagnostic and therapeutic challenge as the mechanisms of DEG toxicity in humans are not completely understood.
• Pharmacokinetics:²

• • No minimal toxic dose has been established, however, doses up to 22 mg seem to be safe for adults from the available literature.
  • DEG is rapidly absorbed when ingested and can reach peak plasma and brain tissue concentrations within four hours of ingestion.
  • The majority of DEG is eliminated unchanged in the urine under normal physiologic conditions.
  • However, up to 40% of DEG is metabolized to diglycolic acid (DGA) which is the proposed toxic metabolite of concern. DGA concentrates in the kidney tissue and causes nephrotoxicity, as well as neurotoxicity.
  • Elimination half-life data is not well established but increases in larger overdoses and as renal injury begins to occur.

Epidemiology/Public Health Implications: 

• Implicated in the Sulfanilamide Disaster of 1937, DEG toxicity was responsible for the death of 105 people across 15 states, one-third of which were children.⁴
• This disaster led to new standards of drug safety with the establishment of the Federal Food, Drug and Cosmetic Act of 1938.⁴
• Despite the policy changes in the United States, epidemic poisonings involving DEG continue to impact adults and children on a global scale with 14 mass poisonings occurring since the Sulfanilamide Disaster.^5,6
• Unfortunately, most patients exposed to epidemic poisonings present after the onset of symptoms, at which point end-organ effects from toxicity have already started to occur and may not be reversible.

Clinical Presentation:  

• Target organs of acute DEG toxicity are the kidney, liver, and nervous system.
• Toxicity typically evolves through three phases:^2,3,7,8,9
  • Phase 1: Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, and hepatotoxicity), elevated osm gap, and anion gap metabolic acidosis
  • Phase 2: Acute oliguric or anuric renal failure secondary to acute tubular necrosis
    • Acute kidney injury (AKI) is the hallmark of DEG toxicity.
  • Phase 3: Neurologic complications, such as neuropathies, cranial nerve palsies, denervation, convulsions, encephalopathy, and coma
    • Patients who develop AKI following DEG exposure are at risk for developing neurologic complications.

Diagnosis: 

• Diagnosis without a clear history of exposure is very challenging.
• The clinician should rely on a high index of suspicion, clinical history and routine lab work including serum electrolytes, kidney function studies, and blood gas measurements.²
• Careful consideration should be given to the use of the osm gap, as this should not be used to exclude toxic alcohol ingestion.²
• Laboratory assays for DEG are not widely available and have long turn-around-times, thus have limited utility in diagnosis in the emergency department.

Management: 

• While limited evidence supports gastrointestinal decontamination due to the severity of clinical effects following DEG exposure, it is reasonable to perform nasogastric/orogastric tube aspiration or give activated charcoal if patient presentation is within 1-2 hours of ingestion.²
• Administration of an alcohol dehydrogenase (ADH) inhibitor, such as fomepizole, is recommended in suspected or known DEG poisoning.

• • The dosing of fomepizole is identical to that used for other toxic alcohols, with a loading dose of 15 mg/kg IV, followed 12 hours later by 10 mg/kg every 12 hours for 4 doses.^2,10
  • If patient requires hemodialysis, then the dosing interval should be every 4 hours.^2,10

• Initial stabilization of DEG toxicity includes correcting acid-base abnormalities, electrolyte abnormalities, and volume resuscitation.
• Pay careful attention to fluid balance, as DEG has osmotic diuretic effects.
• Volume resuscitation as needed while adjusting for any developing acute kidney injury.
• Hemodialysis is indicated if there is evidence of acidosis or end-organ effects (acute kidney injury, coma, etc.)
  • Renal injury often results in patients needing long-term hemodialysis.

• Inpatient/outpatient nerve conduction studies may be helpful in establishing the extent of neuropathy.
• Patients with suspected intoxication or asymptomatic patients with ingestions present the greatest challenge.
  • These patients should be observed for at least 24 hours, following electrolytes and acid-base status closely for any changes.
  • For patients receiving fomepizole, the 24-hour observation should begin 12 hours following the last dose of fomepizole.²

Case Follow-up: 

• Following an investigation, the Nigeria Field Epidemiology and Laboratory Training Program (N-FELTP), CDC, and the Food and Drug Administration (FDA) identified 57 cases of DEG poisoning among children £ 3 years old, of whom 54 died.¹
• Of the 57 children, 96% had confirmed exposures to the acetaminophen-based teething medication.
• Twenty-four of the 57 children identified underwent dialysis and two received fomepizole.

Clinical Pearls:

• DEG toxicity should be considered in cases of unexplained acute kidney, liver, or nervous system dysfunction, especially if occurring in outbreaks or clusters.
• Due to the limited availability of laboratory assays for DEG, clinicians should rely on a high index of suspicion, history, and routine lab work for diagnosing DEG toxicity.²
• Management of suspected or confirmed DEG toxicity encompasses a spectrum including observation, supportive care, ADH inhibitor therapy, and hemodialysis.²
• Contaminated pharmaceutical products should be included in the differential diagnosis of deaths of unknown origin.⁷
• Considering epidemiologic trends, the data suggest that DEG mass poisonings will continue to occur.

References:

1. Abubukar et al. “Fatal Poisoning Among Young Children from Diethylene Glycol-Contaminated Acetaminophen — Nigeria, 2008—2009”. CDC’s Morbidity and Mortality Weekly Report. 11 Dec. 2009.
2. Schier, Capt. Joshua G. “Diethylene Glycol” in Goldfrank’s Toxicologic Emergencies, 11e Eds. Lewis S. Nelson, et al. McGraw Hill, 2019. Accessed August 2022.
3. Besenhofer, Lauren M., et al. “Inhibition of Metabolism of Diethylene Glycol Prevents Target Organ Toxicity in Rats.” Toxicological Sciences, vol. 117, no. 1, 2010, pp. 25–35., https://doi.org/10.1093/toxsci/kfq167.
4. Ballentine, Carol. “Sulfanilamide Disaster.” FDA Consumer Magazine, June 1981, https://www.fda.gov/files/about%20fda/published/The-Sulfanilamide-Disaster.pdf. Accessed August 2022.
5. Conklin, Laura, et al. “Long-Term Renal and Neurologic Outcomes among Survivors of Diethylene Glycol Poisoning.” JAMA Internal Medicine, vol. 174, no. 6, 1 June 2014, pp. 912–917. https://doi.org/10.1001/jamainternmed.2014.344.
6. Bastani P, Jammeh A, Lamar F, Malenfant JH, Adewuyi P, Cavanaugh AM, Calloway K, Crisp C, Fofana N, Hallett TC, Jallow A, Muoneke U, Nyassi M, Thomas J, Troeschel A, Yard E, Yeh M, Bittaye M. Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol-Contaminated Medications – The Gambia, June-September 2022. MMWR Morb Mortal Wkly Rep. 2023 Mar 3;72(9):217-222. doi: 10.15585/mmwr.mm7209a1. PMID: 36862590; PMCID: PMC9997663.
7. O’Brien, Katherine L. “Epidemic of Pediatric Deaths from Acute Renal Failure Caused by Diethylene Glycol Poisoning.” JAMA, vol. 279, no. 15, 15 Apr. 1998, pp. 1175–1180., https://doi.org/10.1001/jama.279.15.1175.
8. Robinson, Corie N., et al. “In-Vivo Evidence of Nephrotoxicity and Altered Hepatic Function in Rats Following Administration of Diglycolic Acid, a Metabolite of Diethylene Glycol.” Clinical Toxicology, vol. 55, no. 3, 11 Jan. 2017, pp. 196–205., https://doi.org/10.1080/15563650.2016.1271128.
9. Schep, Leo J., et al. “Diethylene Glycol Poisoning.” Clinical Toxicology, vol. 47, no. 6, 8 July 2009, pp. 525–535., https://doi.org/10.1080/15563650903086444.
10. Howland, Mary Ann. “Fomepizole” in Goldfrank’s Toxicologic Emergencies, 11e Eds. Lewis S. Nelson, et al. McGraw Hill, 2019. Accessed August 2022.

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

Case 1:

• 42-year-old male, GCS 3, HR 190, BP is 90/48 mm Hg, T 105F. Found in garage, hot, question of illicit drug use. 
• IV fluids started, concern for SVT. Cardioverted, followed by sinus tachycardia, remains GCS 3.
• Intubated with etomidate and rocuronium, propofol started for sedation. Broad-spectrum antibiotics administered.
• Temp 106F on repeat evaluation. Cooling blanket placed, but temperature increases to 107F.
• Immersion cooling completed with ice between body bags. Temperature starts to decrease. Removed from cooling at 102 and admitted to ICU.
• Must consider differential in complex cases.

Learning points:

• Consider differential – sepsis, thyroid storm, thalamic stroke, exertional and classic heat stroke, serotonin syndrome, neuroleptic malignant syndrome, sympathomimetic toxicity, and anticholinergics.
• Complete primary and secondary survey.
• Start cooling as quickly as you can, and stop at 102.
• Resuscitate and administer antibiotics.

Reference:

• EM@3AM – Heat Stroke

Case 2:

• 40-year-0ld female feels unwell but no other specific complaints. ROS unremarkable. On exam, she was febrile, tachycardic, hypotensive and tachypneic, but her oropharynx was unremarkable, lungs were clear, abdomen was soft, no meningismus/nuchal rigidity, no rash, no vaginal discharge.
• Labs demonstrate critical illness. Leukocytosis in the 20sK with 10% bandemia, acute renal failure with electrolyte derangements, elevated LFTs, lactate 8. Clear CXR and normal UA.
• IV fluids administrated, IV vancomycin and piperacillin-tazobactam. Continues to decompensated, so vasopressors started.
• Differential Diagnosis for patient: Infectious endocarditis, CNS infection or abscess, necrotizing soft tissue infection, toxic shock, obstructive pyelonephritis, toxic ingestion, TTP, anaphylaxis with primarily hemodynamic effects, thromembolic phenomenon.
• Shock types: distributive, cardiogenic, obstructive, metabolic, hypovolemic, adrenal.
• Considerations when patients continue to decompensate despite resuscitation and vasopressors: acidosis, endocrine issues like adrenal insufficiency or hypothyroidism, hypocalcemia, anaphylaxis, hemorrhage, multiple causes of shock, ingestion.
• Approach: Focused history and examination, think through differential, consider US (RUSH, etc.).
• Central line placed to continue vasopressors. CT shows occlusive right ureteral stone, pyelonephritis. Arterial line started. Patient intubated, IR performs percutaneous nephrostomy.

Stay tuned for Part 2!

The post emDOCs Podcast – Episode 85: Tricky Cases Part 1 appeared first on emDOCs.net - Emergency Medicine Education.

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

Authors: Sean Trostel, MD (EM Resident Physician, Carolinas Medical Center, Charlotte, NC); Kathryn T Kopec, DO (@KopecToxEM, EM Attending Physician, Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UT Southwestern Medical Center, Dallas, TX); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Please see Part 1 of this series for guidance on the management of the crotalid envenomation.

Case, continued:

A 2-year-old boy was admitted to your hospital in stable condition after a copperhead snake bite to the right lower leg. He was administered 10 vials of Crotalidae equine immune F(ab’)₂ (ANAVIP®) at the outside hospital before transfer to your referral center.

Approximately 12 hours following F(ab’)₂ antivenom administration, the child is noted to have progressive swelling, firmness, tension, and pain of the right calf. Your hospital pharmacy stocks only crotalidae ovine polyvalent immune F(ab) (CroFab®) antivenom.

Questions:

1. What antivenoms are available to treat crotalid envenomations?
2. What are the major similarities and differences between available crotalid antivenoms?
3. What is the dosing schedule for each antivenom?

Background

Crotalidae ovine polyvalent immune F(ab) (CroFab®) is the most widely available crotalid antivenom in the United States and is approved for severe crotalid envenomation with severe or progressive localized symptoms, systemic toxicity, and signs of hematologic toxicity on labs. However, in 2015 crotalidae equine immune F(ab’)₂ (ANAVIP®) was approved by the FDA for rattlesnake envenomations, and distribution of this antivenom began in 2018. In April 2021, after a post-hoc analysis of the original phase 3 study suggested non-inferiority of the F(ab’)₂ antivenin against copperhead envenomation, the FDA expanded approval of this antivenom to include copperhead and cottonmouth envenomations.^1,2

Discussion: F(ab) vs. F(ab’)₂ Antivenoms

While both antivenoms are approved to treat all crotalid envenomations in the United States, the commercially available F(ab) and F(ab’)₂ antivenoms have several noteworthy differences:

1. 1. The F(ab) antivenom is produced from a sheep-derived (ovine) antibody, while F(ab’)₂ is horse-derived (equine).
   2. F(ab) is smaller, consisting of a single antigen binding site, while F(ab’)₂ consists of two antigen-binding sites linked together by an antibody “hinge” region. This size difference may lead to differences in the pharmacokinetic profiles of the two antibodies.
      • Plasma half-life of the F(ab’)₂ antivenom is significantly longer at 5.5 days, compared to 12-23 hours of the F(ab) antivenom, reflecting its tendency to remain in the intravascular compartment.^3,4
      • The smaller size of F(ab) antivenom may promote more rapid tissue penetration as compared to F(ab’)₂.⁵

        

   3. F(ab) antivenom is produced with venoms from four North American pit vipers, including the western diamondback rattlesnake (Crotalus atrox), eastern diamondback rattlesnake (Crotalus adamanteus), Mojave rattlesnake (Crotalus scutulatus), and cottonmouth (Agkistrodon piscivorus) venoms. F(ab’)₂ antivenom is produced with venoms from two South and Central American pit vipers: the South American rattlesnake (Crotalus durissus) and terciopelo (Bothrops asper).

Table 1: Comparison of F(ab) and F(ab’)₂ antivenoms.^3,4,6,7,8

Antivenom	Crotalidae ovine polyvalent immune F(ab)	Crotalidae equine immune F(ab’)2
Brand name, manufacturer	CroFab®, BTG International	ANAVIP®, Instituto Bioclon
Indication	North American crotalid envenomation	North American crotalid envenomation
Structure	Ovine (sheep) derived antibody F(ab) fragments Single venom binding site	Equine (horse) derived antibody F(ab’)2 fragments Two venom binding sites
Venom used in production	Agkistrodon piscivorus (cottonmouth/water moccasin) Crotalus adamanteus (Eastern diamondback rattlesnake) Crotalus atrox (Western diamondback rattlesnake) Crotalus scutulatus (Mojave rattlesnake)	Crotalus durissus (South American rattlesnake) Bothrops asper (Terciopelo or fer-de-lance)
Plasma Half-life	12-23 hours	5.5 days
Dosing	Initial: 4-6 vials, repeated until initial control Maintenance: 2 vials every 6 hours x 3 doses Reemergent symptoms: 2 vials	Initial: 10 vials, repeated until initial control Maintenance: None Reemergent symptoms: 4 vials
Repeat labs	2 to 3 days and 5 to 7 days after last antivenom dose Continue to monitor if trend toward abnormal Reassess labs sooner if risk factors for bleeding are present	5 to 7 days after last antivenom dose Continue to monitor if trend toward abnormal Reassess labs sooner if risk factors for bleeding are present
Relative contraindications	Allergy to: Sheep Bromelain (pineapple enzyme) Papain, chymopapain, papaya extracts α-gal	Allergy to: Horses α-gal
Adverse effects	Allergic reaction / anaphylaxis Serum sickness	Allergic reaction / anaphylaxis Serum sickness

In a phase 3 trial comparing F(ab) to F(ab’)₂ antivenom, the F(ab’)₂ antivenom was associated with significantly lower rates of recurrent or late thrombocytopenia than F(ab) antivenom, possibly attributable to the F(ab’)₂ antivenom’s longer plasma half-life.⁹ This effect may be especially prominent in the setting of rattlesnake envenomation, where coagulopathic effects are more prominent.

The addition of Agkistrodon venoms in the production of the F(ab) antivenom may also provide better specificity and efficacy against these species. As we commonly see in practice, differences exist in the clinical and toxic effects of envenomation by snakes even within the same genus. For example, Mojave rattlesnake envenomation may produce neurotoxic effects not seen in envenomations by most other rattlesnake species. This suggests that venom profiles are not identical between species, and thus different antibodies may be more or less efficacious against specific venoms.^10,11

Expansion of the new F(ab’)₂ antivenom’s indications to include envenomation by the Agkistrodon genus (copperhead/cottonmouth) was based on a single abstract describing a post-hoc non-inferiority analysis of 21 patients from the original F(ab’)₂ antivenom phase 3 trial. This analysis suggested that the F(ab’)₂ antivenom was noninferior to F(ab) antivenom in multiple measures. However, due to the limited sample size, confidence intervals were wide for all of these measures, and only 2 of 3 examined measures met the predetermined non-inferiority assumptions.^1,2 More research is needed to determine whether a difference truly exists in efficacy of these antivenoms against local tissue effects which predominate after Agkistrodon envenomation.

Adverse Effects:

1. F(ab) (CroFab®)⁴
   • Less than 5% of people will experience urticaria, rash, nausea, and pruritus
   • Anaphylaxis & anaphylactoid reactions can occur
   • Recurrent coagulopathy is common and is characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time
2. F(ab’)2 (ANAVIP®)³
   • Less than 2% of people experience pruritus, nausea, rash, arthralgia, peripheral edema, myalgia, and headache
   • Anaphylactic reactions are possible

Case Follow-up:

Secondary to the recurrent, progressive swelling and pain of the right calf, 4 vials of F(ab) antivenom were administered in addition to the initial 10 vials of F(ab’)₂ antivenom. Following this second dose, the firmness and swelling of the leg improved, and the patient had an otherwise uneventful hospital course. Labs including platelets and fibrinogen remained normal, and the patient was discharged on hospital day 4. On follow-up 1 week later, the patient was doing well, ambulating and playing without significant discomfort.

Clinical Pearls:

• Most snake envenomations in the United States are caused by pit vipers (crotalidae) and are characterized by local tissue injury and coagulopathic effects.
• Copperhead and cottonmouth (Agkistrodon) envenomations are generally characterized by more prominent local tissue effects, while rattlesnake (Crotalus) envenomations often cause early, late, and recurrent coagulopathy in addition to local tissue effects.
• F(ab) (CroFab®) and F(ab’)₂ (ANAVIP®) crotalid antivenoms are FDA approved and indicated for severe crotalid envenomation with severe or progressive localized symptoms, systemic symptoms, and/or signs of coagulopathy on labs.
• Research suggests that F(Ab’)₂ antivenom, compared against F(ab) antivenom, may be associated with lower rates of late and recurrent coagulopathy.⁹
• More research is needed to determine whether significant differences exist between antivenoms in efficacy against local tissue injury or efficacy against specific species of snake.

References:

1. Ubani C, DeGelorm A, Sollee D. Poison Control: The F(ab2)ulous Expanded Indication of Anavip | FCEP. Accessed May 7, 2022. https://fcep.org/poison-control-the-fab2ulous-expanded-indication-of-anavip/
2. Gerardo CJ, Keyler DE, Rapp-Olsson AM, Schwarz J, Dart RC. 72 Post Hoc Analysis of the RCT Comparing F(ab’)2to Fab Antivenom: Control of Venom-induced Tissue Injury in Copperhead Snakebite Patients. Ann Emerg Med. 2020;76(4):S29. doi:10.1016/j.annemergmed.2020.09.082
3. Full prescribing information. ANAVIP. Crotalidae Immune F(ab’)2 (Equine). Published online April 2021. Accessed May 7, 2022. https://www.fda.gov/media/92139/download
4. Full prescribing information. CROFAB. Crotalidae polyvalent immune fab (ovine). Published online January 2018. Accessed August 17, 2023. https://www.fda.gov/media/74683/download
5. Li Z, Krippendorff BF, Sharma S, Walz AC, Lavé T, Shah DK. Influence of molecular size on tissue distribution of antibody fragments. mAbs. 2016;8(1):113-119. doi:10.1080/19420862.2015.1111497
6. Antivenom administration North American Crotalinae snakebites – UpToDate. Accessed May 7, 2022. https://www.uptodate.com/contents/image/print?imageKey=EM%2F122011&topicKey=EM%2F8365&source=see_link
7. Blue Ridge Poison Center, University of Virginia Health. Battle of the Antivenoms: CroFab vs ANAVIP. ToxTalks. Published online November 2020. Accessed May 7, 2022. https://med.virginia.edu/toxicology/wp-content/uploads/sites/268/2020/11/Nov20-Crofab-Anavip.pdf
8. Lavonas EJ, Ruha AM, Banner W. et al. Unified Treatment Algorithm for the management of crotalid snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;3(11):2.
9. Bush SP, Ruha AM, Seifert SA, et al. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial. Clin Toxicol Phila Pa. 2015;53(1):37-45. doi:10.3109/15563650.2014.974263
10. Buchanan JT, Thurman J. Crotalidae Envenomation. In: StatPearls. StatPearls Publishing; 2022. Accessed May 17, 2022. http://www.ncbi.nlm.nih.gov/books/NBK551615/
11. Kanaan NC, Ray J, Stewart M, et al. Wilderness Medical Society Practice Guidelines for the Treatment of Pit viper Envenomations in the United States and Canada. Wilderness Environ Med. 2015;26(4):472-487. doi:10.1016/j.wem.2015.05.007

The post ToxCard: Crotalid Envenomation Part 2 – CroFab vs. AnaVip: What’s the Difference? 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. Stories of med mal lawsuits can save lives. If you have a story to share click here.

Chuck Pilcher, MD, FACEP

Editor, Medical Malpractice Insights

The post Medical Malpractice Insights: Failure to detect child abuse results in $45 million verdict appeared first on emDOCs.net - Emergency Medicine Education.

Answer: Oropharyngeal candidiasis (OPC), also known as thrush

Epidemiology

• Typically, an overgrowth of the fungus Candida Albicans
• 3 primary susceptible populations
  • Immunocompromised (i.e. HIV or AIDs, diabetes, on an immunosuppressant, steroid, or antibiotic medications)
    • 80-90% of HIV patients will develop OPC during their disease course²
    • Steroid use to include inhaled (asthma patients) or oral
      • Inhaled steroids reduce salivary production and flow, increasing risk of infection³
      • Asthma users should brush teeth after inhaled treatments to prevent infection
  •  Infants
    • More susceptible due to underdeveloped immune systems
    • Premature infants or those with low birthweight more susceptible to systemic candidiasis
  • Elderly (more common with denture use)
    • More commonly presents as an erythematous, atrophic form under upper dentures, with a prevalence of 15% in denture wearers⁴

Clinical Presentation

• Frequently asymptomatic
• May experience a dry, cotton-mouthed feeling, loss of taste
• Disease severity:
  • Mild disease – usually asymptomatic
  • Moderate disease – may have pain and greater surface area involvement (>50% of oral mucosa)
  • Severe disease – can be painful, can impair the ability to eat
  • Esophageal involvement – can occur with OPC or separately; suspect with pain on swallowing. Diagnosed as esophageal candidiasis
    • Typically occurs in patients with CD4+ count of <100 cells/microL⁵

• Risk Factors
  • Immunocompromised
  • Denture use
  • Inhaled/oral steroid use
  • Infant with low birth weight or prematurity
  • Diagnosis in absence of risk factors may warrant HIV testing

Treatment

Disposition

• Discharge is warranted in most patients, as the infection is typically self-limited
• Admit if concurrent symptoms merit further investigation

Pearls

• In the absence of risk factors, diagnosis of thrush should warrant HIV testing
• Evaluate for esophageal involvement as these patients are prone to esophagitis
• Counsel denture wearers/pediatric patients’ caregivers on the importance of sterilizing/decolonization to prevent recurrence

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

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Today we look at the FABLED trial.

Authors: Brannon L Inman, MD (Critical Care Fellow, Orlando, FL) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

The post 52 in 52 – #42: The “FABLED” Trial appeared first on emDOCs.net - Emergency Medicine Education.

Background:

• Capnography is the noninvasive measurement of carbon dioxide partial pressure.
• Displayed as colorimetric/qualitative, quantitative and waveform
• Normal range for EtCO₂ 35-45 mm Hg
• Waveform has several different phases:
  • Phase 0 – inspiration – clearing of CO₂ 
  • Phase I – expiration – anatomical dead space, should not contains CO₂ 
  • Phase II – expiration – rapid rise in CO₂ concentration, as breath reaches upper airway from the alveoli
  • Phase III – expiration – CO₂ concentration reaches uniform levels in the airway,  height and slope of the line offer important information

Interpretation

• Three aspects of capnography: 
  • EtCO₂ maximum number/plateau
  • Shape of the capnogram
  • Difference/gradient between EtCO₂ and arterial CO₂ pressure
• Capnography reading affected by:
  • CO₂ production & transport, ventilation, and vent-perf ratio changes 
  • Vent settings/malfunctions,  tubing obstruction/disconnection/leaks  & monitor malfunction
• ETCO₂ correlates with blood pressure, lactate & base excess in the critically ill.
• Mortality rate ↑ as EtCO₂ levels ↓

Common uses: 

• Confirmation of ETT placement
  • Sensitivity ~ 100% for placement in trachea
  • More reliable than fogging of ETT, chest wall movement, breath sounds
  • Monitoring ETT during transport – quickly detect displacement
• Cardiac arrest
  • EtCO₂ assesses chest compression efficacy 
  • The level of EtCO₂ = cardiopulmonary blood flow
  • ACLS guidelines: quantitative waveform to monitor compressions & ROSC
  • Level >20 mmHg → higher chance of ROSC 
  • Levels <10 mmHg → lower chance of survival
  • Gradual↓ in EtCO₂ = compressions not optimal or other complications (hemorrhage, pneumothorax, tamponade, myocardial infarction)
  • Sudden ↑ ≥10 mm Hg is specific for ROSC
  • Does not determine cause of arrest
  • PQRST Mnemonic for capnography in cardiac arrest
    • Position of tube – more reliable than other options
    • Quality of compressions – valuable feedback in real time
    • ROSC – sudden ↑ in value suggests ROSC
    • Strategy for further treatment – trends + other diagnostics help decide on diagnosis & treatment (vasopressors, fluids, thrombolytics – trying to optimize perfusion)
    • Termination of resuscitation – <10 mmHg associated with death
• Procedural sedation
  • Assess ventilation at the bedside
  • Detects hypoventilation faster than pulse oximetry
  • Respiratory depression manifests as↑EtCO₂
  • ACEP recommends capnography as adjunct to pulse oximetry

Other indications:

EtCO2 should only be used as an adjunct at the bedside in these conditions. 

• Trauma
  • Associated with severity of injury and need for blood transfusion 
  • ↓ EtCO₂ = ↑ likelihood of needing OR
  • EtCO₂ < 25 mm Hg =↓ cardiac output, ↓ BP  & ↑ mortality 
• Fluid responsiveness
  • 2 mmHg ↑ EtCO₂ with straight leg raise = patient will be fluid responsive
• DKA
  • ↓ EtCO₂ levels = ↑likelihood of diagnosis.   
    • • EtCO₂ > 35 = 98% sens for ruling out DKA
      • EtCO₂ < 24 = 90% sens/spec for diagnosing DKA
• Sepsis
  • EtCO₂ < 31 associated with high mortality
• PE
  • Increased dead space = ↓ EtCO₂  
  • EtCO₂ > 32–36 + low probability Wells score – may rule out PE
  • Another tool  with pre-test probability and D-dimer
  • More studies needed
• Obstructive airway disease
  • Bronchospasm – steep phase III (shark fin capnogram)
  • Early on ↓ EtCO₂ – breathing off extra CO₂ 
  • Later ↑EtCO₂ – poor ventilation, severe exacerbation
  • Monitor treatment – shark fin disappears with improvement of bronchospasm from nebulizer/steroids
• Seizure
  • Useful for monitoring of respiratory status

Limitations:

• Works well for a specific underlying issue – mixed pathophysiology makes interpretation challenging.
• In cardiac arrest, EtCO₂ is dependent on compressions AND the underlying cause.
• Other organ system involvement & hypotension/low perfusion affect EtCO₂.
• False positive CO₂ detection can occur in esophageal intubations if the patient ingested carbonated beverages.
• Acidic solution exposure, such as stomach content fluid or vinegar, can result in qualitative color change.

Pearls:

• Capnography is an overall assessment of the path of CO2 through the entire body.
• Capnography picks up hypoventilation faster than pulse oximetry.
• ETCO₂ correlates with blood pressure, lactate, and base excess in critically ill patients.
• Capnography has several novel uses in other disease states commonly seen in the ED such as trauma, DKA, sepsis and obstructive lung disease.

Further Reading:

1. http://www.emdocs.net/capnography-useful-ed-part/
2. http://www.emdocs.net/capnography-useful-ed-part-ii/

References: 

1. Long B, Koyfman A, Vivirito MA. Capnography in the Emergency Department: A Review of Uses, Waveforms, and Limitations. J Emerg Med. 2017;53(6):829-842. PMID: 28993038
2. Manifold CA, Davids N, Villers LC, Wampler DA. Capnography for the nonintubated patient in the emergency setting. J Emerg Med. 2013;45(4):626-632. PMID: 23871325
3. Nassar BS, Schmidt GA. Capnography During Critical Illness. Chest. 2016;149(2):576-585. PMID: 26447854
4. Godwin SA, Burton JH, Gerardo CJ, et al. Correction: Correction to ‘Clinical Policy: Procedural Sedation and Analgesia in the Emergency Department’ [Annals of Emergency Medicine 63 (2014) 247-258.e18]. Ann Emerg Med. 2017;70(5):758. PMID: 28395927
5. Panchal AR, Berg KM, Hirsch KG, et al. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2019;140(24):e881-e894. PMID: 31722552
6. Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. 2013;14(6):590-594.  PMID: 24381677
7. Bou Chebl R, Madden B, Belsky J, Harmouche E, Yessayan L. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BMC Emerg Med. 2016;16:7. Published 2016 Jan 29. PMID: 26821648
8. Hemnes AR, Newman AL, Rosenbaum B, et al. Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism. Eur Respir J. 2010;35(4):735-741. PMID: 19717480
9. Riaz I, Jacob B. Pulmonary embolism in Bradford, UK: role of end-tidal CO2 as a screening tool. Clin Med (Lond). 2014;14(2):128-133. PMID: 24715122

The post emDOCs Podcast – Episode 84: Capnography appeared first on emDOCs.net - Emergency Medicine Education.

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

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Today we look at the CENSER trial.

Author: Mackenzie Prendergast, DO (EM resident physician, San Antonio, TX); Brannon L Inman, MD (Critical Care Fellow, Orlando, FL) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

The post 52 in 52 – #41: The CENSER Trial appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Sean Trostel, MD (EM Resident Physician, Carolinas Medical Center, Charlotte, NC); Kathryn T Kopec, DO (@KopecToxEM, EM Attending Physician, Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UT Southwestern Medical Center, Dallas, TX); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case:

A 2-year-old boy was transferred to your Emergency Department (ED) with severe pain, swelling, and ecchymosis of the right ankle 5 hours after being bitten by a snake. His father confirmed the snake was a copperhead. He was initially seen at a regional ED and was administered 10 vials of crotalidae equine immune F(ab’)₂ (ANAVIP®) antivenom before transfer to your referral center.

On arrival, the patient is clearly uncomfortable but nontoxic appearing. He has two punctate fang marks at the right lateral ankle with swelling and tenderness extending from the distal foot proximally to the right knee. Vital signs are HR 142 bpm, BP 133/86 mmHg, RR 22 breaths/min, SpO₂ 98% on room air, T 98.7°F. Laboratory testing demonstrated platelets 482 × 10⁹/L, fibrinogen 241 mg/dL, and INR 1.2. He was admitted to the pediatrics service for further management.

Questions:

1. What are the primary clinical manifestations of crotalid envenomation?
2. How do you manage crotalid envenomations?
3. What are the indications for antivenom administration?
4. What antivenoms are available to treat crotalid envenomation?
5. What is the dosing schedule for antivenom?
6. What are the indications for repeat dosing of antivenom?

Background:

• According to the Center for Disease Control (CDC), approximately 7,000-8,000 people in the United States (US) suffer envenomation by a snake each year. Envenomation by crotalidae (pit vipers) represent 99% of snake envenomations in the US.¹
• Copperhead (Agkistrodon contortrix) and cottonmouth / water moccasin (Agkistrodon piscivorus) are the two species of pit viper responsible for the majority of snake envenomations in many regions of eastern and southeastern US²
• Other crotalids found in North America include:
  • Timber/canebrake and pigmy rattlesnakes found in the eastern/southeastern US
  • Eastern and western diamondback rattlesnakes, found in eastern and western North America, respectively
  • Several additional species of rattlesnakes found west of the Mississippi
• Crotalid venom contains a variable mixture of compounds including proteases, metalloproteinases, phospholipases, disintegrins, and rarely neurotoxins.^3,4 These venom components contribute to primarily cytotoxic, hemotoxic, myotoxic, and proinflammatory effects.
• Crotalid envenomation is characterized by rapid onset and progression of local tissue injury characterized by severe pain and hyperalgesia, swelling, ecchymosis, and ultimately necrosis if left untreated
• Systemic effects are primarily coagulopathic and characterized by thrombocytopenia and hypofibrinogenemia
• The genus of snake influences its predominant toxic effects
  • Genus Agkistrodon (copperhead and cottonmouth) envenomations tend to cause primarily local tissue injury, while genus Crotalus (rattlesnake) envenomations will often cause local tissue injury and significant coagulopathic effects, which may rebound even after treatment with antivenom
• For severe crotalid envenomations, rapid administration of antivenom is indicated to halt the progression of both local tissue injury and coagulopathy

Management:

Out of Hospital Initial Management:

• Address scene safety. Avoid additional bites to yourself or the patient and move the patient safely away from the snake. Do NOT attempt to capture or kill the snake.
  • Remember that a dead snake still has a bite reflex and may still cause envenomation
• Do NOT apply tourniquets, ice, or direct pressure
• Do NOT incise the wound, “suck and spit”, or apply a suction device
• Remove any tight-fitting clothing and jewelry
• Immobilize the bite site and attempt to keep in a neutral position until able to reach a healthcare facility with antivenom.
• Evacuate the patient to the nearest ED or hospital with antivenom available
• Consider contacting your local poison control center for further guidance at 800-222-1222

Emergency Department and Inpatient Management:

• Assess airway, breathing, and circulation
• Consult your local poison control center (800-222-1222) and/or medical toxicologist
• Monitor and assess the extent of local swelling, tenderness, and hemorrhagic blebs frequently (every 30-60 minutes) until progression has halted
• Measure and record the circumference of the affected limb at multiple intervals, such as mid-foot, ankle, mid-calf, and thigh for a lower extremity bite
  • Clearly mark these points of measurement for future comparison so measurements are taken at the same locations
    • Remember to mark both sides of the limb and both sides of the tape so that repeat measurements can be performed in the same fashion
  • Small increases in proximal swelling are expected as edema mobilizes with elevation, however progression of swelling more distally may indicate worsening tissue injury
• If there is a well-demarcated line of swelling or discoloration, mark this with a pen, indicating the date and time
• Elevate the affected limb and maintain gentle extension of the joints
  • Mechanisms for elevation may include:
    • Multiple pillows or sheets/blankets under the limb
    • Putting limb up on a table next to the bed
    • Raising the end of the hospital bed
    • Finger traps to keep arm elevation – but if bite is in hand or fingers would be concern for compression and tissue injury
  • Can splint in relative extension if necessary to promote lymphatic drainage.
  • Give analgesics for pain control but avoid NSAIDs due to their inhibitory effect on platelets
  • Obtain initial labs including CBC, BMP, PT/INR, and fibrinogen. Repeat labs approximately 6 hours after initial control and/or prior to discharge.
    • If there is concern for envenomation by rattlesnake, repeat labs may be indicated 2-3 days and 5-7 days after antivenom administration
  • Consider serial negative inspiratory force (NIF)/maximum inspiratory pressure (MIP) or EtCO₂ monitoring if concerned for neurotoxicity
    • Be aware that several species of North American rattlesnake have the potential to cause neurotoxic effects, most notably the Mojave rattlesnake, tiger rattlesnake, Southern Pacific, and some populations of timber/canebrake rattlesnakes^3,5
  • Patients who have minimal or no local symptoms, no evidence of progression after 8 hours, normal labs, and no indication for antivenom may be considered for discharge
  • Patients should be monitored for 12 hours or longer if symptoms are more than minimal⁶
  • Patients with evidence of significant systemic toxicity (hemodynamic instability, airway involvement, neurotoxicity, or evidence of severe hematologic toxicity on labs) should be considered for ICU admission
  • It is unlikely that these patients develop compartment syndrome and do not tend to need surgical procedures/intervention. If you are concerned for elevated compartment pressures, the patient needs to be treated with antivenom.

Which patients require treatment with antivenom?

Indications:^6,7

• Significant or progressive local tissue damage (swelling, tenderness, hemorrhagic blebs)
  • There are controversial and varying opinions on what determines “significant”
    • Some authors used the number of centimeters from envenomation site, others use anything more than “minimal” and others differentiate between snake species.
    • Clinically often swelling and tenderness may be considered significant if they extend beyond one major joint from the bite site (e.g., past ankle or wrist) or there is rapid progression of swelling up the affected extremity
  • Localized signs of tissue injury may be considered significant if they involve the hands, face, neck, or other sensitive areas as determined by the treating provider
• Significant local tissue injury (necrosis) without extensive swelling
• Systemic toxicity (hypotension, airway swelling, neurotoxicity)
• Significant or progressive hematologic toxicity (platelets < 50 × 10⁹/L, fibrinogen < 50 mg/dL)
  • Serial testing is warranted for less severe laboratory abnormalities (fibrinogen < 150 mg/dL, etc.)
• Recurrent progression of symptoms after initial control

Dosing of antivenom:^6,8–10

• F(ab) (CroFab®)
  • Initial dose: 4-6 vials IV over 60 minutes (8-12 vials for shock or serious active bleeding)
  • Reexamine within 1 hour and repeat initial dose until symptoms are no longer progressive
  • Maintenance dose: 2 vials every 6 hours for 3 additional doses
  • Recurrent symptoms: Additional 2 vials
•  F(ab’)₂ (ANAVIP®)
  • Initial dose: 10 vials IV over 60 minutes
  • Reexamine within 1 hour and repeat initial dose until symptoms are no longer progressive
  • Maintenance dose: None
  • Recurrent symptoms: Additional 4 vials
• Note – Pediatric dose is the same as adult dose

Please see Part 2 of this Series for a more in-depth discussion on the similarities and differences between F(ab) and F(ab’)₂ antivenoms as well as the continuation and conclusion of our case!

Clinical Pearls:

• Most snake envenomations in the US are caused by pit vipers (crotalidae) and are characterized by local tissue injury and coagulopathic effects
• Copperhead and cottonmouth (Agkistrodon sp.) envenomations are generally characterized by prominent local tissue effects without laboratory abnormalities, while rattlesnake (Crotalus) envenomations often cause early, late, and recurrent coagulopathy in addition to local tissue effects.
• Initial management steps include elevation, serial exams, and pain control
• F(ab) (CroFab®) and F(ab’)₂ (ANAVIP®) crotalid antivenoms are FDA approved and indicated for severe crotalid envenomation with severe or progressive localized symptoms, systemic symptoms, and/or signs of coagulopathy on labs

References:

1. Smith TA, Figge HL. Treatment of snakebite poisoning. Am J Hosp Pharm. 1991;48(10):2190-2196.
2. Venomous Snakes | NIOSH | CDC. Published April 15, 2022. Accessed May 7, 2022. https://www.cdc.gov/niosh/topics/snakes/default.html
3. Buchanan JT, Thurman J. Crotalidae Envenomation. In: StatPearls. StatPearls Publishing; 2022. Accessed May 17, 2022. http://www.ncbi.nlm.nih.gov/books/NBK551615/
4. Kanaan NC, Ray J, Stewart M, et al. Wilderness Medical Society Practice Guidelines for the Treatment of Pitviper Envenomations in the United States and Canada. Wilderness Environ Med. 2015;26(4):472-487. doi:10.1016/j.wem.2015.05.007
5. Rolan TD. Neurotoxic snakes of the Americas. Neurol Clin Pract. 2015;5(5):383-388. doi:10.1212/CPJ.0000000000000180
6. Lavonas EJ, Ruha AM, Banner W. et al. Unified Treatment Algorithm for the management of crotalid snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;3(11):2.
7. Clinical Practice Statements. AAEM – American Academy of Emergency Medicine. Accessed May 7, 2022. https://www.aaem.org/resources/statements/clinical-practice
8. Antivenom administration North American Crotalinae snakebites – UpToDate. Accessed May 7, 2022. https://www.uptodate.com/contents/image/print?imageKey=EM%2F122011&topicKey=EM%2F8365&source=see_link
9. Highlights of prescribing information. ANAVIP. Crotalidae Immune F(ab’)2 (Equine). Published online April 2021. Accessed May 7, 2022. https://www.fda.gov/media/92139/download
10. CroFab Snakebite Treatment Dosing | CroFab.com. Accessed May 7, 2022. https://crofab.com/treating-with-crofab/dosing

The post ToxCard: Crotalid Envenomation Part 1: Management of the Crotalid Envenomation appeared first on emDOCs.net - Emergency Medicine Education.

Answer: Flexor tendon injury

Epidemiology:

• Secondary to deep penetration with sharp objects or blunt trauma at tendinous attachments to bone²
• Common in young men in manual labor (20-45 years)
• Literature has conflicting data regarding dominance of hand injured^2,3
  • Usually injured when using a sharp object or catching a falling object
  • Overall epidemiology of flexor tendon injuries is not well understood
• Commonly involve nerve injuries²

Anatomy:

• Deeper compared to extensor tendons–injuries more likely to involve neurovascular structures
• Primary wrist flexors: flexor carpi ulnaris and radialis
• Primary thumb flexors: flexor pollicis longus and brevis
• PIP joint flexor: Flexor digitorum superficialis
• DIP joint flexors: Flexor digitorum profundus
  • DIP and PIP flexors operate via a pulley system (Image 4)

Classic injuries: 

Jersey finger

• Athlete grabbing for opponent’s jersey
  • Forced hyperextension while DIP is in flexion
  • Disruption of FDP at distal phalanx (closed injury)^6,7

Clinical Presentation:

• Flexor injuries typically from deeper lacerations to the volar surface of the hand
• Loss of flexion strength or motion in effected digit
• Deeper lacerations may have neurovascular injury with loss of sensation or motor control

Evaluation:

• History should include: mechanism, occupation, handedness, time of injury, tetanus status, prior injuries⁶
• Examine prior to anesthesia to obtain accurate sensorimotor function⁶
• Isolate each joint to test strength against resistance
• Test for neurovascular deficits with light touch/pinprick sensation, doppler
• Evaluate for bruising, wounds, deformities
• Adequate anesthesia should be used for wound exploration and decontamination
• Evaluate wounds by reducing blood flow and irrigation
  • Finger tourniquets should be used⁶
  • Note wounds involving joint spaces or open fractures
• X-ray should be used to identify fractures or retained foreign bodies
  • Ultrasound is effective for identifying hand fractures⁸
• Ultrasound may be useful to evaluate for tendon disruption⁹
• Evaluate the zone of injury

Zones of injury 

• Tendon zones will help identify structures injured and guide further treatment

• Treatment does not vary, however important to identify zone if talking to consultant
• I: Distal to FDS insertion–contains only FDP
• II: FDS insertion to distal palmar crease–contains FDS/FDP
• III: Palm
• IV: Carpal tunnel
• V: Carpal tunnel to forearm
• TI: Distal to thumb interphalangeal (IP) joint
• TII: Base of thumb to IP joint
• TIII: Thenar eminence¹¹
• Zones II-V are the most common areas of injury^{2, 11}

Treatment: 

• Disruption of flexor tendons should not be repaired in the ED
  • Flexor tendon repair is a difficult, delicate, and precise process that requires operation
• Local hemostasis, pain control with a digital, radial, or medial nerve block depending on location of injury, and wound repair with non-absorbable sutures
•  Most patients get a short course of antibiotics in open tendon injuries, but not required
  • Several prospective, randomized control trials show no statistical significance in wound infection with hand lacerations^12-14
• Cephalexin 500mg for 5-7 days is appropriate for the majority of open tendon injuries if they are otherwise clean
• Consider extensive contamination, open fractures, which would warrant orthopedic consultation
  • Type I: open fracture with <1cm clean laceration, minimal soft tissue damage
    • Cefazolin 2 g IV three times daily in adults
      • 30 mg/kg three times daily in children
  •  Type II: open fracture with 1-10 cm clean laceration without extensive injury
    • Same as Type 1
  •  Type III: open fracture >10cm with extensive soft tissue damage or heavily contaminated/farm injury
    • Cefazoline 2 g IV three times daily
    • Gentamicin 5-7 mg/kg IV once daily in adults
      • 2.5 mg/kg IV three times daily in pediatrics¹⁵
•  Depending on local practice, orthopedics consultation versus urgent referral for definitive repair of lacerations¹⁶
  • Open fractures of the hand should warrant orthopedic consultation
  • When in doubt over extent/degree of injury and disruption of tendons, orthopedic/hand consultation for a definitive plan is reasonable
  • If referring, patient will need follow up within 2-3 days for evaluation of extent of injury and possible urgent surgical repair¹⁶
  • If evaluation in the emergency department and no surgery indicated urgently, sutures to be left in place for 10 days or until sooner evaluation in orthopedics clinic

Pearls

• Flexor tendon injuries should have local wound repair, splinting in flexion, and timely orthopedics follow-up for definitive surgical repair
• Complete a thorough physical exam, noting neurovascular status as well as isolated joint mobility and strength
• Patients generally have local tissue repair, splinting, and outpatient hand specialist follow up, however consider hand consultation if damage is extensive or consider transferring if no hand specialist is available for patient to follow up with
• Consider the closed injury “Jersey finger” in the patient with pain/motor deficit at the DIP

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

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Today we look at the DIRECT MT trial.

Author: Brannon L Inman, MD (Critical Care Fellow, Orlando, FL) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Clinical question:

In patients with anterior circulation large vessel occlusion, is thrombectomy alone non-inferior to thrombectomy preceded by alteplase?

Study design:

• Multicenter open label randomized control trial
• Enrolled patients from 41 tertiary care hospitals in China
• Assessing for statistically significant difference in modified Rankin score at 90 days

PICO:

Population: 206 patients were enrolled with 107 in the intervention group and 99 in the control.

– Inclusion criteria:

• Enrolled patients over the age of 18 with acute ischemic stroke with CTA confirmed occlusion of ICA, or M1 or M2 segment of MCA
• Within 4.5 hours of onset
• Eligible for tPA and thrombectomy
• NIHSS ≥ 2

– Exclusion criteria:

• Disability before presenting CVA, defined by modified Rankin score ≥2
• Any contraindication of IV tPA or thrombolytics

Randomization:

• Slightly longer median duration in tPA group (167 vs 177)
• Overall very similar in terms of group baseline characteristics

Intervention:

• Endovascular thrombectomy alone

Comparator:

• Endovascular thrombectomy + tPA

Outcome:

• No statistically significant difference in primary outcome
  • mRS 3 (2-5) vs 3 (2-5)
  • Adjusted value 1.07 (95% CI 0.81-1.40)
• No statistically significant difference in secondary outcomes
• No significant difference in safety outcomes
  • Death 18% vs. 19%, RR 0.94 (0.68-1.30)
  • Intracranial hemorrhage
    • Asymptomatic 33% vs. 36%, RR 0.92 (0.75-1.14)
    • Symptomatic 4% vs. 6%, RR 0.70 (0.36-1.37)
  • Infarction in new territory at 5-7 days 3% vs. 3%, RR 1.23 (0.52-2.93)
  • Large or malignant MCA infarction 13% vs. 13%, RR 0.98 (0.66-1.46)
  • Any procedural complication 15% vs. 14%, RR 1.05 (0.72-1.52)

Take away:

• This trial found no significant difference in thrombectomy alone versus thrombectomy plus alteplase.
• It was a well-conducted multicenter trial. However, given the monochromatic study population there is limited external validity and generalizability, particularly in more heterogeneous patient populations.
• While patients had to be within 4.5 hours to be randomized, the median IQR was 7 hours (4-12) to start of tPA for the control group. This raises concern that patients may have received tPA after 4.5 hours of stroke onset. Based on the data current guidelines lean on, this could raise concern about the expected validity of the tPA therapy (i.e., these patients may have received tPA too late for it to be even plausibly useful).
• Based on the times from tPA to arterial puncture and door to puncture times, this study only really applies tocomprehensive stroke centers with thrombectomy capability. These data cannot be applied to centers that have to transfer patients to higher levels of care.

My take:

It’s entirely possible that in comprehensive stroke centers tPA may confer no added benefit to thrombectomy for anterior circulation LVOs. However at the bedside based on current guidelines, I will continue to offer tPA when indicated or requested by endovascular operators.

Reference:

1. Yang P, Zhang Y, Zhang L, et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.N Engl J Med. 2020;382(21):1981-1993. doi:10.1056/NEJMoa2001123

The post 52 in 52 – #40: DIRECT MT – Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke appeared first on emDOCs.net - Emergency Medicine Education.

Background

• Testicular torsion has essentially no associated mortality, little morbidity, and no literature support for diminished fertility.  However, patients remain concerned about losing a testicle, and there is high medicolegal risk.
• Several mimics of testicular torsion:
  • Epididymitis, orchitis, and UTIs
  • Torsion of the appendix testis or appendix epididymis → Blue dot sign
  • Sexually transmitted infections
  • Oncologic diagnoses 
    • Diffusely hard testicle → lymphoma and leukemia
  • Idiopathic edema, hernia, hydroceles, varicocele 
    • Fluctuating pain/swelling, positional swelling
  • Trauma  → Ecchymoses, visible injury
• Pathophysiology
  • Twisting of the testicle along the spermatic cord → ↓venous outflow → vascular congestion →swollen/painful testicle
  • ↑ pressure and/or further twisting → ↓ arterial flow → ischemia  
    • Severity depends on duration & degree of cord rotation.
    • Severe ischemia and necrosis start in 4-6 hours
•  Two forms: 
  • Intravaginal
    • Adolescents/young adults
    • Abnormal attachment of the tunica vaginalis
    • Bell clapper deformity allows spermatic cord to twist
  • Extravaginal
    • Neonates
    • Tunica vaginalis is not adhered to the gubernaculum
    • Tunica vaginalis and spermatic cord twist together.

What are risk factors?

• Bimodal age of distribution: at birth and 12-18 years 
  • 14% of cases occur in adults; older patients have worse outcomes 
• Bell clapper deformity – bilateral in 80% of patients
• Prior episode of torsion 
• Family history
• Trauma (can be minor)

Clinical Presentation:

• Sudden/severe testicular pain
  • Often unilateral, may radiate.
  • Pain can be intermittent.
  • 84-90% have testicular pain.
  • May start within a few hours of a minor trauma or wake them from sleep.
• Abdominal/flank pain – 20% ONLY have this complaint (check this testicles in a male patient with abdominal/flank pain).
• Diffuse scrotal/testicular tenderness, swelling, and erythema (a later sign).
• Nausea and vomiting.
• Difficulty urinating – 12% of cases.

Exam:

• Tender, swollen, firm, high riding testicle (OR 18-58.8 for diagnosis).
• Long axis of the torsed testicle may be oriented horizontally.
• Erythema of the scrotal wall and reactive hydrocele are late findings.
• Hard, tender knot in spermatic cord.
• Cremasteric reflex 
  • Classically absent/diminished in torsion, but cannot definitively rule in or out torsion. 
  • In one study, ~40% of torsion patients had a cremasteric reflex. 
  • 30% of patients with normal testicles will not have a cremasteric reflex.  
• Prehn’s sign (pain relief with elevation of the testicle)
  • Classically associated with epididymitis.
  • ⅓ of kids with torsion had a positive Prehn’s sign.
  • Don’t rely on the Prehn’s sign in your evaluation of torsion.

The Testicular Workup for Ischemia and Suspected Torsion (TWIST) scoring and risk stratification system (TWIST SCORE):

• 2013 original study and recommendations:
  • 0-2 points = LOW RISK, not torsion – consider other diagnosis
  • 3-4 points = Intermediate Risk – need ultrasound
  • 5-7 points = High Risk – high likelihood of torsion, call urology
  • Found 100% negative and positive predictive values using a cutoff of 2 points for low risk and 5 points for the high risk group.  
• 2016 validation study 
  • 0 points for low risk, 1-5 for intermediate risk and 6-7 for high risk.
• 2022 meta-analysis 
  • 0-2 as low risk and ≥5 or higher as high risk =  AUC of 0.924.
  • 0 as low risk, 1-5 points as intermediate risk and ≥6 points as high risk  = 99.5% sensitive. 
• Keys:
  • Order the ultrasound in a patient with testicular pain, especially with any TWIST score >0.
  • Minimal if any harm to patients by obtaining ultrasound.
• If you are going to use the TWIST score, make sure your department and your urologists are comfortable with it. Figure out what score you’ll use for low risk and high risk. 

Evaluation:  

• US with doppler is the first line imaging modality.  
  • Enlarged, hyperemic testicle with ↑ echogenicity, irregular contour & reactive hydrocele (note: latter might not appear for several hours).
  • Assess for no flow or decreased flow velocity in intratesticular arteries.
    • Power doppler preferred over color doppler as it is sensitive to low-flow states. Color doppler provides flow direction, which we do not care about in torsion.
  • Other signs on US:
    • Whirlpool sign – twisted spermatic cord with spiral pattern.
    • Pseudomass –  congested epididymis/vas deferens/vascular bundle below twisted spermatic cord.
    • Horizontally lying testicle.
  • Sensitivity 86-98%; specificity 90-98%.  
  • POCUS is not as accurate.
  • Even with a normal ultrasound, if the history/exam are concerning – call urology.
• Degrees of torsion:
  • Complete –  testicle twists ≥360^o, US usually shows absence of intratesticular flow.
  • Incomplete – testicle twists <360^o. Flow is decreased but present.
  • Intermittent – testicle torses and detorses.  

Management:

• Definitive therapy = surgical exploration, detorsion, and fixation of the testicle.
  • Contralateral orchiopexy due to risk of torsion of the other testicle .
  • Orchiectomy necessary if necrotic.
  • > 90% salvage rate within the first 6 hours.
  • Systematic review shows testicular survival was 97.2% at 0-6 hours, 79.3% at 7-12 hours, 61.3% at 13-18 hours, 42.5% at 19-24 hours, 24.4% at 25-48 hours, and 7.4% at greater than 48 hours. 
  • Another study found that every 10 minute delay to detorsion increased the risk of testicular nonviability by 5%. 
• If no urologist, attempt manual detorsion:
  • Success rate of 30-70%.
  • Manual detorsion is classically described as “opening the book”.
    • Face the patient, grab the affected testicle between your thumb and index finger, and then rotate the testicle laterally towards the ipsilateral thigh.
    • Some studies suggest the average degree of torsion is 720 degrees, so you may need to “open the book” a couple times.  
    • If no improvement or worsening pain, rotate in the opposite direction as if you are “closing the book”.
  • Analgesia, not sedation, is necessary.
  • Repeat ultrasound after manual detorsion to look for normal blood flow.
  • All patients need admission for exploration and orchiopexy/orchiectomy.

Medicolegal considerations:

• 3rd most common cause of malpractice suits in males 12-17 years old & average settlement of $60,000.
• Missed diagnosis often due to: atypical presentation, torsion not considered, or no testicular exam was done.
• Document consideration of torsion in males with abdominal pain.

Pearls:

• There are findings on history and exam that suggest torsion, but there is no single element that can exclude it including the cremasteric reflex.
• The TWIST score has been validated and can help guide clinical decision making in patients presenting with acute testicular pain.
• US with doppler is the first line imaging modality.
• The diagnosis is time sensitive. Patients have the best outcomes when detorsion occurs in the first 6 hours after symptom onset.
• Definitive management is surgical exploration and detorsion, but if there is going to be a major delay and there is confirmed diagnosis, go with manual detorsion.

References:

1. Rosenberg H, Long B, Keays M. Just the facts: assessment and management of testicular torsion in the emergency department. CJEM. 2021 Nov;23(6):740-743. doi: 10.1007/s43678-021-00189-6. Epub 2021 Aug 18. PMID: 34406643.
2. Mellick LB, Sinex JE, Gibson RW, Mears K. A Systematic Review of Testicle Survival Time After a Torsion Event. Pediatr Emerg Care. 2019 Dec;35(12):821-825. PMID: 28953100.
3. Barbosa JA, Tisea BC, Barayan GA, Rosman BM, Torricelli FCM, Passerotti CC, Srougi M, Retik AB, Hguyen HT. Development and initial validation of a scoring system to diagnose testicular torsion in children. J Urol. 2013;189(5):1859–64. PMID: 2310800
4. Sheth KR, Keays M, Grimsby GM, et al. Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score. J Urol. 2016;195(6):1870-1876.  PMID: 26835833
5. Qin KR, Qu LG. Diagnosing with a TWIST: Systematic Review and Meta-Analysis of a Testicular Torsion Risk Score. J Urol. 2022;208(1):62-70. PMID: 35238603 
6. Gold DD, Lorber A, Levine H, et al. Door To Detorsion Time Determines Testicular Survival. Urology. 2019;133:211-215.  PMID: 31408640

The post emDOCs Podcast – Episode 83: Testicular Torsion appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Lauren Willoughby, MD (Education Fellow, University of Wisconsin); Benjamin H. Schnapp, MD, MEd (Associate Program Director, University of Wisconsin) // Reviewed by: Joshua Lowe, MD (EM Attending Physician, USAF), Marina Boushra (EM-CCM, Cleveland Clinic Foundation); Brit Long, MD (@long_brit)

Case

A 36-year-old pregnant woman at 21 weeks gestation presents to the ED with chest pain. Her past medical history is notable for hypertension and hyperlipidemia. The chest pain started suddenly today while at rest, is located on the right side, and radiates to her back. She denies other symptoms, including leg pain or swelling. Vital signs include BP 130/75 mmHg, HR 115 bpm, RR 24 breaths per minute, oxygen saturation of 93% on room air, and an oral temperature of 98.8° F. Her lungs are clear to auscultation. There is no swelling, redness, or tenderness in her calves.

What are the next steps in the evaluation of this patient?

What is the utility of D-dimer testing in the evaluation of venous thromboembolism (VTE) for this patient?

How does her pregnancy affect the utility of D-dimer levels in the exclusion of VTE?

What is a D-dimer?

Intravascular activation of the coagulation cascade results in the production of a fibrin clot. The enzyme plasmin then degrades the fibrin clot into soluble D-dimer fragments. To maintain a state of homeostasis, any process that activates the coagulation cascade results in the production of both a fibrin clot and D-dimer fragments as that clot is degraded.¹ A D-dimer level can, therefore, be used as a non-specific and indirect biomarker for the presence of intravascular clotting, which may be useful in the diagnosis of VTE. However, D-dimer levels may be elevated for a variety of different physiologic and pathologic reasons. While diagnoses such as pulmonary embolism (PE) and deep vein thrombosis (DVT) are classically associated with D-dimer elevation, many other conditions such as surgery, cancer, inflammation, and infection will also cause activation of the coagulation cascade and production of clots, resulting in an elevation in D-dimer level (Table 1).

Clinical utility of D-dimer in the general population

The use of a D-dimer level in the evaluation of VTE in the general population has been extensively studied and validated. When assessing for VTE, the standard cut-off for a “positive” or elevated result is 500 ng/mL.^2,3  Sensitivity for VTE is high at this cut-off value, ranging between 75 and 96% depending on the assay used.^2,3 However, this high sensitivity comes at the expense of a low specificity, which can range between 45 and 83% depending on the assay used.² Since VTE can be a potentially life-threatening diagnosis, the cut-off value for a negative result must minimize the number of false negatives, or have a high sensitivity.³  If the cut-off value were raised, this would result in a larger number of false negatives and missed VTEs.

Because population incidence affects the negative predictive value (NPV) of D-dimer testing, it is important to determine the pre-test probability of a patient having a VTE prior to obtaining the D-dimer level. Physician gestalt and clinical decision-making tools such as the Wells’ (https://www.mdcalc.com/calc/115/wells-criteria-pulmonary-embolism) or Geneva (https://www.mdcalc.com/calc/1750/geneva-score-revised-pulmonary-embolism) scores are helpful when assessing a patient’s pre-test probability, which is categorized as low, moderate, or high risk.

D-dimer testing is most useful in low- to moderate-risk patients.^1-3 In this patient population, the NPV of a negative D-dimer level is high, such that a negative test makes further evaluation for VTE  unnecessary. Given the low specificity of D-dimer for VTE, if the D-dimer level is found to be elevated in this patient population, imaging tests with greater sensitivity are the recommended next step.^1-3  In patients with a high pre-test probability for VTE, advanced imaging without D-dimer testing is recommended. This is because even if the D-dimer is negative, the high prevalence of VTE in high-risk patients makes the NPV of the test low.²  The diagnostic utility of D-dimer testing in VTE in the general population is illustrated below in Figure 1, which outlines a diagnostic algorithm for the evaluation of PE based on D-dimer testing.

When VTE is suspected in a low- to moderate-risk patient, obtaining a D-dimer level can have numerous benefits. Results of blood work are usually available quicker than results of imaging studies, so the exclusion of VTE will typically be faster using a D-dimer level compared to imaging.^1-3  Since obtaining a D-dimer level may lead to a faster diagnosis, it can decrease the patient’s length of stay. Further, excluding VTE through D-dimer testing will reduce unnecessary radiation by decreasing the need for advanced studies such as CT.

D-dimer and special populations

While an elevated D-dimer level may indicate the presence of a pathologic process, higher levels may be normal in certain populations, particularly pregnant women and older patients. This presents diagnostic challenges for the emergency physician when evaluating these patients for VTE using D-dimer.

Pregnancy

D-dimer levels typically rise throughout pregnancy and reach the highest concentrations by the third trimester.² The physiologic rise in D-dimer levels makes the evaluation of PE in this patient population especially challenging because shortness of breath is common in pregnancy for reasons unrelated to VTE but pregnancy is a known risk factor for VTE.  To address this need, the pregnancy-adapted YEARS algorithm was developed and externally validated.⁴ This algorithm combines D-dimer level with the presence of three YEARS criteria (hemoptysis, clinical signs of DVT, and PE as the most likely diagnosis) to determine the next steps in the evaluation of PE in a pregnant patient (Figure 2).⁴ If the patient meets none of the YEARS criteria, the D-dimer cut-off for a positive test can be increased to 1,000 ng/mL.⁴

The pregnancy-adapted YEARS algorithm has been sho
wn to safely rule out pulmonary embolism in pregnant patients, with the incidence of VTE during a 3-month follow-up period being 0.42%.⁴ The pregnancy-adapted YEARS score has the highest efficacy during the first trimester.⁴ The ability to utilize a D-dimer level to rule out PE in pregnant patients is helpful in avoiding unnecessary radiation exposure to the patient and the fetus.

Older Adults

Elevated D-dimer levels are commonly found in older patients in the absence of pathology.⁵ Given the physiological rise in D-dimer levels with age, studies have investigated the use of an age-adjusted D-dimer cut-off when evaluating for a PE in patients greater than 50 years old. The optimal age-adjusted cut-off was determined to be the patient’s age multiplied by 10 as opposed to the traditionally used cut-off of 500 ng/mL.⁶ For example, a patient who is 70 years old would have an age-adjusted cut-off of 700 ng/mL. A follow-up study showed the age-adjusted D-dimer had a similar 3-month VTE risk as a D-dimer <500 ng/mL or a negative CT pulmonary angiogram.⁷   The American College of Emergency Physicians (ACEP) clinical policy supports the use of age-adjusted D-dimer testing when evaluating for VTE in older patients. ⁸

D-dimer testing beyond VTE  

While a D-dimer level is frequently obtained when evaluating for VTE, it may be useful in the workup of other disorders as well.

Acute Aortic Dissection (AAD)

A meta-analysis found that plasma D-dimer level <500 ng/mL is useful for identifying patients who are unlikely to have an AAD and do not require further aortic imaging. However, the authors do note that D-dimer testing is not applicable in high-risk patients (ie, those with a history Marfan syndrome or Ehlers-Danlos), and its use in specific types of aortic dissection (ascending vs descending) or in specific populations (ie, elderly), has not been extensively studied.⁹ Additionally, a D-dimer level in the evaluation of AAD is most useful within 24 hours of symptom onset.¹⁰ Therefore, though there is some evidence to support the use of obtaining a D-dimer level for evaluating for AAD as part of an overall clinical picture, the American College of Emergency Physicians (ACEP), recommends that physicians not rely on D-dimer results alone to exclude the diagnosis of AAD.¹¹

Disseminated Intravascular Coagulation (DIC)

D-dimer levels are also helpful when evaluating for DIC, a disease process of marked intravascular clot formation and degradation. The International Society of Thrombosis and Hemostasis recommends using a D-dimer level, in addition to other laboratory markers, as part of a scoring system to diagnose DIC.¹² It is important to note that the threshold for a positive result is different when evaluating for DIC, and the exact threshold remains unclear. However, based on prior studies, a D-dimer level of 3-7 mcg/mL has been suggested as a sensitive cut-off level for diagnosis of DIC.¹³

Pearls and Pitfalls

• Many conditions can cause an elevation in D-dimer levels. These conditions include VTE as well as infection, cancer, kidney or liver disease, and recent surgery
• D-dimer test has high sensitivity but low specificity for VTE.
• D-dimer testing is most useful in patients who are low-to-moderate-risk for VTE.
• D-dimer levels rise normally in older adult patients and throughout pregnancy, which requires modification to the typical algorithms used to evaluate for VTE
• D-dimer testing alone cannot rule out the presence of AAD

Case Resolution 

The patient’s D-dimer level was found to be 900 ng/mL. Given that she met no other YEARS criteria and was below the cutoff of 1000 ng/mL, she was deemed low-risk for PE and no additional work-up for PE was indicated.

References:

1. Linkins LA, Takach Lapner S. Review of D-dimer testing: Good, Bad, and Ugly. Int J Lab Hematol. 2017;39 Suppl 1:98-103. doi:10.1111/ijlh.12665
2. Weitz JI, Fredenburgh JC, Eikelboom JW. A Test in Context: D-Dimer. J Am Coll Cardiol. 2017;70(19):2411-2420. doi:10.1016/j.jacc.2017.09.024
3. Pulivarthi S, Gurram MK. Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci. 2014;6(10):491-499. doi:10.4103/1947-2714.143278
4. van der Pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med. 2019;380(12):1139-1149. doi:10.1056/NEJMoa1813865
5. Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J. 2007;37(9):607-613. doi:10.1111/j.1445-5994.2007.01388.x
6. Douma RA, le Gal G, Söhne M, et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ. 2010;340:c1475. Published 2010 Mar 30. doi:10.1136/bmj.c1475
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study [published correction appears in JAMA. 2014 Apr 23-30;311(16):1694]. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135
8. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Thromboembolic Disease:, Wolf SJ, Hahn SA, et al. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease. Ann Emerg Med. 2018;71(5):e59-e109. doi:10.1016/j.annemergmed.2018.03.006
9. Shimony A, Filion KB, Mottillo S, Dourian T, Eisenberg MJ. Meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection. Am J Cardiol. 2011;107(8):1227-1234. doi:10.1016/j.amjcard.2010.12.027
10. Suzuki T, Distante A, Zizza A, et al. Diagnosis of acute aortic dissection by D-dimer: the International Registry of Acute Aortic Dissection Substudy on Biomarkers (IRAD-Bio) experience. Circulation. 2009;119(20):2702-2707. doi:10.1161/CIRCULATIONAHA.108.833004
11.  American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Thoracic Aortic Dissection, Diercks DB, Promes SB, et al. Clinical policy: critical issues in the evaluation and management of adult patients with suspected acute nontraumatic thoracic aortic dissection [published correction appears in Ann Emerg Med. 2017 Nov;70(5):758]. Ann Emerg Med. 2015;65(1):32-42.e12. doi:10.1016/j.annemergmed.2014.11.002
12. Toh CH, Hoots WK; SSC on Disseminated Intravascular Coagulation of the ISTH. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007;5(3):604-606. doi:10.1111/j.1538-7836.2007.02313.x
13. Suzuki K, Wada H, Imai H, et al. A re-evaluation of the D-dimer cut-off value for making a diagnosis according to the ISTH overt-DIC diagnostic criteria: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16(7):1442-1444. doi:10.1111/jth.14134

The post Utility of D-dimer Testing in Special Populations appeared first on emDOCs.net - Emergency Medicine Education.

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

Authors: Eric Sabatini Regueira, MD (Emergency Medicine PGY-3, Carolinas Medical Center, Charlotte, NC) and Ann-Jeannette Geib, MD (Emergency Physician/Medical Toxicologist, Carolinas Medical Center, Charlotte, NC)// Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UT Southwestern Medical Center, Dallas, TX); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case:

A 26-year-old female with history of depression presents to the ED after ingesting 15 g of acetaminophen in a suicide attempt 3 hours prior to arrival. Patient is asymptomatic. A 4-hour acetaminophen level is obtained and results with a level of 180 mcg/mL.

Question:

After emergency stabilization and supportive treatment, what is the next step in treatment?

Answer:

N-acetylcysteine (NAC) is the best next step in treating this patient

Background:

• Indicated for patients presenting with a toxic acetaminophen concentration (above the modified Rumack-Matthew treatment line starting at 150 mcg/mL at 4 hours in the US), hepatotoxicity attributable to acetaminophen overdose, or in patients with reported ingestion in whom the laboratory result will not be available within 8 hours from ingestion
• Acetaminophen mostly undergoes glucuronidation and sulfation into nontoxic metabolites
• In case of large ingestions, the glucuronidation and sulfation pathways become saturated. A minor (CYP2E1) pathway transforms acetaminophen to N-acetyl-p-benzoquinone imine (NAPQI), which is a toxic metabolite.
• NAPQI can be further metabolized into other nontoxic substances, via a glutathione-dependent pathway
• Glutathione is depleted when large quantities of acetaminophen are ingested, leaving NAPQI free to cause oxidative stress, mostly in the liver – where it is produced
• N-acetylcysteine is deacetylated into cysteine; the availability of cysteine is the rate limiting step in glutathione synthesis
• By providing more cysteine, NAC provides substrate for glutathione synthesis, which in turn can be further utilized for detoxifying NAPQI
• NAC is also beneficial in patients with acetaminophen overdose presenting more than 8 hours after ingestion

Dosing:

• Oral and IV regimens are available
• Both oral and IV NAC are effective in treating acetaminophen overdose. IV is usually recommended due to faster onset, ease of administration, and shorter protocol duration.
• Oral dosing (total of 72 hours, 18 doses)
  • Loading dose 140mg/kg
  • Maintenance dose 70mg/kg every 4 hours, for 17 doses
• FDA-approved intravenous dose is in three stages, and as such may be prone to dosing errors
  • Loading dose 150 mg/kg over 1 hour
  • 5 mg/kg/h for 4 hours
  • 25 mg/kg/h for 16 hours,¹ or continue until discontinuation criteria have been met
• Some centers use single-bag or two-bag dosing regimens to reduce the risk of dose interruption and dosing errors. These local protocols vary from the labeled dosing; contacting and using your local poison center’s protocol is recommended.
• Depending on dosing regimen and expected rates of loss, adjustments are required if patient is placed on hemodialysis or continuous renal replacement therapy (CRRT)
  • Depending on the protocol, doubling the NAC rate of infusion might be a reasonable approach during hemodialysis
  • The Extracorporeal Treatment in Poisoning (ExTRIP) Workgroup recommends at least doubling NAC dosing during intermittent hemodialysis^2-4

Discontinuation Criteria:

• Acetaminophen is undetectable
  -AND-
  No signs of hepatotoxicity
  -OR-
• In patients with hepatotoxicity, there’s no clear guideline on when to stop NAC. A reasonable approach recommended by our group in North Carolina is to continue until:
  1. INR is less than 2, AND
  2. Acetaminophen concentration is undetectable AND
  3. ALT is decreasing and less than 1000 IU/L, OR
  4. If peak ALT <1000 IU/L, until a reduction of 50% has been achieved
• Patients with ongoing hepatotoxicity, who continue to have detectable acetaminophen, or who have evidence of hepatic dysfunction beyond the end of the infusion or the 24-hour mark, should have NAC continued until these criteria are met.

Side Effects/Toxicity:

• Oral NAC is associated with up to 20% risk of vomiting
  • Sulfur smell from NAC may be hard for some to tolerate, and may be mitigated by administering in a chilled, strong-tasting soft drink in a covered drink cup with straw
• IV NAC can be associated with anaphylactoid reactions. It does not preclude the continuation of NAC.⁵ Anaphylactoid reactions occur most commonly with the loading dose and seem to be related to the rate of infusion and occur most often in patients with acetaminophen concentrations on the lower end of the toxic range.
  • Reducing the rate of infusion or diluting the solution can reduce the symptoms of the anaphylactoid reaction. In severe cases, the infusions should be held for specific treatment of the side effect and then resumed at a lower rate, if still indicated.
  • Anaphylactoid reactions have not been associated with oral NAC
• Vitamin K-dependent factor inhibition by NAC may lead to mild elevation of the INR,^7,8 generally less than 2. This should be of little clinical relevance in patients who are not receiving supratherapeutic doses of NAC
• Significant overdose (5-10-fold increase in dose) can be associated with cerebral edema, seizures, and respiratory arrest⁹
• IV NAC can be associated with hyponatremia in children, especially those under 40 kg, if concentration of the FDA approved dose is not adjusted
  • The use of more concentrated solutions, such as a 3% solution, can mitigate the risk of hyponatremia¹⁰

Case Follow-up:

• The patient’s acetaminophen level was above the treatment line on the modified Rumack-Matthew nomogram. Patient was started on a single rate regimen of IV NAC and after 24 hours she had undetectable acetaminophen levels with normal INR and LFTs. NAC was discontinued and patient was treated for her underlying psychiatry disease.

Clinical Pearls:

• N-acetylcysteine is a safe medication and should be used in all patients with toxic levels after acetaminophen ingestion, hepatotoxicity, or for those with reported ingestion of 150 mg/kg or greater in which the laboratory studies won’t result within 8 hours from the ingestion
• We suggest using the single maintenance rate of IV NAC to prevent medication errors, check with your local poison center or toxicology group if they support using a single rate system (off-label)
• Dosing should be adjusted in those patients’ receiving dialysis
• NAC should be continued until acetaminophen is no longer detected and clear evidence of improvement is seen
• NAC is generally safe in the recommended doses but can be associated with side effects, mostly vomiting for the PO formulation and anaphylactoid reaction for the IV formulation
• IV NAC may still be used after treating the anaphylactoid reaction and slowing the infusion rate

References:

1. Acetadote (acetylcysteine) package insert. Cumberland Pharmaceuticals, Nashville, TN, 2006.
2. Hernandez SH, Howland M, Schiano TD, Hoffman RS. The pharmacokinetics and extracorporeal removal of N-acetylcysteine during renal replacement therapies. Clin Toxicol (Phila). 2015;53(10):941-949. doi:10.3109/15563650.2015.1100305
3. Gosselin S, Juurlink DN, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, Hoffman RS; Extrip Workgroup. Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. Clin Toxicol (Phila). 2014 Sep-Oct;52(8):856-67. doi: 10.3109/15563650.2014.946994. Epub 2014 Aug 18. PMID: 25133498
4. Ghannoum M, Kazim S, Grunbaum AM, Villeneuve E, Gosselin S. Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics. Clin Toxicol (Phila). 2016 Jul;54(6):519-22. doi: 10.1080/15563650.2016.1175006. Epub 2016 Apr 27. PMID: 27118496.
5. Bebarta VS, Kao L, Froberg B, et al. A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose [published correction appears in Clin Toxicol (Phila). 2010 Aug;48(7):770]. Clin Toxicol (Phila). 2010;48(5):424-430. doi:10.3109/15563650.2010.486381
6. Mant TG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed). 1984;289(6439):217-219. doi:10.1136/bmj.289.6439.217
7. Knudsen TT, Thorsen S, Jensen SA, Dalhoff K, Schmidt LE, Becker U, Bendtsen F. Effect of intravenous N-acetylcysteine infusion on haemostatic parameters in healthy subjects. Gut. 2005 Apr;54(4):515-21. doi: 10.1136/gut.2004.043505. PMID: 15753537; PMCID: PMC1774452.
8. Minhaj, F. S., Leonard, J. B., Seung, H., Anderson, B. D., Klein-Schwartz, W., & King, J. D. (2021). In vitro analysis of N-Acetylcysteine (NAC) interference with the International Normalized Ratio (INR). Clinical Toxicology, 60(4), 489–492. https://doi.org/10.1080/15563650.2021.1979232
9. Heard K, Schaeffer TH. Massive acetylcysteine overdose associated with cerebral edema and seizures. Clin Toxicol (Phila). 2011 Jun;49(5):423-5. doi: 10.3109/15563650.2011.583664. PMID: 21740141.
10. Brush DE, Boyer EW. Intravenous N-acetylcysteine for children. Pediatr Emerg Care. 2004;20(9):649-650. doi:10.1097/01.pec.0000139754.56001.90

The post ToxCard: N-Acetylcysteine for Acetaminophen Toxicity appeared first on emDOCs.net - Emergency Medicine Education.