Authors: Rachel Kelly, MD (EM Residency Physician, Stony Brook University Hospital) and Robert Nocito, MD (EM Attending Physician, Stony Brook University Hospital) // Reviewed by: Jessica Pelletier, DO (EM Education Fellow, Washington University in St. Louis); Marina Boushra (EM-CCM, Cleveland Clinic Foundation); Brit Long, MD (@long_brit)

Case

A 54-year-old female with a past medical history of rheumatoid arthritis presents to the emergency department (ED) with generalized fatigue. She has had several days of intermittent fevers and chills, body aches, and pain in most of her joints, particularly in her left elbow. In the ED her vitals are T 99.6°F, HR 79 BPM, BP 142/76 mm Hg, RR 15 per minute, and saturation of  99% on room air. Examination reveals a patient with generalized pain, stiffness, swelling throughout most joints and a swollen and tender left elbow. The differential diagnosis includes rheumatoid arthritis flare versus septic arthritis. Would inflammatory markers such as erythrocyte sedimentation rate (ESR) and (CRP) change clinical course or management in the ED?

What Are ESR and CRP?

ESR and CRP are acute-phase reactants with concentrations that change in response to inflammation both acutely and chronically (1). ESR and CRP are widely used in monitoring and detecting multiple inflammatory conditions. ESR measures the rate at which red blood cells settle in a test tube, a factor of the concentration of fibrinogen in the blood, which increases during inflammation (1). ESR is an indirect and imperfect measure of the inflammatory response and can be affected by multiple processes aside from an acute-phase response, including hematologic conditions, obesity, renal failure, heart failure, aging, female sex, pregnancy, and medications (1). CRP is produced by the liver in response to acute infection or inflammation and plays a role in cell death and apoptosis (1). CRP is, therefore, a more direct measure of the inflammatory response but can also be affected by many other processes including age, sex, race, and body mass index (1).

Although ESR and CRP are biomarkers for inflammation, the interpretation of their increase in acute inflammation is different, as patterns of response are different for each test. CRP begins to rise within hours of the start of an infection or inflammatory condition, has a constant half-life of about 18 hours, and will return to normal levels in 3-7 days from the resolution of the underlying process (1,2). Conversely, ESR levels are slower to rise in response to inflammation and infection and will remain elevated for longer as long as excess fibrinogen remains in the serum (1,2). As a result, CRP is a more sensitive marker of the acute inflammatory response, especially within the first few days of a process (1,2).

Clinical Utility

Elevations in ESR and CRP indicate that inflammation is present, but the tests and levels do not specify where. Additionally, elevations in levels, especially a rapid increase in CRP, occur across a wide spectrum of disorders and diseases including infection, trauma, tissue necrosis, malignancies, and autoimmune disorders (1). ESR and CRP are neither sensitive nor specific for any condition and should only be used in conjunction with a good clinical history and physical exam (3). Still, these labs continue to serve as an important adjunct in diagnosing, monitoring, and clinically managing acute and chronic inflammatory conditions (3).

Best practices advise not to routinely order an ESR to evaluate for inflammation in an undifferentiated patient and to instead order a CRP when evaluating for acute inflammation (4). This is because CRP will be elevated in the first few days of an acute inflammatory response, making it more sensitive and specific during this phase compared to ESR, which may be normal at this time (4). After the resolution of a known inflammatory source, ESR can remain elevated and may be useful to trend for days, while CRP will return to normal more quickly (4). These temporal trends in CRP and ESR concentrations can help elucidate the timing and nature of an inflammatory process. For example, a patient with elevated CRP and normal ESR likely has an acute infectious, ischemic, or thromboembolic process present (5). On the other hand, a patient with normal CRP and elevated ESR would likely have a more subacute or chronic autoimmune, systemic inflammatory, or malignant process present (5). This is why in general ESR is more useful for monitoring chronic inflammatory conditions while CRP has increased utility in the monitoring and diagnosis of acute inflammatory conditions (6). Notably, in practice, the combination of ESR and CRP interpretation results in higher diagnostic accuracy and utility. This is why both tests are usually ordered simultaneously, even though their peaks theoretically appear at different times during the acute-phase response and some arguments can be made for their individual use (7,8).

Normal Values

While acute phase reactants such as ESR and CRP are not disease-specific or consistently able to distinguish an acute versus chronic inflammatory process, they have utility in certain ED settings. Normal values for ESR and CRP are listed below, and it is important to note that minimal increases in ESR and CRP are less helpful than multifold increases (5).

Normal values for ESR include (9):

Children: < 10 mm/hr

Males and females < 50 yo: < 15 and 20 mm/hr, respectively

Males and females >50 yo: < 20 and 30 mm/hr, respectively

Normal values for the standard CRP test include (10):

Normal: < 1 mg/dL 

Moderate elevation: 1-10 mg/dL 

Significant elevation: > 10 mg/dL 

Of note, there are two available CRP tests: the standard CRP and the high-sensitivity CRP (hs-CRP) test. Both tests perform the same and do not change the interpretation of CRP values, but the hs-CRP test can detect and report lower levels of elevation compared to the standard test (10).

Emergency Department

As in the inpatient setting, ESR and CRP should only be used as adjuncts to the clinical assessment. They are often more valuable in long-term clinical management than in the acute setting of the ED, and they are unlikely to alter the direct care provided in the ED. While normal ranges exist, cut-off values also vary by diagnosis. There are three main instances where ESR and CRP may be of value to the ED clinician:

A. Back pain – In the ED, some crucial diagnoses regarding back pain include vertebral osteomyelitis, spinal epidural abscess, and malignancy. When ESR or CRP are elevated in the setting of back pain, sensitivity can range from 94% to 100%, and often there are significant elevations in ESR and CRP, even in the absence of leukocytosis (11).

Spinal epidural abscess:

– ESR is more sensitive, but CRP is also usually elevated based on available literature (12)

– Consider this diagnosis and need for further imaging with MRI if ESR > 20 mm/hr and CRP > 1 mg/dL (13)

– ESR can be > 100 mm/hr, and there is a worse prognosis if CRP > 11.5 mg/dL (14,15)

Vertebral osteomyelitis 

– 90% of patients of ESR levels >30 mm/h and CRP >10 mg/L (16)

Malignancy/spinal tumors

– ESR and CRP elevations are typically noted, particularly if disease is systemic (12)

Bottom Line: ESR and CRP elevations can help discern the likelihood of an infectious process that would warrant an MRI, but normal values should not be used to rule out serious diagnoses such as spinal epidural abscess or osteomyelitis in high risk patients (those with neurologic deficit). If used as part of a diagnostic pathway for SEA in a patient with intermediate or low pretest probability, an ESR below the threshold may be used to exclude SEA.

B. Skin and soft tissue infections – In the ED, it is important to determine which patients warrant inpatient admission and when to consider necrotizing soft tissue infections (NSTIs) as a potential diagnosis.

Cellulitis:  

– Average ESR and CRP levels for a more severe disease presentation requiring longer hospitalization are 70 mm/h and 10 mg/dL, respectively (17)

– Average ESR and CRP levels for a less severe disease presentation requiring shorter hospitalization are 50 mm/h and 4 mg/dL, respectively (17)

– Often trended to monitor response to therapy (3)

Necrotizing soft tissue infections (NSTI):

– Clinical scoring tools such as Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score incorporate CRP, but it remains a clinical diagnosis (18)

Bottom Line: On the spectrum of skin and soft tissue infections, ESR and CRP can be helpful in noting disease severity and monitoring treatment and can possibly aid in disposition determination, but these should not change ED management or need for surgical consultation in those with NSTI.

C. Joint and bone pain – In the ED, the primary diagnostic objective in assessing patients with bone and joint pain often includes evaluating for septic arthritis and osteomyelitis.

Septic arthritis:

An ESR > 15 mm/h and CRP > 2 mg/dL are > 90% sensitive for the diagnosis of septic arthritis. However, these elevations are not specific, and lower cutoff values have much lower sensitivity (19).  Definitive diagnosis is made based on synovial fluid analysis (20).

Osteomyelitis: 

In non-diabetic patients, the combination of an ESR >45.5 mm/h and CRP >3.45 mg/dL has a sensitivity of 33% and a specificity of 84% for the diagnosis of osteomyeltis (21).  In diabetic patients, the combination of an ESR > 60 mm/h and CRP > 7.9 mg/dL increase the likelihood of osteomyelitis as a diagnosis (22).

Bottom Line: If concerned for a septic joint, ESR and CRP levels should not change the need for arthrocentesis. ESR and CRP levels cannot rule in or out osteomyelitis; however, higher elevations should increase clinical concern.

Of note, many pediatric and neonatal clinical guidelines incorporate ESR, CRP, and other acute phase reactants in their algorithms, which are not discussed here.  

Pearls and Pitfalls

-ESR and CRP are neither sensitive or specific for infection, and cut-off values for meaningful elevations are based on the disease process in question. Inflammatory markers can be falsely elevated or decreased based on concomitant conditions.

–Do not routinely order ESR and CRP, as elevations are common in a spectrum of diseases, and false positives may be distracting. Results of these tests should not replace clinical judgment. 

-There can be utility when ordering ESR and CRP for back pain in the ED, but normal values should not dissuade the clinician from ordering an MRI if suspicion is high for an infectious process.

-There is some utility in ordering ESR and CRP for skin/soft tissue/bone and joint conditions, although the levels may be more useful for long-term management as opposed to ED clinical decision making.

References

(1) Tennant F. Erythrocyte Sedimentation Rate and C-Reactive Protein: Old But Useful Biomarkers for Pain Treatment. Pract Pain Manag. 2013;13(2).

(2) Assasi N, Blackhouse G, Campbell K, et al. Comparative Value of Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Testing in Combination Versus Individually for the Diagnosis of Undifferentiated Patients With Suspected Inflammatory Disease or Serious Infection: A Systematic Review and Economic Analysis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Nov. (Cadth Health Technology Assessment, No. 140.) 1, Introduction. Available from: https://www.ncbi.nlm.nih.gov/books/NBK333366/

(3) Bray C, Bell LN, Liang H, Haykal R, Kaiksow F, Mazza JJ, Yale SH. Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine. WMJ. 2016 Dec;115(6):317-21. PMID: 29094869.

(4) Choosing Wisely Campaign. American Society for Clinical Pathology recommendations. Available: 

https://www.choosingwisely.org/clinician-lists/american-society-clinical-pathology-erythrocyte-sedimentation-rate-for-acute-phase-inflammation/. Accessed 15 Apr 2023. 

(5) Lacy MD. Inflammatory biomarkers in hospitalized adults with suspected infection. The Southwest Respiratory and Critical Care Chronicles 2018;6(26):1–6

(6) Litao MK, Kamat D. Erythrocyte sedimentation rate and C-reactive protein: how best to use them in clinical practice. Pediatr Ann. 2014 Oct;43(10):417-20. doi: 10.3928/00904481-20140924-10. PMID: 25290132.

(7) Lapić I, Padoan A, Bozzato D, Plebani M. Erythrocyte Sedimentation Rate and C-Reactive Protein in Acute Inflammation. Am J Clin Pathol. 2020 Jan 1;153(1):14-29. doi: 10.1093/ajcp/aqz142. PMID: 31598629.

(8) Osei-Bimpong A, Meek JH, Lewis SM. ESR or CRP? A comparison of their clinical utility. Hematology. 2007 Aug;12(4):353-7. doi: 10.1080/10245330701340734. PMID: 17654065.

(9) Tishkowski K, Gupta V. Erythrocyte Sedimentation Rate. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557485/

(10) Nehring SM, Goyal A, Patel BC. C Reactive Protein. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441843/

(11) Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, Hendershot EF, Holtom PD, Huddleston PM 3rd, Petermann GW, Osmon DR, Infectious Diseases Society of America. 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015 Sep 15;61(6):e26-46. doi: 10.1093/cid/civ482. Epub 2015 Jul 29. PMID: 26229122.

(12) Siemionow K, Steinmetz M, Bell G, Ilaslan H, McLain RF. Identifying serious causes of back pain: cancer, infection, fracture. Cleveland Clinic journal of medicine. 2008;75(8):557-566. doi:10.3949/ccjm.75.8.557

(13) Davis DP, Salazar A, Chan TC, et al. Prospective evaluation of a clinical decision guideline to diagnose spinal epidural abscess in patients who present to the emergency department with spine pain. J Neurosurg Spine. 2011;14 (6): 765-70

(14) (medical and surgical) Arko L 4th, Quach E, Nguyen V, Chang D, Sukul V, Kim BS. Medical and surgical management of spinal epidural abscess: a systematic review. Neurosurg Focus. 2014 Aug;37(2):E4. doi: 10.3171/2014.6.FOCUS14127. PMID: 25081964.

(15) Sexton DS, Sampson JH. Spinal epidural abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. (Accessed on April 22, 2023.)

(16) Buensalido JAL, Reyes MP. Erythrocyte Sedimentation Rate, C-Reactive Protein and Procalcitonin in Infections of the Spine and Infections in Spinal Cord Injury Patients. The Open Infectious Disease Journal. 2015 Mar; 1-12 (9). DOI: 10.2174/1874279301509010001

(17) Markanday A. Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians. Open Forum Infect Dis. 2015 Jul 3;2(3):ofv098. doi: 10.1093/ofid/ofv098. PMID: 26258155; PMCID: PMC4525013.

(18) Stevens DL, Baddour LM. Necrotizing soft tissue infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. (Accessed on April 22, 2023.)

(19) Hariharan P, Kabrhel C. Sensitivity of erythrocyte sedimentation rate and C-reactive protein for the exclusion of septic arthritis in emergency department patients. J Emerg Med. 2011 Apr;40(4):428-31. doi: 10.1016/j.jemermed.2010.05.029. Epub 2010 Jul 22. PMID: 20655163.

(20) Goldenberg DL, Sexton DS. Septic arthritis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. (Accessed on April 22, 2023.)

(21) Ryan EC, Ahn J, Wukich DK, Kim PJ, La Fontaine J, Lavery LA. Diagnostic Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein in Osteomyelitis of the Foot in Persons Without Diabetes. J Foot Ankle Surg. 2019 May;58(3):484-488. doi: 10.1053/j.jfas.2018.09.025. Epub 2019 Jan 24. PMID: 30685423.

(22) Lavery LA, Ahn J, Ryan EC, Bhavan K, Oz OK, La Fontaine J, Wukich DK. What are the Optimal Cutoff Values for ESR and CRP to Diagnose Osteomyelitis in Patients with Diabetes-related Foot Infections? Clin Orthop Relat Res. 2019 Jul;477(7):1594-1602. doi: 10.1097/CORR.0000000000000718. Erratum in: Clin Orthop Relat Res. 2020 Apr;478(4):923. PMID: 31268423; PMCID: PMC6999976.

The post Erythrocyte Sedimentation Rate and C-Reactive Protein in the ED appeared first on emDOCs.net - Emergency Medicine Education.

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

Original podcast posted on PEM Currents – Hosted by Brad Sobolewski (@PEMTweets) and co-authored by Dennis Ren (@DennisRenMD)

This podcast series by PEM Currents is a co-production with the Emergency Medical Services for Children Innovation and Improvement Center (EMSC IIC), whose mission is to minimize morbidity and mortality of acutely ill and injured children across the emergency continuum. 

The emDOCs.net team is very happy to collaborate with PEM Currents and EMSC IIC to further disseminate this 5-part podcast series focusing on agitation in children and adolescents.

Podcast: Play in new window | Download (Duration: 17:49 — 24.5MB)

Subscribe: Apple Podcasts | Google Podcasts | RSS

Non-Pharmacologic Management

In episode 1 of this series, we discussed differentiating organic vs psychiatric causes of agitation in children. But what about the patient who is agitated, and is a potential danger to themselves or to the ED staff? Do we Redirect? Restrain? Sedate?

Patient that are agitated should always be treated with dignity and respect. This entails utilizing the least invasive non-pharmacologic means of assisting them, before moving to physical or chemical restraints.

After listening to this episode you will be able to:

• Discuss specific age-appropriate non pharmacologic management strategies for agitated children
• Discuss how we can safely use holds and restraints, and how these are temporary measures

Environment

Remove any dangerous objects/equipment. This should ideally be proactive, and mean that if you have a large volume of mental health patients in your environment, then setting up safe spaces is key.

• No sharp objects in the room
• Walls with rounded corners
• Heavy or immovable furniture to prevent barricading or throwing
• Doors that swing outward
• Tamper-resistant fixtures and breakaway shower rods
• High ceilings 
• Room placement away from entries and exits
• No glass mirrors and televisions placed behind Plexiglass
• Open floor plans for visibility
• Our environment has secure “garage door” style rolling doors that lock in place in front of the monitors and wall mounted equipment. Additionally supply sleeves have a pass through and can be accessed outside of the room
• Removing any triggers which can include family or caregivers
• Dimming lights and minimizing noise (especially in neurodivergent children or children with sensory processing disorders)
• Presence of security staff or law enforcement may make things worse if the child feels threatened. Conversely they may need to be present for patient and staff safety

What if a patient arrives in handcuffs in police custody?

Patients may be brought to hospital by police under restraint (e.g. handcuffs)

• Police officers and handcuffs should remain in place during initial assessment
• Handcuffs can be removed once the patient has been assessed and it is deemed safe to do so
  • Before removal of handcuffs medication may need to be given for the patient’s own protection or that of the staff

Initial steps

• Recognition of warning signs of potential violence before escalation occurs
• Prioritize assessment of escalating patients (delays can worsen the situation)
• Always ensure safety of self, staff and others present (e.g. other patients, family members), and the patient
• Ensure patient cannot obstruct exit route
• Avoid excessive stimulation
• Avoid aggressive postures and prolonged eye contact
• Request aid (e.g. security staff) early if the situation is deteriorating or is expected to deteriorate
• If the patient has an existing behavioral safety plan, employ it as early as possible – this is especially important in neurodivergent children, and patients with diagnoses such as intermittent explosive disorder

Verbal de-escalation

De-escalation is the act of responding to a child’s agitation and in a way that controls, diffuses, and/or calms the situation. The EMSC innovation and Improvement Center has some excellent resources and tip sheets (see resources below for details).

It involves tracing the situation back to the point where things got out of control and addressing the root of the behavior rather than simply trying to quiet the child. Begin by stating your role and use both your own name and the patient’s name (personalize the interaction).

Avoid Trying to Reason With Them

When agitated, a child’s prefrontal cortex is suppressed by the cortisol and epinephrine induced fight-or-flight reaction. This physiological state is due to a perceived threat – deescalate by reassuring them that they are safe, remaining calm, and making sure their physical needs are met.

Validate Their Feelings, Not Their Actions

When a child is overwhelmed by emotions it is best to acknowledge their feelings – “I bet you are angry, I can see how upset that made you.” This establishes a common ground to begin. Be patient and listen, and then listen more — not to reply, but to validate and to understand, responding only with, “I think I understand. That was difficult for you. Tell me more”. The patient may not want advice or examples or anything, but listening and validation. Give the patient time to state their concerns, and avoid giving opinions on issues and grievances beyond your control.

If you are in a position to communicate, this it is important that children understand the error of their behavior and give them alternative ways of managing their emotions.

Be the Child’s Advocate

An agitated child may feel scared, threatened or embarrassed.  If they are having an outburst in triage for instance, let the child know that you are there to help them in a public way. Be their advocate. Escort them safely to a private room or area for discussion. All in all, it is important to be calm, empathetic and non-judgemental in your approach, but also by setting appropriate boundaries.

• You can also provide food, drinks or other assistance as required (e.g. seating, access to a telephone to call a parent or guardian, address physical needs, etc.)
• Offer oral medication to alleviate patient’s stress

This allows assessment of the patient’s responsiveness to verbal de-escalation and allows you to more immediately assess risk of self-harm or harm to others.

If necessary, you may have to show force:

• Involves security staff in view providing back up to the clinician while trying to negotiate with the patient
• In these situations adopting an overly casual posture may not be advised
• Used when verbal de-escalation is ineffective or inappropriate
• May persuade the patient to cooperate with an appropriate clinical intervention. Otherwise physical restraint and/or chemical restraint will be required to ensure safety of the patient, staff and others present

Be patient as these situations are not easy!

Restraints

The use of restraints should be taken seriously. Utmost care in keeping both staff and patient safe. All available alternative options should be considered before administering  physical restraint, as it infringes on a person’s autonomy and dignity. We must also acknowledge that there are racial and other disparities in the use of physical and chemical restraints. We need to be cognizant of this when making the decision to employ them.

Manual restraint 

Only staff trained and certified in the use of manual restraint should use these methods. These are typically temporary as other methods of physical restraint are being prepared. It is beyond the scope of a podcast episode to describe these in detail, but these include therapeutic hold.

Physical restraints

Physical restraint is any manual method, device, or equipment that immobilizes or reduces the ability of a patient to move their body freely.

I should also mention seclusion (aka involuntary confinement), which is the act of placing  of a patient alone in a room or area from which the patient is physically prevented from leaving. This is commonly done while having a “sitter” – a health care provider that is constantly obesrving the patient. This need for 1-on-1 observation is a major challenge for EDs and health care systems from a staffing standpoint.

Physical restraints are indicated when there is actual or high risk of harm to self, others or property, where verbal de-escalation and other treatments are inappropriate or ineffective.

You should not use physical restraints if the patient is medically unstable, if there is a risk of harm to the staff when applying restraints, and again, if other strategies are more appropriate

There are soft limb restraints or elbow splints and mittens, but often when we think of restraints we think of leather restraints on all 4 limbs.

The technique

Again ensure that everyone is safe. This includes adequate numbers of trained personnel, with personal protective equipment. DO NOT attempt physical restraint if inadequate staff available. If it is truly unsafe and the patient attempts to escape or does so, call the Police if appropriate. Ideally you should have policies and care pathways in place with a trained team. 

1. This should be a 6 member team: one for each extremity, one for the head, and one to apply the restraints. The provider at the head of the bed should have airway skills if possible. Allocate roles and state plan of action in an initial huddle. Decide on a trigger word to be used to initiate action plan
2. Remove all objects which are potentially dangerous (pens, stethoscopes, lanyards etc.) and don PPE (ie gloves, gowns and face-masks, Kevlar sleeves)
3. Calmly explain to the patient that restraints are being applied to ensure the safety of the patient and others. It is important to emphasize the restraints are not being used as punishment, but rather have therapeutic value. Give the patient a final chance to comply with requests with restraint team in attendance (‘show of force’)
4. Initiate physical restraint by keeping the patient supine, arms beside and body & legs extended. Alternative is to have one arm up (reduces movement). Medical grade restraints should be applied securely to each extremity and tied to the solid frame of the bed (not side rails).
   • Avoid neck or torso restraint (unsafe for patient), and avoid hobble restraints (i.e. tying hands and legs behind back).
   • Spit hoods have been applied by prehospital providers recently, but these cover the face and encircle the neck representing a possible airway concern.
   • It is key to explain to patient what is happening at all times!
5. Lower extremities should be tied to the opposite side of the bed to prevent flailing or generation of lateral force if possible.
6. After restraints have been applied, the patient should be closely monitored. Restraints should not be applied indefinitely, and multiple reevaluations should be done to determine when it is safe to remove restraints. Document appropriate reassessments per institutional and regional policy (ie every 30 minutes, or every hour)
   • Documentation: Reason for restraint, alternative therapies attempted, assessment of potential injuries and any complications of restraint, monitoring plan, thresholds for further interventions, ongoing sedation options and sedation chart
     
   • Elevate head of bed to 30 degrees if possible (decrease aspiration risk)
   • No pillows (decrease suffocation risk)
   • Perform cyclical limb release if possible
   • Ensure appropriate fluid maintenance, toileting and pressure cares
7. Removal of restraints as soon as possible once patient is calm and/or sedated. Remove restraints from one limb at a time – start with a leg then contra-lateral arm

Physical restraints can be a bridge to safely administering chemical restraints – more on that in episode 3 of this series.

Summary

All right, so that’s it for this episode – hopefully you learned a bit more about how to safely deescalate an agitated child, and how we can keep them and ourselves as providers safe in a stressful environment. The third episode in this series will focus on medical management of acute agitation

Resources

• emDOCs.net Articles
  • emDOCs Cases: ED Approach to Agitation
  • Pediatric EM Morsels: Agitation
  • The Art of the ED Takedown
  • Ketamine for the Agitated/Violent Patient
  • ToxCard: Dexmedetomidine & Ketamine in Toxicologic Causes of Agitation
  • Droperidol Use in the Emergency Department – What’s Old is New Again
• PEM Blog via Brad Sobolewski (@PEMTweets)
• EMSC IIC (Emergency Medical Services for Children Innovation and Improvement Center)
  • EMSC IIC: Pediatric Education and Advocacy Kit (PEAK): Agitation
    • EIIC/TREKK: Care of the Agitated Patient Algorithm
    • EIIC/TREKK: Agitation Medication Dosing Recommendation Table
    • EIIC: De-escalation Tips for Pediatric Agitation Infographic
    • EIIC: Emergency Department Management of the Agitated Pediatric Patient Interactive Learning Module
    • EIIC: Agitation in Neurodivergent Patients with Drs. Alice Kuo and Ilene Claudius Podcast
    • EIIC: Safe Control of the Agitated Patient Webinar Series with Dr. Marianne Gausche-Hill
    • New England EMSC: New England Regional Behavioral Health Toolkit
  • For more info, please email km@emscimprovement.center or follow on Twitter @EMSCImprovement

Other Episodes in the Agitation Series

Episode 1: Differentiating organic versus psychiatric causes of agitation and altered mental status

Episode 2: Non-pharmacologic management of agitated children (Current)

Episode 3: Pharmacologic management of agitated children (Coming May 31, 2023)

Episode 4: Safe pre-hospital transport of the agitated child (Coming June 7, 2023)

Episode 5: Management of the child with mental health problems who is boarded in the Emergency Department (Coming June 14, 2023)

References

Berzlanovich AM, Schöpfer J, Keil W. Deaths due to physical restraint. Dtsch Arztebl Int. 2012 Jan;109(3):27-32. PMC3272587.

Coburn VA, Mycyk MB. Physical and chemical restraints. Emerg Med Clin North Am. 2009 Nov;27(4):655-67, ix. doi: 10.1016/j.emc.2009.07.003. PMID: 19932399.

Downes MA, Healy P, Page CB, Bryant JL, Isbister GK. Structured team approach to the agitated patient in the emergency department. Emerg Med Australas. 2009 Jun;21(3):196-202. PMID: 19527279.

Knox DK, Holloman GH Jr. Use and avoidance of seclusion and restraint: consensus statement of the american association for emergency psychiatry project Beta seclusion and restraint workgroup. West J Emerg Med. 2012 Feb;13(1):35-40. PMC3298214.

Melamed E, Oron Y, Ben-Avraham R, Blumenfeld A, Lin G. The combative multitrauma patient: a protocol for prehospital management. Eur J Emerg Med. 2007 Oct;14(5):265-8. PMID: 17823561.

The post PEM Currents – Agitation in Children – Episode 2: Non-Pharmacologic Management 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. This week we cover the ESETT trial which compares levetiracetam, fosphenytoin, and valproate for treatment of status epilepticus.

Author: Christiaan van Nispen, MD (Resident, Emergency Medicine Physician, San Antonio, TX); Brannon Inman, MD (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Design: Multi-centered, double-blinded, randomized trial

Outcome:

• No statistically significant difference in primary outcome, which was absence of clinically apparent seizures without the need for additional anti-convulsant medications AND improving responsiveness at 60 minutes after the start of trial-drug infusion, as determined by the treating physician.
  • Overall, nearly half of each group achieved the primary outcome:
    • Levetiracetam 47%
    • Fosphenytoin 45%
    • Valproate 46%
  • Amongst the patients not achieving the primary outcome:
    • 144 required additional anti-convulsant medications
    • 52 did not have improving responsiveness at 60 minutes
•  Secondary outcomes were not significantly different amongst the groups, including:
  • Frequency of life-threatening hypotension
  • Frequency of cardiac arrhythmia
  • Need for subsequent endotracheal intubation
  • Seizure recurrence 60 minutes to 12 hours after study drug infused
  • Anaphylaxis
  • Respiratory depression
  • Purple glove syndrome
  • Admission to the ICU
  • Death
• 10% of the enrolled population was ultimately determined to have psychogenic non-epileptic seizures.
• There were many protocol violations that resulted in these patients being included in the intention-to-treat analysis, but excluded from the per-protocol analysis, including:
  • Benzodiazepines administered too long before or two proximal to the administration of study drugs (50 patients)
  • Benzodiazepine dose administered was below the specified study recommendations (26 patients)
  • Enrollment of patients who were not in status epilepticus (33 patients)
  • Unblinding of study drug to the clinical care team (200 patients), although most (154) were unblinded after the primary outcome had been determined at 60 minutes.

Take Aways:

• Negative trial: none of the anticonvulsants under investigation were determined to be superior or inferior to the others.
• Trial stopped early at preplanned interim analysis due to futility.
• Nearly half of all patients treated with the studied anti-convulsant medications had seizure resolution and improving mental state within 60 minutes.
• Study included children, as well as adults. This increases applicability or ED care.
• There were many protocol violations, and 10% of the studied population were not in status epilepticus. These factors in combination limit the conclusion of the study.
• About 200 of the 400 patients were ultimately unblinded.

My Take:

• Amongst patients presenting with status epilepticus refractory to benzodiazepine administration, the administration of levetiracetam (60 mg/kg, or 4500 mg), fosphenytoin (20 mg PE/kg, or 1500 mg PE/kg), and valproate (40 mg/kg, or 3000 mg) appear equally efficacious. In light of these data, I will give levetiracetam due to its less severe side effects and ease of administration.

Editor Note:

The key to status epilepticus is to stop the seizure. Give the first benzodiazepine and have the second dose ready while ordering the antiepileptic (we prefer levetiracetam at 60 mg/kg), but ready your sedative and paralytic for endotracheal intubation. If the adult patient has failed to stop seizing with two doses of benzodiazepines, rapid control of the seizure with either high dose propofol or ketamine can result in seizure cessation.

Reference:

1. Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019; 381(22): 2103-2113. DOI: 10.1056/NEJMoa1905795

The post 52 in 52 – #36: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus 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: Failed communication of incidental mediastinal mass appeared first on emDOCs.net - Emergency Medicine Education.

Today on the emDOCs cast, Brit Long, MD (@long_brit) covers Part 2 in a series on complications of CAR T-cell therapy, specifically immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, cytopenias, graft versus host disease, and cardiac toxicity.

Episode 78: CAR T-cell Therapy, ICANS, and other complications

Immune effector cell-associated neurotoxicity syndrome

• Neurotoxicity (ICANS and cytokine release encephalopathy syndrome (CRES)) can occur days to weeks following CAR T-cell therapy, as well as other types of immunotherapy such as blinatumomab.
• Those with immature B cell diseases are more commonly affected (87% of cases).
• ICANS occurs in 39-64% of patients in the first 8 weeks of therapy. More common with certain regimens (axicabtagene and brexucabtegene), which cause faster T-cell expansion and metabolism.
• Younger age, preexisting comorbidities, higher disease burden, increased intensity of cancer therapies, and concomitant CRS increase the risk of ICANS.
• Up to 90% of those with ICANS also have CRS.

Pathophysiology:

• ICANS is thought to be due to cytokines (L-1, IL-6, IL-8, IL-10, interferon, and TNF-alpha) causing activation of endothelial cells and disruption of the blood-brain barrier, but it’s not completely understood.
• Neurotoxic substances including glutamate and quinolinic acid are also significantly elevated in patients with neurotoxicity. Once the blood-brain barrier is disrupted, the substances and cytokines cause neuronal inflammation and damage.

Features:

• Variable presentation: headache, memory loss, dizziness, meningismus, altered mental status, movement disorders (myoclonus, tremor), speech impairment (aphasia, dysarthria), seizures, encephalopathy, and coma.
• Think about this in the patient with evidence of CRS plus neuro findings.
• Symptoms may last for 6-17 days.

Evaluation:

• Laboratory testing can demonstrate elevated lactate dehydrogenase, thrombocytopenia, and elevated inflammatory markers (ferritin, CRP, ESR).
• If LP performed, findings are typically normal or may demonstrate a mild elevation in protein and pleocytosis.
• CT of the head recommended to look for other complications (bleed, abscess, mets). In severe ICANS, cerebral edema will be present on CT with sulcal effacement and white matter changes. SAH, SDH, and stroke can occur.
• Magnetic resonance imaging (MRI) is the imaging modality of choice, but this is normal in over half of patients. 30% will demonstrate T2/FLAIR hyperintensities.
• EEG can demonstrate findings of encephalopathy in 76%, with theta-delta slowing.

Grading:

Based on the most severe symptoms, considering five components: encephalopathy using the Immune Effector Cell-Associated Encephalopathy (ICE) score

• ICE score, level of consciousness, presence of seizure, motor examination, and elevated intracranial pressure.
• Grade 1 is mild, with some inattentiveness and mild disorientation, grade 2 is moderate, and grades 3-4 are severe.

Management:

• Consult hematology/oncology.
• Supportive care with steroids and seizure treatment.
• Dexamethasone 10 mg 2-4 times per day will improve symptoms in most cases. These are tapered once patient begins to return to baseline neurological status.
• If ICP elevated and patient decompensating, elevate head of bed, provide analgesia/antiemetics, and give HTS or mannitol. However, steroids reduce ICP in most cases.
• Prophylactic seizure therapy is recommended with levetiracetam, which has less cross reactivity with other medications and has lower risk of cardiac or liver toxicity.

Other Complications

• Infusion reactions are usually mild and infrequent. Symptoms include nausea and vomiting, but hypotension and anaphylaxis have been reported.
• Hypogammaglobulinemia: B-cell aplasia and persistence of CAR T-cell therapy effects. Associated with complete response to therapy. IgG levels decrease 1-3 months after CAR T-cell therapy and may remain low up to 4 years. Patients are typically treated with IVIG.
• Cytopenias can occur for several weeks following therapy; the most common is neutropenia.
  • Absolute neutrophil counts are below 1.0 x 10⁹/L in 53-78% of cases, with neutropenic fever occurring in 17-37%.
  • Thrombocytopenia occurs in 11-38%.
• GVHD: May occur in patients receiving donor-derived T cells, but it’s unlikely due to the in vitro modification of T cells to express the CAR through introduction of the encoding by a viral or non-viral vector.
  • Prior episodes of GVHD increase the risk of future GVHD, current literature suggests the risk of GVHD is low in patients receiving CAR T-cell therapy; a meta-analysis found 6.9% of patients receiving CAR T-cell therapy with donor-derived cells developed GVHD. In this meta-analysis, GVHD presented most commonly with skin symptoms or liver involvement.
• Cardiac Toxicity can occur in up to 39% of patients and includes arrhythmias, cardiomyopathy, heart failure, and cardiac arrest
  • Most likely due to IL-6, which has direct cardiac effects. CAR T-cell therapy can also cause direct cardiotoxicity due to the potential of cross-reactivity with proteins expressed by cardiac tissue
  • New onset cardiomyopathy associated with CAR T-cell therapy appears to be more common in patients of older age and those with preexisting cardiovascular risk factors
  • CRS is also associated with cardiac complications, including arrhythmias, cardiomyopathy, and ischemia.
  • Patients with STEMI should be treated similar to those not on CAR T-cell therapy with PCI. Tocilizumab may treat cardiac toxicity related to CAR T-cells.

References:

1. Long B, Yoo MJ, Brady WJ, Holian A, Sudhir A, Gottlieb M. Chimeric antigen receptor T-cell therapy: An emergency medicine focused review. Am J Emerg Med. 2021 Dec;50:369-375.
2. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T cell therapy-assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47–62.
3. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638.
4. Holtzman NG, Xie H, Bentzen S, et al. Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes. Neuro Oncol. 2021 Jan 30;23(1):112-121.
5. Karschnia P, Jordan JT, Forst DA, et al Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood. 2019 May 16;133(20):2212-2221.
6. Rubin DB, Danish HH, Ali AB, et al. Neurological toxicities associated with chimeric antigen receptor T-cell therapy. Brain. 2019 May 1;142(5):1334-1348.
7. Rubin DB, Al Jarrah A, Li K, et al. Clinical Predictors of Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy. JAMA Neurol. 2020 Dec 1;77(12):1536-1542.
8. Rice J, Nagle S, Randall J, Hinson HE. Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment. Curr Treat Options Neurol. 2019 Jul 20;21(8):40.
9. Cruz CR, Hanley PJ, Liu H, et al. Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience. Cytotherapy. 2010;12:743–749
10. Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116:4099–4102.
11. Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–459.
12. Doan A, Pulsipher MA. Hypogammaglobulinemia due to CAR T-cell therapy. Pediatr Blood Cancer. 2018;65:2017–2018.
13. Alvi RM, Frigault MJ, Fradley MG, et al. Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T).J Am Coll Cardiol. 2019;74:3099-108.
14. Lefebvre B, Kang Y, Smith AM, et al. Cardiovascular Effects of CAR T Cell Therapy: A Retrospective Study.JACC CardioOncol. 2020;2:193-203.

The post emDOCs Podcast – Episode 78: CAR T-cell Therapy, ICANS, and other complications appeared first on emDOCs.net - Emergency Medicine Education.

Author: Brit Long, MD (@long_brit) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Manpreet Singh, MD (@MPrizzleER) 

Aneurysmal subarachnoid hemorrhage (aSAH) can be deadly.  Several recent studies on the management of aSAH have been published, requiring an update of current guidelines. This post will look at the Neurocritical Care Society guidelines for the management of aSAH.

Recommendations:

1. In patients with aSAH, what is the impact of blood pressure reduction compared with no blood pressure reduction before aneurysm treatment on mortality, mRS score, Glasgow outcome scale (GOS) score, new cerebral infarction, rebleeding, and delayed cerebral ischemia (DCI)?

• There is insufficient evidence to recommend a blood pressure reduction goal for the treatment of hypertension before aneurysm treatment in aSAH. Lack of evidence to recommend a specific blood pressure reduction goal does not necessarily imply that blood pressure reduction is not helpful before aneurysm treatment.

2. In patients with aSAH, what is the impact of administering antifibrinolytics (e.g., TXA) prior to aneurysm treatment compared with no antifibrinolytics on mortality, mRS, GOS, new cerebral infarction, rebleeding, DCI, and thrombotic events?

• We recommend against the administration of antifibrinolytic therapy to prevent rebleeding of ruptured aneurysms in patients with aSAH (strong recommendation, high-moderate quality of evidence).

3. In patients with aSAH, what is the impact of administering calcium channel blockers compared with no calcium channel blockers on mortality, mRS, GOS, new cerebral infarction, and prevention of DCI?

• We recommend the administration of oral nimodipine in patients with aSAH to reduce DCI and cerebral infarction, and to improve functional outcome (strong recommendation, moderate quality of evidence).
• We recommend against the administration of intravenous (IV) nicardipine for the prevention of DCI because of increased risk of adverse effects (strong recommendation, moderate quality of evidence).
• There is insufficient evidence to recommend for or against the administration of calcium channel blocker other than nicardipine by IV or intraventricular routes.

4. In patients with aSAH, what is the impact of endothelin antagonists compared with no endothelin antagonists on mortality, mRS, GOS, new cerebral infarction, and prevention of DCI?

• We recommend against endothelin receptor antagonist administration because of lack of benefit on mortality and functional outcomes and an increased risk of adverse events (strong recommendation, high quality of evidence).

5. In patients with aSAH, what is the impact of statin treatment compared with no statins on mortality, mRS, GOS, new cerebral infarction, and prevention of DCI?

• We recommend against starting statin treatment to reduce DCI or improve functional outcomes in aSAH because of lack of benefit (strong recommendation, high quality of evidence).

6. In patients with aSAH, what is the impact of targeted therapeutic hypermagnesemia compared with no targeted hypermagnesemia on mortality, mRS, GOS, new cerebral infarction, and prevention of DCI?

• We recommend against the use of targeted hypermagnesemia to improve outcomes in aSAH due to lack of benefit (strong recommendation, moderate quality evidence).

7. In patients with aSAH at risk for DCI, what is the impact of high volume (liberal, targeting hypervolemia) fluid administration compared with conventional fluid management, targeting euvolemia, on mortality, mRS, GOS, new cerebral infarction, DCI, and pulmonary edema?

• We suggest against liberal fluid administration because of an increased risk of pulmonary edema (Conditional recommendation, low quality of evidence).
• We suggest using targeted fluid administration to achieve euvolemia, which may include goal-directed hemodynamic therapy, to reduce the risk of pulmonary edema, prevent DCI, and improve functional outcome (conditional recommendation, very low quality of evidence).

8. In patients with aSAH at risk for DCI or diagnosed with DCI, what is the impact of blood pressure and/or cardiac output augmentation compared with no blood pressure or cardiac output augmentation on mortality, mRS, GOS, new cerebral infarction, DCI prevention, pulmonary edema, myocardial infarction, and arrhythmia?

• There are insufficient quality data to recommend for or against blood pressure or cardiac output augmentation for the prevention and treatment of DCI. Due to the associated risks, use of these interventions should be judicious and tailored to the patient’s individual hemodynamic profile.

9. In patients with aSAH, is treatment triggered by change in examination plus advanced neuroimaging (Computed Tomography (CT) Angiography, CT Perfusion, transcranial Doppler) versus examination alone superior in improving mortality, mRS, GOS, and preventing new cerebral infarction?

• There is insufficient evidence to provide a recommendation on the optimal trigger (change in neurological examination plus findings on advanced neuroimaging vs. change in examination alone) for interventional procedures for the treatment of DCI.

10. In patients with aSAH, what is the impact of treatment with mineralocorticoids compared with no treatment with mineralocorticoids on mortality, mRS, GOS, new cerebral infarction, serum sodium levels, and fluid balance?

• There is insufficient evidence to support mineralocorticoid administration to maintain normal serum sodium concentrations and/or even fluid balance or to improve functional outcome.

11. In patients with aSAH, is a more aggressive transfusion strategy (to keep a hemoglobin > 10 g/dL) more effective than a conservative transfusion strategy (to keep a hemoglobin > 7 g/dL) to improve mortality, mRS, GOS, new cerebral infarction, DCI prevention, and transfusion related complications?

• There is insufficient evidence to provide a recommendation for using a transfusion threshold higher than a hemoglobin of > 7 g/dL in patients with aSAH.

12. In patients with aSAH and an indwelling external ventricular drain (EVD), is a strategy based on direct clamping superior to gradual weaning on mortality, mRS, GOS, new cerebral infarction, incidence of ventriculoperitoneal (VP) shunt placement, rate of infection, and EVD complications?

• There is insufficient evidence to provide a recommendation on direct clamping versus gradual weaning strategy for EVD removal for the management of hydrocephalus in patients with aSAH.

Summary:

Reference:

Treggiari MM, Rabinstein AA, Busl KM, Caylor MM, Citerio G, Deem S, Diringer M, Fox E, Livesay S, Sheth KN, Suarez JI, Tjoumakaris S. Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2023 May 18. doi: 10.1007/s12028-023-01713-5.

#FOAMed

• SAH – Why do we miss it?
• SAH – Critical Care Management
• 52 in 52 – CT sensitivity 

The post Neurocritical Care Society Aneurysmal SAH Guidelines appeared first on emDOCs.net - Emergency Medicine Education.

Original podcast posted on PEM Currents – Hosted by Brad Sobolewski (@PEMTweets) and co-authored by Dennis Ren (@DennisRenMD)

This podcast series by PEM Currents is a co-production with the Emergency Medical Services for Children Innovation and Improvement Center (EMSC IIC), whose mission is to minimize morbidity and mortality of acutely ill and injured children across the emergency continuum. 

The emDOCs.net team is very happy to collaborate with PEM Currents and EMSC IIC to further disseminate this 5-part podcast series focusing on agitation in children and adolescents.

Podcast: Play in new window | Download (Duration: 22:31 — 30.9MB)

Subscribe: Apple Podcasts | Google Podcasts | RSS

Differentiating  Organic versus Psychiatric

Learning Objectives:

• Describe the findings on history and physical examination that differentiate organic vs psychiatric causes of agitation and AMS.
• Develop a strategy to differentiate organic from psychiatric causes of AMS, including using ancillary studies.

Frankly this issue of organic or psychiatric has actually long been derided. In fact Wilson (that Dr. Wilson, the copper disease guy) said that the functional-organic distinction “lingers at the bedside and in medical literature, though it is transparently false and has been abandoned long since by all contemplative minds” – this was in the textbook Neurology, in the 1940s. And yet this distinction persists in medical education, even in podcasts. So it is with that that I acknowledge that this somewhat artificial distinction between psychiatry and neurology is a bit of a naïve discrimination that may encourage the continued stigmatization of mental health problems. So think of this episode less about “is it psych or not” and more about not missing something because you assumed the patient had a mental or behavioral problem.

So, figuring out if it is something medical or psychiatric in instances of acute agitation and AMS is different than “medical clearance” for many mental health visits. I still think it is a useful exercise in sharpening your diagnostic skills.

Definitions:

• Psychosis – Disruption in thinking, accompanied by delusions or hallucinations
• Delusions – False, fixed beliefs that cannot be resolved through logical argument
• Hallucinations – False perceptions that have no basis in external stimuli
• Delirium – Altered sensorium, with waxing and waning deficits in attention and concentration. Orientation and concentration are preserved in functional psychosis. 
• Agitation – Feeling of irritability or restlessness

History

• It is important to get a history from both the patient and caregiver if possible because the information can be different.
  • Ask both parties about why they believe they are presenting to the emergency department.
  • Sometimes we can identify triggers for these episodes (environment, personal), sometimes the behaviors have gradually escalated to the point where the caregiver becomes fearful for their own safety, the safety of the patient, or safety of other family members.
  • Ask about suicidal ideation, homicidal ideation, audio or visual hallucinations
• Past medical history (autism, developmental delay, sensory processing disorder, psychiatric condition) and prior engagement with the mental health system is important to ascertain
• A family history of psychiatric disease or longstanding bizarre behaviors supporting a diagnosis of a psychiatric disease (still – developing a psychotic disorder before the age of 12 is rare, in this population medical >>>psych ). Unless there is a past history of the exact same behavior or an existing psychiatric diagnosis it is dangerous to assume that the cause of true altered mental status is psych.
• Acute onset AMS more common in medical causes, where you need to take an accurate history of when the behaviors changed, and the rate of change, when were they last normal, and if this has ever happened before and if so what was the context.
• History suggesting drug use or exposure (teen coming form music festival, abrupt change in toddler behavior, and suspected ingestion)
  • This is where knowing common toxidromes is helpful
    • Sympathomimetic – ie diphenhydramine ingestion, synthetic cannabinoids, jimson weed, etc. 
• You may also see Tox from current medications (eg, corticosteroids, AEDs, atypical antipsychotics, isoniazid, amoxicillin, clarithromycin, and erythromycin have rarely caused neuropsychiatric symptoms including anxiety and hallucinations. )
• Constitutional symptoms (fevers, chills, headache) indicating an infectious etiology (meningitis, encephalitis)
• Rheum/inflammatory disease history – SLE
• Head trauma (intracranial injury)
• New onset of neurologic deficits (stroke, brain abscess, brain tumor)
• Seizure disorder or signs suggestive of seizure disorder (inattentiveness, rhythmic blinking or other stereotyped movements)
• Prior episodes associated with possible precipitating factors (eg, menstruation, medications, stress), vomiting, or headache suggestive of metabolic disease (urea cycle defects, acute intermittent porphyria [AIP]).

Physical examination

Before detailed exam make sure vitals are normal (brain getting enough oxygen, fever) and that the patient doesn’t have signs of hypoglycemia (altered mental status, diaphoresis, tachycardia, hypotension) – you need to fix those first.

Mental status

Patient with psychiatric illness typically has normal vital signs; normal orientation to person, place, and time; and intact memory with good cognitive functioning. Hallucinations are usually auditory in nature.

Medical psychosis usually abnormal vital signs, altered mental status, and impaired orientation with compromised intellectual function. Visual and tactile hallucinations are more classically “organic.” Note that brief hallucinations can occur in “normal” situations like:

• Falling asleep and waking
• Bereavement
• Sleep deprivation
• Caffeine

The Neurologic exam MUST be normal. Any abnormal neurologic exam finding is medical until proven otherwise.

The pupil exam is particularly “testable” and is often helpful:

• Conditions affecting the brain diffusely spare pupils – except for opiates.
• Miosis
  • Cholinergics, Clonidine
  • Opiates, Organophosphates
  • Phenothiazines, Pilocarpine
  • Sedative-hypnotics
• Mydriasis
  • Antihistamines
  • Antidepressants
  • Anticholinergics (includes Atropine)
  • Sympathomimetics
• Unilateral enlargement >5 mm + coma is herniation until proven otherwise
• Nystagmus can be seen in ketamine ingestions

Now I’ve noted a sea change with regard to how we address patients with functional symptoms. I can recall many times early in my career that I heard “oh, he’s just faking.” 

• Catatonic patients preserve ability to maintain posture
• Patients with functional neurologic problems generally…
  • Avoid hitting their face with a falling arm
  • Resist eyelid opening
  • Raise HR to auditory or painful stimuli (smelling salts)
  • Intact DTR, oculovestibular, and oculocephalic reflexes

Fortunately in my experience a thorough clinician is able to figure out if something is “off” and initiate a workup in many instances. You should tailor your workup towards the findings and your index of suspicion. Reading the differential diagnosis would double the length of this episode – so I won’t do that. However big categories include as alluded to earlier:

• Toxindromes that present with agitation include anticholinergics, sympathomimetics, and hallucinogens (LSD), and marijuana
• CNS – mass, intracranial injury, stroke, seizure (post ictal psychosis, temporal lobe epilepsy), meningoencephalitis , and even subacute sclerosing panencephalitis which occurs with a measles infection (vaccinate people!)
• Infectious
• Lupus encephalitis will have auditory and tactile hallucinations (see – organic!)
• Metabolic Diseases
  • Urea cycle defects – recurrent episodes of bizarre behavior, hallucinations, or delusions during adolescence and adulthood. Typically complain of headache and vomiting. Delayed presentation is most common with partial ornithine transcarbamylase deficiency.  Interestingly these patients eat veggies because lots of protein causes headaches.
  • Acute intermittent porphyria (AIP) leads to psychiatric complaints and psychosis (hysteria, anxiety, apathy, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness) – drugs that induce the P450 microsomal oxidase system (eg, barbiturates), fasting, intercurrent illness, and premenstrual hormonal changes in women
  • Wilson disease is the copper one that presents during adolescence with subacute psychiatric symptoms from depression to frank psychosis (catatonia and paranoia). Labs will show low ceruloplasmin concentrations and elevated urinary copper excretion. Oh yeah, something something. Kayser-Fleischer rings. It is potentially reversible.
  • Uremia and hepatic encephalopathy cause AMS changes with hallucinations.
  • There are MANY others!
• Postpartum psychosis: Seen up to 30 days after childbirth, and has paranoia, delusions, and hallucinations
• Electrolyte Derangements:
  • Hyponatremia or hypernatremia behavior changes and encephalopathy that may be difficult to distinguish from acute psychosis.
  • Hypocalcemia and hypomagnesemia may rarely cause frank psychosis.
• Hashimoto encephalopathy: Rare thyroid psychosis not often seen in children. Thyroid storm will see psychotic symptoms along with HIGH fever and autonomic symptoms. 

Psychiatric causes of acute agitation include depression, bipolar disorder, childhood-onset schizophrenia, and brief reactive psychosis. Again, a history of mental illness in the family, emotional trauma, subacute to chronic symptoms, and coexistent mood disorder suggests a primary psychiatric disorder. 

Management

In the patient with acute agitation start with ABCs, vital signs, IV access, and glucose. If they are a danger to themselves and the team, protecting their airway, and not in cardiorespiratory failure, try non-pharmacologic means first, but note that medical management may be necessary to keep them safe. If they have no prior mental health history, consider BZD (more on that in the upcoming medical management episode #3).

Ventilation may be impaired by declining respiratory drive or muscle dysfunction. Remember hypoxia cause AGITATION, and hypercarbia leads to SOMNOLENCE. Keep your goal O2 sat >95% and use ETCO2 to ensure ventilation. Intubate those who cannot sustain adequate oxygenation or ventilation. Don’t delay that decision!

Any concern for opiate intoxication should follow with a dose of IV or IN Narcan:

• Other antidotes are less widely used: Don’t give flumazenil for benzodiazepine OD as this can precipitate seizures and then you can’t treat them.
• Physostigmine may transiently improve MS in anticholinergic ingestion but you should call a medical toxicologist first.
• Diphenhydramine for dystonia can make a patient agitated.

Labs should ideally be based on concerning findings on H&P, but always ask yourself the following:

• Will the result alter the approach to treatment?
• Will it return in time to affect therapy positively?

Blood and urine tests to consider:

• iSTAT (rapid blood gas) +/- Accucheck
• Renal panel
• CBC and blood culture if febrile or infection suspected
• Tox – Acetaminophen, Salicylate, Ethanol, Urine Drug Screen
• ßhCG in all patients with female reproductive organs
• TSH with reflex to free T4
• Ammonia

Tox levels are routinely sent, but less helpful than we hope:

• APAP: Ingestions are usually symptomatic by 4-6 hours. Per Sporer et al Am J Emerg Med 1996 in a retrospective review of 1820 patients with SI or AMS with suspected ingestion, 0.3% had toxic APAP levels not suggested by history, none required NAC. In Chan et al Hum Exp Toxicol 1995, in a retrospective review of 294 Chinese patients, 4/208 with suspected APAP poisoning had elevated but non-toxic levels.
  • Bottom line- In the absence of history however, still get one. If elevated then repeat at 4 hours
• ASA: Obtain in the unknown ingestion with AMS. Done nomogram no longer routinely used. Levels > 90-100 mg/dL are usually associated with severe toxicity. May need multiple determinations in massive ingestions or sustained release preparations.
• Alcohol (ETOH): Elimination follows zero order kinetics. Rate varies 12-25 mg/dL/h – naive drinkers 10 mg/dL/h. Rough correlation between level and symptoms. Level <300 mg/dL in a comatose patient should prompt search for another cause
• UDS Urine metabolites can be seen for 2-3 days, while blood 6-12 hours.
  • Does a toxicology screen affect the management of a patient who has taken overdose? The cumulative evidence suggests not. Even if positive it rarely alters management. Plus not everything is detected on UDS. You need to know what is screen for and not screened for the sake of your local institution

Other than labs we often obtain EKGs, which is most helpful in suspected ingestions. Diagnostic for serious TCA overdose with QRS widening (≥0.10 sec) & rightward shift of the terminal 40 ms of the frontal plane QRS complex vector (terminal R wave in aVR)

LP with CSF Studies: If you suspect meningitis/encephalitis – are they Stable enough? Is sedation necessary and safe? If the patient is NOT septic, you can defer antibiotics until after CSF studies. Antibiotics to consider are ceftriaxone (meningitis dosing), vancomycin, and acyclovir (remember that HSV can cause temporal lobe encephalitis and behavior changes).

CT Head: Consider in elevated ICP, trauma, CSF shunt, focal neuro findings, and unsupervised child. May need to be a prelude to any LP if you suspect these

Now, with all of this discussion on workup I cannot ignore the face that MOST patients don’t need any studies to establish that they are “medically cleared.” Choosing Wisely released their recommendations for Pediatric Emergency Medicine recently and I’m going to quote their recommendations verbatim here – “Most children with acute mental health issues do not have underlying medical etiologies for these symptoms. A large body of evidence, in both adults and children, has shown that routine laboratory testing without clinical indication is unnecessary and adds to health care costs. Any diagnostic testing should be based on a thorough history and physical examination. Universal requirements for routine testing should be abandoned.”

Summary

OK, so that’s it for episode 1 of the Agitation podcast series. Today we reviewed the organic versus psychiatric divide, where we discussed how a thorough H&P guides any evaluation we perform. In the second episode we will discuss non-pharmacologic management of agitated children, which is the first steps in keeping them calm and safe.

Resources

• emDOCs.net Articles
  • Toxcards: Sympathomimetic vs. Anticholinergic Toxidromes
  • Physostigmine for Management of Anticholinergic Toxidrome
  • ToxCard: TCA Poisoning
• PEM Blog via Brad Sobolewski (@PEMTweets)
• EMSC IIC (Emergency Medical Services for Children Innovation and Improvement Center)
  • EMSC IIC: Pediatric Education and Advocacy Kit (PEAK): Agitation
  • For more info, please email km@emscimprovement.center or follow on Twitter @EMSCImprovement

Other Episodes in the Agitation Series

Episode 2: Non-pharmacologic management of agitated children (Coming May 24, 2023)

Episode 3: Pharmacologic management of agitated children (Coming May 31, 2023)

Episode 4: Safe pre-hospital transport of the agitated child (Coming June 7, 2023)

Episode 5: Management of the child with mental health problems who is boarded in the Emergency Department (Coming June 14, 2023)

References

Hua LL, COMMITTEE ON ADOLESCENCE. Collaborative Care in the Identification and Management of Psychosis in Adolescents and Young Adults. Pediatrics 2021; 147.

Sedel F, Baumann N, Turpin JC, et al. Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. J Inherit Metab Dis 2007; 30:631.

Chun TH, Sargent J, Hodas GR. Psychiatric emergencies. In: Textbook of Pediatric Emergency Medicine, 5th, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott Williams & Wilkins, Philadelphia 2006. P.1820.

Cunqueiro A, Durango A, Fein DM, et al. Diagnostic yield of head CT in pediatric emergency department patients with acute psychosis or hallucinations. Pediatr Radiol 2019; 49:240.

Gerson R, Malas N, Feuer V, Silver GH, Prasad R, Mroczkowski MM. Best Practices for Evaluation and Treatment of Agitated Children and Adolescents (BETA) in the Emergency Department: Consensus Statement of the American Association for Emergency Psychiatry. West J Emerg Med. 2019 Mar;20(2):409-418. doi: 10.5811/westjem.2019.1.41344. Epub 2019 Feb 19. Erratum in: West J Emerg Med. 2019 May;20(3):537. Erratum in: West J Emerg Med. 2019 Jul;20(4):688-689. PMID: 30881565; PMCID: PMC6404720.

The post PEM Currents – Agitation in Children – Episode 1: Differentiating Organic vs Psychiatric 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. This week we cover “Thrombolysis with alteplase 3–4.5 hours after acute ischemic stroke: trial reanalysis adjusted for baseline imbalances”, which is a reanalysis of ECASIII and tPA stroke.

Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Outcome:

Reanalysis of the unadjusted data:

• On reperforming the unadjusted analysis on the original data, 209 patients in the alteplase group (rather than 210 patients) had an NIHSS score of 0 or 1.
  • This discrepancy resulted in the outcomes at 90 days of NIHSS score of 0 or 1 and the global outcome becoming no longer statistically significant.
• On reperforming the unadjusted analysis for ICH, 11 cases of vascular serious adverse events in the placebo group rather than 10 cases originally reported.
• The original analysis in ECASS III was based on the NIHSS score, including two additional distal motor function components, resulting in a range of 0-46.
  • However, the original publication erroneously stated a range of 0-42 based on 15 components.
  • Reanalysis using the standard 0-42 range found that all primary outcomes were not significant.

Analyses adjusted for baseline imbalances:

• Calculated NIHSS scores were based on the 15 component scores in the original NIHSS score definition.
• In case a baseline NIHSS component score was absent, it was filled in with a value of 0. Similarly, if there was a missing value for a 90-day NIHSS component score, it was replaced with the highest possible value for that particular item.
• The only 2 variables that were statistically significant as baseline imbalances were the NIHSS score and history of prior stroke.
• After conducting a best-case sensitivity (Table 4) analysis, it was determined that the outcome of mRS 0 or 1 had a small effect across most analysis methods. However, the results for mRS 0 and mRS 0-2 were inconsistent and varied depending on the method of analysis used.
  • This analysis showed significant increased RR of ICH
• A worst-case sensitivity analysis (Table S4a,b), using either the baseline NIHSS score ranging from 0 to 42 or 0 to 46, showed none of the efficacy end points were statistically significant in either unadjusted analyses or in any analysis that was adjusted for baseline imbalances.

Take Aways:

• This study highlights several of the significant methodological flaws in the original ECASIII study. The authors first acquired the data and then attempted to recreate the results. There were several issues including discrepancies in the reported and actual number of patients in placebo group and lack of transparency in converting continuous data into ordinal data or ordinal data into dichotomous. In summation, recreating the data was difficult. Despite the authors’ best attempts minor changes in outcomes were observed in some outcomes despite the use of the same data.
• In the adjusted analyses, 5 out of 6 analyses showed a significant increase in ICH.
• In the most forgiving of the reanalysis there was a small observed benefit in a mRS of 0-1, vs > 1. This lumps together having a small paresthesia in your arm but living independently with no disability vs living independently with small disability + coma, severe disability and death (2-6). I would argue this is not a meaningful comparison.
• In the most conservative reanalysis there was no benefit, and as mentioned observed increased ICH.
• Using this many tests against the null, the original authors probably should have used a Bonferroni correction. The Bonferroni correction is a conservative means utilized to adjust the significance threshold for multiple hypothesis testing. In application this correction makes the p value required to deem an observation significant much less than 0.05. For example, in table 4, with 14 comparisons you would actually need a p value of 0.00357 for an observation to be significant.

My take:

• This reanalysis highlights several of the issues in the original ECASIII and makes me seriously question if TPA has any role in the 3-4.5 hr window. At the patient level, I will follow the guidelines of my hospital, but at the policy level we really need to be having hard conversations about if we should be giving this medication for this indication. To me, these data do not really provide robust support for the use of TPA.

Reference:

1. Alper BS, Foster G, Thabane L, Rae-Grant A, Malone-Moses M, Manheimer E. Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evid Based Med. 2020;25(5):168-171. doi:10.1136/bmjebm-2020-111386
2. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. doi:10.1056/NEJMoa0804656
3. https://www.nejm.org/doi/full/10.1056/NEJM199512143332401
4. Hoffman JR, Schriger DL. A graphic reanalysis of the NINDS Trial. Ann Emerg Med. 2009;54(3):. doi:10.1016/j.annemergmed.2009.03.019

The post 52 in 52 – #35: ECASIII Reanalysis appeared first on emDOCs.net - Emergency Medicine Education.

Author: Alex Koyfman, MD (@EMHighAK) // Reviewed by: Brit Long, MD (@long_brit) and Manpreet Singh, MD (@MprizzleER)

Welcome back to the EM Educator Series. These posts provide brief mini-cases followed by key questions to consider while working. The featured questions provide important learning points for those working with you, as well as vital items to consider in the evaluation and management of the specific condition discussed.

This week has another downloadable PDF document with questions, links and answers you can share with learners as educators in #MedEd. Please message us over Twitter and let us know if you have any feedback on ways to improve this for you. Enjoy!

Case 1:

A 35-year-old male with no past medical history presents with severe rectal pain and inability to sit still on stretcher despite pain medication. He is tachycardic and appears in severe pain.

Case 2:

A 65-year-old female with history of diabetes and obesity presents with altered mental status.  She is febrile, tachycardic, and hypotensive. On examination you find redness in the perineal region that tracks up the anterior abdominal wall.

Considerations:

• What are the major risk factors for Fournier gangrene?
• How can patients present?
• What laboratory testing may be helpful, and what risk scores are available?
• What is the utility of imaging, including ultrasound?
• What are the ED management priorities?
• What are major pitfalls with Fournier gangrene?

Suggested Resources: 

• #FOAMed
  • emDOCs Fournier Gangrene
  • emDOCS Misdiagnosing and Mismanaging
  • IBCC – NSTI
  • Wik EM
• Journal Articles
  • JEM – Fournier Gangrene
  • JEM – NSTI Pearls and Pitfalls

The post The EM Educator Series: Fournier Gangrene – Simple, raging cellulitis 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. This week we cover the EXTEND-IA TNK study, which evaluates TNK versus tPA before thrombectomy.

Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Take Aways:

• TNK is non-inferior to TPA for vessel re-cannulation and thrombus/embolus obliteration during index intervention.
• This was an open label study, and thus physicians and other staff were not blinded to randomization.
• As these patients were required to have arterial puncture within 6 hours of stroke onset, these data may not apply to patients who are not presenting to a stroke center. For example, a patient with an LVO stroke presenting to a hospital and needing transfer for endovascular thrombectomy, or a patient getting endovascular thrombectomy within 24 hours.
• Prespecified superiority analysis suggests TNK may result in better functional outcomes. However, ultimately this study was powered and conducted as a non-inferiority study, so this is only hypothesis-generating.
• This study did change its enrollment criteria after 80 patients were already enrolled.
• There existed a substantively larger proportion of patients with MCA occlusion in the TNK arm. Given the smaller infarct territory, this could reasonably be expected to have consequential impacts on long term outcomes.

My take:

• These data suggest TNK is non-inferior to TPA for patients requiring thrombectomy for anterior circulation LVO undergoing thrombectomy. Given the ease of use and pharmacodynamics, I would favor use of TNK over TPA for this patient population.

Source Article:

1. Campbell BCV, Mitchell PJ, Churilov L, et al; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405. PMID: 29694815.

The post 52 in 52 – #34: Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke (EXTEND-IA TNK) appeared first on emDOCs.net - Emergency Medicine Education.

Today on the emDOCs cast, Brit Long, MD (@long_brit) covers Part 1 in a series on complications of CAR T-cell therapy, specifically cytokine release syndrome (CRS).

Episode 77: CAR T-cell Therapy and Cytokine Release Syndrome

Background

• Vast array of new cancer therapies, including chimeric antigen receptor (CAR) T-cell therapy, antibodies, cytokines, oncolytic viruses, and vaccines.
• CAR T-cell therapy is a type of immunomodulation which uses genetically modified T-cells to attack malignant cells.
• Primarily used for ALL, CLL, Non-Hodgkin’s, multiple myeloma. Currently under study for Hodgkin’s lymphoma and solid tumors.

Mechanism:

• CAR T cell therapy involves T cells attacking cancer cells.
• Process:
  • 1. T-cells present in the blood are removed from the patient or from a donor (less common).
  • 2. T-cells are incorporated with the gene encoding specific antigen receptors.
  • 3. This results in CAR receptors on the surface of T-cells.
  • 4. The modified T-cells are harvested and grown in a laboratory setting.
  • 5. The patient undergoes chemotherapy for lymphocyte depletion, and then the engineered T-cells are finally administered to the original patient.

Complications

• Infusion usually occurs in the outpatient setting.
• The two major complications of CAR T-cell therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), or CAR T-cell-related encephalopathy syndrome (CRES).
• Others are infusion reaction, hypogammaglobulinemia, tumor lysis syndrome (TLS), cytopenias, cardiac toxicity, and graft-versus-host disease (GVHD).

Cytokine Release Syndrome

• CRS is a serious complication with fever and multiorgan dysfunction (Figure 2).
  • CRS is a supraphysiologic response to CAR T-cell therapy that leads to elevated cytokine activity (interleukin (IL) 6, interferon (IFN), and tumor necrosis factor (TNF) alpha) and activation of endothelial cells, macrophages, and T-cells.
• CRS occurs in 25%-50% of patients treated with CAR T-cell therapy for ALL, but the incidence is lower in patients with NHL, CLL, and multiple myeloma.
• Severity is associated with the disease burden of the malignancy, molecular design, level of T-cell activation in response to CAR T-cell infusion, lymphodepletion prior to infusion, and dose of CAR T-cells
• Onset of symptoms is 1-14 days after therapy, but severe CRS usually occurs shortly after CAR T cell therapy. Duration can be days to weeks.
• Signs/symptoms range from mild, flu-like symptoms to severe, life-threatening inflammation and end organ injury. Fever has to be present for the diagnostic criteria.
  • Mild symptoms include rash, headache, myalgias, and fatigue.
  • Gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are common.
  • Severe, uncontrolled CRS may include circulatory collapse, vascular leakage, edema, renal failure, cardiac dysfunction, and multiorgan failure.
  • Neurologic symptoms can occur several days after the onset of CRS and include aphasia, altered mental status, weakness, seizures, and cerebral edema.
  • Grading is based on cardiopulmonary dysfunction and related treatment intervention; the most severe event noted is used to define the grade

• Consider CRS following CAR T-cell therapy in patients with fever, hypotension, hypoxia, tachypnea, tachycardia, dyspnea, myalgias, fatigue, nausea, vomiting, and diarrhea.
• Nonspecific presentation. Patients look like sepsis or septic shock. Must keep sepsis, heart failure, pulmonary embolism (PE), hemophagocytic lymphohistiocytosis, tumor lysis syndrome, and tumor progression on the differential.

ED Evaluation

• History: symptoms (fever, dyspnea, pain, rash), baseline patient function, disease status, burden of illness, immunotherapy type, dose, and schedule.
• Physical examination should focus on the skin, hearts, lungs, abdomen, and neurologic system.
• Testing: Labs and imaging are nonspecific; diagnosis needs to be based on history and end organ injury.
  • CBC, electrolytes, magnesium/phos/Ca, renal/liver function, uric acid, coags, blood cultures, CRP.
  • ECG, BNP, troponin if cardiopulmonary symptoms present.
    • Significant risk of cardiac ischemia and arrhythmia.
  • May see leukocytosis, leukopenia, neutropenia, and/or thrombocytopenia may be present due to chemotherapy, the malignancy, or other isues
  • Elevated creatinine and liver enzymes are common, as are electrolyte abnormalities, including hypophosphatemia (75%), hypokalemia (56%), and hyponatremia (51%).
  • Coagulation panel abnormalities may occur.
  • Confirmatory tests are interferon gamma, IL-6, IL-10, and soluble IL-2R alpha levels, but not available in the ED.
  • CXR for cardiopulmonary symptoms.

Management:

• Stabilization, evaluation for concomitant pathologies (e.g., sepsis, PE), and providing targeted therapy based upon the CRS grade.
• Involve hematology/oncology early.
• If the patient is critically ill, start with IV fluids, vasopressors, and broad-spectrum antibiotics. These patients will look like sepsis. Respiratory support will be needed for severe cases.
• Targeted therapy is based on CRS severity
  • Mild CRS can typically be treated with antipyretics, intravenous fluids, antihistamines, and monitoring.
  • Other grades may need steroids plus tocilizumab, but this is best left to the heme/onc and critical care specialist.
    • Patients with severe CRS (consisting of some patients with grade 2 CRS and all patients with grades 3-4 CRS) may receive tocilizumab, an IL-6 antagonist, plus a steroid. This combination provides more rapid and complete control compared with either agent alone
    • For those with less severe manifestations meeting criteria for grade 2 CRS, tocilizumab may be used alone.
    • Options for steroids include hydrocortisone 100 mg every 8 hours, dexamethasone 10 mg up to four times per day, or methylprednisolone 1 mg/kg/day.
    • Steroids should be used alone in patients with neurologic findings.
    • Other monoclonal antibodies may be used if tocilizumab is not effective.
  • All patients should be admitted.

Stay tuned for Part 2, where we cover neurotoxicity, infusion reactions, cytopenias, and cardiac toxicity!

References:

1. Long B, Yoo MJ, Brady WJ, Holian A, Sudhir A, Gottlieb M. Chimeric antigen receptor T-cell therapy: An emergency medicine focused review. Am J Emerg Med. 2021 Dec;50:369-375.
2. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer. 2018 Jun 15;6(1):56.
3. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor Tcell therapy-assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47–62.
4. Liu D, Zhao J. Cytokine release syndrome: grading, modeling, and new therapy. J Hematol Oncol. 2018 Sep 24;11(1):121.
5. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638.

The post emDOCs Podcast – Episode 77: CAR T-cell and Cytokine Release Syndrome appeared first on emDOCs.net - Emergency Medicine Education.

Authors: Dave Ediger, MD (EM Chief Resident; Tacoma, WA), Rachel Bridwell, MD (EM Attending Physician; Tacoma, WA) // Reviewed by: Sophia Görgens, MD (EM Resident Physician, Zucker-Northwell NS/LIJ, NY); Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School);Brit Long, MD (@long_brit)

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

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

Author: Alex Koyfman, MD (@EMHighAK) // Reviewed by: Brit Long, MD (@long_brit) and Manpreet Singh, MD (@MprizzleER)

Welcome back to the EM Educator Series. These posts provide brief mini-cases followed by key questions to consider while working. The featured questions provide important learning points for those working with you, as well as vital items to consider in the evaluation and management of the specific condition discussed.

This week has another downloadable PDF document with questions, links and answers you can share with learners as educators in #MedEd. Please message us over Twitter and let us know if you have any feedback on ways to improve this for you. Enjoy!

Case 1:

A 37-year-old male with with a history of polysubstance abuse presents with confusion and unilateral weakness. Vital signs reveal fever.

Case 2:

A 22-year-old female presents with fatigue, headache, and neck pain. She recently completed a course of antibiotics for sinusitis, but she otherwise has no past medical history.

Considerations:

• What are the major risk factors for meningitis?
• How can patients present with meningitis?
• What are high yield components of the history and exam?
• What labs should be obtained?
• When is CT recommended?
• What are considerations with antibiotics?
• When are steroids recommended?

Suggested Resources: 

• Articles
  • IBCC – Meningitis
  • emDOCs – Why we miss meningitis and how to improve
  • emDOCs – Myths in EM: When is CT before LP needed?
  • emDOCs – Meningitis
• Journal Articles
  • American Journal of EM – High Risk/Low Prevalence Diseases: Meningitis

The post The EM Educator Series: Meningitis – Unusual Headache and Fever 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. This week we cover the PREVENT trial. Does low (6 mL/kg) tidal volume reduce ventilator free days in ventilated patients without ARDS compared to intermediate tidal volume (10 mL/kg)?

Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Intervention:

• Patient initiated on 6 mL/kg tidal volume
  • Volume control (VC) or pressure control (PC) were allowed
    • If VC was used the tidal volume was decreased by 1 mL/kg every hour to a minimum of 4 mL/Kg
    • If PC, the minimum pressure was 5 cm H₂O
      • If tidal volume was >8 mL/Kg despite 5 cm H₂O this was tolerated

Comparator:

• Patient initiated on 10 mL/kg tidal volume
  • Volume control (VC) or pressure control (PC) were allowed
    • If VC was used:
      • Plateau pressure was monitored and if >25 cm H₂O, tidal volume was decreased by 1 mL/kg PBW per hour
    • If PC was used:
      • Pressure support was adjusted to goal tidal volume while monitoring the plateau pressure keeping the pressure less than 25 cm H2O

Outcome:

• Primary outcome was ventilator free days and alive at day 28.
  • No statistically significant difference in primary outcome between groups.
  • Patients in both groups had a median of 21 ventilator-free days 28 days after randomization.
    • (IQR, 0-26) (mean difference, –0.27 [95% CI −1.74 to 1.19]; P = .71
• Secondary outcomes included length of ICU and hospital stay, 28 and 90 day mortality in ICU and the hospital, development of ARDS/pneumonia/severe atelectasis/pneumothorax
  • No significant difference in secondary outcomes.

Take Aways:

• Negative trial/no difference between 6 mL/kg and 10 mL/kg tidal volumes on ventilator free days (primary outcome) and a number of secondary outcomes (ie, mortality, length of stay, adverse events).
• This was a large trial, with good methodology and pre-published statistical methods.
• Authors used an intention to treat analysis.
• Unfortunately, the study focused on ventilator free days, rather than mortality as a primary outcome. Mortality is an optimal patient centered outcome, rather than ventilator free days. Families probably care if their family member lived, more than they care if they were off the ventilator a few days earlier.
• The study focuses on a relatively simple metric as a surrogate for preventing lung injury. While overlooking more complicated measures, a focus on this discrete variable is of benefit in its application to the ED patient.

My take:

• While I wouldn’t expressly target tidal volumes above ARDSNet guidelines, based on these data, if patients are transiently on tidal volumes of 6-10 mL/kg, I am not convinced there would be harm. Current evidence still compels me to advise erring toward 6mL/Kg.

Source Article:

1. Writing Group for the PReVENT Investigators; Simonis FD, Serpa Neto A, Binnekade JM, Braber A, Bruin KCM, Determann RM, Goekoop GJ, Heidt J, Horn J, Innemee G, de Jonge E, Juffermans NP, Spronk PE, Steuten LM, Tuinman PR, de Wilde RBP, Vriends M, Gama de Abreu M, Pelosi P, Schultz MJ. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2018 Nov 13;320(18):1872-1880. doi: 10.1001/jama.2018.14280. PMID: 30357256; PMCID: PMC6248136.

The post 52 in 52 – #33: The PREVENT Trial 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

Missed testicular torsion: Is it “gross negligence”?

Be nice, or risk being called “willfully and wantonly negligent”

[Note from Dr. Pilcher: Most med mal cases are evaluated on the basis of ordinary negligence, i.e., a mental error or wrong procedure/treatment that a reasonable practitioner under similar circumstances would have avoided. Some states allow (or even require) a higher bar called “gross negligence.” This is defined as “aggravated negligence that amounts to an indifference to one’s legal obligations with respect to the rights of others.” “Gross negligence” is a subjective finding that requires an assessment of the “state of mind” of the defendant physician. The following is an example of a case claiming gross negligence.]

Facts: An adult male patient presents to a free-standing ED with RLQ abdominal and flank pain (He claims that he told the triage nurse that he also had inner thigh and groin pain, but there is no record of that). The ED physician evaluates him using an “Abdominal Pain” template that includes testicular torsion as a potential cause. He does not check the box labeled “Male Genital Exam,” and torsion appears not to have been considered. The patient is discharged with a non-specific diagnosis but returns the next day unimproved. He asks to see the same physician from the day before, who meets him in the waiting room before he can check in. The doctor allegedly “rushes him out,” telling him to go to [a nearby teaching] Hospital because “there is nothing more to do.” There his torsed testicle is removed. The patient files a lawsuit against the ED physician claiming he was treated with “willful and wanton negligence.” A lower court dismisses that claim based on insufficient evidence. That ruling is appealed.

Plaintiff: I had classic signs and symptoms of testicular torsion and have an expert witness physician who agrees with me. Your own forms instruct you to evaluate me for torsion before discharging me. If you had, you would have gotten an ultrasound exam and made the diagnosis. When I returned the next day, you brushed me off completely as only wanting pain meds and told me to go to [the teaching] hospital. I did not refuse to check in. When I called you after my testicle was removed, you told me it was “no big deal” because I would “not be having any more children because of my age.” You not only misdiagnosed me, but did so with willful disregard of the risk that your behavior posed for my health.

Defense: I considered torsion but didn’t document it. You didn’t need an ultrasound of your testicles. When I saw you the second day, you refused to check in. I told you to go to the other hospital and they fixed you.

Result: The trial court dismissed the claim of “willful and wanton negligence” against the ED physician. The plaintiff appealed and the appellate court over-ruled the lower court, leaving it up to a “fair-minded jury” to determine the “subjective state of mind” of the physician. Prior to trial a settlement was reached for an undisclosed amount.

Takeaways:

• * Be diligent about completing EHR “click-tation” templates as designed.  * Document what you do, including pertinent negatives. Don’t document things you don’t do. [Editor’s note: A 14-point ROS and complete PE is rarely justified for a simple ankle sprain. Documenting these raises a question of one’s honesty and/or billing ethics.]
• Revised CPT coding guidelines for 2023 replace “box-checking” with evidence of the complexity of “Medical Decision Making,” a long overdue decision.
• Be nice to all patients, even those you may dislike.
• “Willful and wanton negligence,” aka “gross negligence” is determined subjectively by a jury through an assessment of the defendant’s state of mind at the time of the alleged incident(s). Exposing yourself to a jury to decide if you are a “nice doctor” is rarely a good idea.
• It’s one thing to make a diagnostic error, but should a jury find one guilty of doing so with “willful and wanton negligence,” one’s career could be over – which likely explains the pre-trial settlement on the charge of “gross negligence.”

Further Reading:

• http://www.emdocs.net/em3am-testicular-torsion/
• http://www.emdocs.net/testicular-torsion-pearls-and-pitfalls/
• http://www.emdocs.net/em-cases-testicular-torsion-a-diagnostic-pathway/

The post Medical Malpractice Insights: Missed testicular torsion – Is it “gross negligence”? appeared first on emDOCs.net - Emergency Medicine Education.

The post emDOCs Podcast – Episode 76: Giant Cell Arteritis appeared first on emDOCs.net - Emergency Medicine Education.

Author: Vivek Medepalli, MD (EM Resident Physician, UTSW / Parkland Memorial Hospital) and Christine Kulstad (EM Attending Physician, UTSW / Parkland Memorial Hospital) // Reviewed by: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX); Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital); Sophia Görgens, MD (EM Resident Physician, Zucker-Northwell NS/LIJ, NY); Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School)

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

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