Olanzapine + Benzodiazepines – What is the FDA warning about?

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At ACEP 2019, a talk by Bryan Hayes (@PharmERToxGuy) was captivating. He addressed use of medications with black box warnings in the ED. One particular warning caught our eye – olanzapine + benzodiazepine.

The FDA has warned of the risk of potentially fatal respiratory depression with concomitant administration of antipsychotics and benzodiazepines, stating “Concomitant administration of intramuscular olanzapine and parenteral benzodiazepine has not been studied and is therefore not recommended.”

References:

  1. Marder SR, Sorsaburu S, Dunayevich E, et al. Case reports of postmarketing adverse event experiences with olanzapine intramuscular treatment in patients with agitation. J Clin Psychiatry. 2010;71(4):433-41.
  2. Cole JB, Moore JC, Dolan BJ, et al. A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department. Ann Emerg Med. 2017;69(3):327-336.e2.

Vaping Associated Lung Injury (VALI)

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Vaping associated lung injury (VALI) has become a frequent topic in the news in the United States (US). The Centers for Disease Control and Prevention (CDC) has released new guidance for clinicians that we review in this episode. We also discuss problems with widespread concern (potential over-screening and radiation exposure) as well as the available evidence on diagnosis and treatment of VALI.

References:

  1. Morbidity and Mortality Weekly Report (MMWR). 2019; 68(40)
  2. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin – Preliminary Report. N Engl J Med. 2019; Sept 6.
  3. Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019;381:1488-1489.

Emergent Treatment of Hyperkalemia – Insulin/Dextrose

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Insulin is a mainstay in the emergent treatment of hyperkalemia but comes at the cost of increased risk of hypoglycemia, which is quite common.

References:

  1. Scott NL, Klein LR, Cales E, Driver BE. Hypoglycemia as a complication of intravenous insulin to treat hyperkalemia in the emergency department. Am J Emerg Med. 2019;37(2):209-213.
  2. Apel J, Reutrakul S, Baldwin D. Hypoglycemia in the treatment of hyperkalemia with insulin in patients with end-stage renal disease. Clin Kidney J. 2014;7(3):248-50.
  3. Coca A, Valencia AL, Bustamante J, Mendiluce A, Floege J. Hypoglycemia following intravenous insulin plus glucose for hyperkalemia in patients with impaired renal function. PLoS ONE. 2017;12(2):e0172961.
  4. Larue HA, Peksa GD, Shah SC. A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal Insufficiency. Pharmacotherapy. 2017;37(12):1516-1522.
  5. Jacob BC, Peasah SK, Chan HL, Niculas D, Shogbonnwaesei A. Hypoglycemia Associated With Insulin Use During Treatment of Hyperkalemia Among Emergency Department Patients. Hosp Pharm. 2019;54(3):197-202.
  6. Harel Z, Kamel KS. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review. PLoS ONE. 2016;11(5):e0154963.
  7. Pierce DA, Russell G, Pirkle JL. Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia. Ann Pharmacother. 2015;49(12):1322-6.

Droperidol (and Haloperidol)

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Droperidol received a black box warning from the US Food & Drug Administration (FDA) in 2001.

 

More on droperidol
Taming the SRU
The Short Coat

References:

  1. Khokhar MA, Rathbone J. Droperidol for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2016;12:CD002830.
  2. Calver L, Drinkwater V, Gupta R, Page CB, Isbister GK. Droperidol v. haloperidol for sedation of aggressive behaviour in acute mental health: randomised controlled trial. Br J Psychiatry. 2015;206(3):223-8.
  3. Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010;56(4):392-401.e1.
  4. Braude D, Soliz T, Crandall C, Hendey G, Andrews J, Weichenthal L. Antiemetics in the ED: a randomized controlled trial comparing 3 common agents. Am J Emerg Med. 2006;24(2):177-82.
  5. Meek R, Mee MJ, Egerton-warburton D, et al. Randomized Placebo-controlled Trial of Droperidol and Ondansetron for Adult Emergency Department Patients With Nausea. Acad Emerg Med. 2019;26(8):867-877.
  6. Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache. 2006;46(5):781-7.
  7. Gaffigan ME, Bruner DI, Wason C, Pritchard A, Frumkin K. A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department. J Emerg Med. 2015;49(3):326-34.
  8. Leong LB, Kelly AM. Are butyrophenones effective for the treatment of primary headache in the emergency department?. CJEM. 2011;13(2):96-104.
  9. Calver L, Page CB, Downes MA, et al. The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015;66(3):230-238.e1.
  10. Jackson CW, Sheehan AH, Reddan JG. Evidence-based review of the black-box warning for droperidol. Am J Health Syst Pharm. 2007;64(11):1174-86.
  11. Habib AS, Gan TJ. Pro: The Food and Drug Administration Black box warning on droperidol is not justified. Anesth Analg. 2008;106(5):1414-7.
  12. Rappaport BA. FDA response to droperidol black box warning editorials. Anesth Analg. 2008;106(5):1585.
  13. Perkins J, Ho JD, Vilke GM, DeMers G. American Academy of Emergency Medicine Position Statement: Safety of Droperidol Use in the Emergency Department. J Emerg Med. 2015;49(1):91–7.

Thromboelastography (TEG) Guided Resuscitation

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Thromboelastography (TEG) or its related counterpart rotational thromboelastometry (ROTEM) have gained in popularity over the past several years. These tests assess viscoelastic clot strength in whole blood. These tests may offer more granular and potentially reliable information on the patient’s clot formation and fibrinolytic state than traditional measures of coagulation such as International Normalized Ratio (INR), partial thromobplastin time (PTT), and prothrombin time (PT).

One of the primary advantages to TEG/ROTEM is the ability to target transfusion related therapies to the patient’s overall coagulation profile. Below are some common patterns that emerge and the recommended therapies.

Evidence for TEG in Cirrhosis

Additional FOAM resources: PulmCrit

References:

  1. Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev. 2016;(8):CD007871.
  2. Kumar M, Ahmad J, Maiwall R, et al. Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial. Hepatology. 2019; In Press
  3. Rout G, Shalimar, Gunjan D, et al. Thromboelastography-guided Blood Product Transfusion in Cirrhosis Patients With Variceal Bleeding: A Randomized Controlled Trial. J Clin Gastroenterol. 2019; In Press.
  4. Goodman MD, Makley AT, Hanseman DJ, Pritts TA, Robinson BR. All the bang without the bucks: Defining essential point-of-care testing for traumatic coagulopathy. J Trauma Acute Care Surg. 2015;79(1):117-24.

You are called to the bedside for a postoperative patient who is hypotensive, febrile, and has acute onset of respiratory distress following the initiation of a blood transfusion. Which of the following is the most appropriate initial action in the management of this patient?

A. Apply oxygen

B. Call the blood bank

C. Order steroids

D. Stop the transfusion

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Transfusion-related acute lung injury is a blood transfusion complication characterized by a rapid onset of non-cardiogenic pulmonary edema. The pathogenesis is thought to be a two-part mechanism involving neutrophil sequestration with priming in the lung microvasculature followed by neutrophil activation by a factor in the blood product. Pre-transfusion risk factors include current smoking, chronic alcohol use, liver transplantation surgery, positive fluid balance, shock, and higher ventilated peak airway pressures. Though there is an association of transfusion-related acute lung injury with all blood products, high-plasma-volume products (plasma, apheresis platelet concentrations, and whole blood) have the greatest risk. Clinical presentation may occur immediately after the initiation of the blood transfusion although it can be delayed up to six hours. The patient may rapidly develop acute respiratory distress syndrome, with symptoms that may include hypoxemia, fever, hypotension, cyanosis, pulmonary infiltrates on chest imaging, and if intubated, pink frothy secretions when suctioned. Treatment involves immediate discontinuation of the transfusion followed by supportive care of the acute respiratory distress syndrome. This includes oxygen supplementation and hemodynamic support. Apply oxygen (A), call the blood bank (B), and order steroids (C) are treatments for transfusion-related acute lung injury but are not the most appropriate in the initial management. Discontinuing the transfusion, which is the cause of the acute lung injury, is the immediate need upon identifying the condition.

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Top Literature of 2019 – Mid Year Review

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Risk Stratification and D-dimer in Pregnant Patients With Suspected Pulmonary Embolism (PE)

Van der pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med. 2019;380(12):1139-1149.

Infectious Disease Society of America (IDSA) Guidelines for Asymptomatic

Nicolle LE, Gupta K, Bradley SF, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019.

Benzodiazepine dosing for seizures

Sathe AG, Tillman C, Coles LD, et al. Underdosing of benzodiazepines in patients with status epilepticus enrolled in Established Status Epilepticus Treatment Trial. Acad Emerg Med. 2019 Jun 4.

  • Outcomes after Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Trauma Patients

Joseph B et al. Nationwide analysis of resuscitative endovascular balloon occlusion of the aorta in civilian trauma. JAMA Surg 2019. Mar 20.

Additional References:

  1. Brophy GM, Bell R, Claasen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-13.
  2. Glauser T, Shinnar S, Gloss D, et al. American Epilepsy Society Guideline Evidence-Based Guideline: Treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61.

Psychogenic Non-epileptic Attacks (PNEA)

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Psychogenic non-epileptic attacks (PNEA) have been formally referred to as pseudoseizures or psychogenic non-epileptic seizures. Recently, this entity has been rebranded to PNEA to reflect that there is no actual seizure activity and potentially prevent confusion and mislabeling among patients.

A 10-year-old girl presents with episodes of brief staring spells that she is unaware of. The patient’s mother states that the onset and termination of the spells are abrupt. The patient is otherwise healthy. She has lots of friends at school and has excellent academic performance. Physical examination and laboratory studies are normal at this time. Which of the following is the most likely diagnosis?

  1. Absence seizure
  2. Attention deficit hyperactivity disorder
  3. Autism spectrum disorder
  4. Complex partial seizure

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  1. Absence seizure is a type of generalized seizure characterized by loss of consciousness sometimes accompanied by myotonic, atonic, clonic, or tonic components, autonomic components (e.g., enuresis), or automatisms. The onset of absence seizure commonly occurs in early childhood with a predilection to the female sex. It usually terminates by the age of 20 years or may transform into another form of generalized seizure. Absence seizure may be typical or atypical. The onset and termination of a typical absence seizure are abrupt while they may be gradual in an atypical absence seizure. Additionally, atypical seizure commonly occurs in patients with multiple seizure types and demonstrates more marked changes in tone. Patients with an atypical absence seizure may also have a developmental delay or mental retardation. Patients with absence seizure may miss a few words or break off mid-sentence during an attack. The attack period is so brief that the patient is unaware of it. Physical examination may be normal. Having the child hyperventilate for three to five minutes may precipitate a staring attack. Diagnosis of typical absence seizure is with electroencephalography that shows bursts of bilateral synchronous and symmetric 3-Hertz spike-wave activity. A slower spike-wave discharge is noted in an atypical absence seizure. Treatment is with antiepileptic medications including ethosuximide and valproic acid. All patients with absence seizure should be referred to a neurologist for management. Drug levels of valproic acid should be monitored.While attention deficit hyperactivity disorder (B) has a childhood onset, it is marked by symptoms of inattentiveness, hyperactivity, and impulsivity that are not present in the vignette above. Autism spectrum disorder (C) may also have an early onset. However, patients suffer from pervasive difficulties with social communication and repetitive interests and behavior that are absent in the vignette above. In complex partial seizure (D), the duration of seizure usually lasts > 30 seconds, automatisms are present, and the termination of the seizure is gradual.

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References:

  1. Lafrance WC, Baker GA, Duncan R, Goldstein LH, Reuber M. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-18.
  2. Wardrope A, Newberry E, Reuber M. Diagnostic criteria to aid the differential diagnosis of patients presenting with transient loss of consciousness: A systematic review. Seizure. 2018;61:139-148.
  3. Chen et al. Value of witness observations in the differential diagnosis of transient loss of consciousness.  Neurology. 2019 Feb 26;92(9):e895-e904. doi: 10.1212/WNL.0000000000007017. Epub 2019 Jan 25.
  4. Shmuely S, Bauer PR, Van zwet EW, Van dijk JG, Thijs RD. Differentiating motor phenomena in tilt-induced syncope and convulsive seizures. Neurology. 2018;90(15):e1339-e1346.
  5. Doğan EA, Ünal A, Ünal A, Erdoğan Ç. Clinical utility of serum lactate levels for differential diagnosis of generalized tonic-clonic seizures from psychogenic nonepileptic seizures and syncope. Epilepsy Behav. 2017;75:13-17.