Toxicology

Acetaminophen, Acetylcysteine, and Anaphylaxis With a Twist

History

A 15 year-old male, with a past medical history of intermittent asthma, presents with a chief complaint of diffuse abdominal pain, nausea, and two episodes of non-bloody, non-bilious emesis. His symptoms began five hours prior to arrival, and are not accompanied by diarrhea, constipation, genitourinary, urologic, or musculoskeletal symptoms. He provides limited history and appears tearful. On direct questioning, he endorses that he attempted suicide the night prior by taking a “handful of ibuprofen.” He does not know the exact number of pills, but estimates somewhere between 50 and 100, and does not know the dose strength. His mother, a clinical pharmacist, believes they were 200 mg tablets, and that there were no other pills in the house. The patient endorses feelings of depression in the prior month, and blames himself for his father having fallen off a roof (without injury) two years prior. He attends high school and is up-to-date on his vaccinations. He is a non-smoker, does not use alcohol, and endorses occasional marijuana use.  His only medication is an albuterol inhaler as needed.

Physical Exam

Initial vital signs: BP 122/82, HR 68 BPM, Temp 98.6 F, RR 20, and SpO2 100% on room air. Physical exam is notable for RUQ and LUQ tenderness without peritoneal signs. There are no scars or superficial cuts. He is tearful, but alert and oriented to person, place, and time.

Results and Management

The patient was placed on a cardiorespiratory monitor. Workup consisted of an EKG plus typical toxicologic labs, and consultation from poison control.

His EKG showed normal intervals and aVR morphology. Labs were notable for an acetaminophen level of 27 ug/mL and a slight elevation in transaminases, with AST 56 IU/L, and ALT 62 IU/L. On further questioning, the patient confessed that multiple types of pills were taken. Ingestion occurred at 2:00 AM, 14 hours prior to arrival. Given the poor history and elevated acetaminophen level, treatment based on the Rumack-Matthew nomogram (Figure 1) was felt to be beneficial.

Figure 1: Rumack-Matthew nomogram for acetaminophen ingestion.

Figure 1: Rumack-Matthew nomogram for acetaminophen ingestion.

The patient’s mother was concerned about his history of asthma, and her knowledge that NAC can cause bronchospasm; however, the benefits of treatment were felt to outweigh the risks. He was started on a standard 21-hour protocol, with a loading dose followed by two tapering doses.

Approximately one hour after the initial loading dose, the patient began to experience wheezing, a diffuse urticarial rash over the face, neck, shoulders, and thorax, and oral angioedema. He also became tachycardic. Given concern for a severe allergic reaction, bronchospasm, and possibly anaphylaxis, the infusion of NAC was held and he was treated with nebulized albuterol, IV diphenhydramine, IM epinephrine, IV normal saline, and IV corticosteroids. He was monitored in the emergency department for three hours, although his reaction resolved within 30 minutes.

Disposition and Resolution

The decision to restart NAC was considered, weighing the risk of possible anaphylaxis against the benefit of NAC to minimize potential hepatic insult. Given the low acetaminophen level, a repeat drug level and hepatic function panel were sent to inform this decision. These repeat labs came back with an undetectable acetaminophen level (now at 15 hours post-ingestion) and unchanged transaminase levels. NAC was not restarted on the basis of presumed completion of metabolism. The patient was admitted to the pediatric intensive care unit for monitoring, serial drug levels, and hepatic function panels. No further treatment was required during hospitalization. He was transferred to the psychiatry service on hospital day three for inpatient management of suicidal ideation and major depressive disorder. He did well with therapy and was discharged.

Case Discussion

This case illustrates elements of toxicity from two common over-the-counter medications, complicated by an adverse reaction to a life-saving treatment. Acetaminophen toxicity is a common emergency department phenomenon, and while ibuprofen is generally well-tolerated, it can cause toxicity at high doses.

Acetaminophen is metabolized by the liver via two pathways. First, conjugation to sulfate or glucuronide, which generates non-toxic metabolites, and second, via the CYP450 system, which generates a toxic free-radical metabolite, N-acetyl-P-benzoquinone (NAPQI).  NAPQI is neutralized by glutathione (Figure 2).

 
Figure 2: Acetaminophen metabolism.

Figure 2: Acetaminophen metabolism.

 

When acetaminophen is consumed in toxic doses, the pathways leading to nontoxic metabolites are overwhelmed and the accumulation of NAPQI depletes glutathione. In turn, the liver is unable to eliminate free oxygen radicals via glutathione, resulting in oxidative damage and mild, moderate, or fulminant liver failure if glutathione is not regenerated.

Patients are typically asymptomatic until 24-48 hours after an acute ingestion. Single doses over 150-200 mg/kg in healthy children pose significant risk of hepatotoxicity. Symptoms initially are nonspecific, with nausea, vomiting, and malaise, and can progress over a course of days to weeks to liver failure, recovery, or death. Treatment depends on the level of ingestion, the time from ingestion, and the presence of hepatic damage, but generally consists of gastric decontamination within the first hour after ingestion, oral or intravenous NAC, and supportive care. [1]

Ibuprofen, a non-steroidal anti-inflammatory drug, acts on cyclooxygenase enzymes to prevent conversion of arachidonic acid to prostaglandins and thromboxane, disrupting the gastric mucosal barrier and renal blood flow. At toxic doses, it can cause nausea, abdominal pain, gastritis, and renal failure. In severe presentations, acidosis and electrolyte disturbances are seen. The therapeutic window of ibuprofen is broad; toxicity typically does not occur until doses reach the 200-400 mg/kg range. Even in such cases, it is often mild and self-resolving with supportive care. The patient in this case likely consumed less than 100-200 mg/kg, which is unlikely to cause significant symptoms. His nausea, vomiting, malaise, and abdominal pain were likely secondary to gastric irritation from both ingestions in the early phase. [2]

NAC can be given orally or intravenously to manage acetaminophen overdose. Considerations for route depend on the severity of presentation and patient tolerance to PO medications. The duration of treatment varies by route. With IV, which was chosen for our patient due to poor PO tolerance and limited clarity around the time and quantity of ingestion, a loading dose (150 mg/kg administered over one hour) is then followed by tapered IV infusions over the next twenty hours (50 mg/kg administered over four hours, and 100 mg/kg administered over sixteen hours).

Unfortunately, NAC administration can be complicated by anaphylactoid reactions. These reactions are commonly limited to cutaneous symptoms of flushing and pruritus, with bronchospasm, angioedema, and shock occurring in <2% of patients. [3] Yarema and colleagues found in 2018 that 75.4% of anaphylactoid reactions to NAC fall within the cutaneous category. Of the total reactions observed, 95.4% of them occurred within the first five hours of treatment, which correlates with the delivery of high concentrations of drug. Female gender was associated with a more severe reaction, while higher serum acetaminophen concentrations were associated with less severe reactions. [4]

Pakravan et al further researched the mechanism of this reaction in 2008. They found that levels of serum histamine correlated with reaction severity, but that regardless of severity, there was no increase in serum tryptase or inflammatory cytokines. This suggests a non-mast-cell source of histamine and thus, a non-IgE-mediated reaction. This distinguishes the reaction from true anaphylaxis, however, the final common histaminergic pathways are similar, making clinical differentiation nearly impossible and arguments for different treatments in the initial stage largely academic. [5]

The pathophysiology of anaphylaxis and anaphylactoid reactions stems from the effect of histamine on vascular and bronchial smooth muscle leading to cutaneous vasodilation and third-spacing (hives, rash, pruritis), bronchospasm (wheezing), and reduced systemic vascular resistance (tachycardia, hypotension). Reversing this pathophysiology and providing supportive care is accomplished through intramuscular epinephrine (increases systemic vascular resistance and decreases bronchoconstriction), intravenous H1/H2 blockers (decreases vasodilation and third-spacing), nebulized beta-agonists (relieves bronchospasm), intravenous glucocorticoids (anti-inflammatory), and intravenous fluids (intravascular resuscitation, increases cardiac output). [7]

Yamamoto et al researched the frequency of occurrence as related to the treatment timeline, finding that the reaction will most commonly occur during the initial loading dose (61%), that a smaller fraction will occur over the next four hours (37%), and that the least frequent fraction occurs during the terminal taper (2%). [6]

Regardless, this anaphylactoid reaction prompts considerations about appropriate treatment and, if stopped, how and whether or not to restart the drug. The reaction itself, even when severe, typically does not necessitate cessation of therapy. A common approach to managing the reaction includes temporarily holding the infusion, initiating the normal anaphylactic countermeasures, then restarting the infusion at half of the previous rate after symptom control. Generally, the ongoing infusion is well-tolerated once histaminergic blockade is in place. This off-target effect has no effect on the critical reaction of regenerating hepatic glutathione stores. NAC is very effective at preventing fulminant hepatic failure, even in severe cases of overdose, and restarting treatment should be a high priority.

In this case, the patient’s parents refused to restart the medication given his severe reaction. He had not been previously exposed to NAC, which suggests that his reaction was likely anaphylactoid as opposed to anaphylaxis. His acetaminophen level at 14 hours had scored onto the lowest acceptable treatment line on the Rumack-Matthew nomogram and his liver function was only notable for a minimal-mild elevation in transaminases. Given the lower concern for severe toxicity, and repeat labs demonstrating an undetectable acetaminophen level with no appreciable change in hepatic function, the parents and treatment team were comfortable without restarting it in this case.

Lastly, an additional complication of NAC relates to coagulopathy. Sandilands et al reported elevations in INR in association with NAC treatment; however, an initial rise in INR, assuming it stabilizes, is not indicative of progressive liver failure. Elevations typically stabilize around an INR of 1.3, which is not concerning for increased risk of bleeding. [8]

In summary, treatment with NAC may be complicated by histamine-mediated anaphylactoid reactions, which are commonly limited to cutaneous reactions easily treated with histamine antagonists. Severe reactions may necessitate adjunct treatment from inhaled or intravenous beta-agonists, intramuscular beta-agonists, intravenous glucocorticoids, and fluids. True anaphylaxis requires previous sensitization. Unless extenuating circumstances or clinical context exist, NAC should be restarted after treating the reaction. Elevations in INR are common and do not imply liver failure unless they continue to rise.

 

Faculty Reviewer: Dr. Jane Preotle


References

  1. Farrell SE, Miller MA. Acetaminophen Toxicity. Wolters Klewer, eMedicine. Updated 22 Jan 2018. Accessed 24 Sep 2018.

  2. Wiegand TJ, Schlamovitz GZ. Nonsteroidal Anti-inflammatory Drug Toxicity. Wolters Klewer, eMedicine. Updated 20 Dec 2017. Accessed 16 Sep 2018.

  3. Blackford MG, Felter T, Gothard MD, Reed MD. Assessment of the clinical use of IV and oral NAC in the treatment of acute acetaminophen poisoning in children: a retrospective review. Clin Ther.  2011; 33(9):1322-30 (ISSN: 1879-114X)

  4. Yarema M, Chopra P, Sivilotti MLA, et. Al. Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning. J Med Toxicol. 2018 Jun;14(2):120-127. Doi: 10.1007/s13181-018-0653-9.

  5. Pakravan N, Waring WS, Sharma S et. Al. Risk Factors and Mechanisms of Anaphylactoid Reactions to Acetylcysteine in Acetaminophen Overdose. J Clin Tox 2008 Jun;46:697-702.

  6. Yamamoto T, Spencer T, Dargan PL, Wood DM. Incidence and management of N-acetylcysteine-related anaphylactoid reactions during the management of acute paracetamol overdose. Eur J Emerg Med. 2014 Feb;21(1):57-60. doi: 10.1097/MEJ.0b013e328364eb22.

  7. Bailey B, McGuigan MA. Management of Anaphylactoid reactions to IV N-acetylcysteine. Ann Emerg Med. 1998 Jun;31(6):710-5.

  8. Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009 Feb;47(2):81-8.

Acetaminophen: Where is it Found? And How to Handle Too Much of It!

INTRODUCTORY CASE

A 14-year-old girl with a history of suicidal behavior presents to a pediatric emergency department with polysubstance ingestion.  Over the last two days she has ingested variable amounts of lorazepam, alcohol, and DayQuil™ (acetaminophen, dextromethorphan, and phenylephrine).  She drank an unknown quantity of DayQuil™ the day prior and admits to drinking an entire bottle on the day of presentation.  The patient denies any current symptoms.

Vital signs:  T 97.9 F, BP 133/83, HR 114, RR 20, SpO2 100%

On examination, she is in no acute distress.  Her neurologic examination is non-focal with a Glasgow Coma Scale of 15.  Her abdomen is benign.  She has linear scars to the left forearm from self-injurious behavior.  She is cooperative, nonchalant about her ingestion, describes her mood as “numb”, and has a flat affect. 

Her laboratory analyses reveal an acetaminophen level of 65 mcg/mL.  Liver function tests are unremarkable, INR is 1.0, and ethanol is zero.  All other diagnostics are unremarkable.  Treatment is initiated, and she is admitted to Pediatrics for acetaminophen overdose.  

DISCUSSION

Acetaminophen, commonly referred to internationally as paracetamol, is one of the most widely used analgesics and antipyretics.  It is a major component of many over-the-counter and prescription medications (Table 1).  Each year, approximately 30,000 patients are hospitalized in the United States for acetaminophen toxicity, with half of overdoses thought to be intentional. (1)  Intentional pediatric ingestions typically occur in adolescents while unintentional ingestions are more common among younger children. (2)  The therapeutic dose in children is 15 mg/kg  every four to six hours.  The minimum toxic dose for an acute ingestion is 150 mg/kg. (3,4)  In chronic overdose, the minimum toxic threshold is 150-175 mg/kg over two to four days. (3,5)  

Table 1: Common Medications Containing Acetaminophen
Alka-Seltzer Plus ® NORCO® Sudafed®
Dayquil® Nyquil® Theraflu®
Excedrin® Paracetamol Tylenol® Brand Products
Hydrocet® Percocet® Vicks®
Lortab® Robitussin® Vicodin®
Mucinex® Singlet®

The clinical manifestations of acute acetaminophen poisoning in children are nonspecific.  Initially, patients may be asymptomatic or have mild symptoms such as nausea and vomiting.  Liver injury can occur after approximately 24 hours and manifest as right upper quadrant pain or tenderness, vomiting, jaundice, and elevations in transaminases and prothrombin time.  At peak liver injury, patients can present with signs of fulminant liver failure such as hepatic encephalopathy, systemic inflammatory response system, hypotension, and death. (6)

All patients in whom acetaminophen toxicity is suspected should have a serum acetaminophen concentration drawn.  In patient with a single acute ingestion, the time of ingestion should be established, as a serum acetaminophen concentration at four hours post-ingestion will determine the need for antidotal therapy with N-acetylcysteine (NAC).  The four-hour concentration should be plotted against the treatment nomogram, and concentrations in the probable hepatic toxicity range should be treated with NAC. (4,6,7)

Figure        SEQ Figure \* ARABIC     1      . Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (      ADDIN EN.CITE
&lt;EndNote&gt;&lt;Cite&gt;&lt;Author&gt;Rumack&lt;/Author&gt;&lt;Year&gt;1975&lt;/Year&gt;&lt;RecNum&gt;16&lt;/RecNum&gt;&lt;DisplayText&gt;&lt;style
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name=&quot;Journal
Article&quot;&gt;17&lt;/ref-type&gt;&lt;contributors&gt;&lt;authors&gt;&lt;author&gt;Rumack,
B. H.&lt;/author&gt;&lt;author&gt;Matthew, H.&lt;/author&gt;&lt;/authors&gt;&lt;/contributors&gt;&lt;titles&gt;&lt;title&gt;Acetaminophen
poisoning and toxicity&lt;/title&gt;&lt;secondary-title&gt;Pediatrics&lt;/secondary-title&gt;&lt;/titles&gt;&lt;periodical&gt;&lt;full-title&gt;Pediatrics&lt;/full-title&gt;&lt;/periodical&gt;&lt;pages&gt;871-6&lt;/pages&gt;&lt;volume&gt;55&lt;/volume&gt;&lt;number&gt;6&lt;/number&gt;&lt;edition&gt;1975/06/01&lt;/edition&gt;&lt;keywords&gt;&lt;keyword&gt;Acetaminophen/adverse
effects/metabolism/*poisoning&lt;/keyword&gt;&lt;keyword&gt;Agranulocytosis/chemically
induced&lt;/keyword&gt;&lt;keyword&gt;*Chemical and Drug Induced Liver
Injury/prevention &amp;amp;
control&lt;/keyword&gt;&lt;keyword&gt;Cysteamine/therapeutic use&lt;/keyword&gt;&lt;keyword&gt;Humans&lt;/keyword&gt;&lt;keyword&gt;Hypoglycemia/chemically
induced&lt;/keyword&gt;&lt;keyword&gt;Kidney Papillary Necrosis/chemically
induced&lt;/keyword&gt;&lt;keyword&gt;Liver/*drug
effects&lt;/keyword&gt;&lt;keyword&gt;Necrosis&lt;/keyword&gt;&lt;keyword&gt;Pericarditis/chemically
induced&lt;/keyword&gt;&lt;keyword&gt;Poison Control
Centers&lt;/keyword&gt;&lt;keyword&gt;Poisoning/diagnosis/therapy&lt;/keyword&gt;&lt;keyword&gt;Prognosis&lt;/keyword&gt;&lt;keyword&gt;Skin
Manifestations&lt;/keyword&gt;&lt;keyword&gt;Substance-Related
Disorders&lt;/keyword&gt;&lt;/keywords&gt;&lt;dates&gt;&lt;year&gt;1975&lt;/year&gt;&lt;pub-dates&gt;&lt;date&gt;Jun&lt;/date&gt;&lt;/pub-dates&gt;&lt;/dates&gt;&lt;isbn&gt;0031-4005
(Print)&amp;#xD;0031-4005
(Linking)&lt;/isbn&gt;&lt;accession-num&gt;1134886&lt;/accession-num&gt;&lt;urls&gt;&lt;related-urls&gt;&lt;url&gt;https://www.ncbi.nlm.nih.gov/pubmed/1134886&lt;/url&gt;&lt;/related-urls&gt;&lt;/urls&gt;&lt;/record&gt;&lt;/Cite&gt;&lt;/EndNote&gt;     7)

Figure 1. Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (7)

In chronic ingestions, the treatment nomogram cannot be used.  Laboratory testing for serum acetaminophen concentration and liver function should be obtained for any at-risk patient.  Patients with evidence of liver injury (AST greater than two times normal or greater than 120 IUL or those with serum acetaminophen levels greater than 30 mcg/mL should have antidotal therapy initiated. (5,6)

Gastric decontamination with activated charcoal is recommended in all pediatric patients who present within four hours of acetaminophen ingestion.  Contraindications include gastrointestinal obstruction or any altered mental status in which airway protection is a concern.  Endotracheal intubation should not be performed solely for the purpose of giving activated charcoal.  Activated charcoal has not been shown to reduce acetaminophen absorption when given greater than four hours after ingestion and is not recommended in this time frame.  Activated charcoal is given as a single dose of 1 g/kg by mouth (maximum 50 g). (8,9) 

Once the need for N-acetylcysteine antidotal therapy is determined, it should be given as soon as possible.  When given within 8 hours of ingestion, the mortality rate approaches 0; however, NAC may be beneficial up to 24 hours after ingestion.  NAC should be given intravenously (IV) if available; however, providers should be aware that IV NAC can cause severe anaphylactoid reactions.  Preparations should be made for immediate interventions if anaphylaxis occurs, and patients should be monitored closely during the initial 30 minutes of the infusion. (6,10)  Providers should also be aware that prothrombin time and INR can be artificially elevated by NAC, which can obscure signs of worsening liver function. (11) 

A well-established protocol for IV NAC dosing involves a 21-hour administration procedure detailed below.  Repeat acetaminophen levels, liver function tests, and INR should be repeated 9 hours into the protocol. (12,13)

Loading dose of 150 mg/kg IV (maximum 15,000 mg) in 200 mL dextrose 5% in water (D5W) infused over 60 minutes

Followed by

First maintenance dose of 50 mg/kg IV (maximum 5,000 mg) in 500 ml D5W infused over 4 hours

Followed by

Second maintenance dose of 100 mg/kg IV (maximum 10,000 mg) in 1000 mL D5W infused over 16 hours

Poor prognostic indicators for liver function include the King’s College Criteria.  Patients with acidosis with pH < 7.3 or patients with the combination of prothrombin time > 100 seconds and creatinine > 3.3 mg/dL and hepatic encephalopathy grade III – IV (marked confusion or coma) are considered high risk for fulminant liver failure and should be transferred to a liver transplant center. (14)

CASE CONCLUSION

Given that the patient had an elevated acetaminophen level greater than 30 mcg/mL with multiple ingestions over the last 48 hours, she was treated with N-acetylcysteine.   Labs were rechecked at 19 hours after initiation of NAC.  Liver function tests and INR were stable.  Repeat acetaminophen level was < 10 mcg/mL.  She was ultimately discharged after Psychiatric evaluation with a home safety plan and outpatient Psychiatry follow up.

Faculty Reviewer: Dr. Jane Preotle

REFERENCES

1.         Blieden M, Paramore LC, Shah D, Ben-Joseph R. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Rev Clin Pharmacol. 2014;7(3):341-348.

2.            Myers WC, Otto TA, Harris E, Diaco D, Moreno A. Acetaminophen overdose as a suicidal gesture: a survey of adolescents' knowledge of its potential for toxicity. J Am Acad Child Adolesc Psychiatry. 1992;31(4):686-690.

3.            Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017;25(1):1-9.

4.            Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen overdose. Clin Pharm. 1991;10(10):765-774.

5.            Sztajnkrycer MJ, Bond GR. Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr. 2001;13(2):177-182.

6.            Walls RM, Hockberger RS, Gausche-Hill M. Rosen's emergency medicine : concepts and clinical practice. In: Ninth edition. ed. Philadelphia, PA: Elsevier,; 2018: https://login.revproxy.brown.edu/login?url=https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20141019850 Full text available from ClinicalKey Flex.

7.            Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871-876.

8.            Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018;2:CD003328.

9.            Spiller HA, Krenzelok EP, Grande GA, Safir EF, Diamond JJ. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med. 1994;23(3):519-523.

10.          Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014;383(9918):697-704.

11.          Pizon AF, Jang DH, Wang HE. The in vitro effect of N-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med. 2011;18(4):351-354.

12.          Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977;2(8035):432-434.

13.          Yarema MC, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54(4):606-614.

14.          O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439-445.

AEM Early Access 14: Cannabis and Mental Health ED Visits in Colorado

Welcome to the fourteenth episode of AEM Early Access, a FOAMed podcast collaboration between the Academic Emergency Medicine Journal and Brown Emergency Medicine. Each month, we'll give you digital open access to an recent AEM Article or Article in Press, with an author interview podcast and suggested supportive educational materials for EM learners.

Find this podcast series on iTunes here.

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM

A FOAM Collaboration: Academic Emergency Medicine Journal and Brown EM

DISCUSSING:(Click title for open access through may 31, 2018)

Mental Health-Related Emergency Department Visits Associated with Cannabis in Colorado. Katelyn E. Hall MPH, Andrew A. Monte MD, Tae Chang, Jacob Fox, Cody Brevik, Daniel I. Vigil MD, MPH,  Mike Van Dyke PhD, CIH,  Katherine A. James PhD, MSPH. Academic Emergency Medicine, 2018.

LISTEN NOW: AUTHOR INTERVIEW

Monte head shot-2014.jpg

Andrew A. Monte, MD

Associate Professor, Departments of Emergency Medicine & PharmaceuticaLSciences
University of Colorado Denver-Anschutz Medical Center Aurora, CO and Rocky Mountain Poison & Drug Center
Denver Health & Hospital Authority
Denver, CO

ARTICLE SUMMARY: 

Objectives:
Across the United States, the liberalization of marijuana use has resulted in a rapid increase in the social acceptability of its use.  Colorado has been at the forefront of marijuana legalization, allowing recreational use beginning in 2014.  Since then, Colorado has positioned itself as the optimal environment to study health-related impacts from marijuana use.  Cannabis use is well-known to exacerbate mental health illness such as schizophrenia, mood disorders, anxiety, and depression.  Since legalization in Colorado, increased healthcare utilization has been associated with acute and chronic marijuana use.  It is currently unknown if cannabis use is associated with increased ED visits in patients with mental illness.  The primary objective of this study was to determine the prevalence ratios of mental health diagnoses among ED visits with cannabis-associated diagnosis compared to those without cannabis-associated diagnoses in Colorado.

Methods:
The study was cross-sectional in design, with discharge diagnostic codes collected from Colorado emergency departments from 2012 to 2014.  Diagnosis codes identified visits associated with both mental health conditions and cannabis.  Prevalence ratios of mental health ED discharges were calculated to compare cannabis-associated visits to those without cannabis.  Rates of mental health and cannabis-associated ED discharges were examined of the study period.  

Results:
State-wide data demonstrated a five-fold higher prevalence of mental health diagnoses in cannabis-associated ED visits (PR: 5.35, 95% CI: 5.27-5.43) compared to visits without cannabis. In the study’s secondary outcome, state-wide rates of ED visits associated with both cannabis and mental health significantly increased from 2012 to 2014 from 224.5 to 268.4 per 100,000 (p<0.0001).

Conclusion:
In Colorado from 2012 to 2014 the prevalence of mental health conditions in ED visits with cannabis-associated diagnostic codes is higher than in those without cannabis.  Due to the nature of the study design, it is unclear if these findings are attributable to cannabis or coincident with increased use and availability.  Per the authors of the paper, ED physicians nationwide should be aware of the detriments of marijuana use on pre-existing mental health conditions and ED management should include counseling on cessation and rehabilitation.