Case Report

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure?,??

Abstract

Synthetic cannabinoid usage has increased in the past decade. Con- currently, emergency management of associated adverse effects due to synthetic cannabinoid usage has also risen. Reported toxicities in- clude psychosis, seizures, cardiotoxicity, acute kidney injury, and death. While cannabis was first described as a cause of acute hyperemesis in 2004, a more recent case series also describes the association between cannabinoid hyperemesis and risk of acute renal failure. Synthetic cannabinoids have also been reported to cause acute hyperemesis and acute renal failure; however, the risk of rhabdomyolysis-induced renal failure has yet to be elucidated. In this article, we report the first known case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure.

Use of synthetic cannabinoid products is on the rise due to a lack of detection by commercial tests and the unregulated, over-the-counter availability. Known toxicities associated with synthetic cannabinoid usage include psychosis, seizures, cardiotoxicity, acute kidney injury, and death [1,2]. A connection between synthetic cannabinoid usage and rhabdomyolysis has not been previously reported in the literature. This is of particular importance because rhabdomyolysis, an emergent condition associated with trauma, infection, and toxin exposure, is an underrecognized cause of acute kidney injury [3]. This article presents a case of acute renal failure attributed to rhabdomyolysis in connection with recreational synthetic cannabinoid usage.

A 27-year-old man, with no significant family history or medical his- tory, presented to the emergency department with complaints of mus- cle pain and weakness. The patient described persistent vomiting and new-onset paresthesia in the extremities over the prior week after in- take of a synthetic marijuana product. On admission, the patient was alert and oriented but complained of chills and sweats. Despite no com- plaints of fever, cough, abdominal pain, or dysuria, the patient was un- able to walk and appeared dehydrated with dry mucous membranes, flat neck veins, and tachycardia. His blood pressure was 159/104 mm Hg. Observable jaw spasms and a positive Trousseau were documented. Upon admission, the initial Laboratory analysis showed a creatine kinase greater than 40 000 U/L, serum myoglobin greater than 1000 ng/mL, lactic acid of 2.9 mmol/L, in addition to hyponatremia and hypocalcemia (Table). The patient had reported no urine output

? Funding: No external support provided.

?? Conflicts of interest: No conflicts of interest to disclose.

for 2 days before admission. The elevated serum creatinine and creatine kinase were diagnostic of renal failure and rhabdomyolysis, respectively [3]. An increased anion gap and pronounced hyperphosphatemia were indicative of severe muscle injury and renal dysfunction. The ratio of blood urea nitrogen to creatinine was less than 10:1, demon- strating the increased conversion of muscle creatine to creatinine seen in rhabdomyolysis. His urinalysis was amber in color and contained 2 + protein and 3 + blood. Urine and blood cultures were negative. In addition, an electrocardiogram showed a prolonged QTc in- terval of 505 milliseconds, and a chest computed tomographic scan showed extensive pneumomediastinum without evidence for airway or Esophageal ruptures.

Given the nonexertional and nontraumatic nature of the patient’s ill- ness, rhabdomyolysis and acute renal failure were presumed secondary to drug-induced prolonged hyperemesis. The release of cellular compo- nents into the bloodstream in rhabdomyolysis explains the presence of myoglobin in the patient’s blood and urine. Myoglobin is toxic to the renal tubules and is a direct cause of acute renal failure in the setting of rhabdomyolysis [3].

Initially, the patient received treatment with Intravenous morphine sulfate and ondansetron, neither of which alleviated the patient’s hyperemesis. Laboratory tests were drawn while fluid and electrolyte Resuscitation protocols were initiated. After a 1.0-L fluid bolus with nor- mal saline, the patient received intravenous potassium chloride and cal- cium gluconate to correct symptomatic electrolyte abnormalities. Nonemergent treatment followed with maintenance fluids, oral calcium carbonate, and oral calcitriol. Pantoprazole was given once daily during the patient’s hospital course, first intravenously and then orally.

Severe hyperemesis contributed to the patient’s severe fluid and

electrolyte disturbances; however, rhabdomyolysis-induced acute renal failure explains the directional shifts in the laboratory values [3]. Although many illicit drugs are known causes of rhabdomyolysis, syn- thetic cannabinoid-induced rhabdomyolysis has not been previously re- ported. Other explanations for rhabdomyolysis include contamination of the recreational product used by the patient and rhabdomyolysis secondary to the hyperemesis-induced electrolyte abnormalities. Importantly, reports in the literature directly implicate synthetic canna- binoids as a cause of Renal damage [4,5]. In the absence of a kidney biopsy and given the negative urine drug screen, the synthetic cannabi- noid product ingested by the patient is the only identifiable cause of the present illness.

Although the initial renal ultrasound showed echogenic kidneys with evidence of medical renal disease, Emergent hemodialysis was unnecessary in this case. According to a novel risk prediction scoring system for patients presenting with rhabdomyolysis, the patient pos- sessed a greater than 61% risk of Inhospital mortality or requirement

0735-6757/(C) 2015

Table

Selected laboratory values

Abbreviations: BUN, blood urea nitrogen; CK, creatine kinase.

of renal replacement therapy [6]. However, despite a severe initial pre- sentation, the patient rapidly recovered without hemodialysis, with normal kidney function regained within a week of initial presentation (Table). Frequent monitoring of patient laboratory values was necessary to assess objective improvement and rule out the need for hemodialysis. Familiarity with the treatment for rhabdomyolysis-induced kidney injury, prompt volume repletion, and urgent electrolyte management were key to the patient’s recovery.

Historically, Cannabinoid hyperemesis syndrome was characterized by cyclic vomiting and compulsive bathing in chronic users of cannabis [7]. More recently, the association between cannabinoid hyperemesis and acute renal failure was identified as a new condition, cannabinoid hyperemesis acute renal failure [8]. Synthetic cannabinoids are also reported to cause acute hyperemesis, kidney damage, and renal failure [4,5,9]. As these products increase in popularity, it will be necessary to monitor for trends in reports of serious adverse effects associated with consumption of these chemicals. Earlier recognition of a precipi- tating cause in patients presenting with hyperemesis may prevent severe complications.

Jacqueline R. Argamany, PharmD Kelly R. Reveles, PharmD, PhD

College of Pharmacy, The University of Texas at Austin, Austin, TX, USA Pharmacotherapy Education and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

Bryson Duhon, PharmD College of Pharmacy, The University of Texas at Austin, Austin, TX, USA Pharmacotherapy Education and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Pharmacy Department, University Health System, San Antonio, TX, USA Corresponding author. 7703 Floyd Curl Drive, MC-6220, San Antonio TX 78229, Tel.: +1 210 567 8365; fax: +1 210 567 8328

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2015.08.051

References

1. Trecki J, Gerona RR, Schwartx MD. Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 2015;373(2):103-7.
2. Hoyte CO, Jacob J, Monte AA, Al-Jumaan M, Bronstein AC, Heard KJ. A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010. Ann Emerg Med 2012;60(4):435-8.
3. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361(1):62-72.
4. Centers for Disease Control and Prevention. Acute kidney injury associated with synthetic cannabinoid use-multiple states, 2012. MMWR Morb Mortal Wkly Rep 2013;62(6):93-8.
5. Buser GL, Berona RR, Horowitz BZ, Vian KP, Troxell ML, Hendrickson RG, et al. Acute kidney injury associated with smoking synthetic cannabinoid. Clin Toxicol 2014;52(7):664-73.
6. McMahon GM, Zeng X, Waikar SS. A Risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med 2013;173(19):1821-8.
7. Allen JH, de Moore GM, Heddle R, Twartz JC. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut 2004;53(11):1566-70.
8. Habboushe J, Sedor J. Cannabinoid hyperemesis acute renal failure: a common se-

   quela of cannabinoid hyperemesis syndrome. Am J Emerg Med 2014;32(6):690e1-2.

   Hopkins CY, Gilchrist BL. A case of cannabinoid hyperemesis syndrome caused by synthetic cannabinoids. J Emerg Med 2013;45(4):544-6.