CASE REPORT Suspected Compartment Syndrome and Rhabdomyolysis after "Pseudoephedrine" Use - A Case report Eric Medrano a Jake Goliver b Corresponding author(s): Eric.Medrano@utoledo.edu aThe University of Toledo Medical Center Toledo, OH 43614, USA, and bThe University of Toledo Medical Center Director of Emergency Medicine Residency, Toledo, OH 43614 , USA Acute compartment syndrome and rhabdomyolysis are two life threatening diagnoses that cannot be missed in the emergency room. The increased pressure in the closed compartments of extremities can eventually lead to loss of peripheral pulses, de- creased tissue perfusion, and ultimately muscle necrosis. This breakdown of muscle byproducts will ultimately lead to kid- ney damage and rhabdomyolysis. Although the most common cause of compartment syndromes are secondary orthopedic causes such as lower extremity fractures there are known docu- mented toxicological causes. (1,2) Pseudoephedrine, a sympa- thomimetic amine, is commonly used in the treatment of nasal congestion. Its primary mechanism directly acts on the adren- ergic receptor system which stimulates release of stored nore- pinephrine from neurons. Its alpha-adrenergic effect is believed to be the cause of vasoconstriction in the body (3). Clinically, intoxication from sympathomimetic drugs have produced tox- idromes with prominent features such as tachycardia, hyperten- sion, hyperthermia, agitation, and delirium. However, it is incred- ibly rare to see an association with pseudoephedrine overdose and rhabdomyolysis and compartment syndrome. There are documented cases where sympathomimetic drugs have been as- sociated with compartment syndrome (2,4,5). This case of a 29- year-old male with suspected pseudoephedrine abuse highlights the need for consideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose. Pseudoephedrine | rhabdomyolysis | compartment | syndrome | toxicology | emergency This is a case report of a 29-year-old Caucasian male with a his-tory of untreated hepatitis C, alcohol abuse, drug abuse, and suicidal ideation presented to the Emergency Department with al- tered mental status, Rhabdomyolysis, concerning signs of Compart- ment syndrome after suspected pseudoephedrine use. Case Report Patient Information Age: 30 years old. Gender: Male. Ethnicity: African Ameri- can. Related Medical Problems: Schizophrenia with catatonic fea- tures, polysubstance abuse disorder. Objective for Case Reporting Objectives for this case report is to highlight the need for con- sideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose. As well as bring to light the possibility to keep these conditions in the emer- gency medicine physicians’ differential. The possibility of compart- ment syndrome and rhabdomyolysis after pseudoephedrine over- dose is a differential that all emergency medicine physicians should be aware of. Case A 29-year-old Caucasian male with a history of untreated hep- atitis C, alcohol abuse, drug abuse, and suicidal ideation presented Submitted: 06/22/2021, published: 08/18/2021. Freely available online through the UTJMS open access option 16–18 UTJMS 2021 Vol. 9 translation@utoledo.edu mailto:Eric.Medrano@utoledo.edu to the Emergency Department via Emergency Medicine Services af- ter being found down by his significant other. Patient was reported to be drinking with his friends earlier that night. Eventually he was seen going to bed late in the evening. The following afternoon, the family found him unresponsive in the apartment with dry foam around his mouth and blood in the nostrils. Emergency Medicine Services were called, and he was transferred to the emergency de- partment for further care. The patient’s family believed that he overdosed on pseu- doephedrine which were found in his pockets by Emergency Medicine Services. The girlfriend was also concerned because the patient had recently stated a desire to kill himself. Chart review showed he was recently admitted and discharged from a separate hospital the day prior for overdose of narcotics. When patient presented to the Emergency Department, he was found awake, but only occasionally responsive to both painful and verbal stimuli. Initial vital signs were: Heart rate 127/min, BP 150/96; respiratory rate 20; and temperature of 37.2 C. Physical exam showed no sign of external trauma. His pupils were 8mm di- lated bilaterally. Skin was hot to the touch. It was noted he had dif- fuse upper and lower extremity rigidity. On examination of patient’s personal effects, pseudoephedrine was found in his pants pocket. No other medications were found during the physical exam. Initial laboratory findings were white blood cell 8.7, hemoglobin 14, platelets 182, PT 13.3, international normalized ratio 1.2, sodium 145 potassium 4.4, chloride 111, bicarbonate 17, anion gap 17, blood urea nitrogen 28, creatinine 2.09, glomerular filtration rate 38. Serum myoglobin was 23,639 and creatine kinase 35,717, Lac- tate 2.0, aspartate aminotransferase, 3,980, alanine transaminase, 2,838. urinalysis protein 100, negative for glucose, ketones 10, hemoglobin large, arterial blood gas 7.34/35.9/93/19.4. Troponin was 2.64. During the patient’s ED course, he was given intravenous normal saline boluses, 1 mg Ativan and placed on oxygen via nasal cannula. Due to the patient’s diffuse lower extremity rigidity, the de- cision was made to consult orthopedics for possible compartment syndrome. On their initial exam, they noted that the patient’s lateral thigh compartments were firm, however the patient’s gluteal com- partments were soft and compressible. The patient was also noted to have 2+ distal pulses pulses. When they returned to bedside with a Stryker compartment measuring kit, the patient’s thighs were noted to be much softer on repeat examination and they decided not to proceed with measurements at the time due to lower concern for compartment syndrome. The quantitative urine and blood screen showed that the patient’s initial blood ethanol level was less than 0.01, acetaminophen level less than 10, salicylate less than 2.5. Co- caine, tetrahydrocannabinol, opiates, ecstasy, methadone, phency- clidine, and amphetamines were also found to be negative on urine drug screen. Patient’ initial laboratory studies were consistent with rhab- domyolysis with a creatine kinase of 35,717, myoglobin is 23,639, and an initial creatinine of 2.09. Due to the patient’s troponin of 2.64, AST of 3,980, and Alt of 2,838. there was a concern for pos- sible acetaminophen overdose, even with a negative acetaminophen OD level. The ED physician contacted poison control regarding the patient’s case and lab results who recommended giving the patient Acetadote, and he was subsequently admitted to the ICU. The patient continued to have elevated liver and kidney en- zymes while in the ICU necessitating temporary dialysis. There was further discussion of transfer to a transplant center if his liver enzymes did not improve. Through supportive care measures, he did have gradual improvement and was ultimately discharged from the hospital on day 6. Discussion This case describes the development of rhabdomyolysis and near compartment syndrome after this patient’s suspected pseu- doephedrine overdose. Although causality cannot be established with this case alone, the patient had established rhabdomyolysis based on his elevated creatine kinase and myoglobin which required intensive care unit admission which raises further investigation into the topic. Rhabdomyolysis and Compartment syndrome can occur for many reasons, including infection, trauma, and drug use. Phar- macological compartment syndrome can occur due to direct my- otoxic and muscle overuse (6). There is suspicion that the pathophysiology of the patient’s stimulant induced rhabdomyolysis is multifactorial. Patient was known to be found down for an unsuspected prolonged amount of time. Concerns about skeletal overuse secondary to excited delir- ium, vasoconstriction, and hyperthermia, all of which are known side effects of pseudoephedrine and synthetic catholine overdoses, can lead to increased muscle metabolic demand leading to muscle breakdown. Furthermore, based on the patient’s initial presenta- tion of depressed level of consciousness and rigid thighs on initial presentation in the emergency room, there was a concern for com- partment syndrome likely secondary to compression. Lastly, seizure activity is a known complication of pseudoephedrine overdose (5,6), which can also be a contributing factor to the patients unwitnessed down time and his elevated creatinine kinase and myoglobin leading to rhabdomyolysis. In one study, patients were found to have an increase of their maximal creatinine kinase after exposure to synthetic cathinones. This resulted in an increase probability of developing rhabdomy- olysis compared to the non-exposed patient group. (6,7) Known complication from sympathomimetic toxicity include altered men- tal status, metabolic acidosis, seizures, rhabdomyolysis, acute kid- ney injury, hepatic injury, disseminated intravascular coagulation, and death. (8) In one case report, pseudoephedrine has also been associated with biphasic elevation of creatine kinase and elevated myoglobin leading to Rhabdomyolysis (9). This case report demonstrates that patients are at a higher risk of developing rhabdomyolysis and possibly compartment syndrome when exposed to higher levels of synthetic catecholamine medica- tion such as pseudoephedrine. Treatment of alpha1 adrenergic de- congestants such as pseudoephedrine is primarily supportive with aggressive intravenous hydration being the main therapy. Like am- phetamine overdose, hypertension and agitation can occur due to the adrenergic effects caused by pseudoephedrine, therefore the use of benzodiazepines can help reduce muscle activity and metabolic demand in agitated patients, which was evidenced in this case as the patient had an symptomatic improvement after Aitvan administra- tion. Finally, maintaining a urine output of >2mL/kg/h should be a key treatment during intravenous hydration (6). Conclusion This case of a 29-year-old male with suspected pseu- doephedrine use highlights the need for consideration of rhabdomy- olysis and compartment syndrome being a possible complication from pseudoephedrine overdose. The possibility of compartment syndrome and rhabdomyolysis after pseudoephedrine overdose is an important differential that all physicians should be aware of in Medrano et al. UTJMS 2021 Vol. 9 17 the Emergency Department. Conflict of interest Authors declare no conflict of interest. Authors’ contributions EM wrote this case report. JG conceived of the presented idea, supervised the findings of this work and provided critical feedback to the contribution of this report. All authors read and approved the final document. 1. Tiwari, A., A. I. Haq, F. Myint, and G. Hamilton. (2002) Acute compartment syn- dromes." British Journal of Surgery 89, no. 4, 397-412. 2. Levine, Michael, Rachel Levitan, and Aaron Skolnik. 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