Michael Hodgman

A review of acetaminophen poisoning

Acetaminophen poisoning remains one of the more common drugs taken in overdose with potentially fatal consequences. Early recognition and prompt treatment with N-acetylcysteine can prevent hepatic injury. With acute overdose, the Rumack-Matthew nomogram is a useful tool to assess risk and guide management. Equally common to acute overdose is the repeated use of excessive amounts of acetaminophen. Simultaneous ingestion of several different acetaminophen-containing products may result in excessive dosage. These patients also benefit from N-acetylcysteine. Standard courses of N-acetylcysteine may need to be extended in patients with persistently elevated plasma concentrations of acetaminophen or with signs of hepatic injury.

Cardiac conduction disturbance after loperamide abuse

Abstract Context. Prescription opioid abuse is a major public health concern and an ongoing epidemic in the United States. Loperamide is a widely available and inexpensive over-the-counter antidiarrheal with peripheral mu-opioid receptor activity. Online resources discuss the use of loperamide for the amelioration of withdrawal symptoms or recreational abuse. We describe the clinical course of 5 patients abusing loperamide, 3 of whom had life-threatening cardiac arrhythmias. Methods. In this observational case series, patients with cardiac arrhythmias or history of loperamide abuse with cardiac arrhythmias were identified; 5 patients were identified and 4 of the 5 patients were seen directly at the bedside. Clinical profile and outcome of patients is reported. Results. We report 5 patients with history of loperamide abuse; 3 of the 5 patients had life-threatening cardiac arrhythmias. One of the patients experienced a second life-threatening arrhythmia after he resumed loperamide abuse. Loperamide levels were obtained in 4 of the 5 patients and were at least one order of magnitude greater than therapeutic concentrations. Discontinuation of loperamide resulted in complete resolution of cardiac conduction disturbances. Conclusion. This case series describes several patients with cardiac conduction abnormalities and life-threatening ventricular arrhythmias temporally related to loperamide abuse. With the recent efforts to restrict the diversion of prescription opioids, increasing abuse of loperamide as an opioid substitute may be seen. Toxicologists should be aware of these risks and we urge all clinicians to report such cases to FDA Medwatch®.

Baclofen overdose mimicking brain death

Abstract Context. Brain death guidelines should be used with caution in patients with drug intoxication. It is often suggested that physicians use five half-lives of a drug when observing a patient with an overdose. We report two cases of baclofen intoxication where brain death was entertained as an explanation for prolonged coma, with arousal seen days later, suggesting that routine use of a 5-half-life observation period is insufficient with baclofen intoxication. Case presentation. A 40-year-old woman was found unresponsive by her family. Baclofen was found to be the responsible overdose. The patient had absent brain stem reflexes and was intubated and in the ICU for several days. Although EEG and Apnea test were inconclusive, the patient was thought to be brain dead and organ procurement was arranged. On hospital day 5, the patient started having purposeful movements. The patient had progressive arousal and was eventually transferred without neurologic sequelae to psychiatry. The second patient also had a massive baclofen overdose, had absence of almost all brain stem reflexes and was also intubated and in the ICU. Brain death was felt to be imminent, but the patient began to awake on hospital day 7. Discussion. Our two cases suggest that baclofen intoxication may result in very prolonged and profound coma and may, in fact, mimic brain death. Conclusion. The determination of brain death in the comatose overdose patient must proceed with caution. An adequate period of time to allow drug clearance must be allowed.

Profound metabolic acidosis and oxoprolinuria in an adult

IntroductionProfound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation.Case ReportA 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline.DiscussionOriginally described in children with an inherited defect of glutathione synthetase, 5-Oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative.ConclusionIn critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.

Tacrolimus (FK 506) Overdose: A Report of Five Cases

INTRODUCTION Tacrolimus (FK 506), a potent anti-T cell agent, has been shown to be effective in preventing the rejection of transplanted organs. Published research on tacrolimus has focused on effects associated with therapeutic use. Virtually no literature addresses the acute toxicity or the management of tacrolimus overdose. We report five cases of acute overdose with tacrolimus. CASE REPORTS A 2-year-old female with no prior medical history ingested 10 mg of tacrolimus. She remained asymptomatic. A 2-year-old female with a history of multiple visceral organ transplants ingested 11 mg of her tacrolimus. She was admitted to the hospital and activated charcoal was administered. Her renal function was monitored and no changes were noted in a 24 h period. She was discharged. A 29-year-old male renal transplant patient took 150 mg of tacrolimus. He recovered with only a minimal creatinine elevation. A 23-year-old heart and lung transplant patient ingested 375 mg of tacrolimus. She had no effects from the overdose. A 34-year-old female experienced an acute/chronic overdose of 7-9 mg and remained asymptomatic. DISCUSSION Tacrolimus is a neutral macrolide antibiotic that is extracted from the fermentation broth of the soil fungus Streptomyces tsukubaensis. Chronic oral dosing has been associated with numerous side effects. Although these patients ingested significant doses of tacrolimus, they suffered few toxic manifestations associated with tacrolimus. CONCLUSION Little information is available regarding acute tacrolimus overdosage. In this small series of patients, tacrolimus did not produce acute physiologic incapacitation.

Acute Chemical Pancreatitis Associated with a Tricyclic Antidepressant (Clomipramine) Overdose

A case of acute chemical pancreatitis and associated prolonged ileus following an acute overdose of the tricyclic antidepressant clomipramine by an adult is reported. Pancreatitis is a rarely-reported serious complication of antidepressant overdose and may lead to prolonged ileus and extended hospitalization.

Serum Calcium Concentration in Ethylene Glycol Poisoning

IntroductionThe diagnosis of ethylene glycol intoxication can be challenging. Definitive testing for ethylene glycol is not readily available and clinical decisions are often based on clinical suspicion and the results of more readily available tests. One of these findings is hypocalcemia, presumable through complexation with the ethylene glycol metabolite oxalate.MethodsWe performed a retrospective review of all patients admitted to a tertiary care hospital between 2005 and 2013 with laboratory confirmed ethylene glycol intoxication. Serum calcium on presentation was compared to blood gas pH on presentation as well as presentation serum bicarbonate.ResultsWe did not find any relationship between calcium and serum pH either by linear regression or when dichotomized by pH ≥ or <7.3. We did observe an inverse relationship between serum calcium and bicarbonate.ConclusionsHypocalcemia is not commonly observed following ethylene glycol poisoning, even in acidotic patients.

Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor

Abstract Metaxalone has only recently been associated with serotonin syndrome. The mechanism of action of this centrally acting muscle relaxant is unknown; however, the observation of serotonin syndrome in patients with metaxalone overdose suggests a role in the serotonergic pathway. Case report. (Case 1) A 29-year-old woman with overdose of metaxalone presented to the emergency department with altered mental status, seizure-like activity, hyperthermia, rigidity in the lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 168/80 mmHg, heart rate of 208 beats per minute (bpm), respirations of 20/min, a temperature of 41.6° C rectally, and room air oxygen saturation of 97%. She was intubated and sedated with benzodiazepines, and actively cooled. Serum paroxetine concentration was 23 (therapeutic range: 20–200) ng/mL, and serum metaxalone concentration was 31 mcg/mL (peak plasma concentrations average 0.9 mcg/mL at 3.3 h following a single oral dose of 400 mg). (Case 2) A 27-year-old man presented to the emergency department with altered mental status, rigidity in his lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 158/131 mmHg, heart rate of 126 bpm, respiratory rate of 20 breaths per minute, and temperature of 37.2°C, with oxygen saturation of 98% on room air. His medication list included metaxalone and escitalopram. He was managed aggressively with IV boluses of diazepam, in total 80 mg, in the emergency department. Serum escitalopram concentration was 24 ng/mL with a therapeutic range of 21–64 ng/mL, and serum metaxalone concentration was 58 mcg/mL. Conclusion. These two cases suggest that at supratherapeutic concentrations metaxalone has serotonergic effects. Severe serotonin toxicity may result from metaxalone abuse in individuals using a selective serotonin reuptake inhibitor therapeutically.

Can elevated lactate and LDH produce a false positive enzymatic ethanol result in live patients presenting to the emergency department

Abstract Background: There have been allegations in the courtroom that elevated serum lactic acid in trauma victims can yield a falsely elevated serum ethanol assay. Most hospitals utilize an indirect method of ethanol measurement where a serum sample is added to a mix of alcohol dehydrogenase and oxidized nicotinamide adenine dinucleotide (NAD+). This allows any ethanol in the patient’s serum to be metabolized to acetaldehyde, and in the process results in the reduction of NAD + to NADH. NADH is then measured using spectrophotometry. The courtroom allegation stems from the concept that oxidation of lactate to pyruvate by lactate dehydrogenase (LDH) results in the same molar-for-molar reduction of NAD + to NADH, and could therefore theoretically cause patients with elevated lactate and LDH to have a falsely elevated ethanol concentration. Methods: Patients with elevated lactic acid and LDH concentrations who presented to a university hospital from 20 April 2015 to 13 December 2015 were identified to provide possible test specimens. If a sufficient amount of serum was available, the sample was used to re-run the lactate and LDH concentration simultaneously with an enzymatic ethanol assay. Any samples that had elevated lactic acid and LDH concentrations on this retesting, and also yielded a positive ethanol concentration, were sent for confirmatory gas chromatography testing of ethanol concentrations. A control group of 20 samples with normal lactate and LDH were included. Results: A total of 37 samples were included in the final analysis. Only 4 patients had an elevated enzymatic ethanol concentration, and all 4 also had a measurable GC ethanol concentration. The lactate in this dataset ranged from 2.4 to 24.2 mmol/L, with a mean of 6.53 mmol/L (normal value 0.5–2.2). The LDH ranged from 242 to 8838 U/L with a mean of 1695 U/L (normal value 122–225 U/L). Twenty control samples were run on patients with normal lactate and LDH, none of which yielded a positive enzymatic ethanol result. Conclusions: This data does not support the contention that an elevated LDH and lactate can yield a false positive serum ethanol result as run by enzymatic ethanol assay in live patients presenting to the emergency department.

Case 7 Delirium and Bradycardia Following Opioid Dependency Treatment

This case involves a 69-year-old male who presented to the emergency department from the primary care provider with acute delirium and agitation following the administration of a medication to treat opioid dependency. The patient was agitated and moved all extremities purposefully, but did not follow any commands. He was given benzodiazepines, but ultimately required intubation. He made a complete recovery. This case discusses various medications and regimens to treat opioid withdrawal. In addition, this case discusses treatment options for patients with acute pain who are concurrently taking medications to facilitate abstinence.