Jason B. Hack

Resistant Alcohol Withdrawal: Does an Unexpectedly Large Sedative Requirement Identify These Patients Early?

IntroductionWhile most patients with alcohol withdrawal (AW) respond to standard treatment that includes doses of benzo-diazepines, nutrition and good supportive care (non resistant alcohol withdrawal-NRAW), a subgroup may resist therapy (resistant alcohol withdrawal-RAW). This study describes a distinct group of AW patients, their sedative requirements, and hospital courses.MethodsOver a period of 6 months, AW patients requiring 50 mg diazepam IV in the first hour were followed. We recorded admission indices and diazepam doses with vital signs at 1, 2, 3, 6, 12, and 24 hours. Patients were considered to have RAW if they required additional sedatives for control of symptoms and/or were having persistent abnormal vital signs despite the physicians’ choices of therapy.ResultsNineteen patients were enrolled; all had similar admission indices. While the 4 NRAW had normal vital signs within 3 hours, all 15 RAW patients had abnormal vital signs; 15 RAW patients required escalating diazepam doses — 14 required barbiturates, 7 were intubated, and 5 had hypotension. Comparing groups: interval and total diazepam doses were not different at 1, 2, and 3 hours; interval doses at 6 and 12 hours, and total doses at 6, 12, and 24 hours were significantly different.ConclusionsRAW patients require large doses of benzodiazepine administration, additional sedatives, and undergo complicated hospitalizations.

Thiamine Before Glucose to Prevent Wernicke Encephalopathy: Examining the Conventional Wisdom

merely lead to vagueness, ambiguity, or nonsense. For example, “Cohesiveness is the thread-forming ability of mucus under the influence of large amplitude deformation,” probably means, “Cohesiveness refers to mucus forming threads when mucus is stretched.” This practice is clearly becoming more common in medical writing. Reviewers should be encouraged to review manuscripts not only for scientific content but also for sound rules and principles of composition. Authors who wish to publish in medical journals should be encouraged to spend as much time and effort on their writing as they do on other aspects of research. Editors can effect change by making a distinction between good writing and bad writing and using the ultimate sanction, which is to accept or reject.

Levamisole Exposure and Hematologic Indices in Cocaine Users

OBJECTIVES Levamisole is an antihelminthic agent found in nearly 70% of seized U.S. cocaine. Sporadic case literature describes a life-threatening agranulocytosis associated with levamisole exposure secondary to cocaine use. The authors compared the distribution of hematologic indices in a population of cocaine users with and without a confirmed exposure to levamisole. METHODS The records of all patients in the Lifespan hospital system who underwent comprehensive toxicologic testing between September 2009 and December 2009 (n = 799) were reviewed. Of these, 95 patients were eligible for inclusion (cocaine-positive with a simultaneous complete blood count). Patients were grouped into levamisole-positive (n = 47) and -negative (n = 48) groups. The primary outcome measures were total white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC); secondary outcome measures included percent neutrophils, lymphocytes, eosinophils, monocytes, and basophils, as well as identified co-ingestants. RESULTS Both groups had a similar makeup of age, sex, and race. The total WBC count, ANC, and ALC were not significantly different between the two groups. There was no significant difference in relative proportion of neutrophils, eosinophils, basophils, or monocytes between the groups. There was one neutropenic patient in the levamisole-positive group, while three patients were neutropenic in the negative group. Additionally, a literature review of case reports describing levamisole-induced agranulocytosis (n = 33) was conducted. In 52% of these cases, patients presented with an oropharyngeal chief complaint; in an additional 27%, patients presented with soft tissue infections or purpura. CONCLUSIONS The overall incidence of neutropenia was 4.2% in all cocaine users and 2.1% in the levamisole-positive group. A striking number of the reported patients with levamisole-associated neutropenia have presented to care with oropharyngeal complaints, vasculitis, or fever. A clinical algorithm for identifying levamisole toxicity in the emergency department setting is provided. Further research is necessary to determine the circumstances required for levamisole-associated neutropenia.

Lithium overdose with electrocardiogram changes suggesting ischemia

BackgroundLithium toxicity is associated with electrocardiogram (ECG) changes, but changes suggestive of an ST segment elevation myocardial infarction have not been reported.Case ReportA 46-year-old incarcerated man suffering from diabetes, hypertension, and schizoaffective/bipolar disorder was treated with lithium 1,200 mg twice daily. Two days prior to presentation the patient became confused, ataxic, and anorexic in jail. Lithium level was 4.69 mmol/L. He was transferred to the emergency department. On arrival, vital signs were normal. The ECG showed a normal sinus rhythm. ST segments were elevated in the anterior leads with downward concavity. T waves were biphasic. Since these changes suggested cardiac ischemia and the patient was unable to respond to questions about chest pain, cardiac enzymes and an emergent echocardiogram were done. Troponin I was less than 0.1 μg/L. Echocardiogram was normal, without wall motion abnormalities. Treatment was with hemodialysis and whole-bowel irrigation. Postdialysis lithium level was 1.30 mmol/L. Over the next several days, electrocardiogram normalized. His speech gradually became coherent. After a 1-week hospitalization, he returned to jail.ConclusionLithium intoxication can cause transient ST segment elevations suggesting an acute myocardial infarction. In the absence of a clear history, echocardiogram and cardiac enzymes can be used to rule out a myocardial infarction.

Pralidoxime in carbaryl poisoning : an animal model

Introduction: Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning. Methods: Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD 50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fishers exact test. Results: Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%. Conclusion: When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose. Human & Experimental Toxicology (2007) 26, 125-129

The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model.

Background. The administration of intravenous (IV) calcium to treat hyperkalemia resulting from digoxin poisoning is considered potentially dangerous, based on a body of older literature which, in sum, reported increased cardiac glycoside toxicity with calcium administration (increased arrhythmias, higher rate of death). Objective. This pilot study sought to determine if the administration of calcium chloride when compared to normal saline would affect time to death when given to hyperkalemic, digoxin toxic swine. Methods. Digoxin IV at 0.25 mg/kg was determined to be appropriately toxic for this study. When arrhythmias consistent with hyperkalemia developed, animals were given either IV calcium chloride (CaCl) bolus (10 mg/kg, Group 1, n = 6) or normal saline volume equivalent (Group 2, n = 6). Three intervals were observed: Interval 1: time interval from digoxin administration (T0) to when ECG changes consistent with hyperkalemia developed (at which point calcium chloride or normal saline was administered); Interval 2: time interval from the development of ECG changes consistent with hyperkalemia to asystole; Interval 3: time interval from digoxin administration to asystole. Both groups were monitored for changes in heart rhythms, serum potassium levels, and time to asystole. Results. The intravenous digoxin dose of 0.25 mg/kg induced hyperkalemia, arrhythmias, and death approximately 1 h after administration in all animals studied. Group 1: Interval 1 averaged 18.75 (S.D. ± 7.96) min, Interval 2 averaged 16.75 (S.D. ± 17.17) min, and Interval 3 averaged 35.5 (S.D. ± 14.49) min range; Group 2: average Interval 1 24.8 (S.D. ± 4.71) min, Interval 2 averaged 19.5 (S.D. ± 15.92), Interval 3 averaged 44.3 (S.D. ± 13.80) minutes. There was no statistically significant difference between the groups at any time interval, Interval 1 (p = 0.43), Interval 2 (p = 0.65), Interval 3 (p = 0.40). There was no difference in serum potassium throughout the study period. Conclusion. The administration of intravenous CaCl in the setting of hyperkalemia from acute digoxin toxicity did not affect mortality or time to death at the dose administered.

Pretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat Model

STUDY OBJECTIVE We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. METHODS Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. RESULTS In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). CONCLUSION Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity.

METHADONE, ANOTHER CAUSE OF OPIOID-ASSOCIATED HEARING LOSS: A CASE REPORT

BACKGROUND Methadone has been used for many years in the clinical setting and has many well-described side effects. In recent years, the use of methadone and other opioids have been increasing throughout the United States (US), and presentations to US Emergency Departments (EDs) due to opioid use and abuse are increasing as well. OBJECTIVES As methadone and opioid use increases, ED physicians should be aware of infrequently seen side effects and toxicities associated with the use of these drugs. CASE REPORT We report the case of a previously healthy 20-year-old man who presented with acute onset of bilateral hearing loss secondary to an unintentional methadone overdose. At follow-up, the patients hearing had returned to normal, with the only intervention being abstinence from methadone. CONCLUSION Although bilateral hearing loss is a rare toxic finding of opioid ingestion, given the prevalence of opioid use, this etiology should be considered in any patient presenting with this chief complaint.

Oral Sumatriptan‐Induced Myocardial Infarction

Background. Sumatriptan has been used in the treatment of migraine and other vascular headaches since 1993 in the United States. Its side effects include chest pains in 3% to 8% of patients who have known cardiac risk factors. This is a case report of a 45‐year‐old woman with no history of cardiac risk factors who had a myocardial infarction after her monthly dose of oral sumatriptan. Methods. The patient was examined in the emergency room, evaluated by electrocardiography, and serial evaluations of cardiac enzymes over the next 24 h. She was admitted to the cardiology ward. A cardiac catherization and additional laboratory studies were performed the following day. Results. The catherization revealed normal heart function, but a 60% to 70% non‐flowing stenosis within the first septal perforator. Laboratory indices for cardiac risk were within normal ranges. Conclusions. Patients without cardiac risk factors may experience myocardial infarction following an oral dose of sumatriptan.

A Localizing Circumferential Compression Device Increases Survival after Coral Snake Envenomation to the Torso of an Animal Model

BACKGROUND Pressure immobilization bandages have been shown to delay onset of systemic toxicity after Eastern coral snake (Micrurus fulvius) envenomation to the distal extremity. OBJECTIVES To assess the efficacy of a novel compression device in delaying onset of systemic toxicity after truncal envenomations with Eastern coral snake (Micrurus fulvius) venom in a porcine model. METHODS With University approval, nine juvenile pigs (11 kg to 22 kg) were sedated, anesthetized, and intubated but not paralyzed to ensure continuous spontaneous respirations in a university animal laboratory. Each animal was injected subcutaneously with 10 mg of M. fulvius venom in a pre-selected area of the trunk. After 1 min, six animals had the application of a novel, localizing circumferential compression (LoCC) device applied to the bite site (treatment group) and three animals had no treatment (control group). The device was composed of a rigid polymer clay form molded into a hollow fusiform shape with an internal dimension of 8 × 5 × 3 cm and an elastic belt wrapped around the animal securing the device in place. Vital signs were recorded at 30-min intervals. End points included a respiratory rate below 3 breaths/min, oxygen saturation < 80%, or survival to 8 h. Survival to 8 h was analyzed using Fishers exact test, with p < 0.05 indicating significance. Survival analysis was performed using the Mantel-Cox test to assess time to death with outcomes represented in a Kaplan-Meier Cumulative survival plot. RESULTS Five of the six pigs in the treatment group survived 8 h (293-480 min). None of the control pigs survived to 8 h (Fishers exact p = 0.04), with mean time of respiratory failure 322 min (272-382 min). Survival analysis showed a significant delay in time to event in the treatment group compared to the control group (p = 0.04). CONCLUSIONS The LoCC device used in this study delayed the onset of systemic toxicity and significantly increased survival time after artificial truncal envenomation by Eastern coral snake venom.