Shawn M. Varney

A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose

Oral and intravenous (IV) N-acetylcysteine (NAC) are used for the treatment of acetaminophen poisoning. The objective of this multicenter study was to compare the safety of these two routes of administration. Methods. We conducted a multicenter chart review of all patients treated with NAC for acetaminophen poisoning. The primary safety outcome was the percentage of patients with NAC-related adverse events. Results. A total of 503 subjects were included in the safety analysis (306 IV-only, 145 oral-only, and 52 both routes). There were no serious adverse events related to NAC for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23 vs. 9%). Anaphylactoid reactions were more common with IV administration (6 vs. 2%). Conclusions. IV and oral NAC are generally mild adverse drug reactions.

Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

OBJECTIVES Tricyclic antidepressants (TCAs) are highly lipophilic medications used to treat posttraumatic stress disorder and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in TCA overdose in small animals, and cases are reported in humans, but controlled studies in a larger animal model are lacking. Given the high lipophilicity of amitriptyline, a TCA, the hypothesis was that ILE would be more effective than the standard antidote sodium bicarbonate in improving amitriptyline-induced hypotension. The objective was to determine if ILE improved hypotension (defined by a mean arterial pressure [MAP] < 60% baseline) compared to sodium bicarbonate for amitriptyline overdose in a critically ill porcine model. METHODS In this prospective, randomized, controlled trial, 24 female Sus scrofa swine weighing 45 to 55 kg were infused with amitriptyline at 0.5 mg/kg/min until the MAP reached 60% of baseline values. Animals were randomized to the experimental treatment group (ILE 7 mL/kg bolus, then 0.25 mL/kg/min) or the standard treatment group (sodium bicarbonate 2 mEq/kg plus an equal volume of saline). The primary outcome was a 50% improvement in MAP after ILE administration. We continuously monitored heart rate (HR), systolic blood pressure (sBP), MAP, and cardiac output. Electrocardiograms were recorded every 15 minutes. Serum pH, pCO2 , bicarbonate, lactate, and electrolytes were measured. Amitriptyline levels were measured by liquid chromatography/tandem mass spectrometry. Statistical methods used to detect a difference in MAP between the two treatment groups included repeated-measures analysis of variance, adjusted for treatment, time, and the interaction of treatment by time. A sample size of 12 animals per group provided a power of 0.8 and an alpha of 0.05 to detect a 50% difference in MAP. RESULTS There was no difference at baseline between ILE and sodium bicarbonate groups in mean HR, sBP, MAP, or cardiac output. Mean amounts of amitriptyline to reach hypotension and time to hypotension were similar between groups. After hypotension there was no difference between groups for mean HR, sBP, MAP, or cardiac output. The median time from hypotension to death was greater for the sodium bicarbonate group (10 minutes [IQR = 6 to 61 minutes] vs. 5 minutes [IQR = 4.5 to 6 minutes] for the ILE group; p = 0.003), but overall survival was not different. One ILE and four sodium bicarbonate pigs survived. Additionally, no difference was detected in QRS intervals between the two groups. The mean (±SD) amitriptyline level in the lipid layer was 3.34 (±2.12) μg/mL, and in the aqueous layer, 4.69 (±2.44) μg/mL. The ILE fatty layer contained 38.2% of total measurable amitriptyline, while the aqueous layer contained 53.6%. CONCLUSIONS Intravenous lipid emulsion treatment failed to improve amitriptyline-induced hypotension when compared to the standard treatment of sodium bicarbonate in a large animal model of severe TCA overdose. Larger groups with better survival may yield different results from the high mortality observed in this pilot study. Similar amounts of amitriptyline were found in the aqueous and lipid layers. These conclusions are limited to a single ILE regimen.

Gabapentin Overdose in a Military Beneficiary

We report the case of a 59-year-old military beneficiary that presented to the emergency department after ingesting approximately 90 g of gabapentin immediate-release capsules during a deliberate self-harm attempt. Her serum gabapentin level was 72.8 mcg/mL approximately 3 hours after ingestion. Her renal function panel, complete blood count, and liver function panel were normal. Her urine drug screen, aspirin, ethanol, and acetaminophen level were negative. Her electrocardiogram was normal, including a normal QTc interval. Her only symptoms were nausea and mild sedation. She was admitted for observation with no sequelae noted. She was transferred to a psychiatric facility at that time for further evaluation and treatment. We report a case of gabapentin overdose that presented to the emergency department. Given the large volume ingestion with minimal morbidity, it appears that gabapentin has a wide therapeutic margin and may be safe in overdose.

Intravenous Lipid Emulsion Therapy for Severe Diphenhydramine Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

STUDY OBJECTIVE Diphenhydramine is a moderately lipophilic antihistamine with sodium channel blockade properties. It is consumed recreationally for mild hallucinogenic and hypnotic effects and causes dysrhythmias, seizures, and death with overdose. Intravenous lipid emulsion is a novel agent used to treat lipophilic drug overdose. Two case reports describe clinical improvement with intravenous lipid emulsion after diphenhydramine toxicity, but no prospective studies have been reported. Our objective is to determine whether intravenous lipid emulsion improved hypotension compared with sodium bicarbonate for severe diphenhydramine toxicity in a model of critically ill swine. METHODS Twenty-four swine weighing 45 to 55 kg were infused with diphenhydramine at 1 mg/kg per minute until the mean arterial pressure reached 60% of baseline. Subjects were randomized to receive intravenous lipid emulsion (bolus of 7 mL/kg and then 0.25 mL/kg per minute) or sodium bicarbonate (2 mEq/kg plus an equal volume of normal saline solution). We measured pulse rate, systolic blood pressure, mean arterial pressure, cardiac output, QRS interval, and serum diphenhydramine level. Twelve animals per group provided a power of 0.8 and α of .05 to detect a 50% difference in mean arterial pressure. We assessed differences between groups with a repeated-measures linear model (MIXED) and Kaplan-Meier estimation methods. We compared systolic blood pressure, mean arterial pressure, and cardiac output with repeated measures ANOVA. RESULTS Baseline weight, hemodynamic parameters, QRS interval, time to hypotension, and diphenhydramine dose required to achieve hypotension were similar between groups. After hypotension was reached, there was no overall difference between intravenous lipid emulsion and sodium bicarbonate groups for cardiac output or QRS intervals; however, there were transient differences in mean arterial pressure and systolic blood pressure, favoring intravenous lipid emulsion (difference: mean arterial pressure, sodium bicarbonate versus intravenous lipid emulsion -20.7 [95% confidence interval -31.6 to -9.8]; systolic blood pressure, sodium bicarbonate versus intravenous lipid emulsion -24.8 [95% confidence interval -37.6 to -12.1]). Time to death was similar. One intravenous lipid emulsion and 2 sodium bicarbonate pigs survived. End-of-study mean total serum diphenhydramine levels were similar. The mean lipid layer diphenhydramine level was 6.8 μg/mL (SD 3.1 μg/mL) and mean aqueous layer level 8.6 μg/mL (SD 5.5 μg/mL). CONCLUSION In our study of diphenhydramine-induced hypotensive swine, we found no difference in hypotension, QRS widening, or diphenhydramine levels in aqueous layers between intravenous lipid emulsion and sodium bicarbonate.

Opioid-induced hyperalgesia—worsening pain in opioid-dependent patients☆

Abstract : Patients with chronic opioid use are commonly treated in the emergency department (ED). Opioid-induced hyper- algesia occurs in patients consuming opioids chronically and is a paradoxical response o f increased pain with opioid administration. It is difficult to diagnose and is often underrecognized, and therapies are unconventional. We report a case of a young service member with chronic pain and opioid use who presented to the ED with opioid- induced hyperalgesia.

Survey in the Emergency Department of Parents' Understanding of Cough and Cold Medication Use in Children Younger Than 2 Years

Objectives In August 2007, the Food and Drug Administration (FDA) released a public health advisory recommending that over-the-counter cough and cold medications (CCMs) not be used in children younger than 2 years. Our objective was to assess parents’ awareness and understanding of the guidelines. Methods We surveyed caregivers of children younger than 2 years in the emergency department of an urban tertiary care military hospital where civilian patients are also treated. After completing the survey, caregivers received a handout explaining the FDA’s recommendations. Results Our response rate was 99% (264/265). First-time parents constituted 45% (114/251) of responders. Education level was high school, 21%; some college, 36%; and college graduate, 40%. Thirty-one percent (77/247) were aware of the FDA guidelines. Of these 77, 44 (57%) reported the guidelines indicated CCMs were not safe in children younger than 2 years, and 18 (23%) said CCMs have caused death. Twenty-six percent (68/264) did not give CCMs to their children younger than 2 years, and 40% of these reported it was because of learning about the guidelines; 63% (165/264) reported CCMs were effective, 11% ineffective, and 27% did not know. Fifty-seven percent (151/263) reported CCMs were safe, 12% unsafe, and 31% unsure. Twenty-two percent (31/143) planned to use or continue to use CCMs in their children, 34% did not, 23% not sure, and 21% only if their doctor advised it. Conclusions The majority of caregivers were not aware of the FDA guidelines on CCM use in children younger than 2 years. Most thought CCMs were safe and effective.

Misuse of prescribed pain medication in a military population: a self-reported survey to assess a correlation with age, deployment, combat illnesses, or injury?

Opioid misuse is a growing epidemic among the civilian and military communities. Five hundred prospective, anonymous surveys were collected in the emergency department waiting room of a military tertiary care hospital over 3 weeks. Demographics, medical and military characteristics were investigated for association with opioid use. Univariate logistic models were used to characterize the probability of misuse in relation to the demographic, medical, and military-specific variables. Traumatic brain injury (TBI) and posttraumatic stress disorder were investigated within different age cohorts with adjustment for deployment. The opioid misuse rate disclosed by the subject was 31%. Subjects with TBI were less likely to misuse opioids. We found a trend among younger cohorts to have a higher likelihood for misusing opioids when diagnosed with TBI or posttraumatic stress disorder with history of deployment in the past 5 years. The most common form of misuse was using a previously prescribed medication for a new pain. Traumatic brain injury and/or enrollment in post-deployment recovery programs maybe protective against opioid misuse. Chronic opioid use among young soldiers maybe viewed as a weakness that could influence opioid misuse. Younger cohorts of active duty service members could be at higher risk for misuse. Efforts to enhance close monitoring of misuse should address these at-risk populations.

Acetylcysteine for acetaminophen overdose in patients who weigh >100 kg.

N-Acetylcysteine (NAC) dosing for acetaminophen (APAP) overdose is weight based (150 mg/kg intravenous or 140-mg/kg oral loading dose) and, in the United States, the dosing protocol recommends using a maximum patient weight of 100 and 110 kg, respectively. Little clinical data describe the use of NAC for APAP poisoning in patients weighing >100 kg. The aim of this study was to describe the demographics, outcomes, and adverse event (AE) rates of patients weighing >100 kg treated with oral or IV NAC for APAP poisoning. Patients were identified from a multicenter retrospective NAC safety study for APAP overdose. We included patients with a recorded weight. Trained chart abstractors used a standardized form. Selected data included age, gender, weight, serum alanine transaminase, and aspartate transaminases, coingestants, NAC administration route, ingestion type, AEs, and outcome [hepatotoxicity (alanine transaminase > 1000 U/L), liver transplant, or death]. Descriptive statistics were used. Of 503 study patients, 37 (7.4%) had recorded weights >100 kg. The median (range) weight was 110 kg (101–160). The median (range) dosing for patients treated with oral NAC was 140 mg/kg (127–143 mg/kg) and 150 (108–168) mg/kg for IV NAC. Hepatotoxicity occurred in 12/36 (33.3%) patients. Death occurred in 4/36 (11.1%) patients. Thirteen NAC-related AEs occurred in 8 patients (1.6 per person). All AEs were related to NAC and were rated nonserious by the reviewer. Clinicians use an actual weight-based NAC dose rather than a maximum weight cutoff dose. Hepatotoxicity was common in our cohort. AEs were relatively common but not serious.

Complication of Spice Use in a Deployed Combat Setting—Seizure while on Duty

Abstract : Synthetic cannabinoids, also known as Spice, have become increasingly popular since they went on the public market in 2004. Due to the inability to detect Spice on routine urine drug screens, easy accessibility online and in local stores, and the legal high it provides, it is appealing to military communities. In addition, soldiers and sailors were among the earliest users of Spice in the United States. Reports describing the adverse reactions, clinical effects, and complications of Spice are limited. The normal effects of Spice are generally similar to the euphoria provided by cannabis. Commonly reported adverse reactions to Spice include paranoia, scleral injection, xerostomia, visual persecutory hallucinations, sedation, and agitation. We present a case of a deployed soldier who had a seizure after smoking Spice while on duty, and just after working with heavy machinery.

Reasons military patients with primary care access leave an emergency department waiting room before seeing a provider.

Objectives Our objective was to assess patients’ understanding of emergency department (ED) wait times and why patients may leave the waiting room before seeing a provider. Methods Survey of patients in the ED waiting room of an urban tertiary care military hospital where civilian and military patients are treated. Results A total of 508/517 surveys (98%) were completed. Age ranges were 18 to 35 years (49%), 36 to 60 (31%), or older than 60 (20%). Education levels were high school (20%), some college (37%), or college graduate (39%). Of 503 respondents, 125 (25%) had left an ED waiting room before seeing a provider. The reasons included excessive wait times (91%) and family responsibilities (5%). Five hundred eight reported the factors that would motivate them to wait to see the physician (not leave without being seen [LWOBS]) were the severity of illness (64%), and if they received an update of wait times (26%); 82% (391/480) understood that severely ill patients were seen first. Patients attributed long wait times to doctors and nurses caring for other patients (292/583, 50%) and insufficient physician and nurse staffing (245, 42%). Of 802 responses for ideas to improve the wait, 34% said regular updates on estimated wait times, 21% said television shows or movies to view, 20% said books and magazines to read, and 11% said computers to access. Conclusions Long wait times were the primary reason that patients left before seeing a provider, despite having ready access to care. Respondents attributed long wait times to patient volume and inadequate staffing. Regular updates on wait times and material for entertainment may improve the waiting experience and reduce LWOBS.