Lee A. Zarzabal

Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model

STUDY OBJECTIVE Hydroxocobalamin is a Food and Drug Administration-approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control). METHODS Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an α of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA. RESULTS Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (P<.001 between the 2 treated groups and the saline solution group). Time to return of spontaneous breathing after antidote was similar between hydroxocobalamin and cobinamide (1 minute 48 seconds versus 1 minute 49 seconds, respectively). Blood cyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences were detected between the 2 groups for mean arterial pressure, cardiac output, respiratory rate, lactate, or pH. CONCLUSION Both hydroxocobalamin and cobinamide rescued severely cyanide-poisoned swine from apnea in the absence of assisted ventilation. The dose of cobinamide was one fifth that of hydroxocobalamin.

A Comparison of Obesity Prevalence: Military Health System and United States Populations, 2009–2012

Overweight and obesity prevalence has increased over the past 30 years. Few studies have looked at the enrolled Military Health System (MHS) population (2.2 million per year). This descriptive study examined trends in overweight and obesity in both children and adults from fiscal years 2009 to 2012 and compared them to the U.S. population. Prevalence in MHS children decreased over time for overweight (14.2-13.8%) and obesity (11.7-10.9%). Active duty adults showed an increase in overweight prevalence (52.7-53.4%) and a decrease in obesity prevalence (18.9-18.3%). For nonactive duty, both overweight and obesity prevalence remained relatively unchanged around 33%. For both children and adults, overweight and obesity prevalence increased with age, except for obesity in the nonactive duty ≥ 65 subgroup. When compared to the United States by gender and age, MHS children generally had a lower overweight and obesity prevalence, active duty adults had higher overweight and lower obesity prevalence, and nonactive duty adults had comparable overweight and obesity prevalence, except for obesity in both men in the 40 to 59 subgroup and women in ≥ 60 subgroup. More research on the MHS population is needed to identify risk factors and modifiable health behaviors that could defeat the disease of obesity.

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.

Abdominal circumference is superior to body mass index in estimating musculoskeletal injury risk.

PURPOSE The purpose of this study was to compare body mass index (BMI) and abdominal circumference (AC) in discriminating individual musculoskeletal injury risk within a large population. We also sought to determine whether age or sex modulates the interaction between body habitus and injury risk. METHODS We conducted a retrospective cohort study involving 67,904 US Air Force personnel from 2005 to 2011. Subjects were stratified by age, sex, BMI, adjusted BMI, and AC. New musculoskeletal injuries were recorded relative to body habitus and time elapsed from the start of study. RESULTS Cox proportional hazards regression revealed increased HR for musculoskeletal injury in those with high-risk AC (males, >39 inches; females, >36 inches) compared with HR in those with low-risk AC (males, ≤35 inches; females, ≤32 inches) in all age categories (18-24 yr: HR = 1.567, 95% confidence interval (CI) = 1.327-1.849; 25-34 yr: HR = 2.089, 95% CI = 1.968-2.218; ≥35 yr: HR = 1.785, 95% CI = 1.651-1.929). HR for obese (BMI, ≥30 kg·m) compared with that for normal individuals (BMI, <25 kg·m) were less elevated. Kaplan-Meier curves showed a dose-response relation in all age groups but most prominently in 25- to 34-yr-old participants. Time to injury was consistently lowest in 18- to 24-yr-old participants. Score chi-square values, indicating comparative strength of each model for injury risk estimation in our cohort, were higher for AC than those for BMI or adjusted BMI within all age groups. CONCLUSIONS AC is a better predictor of musculoskeletal injury risk than BMI in a large military population. Although absolute injury risk is greatest in 18- to 24-yr-old participants, the effect of obesity on injury risk is greatest in 25- to 34-yr-old participants. There is a dose-response relation between obesity and musculoskeletal injury risk, an effect seen with both BMI and AC.

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.

Estimating diabetes prevalence in the Military Health System population from 2006 to 2010.

Evidence-based articles have demonstrated an increase in diabetes prevalence, but diabetes prevalence in the enrolled Military Health System population was previously understudied. Variability in diabetes prevalence rates calculated from 5 groups of algorithms was examined in the Military Health System population (3 million enrollees per year) from fiscal years 2006 to 2010. Time trend analysis and rate comparisons to the U.S. population were also performed. Increasing linear trends in diabetes prevalence from 2006 to 2010 were seen in all algorithms, though considerable rate variation was observed within each study year. Prevalence increased with age, except for a slight decrease in those ≥75 years. Overall diagnosed diabetes prevalence ranged from 7.26% to 11.22% in 2006 and from 8.29% to 13.55% in 2010. Prevalence among active duty members remained stable, but a significant upward trend was observed among nonactive duty members across study years. Age-standardized rates among nonactive duty females were higher than the U.S. population rates from 2006 to 2010. This study demonstrates prevalence rate variability because of differing case algorithms and shows evidence of a growing diabetes population in the Military Health System, specifically within the nonactive duty 45 years and older demographic groups. Further research of this population should focus on validation of case definitions.

Prescription stimulant misuse in a military population

BACKGROUND Increased prescription drug misuse has been reported in veterans, yet there has not been a focused look at stimulant misuse in the military community or correlation with deployment injuries and illnesses. Our objective was to identify rates of stimulant misuse and any correlation with deployment in the military population. METHODS A prospective, anonymous institutional review board-approved survey in the emergency department waiting room of a military tertiary care hospital using a 12-item questionnaire created with fixed response and multiple-choice questions. Stimulant misuse was defined as taking more than prescribed, obtaining stimulants from others, and taking it for a nonprescribed reason. Proportions were assessed by Chi-square test and Fishers exact test. RESULTS 26/498 (5%) of respondents reported misusing stimulants in the last 5 years. Misusers were more likely to have a mental health diagnosis, and they suffered either a deployment-related injury or another injury, as compared to those who used stimulants properly (p<0.05). The stimulant misuse did not correlate with age, gender, active duty status, education, location of deployment, number of times deployed, traumatic brain injury diagnosis, or enlistment status. CONCLUSION Stimulant drug misuse in the military community is associated with mental health conditions, deployment-related injuries, or new physical injuries.