Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

High dose insulin therapy for inotropic support during veno-arterial extracorporeal membrane oxygenation decannulation: A case report.

RATIONALE: High-dose insulin (HDI) therapy has been used as inotropic support for toxin-induced cardiogenic shock, but literature suggests that it can also be used in non-toxin-induced cardiogenic shock states. Its use has not been reported in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation. PATIENT CONCERNS: A 56-year-old male presented with progressive dyspnea and lower extremity edema without any reported toxic ingestion. DIAGNOSIS: After left heart catheterization, he was diagnosed with acute biventricular nonischemic cardiac failure that ultimately required VA-ECMO support for 8 days, after which decannulation was planned. INTERVENTIONS: During decannulation, he was initiated on HDI therapy via a 1 U/kg regular insulin bolus with 25 g of dextrose and a 1 U/kg/hr insulin infusion. OUTCOMES: During the decannulation, he was monitored with transesophageal echocardiography. Initially, left ventricular (LV) ejection fraction (EF) was estimated at 10% to 15%. Transesophageal echocardiography after HDI but prior to decannulation showed LVEF 30% to 40%. Transthoracic echocardiography 3.5 hours after HDI bolus and decannulation revealed normal LV systolic function; LVEF 50% to 55%. LESSONS: While multiple interventions occurred during decannulation, HDI therapy may have assisted in transitioning off ECMO support, and HDI should be investigated as an adjunctive option in future decannulations and other non-toxin-induced cardiogenic shock states.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Apical Hypertrophic Cardiomyopathy: A Concerning Electrocardiogram in the Emergency Department.

BACKGROUND: Apical hypertrophic cardiomyopathy is a rare, complex phenotypic variant of the classically taught hypertrophic cardiomyopathy. It is highly variable in its pathophysiology as well as its clinical course, spanning the spectrum from a healthy asymptomatic lifestyle to sudden cardiac death and severe diastolic dysfunction. The hallmark electrocardiographic findings of unusually large T-wave inversions, in conjunction with the most common presenting symptom being chest pain, makes this disease entity concerning in the emergency department (ED) setting. CASE REPORT: A 61-year-old man with a history of hypertension presented to the ED with chest pain. His electrocardiogram exhibited a biphasic T wave in lead V2 with ST depressions in leads V3-V6 with deep symmetrical T-wave inversions in these leads as well. His troponin was negative and the patient was taken for cardiac catheterization. Catheterization revealed no coronary artery disease; however, it revealed a "spade like" filling pattern of the left ventricle, suggestive of an apical variant of hypertrophic cardiomyopathy. Subsequent cardiac magnetic resonance imaging confirmed the diagnosis of apical hypertrophic cardiomyopathy and the patient was started on a beta-blocker and discharged with cardiology follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Electrocardiographic interpretation is a critical skill of the emergency physician. Awareness of the syndrome and its specific electrocardiogram findings may help facilitate further testing that will aid in timely diagnosis and interventions.

An unusual case of sudden hearing loss in a young man.

Acute-onset hearing loss of unknown cause may be the result of a tranverse temporal bone fracture. CT imaging is indicated for patients with acute focal neurologic deficits of uncertain cause.

Clinical experience with intravenous lipid emulsion for drug-induced cardiovascular collapse.

Intravenous lipid emulsion (ILE) is an emerging therapy for refractory cardiotoxicity due to lipid-soluble drugs. The purpose of this study was to assess survival to hospital discharge, effects on hemodynamic parameters, and adverse event occurrence for patients who were treated with ILE as part of the resuscitative effort for drug-induced cardiotoxicity. This is a multicenter retrospective chart review of inpatients at three tertiary referral medical centers receiving ILE for drug-induced cardiotoxicity between November 2007 and March 2009. Nine cases with drug-induced cardiovascular collapse, defined as cardiac arrest or refractory shock, were selected for review if patients received either bolus or infusion of ILE in any combination. No interventions were done. The main outcome measures were survival to hospital discharge, effect on hemodynamic parameters, and adverse event. Hemodynamic vital signs (heart rate, systolic blood pressure, diastolic blood pressure, calculated mean arterial pressure [MAP]) were measured before administration of ILE and up to five measurements (if available) were recorded after administration of ILE. Attribution of adverse events was determined by assignment of Naranjo adverse drug reaction (ADR) likelihood score (3) with adjudication of three medical toxicologists; disagreements were settled by majority consensus. Of nine cases identified based on inclusion criteria (three cardiac arrest, six refractory shock), five (55%) survived to hospital discharge. ILE regimens were bolus alone in five patients and bolus plus infusion in four patients. Hemodynamic trends in response to ILE demonstrated no difference in MAP immediately pre- and post-administration of ILE (p = NS). Administration of infusion (versus boluses alone) did not demonstrate a statistically significant improvement in MAP. Adverse events due to ILE therapy that were categorized as "possible" or "probable" based on Naranjo scores included lipemia, digit amputation, lung injury, renal failure, and deep venous thrombosis. ILE administered to patients with drug-induced cardiovascular collapse was associated with 55% survival but with clinically significant adverse effects. At this time, ILE should be restricted to cardiotoxicity involving cardiac arrest or refractory shock until further prospective studies can better evaluate risks and benefits of ILE therapy.

Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil.

BACKGROUND: Overdoses of calcium channel blocker agents result in hyperglycemia, primarily due to the blockade of pancreatic L-type calcium channels and insulin resistance on the cellular level. The clinical significance of the hyperglycemia in this setting has not previously been described. METHODS: This study is a retrospective review of all adult (age, >or=15 yrs) patients with a discharge diagnosis of acute verapamil or diltiazem overdose at five university-affiliated teaching hospitals. The severity of overdose was assessed by determining whether a patient met the composite end points of in-hospital mortality, the necessity for a temporary pacemaker, or the need for vasopressors. We compared the initial and peak serum glucose concentrations with hemodynamic variables between patients who did and did not meet the composite end points. RESULTS: A total of 40 patients met inclusion criteria, with verapamil and diltiazem accounting for 27 of 40 (67.5%) and 13 of 40 (32.5%) of the ingestions, respectively. For those patients who did and did not meet the composite end points, the median initial serum glucose concentrations were 188 (interquartile range, 143.5-270.5) mg/dL and 129 (98.5-156.5) mg/dL, respectively (p = .0058). The median peak serum glucose concentrations for these two groups were 364 (267.5-408.5) mg/dL and 145 (107.5-160.5) mg/dL, respectively (p = .0001). The median increase in blood glucose was 71.2% for those who met composite end points vs. 0% for those who did not meet composite end points (p = .0067). Neither the change in the median heart rate nor the change in systolic blood pressure was significantly different in any group. CONCLUSION: Serum glucose concentrations correlate directly with the severity of the calcium channel blocker intoxication. The percentage increase of the peak glucose concentration is a better predictor of severity of illness than hemodynamic derangements. If validated prospectively, serum glucose concentration alone might be an indicator to begin hyperinsulinemia-euglycemia therapy.

Adverse effects in children after unintentional buprenorphine exposure.

Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine's partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population.