Faculty Bibliography

OBJECTIVES: To develop key messages for methadone and buprenorphine safety education material based on an analysis of calls to the NYC Poison Control Center (NYC PCC) and designed for distribution to caregivers of young children. METHODS: Retrospective review of all calls for children 5 years of age and younger involving methadone or buprenorphine from January 1, 2000, to June 15, 2014. A data abstraction form was completed for each case to capture patient demographics, exposure and caller sites, caller relation to patient, qualitative information regarding the exposure scenario, the product information, if naloxone was given, and the medical outcome of the case. RESULTS: A total of 123 cases were identified. The ages of the children ranged from 4 days to 5 years; 55% were boys. All exposures occurred in a home environment. The majority of the calls were made to the NYC PCC by the doctor (74%) or nurse (2%) at a health care facility. Approximately one-fourth of the calls came from the home and were made by the parent (22%) or grandparent (2%). More than one-half of the exposures involved methadone (64%). Naloxone was administered in 28% of cases. Approximately one-fourth of the children did not experience any effect after the reported exposure, one-half (51%) experienced some effect (minor, moderate, or major), and there was 1 death (1%). More than one-half of the children were admitted to the hospital, with 40% admitted to critical care and 13% to noncritical care. Approximately 23% were treated and released from the hospital, and 20% were lost to follow-up or never arrived to the hospital. The remaining 4% were managed on site without a visit to the hospital. CONCLUSION: Exposures to methadone and buprenorphine are dangerous with some leading to serious health effects. Safe storage and disposal instructions are needed for homes where children may be present.

Background: Metformin causes hyperlactatemia by inhibiting hepatic lactate uptake and the conversion of lactate to glucose. Lactic acidosis is a known complication, but clinical risk and prognosis remain unclear. Research Question: To describe the incidence of hyperlactatemia and clinical risk factors for lactic acidosis in patients with acute metformin overdose. Methods: This was a secondary data analysis of a prospective observational cohort of adult ED patients presenting with acute drug overdose at two urban tertiary care hospitals over 5 years. Chronic, pediatric, and nondrug overdoses were excluded as were those missing outcome information. We collected demographics, exposure details, laboratory information, initial serum lactate, and extracorporeal indications per EXTRIP guidelines. Missing lactate data were accounted for by multiple imputations using a derived bicarbonate correlation. The outcomes were hyperlactatemia (lactate >2 mmol/L) and lactic acidosis (MALA, lactate >5 mmol/L with pH <7.35). Assuming 20% outcome prevalence, we needed 50 patients to show twofold increased risk with 80% power and 5% alpha. Clinical risk factors for MALA were derived using multivariable logistic regression in SPSSv22. Results:We screened 3739 acute overdoses; 2872 met eligibility, and 56 self-reported metformin overdose (57% female, mean age 55.7, 0% endstage renal disease). There was a high incidence of hyperlactatemia during hospital stay (53.6%); MALA was less frequent (30.4%); there were no inpatient deaths. Initial serum bicarbonate and lactate were highly correlated (r² = 0.63, p < 0.01). Repeat serum lactate increased in only three patients (hyperlactatemia rose by 1.8%, MALA by 3.8%). EXTRIP guidelines indicated hemodialysis for three, all of whom received it. Clinical risk factors for MALA were lower PCO2 (p = 0.02), older age (5% increased risk per year of age, p = 0.078), and acetaminophen coexposure (adjusted OR = 15.6, p = 0.07). Discussion: These data suggest a good prognosis for ED patients with acute metformin overdose; hyperlactatemia occurred in over half, but MALA in less than one-third. Additionally, indications for hemodialysis were rare, and none died. There was minimal utility in trending lactate, as rising lactate was exceedingly rare. Conclusion: Hyperlactatemia was common in ED patients with acute metformin overdose. Independent clinical risk factors for MALA were acetaminophen co-exposure, compensatory respiratory alkalosis, and older age

Background:We previously demonstrated that the initial ED lactate had prognostic utility for in-hospital mortality from acute drug poisoning. Research Question: To validate the prognostic utility of initial lactate for drug overdose fatality in ED patients. Methods: This was an observational, prospective, cohort study over 5 years at two urban teaching hospitals. Subjects were consecutive adult (>18 years) ED acute drug overdose patients; we excluded children, prehospital cardiac arrest, alternative diagnoses, non-drug overdose, and missing data. Demographics, history, vitals, and drug exposures were obtained from medical records using standardized data abstraction. Initial lactate was drawn as part of clinical care by ED clinicians; the primary outcome was inpatient fatality, and the secondary outcome was occurrence of shock (vasopressor requirement). Receiver operating characteristics (ROC) were plotted using SPSSv22 to determine optimal lactate cutpoint (point that maximizes sensitivity + specificity), along with test characteristics (sensitivity/specificity), area under the curve (AUC), odds ratios (OR), and 95% confidence intervals (CI). Results: Out of 3739 patients screened, 2333 met exclusion criteria (1487 missing lactate, 376 children, 278 missing outcomes, 141 alternate diagnoses, 37 non-drugs, 14 prehospital arrests), leaving 1406 patients for analysis (56% female,mean age 43.1 years), of whom 54 patients had shock (3.9%) and 24 died (1.7%). Mean initial lactate (mmol/L) was 8.1 +/- 5.6 for fatalities and 2.4 +/- 6.7 for survivors (p < 0.001). The AUC for prediction of fatality was 0.85 (CI 0.73-0.95). The optimal lactate cutpoint for fatality was 5.0 mmol/L (OR 34.2, CI 13.7-84.2, 70.8% sensitive, 93.3% specific) and the occurrence of either shock or death was 2.7 mmol/L (OR 7.9, CI 4.5-13.9). Initial lactate under 2.0 mmol/L had 99.5% negative predictive value (CI 98.8-99.9). Drug classes for which initial lactate had the highest utility for prediction of fatality were as follows: salicylates (AUC = 0.98, cutpoint = 6.0), sympathomimetics (AUC = 0.98, cutpoint = 7.8), acetaminophen (AUC = 0.98, cutpoint = 10.0), opioids (AUC = 0.97, cutpoint = 3.1), digoxin (AUC = 0.92, cutpoint = 2.4), anti-convulsants (AUC = 0.91, cutpoint = 3.0); lactate had lowest utility for beta-/Ca-channel blockers (AUC = 0.73, cutpoint = 7.1), diuretics (AUC = 0.55, cutpoint = 1.1), and ACE inhibitors (AUC = 0.16, cutpoint = 0.9). Discussion: The highest prognostic utility was for salicylates, sympathomimetics, and acetaminophen. Conclusion: Lactate should be used as a biomarker for early decisionmaking in ED patients with acute drug overdose

CONTEXT: Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States. OBJECTIVE: We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning. METHODS: This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were included based on confirmed salicylate ingestion and enrolled consecutively. Demographics, clinical parameters, treatment and disposition were collected from the medical record. Severe outcome was defined as a composite occurrence of acidemia (pH <7.3 or bicarbonate <16 mEq/L), hemodialysis, and/or death. RESULTS: Out of 1997 overdoses screened, 48 patients met inclusion/exclusion criteria. Patient characteristics were 43.8% male, median age 32 (range 18-87), mean initial salicylate concentration 28.1 mg/dL (SD 26.6), and 20.8% classified as severe outcome. Univariate analysis indicated that age, respiratory rate, lactate, coma, and the presence of co-ingestions were significantly associated with severe outcome, while initial salicylate concentration alone had no association. However, when adjusted for salicylate concentration, only age (OR 1.13; 95% CI 1.02-1.26) and respiratory rate (OR 1.29; 95% CI 1.02-1.63) were independent predictors. Additionally, lactate showed excellent test characteristics to predict severe outcome, with an optimal cutpoint of 2.25 mmol/L (78% sensitivity, 67% specificity). CONCLUSIONS: In adult Emergency Department patients with acute salicylate poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate, while initial salicylate concentration alone was not predictive.

BACKGROUND: While it is certain that some emergency department patients with acute drug overdose suffer adverse cardiovascular events (ACVE), predicting ACVE is difficult. The prognostic utility of the ECG for heterogeneous drug overdose patients remains to be proven. This study was undertaken to validate previously derived features of the initial ECG associated with ACVE in this population. METHODS AND RESULTS: We performed a prospective validation cohort study to evaluate adult emergency department patients with acute drug overdose at 2 urban university hospitals over 5 years in whom an emergency department admission ECG was performed. Exclusion criteria were alternate diagnoses, anaphylaxis, chronic drug toxicity, and missing outcome data. ACVE was defined as any of the following: circulatory shock, myocardial injury, ventricular dysrhythmia, or cardiac arrest. Blinded cardiologists interpreted ECGs for previously derived predictors of ACVE (ectopy, QT prolongation, nonsinus rhythm, ischemia/infarction), QT dispersion, and prominent R wave in lead AVR. Of 589 patients who met inclusion criteria (48% male, mean age 42), there were 95 ACVEs (39 shock, 64 myocardial injury, 26 dysrhythmia, 16 cardiac arrest). The most common drug exposures were as follows: benzodiazepines, opioids, and acetaminophen. Previously derived criteria were highly predictive of ACVE, with QT correction >500 ms as the highest risk feature (OR 11.2, CI 4.6-27). CONCLUSIONS: This study confirms that early ECG evaluation is essential to assess the cardiovascular prognosis and medical clearance of emergency department patients with acute drug overdose. Furthermore, this study validates previously derived high-risk features of the admission ECG to risk stratify for ACVE in this patient population.