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.

Heart-Brain 346-7 Score: the development and validation of a simple mortality prediction score for carbon monoxide poisoning utilizing deep learning.

INTRODUCTION: Acute mortality from carbon monoxide poisoning is 1-3%. The long-term mortality risk of survivors of carbon monoxide poisoning is doubled compared to age-matched controls. Cardiac involvement also increases mortality risk. We built a clinical risk score to identify carbon monoxide-poisoned patients at risk for acute and long-term mortality. METHODS: We performed a retrospective analysis. We identified 811 adult carbon monoxide-poisoned patients in the derivation cohort, and 462 adult patients in the validation cohort. We utilized baseline demographics, laboratory values, hospital charge transactions, discharge disposition, and clinical charting information in the electronic medical record in Stepwise Akaike's Information Criteria with Firth logistic regression to determine optimal parameters to create a prediction model. RESULTS: In the derivation cohort, 5% had inpatient or 1-year mortality. Three variables following the final Firth logistic regression minimized Stepwise Akaike's Information Criteria: altered mental status, age, and cardiac complications. The following predict inpatient or 1-year mortality: age > 67, age > 37 with cardiac complications, age > 47 with altered mental status, or any age with cardiac complications and altered mental status. The sensitivity of the score was 82% (95% confidence interval: 65-92%), the specificity was 80% (95% confidence interval: 77-83%), negative predictive value was 99% (95% confidence interval: 98-100%), positive predictive value 17% (95% confidence interval: 12-23%), and the area under the receiver operating characteristic curve was 0.81 (95% confidence interval: 0.74-0.87). A score above the cut-off point of -2.9 was associated with an odds ratio of 18 (95% confidence interval: 8-40). In the validation cohort (462 patients), 4% had inpatient death or 1-year mortality. The score performed similarly in the validation cohort: sensitivity was 72% (95% confidence interval: 47-90%), specificity was 69% (95% confidence interval: 63-73%), negative predictive value was 98% (95% confidence interval: 96-99%), positive predictive value was 9% (95% confidence interval: 5-15%) and the area under the receiver operating characteristic curve was 0.70 (95% confidence interval: 60%-81%). CONCLUSIONS: We developed and validated a simple, clinical-based scoring system, the Heart-Brain 346-7 Score to predict inpatient and long-term mortality based on the following: age > 67, age > 37 with cardiac complications, age > 47 with altered mental status, or any age with cardiac complications and altered mental status. With further validation, this score will hopefully aid decision-making to identify carbon monoxide-poisoned patients with higher mortality risk.

Risk Factors and Clinical Correlates of Pediatric Serotonin Syndrome in Hospitalized Suicide Attempters.

Objective: To evaluate the risk factors and clinical correlates of pediatric serotonin syndrome (SS) given that research on SS in adults exists, there is a dearth of literature on pediatric SS. Study design: We conducted a retrospective chart review of 183 pediatric patients who were medically hospitalized after a suicide attempt. We investigated associations between SS and several of its risk factors and clinical correlates. We also assessed the sensitivity/specificity of Hunter's criteria and criterion symptoms in predicting SS. Results: SS occurred in 21.7% of patients with a serotonergic overdose. Recent marijuana use and overdose on a selective serotonin reuptake inhibitor were significantly associated with SS. Individuals with SS required a greater number of days to be medically stabilized and had a greater likelihood of being placed on a ventilator during treatment. Hunter's criteria had 66.7% sensitivity and 92.3% specificity in diagnosing SS. Conclusions: Our study reveals both novel risk factors associated with SS (eg, recent marijuana use) and clinical correlates for patients with pediatric SS. In children, Hunter's criteria appeared to have good specificity but poor sensitivity in identifying SS. Our results set the stage for future work aimed at enhancing clinicians' ability to more rapidly identify and treat pediatric SS.

Opioid overdoses involving xylazine in emergency department patients: a multicenter study.

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Severe, persistent thrombocytopenia in Crotalus horridus envenomation despite antivenom: A retrospective review.

BACKGROUND: In the late nineties, Bond and Burkhardt described a severe thrombocytopenic phenomenon from envenomation by Crotalus horridus. This thrombocytopenia persisted despite administration of platelets and antivenom. Questions remain regarding the clinical significance and time to resolution of this thrombocytopenia. In addition, as new antivenoms are available in North America, the response to current treatment is not well reported. The purpose of this study is to provide further insight into the approach to treatment of Crotalus horridus envenomation. METHODS: This is a retrospective chart review of 21 cases of presumed envenomation by C. horridus. Data collected included age, sex, antivenom administration, laboratory data, length of hospital stay, blood products administered, and general clinical course. We also evaluated platelet response to antivenom, bleeding outcomes, and complications from envenomation. RESULTS: Patients' ages ranged from 19 to 71 years. All patients were men. Most patients presented with thrombocytopenia and all had limb swelling. Patients responded initially to antivenom treatment, however subsequently developed a profound thrombocytopenia, including fourteen with platelet counts less than 20 × 109/L. Abnormalities in thromboelastography (TEG) were noted in conjunction with thrombocytopenia. Patients displayed persistent thrombocytopenia despite administration of Crotalidae polyvalent immune Fab or Crotalidae immune F(ab')2. Median time to rebound platelet count greater than 20 × 109/L was ten days (range 6-12 days) from envenomation. Complications included a partial finger amputation in one patient, bleeding gums in four patients, bloody stools in two patients, bloody nasogastric output in one patient. No patients required red blood cell transfusion and no deaths occurred. CONCLUSION: Practitioners treating C. horridus should recognize the possibility of severe thrombocytopenia and its persistence despite antivenom. They should counsel patients on appropriate abstention from activities that could lead to trauma, as well as the importance of follow up for repeat laboratory studies to ensure the resolution of thrombocytopenia.

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting.

Ketamine, in research settings, rapidly reduces suicidal thoughts 2-24 h after a single infusion in patients with high suicidal ideation. In this study, the authors investigate ketamine's effects on suicidality in a real-world sample of recent suicide attempters on a tertiary-care Consultation-Liaison (CL) psychiatry service. Using an open-label design, 16 transdiagnostic CL patients were recruited, 18-65 years old, to receive a single dose of intravenous ketamine (0.5 mg/kg) in the acute medical setting. All were psychiatrically hospitalized post-infusion. Baseline suicidality and depression measures were compared to ratings taken at 24 h, 5 days, 12 days, and 1, 3 and 6 months post-infusion using paired t-tests. Across all measures, rapid, statistically significant decreases (p's < 0.001) were observed with large to very large effect sizes (Cohen's d's: 1.7-8.8) at acute timepoints (24 h; 5 days). These gains were uniformly maintained to 6 months post-infusion. Open-label ketamine appeared to rapidly and robustly reduced suicidal symptoms in an ultra-high-risk, heterogeneous, real-world sample. Ketamine infusion may therefore be a safe, feasible, viable method to rapidly reduce suicidality among medically hospitalized patients after a suicide attempt, with potentially enduring benefits. The current pilot findings suggest ketamine could be readily integrated into the settings where high-risk CL patients already receive healthcare, with the potential to become an important and novel tool in the treatment of suicidality.

Failure of Crotalidae Immune F(ab')2 Equine Antivenom to Achieve Control in a Southern Pacific Rattlesnake Envenomation.

Rattlesnake envenomation can result in significant cutaneous and hematologic toxicity. While Cotalidae polyvalent immune Fab (ovine) antivenom (marketed as CroFab) was available for years, it is associated with increased late hematologic toxicity compared with its predecessor. Consequently, Crotalidae Immune F(ab')2 equine antivenom [marketed as Anavip; F(ab')2AV] has been recently become available. In this paper, we report a case of a 53 year-old man envenomated on his right hand by a Southern Pacific rattlesnake (Crotalus helleri). Edema was present, and his initial platelets were not able to be measured, prompting the administration of 10 vials of F(ab')2AV. Ultimately, he received a total of 52 vials of antivenom, before his platelets peaked at 102,000/µL, 56 hours post envenomation. Within hours, his platelets began to fall again. Ultimately, his platelets reached a post-antivenom nadir of 65,000/µL. He was observed closely as an outpatient without additional antivenom, and ultimately had normalization of his platelets (211,000/µL) 20 days post envenomation. This case is one of the first cases demonstrating an inability to achieve control of the hematologic toxicity following Southern Pacific rattlesnake envenomation after treatment with F(ab')2AV.

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.

Outcomes following Naloxone Administration by Bystanders and First Responders.

Background: Naloxone is widely available to bystanders and first responders to treat patients with suspected opioid overdose. In these patients, the prognostic factors and potential benefits associated with additional naloxone administered by emergency medical services (EMS) are uncertain. Objectives: We sought to identify prognostic factors for admission to the hospital following prehospital administration of naloxone for suspected opioid overdose by bystanders and first responders. We secondarily examined whether administration of additional naloxone by paramedics after initial treatment by non-EMS personnel was associated with improvement in level of consciousness prior to hospital arrival. Methods: This is a retrospective cross-sectional study of patients treated within a single urban EMS system from 2013 to 2016. Inclusion criteria were administration of naloxone by bystanders or first responders and transport to one of three academic medical centers. For the secondary analysis, only patients with a Glasgow Coma Scale (GCS) score ≤12 on paramedic arrival were included. We performed univariate and multivariable analyses examining a primary outcome of hospital admission and secondary outcome of improvement in consciousness as defined by GCS >12 in patients with initial GCS ≤12. Results: Of 359 patients identified for the primary analysis, 60 were admitted to the hospital. Factors associated with increased rate of admission included higher total naloxone dosage (OR 1.36, 95% CI 1.09-1.70) and presence of alternate/additional non-opioid central nervous system (CNS) depressants (OR 2.51, 95% CI 1.13-5.56). Among 178 patients who had poor neurologic status (GCS ≤12) on paramedic arrival following naloxone administered by bystander or first responder, administration of additional naloxone was not associated with a better rate of neurologic improvement prior to hospital arrival (77% improved with additional naloxone, 81% improved without additional naloxone; OR 0.82, 95% CI 0.39-1.76). Conclusions: Among patients with suspected opioid overdose treated with naloxone by bystanders and first responders, a higher total dose of naloxone and polysubstance intoxication with additional CNS depressants were predictors of admission. Administration of additional naloxone by paramedics was not associated with a higher rate of neurologic improvement prior to hospital arrival, suggesting a ceiling effect on naloxone efficacy in opioid overdose.

Alcohol withdrawal syndrome: improving outcomes in the emergency department with aggressive management strategies.

Alcohol use disorder is a prevalent medical and psychiatric disease, and consequently, alcohol withdrawal is encountered frequently in the emergency department. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, administration of intravenous sedatives, and frequently, adjunctive pharmacotherapy. This issue reviews the pathophysiology of alcohol withdrawal syndrome, describes the manifestations of alcohol withdrawal, and examines the available evidence for optimal treatment of alcohol withdrawal. An aggressive frontloading approach with benzodiazepines is presented, and the management of benzodiazepine-resistant disease is addressed.

Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity.

BACKGROUND: In cases of ethylene glycol (EG) toxicity requiring hemodialysis (HD), fomepizole is dosed every four hours. HD efficiently clears EG and its toxic metabolites, and it's unclear if multiple doses (MD) of fomepizole improve patient outcomes or whether a single dose (SD) prior to initiation of HD is sufficient. METHODS: We reviewed cases of EG toxicity at a toxicology referral center from 2008 to 2018. Patients treated with HD with EG levels greater than 20 mg/dL were included. Duration of dialysis, creatinine at discharge, hospital length of stay (LOS), and complications were analyzed. We compared patients who received a single dose of fomepizole prior to HD to those who received continued dosing during and after HD. RESULTS: Twenty-five patient encounters were identified (MD: 20; SD: 5). Initial bicarbonate (11 [SD] vs. 9 mg/dL [MD]) and pH (7.1 vs. 7.1) were similar between the groups; however, there was a trend toward a greater proportion of patients with renal dysfunction in the MD group: 11 (55%) vs. 1 (20%). HD was initiated a median interval of 5.2 h [SD] vs. 5.7 h [MD] after a dose of fomepizole. There was one death in the MD group and none in the SD group. Median creatinine on the day of discharge was 0.7 mg/dL (IQR: 0.57-3.8) in the SD group and 2.0 mg/dL (0.90-7.0) in the MD group. LOS was similar (5.8 days [95% CI 3.6-8.0] vs. 7.6 days [5.3-9.9]) (p = .61). CONCLUSION: Patients with moderately severe EG toxicity (acidosis and no initial renal dysfunction) treated with a single dose of fomepizole prior to HD had similar outcomes to those receiving continued dosing of fomepizole during or after HD. This raises the possibility that a single dose of fomepizole may be sufficient if HD is initiated quickly.

Drug-specific risk of severe QT prolongation following acute drug overdose.

Background: Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose.Methods: This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease).Results: From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron.Conclusions: This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.

Contemporary Characteristics and Lethality Correlates of Serious Suicide Attempts in Children and Adolescents.

OBJECTIVE: Adolescent suicide rates have increased in the past decade. Few studies have examined contemporary pediatric suicide attempters with medically serious suicide attempts, particularly among younger pediatric suicide attempters. METHOD: This preliminary chart review study examined 200 adolescents with medically serious suicide attempts and sought to identify general cohort characteristics, differences in cohort characteristics based on age, correlates of lethality, and correlates of rescue (likelihood of prompt medical attention). RESULTS: Our study found that younger adolescents specifically endorsed increased cyberbullying (ß = 1.1, p = .046) and less hopelessness (ß = -0.83, p = .02) compared to older adolescents. Suicide attempt lethality was negatively associated with female gender (ß = -0.59, p = .041), rescue (ß = -0.19, p = .005), an anxiety diagnosis (ß = -0.81, p = .0003), and history of consensual sexual activity (ß = -0.79, p = .002). Rescue was positively associated with an ADHD diagnosis (ß = 0.73, p = .018) and less attempt planning (ß = 0.96, p = .01), while a history of previous suicide attempt (ß = -0.54, p = .04) and more proximal suicide attempt (ß = -0.045, p = .008) were associated with a lower rescue score. CONCLUSION: Our preliminary findings suggest clinicians and future researchers may need to assess certain social and diagnostic factors in children and adolescents at particularly high risk for death by suicide.

Pulmonary Complications of Opioid Overdose Treated With Naloxone.

STUDY OBJECTIVE: We aim to determine whether administration of higher doses of naloxone for the treatment of opioid overdose is associated with increased pulmonary complications. METHODS: This was a retrospective, observational, cross-sectional study of 1,831 patients treated with naloxone by the City of Pittsburgh Bureau of Emergency Medical Services. Emergency medical services and hospital records were abstracted for data in regard to naloxone dosing, route of administration, and clinical outcomes, including the development of complications such as pulmonary edema, aspiration pneumonia, and aspiration pneumonitis. For the purposes of this investigation, we defined high-dose naloxone as total administration exceeding 4.4 mg. Multivariable analysis was used to attempt to account for confounders such as route of administration and pretreatment morbidity. RESULTS: Patients receiving out-of-hospital naloxone in doses exceeding 4.4 mg were 62% more likely to have a pulmonary complication after opioid overdose (42% versus 26% absolute risk; odds ratio 2.14; 95% confidence interval 1.44 to 3.18). This association remained statistically significant after multivariable analysis with logistic regression (odds ratio 1.85; 95% confidence interval 1.12 to 3.04). A secondary analysis showed an increased risk of 27% versus 13% (odds ratio 2.57; 95% confidence interval 1.45 to 4.54) when initial naloxone dosing exceeded 0.4 mg. Pulmonary edema occurred in 1.1% of patients. CONCLUSION: Higher doses of naloxone in the out-of-hospital treatment of opioid overdose are associated with a higher rate of pulmonary complications. Furthermore, prospective study is needed to determine the causality of this relationship.

Exploratory Ingestions of Novel Anticoagulants and Antiplatelets: What Is the Risk?

BACKGROUND: Historically, anticoagulants and antiplatelet agents included warfarin and aspirin, respectively. In recent years, numerous novel anticoagulants (eg, direct thrombin inhibitors and factor Xa inhibitors) as well as the adenosine diphosphate receptor antagonists have increased significantly. Little information on the bleeding risk after exploratory ingestion of these agents is available. The primary purpose of this study is to evaluate the bleeding risk of these agents after an exploratory ingestion in children 6 years or younger. METHODS: This retrospective multicenter poison control center study was conducted on calls between 2005 and 2014. The following agents were included: apixaban, clopidogrel, dabigatran, edoxaban, prasugrel, rivaroxaban, or ticagrelor. Bleeding characteristics and treatment rendered were recorded. RESULTS: A total of 638 cases were identified. Most cases involved antiplatelet agents. No patient developed any bleeding complication. The administration of charcoal was independent of the amount of drug ingested. CONCLUSION: Accidental, exploratory ingestions of these agents seem well tolerated, with no patient developing bleeding complications.