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Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author receives funding from the American Heart Association, through his employer, for performing editorial services.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation., Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting., Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species., Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings., (Copyright © 2023 SFMTSI.)

This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed., (Copyright © 2023 by the American Academy of Pediatrics.)

This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research., (Copyright © 2021 European Resuscitation Council, American Heart Association, Inc. and International Liaison Committee on Resuscitation. Published by Elsevier B.V. All rights reserved.)

To categorize the Patient-specific Functional Scale (PSFS) activities in snakebite envenoming (SBE) using the International Classification of Function (ICF) model in order to describe the impact of SBE on patients' activities and daily lives and to develop a theoretical SBE model of functioning, we performed a post-hoc analysis of two multi-center, prospective studies, conducted at 14 clinical sites in the United States with consecutive SBE patients presenting to the emergency department. Qualitative content analysis and natural language processing were used to categorize activities reported in the PSFS using the ICF model. Our sample included 93 patients. The mean age was 43.0 (SD 17.9) years, most had lower extremity injuries (59%). A total of 99 unique activities representing eight domains came within the Activity and Participation component of the ICF model, with the majority in the Mobility and General Tasks and Demands domains. The main concerns of SBE patients are the ability to perform daily activities and to engage within their social environment. Applying the ICF model to SBE can facilitate the creation of a patient-centered treatment approach, moving beyond body-structural impairments towards a function-based treatment approach and facilitate early integration of rehabilitation services.

Opioid overdose is the leading cause of death for Americans 25 to 64 years of age, and opioid use disorder affects >2 million Americans. The epidemiology of opioid-associated out-of-hospital cardiac arrest in the United States is changing rapidly, with exponential increases in death resulting from synthetic opioids and linear increases in heroin deaths more than offsetting modest reductions in deaths from prescription opioids. The pathophysiology of polysubstance toxidromes involving opioids, asphyxial death, and prolonged hypoxemia leading to global ischemia (cardiac arrest) differs from that of sudden cardiac arrest. People who use opioids may also develop bacteremia, central nervous system vasculitis and leukoencephalopathy, torsades de pointes, pulmonary vasculopathy, and pulmonary edema. Emergency management of opioid poisoning requires recognition by the lay public or emergency dispatchers, prompt emergency response, and effective ventilation coupled to compressions in the setting of opioid-associated out-of-hospital cardiac arrest. Effective ventilation is challenging to teach, whereas naloxone, an opioid antagonist, can be administered by emergency medical personnel, trained laypeople, and the general public with dispatcher instruction to prevent cardiac arrest. Opioid education and naloxone distributions programs have been developed to teach people who are likely to encounter a person with opioid poisoning how to administer naloxone, deliver high-quality compressions, and perform rescue breathing. Current American Heart Association recommendations call for laypeople and others who cannot reliably establish the presence of a pulse to initiate cardiopulmonary resuscitation in any individual who is unconscious and not breathing normally; if opioid overdose is suspected, naloxone should also be administered. Secondary prevention, including counseling, opioid overdose education with take-home naloxone, and medication for opioid use disorder, is important to prevent recurrent opioid overdose.

Survival after cardiac arrest requires an integrated system of people, training, equipment, and organizations working together to achieve a common goal. Part 7 of the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care focuses on systems of care, with an emphasis on elements that are relevant to a broad range of resuscitation situations. Previous systems of care guidelines have identified a Chain of Survival, beginning with prevention and early identification of cardiac arrest and proceeding through resuscitation to post-cardiac arrest care. This concept is reinforced by the addition of recovery as an important stage in cardiac arrest survival. Debriefing and other quality improvement strategies were previously mentioned and are now emphasized. Specific to out-of-hospital cardiac arrest, this Part contains recommendations about community initiatives to promote cardiac arrest recognition, cardiopulmonary resuscitation, public access defibrillation, mobile phone technologies to summon first responders, and an enhanced role for emergency telecommunicators. Germane to in-hospital cardiac arrest are recommendations about the recognition and stabilization of hospital patients at risk for developing cardiac arrest. This Part also includes recommendations about clinical debriefing, transport to specialized cardiac arrest centers, organ donation, and performance measurement across the continuum of resuscitation situations.

The 2020 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care is based on the extensive evidence evaluation performed in conjunction with the International Liaison Committee on Resuscitation. The Adult Basic and Advanced Life Support, Pediatric Basic and Advanced Life Support, Neonatal Life Support, Resuscitation Education Science, and Systems of Care Writing Groups drafted, reviewed, and approved recommendations, assigning to each recommendation a Class of Recommendation (ie, strength) and Level of Evidence (ie, quality). The 2020 Guidelines are organized in knowledge chunks that are grouped into discrete modules of information on specific topics or management issues. The 2020 Guidelines underwent blinded peer review by subject matter experts and were also reviewed and approved for publication by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. The AHA has rigorous conflict-of-interest policies and procedures to minimize the risk of bias or improper influence during development of the guidelines. Anyone involved in any part of the guideline development process disclosed all commercial relationships and other potential conflicts of interest.

Cardiac arrest results from a broad range of etiologies that can be broadly grouped as sudden and asphyxial. Animal studies point to differences in injury pathways invoked in the heart and brain that drive injury and outcome after these different forms of cardiac arrest. Present guidelines largely ignore etiology in their management recommendations. Existing clinical data reveal significant heterogeneity in the utility of presently employed resuscitation and postresuscitation strategies based on etiology. The development of future neuroprotective and cardioprotective therapies should also take etiology into consideration to optimize the chances for successful translation., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In recent years the prescription opioid overdose epidemic has decreased, but has been more than offset by increases in overdose caused by fentanyl and fentanyl analogues. Opioid overdose patients should receive naloxone if they have significant respiratory depression and/or loss of protective airway reflexes. Patients who receive naloxone should be observed for recurrent opioid effects. Patients with opioid overdose may be admitted to the intensive care unit for naloxone infusions, treatment of noncardiogenic pulmonary edema, autonomic instability, or sequelae of hypoxia-ischemia or cardiac arrest. Primary and secondary prevention are important to reduce the number of people with life-threatening opioid overdose., Competing Interests: Disclosure Dr. Lavonas has served as a paid consultant for the American Heart Association., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Few data exist to understand the recovery phase of pit viper envenomation. A recently published placebo-controlled clinical trial affords this opportunity. The purpose of this study is to examine the time course of recovery from copperhead snake (Agkistrodon contortrix) envenomation patients managed with and without the use of antivenom, stratified by age, sex, anatomic site of envenomation, initial severity of envenomation, and geographic region., Methods: This is a post-hoc subgroup analysis of data from a multi-center double-blinded clinical trial of Fab antivenom (FabAV) vs. placebo. Outcomes were the Patient-Specific Functional Scale (PSFS) score at 3, 7, 10, and 14 days after envenomation. Least-squares mean PSFS score curves were calculated for each subgroup, and repeated measures ANOVA was used to estimate between-group comparisons., Results: Seventy-two subjects were included, of whom 44 received FabAV. Males demonstrated better overall recovery than females (model predicted PSFS score 6.18 vs 4.99; difference 1.19; 95% CI 0.12 to 2.25; p = 0.029). No sex difference was found in response to FabAV. Overall recovery and effect of FabAV were similar in adult vs adolescent patients, patients with upper vs lower extremity envenomation, and patients with initially mild vs moderate envenomation signs. Analysis by geographic location was not successful due to ANOVA mode instability., Conclusions: Male victims of copperhead snake envenomation demonstrate slightly better recovery than females, but response to Fab antivenom overall is similar across all subgroups studied.

Objectives: Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone., Methods: This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach's alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman's correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen's kappa. Bland Altman analysis was used to assess differential bias in low and high score results., Results: Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach α: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman's ρ: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen's κ 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias., Conclusions: Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Rose reports speakers bureau fees from BTG International Inc outside the submitted work. Dr. Greene reports receiving consulting fees and honoraria from BTGInternational Inc outside the submitted work. Drs. Gerardo, Charlton, Mullins, Lavonas and Kleinschmidt and Ms. Anderson report receiving prior study-related grants from BTG International Inc.

Introduction: Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use., Methods: We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients' functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids., Results: We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial's predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery., Conclusion: In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The original trial was funded by BTG International Inc. Funding for the statistical analysis for this secondary analysis was also provided by BTG International Inc. Drs Gerardo and Lavonas report receiving grants from BTG during the original trial and outside of the submitted work. Dr. Kleinschmidt and Ms. Anderson report receiving study-related funds from BTG.

Aim: To assess the use of advanced airway interventions (tracheal intubation (TI) or supraglottic airway (SGA) placement), compared with bag mask ventilation (BMV) alone, for resuscitation of children in cardiac arrest., Methods: We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human trials and observational studies published before September 24, 2018 for clinical trials and observational studies with a comparison group. Two investigators reviewed studies for relevance, extracted data, and assessed risk of bias using the GRADE and CLARITY frameworks. Study authors were contacted when necessary to obtain additional data. Critically important outcomes included survival to hospital discharge and survival with good neurological outcome., Results: We identified 14 studies, including 1 pseudorandomised clinical trial, 3 observational cohort studies using propensity matching, and 8 simple cohort studies suitable for meta-analysis. The overall certainty of evidence was low to very low. For the critically important outcomes of survival to hospital discharge with good neurologic outcome and survival to hospital discharge results suggested better outcomes achieved with BMV than either TI or SGA; limited data favored SGA over TI. The majority of studies involved out-of-hospital cardiac arrest, with few studies of in-hospital cardiac arrest., Conclusions: TI or SGA are not superior to BMV for resuscitation of children in cardiac arrest, but the overall certainty of evidence is low to very low. Well designed randomised efficacy trials are needed to address this important question., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Venomous snakebite severity ranges from an asymptomatic dry bite to severe envenomation and death. The clinical evaluation aids in prognosis and is essential to determine the risks and potential benefits of antivenom treatment., Objectives: To identify historical features, clinical examination findings, basic laboratory testing, and clinical grading scales that will risk-stratify patients with pit viper snake envenomation for severe systemic envenomation, severe tissue injury, and/or severe hematologic venom effects., Data Sources: We conducted a structured search of PubMed (1966-October 3, 2017) and Embase database (1980-October 3, 2017) to identify English-language studies that evaluated clinical features predictive of severe envenomation., Study Selection: We included studies that evaluated the test performance of at least 1 clinical finding with an acceptable reference standard of severe envenomation for venomous snakes of the Western Hemisphere. Only studies involving the most common subfamily, Crotalinae (pit vipers), were evaluated. Seventeen studies with data were available for abstraction., Data Extraction and Synthesis: The clinical features assessed and severity outcome measures were extracted from each original study. We assessed severity in 3 categories: systemic toxicity, tissue injury, and hematologic effects. Differences were resolved by author consensus., Results: The pooled prevalence of severe systemic envenomation was 14% (95% CI, 9%-21%). The pooled prevalence of severe tissue injury and severe hematologic venom effects were 14% (95% CI, 12%-16%) and 18% (95% CI, 8%-27%), respectively. Factors increasing the likelihood of severe systemic envenomation included the time from bite to care of 6 or more hours (likelihood ratio [LR], 3.4 [95% CI, 1.1-6.4]), a patient younger than 12 years (LRs, 3.2 [95% CI, 1.5-7.1] and 2.9 [95% CI, 1.3-6.2]), large snake size (LR, 3.1 [95% CI, 1.5-5.7]), and ptosis (LRs, 1.4 [95% CI, 1.0-2.1] and 3.8 [95% CI, 1.8-8.3]). Envenomation by the genus Agkistrodon (copperhead and cottonmouth), as opposed to rattlesnakes, decreased the likelihood of severe systemic envenomation (LR, 0.28 [95% CI, 0.10-0.78]). Initial hypofibrinogenemia (LR, 5.1 [95% CI, 1.7-15.0]) and thrombocytopenia (LR, 3.7 [95% CI, 1.9-7.3]) increased the likelihood of severe hematologic venom effects. Other clinical features from history, physical examination, or normal laboratory values were not discriminative., Conclusions: Clinical features can identify patients at increased risk of severe systemic envenomation and severe hematologic venom effects, but there are few features that are associated with severe tissue injury or can confidently exclude severe envenomation. Physicians should monitor patients closely and be wary of progression from nonsevere to a severe envenomation and have a low threshold to escalate therapy as needed.

Objective: Valid, reliable, and clinically relevant outcome measures are necessary in clinical studies of snake envenomation. The aim of this study was to evaluate the psychometric (validity and reliability) and clinimetric (minimal clinically important difference [MCID]) properties of the Patient-Specific Functional Scale (PSFS) in snakebite envenomation., Methods: We performed a secondary analysis of two existing snakebite trials that measured clinical outcomes using the PSFS as well as other quality of life and functional assessments. Data were collected at 3, 7, 10, and 17 days. Reliability was determined using Cronbach's alpha for internal consistency and the intraclass correlation coefficient (ICC) for temporal stability at 10 and 17 days. Validity was assessed using concurrent validity correlating with the other assessments. The MCID was evaluated using the following criteria: (1) the distribution of stable patients according to both standard error of measurement (SEM) and responsiveness techniques, and (2) anchor-based methods to compare between individuals and to detect discriminant ability of a positive change with a receiver operator characteristic (ROC) curve and optimal cutoff point., Results: A total of 86 patients were evaluated in this study. The average PSFS scores were 5.37 (SD 3.23), 7.95 (SD 2.22), and 9.12 (SD 1.37) at 3, 7, and 10 days, respectively. Negligible floor effect was observed (maximum of 8% at 3 days); however, a ceiling effect was observed at 17 days (25%). The PSFS showed good reliability with an internal consistency of 0.91 (Cronbach's alpha) (95% CI 0.88, 0.95) and a temporal stability of 0.83 (ICC) (95% CI 0.72, 0.89). The PSFS showed a strong positive correlation with quality of life and functional assessments. The MCID was approximately 1.0 for all methods., Conclusions: With an MCID of approximately 1 point, the PSFS is a valid and reliable tool to assess quality of life and functionality in patients with snake envenomation., Competing Interests: Dr. Rose reports speakers bureau fees from BTG International Inc outside the submitted work. Dr. Greene reports receiving consulting fees and honoraria from BTGInternational Inc outside the submitted work. Drs. Gerardo, Charlton, Mullins, Lavonas and Kleinschmidt and Ms. Anderson report receiving prior study-related grants from BTG International Inc. The parent studies from which data were derived, were funded by BTG International Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: No previous research has studied whether early snake antivenom administration leads to better clinical outcomes than late antivenom administration in North American pit viper envenomation., Methods: A secondary analysis of data from a clinical trial of Fab antivenom (FabAV) versus placebo for copperhead snake envenomation was conducted. Patients treated before the median time to FabAV administration were classified as receiving early treatment and those treated after the median time were defined as the late treatment group. A Cox proportional hazards model was used to compare time to full recovery on the Patient-Specific Functional Scale (PSFS) instrument between groups. Secondary analyses compared estimated mean PSFS scores using a generalized linear model and the estimated proportion of patients with full recovery at each time point using logistic regression. To evaluate for confounding, the main analysis was repeated using data from placebo-treated subjects., Results: Forty-five subjects were treated with FabAV at a median of 5.47 h after envenomation. Patients in the early treatment group had a significantly shorter time to full recovery than those treated late (median time: 17 versus 28 days, p = .025). Model-estimated PSFS scores were numerically higher at each time point in the early group. No difference was found between patients treated early versus late with placebo., Conclusions: In this secondary analysis of trial data, recovery of limb function was faster when Fab antivenom was administered soon after envenomation, as opposed to late administration.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the second annual summary of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations that includes the most recent cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation. This summary addresses the role of antiarrhythmic drugs in adults and children and includes the Advanced Life Support Task Force and Pediatric Task Force consensus statements, which summarize the most recent published evidence and an assessment of the quality of the evidence based on Grading of Recommendations, Assessment, Development, and Evaluation criteria. The statements include consensus treatment recommendations approved by members of the relevant task forces. Insights into the deliberations of each task force are provided in the Values and Preferences and Task Force Insights sections. Finally, the task force members have listed the top knowledge gaps for further research.

Objective: To compare the incidence of hypersensitivity reactions following copperhead envenomation treated with Fab antivenom (FabAV) or placebo., Methods: Patients with copperhead snakebites received treatment and follow-up in a prospective, randomized, double-blind, placebo-controlled trial of FabAV or placebo. The treatment allocation ratio was 2:1 (FabAV:placebo). All of the included patients received at least one dose of study treatment. We reviewed all treatment-emergent adverse events (AEs) using a previously published scale to classify likely hypersensitivity reactions as mild, moderate, or severe., Results: We enrolled 74 patients at 13 sites. Forty-five patients received FabAV, and 29 patients received placebo. Five FabAV patients and 4 placebo patients had moderate envenomations; the rest were mild. Twenty-five FabAV patients and 8 placebo patients had at least 1 AE. Mild skin reactions occurred in 11 (24%) FabAV patients (pruritis, urticaria, rash, ecchymosis, erythema) and 1 (3%) placebo patient (pruritis). Moderate gastrointestinal AEs occurred in 7 (16%) FabAV patients (nausea, vomiting, constipation, diarrhea, oral paresthesia) and in 2 (7%) placebo patients (nausea). Respiratory AEs occurred in 3 (7%) FabAV patients (dyspnea, pulmonary embolism, nasal congestion, sneezing) and no placebo patients. Hypotension occurred in 1 patient in each group., Conclusions: In a randomized controlled trial of FabAV for copperhead bites, the incidence of hypersensitivity reactions was low. Most reactions were mild skin reactions.

Context: Serum paracetamol-protein adducts (PPAs) are a novel potential biomarker of paracetamol exposure. The relationship between serum PPA concentrations and reported paracetamol use in ambulatory adults has not been previously described., Materials and Methods: This was a cross-sectional study of ambulatory adults. A detailed medication history was obtained from all subjects and subjects were stratified by reported paracetamol use in the 2 weeks prior to enrolment. Serum PPAs were measured in all subjects and correlated with reported dose, time of last ingestion and demographics., Results: We enrolled 230 in the paracetamol exposure arm and 74 in the no exposure arm. 98/230 (42.6%)of subjects who reported paracetamol exposure had PPA detected and 68/74 (91.9%) of subjects who denied paracetamol exposure had no PPA detected. PPA concentrations were positively correlated with total paracetamol dose and with more recent ingestion., Discussion: Detection of serum PPA generally reflects paracetamol exposure histories in ambulatory adults. Concentrations are well correlated with reported dose and time from last dose., Conclusions: Serum PPA can be detected with reported therapeutic use of paracetamol but may not be detected in all patients who report taking paracetamol.

Study Objective: Copperhead snake (Agkistrodon contortrix) envenomation causes limb injury resulting in pain and disability. It is not known whether antivenom administration improves limb function. We determine whether administration of antivenom improves recovery from limb injury in patients envenomated by copperhead snakes., Methods: From August 2013 through November 2015, we performed a multicenter, randomized, double-blind, placebo-controlled, clinical trial to evaluate the effect of ovine Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) antivenom therapy on recovery of limb function in patients with copperhead snake envenomation at 14 days postenvenomation. The study setting was 18 emergency departments in regions of the United States where copperhead snakes are endemic. Consecutive patients aged 12 years or older with mild- to moderate-severity envenomation received either FabAV or placebo. The primary outcome was limb function 14 days after envenomation, measured by the Patient-Specific Functional Scale. Additional outcomes included the Patient-Specific Functional Scale at other points; the Disorders of the Arm, Shoulder, and Hand, Lower Extremity Functional Scale, and Patient's Global Impression of Change instruments; grip strength; walking speed; quality of life (Patient-Reported Outcomes Measurement Information System Physical Fucntion-10); pain; and analgesic use., Results: Seventy-four patients received study drug (45 FabAV, 29 placebo). Mean age was 43 years (range 12 to 86 years). Fifty-three percent were men, 62% had lower extremity envenomation, and 88% had mild initial severity. The primary outcome, the least square mean Patient-Specific Functional Scale score at 14 days postenvenomation, was 8.6 for FabAV-treated subjects and 7.4 for placebo recipients (difference 1.2; 95% confidence interval 0.1 to 2.3; P=.04). Additional outcome assessments generally favored FabAV. More FabAV-treated subjects experienced treatment-emergent adverse events (56% versus 28%), but few were serious (1 in each group)., Conclusion: Treatment with FabAV reduces limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure., Methods: A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS., Results: One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion., Conclusions: APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.

Objective: To provide a management approach for adults with calcium channel blocker poisoning., Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits., Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D)., Conclusion: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low.