Emergence of xylazine as a public health threat: what does the anesthesiologist need to know for perioperative care?

This paper explores the rapid emergence of xylazine exposure in the USA and its implications for anesthesiologists. Xylazine, a non-opioid sedative and analgesic often used in veterinary medicine, has increasingly been found as an adulterant in the illicit substance supply, leading to serious health implications. The pharmacological properties of xylazine, its clinical effects, and the challenges it poses for clinicans will be discussed. Perioperative strategies for anesthesiologists to manage these potential cases are provided. Furthermore, this paper necessitates an epidemiological understanding for detection and multidisciplinary collaboration in addressing this emerging public health threat. The manuscript concludes by emphasizing the role anesthesiologists will have to play in managing the clinical implications of xylazine and contributing to public health strategies aimed at curbing its misuse.

Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C.

Importance: It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. Objective: To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. Design, Setting, and Participants: This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. Exposure: TTM at 36 °C or 33 °C. Main Outcomes and Measures: Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Results: Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. Conclusions and Relevance: In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Unsupervised learning of early post-arrest brain injury phenotypes.

INTRODUCTION: Trials may be neutral when they do not appropriately target the experimental intervention. We speculated multimodality assessment of early hypoxic-ischemic brain injury would identify phenotypes likely to benefit from therapeutic interventions. METHODS: We performed a retrospective study including comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) by one of 126 emergency medical services or in-hospital arrest at one of 26 hospitals from 2011 to 2019. All patients were ultimately transported to a single tertiary center for care including standardized initial neurological examination, brain imaging and electroencephalography; targeted temperature management (TTM); hemodynamic optimization targeting mean arterial pressure (MAP) >80 mmHg; and, coronary angiography for clinical suspicion for acute coronary syndrome. We used unsupervised learning to identify brain injury phenotypes defined by admission neurodiagnostics. We tested for interactions between phenotype and TTM, hemodynamic management and cardiac catheterization in models predicting recovery. RESULTS: We included 1086 patients with mean (SD) age 58 (17) years of whom 955 (88%) were resuscitated from OHCA. Survival to hospital discharge was 27%, and 248 (23%) were discharged with Cerebral Performance Category (CPC) 1-3. We identified 5 clusters defining distinct brain injury phenotypes, each comprising 14% to 30% of the cohort with discharge CPC 1-3 in 59% to <1%. We found significant interactions between cluster and TTM strategy (P = 0.01), MAP (P < 0.001) and coronary angiography (P = 0.04) in models predicting outcomes. CONCLUSIONS: We identified patterns of early hypoxic-ischemic injury based on multiple diagnostic modalities that predict responsiveness to several therapeutic interventions recently tested in neutral clinical trials.

Sensitivity of Continuous Electroencephalography to Detect Ictal Activity After Cardiac Arrest.

Importance: Epileptiform electroencephalographic (EEG) patterns are common after resuscitation from cardiac arrest, are associated with patient outcome, and may require treatment. It is unknown whether continuous EEG monitoring is needed to detect these patterns or if brief intermittent monitoring is sufficient. If continuous monitoring is required, the necessary duration of observation is unknown. Objective: To quantify the time-dependent sensitivity of continuous EEG for epileptiform event detection, and to compare continuous EEG to several alternative EEG-monitoring strategies for post-cardiac arrest outcome prediction. Design, Setting, and Participants: This observational cohort study was conducted in 2 academic medical centers between September 2010 and January 2018. Participants included 759 adults who were comatose after being resuscitated from cardiac arrest and who underwent 24 hours or more of EEG monitoring. Main Outcomes and Measures: Epileptiform EEG patterns associated with neurological outcome at hospital discharge, such as seizures likely to cause secondary injury. Results: Overall, 759 patients were included in the analysis; 281 (37.0%) were female, and the mean (SD) age was 58 (17) years. Epileptiform EEG activity was observed in 414 participants (54.5%), of whom only 26 (3.4%) developed potentially treatable seizures. Brief intermittent EEG had an estimated 66% (95% CI, 62%-69%) to 68% (95% CI, 66%-70%) sensitivity for detection of prognostic epileptiform events. Depending on initial continuity of the EEG background, 0 to 51 hours of monitoring were needed to achieve 95% sensitivity for the detection of prognostic epileptiform events. Brief intermittent EEG had a sensitivity of 7% (95% CI, 4%-12%) to 8% (95% CI, 4%-12%) for the detection of potentially treatable seizures, and 0 to 53 hours of continuous monitoring were needed to achieve 95% sensitivity for the detection of potentially treatable seizures. Brief intermittent EEG results yielded similar information compared with continuous EEG results when added to multivariable models predicting neurological outcome. Conclusions and Relevance: Compared with continuous EEG monitoring, brief intermittent monitoring was insensitive for detection of epileptiform events. Monitoring EEG results significantly improved multimodality prediction of neurological outcome, but continuous monitoring appeared to add little additional information compared with brief intermittent monitoring.

Association of antiepileptic drugs with resolution of epileptiform activity after cardiac arrest.

INTRODUCTION: We tested the impact of antiepileptic drug (AED) administration on post-cardiac arrest epileptiform electroencephalographic (EEG) activity. METHODS: We studied an observational cohort of comatose subjects treated at a single academic medical center after cardiac arrest from September 2010 to January 2018. We aggregated the observed EEG patterns into 5 categories: suppressed; discontinuous background with superimposed epileptiform activity; discontinuous background without epileptiform features; continuous background with epileptiform activity; and continuous background without epileptiform activity. We calculated overall probabilities of transitions between EEG states in a multistate model, then used Aalen's additive regression to test if AEDs or hypothermia are associated with a change in these probabilities. RESULTS: Overall, 828 subjects had EEG-monitoring for 42,840 h with a median of 40 [IQR 23-64] h per subject. Among patients with epileptiform findings on initial monitoring, 50% transitioned at least once to a non-epileptiform, non-suppressed state. By contrast, 19% with non-epileptiform initial activity transitioned to an epileptiform state at least once. Overall, 568 (78%) patients received at least one AED. Among patients with continuous EEG background activity, valproate, levetiracetam and lower body temperature were each associated with an increased probability of transition from epileptiform states to non-epileptiform states, where patients with discontinuous EEG background activity no agent linked to an increased probability of transitioning from epileptiform states. CONCLUSION: After cardiac arrest, the impact of AEDs may depend on the presence of continuous cortical background activity. These data serve to inform experimental work to better define the opportunities to improve neurologic care post-cardiac arrest.

Carotid artery stenosis as an independent risk factor for perioperative strokes following mitral valve surgical intervention.

OBJECTIVE: To examine the role of carotid stenosis (CS) and other independent risk factors of perioperative stroke following either mitral valve repair or replacement. METHODS: Using data from the National Inpatient Sample (NIS) database for analysis, all patients who underwent either mitral valve repair or replacement were identified using ICD-9 codes. RESULTS: A total of 79,583 patients who underwent either mitral valve replacement or repair were studied. 3.39% of the total cohort developed perioperative stroke. With a mean age of 62.78±0.23, there was a statistically significant amount of stroke cases in age ranges 65-74 and 75-84 (p<0.05). Risk stratification was done using Van Walraven (VWR) scoring and the cohort had a mean of 2.73±0.06. The following independent predictors were found to be significant: age, female gender, moderate and high VWR risk, both symptomatic and asymptomatic CS, atrial fibrillation, previous h/o smoking, and other cardiac valve procedures performed, and congestive heart failure (CHF). CONCLUSION: CS is a significant risk factor for perioperative strokes following mitral valve surgery. Further prospective clinical studies are needed that look into risk stratification of patients for better patient selection and the question of whether carotid revascularization procedures will be beneficial in reducing stroke rates.