The performance of COBRA, a decision rule to predict the need for intensive care interventions in intentional drug overdose

BACKGROUND: COBRA was developed as a decision rule to predict which patients visiting the emergency department (ED) following intentional drug overdose will not require intensive care unit (ICU) interventions. COBRA uses parameters from five vital systems (cardiac conduction, oxygenation, blood pressure, respiration, and awareness) that are readily available in the ED. COBRA recommends against ICU admission when all these parameters are normal. OBJECTIVE: The primary aim of this study was to determine the negative predictive value (NPV) of COBRA in predicting ICU interventions. Secondary outcomes were the sensitivity, specificity and positive predictive value (PPV), and the observation time required for a reliable prediction. DESIGN: Observational cohort study. SETTINGS AND PARTICIPANTS: Patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function were included, and data necessary to complete the decision rule was collected. The attending physician in the ED made the actual admission decision, on the basis of clinical judgement. COBRA was measured 0, 3 and 6 h after arrival at the ED. OUTCOME MEASURES: Need for ICU interventions (treatment of convulsion; defibrillation; mechanical or noninvasive ventilation; intravenous administration of vasopressive agents, antiarrhythmics, atropine, calcium, magnesium or sedation; continuous hemofiltration or administration of antagonist/antidote and fluid resuscitation). MAIN RESULTS: Of 230 new cases (144 unique patients), 59 were immediately referred to the psychiatric services and/or sent home by the attending physician, 27 went to a regular ward, and 144 were admitted to the ICU. Of these 144 cases, 40 required one or more ICU interventions. By the time the first parameters were collected, the NPV of COBRA was 95.6%. After 3 h of observation, NPV was 100%, while sensitivity, specificity and PPV were 100, 61.1 and 35.1%, respectively. None of these values improved by prolonging the observation time to 6 h. CONCLUSION: In patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function, the COBRA decision rule showed good performances in predicting the need for intensive care interventions, with a NPV of 100% after 3 h of observation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Spinal anesthesia as a complication of brachial plexus block using the posterior approach

IMPLICATIONS: In this case report we describe a technique used to provide local analgesia for surgical procedures. Although this technique has a reduced risk of complications, we present a patient who experienced a life-threatening paralysis without loss of consciousness during an attempted brachial plexus block with a posterior approac

D-Dimer Assessment to Predict Pulmonary Embolism in ICU Patients with COVID-19 Pneumonia

The value of D-dimer assessments in ICU patients with COVID-19 for the prediction of pulmonary embolism (PE) is unclear. The present study had two purposes: 1. To assess the specificity of elevated absolute D-dimer values for PE on admission to the ICU. 2. To assess the specificity of a D-dimer increment for the development of PE during an ICU stay. D-dimer values were paired with the results of a CT pulmonary angiogram (CTPA) and compared in patients with and without PE on admission. In patients without PE on initial imaging and available repeat CTPA during an ICU stay, D-dimer increments between initial and repeat imaging of patients developing PE during an ICU stay were compared with those with persistently no PE. On admission, D-dimers in patients with PE were higher than those in patients without PE (median 850 vs. 6060 μg/L; p p < 0.005). Using a cut-off of 8000 μg/L, specificity was 100% (CI 79.4–100%). Strongly elevated D-dimer values on admission and marked increases in D-dimer during ICU stays have a high specificity for predicting pulmonary embolism in critically ill COVID-19 patients

Clinical parameters that predict the need for medium or intensive care admission in intentional drug overdose patients:A retrospective cohort study

INTRODUCTION: Many patients with intentional drug overdose (IDO) are admitted to a medium (MC) or intensive care unit (IC) without ever requiring MC/IC related interventions. The objective of this study was to develop a decision tool, using parameters readily available in the emergency room (ER) for patients with an IDO, to identify patients requiring admission to a monitoring unit. METHODS: Retrospective cohort study among cases of IDO with drugs having potentially acute effects on neurological, circulatory or ventilatory function, admitted to the MC/IC unit between 2007 and 2013. A decision tool was developed, using 6 criteria, representing intubation, breathing, oxygenation, cardiac conduction, blood pressure, and consciousness. Cases were labeled as 'high acuity' if one or more criteria were present. RESULTS: Among 255 cases of IDO that met the inclusion criteria, 197 were identified as "high acuity". Only 70 of 255 cases underwent one or more MC/IC related interventions, of which 67 were identified as 'high acuity by the decision tool (sensitivity 95.7%). CONCLUSION: In a population of patients with intentional drug overdose with agents having potentially acute effect on vital functions, 95.7% of MC/IC interventions could be predicted by clinical assessment, supplemented with electrocardiogram and blood gas analysis, in the ER

Feasibility of Exercise Testing in Patients Who Are Critically Ill: A Prospective, Observational Multicenter Study

Objective: To evaluate the feasibility and safety of exercise testing and to describe the physiological response to exercise of patients in the Intensive Care Unit (ICU). Design: A prospective observational multicenter study. Setting: Two mixed medical-surgical ICUs. Participants: Patients (N=37; with no primary neurological disorders, 59% men; median age 50y; ICU length of stay 14.5d; Acute Physiology and Chronic Health Evaluation IV 73.0) who had been mechanically ventilated for more than 48 hours and were hemodynamically stable enough to perform physical exercise. Interventions: A passive or active incremental exercise test, depending on muscle strength, on a bed-based cycle ergometer. Main Outcome Measures: Feasibility and safety were evaluated based on protocol adherence and adverse events. Physiological responses to exercise quantified as changes in respiratory frequency (RF), oxygen uptake (VO2), carbon dioxide output (VCO2), respiratory exchange ratio (RER), and blood lactate. Results: Thirty-seven patients of whom 18 were mechanically ventilated underwent the exercise test. The active incremental test was performed by 28, and the passive test by 9 participants. Thirty-three (89%) accomplished the test according to the protocol and 1 moderate severe adverse event (bradycardia; heart rate 44) occurred shortly after the test. RF, VO2, VCO2, and lactate increased significantly, whereas RER did not change during the active incremental exercise test. No changes were observed during the passive exercise test. Conclusions: It is safe and feasible to perform exercise testing on a bed-based cycle ergometer in patients who are critically ill and a physiological response could be measured. Future research should investigate the clinical value of exercise testing in daily ICU practice and whether exercise capacity and its limiting factors could be determined by incremental exercise testing

Optimising the dose of clonidine to achieve sedation in intensive care unit patients with population pharmacokinetics

Aims: The aim of this study was to investigate the population pharmacokinetics (PK) of clonidine in intensive care unit (ICU) patients in order to develop a dosing regimen for sedation. Methods: We included 24 adult mechanically ventilated, sedated patients from a mixed medical and surgical ICU. Intravenous clonidine was added to standard sedation in doses of 600, 1200 or 1800 μg/d. Within each treatment group, 4 patients received a loading dose of half the daily dose administered in 4 hours. Patients gave an average of 12 samples per individual. In total, 286 samples were available for analysis. Model development was conducted with NONMEM and various covariates were tested. After modelling, doses to achieve a target steady-state plasma concentration of >1.5 μg/L were explored using stochastic Monte Carlo simulations for 1000 virtual patients. Results: A 2-compartment model was the best fit for the concentration-time data. Clearance (CL) increased linearly with 0.213%/h; using allometric scaling, body weight was a significant covariate on the central volume of distribution (V1). Population PK parameters were: CL 17.1 (L/h), V1 124 (L/70 kg), intercompartmental CL 83.7 (L/h), and peripheral volume of distribution 178 (L), with 33.3% CV interindividual variability on CL and 66.8% CV interindividual variability on V1. Simulations revealed that a maintenance dose of 1200 μg/d provides target sedation concentrations of >1.5 μg/L in 95% of the patients. Conclusion: A population PK model for clonidine was developed in an adult ICU. A dosing regimen of 1200 μg/d provided a target sedation concentration of >1.5 μg/L