Citations

AbstractBackgroundTransvenous implantable cardioverter defibrillators (TV ICD) provide life‐saving therapy for millions of patients worldwide. However, they are susceptible to several potential short‐ and long‐ term complications including cardiac perforation and pneumothorax, lead dislodgement, venous obstruction, and infection. The extravascular ICD system's novel design and substernal implant approach avoids the risks associated with TV ICDs while still providing pacing features and similar generator size to TV ICDs.Study DesignThe EV ICD pivotal study is a prospective, multicenter, single‐arm, nonrandomized, premarket clinical study designed to examine the safety and acute efficacy of the system. This study will enroll up to 400 patients with a Class I or IIa indication for implantation of an ICD. Implanted subjects will be followed up to approximately 3.5 years, depending on when the patient is enrolled.ObjectiveThe clinical trial is designed to demonstrate safety and effectiveness of the EV ICD system in human use. The safety endpoint is freedom from major complications, while the efficacy endpoint is defibrillation success. Both endpoints will be assessed against prespecified criteria. Additionally, this study will evaluate antitachycardia pacing performance, electrical performance, extracardiac pacing sensation, asystole pacing, appropriate and inappropriate shocks, as well as a summary of adverse events.ConclusionThe EV ICD pivotal study is designed to provide clear evidence addressing the safety and efficacy performance of the EV ICD System.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3–4 toxicities (66.7%); 15.2% had grade 3–4 cytokine release syndrome and 64% grade 3–4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64–not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Background: Obesity paradox is a phenomenon in which obesity increases the risk of obesity-related chronic diseases but paradoxically is associated with improved survival among obese patients with these diagnoses. Objectives: The aim of this study was to explore the obesity paradox among critically ill patients with cirrhosis admitted to the Intensive Care Unit. Methods: A retrospective cohort of 1,143 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Primary outcome of interest was in-hospital mortality with secondary end points including ICU and short-term mortality at 30 days post ICU admission. Results: Logistic regression with generalized additive models was used, controlling for clinically relevant and statistically significant factors to determine the adjusted relationship between body mass index (BMI) and ICU, post-ICU in-hospital, and 30 day mortality following ICU discharge. ICU and hospital length of stay was similar across all BMI classes. Adjusted ICU mortality was also similar when stratified by BMI. However, a significant reduction in post-ICU hospital mortality was observed in class I and II obese patients with cirrhosis (BMI 30-39.9 kg/m 2 ) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m 2 ) and class I and II obese patients with cirrhosis had significantly lower 30-day mortality following ICU discharge (OR = 0.52, 95% CI 0.31 to 0.87; P = 0.014; OR = 0.50, 95% CI 0.29 to 0.86; P = 0.012, respectively) compared to those with normal BMI. Conclusion: The signal of obesity paradox is suggested among critically ill patients with cirrhosis.

Introduction: Hydrogen ion concentration which is expressed as pH value is in human blood maintained in narrow physiological range (7.36-7.44 in arterial blood). This range is crucial for normal functioning of most biochemical reactions. Extreme acidosis with pH < 6.8 is incompatible with life, unless pathophysiologic process is rapidly reversed. Timely, standardized, and structured approach to assessment and management of extreme critical illness is essential to maximize the chances of patient’s survival. Cases: We present a series of 3 critically ill patients admitted to Medical intensive care unit (MICU) diagnosed with extreme metabolic acidosis (pH ⩽ 6.8). Each patient was treated using Checklist for Early Recognition and Treatment of Acute Illness and INjury (CERTAIN) which is a standard decision support tool in our MICU. Causes of extreme metabolic acidosis included hemorrhagic shock, sepsis, and acute renal failure and diabetic ketoacidosis. Rapid assessment, prompt resuscitation (IV fluids, vasopressors, mechanical ventilation, and renal replacement), and application of specific causal treatment led to positive outcomes in all 3 patients. Discussion: Medical physiology textbooks set the lower limit of pH value at which life is possible to 6.8. However, examples from clinical practice show that if adequate resuscitation measures are taken early in the acute phase of the disease, the biochemical cascade of reactions that are considered irreversible (at pH ⩽ 6.8) may be reversed after all. Conclusion: Critical care approach to extreme metabolic acidosis is a prime example of applied clinical physiology where basic science and clinical practice connect. With these case series we show that timely and structured approach to critical illness shifts the boundaries of reversibility for some of the most severe physiologic derangements.

OBJECTIVES: Beta-lactam antibiotics exhibit high interindividual variability in drug concentrations in patients with critical illness which led to an interest in the use of therapeutic drug monitoring to improve effectiveness and safety. To implement therapeutic drug monitoring, it is necessary to define the beta-lactam therapeutic range—in essence, what drug concentration would prompt a clinician to make dose adjustments up or down. This objective of this narrative review was to summarize evidence for the “floor” (for effectiveness) and “ceiling” (for toxicity) for the beta-lactam therapeutic range to be used with individualized therapeutic drug monitoring. DATA SOURCES: Research articles were sourced from PubMed using search term combinations of “pharmacokinetics,” “pharmacodynamics,” “toxicity,” “neurotoxicity,” “therapeutic drug monitoring,” “beta-lactam,” “cefepime,” “meropenem,” “piperacillin/tazobactam,” “ICU,” and “critical illness.” STUDY SELECTION: Articles were selected if they included preclinical, translational, or clinical data on pharmacokinetic and pharmacodynamic thresholds for effectiveness and safety for beta-lactams in critical illness. DATA SYNTHESIS: Experimental data indicate a beta-lactam concentration above the minimum inhibitory concentration of the organism for greater than or equal to 40–60% of the dosing interval is needed, but clinical data indicate that higher concentrations may be preferrable. In the first 48 hours of critical illness, a free beta-lactam concentration at or above the susceptibility breakpoint of the most likely pathogen for 100% of the dosing interval would be reasonable (typically based on Pseudomonas aeruginosa). After 48 hours, the lowest acceptable concentration could be tailored to 1–2× the observed minimum inhibitory concentration of the organism for 100% of the dosing interval (often a more susceptible organism). Neurotoxicity is the primary dose-dependent adverse effect of beta-lactams, but the evidence remains insufficient to link a specific drug concentration to greater risk. CONCLUSIONS: As studies advance the understanding of beta-lactam exposure and response in critically ill patients, it is essential to clearly define the acceptable therapeutic range to guide regimen selection and adjustment.

Abstract Early diagnosis of AKI and preventive measures can likely decrease the severity of the injury and improve patient outcomes. Current hemodynamic monitoring variables, including BP, heart and respiratory rates, temperature, and oxygenation status, have been used to identify patients at high risk for AKI. Despite the widespread use of such variables, their ability to accurately and timely detect patients who are high risk has been questioned. Therefore, there is a critical need to develop and validate tools that can measure new and more kidney-specific hemodynamic and laboratory variables, potentially assisting with AKI risk stratification, implementing appropriate and timely preventive measures, and hopefully improved outcomes. The new ultrasonography techniques provide novel insights into kidney hemodynamics and potential management and/or therapeutic targets. Contrast-enhanced ultrasonography; Doppler flow patterns of hepatic veins, portal vein, and intrakidney veins; and ultrasound elastography are among approaches that may provide such information, particularly related to vascular changes in AKI, venous volume excess or congestion, and fluid tolerance. This review summarizes the current state of these techniques and their relevance to kidney hemodynamic management.

IMPORTANCE: Propofol, ketamine, and etomidate are common anesthetic agents for induction of anesthesia in the ICU. The choice between these agents is complex and may not depend solely upon severity of illness. OBJECTIVES: To evaluate the association between the administration of propofol, ketamine, and etomidate and ICU, hospital mortality, and length of stay. DESIGN, SETTING, AND PARTICIPANTS: Retrospective single-center cohort study. ICUs in a tertiary medical center, between January 01, 2012, and December 31, 2017. Critically ill adult patients given a single IV anesthetic for intubation. MAIN OUTCOME AND MEASURES: Primary outcomes were ICU and hospital mortality. Secondary outcomes were ICU- and hospital-free days through 28 days. An inverse probability of treatment weighed approach was used. The propensity score was estimated using a generalized logit model as a function of patient characteristics, admission source, ICU type, readmission status, length of ICU stays prior to intubation, and acute physiology score. Mortality outcomes were assessed with weighted logistic regression and -free days assessed by weighted linear regression with Bonferroni correction for pairwise comparisons. RESULTS: Of 2,673 patients, 36% received propofol, 30% ketamine and 34% etomidate. Overall ICU and hospital mortality were 19% and 29%, respectively. Patients given ketamine had higher odds of ICU mortality (1.45; [95% CI, 1.07–1.94]; p = 0.015) and patients given etomidate had higher odds of ICU mortality (1.87; 1.40–2.49; p < 0.001), hospital mortality (1.43; 1.09–1.86; p = 0.009), and less ICU-free days (–2.10; –3.21 to –1.00; p < 0.001) than those given propofol. Patients given ketamine and etomidate had similar odds of hospital mortality (1.06; 0.80–1.42; p = 0.761) and similar hospital-free days (0.30; –0.81 to 1.40; p = 0.600). CONCLUSIONS AND RELEVANCE: Compared with ketamine and etomidate, propofol was associated with better outcome in critically ill patients undergoing anesthesia for intubation. Even after adjusting for severity of illness prior to intubation, residual confounders cannot be excluded.