Temporal trends in mortality and provision of intensive care in younger women and men with acute myocardial infarction or stroke

BACKGROUND Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland. METHODS Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019. RESULTS Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (- 6.4% in women versus - 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10-1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94-1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85-0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94-1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions. CONCLUSION Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed

Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial.

BACKGROUND Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. METHODS All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. INTERVENTION Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. ETHICS AND DISSEMINATION The study was approved by the respective ethical committees (No 2020-02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT04931485

Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial (PRIDe): a phase IV multicenter, randomized, placebo-controlled, double-blind clinical trial of ketamine versus haloperidol for prevention of postoperative delirium

BACKGROUND: Delirium is a neurobehavioural syndrome that frequently develops in the postoperative setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 10 to 80% (Schonauer et al., J Pept Sci. 2017). Delirium was first described more than half a century ago in the cardiac surgery population (Blachy and Starr, Am J Psychiatry 121:371-5, 1964), where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population (Sessler et al., Am J Respir Crit Care Med 166:1338-44, 2002). This long-term experience with delirium suggests a high socioeconomic burden and has been a focus of many studies (Nishio et al., Crit Care Med 5:953-7, 1997; Ehlenbach et al., JAMA 303:763-70, 2010; Jahangir et al., World J Cardiol 3:383-7, 2011; Abegunde et al., Lancet 370:1929-1938, 2007; Darmon et al., Intensive Care Med 43:829-840, 2017; Marino et al., J Nephrol 28:717-24, 2015; Ng LL et al., J Am Coll Cardiol 69:56-69, 2017; Sezen et al., J Pharmacol Exp Ther 287:238-45, 1998; Kim et al., Ann Lab Med 37:388-97, 2017). Due to the multifactorial origin of delirium, we have several but no incontestable options for prevention and symptomatic treatment. Overall, delirium represents a high burden not only for patient and family members, but also for the medical care team that aims to prevent postoperative delirium to avoid serious consequences associated with it. The purpose of this study is to determine whether postoperative delirium can be prevented by the combination of established preventive agents. In addition, measured levels of pre- and postoperative cortisol, neuron specific enolase (NSE) and S-100β will be used to investigate dynamics of these parameters in delirious and non-delirious patients after surgery. METHODS/DESIGN: The Baden PRIDe Trial is an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial for the prevention of delirium with haloperidol, ketamine, and the combination of both vs. placebo in 200 patients scheduled for surgery. We would like to investigate superiority of one of the three treatment arms (i.e., haloperidol, ketamine, combined treatment) to placebo. DISCUSSION: There is limited but promising evidence that haloperidol and ketamine can be used to prevent delirium. Clinical care for patients might improve as the results of this study may lead to better algorithms for the prevention of delirium. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02433041 . Registered on 7 April 2015. Swiss National Clinical Trial Portal, SNCTP000001628. Registered on 9 December 2015

Preoperative Noninvasive Mapping Allowed Targeted Concomitant Surgical Ablation and Revealed COVID-19 Infection

In March 2020, a 64-year-old female with mitral valve insufficiency and persistent atrial fibrillation underwent preoperative noninvasive mapping for developing an ablation strategy. In the computed tomography (CT) scan, typical signs of COVID-19 were described. Since the consecutive polymerase chain reaction (PCR) test was negative, the severely symptomatic patient was planned for urgent surgery. Noninvasive mapping showed that atrial fibrillation was maintained by left atrial structures and pulmonary veins only. On admission day, the preoperative routine COVID-19 PCR test was positive, and after recovery, uneventful mitral valve repair with cryoablation of the left atrium and pulmonary veins was performed. Our case describes the potential benefit of preoperative noninvasive mapping for the development of a surgical ablation strategy, as well as the challenges in managing urgent surgical patients during the COVID-19 pandemic and the corresponding diagnostic relevance of CT

Pain-Phenotyping in Osteoarthritis: Current Concepts, Evidence, and Considerations towards a Comprehensive Framework for Assessment and Treatment

Objectives Pain as central symptom of osteoarthritis (OA) needs to be addressed as part of successful treatment. The assessment of pain as feature of disease or outcome in clinical practice and drug development remains a challenge due to its multidimensionality and the plethora of confounders. This article aims at providing insights into our understanding of OA pain-phenotypes and suggests a framework for systematic and comprehensive assessments. Methods This narrative review is based on a search of current literature for various combinations of the search terms “pain-phenotype” and “knee OA” and summarizes current knowledge on OA pain-phenotypes, putting OA pain and its assessment into perspective of current research efforts. Results Pain is a complex phenomenon, not necessarily associated with tissue damage. Various pain-phenotypes have been described in knee OA. Among those, a phenotype with high pain levels not necessarily matching structural changes and a phenotype with low pain levels and impact are relatively consistent. Further subgroups can be differentiated based on patient reported outcome measures, assessments of comorbidities, anxiety and depression, sleep, activity and objective measures such as quantitative sensory testing. Conclusions The complexity of both OA as disease and pain in OA prompt the definition of a set of variables that facilitate assessments comparable across studies to maximize our understanding of pain, as central concern for the patient

Medical Nutrition Therapy in Critically Ill Patients Treated on Intensive and Intermediate Care Units: A Literature Review

Medical nutrition therapy in critically ill patients remains challenging, not only because of the pronounced stress response with a higher risk for complications, but also due to their heterogeneity evolving from different phases of illness. The present review aims to address current knowledge and guidelines in order to summarize how they can be best implemented into daily clinical practice. Further studies are urgently needed to answer such important questions as best timing, route, dose, and composition of medical nutrition therapy for critically ill patients and to determine how to assess and to adapt to patients’ individual needs.</p

Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis

Abstract Background To determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit (ICU) delirium. Methods The literature search using PubMed and the Cochrane Central Register of Controlled Trials was performed (August 1, 2018) to detect all randomized controlled trials (RCTs) of adult ICU patients receiving dexmedetomidine. Articles were included if they assessed the influence of dexmedetomidine compared to a sedative agent on incidence of ICU delirium or treatment of this syndrome. Accordingly, relevant articles were allocated to the following two groups: (1) articles that assessed the delirium incidence (incidence comparison) or articles that assessed the treatment of delirium (treatment comparison). Incidence of delirium and delirium resolution were the primary outcomes. We combined treatment effects comparing dexmedetomidine versus (1) placebo, (2) standard sedatives, and (3) opioids in random-effects meta-analyses. Risk of bias for each included RCT was assessed following Cochrane standards. Results The literature search resulted in 28 articles (25 articles/4975 patients for the incidence comparison and three articles/166 patients for the treatment comparison). In the incidence comparison, heterogeneity was present in different subgroups. Administration of dexmedetomidine was associated with significantly lower overall incidence of delirium when compared to placebo (RR 0.52; 95% CI 0.39–0.70; I 2 = 37%), standard sedatives (RR 0.63; 95% CI 0.46–0.86; I 2 = 69%), as well as to opioids (RR 0.61; 95% CI 0.44–0.83; I 2 = 0%). Use of dexmedetomidine significantly increased the risks of bradycardia and hypotension. Limited data were available on circulatory insufficiency and mortality. In the treatment comparison, the comparison drugs in the three RCTs were placebo, midazolam, and haloperidol. The resolution of delirium was measured differently in each study. Two out of the three studies indicated clear favorable effects for dexmedetomidine (i.e., compared to placebo and midazolam). The study comparing dexmedetomidine with haloperidol was a pilot study (n = 20) with high variability in the results. Conclusion Findings suggest that dexmedetomidine reduces incidence and duration of ICU delirium. Furthermore, our systematic searches show that there is limited evidence if a delirium shall be treated with dexmedetomidine