Guy Glover

Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design

BACKGROUND Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. METHODS The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. DISCUSSION The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.

Prevalence of Venous Thrombosis Following Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Respiratory Failure.

Objectives:Venovenous extracorporeal membrane oxygenation for patients with severe respiratory failure is increasingly common. There has been a significant change in the population, technology, and approach used for venovenous extracorporeal membrane oxygenation over the last 10 years. The objective of this study is to describe the prevalence of postdecannulation deep vein thrombosis in the cannulated vessel in adults who have received venovenous extracorporeal membrane oxygenation for severe respiratory failure. Design:A single-center, retrospective, observational cohort, electronic note review study. Setting:Tertiary referral university teaching hospital. Patients:Patients commenced on venovenous extracorporeal membrane oxygenation for severe respiratory failure. Interventions:None. Measurements and Main Results:We identified 103 patients commenced on extracorporeal membrane oxygenation with 81 survivors from December 2011 to February 2014. We performed postdecannulation venous Doppler ultrasound in 88.9% of extracorporeal membrane oxygenation survivors. The prevalence of deep vein thrombosis in the cannulated vessel following extracorporeal membrane oxygenation is 8.1/1,000 cannula days in patients who were screened. Conclusions:The prevalence of deep vein thrombosis following decannulation from extracorporeal membrane oxygenation for severe respiratory failure is clinically significant, and routine venous Doppler ultrasound following decannulation is warranted in this population.

Capabilities of a mobile extracorporeal membrane oxygenation service for severe respiratory failure delivered by intensive care specialists

We conducted a single‐centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist‐delivered retrieval service has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2/FIO2 ratio at referral was 10.2 (4.1) kPa and median (IQR [range]) Murray score was 3.25 (3.0–3.5 [1.5–4.0]). Forty‐eight patients (80%) required veno‐venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation‐related complications. The median (IQR [range]) retrieval distance was 47.2 (14.9–77.0 [2.3–342.0]) miles. There were no major adverse events during retrieval. Thirty‐seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist‐initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.

Development of a standard operating procedure and checklist for rapid sequence induction in the critically ill

IntroductionRapid sequence induction (RSI) of critically ill patients outside of theatres is associated with a higher risk of hypoxia, cardiovascular collapse and death. In the prehospital and military environments, there is an increasing awareness of the benefits of standardised practice and checklists.MethodsWe conducted a non-systematic review of literature pertaining to key components of RSI preparation and management. A standard operating procedure (SOP) for in-hospital RSI was developed based on this and experience from large teaching hospital anaesthesia and critical care departments.ResultsThe SOP consists of a RSI equipment set-up sheet, pre-RSI checklist and failed airway algorithm. The SOP should improve RSI preparation, crew resource management and first pass intubation success while minimising adverse events.ConclusionBased on the presented literature, we believe the evidence is sufficient to recommend adoption of the core components in the suggested SOP. This standardised approach to RSI in the critically ill may reduce the current high incidence of adverse events and hopefully improve patient outcomes.

Extracorporeal Carbon Dioxide Removal as an Alternative to Endotracheal Intubation for Non-Invasive Ventilation Failure in Acute Exacerbation of COPD

Extracorporeal carbon dioxide removal (ECCO2R) is an efficient technique used in the management of hypercapnic respiratory failure. Its application in mechanically ventilated patients has been studied for over 30 years. We describe a case of severe, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) unresponsive to non-invasive ventilation (NIV), where initiation of ECCO2R was used effectively to prevent endotracheal intubation.

Dysglycemia, Glycemic Variability, and Outcome After Cardiac Arrest and Temperature Management at 33°C and 36°C.

Objectives: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Design: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as “Cerebral Performance Category.” Setting: Thirty-six sites in Europe and Australia. Patients: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Interventions: Targeted temperature management at 33°C or 36°C. Measurements and Main Results: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3–5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03–1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. Conclusion: Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.

Healthcare-associated bloodstream infections in critically ill patients: descriptive cross-sectional database study evaluating concordance with clinical site isolates.

BackgroundHealthcare-associated bloodstream infections are related to both increased antibiotic use and risk of adverse outcomes. An in-depth understanding of their epidemiology is essential to reduce occurrence and to improve outcomes by targeted prevention strategies. The objectives of the study were to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates.MethodsWe conducted a descriptive cross-sectional study in critically ill adults admitted to a tertiary semi-closed intensive care unit in England to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. All nosocomial positive blood cultures over a 4-year study period were identified. Pathogens detected and concordances with clinical site are reported as proportions.ResultsContaminant pathogens accounted for half of the isolates. The most common non-contaminant pathogens cultured were Pseudomonas spp. (8.0%), Enterococcus spp. (7.3%) and Escherichia coli (5.6%). Central venous catheter-linked bloodstream infections represent only 6.0% of the positive blood cultures. Excluding contaminants and central venous line infections, in only 39.5% of the bloodstream infections could a concordant clinical site source be identified, the respiratory and urinary tracts being the most common.ConclusionsClinical practice should focus on a) improving blood culture techniques to reduce detection of contaminant pathogens and b) ensuring paired clinical site cultures are performed alongside all blood cultures to better understand the epidemiology and potential implications of primary and secondary discordant health-care associated bloodstream infections.

An observational cohort study to determine efficacy, adherence and outcome of the early initiation of pressure support ventilation during mechanical ventilation

Background Timely initiation of weaning from mechanical ventilation (MV) is important. Non-validated screening criteria may delay weaning if too prescriptive. This study observed physician-led utilisation of pressure support ventilation (PSV), referenced to four reported conventional screening criteria hypothesising that these criteria would have delayed the weaning progress. Methods A prospective observational cohort study of adult patients receiving MV in a 30-bed university hospital intensive care unit (ICU). Logistic regression analysis identified factors associated with PSV failure. Outcome is reported according to adherence to the screening criteria. Results 209 patients were included (age 62.6±15.9 years, male:female 115:94, Acute Physiology and Chronic Health Evaluation (APACHE) II 16.7±6.1). Median (IQR) time to initiate PSV was 11.0 (5.0–22.0) h, and duration of weaning to extubation was 43.0 (13.0–121.5) h. PSV weaning was initiated despite significant hypoxia (partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) 35.8±15.9 kPa), moderate positive end-expiratory pressure levels (7.5±2.5 cm H2O), deep sedation (44% Richmond Agitation and Sedation Scale (RASS) ≤−3) and cardiovascular instability (48.8%). At PSV initiation, 85% of patients violated at least one screening criterion, yet 74.6% of patients remained stable for 24 h and 25.4% of patients were successfully extubated within 12 h. There was no association between individual screening criteria and PSV failure. Failure to sustain a PSV trial was associated with ventilation >7 days (RR=2.12 (1.33 to 3.38), p=0.002) and ICU mortality (RR=2.94 (1.46 to 5.94), p=0.002). Conclusions Physician-led transition to PSV and weaning was often initiated early and successfully before patients fulfilled conventional screening criteria. Failure to sustain a PSV trial could be an early indicator of prolonged MV and ICU mortality and warrants further investigation. These data support the view that current screening criteria may delay initiation of weaning.

Acceptance and transfer to a regional severe respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO) service: predictors and outcomes

The use of extracorporeal membrane oxygenation for respiratory failure is high risk and resource intensive. In England, five centres provide this service and patients who are referred have four possible outcomes: declined transfer due to perceived futility; accepted in principle but remain at the referring centre with ongoing surveillance; retrieved using conventional ventilation; or retrieved on extracorporeal support. The decision‐making process leading to these outcomes has not previously been examined. We evaluated referrals to one centre and identified factors associated with each decision outcome. Five hundred and sixty‐four patients were analysed from January 2012 to October 2015. One hundred and fifty‐seven patients were declined; multivariate analysis demonstrated associated factors to be: age (odds ratio (95% confidence interval) 1.05 (1.04–1.07)); immunocompromise (4.95 (2.58–9.67)); lactate (1.11 (1.01–1.22)); duration of ventilation (1.08 (1.04–1.14)); and cardiac failure (3.22 (1.04–10.51)). Factors associated with the decision to retrieve an accepted patient were: plateau pressure (1.05 (1.01–1.10)); ratio of arterial oxygen partial pressure to fractional inspired oxygen (0.89 (0.85–0.93)); partial pressure of carbon dioxide in arterial blood (1.13 (1.03–1.25)); and the absence of non‐pulmonary infection (0.31 (0.15–0.61)). Only pH was independently associated with the decision to transfer on extracorporeal support (0.020 (0.002–0.017)). Six‐month survival in the declined, non‐retrieved, conventionally retrieved and extracorporeal‐retrieved groups was 16.6%, 71.1%, 76.7% and 72.1%, respectively, substantially supporting the decision‐making model. Survival in the accepted group exceeds that reported previously. However, a proportion of those declined do survive and some remotely managed patients die. This suggests the approach does not account for some important survival‐determining factors.

Dysglycemia, glycemic variability and outcome after cardiac arrest and temperature management at 33 °C and 36 °C (a post-hoc analysis of the target temperature management trial).

Dysglycemia and glycemic variability (GV) are associated with poor outcomes in critically ill patients. Target temperature management alters blood glucose (BG) homeostasis.