Dirk W. Donker

Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial

Importance Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. Objective To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. Design, Setting, and Participants Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. Interventions Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. Main Outcome and Measures The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. Results All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, −3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 [0.3%] for the 2-mg haloperidol group vs 1 [0.1%] for the placebo group). Conclusions and Relevance Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults. Trial Registration clinicaltrials.gov Identifier: NCT01785290

A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries—The SPAME trial results

INTRODUCTION International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. METHODS This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. RESULTS The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34°C for 24h, and 33% had changed the target temperature to 36°C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p<0.01), as well as the use of a computer feedback device (p=0.03) for TTM. CONCLUSION This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.

Individualized real-time clinical decision support to monitor cardiac loading during venoarterial ECMO

Veno-arterial extracoporeal membrane oxygenation (VA ECMO) is increasingly used for acute and refractory cardiogenic shock. Yet, in clinical practice, monitoring of cardiac loading conditions during VA ECMO can be cumbersome. To this end, we illustrate the validity and clinical applicability of a real-time cardiovascular computer simulation, which allows to integrate hemodynamics, cardiac dimensions and the corresponding degree of VA ECMO support and ventricular loading in individual patients over time.

Brain monitoring in adult and pediatric ECMO patients: The importance of early and late assessments

Monitoring brain integrity and neurocognitive function is a new and important target for the management of a patient treated with extracorporeal membrane oxygenation (ECMO), in particular because of the increasing awareness of cerebral abnormalities that may potentially occur in this setting. Continuous regular monitoring, as well as repeated assessment for cerebral complications has become an essential element of the ECMO patient management. Besides well-known complications, like bleeding, ischemic stroke, seizures, and brain hypoperfusion, other less defined yet relevant injury and clinical manifestations are increasingly reported and impacting on ECMO patient prognosis at short term. Furthermore, it is becoming more evident that neurologic complication may not occur only in the early phase. Indeed, other potential adverse events related to the long-term neurocognitive function have been also recently documented either in children or adult ECMO patients. Despite increasing awareness of these aspects, generally accepted protocols and clinical management strategies in this respect are still lacking. Current means to monitor brain perfusion or detecting ongoing cerebral tissue injury are rather limited, and most techniques provide indirect or post-insult recognition of irreversible tissue injury. Continuous monitoring of brain perfusion, serial assessment of brain-derived serum biomarkers, timely neuro-imaging, and post-discharge counselling for neurocognitive dysfunction, particularly in pediatric patients, are novel pathways focusing on neurologic assessment with important implications in daily practice to assess brain function and integrity not only during the ECMO-related hospitalization, but also at long-term to re-evaluate the neuropsychological integrity, although well designed studies will be necessary to elucidate the cost-effectiveness of these management strategies.

Non-intubated recovery from refractory cardiogenic shock on percutaneous VA-extracorporeal membrane oxygenation

We report on the use of percutaneous femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in a fully awake, non-intubated and spontaneously breathing patient suffering from acute, severe and refractory cardiogenic shock due to a (sub)acute anterior myocardial infarction. Intensified heart failure therapy was closely monitored with a pulmonary artery catheter and allowed gradual weaning off the ECMO support without additional invasive measures, notably without mechanical ventilation. Neurological assessment was possible at all times and complete physical mobilisation was straightforward directly after weaning from ECMO. This limited invasive approach may encourage a more widespread use of percutaneous VA-ECMO.

Extracorporeal life support in cardiogenic shock : Indications and management in current practice

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.

Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome

Background: Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. Methods and Results: We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14–2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10–2.62 for hs-cTnI concentrations of 100–500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04–1.50). Conclusions: Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early—but not late—mortality, as well as postdischarge cardiovascular morbidity.

Awake' Extracorporeal Membrane Oxygenation Requires Adequate Lower Body Muscle Training and Mobilisation As Successful Bridge to Lung Transplant

‘Awake’ extracorporeal membrane oxygenation (ECMO) is being used increasingly as a bridge to lung transplant (LuTx) to support refractory respiratory failure as an alternative to invasive mechanical ventilation and associated immobilisation and deconditioning which are associated with poor outcome. the ideal combination of ECMO cannulation and muscle training has yet to be determined and depends largely on patient-specific needs and procedural limitations.

Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions

Short-term mechanical support by veno-arterial extracorporeal membrane oxygenation (VA ECMO) is more and more applied in patients with severe cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent increase of left ventricular (LV) mechanical load, which may aggravate pulmonary edema and hamper cardiac recovery. In order to mitigate these negative sequelae of VA ECMO, different adjunct LV unloading interventions have gained a broad interest in recent years. Here, we review the whole spectrum of percutaneous and surgical techniques combined with VA ECMO reported to date.

Echocardiography in extracorporeal life support: A key player in procedural guidance, tailoring and monitoring:

Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.