Lower versus higher hemoglobin threshold for transfusion in septic shock.

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS: We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study.

PURPOSE: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively. CONCLUSIONS: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial.

BACKGROUND: Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients. METHODS/DESIGN: The non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%). DISCUSSION: The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients. TRIAL REGISTER: ClinicalTrials.gov NCT0196768, 09.01.2014.

[There is a need for further studies exploring the sleep in patients during intensive care unit admission]. / Behov for mere viden om søvn hos intensivpatienter.

We have been reviewing the literature on sleep in intensive care unit (ICU) patients, concluding that lack of normal sleep is a common problem. Polysomnography studies have demonstrated sleep deprivation and fragmentation. Delirium commonly coincides with sleep deprivation and shares the same symptoms. Mechanically ventilated patients have traditionally been sedated, making sleep scoring unreliable. There is a need for further studies exploring the relationship between circadian rhythm disturbance, sleep disorders, delirium and sedation in ICU patients.

Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS/DESIGN: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. DISCUSSION: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.