Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial

This article by the Writing Group for PReVENT Investigators was published in JAMA during October 2018.
Importance:  It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS).
Objective:  To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy.
Design, Setting, and Participants:  A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands.
Interventions:  Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484).
Main Outcomes and Measures:  The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax.
Results:  In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19] P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89] ; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55).
Conclusions and Relevance:  In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

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Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

This article by Krag and colleagues was published in the New England Journal of Medicine in October 2018.
Background:  Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear.
Methods:  In this European, multi-centre, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization.
Results:  A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups.
Conclusions:  Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo.
The printed copy of the New England Journal of Medicine is available in the Health Care Library on D Level of Rotherham Hospital.

Critical Care Reviews Newsletter 358 22nd October 2018

Critical Care Reviews Newsletter provides you with the best critical care research and open access articles from across the medical literature during the last week.  The annual ESICM LIVES congress in Paris presents three days of trial results being presented. “Today, there are the TARGET (standard vs augmented calorie delivery), POPPI (nurse-led preventative psychological intervention for critically ill patients) and MIND-USA trials (antipsychotics for ICU delirium), and on Wednesday there is SUP-ICU (proton pump inhibitor vs. placebo for stress ulcer prophylaxis) and POLAR (prophylactic hypothermia in patients with severe traumatic brain injuries).”  Also included are “three of the trials being presented on Tuesday in Paris just published in Intensive Care Medicine, as well as an interesting trial in JAMA Surgery on cricoid pressure.”
The full text of the newsletter is available via this link.

Neuromuscular electrical stimulation combined with exercise decreases duration of mechanical ventilation in ICU patients: A randomized controlled trial.

This article by Dos Santos and colleagues was published in “Physiotherapy Theory and Practice”
Background:  Early mobilization can be employed to minimize the duration of intensive care. However, a protocol combining neuromuscular electrical stimulation (NMES) with early mobilization has not yet been tested in ICU patients. Our aim was to assess the efficacy of NMES, exercise (EX), and combined therapy (NMES + EX) on duration of mechanical ventilation (MV) in critically ill patients.
Methods:  The participants in this randomized double-blind trial were prospectively recruited within 24 hours following admission to the intensive care unit of a tertiary hospital. Eligible patients had 18 years of age or older; MV for less than 72 hours; and no known neuromuscular disease. Computer-generated permuted block randomization was used to assign patients to NMES, EX, NMES + EX, or standard care (control group). The main endpoint was duration of MV. Clinical characteristics were also evaluated and intention to treat analysis was employed.
Results:  One hundred forty-four patients were assessed for eligibility to participate in the trial, 51 of whom were enrolled and randomly allocated into four groups: 11 patients in the NMES group, 13 in the EX group, 12 in the NMES + EX group, and 15 in the control group (CG). Duration of MV (days) was significantly shorter in the combined therapy (5.7 ± 1.1) and NMEN (9.0 ± 7.0) groups in comparison to CG (14.8 ± 5.4).
Conclusions:  NMES + EX consisting of NMES and active EXs was well tolerated and resulted in shorter duration of MV in comparison to standard care or isolated therapy (NMES or EX alone).
To access the full text of this article via the journal’s homepage you require a personal subscription to the journal.  Some articles may be available freely without a password.  Library members can order individual articles via the Rotherham NHS Foundation Trust Library and Knowledge Service using the article requests online via this link.

Don’t Sugar Coat It: Glycemic Control in the Intensive Care Unit

This article by Stodt and Chawla was published in the Journal of Intensive Care Medicine in October 2018.
Stress hyperglycemia is the transient increase in blood glucose as a result of complex hormonal changes that occur during critical illness. It has been described in the critically ill for nearly 200 years; patient harm, including increases in morbidity, mortality, and lengths of stay, has been associated with hyperglycemia, hypoglycemia, and glucose variability. However, there remains a contentious debate regarding the optimal glucose ranges for this population, most notably within the past 15 years. Recent landmark clinical trials have dramatically changed the treatment of stress hyperglycemia in the intensive care unit (ICU). Earlier studies suggested that tight glucose control improved both morbidity and mortality for ICU patients, but later studies have suggested potential harm related to the development of hypoglycemia. Multiple trials have tried to elucidate potential glucose target ranges for special patient populations, including those with diabetes, trauma, sepsis, cardiac surgery, and brain injuries, but there remains conflicting evidence for most of these sub-populations. Currently, most international organizations recommend targeting moderate blood glucose concentration to levels <180 mg/dL for all patients in the intensive care unit. In this review, the history of stress hyperglycemia and its treatment will be discussed including optimal glucose target ranges, devices for monitoring blood glucose, and current professional organizations’ recommendations regarding glucose control in the ICU.
To access the full text of this article via the journal’s homepage you require a personal subscription to the journal.  Some articles may be available freely without a password.  Library members can order individual articles via the Rotherham NHS Foundation Trust Library and Knowledge Service using the article requests online via this link.

Information or education interventions for adult intensive care unit (ICU) patients and their carers

This research by Lewis and colleagues was published in the Cochrane database of systematic reviews in October 2018.
Backgcochrane-57-1round:  During intensive care unit (ICU) admission, patients and their carers experience physical and psychological stressors that may result in psychological conditions including anxiety, depression, and post-traumatic stress disorder (PTSD). Improving communication between healthcare professionals, patients, and their carers may alleviate these disorders. Communication may include information or educational interventions, in different formats, aiming to improve knowledge of the prognosis, treatment, or anticipated challenges after ICU discharge.
Objectives:  To assess the effects of information or education interventions for improving outcomes in adult ICU patients and their carers.
Search Methods:  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO from database inception to 10 April 2017. We searched clinical trials registries and grey literature, and hand searched reference lists of included studies and related reviews.
Selection Criteria:  We included randomised controlled trials (RCTs), and planned to include quasi-RCTs, comparing information or education interventions presented to participants versus no information or education interventions, or comparing information or education interventions as part of a complex intervention versus a complex intervention without information or education. We included participants who were adult ICU patients, or their carers; these included relatives and non-relatives, including significant representatives of patients.
Data Collection and Analysis:  Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and applied GRADE criteria to assess certainty of the evidence.
Main Results:  We included eight RCTs with 1157 patient participants and 943 carer participants. We found no quasi-RCTs. We identified seven studies that await classification, and three ongoing studies.  Three studies designed an intervention targeted at patients, four at carers, and one at both patients and carers. Studies included varied information: standardised or tailored, presented once or several times, and that included verbal or written information, audio recordings, multimedia information, and interactive information packs. Five studies reported robust methods of randomisation and allocation concealment. We noted high attrition rates in five studies. It was not feasible to blind participants, and we rated all studies as at high risk of performance bias, and at unclear risk of detection bias because most outcomes required self reporting.  We attempted to pool data statistically, however this was not always possible due to high levels of heterogeneity. We calculated mean differences (MDs) using data reported from individual study authors where possible, and narratively synthesised the results. We reported the following two comparisons.  Information or education intervention versus no information or education intervention (4 studies)For patient anxiety, we did not pool data from three studies (332 participants) owing to unexplained substantial statistical heterogeneity and possible clinical or methodological differences between studies. One study reported less anxiety when an intervention was used (MD -3.20, 95% confidence interval (CI) -3.38 to -3.02), and two studies reported little or no difference between groups (MD -0.40, 95% CI -4.75 to 3.95; MD -1.00, 95% CI -2.94 to 0.94). Similarly, for patient depression, we did not pool data from two studies (160 patient participants). These studies reported less depression when an information or education intervention was used (MD -2.90, 95% CI -4.00 to -1.80; MD -1.27, 95% CI -1.47 to -1.07). However, it is uncertain whether information or education interventions reduce patient anxiety or depression due to very low-certainty evidence.  It is uncertain whether information or education interventions improve health-related quality of life due to very low-certainty evidence from one study reporting little or no difference between intervention groups (MD -1.30, 95% CI -4.99 to 2.39; 143 patient participants). No study reported adverse effects, knowledge acquisition, PTSD severity, or patient or carer satisfaction.  We used the GRADE approach and downgraded certainty of the evidence owing to study limitations, inconsistencies between results, and limited data from few small studies.  Information or education intervention as part of a complex intervention versus a complex intervention without information or education (4 studies)One study (three comparison groups; 38 participants) reported little or no difference between groups in patient anxiety (tailored information pack versus control: MD 0.09, 95% CI -3.29 to 3.47; standardised general ICU information versus control: MD -0.25, 95% CI -4.34 to 3.84), and little or no difference in patient depression (tailored information pack versus control: MD -1.26, 95% CI -4.48 to 1.96; standardised general ICU information versus control: MD -1.47, 95% CI -6.37 to 3.43). It is uncertain whether information or education interventions as part of a complex intervention reduce patient anxiety and depression due to very low-certainty evidence.  One study (175 carer participants) reported fewer carer participants with poor comprehension among those given information (risk ratio 0.28, 95% CI 0.15 to 0.53), but again this finding is uncertain due to very low-certainty evidence.  Two studies (487 carer participants) reported little or no difference in carer satisfaction; it is uncertain whether information or education interventions as part of a complex intervention increase carer satisfaction due to very low-certainty evidence. Adverse effects were reported in only one study: one participant withdrew because of deterioration in mental health on completion of anxiety and depression questionnaires, but the study authors did not report whether this participant was from the intervention or comparison group.  We downgraded certainty of the evidence owing to study limitations, and limited data from few small studies.  No studies reported severity of PTSD, or health-related quality of life.
Authors’ Conclusions:  We are uncertain of the effects of information or education interventions given to adult ICU patients and their carers, as the evidence in all cases was of very low certainty, and our confidence in the evidence was limited.  Ongoing studies may contribute more data and introduce more certainty when incorporated into future updates of the review.
The full text of this Cochrane Review is freely available via this link to the Cochrane Database of Systematic Reviews.

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis

This article by the IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network was published in the New England journal of medicine in October 2018.
Background:  Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.
Methods:  In a multicentre, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.
Results:  The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).
Conclusions:  Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy.
The printed copy of the New England Journal of Medicine is available in the Health Care Library on D Level of Rotherham Hospital.