Prone position for acute respiratory failure in adults.

BACKGROUND: Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes. OBJECTIVES: The objectives of this review are (1) to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation, and (2) to supplement previous systematic reviews on prone ventilation for hypoxaemic respiratory failure in an adult population. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1), Ovid MEDLINE (1950 to 31 January 2014), EMBASE (1980 to 31 January 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 31 January 2014) and Latin American Caribbean Health Sciences Literature (LILACS) (1992 to 31 January 2014) in Ovid MEDLINE for eligible randomized controlled trials. We also searched for studies by handsearching reference lists of relevant articles, by contacting colleagues and by handsearching published proceedings of relevant journals. We applied no language constraints, and we reran the searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. We added five new studies of potential interest to the list of "Studies awaiting classification" and will incorporate them into formal review findings during the review update. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that examined the effects of prone position versus supine/semi recumbent position during conventional mechanical ventilation in adult participants with acute hypoxaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all trials identified by the search and assessed them for suitability, methods and quality. Two review authors extracted data, and three review authors reviewed the data extracted. We analysed data using Review Manager software and pooled included studies to determine the risk ratio (RR) for mortality and the risk ratio or mean difference (MD) for secondary outcomes; we also performed subgroup analyses and sensitivity analyses. MAIN RESULTS: We identified nine relevant RCTs, which enrolled a total of 2165 participants (10 publications). All recruited participants suffered from disorders of lung function causing moderate to severe hypoxaemia and requiring mechanical ventilation, so they were fairly comparable, given the heterogeneity of specific disease diagnoses in intensive care. Risk of bias, although acceptable in the view of the review authors, was inevitable: Blinding of participants and carers to treatment allocation was not possible (face-up vs face-down).Primary analyses of short- and longer-term mortality pooled from six trials demonstrated an RR of 0.84 to 0.86 in favour of the prone position (PP), but findings were not statistically significant: In the short term, mortality for those ventilated prone was 33.4% (363/1086) and supine 38.3% (395/1031). This resulted in an RR of 0.84 (95% confidence interval (CI) 0.69 to 1.02) marginally in favour of PP. For longer-term mortality, results showed 41.7% (462/1107) for prone and 47.1% (490/1041) for supine positions, with an RR of 0.86 (95% CI 0.72 to 1.03). The quality of the evidence for both outcomes was rated as low as a result of important potential bias and serious inconsistency.Subgroup analyses for mortality identified three groups consistently favouring PP: those recruited within 48 hours of meeting entry criteria (five trials; 1024 participants showed an RR of 0.75 (95% CI 0.59 to 94)); those treated in the PP for 16 or more hours per day (five trials; 1005 participants showed an RR of 0.77 (95% CI 0.61 to 0.99)); and participants with more severe hypoxaemia at trial entry (six trials; 1108 participants showed an RR of 0.77 (95% CI 0.65 to 0.92)). The quality of the evidence for these outcomes was rated as moderate as a result of potentially important bias.Prone positioning appeared to influence adverse effects: Pressure sores (three trials; 366 participants) with an RR of 1.37 (95% CI 1.05 to 1.79) and tracheal tube obstruction with an RR of 1.78 (95% CI 1.22 to 2.60) were increased with prone ventilation. Reporting of arrhythmias was reduced with PP, with an RR of 0.64 (95% CI 0.47 to 0.87). AUTHORS' CONCLUSIONS: We found no convincing evidence of benefit nor harm from universal application of PP in adults with hypoxaemia mechanically ventilated in intensive care units (ICUs). Three subgroups (early implementation of PP, prolonged adoption of PP and severe hypoxaemia at study entry) suggested that prone positioning may confer a statistically significant mortality advantage. Additional adequately powered studies would be required to confirm or refute these possibilities of subgroup benefit but are unlikely, given results of the most recent study and recommendations derived from several published subgroup analyses. Meta-analysis of individual patient data could be useful for further data exploration in this regard. Complications such as tracheal obstruction are increased with use of prone ventilation. Long-term mortality data (12 months and beyond), as well as functional, neuro-psychological and quality of life data, are required if future studies are to better inform the role of PP in the management of hypoxaemic respiratory failure in the ICU.

Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1).

CONTEXT: Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE: To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS: A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE: Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS: Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION: For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients.

OBJECTIVE: To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients. DESIGN: Randomised, double blinded, factorial, controlled trial. SETTING: Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated. PARTICIPANTS: 502 adults in intensive care units and high dependency units for ≥ 48 hours, with gastrointestinal failure and requiring parenteral nutrition. INTERVENTIONS: Parenteral glutamine (20.2 g/day) or selenium (500 µg/day), or both, for up to seven days. MAIN OUTCOME MEASURES: Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥ 5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsis-related Organ Failure Assessment) score. RESULTS: Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥ 5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥ 5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation. CONCLUSIONS: The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥ 5 days did show a reduction in new infections. This finding requires confirmation. Trial registration Current Controlled Trials ISRCTN87144826.

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients. Protocol Version 9, 19 February 2007 known as SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial).

BACKGROUND: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2-3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. METHODS/DESIGN: 2 x 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrollment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. DISCUSSION: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. TRIAL REGISTRATION: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826.

Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit.

We aimed to establish whether screening for methicillin-resistant Staphylococcus aureus (MRSA) and body decontamination upon admission to an Intensive Care Unit (ICU), in combination with barrier precautions, reduced rates of MRSA infection acquired on the unit. This was an interrupted time series study employing segmented regression analysis of data collected for all patients admitted to a 16-bed adult ICU over 48 months. Before the intervention (24 months; 1232 patients (44% female)), MRSA was sought from clinical cultures only and positive patients were barrier nursed in isolation. During the intervention (24 months; 1421 patients (54% female)), all ICU patients were screened for MRSA on admission and were barrier nursed in single rooms when established as MRSA-positive; all were given topical nasal anti-MRSA preparations and daily bed baths with 4% chlorhexidine throughout their stay. Changes in the proportion of patients colonised or infected with MRSA in the ICU were assessed. Before the intervention, 193 new MRSA cases (16%) were identified from 1232 ICU admissions; during the intervention, this was reduced to 92 cases (6%) of 1421 admissions. By time series regression analysis, the proportion of patients with MRSA decreased by 11.38% from ca. 15% to ca. 5% (ca. three-fold reduction) (95% confidence interval 3.5-19.3%; P=0.005). Thus, treatment of 11 patients prevented 1 clinical case of MRSA. Mean length of stay decreased significantly (P<0.001). Although MRSA and methicillin-susceptible S. aureus bacteraemia rates dropped, the changes detected were not statistically significant. The proportion of patients with coagulase-negative staphylococcal bacteraemia decreased significantly (P<0.001) and the trend changed from increasing to decreasing (P<0.001), as did the trend in glycopeptide use (P=0.014). An inexpensive and easy to implement intervention to control MRSA in the ICU was highly successful without compromising antimicrobial susceptibility.

Etomidate, pharmacological adrenalectomy and the critically ill: a matter of vital importance.

Etomidate is a potent suppressant of adrenal steroidogenesis,effectively inducing reversible pharmacological adrenalectomy. Recent evidence suggests that for every five patients with septic shock given etomidate without corticosteroid supplementation, one patient will die as a consequence. Other critically ill patients are also at possible risk, and this risk requires further exploration. Etomidate will also confound investigations into the effects of disease states on adrenal function, and should therefore be avoided. A moratorium on the use of etomidate in critically ill patients outside clinical trials may be prudent until its safety is established.

Accuracy of weight and height estimation in an intensive care unit: Implications for clinical practice and research.

OBJECTIVE: Numerous calculations routinely used in the intensive care require the knowledge of patients' weight and height, although these measurements are not always made. Estimates by doctors or nurses are often substituted. This study sought to ascertain the accuracy of estimates of weight and height of patients made by intensive care unit (ICU) staff. DESIGN: : Prospective clinical study. SETTING: Sixteen-bed mixed medical and surgical ICU in a university teaching hospital. PATIENTS: Fourteen patients had their height and weight estimated by 20 members of the medical and nursing staff. MEASUREMENTS: After all estimates had been recorded, measurements of weight and height were obtained. Weight was measured by means of a patient hoist with a calibrated weighing facility and height using a steel tape measure. MAIN RESULTS: Estimation of weight was poor, with 47% of estimates at least 10% different and 19% of estimates at least 20% different from the measured values. The majority of height estimates were within 10% of the measured values. CONCLUSIONS: Individual estimates of weight and height are frequently inaccurate. These errors of estimation could compromise application of effective therapies, as well as contribute to a reduction in design sensitivity of clinical trials.