Chlorhexidine bathing of the critically ill for the prevention of hospital-acquired infection.

BACKGROUND: Hospital-acquired infection is a frequent adverse event in patient care; it can lead to longer stays in the intensive care unit (ICU), additional medical complications, permanent disability or death. Whilst all hospital-based patients are susceptible to infections, prevalence is particularly high in the ICU, where people who are critically ill have suppressed immunity and are subject to increased invasive monitoring. People who are mechanically-ventilated are at infection risk due to tracheostomy and reintubation and use of multiple central venous catheters, where lines and tubes may act as vectors for the transmission of bacteria and may increase bloodstream infections and ventilator-associated pneumonia (VAP). Chlorhexidine is a low-cost product, widely used as a disinfectant and antiseptic, which may be used to bathe people who are critically ill with the aim of killing bacteria and reducing the spread of hospital-acquired infections. OBJECTIVES: To assess the effects of chlorhexidine bathing on the number of hospital-acquired infections in people who are critically ill. SEARCH METHODS: In December 2018 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared chlorhexidine bathing with soap-and-water bathing of patients in the ICU. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and undertook risk of bias and GRADE assessment of the certainty of the evidence . MAIN RESULTS: We included eight studies in this review. Four RCTs included a total of 1537 individually randomised participants, and four cluster-randomised cross-over studies included 23 randomised ICUs with 22,935 participants. We identified one study awaiting classification, for which we were unable to assess eligibility.The studies compared bathing using 2% chlorhexidine-impregnated washcloths or dilute solutions of 4% chlorhexidine versus soap-and-water bathing or bathing with non-antimicrobial washcloths.Eight studies reported data for participants who had a hospital-acquired infection during the ICU stay. We are uncertain whether using chlorhexidine for bathing of critically ill people reduces the rate of hospital-acquired infection, because the certainty of the evidence is very low (rate difference 1.70, 95% confidence interval (CI) 0.12 to 3.29; 21,924 participants). Six studies reported mortality (in hospital, in the ICU, and at 48 hours). We cannot be sure whether using chlorhexidine for bathing of critically-ill people reduces mortality, because the certainty of the evidence is very low (odds ratio 0.87, 95% CI 0.76 to 0.99; 15,798 participants). Six studies reported length of stay in the ICU. We noted that individual studies found no evidence of a difference in length of stay; we did not conduct meta-analysis because data were skewed. It is not clear whether using chlorhexidine for bathing of critically ill people reduced length of stay in the ICU, because the certainty of the evidence is very low. Seven studies reported skin reactions as an adverse event, and five of these reported skin reactions which were thought to be attributable to the bathing solution. Data in these studies were reported inconsistently and we were unable to conduct meta-analysis; we cannot tell whether using chlorhexidine for bathing of critically ill people reduced adverse events, because the certainty of the evidence is very low.We used the GRADE approach to downgrade the certainty of the evidence of each outcome to very low. For all outcomes, we downgraded evidence because of study limitations (most studies had a high risk of performance bias, and we noted high risks of other bias in some studies). We downgraded evidence due to indirectness, because some participants in studies may have had hospital-acquired infections before recruitment. We noted that one small study had a large influence on the effect for hospital-acquired infections, and we assessed decisions made in analysis of some cluster-randomised cross-over studies on the effect for hospital-acquired infections and for mortality; we downgraded the evidence for these outcomes due to inconsistency. We also downgraded the evidence on length of stay in the ICU, because of imprecision. Data for adverse events were limited by few events and so we downgraded for imprecision. AUTHORS' CONCLUSIONS: Due to the very low-certainty evidence available, it is not clear whether bathing with chlorhexidine reduces hospital-acquired infections, mortality, or length of stay in the ICU, or whether the use of chlorhexidine results in more skin reactions.

Follow-up services for improving long-term outcomes in intensive care unit (ICU) survivors.

BACKGROUND: The intensive care unit (ICU) stay has been linked with a number of physical and psychological sequelae, known collectively as post-intensive care syndrome (PICS). Specific ICU follow-up services are relatively recent developments in health systems, and may have the potential to address PICS through targeting unmet health needs arising from the experience of the ICU stay. There is currently no single accepted model of follow-up service and current aftercare programmes encompass a variety of interventions and materials. There is uncertain evidence about whether follow-up services effectively address PICS, and this review assesses this. OBJECTIVES: Our main objective was to assess the effectiveness of follow-up services for ICU survivors that aim to identify and address unmet health needs related to the ICU period. We aimed to assess effectiveness in relation to health-related quality of life (HRQoL), mortality, depression and anxiety, post-traumatic stress disorder (PTSD), physical function, cognitive function, ability to return to work or education and adverse effects.Our secondary objectives were to examine different models of follow-up services. We aimed to explore: the effectiveness of service organisation (physician- versus nurse-led, face-to-face versus remote, timing of follow-up service); differences related to country (high-income versus low- and middle-income countries); and effect of delirium, which can subsequently affect cognitive function, and the effect of follow-up services may differ for these participants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL on 7 November 2017. We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomised and non-randomised studies with adult participants, who had been discharged from hospital following an ICU stay. We included studies that compared an ICU follow-up service using a structured programme and co-ordinated by a healthcare professional versus no follow-up service or standard care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included five studies (four randomised studies; one non-randomised study), for a total of 1707 participants who were ICU survivors with a range of illness severities and conditions. Follow-up services were led by nurses in four studies or a multidisciplinary team in one study. They included face-to-face consultations at home or in a clinic, or telephone consultations or both. Each study included at least one consultation (weekly, monthly, or six-monthly), and two studies had up to eight consultations. Although the design of follow-up service consultations differed in each study, we noted that each service included assessment of participants' needs with referrals to specialist support if required.It was not feasible to blind healthcare professionals or participants to the intervention and we did not know whether this may have introduced performance bias. We noted baseline differences (two studies), and services included additional resources (two studies), which may have influenced results, and one non-randomised study had high risk of selection bias.We did not combine data from randomised studies with data from one non-randomised study. Follow-up services for improving long-term outcomes in ICU survivors may make little or no difference to HRQoL at 12 months (standardised mean difference (SMD) -0.0, 95% confidence interval (CI) -0.1 to 0.1; 1 study; 286 participants; low-certainty evidence). We found moderate-certainty evidence from five studies that they probably also make little or no difference to all-cause mortality up to 12 months after ICU discharge (RR 0.96, 95% CI 0.76 to 1.22; 4 studies; 1289 participants; and in one non-randomised study 79/259 deaths in the intervention group, and 46/151 in the control group) and low-certainty evidence from four studies that they may make little or no difference to PTSD (SMD -0.05, 95% CI -0.19 to 0.10, 703 participants, 3 studies; and one non-randomised study reported less chance of PTSD when a follow-up service was used).It is uncertain whether using a follow-up service reduces depression and anxiety (3 studies; 843 participants), physical function (4 studies; 1297 participants), cognitive function (4 studies; 1297 participants), or increases the ability to return to work or education (1 study; 386 participants), because the certainty of this evidence is very low. No studies measured adverse effects.We could not assess our secondary objectives because we found insufficient studies to justify subgroup analysis. AUTHORS' CONCLUSIONS: We found insufficient evidence, from a limited number of studies, to determine whether ICU follow-up services are effective in identifying and addressing the unmet health needs of ICU survivors. We found five ongoing studies which are not included in this review; these ongoing studies may increase our certainty in the effect in future updates. Because of limited data, we were unable to explore whether one design of follow-up service is preferable to another, or whether a service is more effective for some people than others, and we anticipate that future studies may also vary in design. We propose that future studies are designed with robust methods (for example randomised studies are preferable) and consider only one variable (the follow-up service) compared to standard care; this would increase confidence that the effect is due to the follow-up service rather than concomitant therapies.

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

BACKGROUND: 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 handsearched 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.

Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery.

BACKGROUND: The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced awareness of the environment and a disturbance in attention, typically occurs between 24 and 72 hours after surgery and can affect up to 60% of elderly surgical patients. Postoperative cognitive dysfunction (POCD) is a new-onset of cognitive impairment which may persist for weeks or months after surgery.Traditionally, surgical anaesthesia has been maintained with inhalational agents. End-tidal concentrations require adjustment to balance the risks of accidental awareness and excessive dosing in elderly people. As an alternative, propofol-based total intravenous anaesthesia (TIVA) offers a more rapid recovery and reduces postoperative nausea and vomiting. Using TIVA with a target controlled infusion (TCI) allows plasma and effect-site concentrations to be calculated using an algorithm based on age, gender, weight and height of the patient.TIVA is a viable alternative to inhalational maintenance agents for surgical anaesthesia in elderly people. However, in terms of postoperative cognitive outcomes, the optimal technique is unknown. OBJECTIVES: To compare maintenance of general anaesthesia for elderly people undergoing non-cardiac surgery using propofol-based TIVA or inhalational anaesthesia on postoperative cognitive function, mortality, risk of hypotension, length of stay in the postanaesthesia care unit (PACU), and hospital stay. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE (1946 to November 2017), Embase (1974 to November 2017), PsycINFO (1887 to November 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized controlled trials (RCTs) with participants over 60 years of age scheduled for non-cardiac surgery under general anaesthesia. We planned to also include quasi-randomized trials. We compared maintenance of anaesthesia with propofol-based TIVA versus inhalational maintenance of anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings. MAIN RESULTS: We included 28 RCTs with 4507 randomized participants undergoing different types of surgery (predominantly cardiovascular, laparoscopic, abdominal, orthopaedic and ophthalmic procedures). We found no quasi-randomized trials. Four studies are awaiting classification because we had insufficient information to assess eligibility.All studies compared maintenance with propofol-based TIVA versus inhalational maintenance of anaesthesia. Six studies were multi-arm and included additional TIVA groups, additional inhalational maintenance or both. Inhalational maintenance agents included sevoflurane (19 studies), isoflurane (eight studies), and desflurane (three studies), and was not specified in one study (reported as an abstract). Some studies also reported use of epidural analgesia/anaesthesia, fentanyl and remifentanil.We found insufficient reporting of randomization methods in many studies and all studies were at high risk of performance bias because it was not feasible to blind anaesthetists to study groups. Thirteen studies described blinding of outcome assessors. Three studies had a high of risk of attrition bias, and we noted differences in the use of analgesics between groups in six studies, and differences in baseline characteristics in five studies. Few studies reported clinical trials registration, which prevented assessment of risk of selective reporting bias.We found no evidence of a difference in incidences of postoperative delirium according to type of anaesthetic maintenance agents (odds ratio (OR) 0.59, 95% confidence interval (CI) 0.15 to 2.26; 321 participants; five studies; very low-certainty evidence); we noted during sensitivity analysis that using different time points in one study may influence direction of this result. Thirteen studies (3215 participants) reported POCD, and of these, six studies reported data that could not be pooled; we noted no difference in scores of POCD in four of these and in one study, data were at a time point incomparable to other studies. We excluded one large study from meta-analysis because study investigators had used non-standard anaesthetic management and this study was not methodologically comparable to other studies. We combined data for seven studies and found low-certainty evidence that TIVA may reduce POCD (OR 0.52, 95% CI 0.31 to 0.87; 869 participants).We found no evidence of a difference in mortality at 30 days (OR 1.21, 95% CI 0.33 to 4.45; 271 participants; three studies; very low-certainty evidence). Twelve studies reported intraoperative hypotension. We did not perform meta-analysis for 11 studies for this outcome. We noted visual inconsistencies in these data, which may be explained by possible variation in clinical management and medication used to manage hypotension in each study (downgraded to low-certainty evidence); one study reported data in a format that could not be combined and we noted little or no difference between groups in intraoperative hypotension for this study. Eight studies reported length of stay in the PACU, and we did not perform meta-analysis for seven studies. We noted visual inconsistencies in these data, which may be explained by possible differences in definition of time points for this outcome (downgraded to very low-certainty evidence); data were unclearly reported in one study. We found no evidence of a difference in length of hospital stay according to type of anaesthetic maintenance agent (mean difference (MD) 0 days, 95% CI -1.32 to 1.32; 175 participants; four studies; very low-certainty evidence).We used the GRADE approach to downgrade the certainty of the evidence for each outcome. Reasons for downgrading included: study limitations, because some included studies insufficiently reported randomization methods, had high attrition bias, or high risk of selective reporting bias; imprecision, because we found few studies; inconsistency, because we noted heterogeneity across studies. AUTHORS' CONCLUSIONS: We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes.

Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery.

BACKGROUND: Antiplatelet agents are recommended for people with myocardial infarction and acute coronary syndromes, transient ischaemic attack or stroke, and for those in whom coronary stents have been inserted. People who take antiplatelet agents are at increased risk of adverse events when undergoing non-cardiac surgery because of these indications. However, taking antiplatelet therapy also introduces risk to the person undergoing surgery because the likelihood of bleeding is increased. Discontinuing antiplatelet therapy before surgery might reduce this risk but subsequently it might make thrombotic problems, such as myocardial infarction, more likely. OBJECTIVES: To compare the effects of continuation versus discontinuation for at least five days of antiplatelet therapy on the occurrence of bleeding and ischaemic events in adults undergoing non-cardiac surgery under general, spinal or regional anaesthesia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE (1946 to January 2018), and Embase (1974 to January 2018). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized controlled trials of adults who were taking single or dual antiplatelet therapy, for at least two weeks, and were scheduled for elective non-cardiac surgery. Included participants had at least one cardiac risk factor. We planned to include quasi-randomized studies.We excluded people scheduled for minor surgeries under local anaesthetic or sedation in which bleeding that required transfusion or additional surgery was unlikely. We included studies which compared perioperative continuation of antiplatelet therapy versus discontinuation of antiplatelet therapy or versus substitution of antiplatelet therapy with a placebo for at least five days before surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. Our primary outcomes were: all-cause mortality at longest follow-up (up to six months); all-cause mortality (up to 30 days). Secondary outcomes included: blood loss requiring transfusion of blood products; blood loss requiring further surgical intervention; risk of ischaemic events. We used GRADE to assess the quality of evidence for each outcome MAIN RESULTS: We included five RCTs with 666 randomized adults. We identified three ongoing studies.All study participants were scheduled for elective general surgery (including abdominal, urological, orthopaedic and gynaecological surgery) under general, spinal or regional anaesthesia. Studies compared continuation of single or dual antiplatelet therapy (aspirin or clopidogrel) with discontinuation of therapy for at least five days before surgery.Three studies reported adequate methods of randomization, and two reported methods to conceal allocation. Three studies were placebo-controlled trials and were at low risk of performance bias, and three studies reported adequate methods to blind outcome assessors to group allocation. Attrition was limited in four studies and two studies had reported prospective registration with clinical trial registers and were at low risk of selective outcome reporting bias.We reported mortality at two time points: the longest follow-up reported by study authors up to six months, and time point reported by study authors up to 30 days. Five studies reported mortality up to six months (of which four studies had a longest follow-up at 30 days, and one study at 90 days) and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality up to six months (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.34 to 4.27; 659 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from eight fewer to 40 more). Combining the four studies with a longest follow-up at 30 days alone showed the same effect estimate, and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality at 30 days after surgery (RR 1.21, 95% CI 0.34 to 4.27; 616 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from nine fewer to 42 more).We found that either continuation or discontinuation of antiplatelet therapy probably makes little or no difference in incidences of blood loss requiring transfusion (RR 1.37, 95% CI 0.83 to 2.26; 368 participants; absolute effect of 42 more participants per 1000 requiring transfusion in the continuation group, ranging from 19 fewer to 119 more; four studies; moderate-certainty evidence); and may make little or no difference in incidences of blood loss requiring additional surgery (RR 1.54, 95% CI 0.31 to 7.58; 368 participants; absolute effect of six more participants per 1000 requiring additional surgery in the continuation group, ranging from seven fewer to 71 more; four studies; low-certainty evidence). We found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to incidences of ischaemic events (to include peripheral ischaemia, cerebral infarction, and myocardial infarction) within 30 days of surgery (RR 0.67, 95% CI 0.25 to 1.77; 616 participants; absolute effect of 17 fewer participants per 1000 with an ischaemic event in the continuation group, ranging from 39 fewer to 40 more; four studies; low-certainty evidence).We used the GRADE approach to downgrade evidence for all outcomes owing to limited evidence from few studies. We noted a wide confidence in effect estimates for mortality at the end of follow-up and at 30 days, and for blood loss requiring transfusion which suggested imprecision. We noted visual differences in study results for ischaemic events which suggested inconsistency. AUTHORS' CONCLUSIONS: We found low-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery may make little or no difference to mortality, bleeding requiring surgical intervention, or ischaemic events. We found moderate-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery probably makes little or no difference to bleeding requiring transfusion. Evidence was limited to few studies with few participants, and with few events. The three ongoing studies may alter the conclusions of the review once published and assessed.

Enteral versus parenteral nutrition and enteral versus a combination of enteral and parenteral nutrition for adults in the intensive care unit.

BACKGROUND: Critically ill people are at increased risk of malnutrition. Acute and chronic illness, trauma and inflammation induce stress-related catabolism, and drug-induced adverse effects may reduce appetite or increase nausea and vomiting. In addition, patient management in the intensive care unit (ICU) may also interrupt feeding routines. Methods to deliver nutritional requirements include provision of enteral nutrition (EN), or parenteral nutrition (PN), or a combination of both (EN and PN). However, each method is problematic. This review aimed to determine the route of delivery that optimizes uptake of nutrition. OBJECTIVES: To compare the effects of enteral versus parenteral methods of nutrition, and the effects of enteral versus a combination of enteral and parenteral methods of nutrition, among critically ill adults, in terms of mortality, number of ICU-free days up to day 28, and adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase on 3 October 2017. We searched clinical trials registries and grey literature, and handsearched reference lists of included studies and related reviews. SELECTION CRITERIA: We included randomized controlled studies (RCTs) and quasi-randomized studies comparing EN given to adults in the ICU versus PN or versus EN and PN. We included participants that were trauma, emergency, and postsurgical patients in the ICU. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 25 studies with 8816 participants; 23 studies were RCTs and two were quasi-randomized studies. All included participants were critically ill in the ICU with a wide range of diagnoses; mechanical ventilation status between study participants varied. We identified 11 studies awaiting classification for which we were unable to assess eligibility, and two ongoing studies.Seventeen studies compared EN versus PN, six compared EN versus EN and PN, two were multi-arm studies comparing EN versus PN versus EN and PN. Most studies reported randomization and allocation concealment inadequately. Most studies reported no methods to blind personnel or outcome assessors to nutrition groups; one study used adequate methods to reduce risk of performance bias.Enteral nutrition versus parenteral nutritionWe found that one feeding route rather than the other (EN or PN) may make little or no difference to mortality in hospital (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.80 to 1.77; 361 participants; 6 studies; low-certainty evidence), or mortality within 30 days (RR 1.02, 95% CI 0.92 to 1.13; 3148 participants; 11 studies; low-certainty evidence). It is uncertain whether one feeding route rather than the other reduces mortality within 90 days because the certainty of the evidence is very low (RR 1.06, 95% CI 0.95 to 1.17; 2461 participants; 3 studies). One study reported mortality at one to four months and we did not combine this in the analysis; we reported this data as mortality within 180 days and it is uncertain whether EN or PN affects the number of deaths within 180 days because the certainty of the evidence is very low (RR 0.33, 95% CI 0.04 to 2.97; 46 participants).No studies reported number of ICU-free days up to day 28, and one study reported number of ventilator-free days up to day 28 and it is uncertain whether one feeding route rather than the other reduces the number of ventilator-free days up to day 28 because the certainty of the evidence is very low (mean difference, inverse variance, 0.00, 95% CI -0.97 to 0.97; 2388 participants).We combined data for adverse events reported by more than one study. It is uncertain whether EN or PN affects aspiration because the certainty of the evidence is very low (RR 1.53, 95% CI 0.46 to 5.03; 2437 participants; 2 studies), and we found that one feeding route rather than the other may make little or no difference to pneumonia (RR 1.10, 95% CI 0.82 to 1.48; 415 participants; 7 studies; low-certainty evidence). We found that EN may reduce sepsis (RR 0.59, 95% CI 0.37 to 0.95; 361 participants; 7 studies; low-certainty evidence), and it is uncertain whether PN reduces vomiting because the certainty of the evidence is very low (RR 3.42, 95% CI 1.15 to 10.16; 2525 participants; 3 studies).Enteral nutrition versus enteral nutrition and parenteral nutritionWe found that one feeding regimen rather than another (EN or combined EN or PN) may make little or no difference to mortality in hospital (RR 0.99, 95% CI 0.84 to 1.16; 5111 participants; 5 studies; low-certainty evidence), and at 90 days (RR 1.00, 95% CI 0.86 to 1.18; 4760 participants; 2 studies; low-certainty evidence). It is uncertain whether combined EN and PN leads to fewer deaths at 30 days because the certainty of the evidence is very low (RR 1.64, 95% CI 1.06 to 2.54; 409 participants; 3 studies). It is uncertain whether one feeding regimen rather than another reduces mortality within 180 days because the certainty of the evidence is very low (RR 1.00, 95% CI 0.65 to 1.55; 120 participants; 1 study).No studies reported number of ICU-free days or ventilator-free days up to day 28. It is uncertain whether either feeding method reduces pneumonia because the certainty of the evidence is very low (RR 1.40, 95% CI 0.91 to 2.15; 205 participants; 2 studies). No studies reported aspiration, sepsis, or vomiting. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether EN is better or worse than PN, or than combined EN and PN for mortality in hospital, at 90 days and at 180 days, and on the number of ventilator-free days and adverse events. We found fewer deaths at 30 days when studies gave combined EN and PN, and reduced sepsis for EN rather than PN. We found no studies that reported number of ICU-free days up to day 28. Certainty of the evidence for all outcomes is either low or very low. The 11 studies awaiting classification may alter the conclusions of the review once assessed.

Melatonin for the promotion of sleep in adults in the intensive care unit.

BACKGROUND: Patients in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and patients perceive the quality of their sleep to be poor whilst in the ICU. Artificial lighting during night-time hours in the ICU may contribute to reduced production of melatonin in critically ill patients. Melatonin is known to have a direct effect on the circadian rhythm, and it appears to reset a natural rhythm, thus promoting sleep. OBJECTIVES: To assess whether the quantity and quality of sleep may be improved by administration of melatonin to adults in the intensive care unit. To assess whether melatonin given for sleep promotion improves both physical and psychological patient outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE (1946 to September 2017), Embase (1974 to September 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to September 2017), and PsycINFO (1806 to September 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials with adult participants (over the age of 16) admitted to the ICU with any diagnoses given melatonin versus a comparator to promote overnight sleep. We included participants who were mechanically ventilated and those who were not mechanically ventilated. We planned to include studies that compared the use of melatonin, given at an appropriate clinical dose with the intention of promoting night-time sleep, against no agent; or against another agent administered specifically to promote sleep. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings. We assessed the quality of evidence with GRADE. MAIN RESULTS: We included four studies with 151 randomized participants. Two studies included participants who were mechanically ventilated, one study included a mix of ventilated and non-ventilated participants and in one study participants were being weaned from mechanical ventilation. Three studies reported admission diagnoses, which varied: these included sepsis, pneumonia and cardiac or cardiorespiratory arrest. All studies compared melatonin against no agent; three were placebo-controlled trials; and one compared melatonin with usual care. All studies administered melatonin in the evening.All studies reported adequate methods for randomization and placebo-controlled trials were blinded at the participant and personnel level. We noted high risk of attrition bias in one study and were unclear about potential bias introduced in two studies with differences between participants at baseline.It was not appropriate to combine data owing to differences in measurement tools, or methods used to report data.The effects of melatonin on subjectively rated quantity and quality of sleep are uncertain (very low certainty evidence). Three studies (139 participants) reported quantity and quality of sleep as measured through reports of participants or family members or by personnel assessments. Study authors in one study reported no difference in sleep efficiency index scores between groups for participant assessment (using Richards-Campbell Sleep Questionnaire) and nurse assessment. Two studies reported no difference in duration of sleep observed by nurses.The effects of melatonin on objectively measured quantity and quality of sleep are uncertain (very low certainty evidence). Two studies (37 participants) reported quantity and quality of sleep as measured by polysomnography (PSG), actigraphy, bispectral index (BIS) or electroencephalogram (EEG). Study authors in one study reported no difference in sleep efficiency index scores between groups using BIS and actigraphy. These authors also reported longer sleep in participants given melatonin which was not statistically significant, and improved sleep (described as "better sleep") in participants given melatonin from analysis of area under the curve (AUC) of BIS data. One study used PSG but authors were unable to report data because of a large loss of participant data.One study (82 participants) reported no evidence of a difference in anxiety scores (very low certainty evidence). Two studies (94 participants) reported data for mortality: one study reported that overall one-third of participants died; and one study reported no evidence of difference between groups in hospital mortality (very low certainty). One study (82 participants) reported no evidence of a difference in length of ICU stay (very low certainty evidence). Effects of melatonin on adverse events were reported in two studies (107 participants), and are uncertain (very low certainty evidence): one study reported headache in one participant given melatonin, and one study reported excessive sleepiness in one participant given melatonin and two events in the control group (skin reaction in one participant, and excessive sleepiness in another participant).The certainty of the evidence for each outcome was limited by sparse data with few participants. We noted study limitations in some studies due to high attrition and differences between groups in baseline data; and doses of melatonin varied between studies. Methods used to measure data were not consistent for outcomes, and use of some measurement tools may not be effective for use on the ICU patient. All studies included participants in the ICU but we noted differences in ICU protocols, and one included study used a non-standard sedation protocol with participants which introduced indirectness to the evidence. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether administration of melatonin would improve the quality and quantity of sleep in ICU patients. We identified sparse data, and noted differences in study methodology, in ICU sedation protocols, and in methods used to measure and report sleep. We identified five ongoing studies from database and clinical trial register searches. Inclusion of data from these studies in future review updates would provide more certainty for the review outcomes.

Propofol for the promotion of sleep in adults in the intensive care unit.

BACKGROUND: People in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and people perceive the quality of their sleep to be poor whilst in the ICU. Propofol is an anaesthetic agent which can be used in the ICU to maintain patient sedation and some studies suggest it may be a suitable agent to replicate normal sleep. OBJECTIVES: To assess whether the quantity and quality of sleep may be improved by administration of propofol to adults in the ICU and to assess whether propofol given for sleep promotion improves both physical and psychological patient outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 10), MEDLINE (1946 to October 2017), Embase (1974 to October 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to October 2017) and PsycINFO (1806 to October 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials with adults, over the age of 16 years, admitted to the ICU with any diagnoses, given propofol versus a comparator to promote overnight sleep. We included participants who were and were not mechanically ventilated. We included studies that compared the use of propofol, given at an appropriate clinical dose with the intention of promoting night-time sleep, against: no agent; propofol at a different rate or dose; or another agent, administered specifically to promote sleep. We included only studies in which propofol was given during 'normal' sleeping hours (i.e. between 10 pm and 7 am) to promote a sleep-like state with a diurnal rhythm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. MAIN RESULTS: We included four studies with 149 randomized participants. We identified two studies awaiting classification for which we were unable to assess eligibility and one ongoing study.Participants differed in severity of illness as assessed by APACHE II scores in three studies and further differences existed between comparisons and methods. One study compared propofol versus no agent, one study compared different doses of propofol and two studies compared propofol versus a benzodiazepine (flunitrazepam, one study; midazolam, one study). All studies reported randomization and allocation concealment inadequately. We judged all studies to have high risk of performance bias from personnel who were unblinded. We noted that some study authors had blinded study outcome assessors and participants for relevant outcomes.It was not appropriate to combine data owing to high levels of methodological heterogeneity.One study comparing propofol with no agent (13 participants) measured quantity and quality of sleep using polysomnography; study authors reported no evidence of a difference in duration of sleep or sleep efficiency, and reported disruption to usual REM (rapid eye movement sleep) with propofol.One study comparing different doses of propofol (30 participants) measured quantity and quality of sleep by personnel using the Ramsay Sedation Scale; study authors reported that more participants who were given a higher dose of propofol had a successful diurnal rhythm, and achieved a greater sedation rhythmicity.Two studies comparing propofol with a different agent (106 participants) measured quantity and quality of sleep using the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale; one study reported fewer awakenings of reduced duration with propofol, and similar total sleep time between groups, and one study reported no evidence of a difference in sleep quality. One study comparing propofol with another agent (66 participants) measured quantity and quality of sleep with the Bispectral Index and reported longer time in deep sleep, with fewer arousals. One study comparing propofol with another agent (40 participants) reported higher levels of anxiety and depression in both groups, and no evidence of a difference when participants were given propofol.No studies reported adverse events.We used the GRADE approach to downgrade the certainty of the evidence for each outcome to very low. We identified sparse data with few participants, and methodological differences in study designs and comparative agents introduced inconsistency, and we noted that measurement tools were imprecise or not valid for purpose. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether administration of propofol would improve the quality and quantity of sleep in adults in the ICU. We noted differences in study designs, methodology, comparative agents and illness severity amongst study participants. We did not pool data and we used the GRADE approach to downgrade the certainty of our evidence to very low.

Hypothermia for traumatic brain injury.

BACKGROUND: Hypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. OBJECTIVES: To determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long-term functional outcomes and complications. SEARCH METHODS: We ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registers, and screened reference lists. We also re-ran these searches pre-publication in June 2017; the result from this search is presented in 'Studies awaiting classification'. SELECTION CRITERIA: We included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC). DATA COLLECTION AND ANALYSIS: Two review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia. MAIN RESULTS: We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta-analysis. We considered duration of hypothermia therapy and the length of follow-up in collected data for these subgroups; differences in study data remained such that we did not perform meta-analysis.Studies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low. AUTHORS' CONCLUSIONS: Despite a large number studies, there remains no high-quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.

Occupational therapy for adults with problems in activities of daily living after stroke.

BACKGROUND: A stroke occurs when the blood supply to part of the brain is cut off. Activities of daily living (ADL) are daily home-based activities that people carry out to maintain health and well-being. ADLs include the ability to: eat and drink unassisted, move, go to the toilet, carry out personal hygiene tasks, dress unassisted, and groom. Stroke causes impairment-related functional limitations that may result in difficulties participating in ADLs independent of supervision, direction, or physical assistance.For adults with stroke, the goal of occupational therapy is to improve their ability to carry out activities of daily living. Strategies used by occupational therapists include assessment, treatment, adaptive techniques, assistive technology, and environmental adaptations. This is an update of the Cochrane review first published in 2006. OBJECTIVES: To assess the effects of occupational therapy interventions on the functional ability of adults with stroke in the domain of activities of daily living, compared with no intervention or standard care/practice. SEARCH METHODS: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 30 January 2017), the Cochrane Controlled Trials Register (The Cochrane Library, January 2017), MEDLINE (1946 to 5 January 2017), Embase (1974 to 5 January 2017), CINAHL (1937 to January 2017), PsycINFO (1806 to 2 November 2016), AMED (1985 to 1 November 2016), and Web of Science (1900 to 6 January 2017). We also searched grey literature and clinical trials registers. SELECTION CRITERIA: We identified randomised controlled trials of an occupational therapy intervention (compared with no intervention or standard care/practice) where people with stroke practiced activities of daily living, or where performance in activities of daily living was the focus of the occupational therapy intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, and extracted data for prespecified outcomes. The primary outcomes were the proportion of participants who had deteriorated or were dependent in personal activities of daily living and performance in activities of daily living at the end of follow-up. MAIN RESULTS: We included nine studies with 994 participants in this update. Occupational therapy targeted towards activities of daily living after stroke increased performance scores (standardised mean difference (SMD) 0.17, 95% confidence interval (CI) 0.03 to 0.31, P = 0.02; 7 studies; 749 participants; low-quality evidence) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio (OR) 0.71, 95% CI 0.52 to 0.96; P = 0.03; 5 studies; 771 participants; low-quality evidence). We also found that those who received occupational therapy were more independent in extended activities of daily living (OR 0.22 (95% CI 0.07 to 0.37); P = 0.005; 5 studies; 665 participants; low-quality evidence). Occupational therapy did not influence mortality (OR: 1.02 (95% CI 0.65 to 1.61); P = 0.93; 8 studies; 950 participants), or reduce the combined odds of death and institutionalisation (OR 0.89 (95% CI 0.60 to 1.32); P = 0.55; 4 studies; 671 participants), or death and dependency (OR 0.89 (95% CI 0.64 to 1.23); P = 0.47; 4 trials; 659 participants). Occupational therapy did not improve mood or distress scores (OR 0.08 (95% CI -0.09 to 0.26); P = 0.35; 4 studies; 519 participants; low-quality evidence). There were insufficient data to determine the effects of occupational therapy on health-related quality of life. We found no studies of consenting carers prior to study participation and therefore there were no carer-related outcomes in our review. There were insufficient data to determine participants' and carers' satisfaction with services.Using GRADE, the quality of evidence was low. The major limitation was the number of studies at unclear risk of selection bias and an inevitable high risk of performance and detection bias, as both participants and occupational therapists could not be blinded to the intervention. In addition, there was a sparseness of data for our outcomes of interest and we downgraded the quality of our evidence for these reasons. AUTHORS' CONCLUSIONS: We found low-quality evidence that occupational therapy targeted towards activities of daily living after stroke can improve performance in activities of daily living and reduce the risk of deterioration in these abilities. Because the included studies had methodological flaws, this research does not provide a reliable indication of the likely effect of occupational therapy for adults with stroke.