Patient safety practices in European anaesthesiology: Expert evaluation and ranking.

BACKGROUND: Patient safety is a key concern of anaesthesiology practice. However, good practices are often not widely shared between departments and hospitals, whether within or between countries. OBJECTIVE: We aimed to collect and analyse safety practices and tips from anaesthesiology departments around Europe in order to facilitate successful transfer of safety knowledge. DESIGN: Review of previously collected safety practices; allocation of numerical scores in order to rank them on 0-5 scales in terms of anticipated impact, and speed, cost, and ease of implementation; free text comment on any possible difficulties or unintended harms which might arise from adopting any of the collected practices. SETTING: Collaborative remote working of expert group. PARTICIPANTS: Nineteen experts in patient safety in anaesthesiology from nine European countries. MAIN OUTCOME MEASURES: Rankings of safety practices for anticipated practice impact, cost, speed, and ease of implementation. RESULTS: We collected 117 practices. The highest-ranked items for potential beneficial impact were: standardising the layout of drug trolleys (4.82); involving all staff in new safety initiatives in the operating theatre (4.73); ensuring patients' medical records are available at the time of surgery (4.71); running regular simulation training sessions in departments of anaesthesia (4.67); and creating a difficult airway management trolley (4.65). A major theme to emerge from the qualitative analysis of the experts' free text comments was the risk that practices aimed at enhancing patient safety might not achieve the effect intended, as introducing new safety activities can cause more mistakes during the implementation phase. CONCLUSION: Many useful practices to promote patient safety were identified, but as some practices appear to be context-dependent, we recommend that a proper, prospective risk assessment is carried out before they are introduced in a new setting. The full list of items is available online as Supplementary Digital Content, http://links.lww.com/EJA/A785 . TRIAL REGISTRATION: Not applicable.

Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation: a Cochrane systematic review and meta-analysis update.

BACKGROUND: Tracheal intubation is a commonly performed procedure that can be associated with complications and result in patient harm. Videolaryngoscopy (VL) may decrease this risk as compared with Macintosh direct laryngoscopy (DL). This review evaluates the risk and benefit profile of VL compared with DL in adults. METHODS: We searched MEDLINE, Embase, CENTRAL, and Web of Science on February 27, 2021. We included RCTs comparing VL with DL in patients undergoing tracheal intubation in any setting. We separately compared outcomes according to VL design: Macintosh-style, hyperangulated, and channelled. RESULTS: A total of 222 RCTs (with 26 149 participants) were included. Most studies had unclear risk of bias in at least one domain, and all were at high risk of performance and detection bias. We found that videolaryngoscopes of any design likely reduce rates of failed intubation (Macintosh-style: risk ratio [RR]=0.41; 95% confidence interval [CI], 0.26-0.65; hyperangulated: RR=0.51; 95% CI, 0.34-0.76; channelled: RR=0.43, 95% CI, 0.30-0.61; moderate-certainty evidence) with increased rates of successful intubation on first attempt and better glottic views across patient groups and settings. Hyperangulated designs are likely favourable in terms of reducing the rate of oesophageal intubation, and result in improved rates of successful intubation in individuals presenting with difficult airway features (P=0.03). We also present other patient-oriented outcomes. CONCLUSIONS: In this systematic review and meta-analysis of trials of adults undergoing tracheal intubation, VL was associated with fewer failed attempts and complications such as hypoxaemia, whereas glottic views were improved. SYSTEMATIC REVIEW REGISTRATION: This article is based on a Cochrane Review published in the Cochrane Database of Systematic Reviews (CDSR) 2022, Issue 4, DOI: 10.1002/14651858.CD011136.pub3 (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review.

Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation.

BACKGROUND: Tracheal intubation is a common procedure performed to secure the airway in adults undergoing surgery or those who are critically ill. Intubation is sometimes associated with difficulties and complications that may result in patient harm. While it is traditionally achieved by performing direct laryngoscopy, the past three decades have seen the advent of rigid indirect videolaryngoscopes (VLs). A mounting body of evidence comparing the two approaches to tracheal intubation has been acquired over this period of time. This is an update of a Cochrane Review first published in 2016. OBJECTIVES: To assess whether use of different designs of VLs in adults requiring tracheal intubation reduces the failure rate compared with direct laryngoscopy, and assess the benefits and risks of these devices in selected population groups, users and settings. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and Web of Science on 27 February 2021. We also searched clinical trials databases, conference proceedings and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs with adults undergoing laryngoscopy performed with either a VL or a Macintosh direct laryngoscope (DL) in any clinical setting. We included parallel and cross-over study designs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for the following outcomes: failed intubation, hypoxaemia, successful first attempt at tracheal intubation, oesophageal intubation, dental trauma, Cormack-Lehane grade, and time for tracheal intubation. MAIN RESULTS: We included 222 studies (219 RCTs, three quasi-RCTs) with 26,149 participants undergoing tracheal intubation. Most studies recruited adults undergoing elective surgery requiring tracheal intubation. Twenty-one studies recruited participants with a known or predicted difficult airway, and an additional 25 studies simulated a difficult airway. Twenty-one studies were conducted outside the operating theatre environment; of these, six were in the prehospital setting, seven in the emergency department and eight in the intensive care unit.  We report here the findings of the three main comparisons according to videolaryngoscopy device type. We downgraded the certainty of the outcomes for imprecision, study limitations (e.g. high or unclear risks of bias), inconsistency when we noted substantial levels of statistical heterogeneity and publication bias. Macintosh-style videolaryngoscopy versus direct laryngoscopy (61 studies, 9883 participants) We found moderate-certainty evidence that a Macintosh-style VL probably reduces rates of failed intubation (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.26 to 0.65; 41 studies, 4615 participants) and hypoxaemia (RR 0.72, 95% CI 0.52 to 0.99; 16 studies, 2127 participants). These devices may also increase rates of success on the first intubation attempt (RR 1.05, 95% CI 1.02 to 1.09; 42 studies, 7311 participants; low-certainty evidence) and probably improve glottic view when assessed as Cormack-Lehane grade 3 and 4 (RR 0.38, 95% CI 0.29 to 0.48; 38 studies, 4368 participants; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.51, 95% CI 0.22 to 1.21; 14 studies, 2404 participants) but this finding was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of this evidence was very low (RR 0.68, 95% CI 0.16 to 2.89; 18 studies, 2297 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 96%). Hyperangulated videolaryngoscopy versus direct laryngoscopy (96 studies, 11,438 participants) We found moderate-certainty evidence that hyperangulated VLs probably reduce rates of failed intubation (RR 0.51, 95% CI 0.34 to 0.76; 63 studies, 7146 participants) and oesophageal intubation (RR 0.39, 95% CI 0.18 to 0.81; 14 studies, 1968 participants). In subgroup analysis, we noted that hyperangulated VLs were more likely to reduce failed intubation when used on known or predicted difficult airways (RR 0.29, 95% CI 0.17 to 0.48; P = 0.03 for subgroup differences; 15 studies, 1520 participants). We also found that these devices may increase rates of success on the first intubation attempt (RR 1.03, 95% CI 1.00 to 1.05; 66 studies, 8086 participants; low-certainty evidence) and the glottic view is probably also improved (RR 0.15, 95% CI 0.10 to 0.24; 54 studies, 6058 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). However, we found low-certainty evidence of little or no clear difference in rates of hypoxaemia (RR 0.49, 95% CI 0.22 to 1.11; 15 studies, 1691 participants), and the findings for dental trauma were unclear because the certainty of this evidence was very low (RR 0.51, 95% CI 0.16 to 1.59; 30 studies, 3497 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 99%). Channelled videolaryngoscopy versus direct laryngoscopy (73 studies, 7165 participants) We found moderate-certainty evidence that channelled VLs probably reduce rates of failed intubation (RR 0.43, 95% CI 0.30 to 0.61; 53 studies, 5367 participants) and hypoxaemia (RR 0.25, 95% CI 0.12 to 0.50; 15 studies, 1966 participants). They may also increase rates of success on the first intubation attempt (RR 1.10, 95% CI 1.05 to 1.15; 47 studies, 5210 participants; very low-certainty evidence) and probably improve glottic view (RR 0.14, 95% CI 0.09 to 0.21; 40 studies, 3955 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.54, 95% CI 0.17 to 1.75; 16 studies, 1756 participants) but this was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of the evidence was very low (RR 0.52, 95% CI 0.13 to 2.12; 29 studies, 2375 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 98%). AUTHORS' CONCLUSIONS: VLs of all designs likely reduce rates of failed intubation and result in higher rates of successful intubation on the first attempt with improved glottic views. Macintosh-style and channelled VLs likely reduce rates of hypoxaemic events, while hyperangulated VLs probably reduce rates of oesophageal intubation. We conclude that videolaryngoscopy likely provides a safer risk profile compared to direct laryngoscopy for all adults undergoing tracheal intubation.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. OBJECTIVES: To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. AUTHORS' CONCLUSIONS: HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.

ANTECEDENTES: Las cánulas nasales de alto flujo (HFNC) administran flujos elevados de una mezcla humedecida de aire y oxígeno a través de cánulas nasales de gran calibre y pueden ser útiles para proporcionar asistencia respiratoria a los adultos que presentan insuficiencia respiratoria aguda, o que tienen riesgo de presentarla, en la unidad de cuidados intensivos (UCI). Esta es una actualización de una versión anterior de la revisión. OBJETIVOS: Evaluar la eficacia de las HFNC en comparación con la oxigenoterapia estándar, o la ventilación no invasiva (VNI) o la ventilación con presión positiva no invasiva (VPPNI), para la asistencia respiratoria de adultos en la UCI. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, Web of Science y en el Registro Cochrane de covid­19 (17 de abril de 2020), registros de ensayos clínicos (6 de abril de 2020) y se realizaron búsquedas de citas prospectivas y retrospectivas. CRITERIOS DE SELECCIÓN: Se incluyeron los estudios controlados aleatorizados (ECA) con un diseño de grupos paralelos o cruzados que compararon el uso de HFNC versus otro tipo de asistencia respiratoria no invasiva (oxigenoterapia estándar a través de cánulas nasales o mascarilla; o VNI o VPPNI que incluía la presión positiva continua en las vías respiratorias y la presión positiva de dos niveles en las vías respiratorias) en adultos ingresados en la UCI. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane. RESULTADOS PRINCIPALES: Se incluyeron 31 estudios (22 de grupos paralelos y nueve de diseño cruzado) con 5136 participantes; esta actualización incluyó 20 estudios nuevos. Veintiún estudios compararon la HFNC con la oxigenoterapia estándar, y 13 compararon la HFNC con la VNI o la VPPNI; tres estudios incluyeron ambas comparaciones. Se encontraron 51 estudios en curso (con una estimación de 12 807 participantes) y 19 estudios en espera de clasificación en los que no fue posible determinar la información de elegibilidad del estudio. En 18 estudios el tratamiento se inició después de la extubación. En el resto de los estudios, los participantes no habían recibido de forma previa ventilación mecánica. HFNC versus oxigenoterapia estándar La HFNC podría conducir a un menor fracaso del tratamiento, según lo indicado por el escalamiento a tipos alternativos de oxigenoterapia (razón de riesgos [RR] 0,62; intervalo de confianza [IC] del 95%: 0,45 a 0,86; 15 estudios, 3044 participantes; evidencia de certeza baja). La HFNC probablemente da lugar a poca o ninguna diferencia en la mortalidad cuando se compara con la oxigenoterapia estándar (RR 0,96; IC del 95%: 0,82 a 1,11; 11 estudios, 2673 participantes; evidencia de certeza moderada). La HFNC probablemente da lugar a poca o ninguna diferencia con respecto a los casos de neumonía (RR 0,72; IC del 95%: 0,48 a 1,09; cuatro estudios, 1057 participantes; evidencia de certeza moderada), y no se sabe con certeza su efecto sobre la mucosa nasal ni el traumatismo cutáneo (RR 3,66; IC del 95%: 0,43 a 31,48; dos estudios, 617 participantes; evidencia de certeza muy baja). Se encontró evidencia de certeza baja de que la HFNC podría dar lugar a poca o ninguna diferencia en la duración de la estancia en la UCI según el tipo de asistencia respiratoria utilizada (DM 0,12 días; IC del 95%: ­0,03 a 0,27; siete estudios, 1014 participantes). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en el cociente entre la presión parcial de oxígeno arterial y la fracción de oxígeno inspirado (PaO2/FiO2) en las primeras 24 horas del tratamiento (DM 10,34 mmHg; IC del 95%: ­17,31 a 38; cinco estudios, 600 participantes; evidencia de certeza muy baja). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en la comodidad a corto plazo (DM 0,31; IC del 95%: ­0,60 a 1,22; cuatro estudios, 662 participantes, evidencia de certeza muy baja), o en la comodidad a largo plazo (DM 0,59; IC del 95%: ­2,29 a 3,47; dos estudios, 445 participantes, evidencia de certeza muy baja). HFNC versus VNI o VPPNI No se encontró evidencia de una diferencia entre los grupos en el fracaso del tratamiento cuando se utilizó la HFNC después de la extubación o sin el uso previo de ventilación mecánica (RR 0,98; IC del 95%: 0,78 a 1,22; cinco estudios, 1758 participantes; evidencia de certeza baja), ni en la mortalidad hospitalaria (RR 0,92; IC del 95%: 0,64 a 1,31; cinco estudios, 1758 participantes; evidencia de certeza baja). No hay certeza sobre el efecto del uso de la HFNC en la incidencia de la neumonía (RR 0,51; IC del 95%: 0,17 a 1,52; tres estudios, 1750 participantes; evidencia de certeza muy baja), y la HFNC podría dar lugar a poca o ninguna diferencia en el barotraumatismo (RR 1,15; IC del 95%: 0,42 a 3,14; un estudio, 830 participantes; evidencia de certeza baja). La HFNC podría suponer una diferencia escasa o nula en la duración de la estancia en la UCI (DM ­0,72 días; IC del 95%: ­2,85 a 1,42; dos estudios, 246 participantes; evidencia de certeza baja). El cociente PaO2/FiO2 podría ser menor hasta 24 horas con el uso de la HFNC (DM ­58,10 mmHg; IC del 95%: ­71,68 a ­44,51; tres estudios, 1086 participantes; evidencia de certeza baja). No se sabe si la HFNC mejoró la comodidad a corto plazo cuando se midió mediante puntuaciones de comodidad (DM 1,33; IC del 95%: 0,74 a 1,92; dos estudios, 258 participantes) y respuestas a cuestionarios (RR 1,30; IC del 95%: 1,10 a 1,53; un estudio, 168 participantes); la evidencia para la comodidad a corto plazo fue de certeza muy baja. Ningún estudio informó sobre la mucosa nasal ni el traumatismo cutáneo. CONCLUSIONES DE LOS AUTORES: La HFNC podría dar lugar a un menor fracaso del tratamiento en comparación con la oxigenoterapia estándar, pero probablemente suponga una escasa o nula diferencia en el fracaso del tratamiento en comparación con la VNI o la VPPNI. Para la mayoría de los demás desenlaces de la revisión, no se encontró evidencia de una diferencia en el efecto. Sin embargo, la certeza de la evidencia se consideró baja o muy baja. Se encontró un gran número de estudios en curso; incluirlos en futuras actualizaciones podría aumentar la certeza o podría alterar la dirección de estos efectos.

Oxygen targets in the intensive care unit during mechanical ventilation for acute respiratory distress syndrome: a rapid review.

BACKGROUND: Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required. OBJECTIVES: To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs). SELECTION CRITERIA: Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask. DATA COLLECTION AND ANALYSIS: One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy. MAIN RESULTS: We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported. AUTHORS' CONCLUSIONS: We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.

Ten years of the Helsinki Declaration on patient safety in anaesthesiology: An expert opinion on peri-operative safety aspects.

: Patient safety is an activity to mitigate preventable patient harm that may occur during the delivery of medical care. The European Board of Anaesthesiology (EBA)/European Union of Medical Specialists had previously published safety recommendations on minimal monitoring and postanaesthesia care, but with the growing public and professional interest it was decided to produce a much more encompassing document. The EBA and the European Society of Anaesthesiology (ESA) published a consensus on what needs to be done/achieved for improvement of peri-operative patient safety. During the Euroanaesthesia meeting in Helsinki/Finland in 2010, this vision was presented to anaesthesiologists, patients, industry and others involved in health care as the 'Helsinki Declaration on Patient Safety in Anaesthesiology'. In May/June 2020, ESA and EBA are celebrating the 10th anniversary of the Helsinki Declaration on Patient Safety in Anaesthesiology; a good opportunity to look back and forward evaluating what was achieved in the recent 10 years, and what needs to be done in the upcoming years. The Patient Safety and Quality Committee (PSQC) of ESA invited experts in their fields to contribute, and these experts addressed their topic in different ways; there are classical, narrative reviews, more systematic reviews, political statements, personal opinions and also original data presentation. With this publication we hope to further stimulate implementation of the Helsinki Declaration on Patient Safety in Anaesthesiology, as well as initiating relevant research in the future.

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.

Pharmacological agents for adults with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by direct or indirect injury to the lungs. Despite improvements in clinical management (for example, lung protection strategies), mortality in this patient group is at approximately 40%. This is an update of a previous version of this review, last published in 2004. OBJECTIVES: To evaluate the effectiveness of pharmacological agents in adults with ARDS on mortality, mechanical ventilation, and fitness to return to work at 12 months. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and CINAHL on 10 December 2018. We searched clinical trials registers and grey literature, and handsearched reference lists of included studies and related reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing pharmacological agents with control (placebo or standard therapy) to treat adults with established ARDS. We excluded trials of nitric oxide, inhaled prostacyclins, partial liquid ventilation, neuromuscular blocking agents, fluid and nutritional interventions and medical oxygen. We excluded studies published earlier than 2000, because of changes to lung protection strategies for people with ARDS since this date. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 48 RCTs with 6299 participants who had ARDS; two included only participants with mild ARDS (also called acute lung injury). Most studies included causes of ARDS that were both direct and indirect injuries. We noted differences between studies, for example the time of administration or the size of dose, and because of unclear reporting we were uncertain whether all studies had used equivalent lung protection strategies.We included five types of agents as the primary comparisons in the review: corticosteroids, surfactants, N-acetylcysteine, statins, and beta-agonists. We included 15 additional agents (sivelestat, mesenchymal stem cells, ulinastatin, anisodimine, angiotensin-converting enzyme (ACE) inhibitor, recombinant human ACE2 (palifermin), AP301, granulocyte-macrophage colony stimulating factor (GM-CSF), levosimendan, prostacyclins, lisofylline, ketaconazole, nitroglycerins, L-2-oxothiazolidine-4-carboxylic acid (OTZ), and penehyclidine hydrochloride).We used GRADE to downgrade outcomes for imprecision (because of few studies and few participants), for study limitations (e.g. high risks of bias) and for inconsistency (e.g. differences between study data).Corticosteroids versus placebo or standard therapyCorticosteroids may reduce all-cause mortality within three months by 86 per 1000 patients (with as many as 161 fewer to 19 more deaths); however, the 95% confidence interval (CI) includes the possibility of both increased and reduced deaths (risk ratio (RR) 0.77, 95% CI 0.57 to 1.05; 6 studies, 574 participants; low-certainty evidence). Due to the very low-certainty evidence, we are uncertain whether corticosteroids make little or no difference to late all-cause mortality (later than three months) (RR 0.99, 95% CI 0.64 to 1.52; 1 study, 180 participants), or to the duration of mechanical ventilation (mean difference (MD) -4.30, 95% CI -9.72 to 1.12; 3 studies, 277 participants). We found that ventilator-free days up to day 28 (VFD) may be improved with corticosteroids (MD 4.09, 95% CI 1.74 to 6.44; 4 studies, 494 participants; low-certainty evidence). No studies reported adverse events leading to discontinuation of study medication, or fitness to return to work at 12 months (FTR).Surfactants versus placebo or standard therapyWe are uncertain whether surfactants make little or no difference to early mortality (RR 1.08, 95% CI 0.91 to 1.29; 9 studies, 1338 participants), or whether they reduce late all-cause mortality (RR 1.28, 95% CI 1.01 to 1.61; 1 study, 418 participants). Similarly, we are uncertain whether surfactants reduce the duration of mechanical ventilation (MD -2.50, 95% CI -4.95 to -0.05; 1 study, 16 participants), make little or no difference to VFD (MD -0.39, 95% CI -2.49 to 1.72; 2 studies, 344 participants), or to adverse events leading to discontinuation of study medication (RR 0.50, 95% CI 0.17 to 1.44; 2 studies, 88 participants). We are uncertain of these effects because we assessed them as very low-certainty. No studies reported FTR.N-aceytylcysteine versus placeboWe are uncertain whether N-acetylcysteine makes little or no difference to early mortality, because we assessed this as very low-certainty evidence (RR 0.64, 95% CI 0.32 to 1.30; 1 study, 36 participants). No studies reported late all-cause mortality, duration of mechanical ventilation, VFD, adverse events leading to study drug discontinuation, or FTR.Statins versus placeboStatins probably make little or no difference to early mortality (RR 0.99, 95% CI 0.78 to 1.26; 3 studies, 1344 participants; moderate-certainty evidence) or to VFD (MD 0.40, 95% CI -0.71 to 1.52; 3 studies, 1342 participants; moderate-certainty evidence). Statins may make little or no difference to duration of mechanical ventilation (MD 2.70, 95% CI -3.55 to 8.95; 1 study, 60 participants; low-certainty evidence). We could not include data for adverse events leading to study drug discontinuation in one study because it was unclearly reported. No studies reported late all-cause mortality or FTR.Beta-agonists versus placebo controlBeta-blockers probably slightly increase early mortality by 40 per 1000 patients (with as many as 119 more or 25 fewer deaths); however, the 95% CI includes the possibility of an increase as well as a reduction in mortality (RR 1.14, 95% CI 0.91 to 1.42; 3 studies, 646 participants; moderate-certainty evidence). Due to the very low-certainty evidence, we are uncertain whether beta-agonists increase VFD (MD -2.20, 95% CI -3.68 to -0.71; 3 studies, 646 participants), or make little or no difference to adverse events leading to study drug discontinuation (one study reported little or no difference between groups, and one study reported more events in the beta-agonist group). No studies reported late all-cause mortality, duration of mechanical ventilation, or FTR. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine with certainty whether corticosteroids, surfactants, N-acetylcysteine, statins, or beta-agonists were effective at reducing mortality in people with ARDS, or duration of mechanical ventilation, or increasing ventilator-free days. Three studies awaiting classification may alter the conclusions of this review. As the potential long-term consequences of ARDS are important to survivors, future research should incorporate a longer follow-up to measure the impacts on quality of life.

Patient safety and the role of the Helsinki Declaration on Patient Safety in Anaesthesiology: A European survey.

BACKGROUND: The Helsinki Declaration on Patient Safety was launched in 2010 by the European Society of Anaesthesiology and the European Board of Anaesthesiology. It is not clear how widely its vision and standards have been adopted. OBJECTIVE: To explore the role of the Helsinki Declaration in promoting and maintaining patient safety in European anaesthesiology. DESIGN: Online survey. SETTING: A total of 38 countries within Europe. PARTICIPANTS: Members of the European Society of Anaesthesiology who responded to an invitation to take part by electronic mail. MAIN OUTCOME MEASURES: Responses from a 16-item online survey to explore each member anaesthesiologist's understanding of the Declaration and compliance with its standards. RESULTS: We received 1589 responses (33.4% response rate), with members from all countries responding. The median [IQR] response rate of members was 20.5% [11.7 to 37.0] per country. There were many commonalities across Europe. There were very high levels of use of monitoring (pulse oximetry: 99.6%, blood pressure: 99.4%; ECG: 98.1% and capnography: 96.0%). Protocols and guidelines were also widely used, with those for pre-operative assessment, and difficult and failed intubation being particularly popular (mentioned by 93.4% and 88.9% of respondents, respectively). There was evidence of widespread use of the WHO Safe Surgery checklist, with only 93 respondents (6.0%) suggesting that they never used it. Annual reports of measures taken to improve patient safety, and of morbidity and mortality, were produced in the hospitals of 588 (37.3%) and 876 (55.7%) respondents, respectively. Around three-quarters of respondents, 1216, (78.7%) stated that their hospital used a critical incident reporting system. Respondents suggested that measures to promote implementation of the Declaration, such as a formal set of checklist items for day-to-day practice, publicity, translation and simulation training, would currently be more important than possible changes to its content. CONCLUSION: Many patient safety practices encouraged by the Declaration are well embedded in many European countries. The data have highlighted areas where there is still room for improvement.

Automated tools for comparative sequence analysis of genic regions using the GenePalette application.

Comparative sequence analysis methods, such as phylogenetic footprinting, represent one of the most effective ways to decode regulatory sequence functions based upon DNA sequence information alone. The laborious task of assembling orthologous sequences to perform these comparisons is a hurdle to these analyses, which is further aggravated by the relative paucity of tools for visualization of sequence comparisons in large genic regions. Here, we describe a second-generation implementation of the GenePalette DNA sequence analysis software to facilitate comparative studies of gene function and regulation. We have developed an automated module called OrthologGrabber (OG) that performs BLAT searches against the UC Santa Cruz genome database to identify and retrieve segments homologous to a region of interest. Upon acquisition, sequences are compared to identify high-confidence anchor-points, which are graphically displayed. The visualization of anchor-points alongside other DNA features, such as transcription factor binding sites, allows users to precisely examine whether a binding site of interest is conserved, even if the surrounding region exhibits poor sequence identity. This approach also aids in identifying orthologous segments of regulatory DNA, facilitating studies of regulatory sequence evolution. As with previous versions of the software, GenePalette 2.1 takes the form of a platform-independent, single-windowed interface that is simple to use.

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.

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.

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.

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.

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.

Colloids versus crystalloids for fluid resuscitation in critically ill people.

BACKGROUND: Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy (RRT), and adverse events (specifically: allergic reactions, itching, rashes). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two other databases on 23 February 2018. We also searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of critically ill people who required fluid volume replacement in hospital or emergency out-of-hospital settings. Participants had trauma, burns, or medical conditions such as sepsis. We excluded neonates, elective surgery and caesarean section. We compared a colloid (suspended in any crystalloid solution) versus a crystalloid (isotonic or hypertonic). DATA COLLECTION AND ANALYSIS: Independently, two review authors assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 69 studies (65 RCTs, 4 quasi-RCTs) with 30,020 participants. Twenty-eight studied starch solutions, 20 dextrans, seven gelatins, and 22 albumin or fresh frozen plasma (FFP); each type of colloid was compared to crystalloids.Participants had a range of conditions typical of critical illness. Ten studies were in out-of-hospital settings. We noted risk of selection bias in some studies, and, as most studies were not prospectively registered, risk of selective outcome reporting. Fourteen studies included participants in the crystalloid group who received or may have received colloids, which might have influenced results.We compared four types of colloid (i.e. starches; dextrans; gelatins; and albumin or FFP) versus crystalloids.Starches versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using starches or crystalloids in mortality at: end of follow-up (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09; 11,177 participants; 24 studies); within 90 days (RR 1.01, 95% CI 0.90 to 1.14; 10,415 participants; 15 studies); or within 30 days (RR 0.99, 95% CI 0.90 to 1.09; 10,135 participants; 11 studies).We found moderate-certainty evidence that starches probably slightly increase the need for blood transfusion (RR 1.19, 95% CI 1.02 to 1.39; 1917 participants; 8 studies), and RRT (RR 1.30, 95% CI 1.14 to 1.48; 8527 participants; 9 studies). Very low-certainty evidence means we are uncertain whether either fluid affected adverse events: we found little or no difference in allergic reactions (RR 2.59, 95% CI 0.27 to 24.91; 7757 participants; 3 studies), fewer incidences of itching with crystalloids (RR 1.38, 95% CI 1.05 to 1.82; 6946 participants; 2 studies), and fewer incidences of rashes with crystalloids (RR 1.61, 95% CI 0.90 to 2.89; 7007 participants; 2 studies).Dextrans versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using dextrans or crystalloids in mortality at: end of follow-up (RR 0.99, 95% CI 0.88 to 1.11; 4736 participants; 19 studies); or within 90 days or 30 days (RR 0.99, 95% CI 0.87 to 1.12; 3353 participants; 10 studies). We are uncertain whether dextrans or crystalloids reduce the need for blood transfusion, as we found little or no difference in blood transfusions (RR 0.92, 95% CI 0.77 to 1.10; 1272 participants, 3 studies; very low-certainty evidence). We found little or no difference in allergic reactions (RR 6.00, 95% CI 0.25 to 144.93; 739 participants; 4 studies; very low-certainty evidence). No studies measured RRT.Gelatins versus crystalloidsWe found low-certainty evidence that there may be little or no difference between gelatins or crystalloids in mortality: at end of follow-up (RR 0.89, 95% CI 0.74 to 1.08; 1698 participants; 6 studies); within 90 days (RR 0.89, 95% CI 0.73 to 1.09; 1388 participants; 1 study); or within 30 days (RR 0.92, 95% CI 0.74 to 1.16; 1388 participants; 1 study). Evidence for blood transfusion was very low certainty (3 studies), with a low event rate or data not reported by intervention. Data for RRT were not reported separately for gelatins (1 study). We found little or no difference between groups in allergic reactions (very low-certainty evidence).Albumin or FFP versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using albumin or FFP or using crystalloids in mortality at: end of follow-up (RR 0.98, 95% CI 0.92 to 1.06; 13,047 participants; 20 studies); within 90 days (RR 0.98, 95% CI 0.92 to 1.04; 12,492 participants; 10 studies); or within 30 days (RR 0.99, 95% CI 0.93 to 1.06; 12,506 participants; 10 studies). We are uncertain whether either fluid type reduces need for blood transfusion (RR 1.31, 95% CI 0.95 to 1.80; 290 participants; 3 studies; very low-certainty evidence). Using albumin or FFP versus crystalloids may make little or no difference to the need for RRT (RR 1.11, 95% CI 0.96 to 1.27; 3028 participants; 2 studies; very low-certainty evidence), or in allergic reactions (RR 0.75, 95% CI 0.17 to 3.33; 2097 participants, 1 study; very low-certainty evidence). AUTHORS' CONCLUSIONS: Using starches, dextrans, albumin or FFP (moderate-certainty evidence), or gelatins (low-certainty evidence), versus crystalloids probably makes little or no difference to mortality. Starches probably slightly increase the need for blood transfusion and RRT (moderate-certainty evidence), and albumin or FFP may make little or no difference to the need for renal replacement therapy (low-certainty evidence). Evidence for blood transfusions for dextrans, and albumin or FFP, is uncertain. Similarly, evidence for adverse events is uncertain. Certainty of evidence may improve with inclusion of three ongoing studies and seven studies awaiting classification, in future updates.

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.

Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients.

BACKGROUND: Sepsis is a life-threatening condition that is usually diagnosed when a patient has a suspected or documented infection, and meets two or more criteria for systemic inflammatory response syndrome (SIRS). The incidence of sepsis is higher among people admitted to critical care settings such as the intensive care unit (ICU) than among people in other settings. If left untreated sepsis can quickly worsen; severe sepsis has a mortality rate of 40% or higher, depending on definition. Recognition of sepsis can be challenging as it usually requires patient data to be combined from multiple unconnected sources, and interpreted correctly, which can be complex and time consuming to do. Electronic systems that are designed to connect information sources together, and automatically collate, analyse, and continuously monitor the information, as well as alerting healthcare staff when pre-determined diagnostic thresholds are met, may offer benefits by facilitating earlier recognition of sepsis and faster initiation of treatment, such as antimicrobial therapy, fluid resuscitation, inotropes, and vasopressors if appropriate. However, there is the possibility that electronic, automated systems do not offer benefits, or even cause harm. This might happen if the systems are unable to correctly detect sepsis (meaning that treatment is not started when it should be, or it is started when it shouldn't be), or healthcare staff may not respond to alerts quickly enough, or get 'alarm fatigue' especially if the alarms go off frequently or give too many false alarms. OBJECTIVES: To evaluate whether automated systems for the early detection of sepsis can reduce the time to appropriate treatment (such as initiation of antibiotics, fluids, inotropes, and vasopressors) and improve clinical outcomes in critically ill patients in the ICU. SEARCH METHODS: We searched CENTRAL; MEDLINE; Embase; CINAHL; ISI Web of science; and LILACS, clinicaltrials.gov, and the World Health Organization trials portal. We searched all databases from their date of inception to 18 September 2017, with no restriction on country or language of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared automated sepsis-monitoring systems to standard care (such as paper-based systems) in participants of any age admitted to intensive or critical care units for critical illness. We defined an automated system as any process capable of screening patient records or data (one or more systems) automatically at intervals for markers or characteristics that are indicative of sepsis. We defined critical illness as including, but not limited to postsurgery, trauma, stroke, myocardial infarction, arrhythmia, burns, and hypovolaemic or haemorrhagic shock. We excluded non-randomized studies, quasi-randomized studies, and cross-over studies . We also excluded studies including people already diagnosed with sepsis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: time to initiation of antimicrobial therapy; time to initiation of fluid resuscitation; and 30-day mortality. Secondary outcomes included: length of stay in ICU; failed detection of sepsis; and quality of life. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We included three RCTs in this review. It was unclear if the RCTs were three separate studies involving 1199 participants in total, or if they were reports from the same study involving fewer participants. We decided to treat the studies separately, as we were unable to make contact with the study authors to clarify.All three RCTs are of very low study quality because of issues with unclear randomization methods, allocation concealment and uncertainty of effect size. Some of the studies were reported as abstracts only and contained limited data, which prevented meaningful analysis and assessment of potential biases.The studies included participants who all received automated electronic monitoring during their hospital stay. Participants were randomized to an intervention group (automated alerts sent from the system) or to usual care (no automated alerts sent from the system).Evidence from all three studies reported 'Time to initiation of antimicrobial therapy'. We were unable to pool the data, but the largest study involving 680 participants reported median time to initiation of antimicrobial therapy in the intervention group of 5.6 hours (interquartile range (IQR) 2.3 to 19.7) in the intervention group (n = not stated) and 7.8 hours (IQR 2.5 to 33.1) in the control group (n = not stated).No studies reported 'Time to initiation of fluid resuscitation' or the adverse event 'Mortality at 30 days'. However very low-quality evidence was available where mortality was reported at other time points. One study involving 77 participants reported 14-day mortality of 20% in the intervention group and 21% in the control group (numerator and denominator not stated). One study involving 442 participants reported mortality at 28 days, or discharge was 14% in the intervention group and 10% in the control group (numerator and denominator not reported). Sample sizes were not reported adequately for these outcomes and so we could not estimate confidence intervals.Very low-quality evidence from one study involving 442 participants reported 'Length of stay in ICU'. Median length of stay was 3.0 days in the intervention group (IQR = 2.0 to 5.0), and 3.0 days (IQR 2.0 to 4.0 in the control).Very low-quality evidence from one study involving at least 442 participants reported the adverse effect 'Failed detection of sepsis'. Data were only reported for failed detection of sepsis in two participants and it wasn't clear which group(s) this outcome occurred in.No studies reported 'Quality of life'. AUTHORS' CONCLUSIONS: It is unclear what effect automated systems for monitoring sepsis have on any of the outcomes included in this review. Very low-quality evidence is only available on automated alerts, which is only one component of automated monitoring systems. It is uncertain whether such systems can replace regular, careful review of the patient's condition by experienced healthcare staff.

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.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adult patients experiencing acute respiratory failure in the intensive care unit (ICU). OBJECTIVES: We evaluated studies that included participants 16 years of age and older who were admitted to the ICU and required treatment with HFNC. We assessed the safety and efficacy of HFNC compared with comparator interventions in terms of treatment failure, mortality, adverse events, duration of respiratory support, hospital and ICU length of stay, respiratory effects, patient-reported outcomes, and costs of treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, proceedings from four conferences, and clinical trials registries; and we handsearched reference lists of relevant studies. We conducted searches from January 2000 to March 2016 and reran the searches in December 2016. We added four new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update. SELECTION CRITERIA: We included randomized controlled studies with a parallel or cross-over design comparing HFNC use in adult ICU patients versus other forms of non-invasive respiratory support (low-flow oxygen via nasal cannulae or mask, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP)). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. MAIN RESULTS: We included 11 studies with 1972 participants. Participants in six studies had respiratory failure, and in five studies required oxygen therapy after extubation. Ten studies compared HFNC versus low-flow oxygen devices; one of these also compared HFNC versus CPAP, and another compared HFNC versus BiPAP alone. Most studies reported randomization and allocation concealment inadequately and provided inconsistent details of outcome assessor blinding. We did not combine data for CPAP and BiPAP comparisons with data for low-flow oxygen devices; study data were insufficient for separate analysis of CPAP and BiPAP for most outcomes. For the primary outcomes of treatment failure (1066 participants; six studies) and mortality (755 participants; three studies), investigators found no differences between HFNC and low-flow oxygen therapies (risk ratio (RR), Mantel-Haenszel (MH), random-effects 0.79, 95% confidence interval (CI) 0.49 to 1.27; and RR, MH, random-effects 0.63, 95% CI 0.38 to 1.06, respectively). We used the GRADE approach to downgrade the certainty of this evidence to low because of study risks of bias and different participant indications. Reported adverse events included nosocomial pneumonia, oxygen desaturation, visits to general practitioner for respiratory complications, pneumothorax, acute pseudo-obstruction, cardiac dysrhythmia, septic shock, and cardiorespiratory arrest. However, single studies reported adverse events, and we could not combine these findings; one study reported fewer episodes of oxygen desaturation with HFNC but no differences in all other reported adverse events. We downgraded the certainty of evidence for adverse events to low because of limited data. Researchers noted no differences in ICU length of stay (mean difference (MD), inverse variance (IV), random-effects 0.15, 95% CI -0.03 to 0.34; four studies; 770 participants), and we downgraded quality to low because of study risks of bias and different participant indications. We found no differences in oxygenation variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) (MD, IV, random-effects 7.31, 95% CI -23.69 to 41.31; four studies; 510 participants); PaO2 (MD, IV, random-effects 2.79, 95% CI -5.47 to 11.05; three studies; 355 participants); and oxygen saturation (SpO2) up to 24 hours (MD, IV, random-effects 0.72, 95% CI -0.73 to 2.17; four studies; 512 participants). Data from two studies showed that oxygen saturation measured after 24 hours was improved among those treated with HFNC (MD, IV, random-effects 1.28, 95% CI 0.02 to 2.55; 445 participants), but this difference was small and was not clinically significant. Along with concern about risks of bias and differences in participant indications, review authors noted a high level of unexplained statistical heterogeneity in oxygenation effect estimates, and we downgraded the quality of evidence to very low. Meta-analysis of three comparable studies showed no differences in carbon dioxide clearance among those treated with HFNC (MD, IV, random-effects -0.75, 95% CI -2.04 to 0.55; three studies; 590 participants). Two studies reported no differences in atelectasis; we did not combine these findings. Data from six studies (867 participants) comparing HFNC versus low-flow oxygen showed no differences in respiratory rates up to 24 hours according to type of oxygen delivery device (MD, IV, random-effects -1.51, 95% CI -3.36 to 0.35), and no difference after 24 hours (MD, IV, random-effects -2.71, 95% CI -7.12 to 1.70; two studies; 445 participants). Improvement in respiratory rates when HFNC was compared with CPAP or BiPAP was not clinically important (MD, IV, random-effects -0.89, 95% CI -1.74 to -0.05; two studies; 834 participants). Results showed no differences in patient-reported measures of comfort according to oxygen delivery devices in the short term (MD, IV, random-effects 0.14, 95% CI -0.65 to 0.93; three studies; 462 participants) and in the long term (MD, IV, random-effects -0.36, 95% CI -3.70 to 2.98; two studies; 445 participants); we downgraded the certainty of this evidence to low. Six studies measured dyspnoea on incomparable scales, yielding inconsistent study data. No study in this review provided data on positive end-expiratory pressure measured at the pharyngeal level, work of breathing, or cost comparisons of treatment. AUTHORS' CONCLUSIONS: We were unable to demonstrate whether HFNC was a more effective or safe oxygen delivery device compared with other oxygenation devices in adult ICU patients. Meta-analysis could be performed for few studies for each outcome, and data for comparisons with CPAP or BiPAP were very limited. In addition, we identified some risks of bias among included studies, differences in patient groups, and high levels of statistical heterogeneity for some outcomes, leading to uncertainty regarding the results of our analysis. Consequently, evidence is insufficient to show whether HFNC provides safe and efficacious respiratory support for adult ICU patients.