A survey of emergency medical service providers' perspectives regarding relatives influence on acute prehospital treatment of adult patients.

BACKGROUND: In the field of prehospital emergency medicine, specialized emergency medical service (EMS) providers interact with acutely ill patients and their relatives. The influence of family presence during in-hospital resuscitation is well described. However, no studies have previously assessed the influence of relatives' presence in the acute prehospital setting. The aim of this study was to investigate EMS providers' perspectives on relatives' impact on the acute prehospital treatment of adult patients. METHODS: An online anonymous survey was distributed to all prehospital EMS providers in the Capital Region of Denmark. The survey included 25 research questions on a 5-point Likert scale, investigating relatives' influence on treatment in three different domains: positive, negative, and resuscitation. A higher domain score indicates a high level of agreement or frequency. RESULTS: Two hundred forty-six EMS providers completed the survey (84 ambulance technicians, 87 paramedics, and 75 physicians). There were no significant differences in the positive domain across professions (p = .175). Physicians had a statistically significant lower median score in the negative domain, compared with ambulance technicians and paramedics (2.50 vs. 2.63 and 2.63, p = .024). In the resuscitation domain, paramedics and physicians had a significant lower median score compared with ambulance technicians (3.00 and 3.00 vs. 3.14, p = .003). CONCLUSION: All professions were equally positive towards the relatives' presence and involvement in the acute prehospital setting. Physicians were less likely to be negatively influenced by the presence of relatives compared with ambulance technicians and paramedics. In all professions, increased experience led to improved comfort with handling relatives.

Parturients feel capable of giving informed consent for epidural analgesia: A qualitative and quantitative analysis.

INTRODUCTION: The patient's right to autonomy confirmed by informed consent is a cornerstone in modern medicine. Epidural analgesia is increasingly popular in obstetric analgesia, but physicians disagree whether labour pain impairs parturient decision-making. We investigated the fraction of parturients feeling capable of giving informed consent including their knowledge of risks. METHODS: Bedside survey postpartum women at the Herlev Hospital, Denmark. The inclusion criteria were recipient of epidural analgesia during labour. A power calculation based on the recognition of genuine and false side effects required the inclusion of 50 participants. RESULTS: Forty out of fifty (80%) of the participants felt they could make a judicious consent during labour and 46 out of 50 (92%) felt they knew enough about epidural analgesia to give consent to the procedure again if necessary. Participants spontaneously reported a median of two risks associated with epidural analgesia. Additionally, when prompted with a cued list of true and false risks from epidural analgesia, the participants reported on average 5.1 genuine risks compared with 0.4 made-up risks. The difference (4.7) suggests the included women could discern genuine risks from made-up risks. DISCUSSION: The majority of participants reported the capacity to give informed consent. Our quantitative results show the participants could clearly distinguish genuine risks of epidural labour analgesia from made-up risks. Our qualitative data likewise suggest that participants understood the information and consequently their informed consent was genuine. Accordingly, parturients are able to give informed consent. This is supported by parturients' ability to identify risks from epidural labour analgesia.

The healthcare professionals' perspectives and experiences with family presence during resuscitation: A qualitative evidence synthesis.

INTRODUCTION: Family presence during resuscitation (FPDR) is a growing hospital praxis despite lack of high-quality evidence. The aim of this qualitative evidence synthesis review was to synthesize current evidence regarding healthcare professionals (HCP) perspectives on barriers and facilitating factors of FPDR and the potential impact of FPDR on HCP performance. METHODS: We conducted a systematic literature search May 17, 2023 including primary studies with qualitative study designs. We applied NVivo for data analysis. Data was coded with line-by-line coding and organized into themes and categories following the method for thematic synthesis described by Thomas and Harden to analyse data. The studies underwent quality appraisal by Critical Appraisal Skills Program. We used GRADE CERQual to assess the confidence in the evidence. RESULTS: We identified 8241 articles suitable for screening, 141 articles were full text screened, and nine studies included from Australia, UK and USA. In total, 134 HCP participated, between 2005 and 2019. Most studies lacked sufficiently rigorous data analysis and findings were appraised to have moderate GRADE CERQual confidence. We identified three analytical themes ("Facilitating factors for FPDR", "Barriers for FPDR" and "How staff are affected by FPDR") with eight descriptive subthemes. One finding was of high GRADE CERQual confidence: a belief that FPDR is "the right thing to do" which was a "Facilitating factor of FPDR." CONCLUSION: The evidence on HCP perspectives is of low to moderate confidence. The interviewed consent that FPDR is the "right thing to do", and an ethical principle of beneficence is dominant, especially regarding children.

Family presence during resuscitation.

BACKGROUND: Patients and their relatives often expect to be actively involved in decisions of treatment. Even during resuscitation and acute medical care, patients may want to have their relatives nearby, and relatives may want to be present if offered the possibility. The principle of family presence during resuscitation (FPDR) is a triangular relationship where the intervention of family presence affects the healthcare professionals, the relatives present, and the care of the patient involved. All needs and well-being must be balanced in the context of FPDR as the actions involving all three groups can impact the others. OBJECTIVES: The primary aim of this review was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of post-traumatic stress disorder (PTSD)-related symptoms in the relatives. The secondary aim was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of other psychological outcomes in the relatives and what effect family presence compared to no family presence during resuscitation of patients has on patient morbidity and mortality. We also wanted to investigate the effect of FPDR on medical treatment and care during resuscitation. Furthermore, we wanted to investigate and report the personal stress seen in healthcare professionals and if possible describe their attitudes toward the FPDR initiative. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL from inception to 22 March 2022 without any language limits. We also checked references and citations of eligible studies using Scopus, and searched for relevant systematic reviews using Epistomonikos. Furthermore, we searched ClinicalTrials.gov, WHO ICTRP, and ISRCTN registry for ongoing trials; OpenGrey for grey literature; and Google Scholar for additional trials (all on 22 March 2022). SELECTION CRITERIA: We included randomized controlled trials of adults who have witnessed a resuscitation attempt of a patient (who was their relative) at the emergency department or in the pre-hospital emergency medical service.  The participants of this review included relatives, patients, and healthcare professionals during resuscitation.  We included relatives aged 18 years or older who have witnessed a resuscitation attempt of a patient (who is their relative) in the emergency department or pre-hospital. We defined relatives as siblings, parents, spouses, children, or close friends of the patient, or any other descriptions used by the study authors. There were no limitations on adult age or gender. We defined patient as a patient with cardiac arrest in need of cardiopulmonary resuscitation (CPR), a patient with a critical medical or traumatic life-threatening condition, an unconscious patient, or a patient in any other way at risk of sudden death. We included all types of healthcare professionals as described in the included studies. There were no limitations on age or gender. DATA COLLECTION AND ANALYSIS: We checked titles and abstracts of studies identified by the search, and obtained the full reports of those studies deemed potentially relevant. Two review authors independently extracted data. As it was not possible to conduct meta-analyses, we synthesized data narratively. MAIN RESULTS: The electronic searches yielded a total of 7292 records after deduplication. We included 2 trials (3 papers) involving a total of 595 participants: a cluster-randomized trial from 2013 involving pre-hospital emergency medical services units in France, comparing systematic offer for a relative to witness CPR with the traditional practice, and its 1-year assessment; and a small pilot study from 1998 of FPDR in an emergency department in the UK. Participants were 19 to 78 years old, and between 56% and 64% were women. PTSD was measured with the Impact of Event Scale, and the median score ranged from 0 to 21 (range 0 to 75; higher scores correspond to more severe disease). In the trial that accounted for most of the included participants (570/595), the frequency of PTSD-related symptoms was significantly higher in the control group after 3 and 12 months, and in the per-protocol analyses a significant statistical difference was found in favor of FPDR when looking at PTSD, anxiety and depression, and complicated grief after 1 year.  One of the included studies also measured duration of patient resuscitation and personal stress in healthcare professionals during FPDR and found no difference between groups. Both studies had high risk of bias, and the evidence for all outcomes except one was assessed as very low certainty. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw any firm conclusions on the effects of FPDR on relatives' psychological outcomes.   Sufficiently powered and well-designed randomized controlled trials may change the conclusions of the review in future.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Patient Satisfaction of Propofol Versus Midazolam and Fentanyl Sedation During Colonoscopy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy is essential for optimal management of inflammatory bowel disease. However, many patients opt out due to unpleasantness related to this procedure. We investigated if Nurse Administered Propofol Sedation (NAPS) would improve patient satisfaction and attitude towards future colonoscopies. METHODS: Randomized clinical trial of deep sedation with NAPS (n = 63) versus moderate midazolam and fentanyl sedation (n = 67). To assess the primary end point of patient satisfaction at discharge, we developed a Satisfaction Questionnaire comprising 13 items each rated by a 5-point Likert scale and with higher scores reflecting more positive outcomes (13-65 points). RESULTS: Fifty-six patients (43%) with ulcerative colitis, 48 (37%) with Crohn's disease, and 26 (20%) with high suspicion of inflammatory bowel disease were included. Most (88%) had previously had a colonoscopy and pre-procedure expectations were similar between groups. Patients receiving deep sedation had significantly higher satisfaction score (mean 60.1, SD 3.4) than those receiving moderate sedation (51.2, 8.4; P < .001). This was driven especially by less pain, more amnesia, sedation more to their liking, and better experience with the current than previous sedations. Importantly, these patients significantly more often preferred the same sedation for a future colonoscopy and were also inclined to accept more frequent colonoscopies. Assistance from another colonoscopist and disruption of the procedure due to pain occurred significantly more frequent in the moderate sedation group. There were no safety signals associated with NAPS. CONCLUSIONS: Patients with inflammatory bowel disease favor deep propofol sedation over moderate midazolam and fentanyl sedation. Availability of NAPS may facilitate patient adherence to endoscopy-based monitoring programs. Clinicaltrials.gov NCT01934088.

The prognostic value of surgical delay in patients undergoing major emergency abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Mortality following major emergency abdominal surgery is high. Surgical delay is regarded as an important modifiable prognostic factor. Current care-bundles aim at reducing surgical delay, most often using a six-hour cut-off. We aimed to investigate the evidence supporting the in-hospital delay cutoffs currently used. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched. We included studies assessing in-hospital surgical delay in major emergency abdominal surgery patients. Studies were only included if they performed adjusted analysis. Surgical delay beyond six hours was the primary cutfrom interest. The primary outcome was mortality at longest follow-up. Meta-analyses were conducted if possible. RESULTS: Eleven observational studies were included with 16,772 participants. Two studies evaluated delay in unselected major emergency abdominal surgery patients. Three studies applied a six-hour cutoff, but only a study on acute mesenteric ischemia showed an association between delay and mortality. Meta-analysis showed no association with mortality at this cutoff. An association was seen between hourly delay and mortality risk estimate, 1.02 (95% confidence interval [CI], 1.00 - 1.03), and on subgroup analysis of hourly delay in perforated peptic ulcer patients, risk estimate, 1.02 (95% CI, 1.0 - 1.03). All risk estimates had a very low Grading of Recommendations Assessment, Development, and Evaluation score. CONCLUSION: Little evidence supports a six-hour cutoff in unselected major emergency abdominal surgical patients. We found an association between hourly delay and increased mortality; however, evidence supporting this was primarily in patients undergoing surgery for perforated peptic ulcer. This review is limited by the quality of the individual studies.

Pre-operative epidural analgesia in hip fracture patients - A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a common, painful injury with increasing global incidence. Patients require optimal acute pain management. Systematic reviews have investigated the postoperative use of epidural analgesia and found that it may have advantages over systemic analgesia. It is of interest to determine whether pre-operative use of epidural analgesia is also advantageous. We conducted a systematic review and meta-analyses on the effect of epidural analgesia on pre-operative pain management in hip fracture patients. METHODS: We included randomized controlled trials comparing pre-operatively initiated epidural analgesia with any other method of analgesia, in adults aged ≥55 years scheduled for hip fracture surgery. The main outcome was pre-operative pain at rest. Electronic searches of four medical databases were performed. Two authors independently screened for eligibility, extracted data, and assessed risk of bias. We conducted meta-analyses and assessed the certainty of the evidence by Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Three articles were included, with 179 randomized patients. All studies compared epidural analgesia with systemic analgesia, one additionally with 3-in-1-block. Meta-analyses of pre-operative pain measurements resulted in a mean difference of -5.85 95% CI [-14.90; 3.19] on a 0-100 Visual Analogue Scale with a p-value of 0.17 and a very low certainty of evidence according to the GRADE rating. CONCLUSIONS: We did not find a difference in pre-operative pain at rest between epidural analgesia and any other method of pre-operatively initiated analgesia. The studies were few, of low quality and the difference between the two interventions remains unknown.

Freeze-dried plasma in major haemorrhage: a systematic review.

BACKGROUND AND OBJECTIVES: Freeze-dried plasma (FDP) has logistical advantages in terms of storage and reconstitution time compared to fresh-frozen plasma. In vitro studies show FDP to be equivalent to fresh-frozen plasma regarding coagulation and clotting capacities. FDP is used in an increasing number of countries. We wanted to evaluate the clinical effects of FDP in major haemorrhage compared to standard care. METHODS: MEDLINE, Embase, Central, Biosis Previews, WHO ICTRP, Clinical Trials and Open Grey were systematically searched from inception until September 2018, without language restriction. Studies were eligible if they examined haemorrhagic adult patients transfused with FDP. Our primary outcome was mortality. Two reviewers independently assessed studies for eligibility, extracted data and assessed bias. RESULTS: Nine studies were eligible for inclusion. Three studies had a comparison group: one was a randomized controlled trial and two were before and after comparisons. Six studies were uncontrolled. A total of 606 patients received FDP, while 72 patients received non-FDP transfusion. In total, five minor adverse effects were documented. Two studies compared FDP to fresh-frozen plasma and found no difference in 30-day mortality between the groups. The included studies were heterogenous and had several methodological weaknesses, such as no control group, missing data or no protocol. CONCLUSIONS: The available research does not document the clinical effects of FDP. We cannot recommend or discourage use of FDP in major haemorrhage on base of available research.

Melatonin for preoperative and postoperative anxiety in adults.

BACKGROUND: Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods. OBJECTIVES: To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines. SEARCH METHODS: We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia. DATA COLLECTION AND ANALYSIS: One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures. MAIN RESULTS: We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines. AUTHORS' CONCLUSIONS: When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.

ANTECEDENTES: La ansiedad relacionada con la cirugía es un problema conocido. La melatonina ofrece un tratamiento alternativo a las benzodiazepinas para mejorar esta afección en los períodos pre y posoperatorio. OBJETIVOS: Evaluar los efectos de la melatonina en la ansiedad pre y posoperatoria en comparación con el placebo o las benzodiazepinas. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en las siguientes bases de datos el 10 de julio de 2020: CENTRAL, MEDLINE, Embase, CINAHL y Web of Science. Para los ensayos y protocolos en curso, se buscó en clinicaltrials.gov y en la Plataforma de registros internacionales de ensayos clínicos de la Organización Mundial de la Salud (OMS). CRITERIOS DE SELECCIÓN: Estudios aleatorizados controlados con placebo o controlados con tratamiento estándar, o ambos, que evaluaron los efectos de la melatonina administrada de forma preoperatoria para la ansiedad preoperatoria o posoperatoria. Se incluyeron pacientes adultos de ambos sexos (15 a 90 años de edad) a los que se les realizó cualquier clase de procedimiento quirúrgico donde fue necesario utilizar anestesia general, regional o tópica. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Un autor de la revisión realizó la extracción de los datos por duplicado. Los datos que se extrajeron incluyeron información acerca del diseño del estudio, el país de origen, el número de participantes y los detalles demográficos, el tipo de cirugía, el tipo de anestesia, la intervención y el régimen de dosis, medidas de desenlace de ansiedad preoperatoria y medidas de desenlace de ansiedad posoperatoria. RESULTADOS PRINCIPALES: Se incluyeron 27 ensayos controlados aleatorizados (ECA), con 2319 participantes, que evaluaron la melatonina para el tratamiento de la ansiedad preoperatoria, la ansiedad posoperatoria o ambas. Veinticuatro estudios compararon la melatonina con el placebo. Once estudios compararon la melatonina con una benzodiazepina (siete estudios con midazolam, tres estudios con alprazolam y un estudio con oxazepam). Otros comparadores en un escaso número de estudios fueron la gabapentina, la clonidina y la pregabalina. No se consideró que ningún estudio tuviera un riesgo bajo de sesgo en todos los dominios. La mayoría de los estudios se consideraron con riesgo incierto de sesgo en general. Se consideró que ocho estudios tenían un alto riesgo de sesgo en uno o más dominios y, por lo tanto, un alto riesgo de sesgo en general. Melatonina versus placebo La melatonina probablemente da lugar a una reducción de la ansiedad preoperatoria medida por una escala visual analógica (EVA, 0 a 100 mm) en comparación con el placebo (diferencia de medias [DM] ­11,69; intervalo de confianza [IC] del 95%: ­13,80 a ­9,59; 18 estudios, 1264 participantes; evidencia de certeza moderada), sobre la base de un metanálisis de 18 estudios. La melatonina podría reducir la ansiedad posoperatoria inmediata medida en una EVA de 0 a 100 mm en comparación con el placebo (DM ­5,04; IC del 95%: ­9,52 a ­0,55; siete estudios, 524 participantes; evidencia de certeza baja), y podría reducir la ansiedad posoperatoria tardía medida seis horas después de la cirugía mediante el State­Trait Anxiety Inventory (STAI) (DM ­5,31; IC del 95%: ­8,78 a ­1,84; dos estudios; 73 participantes; evidencia de certeza baja). Melatonina versus benzodiazepinas (midazolam y alprazolam) La melatonina probablemente da lugar a poca o ninguna diferencia en la ansiedad preoperatoria medida en una EVA de 0 a 100 mm (DM 0,78; IC del 95%: ­2,02 a 3,58; siete estudios, 409 participantes; evidencia de certeza moderada) y podría haber poca o ninguna diferencia en la ansiedad posoperatoria inmediata (DM ­2,12; IC del 95%: ­4,61 a 0,36; tres estudios, 176 participantes; evidencia de certeza baja). Eventos adversos Catorce estudios no informaron sobre los eventos adversos. Seis estudios informaron específicamente que no se observaron efectos secundarios y los siete estudios restantes informaron casos de náuseas, somnolencia, mareos y cefalea; sin embargo, no se informaron eventos adversos graves. Once estudios midieron la función psicomotora y cognitiva, o ambas, y en general, estos estudios encontraron que las benzodiazepinas deterioraron la función psicomotora y cognitiva más que el placebo y la melatonina. Catorce estudios evaluaron la sedación y en general encontraron que la benzodiazepina causaba el mayor grado de sedación, pero la melatonina también mostró propiedades sedantes en comparación con el placebo. Varios estudios no informaron sobre los efectos adversos; por lo tanto, no es posible concluir con certeza, a partir de los datos sobre los efectos adversos obtenidos en esta revisión, que la melatonina se tolera mejor que las benzodiazepinas. CONCLUSIONES DE LOS AUTORES: Cuando se compara con el placebo, la melatonina administrada como premedicación (en forma de comprimidos o sublingual) probablemente reduce la ansiedad preoperatoria en los adultos (medida entre 50 y 120 minutos después de la administración), lo que es potencialmente relevante desde el punto de vista clínico. El efecto de la melatonina sobre la ansiedad posoperatoria en comparación con el placebo (medido en la sala de recuperación y seis horas después de la cirugía) también fue evidente, pero fue mucho menor, y la relevancia clínica de este hallazgo no está clara. Hubo poca o ninguna diferencia en la ansiedad cuando la melatonina se comparó con las benzodiazepinas. Por lo tanto, la melatonina puede tener un efecto similar al de las benzodiazepinas en la reducción de la ansiedad pre y posoperatoria en los adultos.

Perioperative alcohol cessation intervention for postoperative complications.

BACKGROUND: Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures.Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery.This review was first published in 2012 and was updated in 2018. OBJECTIVES: To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption. SEARCH METHODS: We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention.We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies. DATA COLLECTION AND ANALYSIS: We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study.Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate.In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low.Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate.All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term. AUTHORS' CONCLUSIONS: This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term.Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.

Interventions for preventing intensive care unit delirium in adults.

BACKGROUND: Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to the environment. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect both them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay and long-term cognitive impairment. It also results in increased costs for society. OBJECTIVES: To assess existing evidence for the effect of preventive interventions on ICU delirium, in-hospital mortality, the number of delirium- and coma-free days, ventilator-free days, length of stay in the ICU and cognitive impairment. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, Latin American Caribbean Health Sciences Literature, CINAHL from 1980 to 11 April 2018 without any language limits. We adapted the MEDLINE search for searching the other databases. Furthermore, we checked references, searched citations and contacted study authors to identify additional studies. We also checked the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and CenterWatch.com (all on 24 April 2018). SELECTION CRITERIA: We included randomized controlled trials (RCTs) of adult medical or surgical ICU patients receiving any intervention for preventing ICU delirium. The control could be standard ICU care, placebo or both. We assessed the quality of evidence with GRADE. DATA COLLECTION AND ANALYSIS: We checked titles and abstracts to exclude obviously irrelevant studies and obtained full reports on potentially relevant ones. Two review authors independently extracted data. If possible we conducted meta-analyses, otherwise we synthesized data narratively. MAIN RESULTS: The electronic search yielded 8746 records. We included 12 RCTs (3885 participants) comparing usual care with the following interventions: commonly used drugs (four studies); sedation regimens (four studies); physical therapy or cognitive therapy, or both (one study); environmental interventions (two studies); and preventive nursing care (one study). We found 15 ongoing studies and five studies awaiting classification. The participants were 48 to 70 years old; 48% to 74% were male; the mean acute physiology and chronic health evaluation (APACHE II) score was 14 to 28 (range 0 to 71; higher scores correspond to more severe disease and a higher risk of death). With the exception of one study, all participants were mechanically ventilated in medical or surgical ICUs or mixed. The studies were overall at low risk of bias. Six studies were at high risk of detection bias due to lack of blinding of outcome assessors. We report results for the two most commonly explored approaches to delirium prevention: pharmacologic and a non-pharmacologic intervention.Haloperidol versus placebo (two RCTs, 1580 participants)The event rate of ICU delirium was measured in one study including 1439 participants. No difference was identified between groups, (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.87 to 1.17) (moderate-quality evidence). Haloperidol versus placebo neither reduced or increased in-hospital mortality, (RR 0.98, 95% CI 0.80 to 1.22; 2 studies; 1580 participants (moderate-quality evidence)); the number of delirium- and coma-free days, (mean difference (MD) -0.60, 95% CI -1.37 to 0.17; 2 studies, 1580 participants (moderate-quality of evidence)); number of ventilator-free days (mean 23.8 (MD -0.30, 95% CI -0.93 to 0.33) 1 study; 1439 participants, (high-quality evidence)); length of ICU stay, (MD 0.18, 95% CI -0.60 to 0.97); 2 studies, 1580 participants; high-quality evidence). None of the studies measured cognitive impairment. In one study there were three serious adverse events in the intervention group and five in the placebo group; in the other there were five serious adverse events and three patients died, one in each group. None of the serious adverse events were judged to be related to interventions received (moderate-quality evidence).Physical and cognitive therapy interventions (one study, 65 participants)The study did not measure the event rate of ICU delirium. A physical and cognitive therapy intervention versus standard care neither reduced nor increased in-hospital mortality, (RR 0.94, 95% CI 0.40 to 2.20, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of delirium- and coma-free days, (MD -2.8, 95% CI -10.1 to 4.6, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of ventilator-free days (within the first 28/30 days) was median 27.4 (IQR 0 to 29.2) and 25 (IQR 0 to 28.9); 1 study, 65 participants; very low-quality evidence, length of ICU stay, (MD 1.23, 95% CI -0.68 to 3.14, I² = 0; 1 study, 65 participants; very low-quality evidence); cognitive impairment measured by the MMSE: Mini-Mental State Examination with higher scores indicating better function, (MD 0.97, 95% CI -0.19 to 2.13, I² = 0; 1 study, 30 participants; very low-quality evidence); or measured by the Dysexecutive questionnaire (DEX) with lower scores indicating better function (MD -8.76, 95% CI -19.06 to 1.54, I² = 0; 1 study, 30 participants; very low-quality evidence). One patient experienced acute back pain accompanied by hypotensive urgency during physical therapy. AUTHORS' CONCLUSIONS: There is probably little or no difference between haloperidol and placebo for preventing ICU delirium but further studies are needed to increase our confidence in the findings. There is insufficient evidence to determine the effects of physical and cognitive intervention on delirium. The effects of other pharmacological interventions, sedation, environmental, and preventive nursing interventions are unclear and warrant further investigation in large multicentre studies. Five studies are awaiting classification and we identified 15 ongoing studies, evaluating pharmacological interventions, sedation regimens, physical and occupational therapy combined or separately, and environmental interventions, that may alter the conclusions of the review in future.

A Description of Deaths Following Emergency Abdominal Surgery.

OBJECTIVE: Emergency major abdominal surgery carries a high mortality rate. The aim of this present study was to characterize a population of deceased abdominal surgical patients, to examine how many died unexpectedly and how many were subject to treatment limitations. MATERIALS AND METHODS: We included adult emergency abdominal surgical patients who died within 30 days postoperatively. We collected data from January 1, 2013, to December 31, 2014, in a Danish tertiary care hospital (Herlev). RESULTS: A total of 138 patients were included which corresponded to a crude mortality rate of 16.5% in the population. Four percent (5 of 138) of the patients died unexpectedly without any prior signs of deterioration and 46% (65 of 138) experienced a complicated treatment course, 67% of which was treated in the intensive care unit (ICU). The remaining 50% (68 of 138) had treatment limitations, applied pre- or postoperatively, of which 4% were treated in the ICU ward. CONCLUSIONS: In the present study, we found a high number of patients with treatment limitations, offering one explanation to why so relatively few high-risk surgical patients are admitted to the ICU ward. Whether intermediary wards could serve as a viable alternative for these patients, securing a sufficient level of treatment without taking up scarce beds in the intensive care unit, remains an important question for future studies. Furthermore, five patients died unexpectedly, without any clear cause of death, proving that continual strides toward improving the overall process of postoperative care are still demanded.

Total intravenous anaesthesia versus inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic surgery.

BACKGROUND: Rapid implementation of robotic transabdominal surgery has resulted in the need for re-evaluation of the most suitable form of anaesthesia. The overall objective of anaesthesia is to minimize perioperative risk and discomfort for patients both during and after surgery. Anaesthesia for patients undergoing robotic assisted surgery is different from anaesthesia for patients undergoing open or laparoscopic surgery; new anaesthetic concerns accompany robotic assisted surgery. OBJECTIVES: To assess outcomes related to the choice of total intravenous anaesthesia (TIVA) or inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016 Issue 5), Ovid MEDLINE (1946 to May 2016), Embase via OvidSP (1982 to May 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost (1982 to May 2016) and the Institute for Scientific Information (ISI) Web of Science (1956 to May 2016). We also searched the International Standard Randomized Controlled Trial Number (ISRCTN) Registry and Clinical trials gov for ongoing trials (May 2016). SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) including adults, aged 18 years and older, of both genders, treated with transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery and focusing on outcomes of TIVA or inhalational anaesthesia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of Cochrane. Study findings were not suitable for meta-analysis. MAIN RESULTS: We included three single-centre, two-arm RCTs involving 170 participants. We found one ongoing trial. All included participants were male and were undergoing radical robotic assisted laparoscopic radical prostatectomy (RALRP). The men were between 50 and 75 years of age and met criteria for American Society of Anesthesiologists physical classification scores (ASA) I, ll and III.We found evidence showing no clinically meaningful differences in postoperative pain between the two types of anaesthetics (mean difference (MD) in visual analogue scale (VAS) scores at one to six hours was -2.20 (95% confidence interval (CI) -10.62 to 6.22; P = 0.61) in a sample of 62 participants from one study. Low-quality evidence suggests that propofol reduces postoperative nausea and vomiting (PONV) over the short term (one to six hours after surgery) after RALRP compared with inhalational anaesthesia (sevoflurane, desflurane) (MD -1.70, 95% CI -2.59 to -0.81; P = 0.0002).We found low-quality evidence suggesting that propofol may prevent an increase in intraocular pressure (IOP) after pneumoperitoneum and steep Trendelenburg positioning compared with sevoflurane (MD -3.90, 95% CI -6.34 to -1.46; P = 0.002) with increased IOP from baseline to 30 minutes in steep Trendelenburg. However, it is unclear whether this surrogate outcome translates directly to clinical avoidance of ocular complications during surgery. No studies addressed the secondary outcomes of adverse effects, all-cause mortality, respiratory or circulatory complications, cognitive dysfunction, length of stay or costs. Overall the quality of evidence was low to very low, as all studies were small, single-centre trials providing unclear descriptions of methods. AUTHORS' CONCLUSIONS: It is unclear which anaesthetic technique is superior - TIVA or inhalational - for transabdominal robotic assisted surgery in urology, gynaecology and gastroenterology, as existing evidence is scarce, is of low quality and has been generated from exclusively male patients undergoing robotic radical prostatectomy.An ongoing trial, which includes participants of both genders with a focus on quality of recovery, might have an impact on future evidence related to this topic.

Avoidance versus use of neuromuscular blocking agents for improving conditions during tracheal intubation or direct laryngoscopy in adults and adolescents.

BACKGROUND: Tracheal intubation during induction of general anaesthesia is a vital procedure performed to secure a patient's airway. Several studies have identified difficult tracheal intubation (DTI) or failed tracheal intubation as one of the major contributors to anaesthesia-related mortality and morbidity. Use of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a widely accepted practice. However, because of adverse effects, NMBA may be undesirable. Cohort studies have indicated that avoiding NMBA is an independent risk factor for difficult and failed tracheal intubation. However, no systematic review of randomized trials has evaluated conditions for tracheal intubation, possible adverse effects, and postoperative discomfort. OBJECTIVES: To evaluate the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on difficult tracheal intubation (DTI) for adults and adolescents allocated to tracheal intubation with direct laryngoscopy. To look at various outcomes, conduct subgroup and sensitivity analyses, examine the role of bias, and apply trial sequential analysis (TSA) to examine the level of available evidence for this intervention. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, LILACS, advanced Google, CINAHL, and the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and www.centerwatch.com, up to January 2017. We checked the reference lists of included trials and reviews to look for unidentified trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the effects of avoiding versus using NMBA in participants 14 years of age or older. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We conducted random-effects and fixed-effect meta-analyses and calculated risk ratios (RRs) and their 95% confidence intervals (CIs). We used published data and data obtained by contacting trial authors. To minimize the risk of systematic error, we assessed the risk of bias of included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta-analyses, we applied TSA. MAIN RESULTS: We identified 34 RCTs with 3565 participants that met our inclusion criteria. All trials reported on conditions for tracheal intubation; seven trials with 846 participants described 'events of upper airway discomfort or injury', and 13 trials with 1308 participants reported on direct laryngoscopy. All trials used a parallel design. We identified 18 dose-finding studies that included more interventions or control groups or both. All trials except three included only American Society of Anesthesiologists (ASA) class I and II participants, 25 trials excluded participants with anticipated DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen trials used suxamethonium, and 18 trials used non-depolarizing NMBA.Trials with an overall low risk of bias reported significantly increased risk of DTI with no use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001; 508 participants; four trials; number needed to treat for an additional harmful outcome (NNTH) = 1.9, I2 = 0%, D2 = 0%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of results and of significantly increased risk of DTI when an NMBA was avoided (random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565 participants; 34 trials; NNTH = 6.3, I2 = 70%, D2 = 82%, GRADE = low). Again the cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful effects of avoiding NMBA on the proportion of DTI with minimal risk of random error. We categorized only one trial reporting on upper airway discomfort or injury as having overall low risk of bias. Inclusion of all trials revealed significant risk of upper airway discomfort or injury when an NMBA was avoided (random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846 participants; seven trials; NNTH = 9.1, I2 = 13%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality. In terms of our secondary outcome 'difficult laryngoscopy', we categorized only one trial as having overall low risk of bias. All trials avoiding NMBA were significantly associated with difficult laryngoscopy (random-effects model) (RR 2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6, I2 = 0%, D2= 0%, GRADE = low); however, TSA showed that only 6% of the information size required to detect or reject a 20% relative risk reduction (RRR) was accrued, and the trial sequential monitoring boundary was not crossed. AUTHORS' CONCLUSIONS: This review supports that use of an NMBA may create the best conditions for tracheal intubation and may reduce the risk of upper airway discomfort or injury following tracheal intubation. Study results were characterized by indirectness, heterogeneity, and high or uncertain risk of bias concerning our primary outcome describing difficult tracheal intubation. Therefore, we categorized the GRADE classification of quality of evidence as moderate to low. In light of defined outcomes of individual included trials, our primary outcomes may not reflect a situation that many clinicians consider to be an actual difficult tracheal intubation by which the patient's life or health may be threatened.

Development and validation of a theoretical test in non-anaesthesiologist-administered propofol sedation for gastrointestinal endoscopy.

OBJECTIVE: Safety with non-anaesthesiologist-administered propofol sedation (NAAP) during gastrointestinal (GI) endoscopy is related to theoretical knowledge. A summative testing of knowledge before attempting supervised nurse-administered propofol sedation (NAPS) in the clinic is advised. The aims of this study were to develop a theoretical test about propofol sedation, to gather validity evidence for the test and to measure the effect of a NAPS-specific training course. MATERIAL AND METHODS: A three-phased psychometric study on multiple choice questionnaire (MCQ) test development, gathering of validity evidence and evaluation of the effect of a specific NAAP course on the test result. A MCQ containing 86 questions was developed and administered 113 times to 91 participants representing novices, intermediates and experienced. RESULTS: Question difficulty analyses revealed 50 level I and II questions. The 50 MCQs showed mean (SD) intergroup differences (p = 0.001) between novices = 28.6 (4.82), intermediates = 36.8 (5.43) and experienced = 41.8 (4.65) and provided a pass score of 35.2. The course with pre-course test had significant effect on the knowledge of nurses (18% increase) and physicians (19% increase; p = 0.001 and 0.001, respectively). CONCLUSIONS: Data supported the validity of the developed MCQ test. The NAPS-specific course with pre-course testing adds theoretical knowledge to already well-prepared participants.

Perioperative dexmedetomidine for acute pain after abdominal surgery in adults.

BACKGROUND: Acute postoperative pain is still an issue in patients undergoing abdominal surgery. Postoperative pain and side effects of analgesic treatment, in particular those of opioids, need to be minimized. Opioid-sparing analgesics, possibly including dexmedetomidine, seem a promising avenue by which to improve postoperative outcomes. OBJECTIVES: Our primary aim was to determine the analgesic efficacy and opioid-sparing effect of perioperative dexmedetomidine for acute pain after abdominal surgery in adults.Secondary aims were to establish effects of dexmedetomidine on postoperative nausea and vomiting (PONV), gastrointestinal function and mobilization, together with the side effect profile of dexmedetomidine. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Institute for Scientific Information (ISI), Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL), and reference lists of articles to May 2014. We searched the Science Citation Index, ClinicalTrials.gov and Current Controlled Trials, and we contacted pharmaceutical companies to identify unpublished and ongoing studies. We applied no language restrictions. We reran the search in May 2015 and found nine studies of interest. We will deal with the studies of interest when we update the review. SELECTION CRITERIA: We included randomized, controlled trials of perioperative dexmedetomidine versus placebo or other drug during abdominal surgery in adults. Trials included one of the following outcomes: amount of 'rescue' opioid, postoperative pain, time to 'rescue' analgesia, participants requiring 'rescue' analgesia, postoperative sedation, PONV, time to first passage of flatus and stool or time to first out-of-bed mobilization. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts for eligibility. We retrieved full trial reports if necessary, and we extracted relevant data from the included studies using a data collection form and assessed risk of bias. We resolved disagreements by discussion with the third review author. We sought additional information of relevance for risk of bias assessment or extraction of data by contacting study authors or, if necessary, co-authors from present or former studies. MAIN RESULTS: Our systematic review included seven studies with a total of 492 participants. We included 422 participants in our analysis. Thirteen studies are awaiting classification. For the comparison dexmedetomidine versus placebo (six studies, 402 participants), most studies found a reduction in 'rescue' opioid consumption in the first 24 hours after surgery, together with in general no clinically important differences in postoperative pain (visual analogue scale (VAS) 0 to 100 mm, where 0 = no pain and 100 = worst imaginable pain) in the first 24 hours after surgery - except for one study (80 participants) with a reduction in VAS pain at two hours after surgery in favour of dexmedetomidine, with a mean difference of -30.00 mm (95% confidence interval (CI) -38.25 to -21.75). As the result of substantial heterogeneity, pooling of data in statistical meta-analyses was not appropriate. The quality of evidence was very low for our primary outcomes because of imprecision of results and risk of bias. Regarding our secondary aims, evidence was too scant in general to allow robust conclusions, or the estimates too imprecise or of poor methodological quality. Regarding adverse effects, low quality data (one study, 80 participants) suggest that the proportion of participants with hypotension requiring intervention was slightly higher in the high-dose dexmedetomidine group with a risk ratio of 2.50 (95% CI 0.94 to 6.66), but lower doses of dexmedetomidine led to no differences compared with control. Evidence for the comparison dexmedetomidine versus fentanyl was insufficient to permit robust conclusions (one study, 20 participants). AUTHORS' CONCLUSIONS: Dexmedetomidine, when administered perioperatively for acute pain after abdominal surgery in adults, seemed to have some opioid-sparing effect together with in general no important differences in postoperative pain when compared with placebo. However the quality of the evidence was very low as the result of imprecision, methodological limitations and substantial heterogeneity among the seven included studies. The clinical importance for patients is uncertain, in as much as the influence of dexmedetomidine on patient-important outcomes such as gastrointestinal function, mobilization and adverse effects could not be satisfactorily determined. All included studies were relatively small, and publication bias could not be ruled out. Applicability of evidence was limited to middle-aged participants who were relatively free of co-morbidity and were undergoing elective abdominal surgery. A potential bias was a considerable quantity of unobtainable data from studies with mixed surgery. To detect and investigate patient-important outcomes, larger studies with longer periods of follow-up are needed.

Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding.

BACKGROUND: Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016. OBJECTIVES: We assessed the benefits and harms of thromboelastography (TEG)-guided or thromboelastometry (ROTEM)-guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far. SEARCH METHODS: In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010. SELECTION CRITERIA: We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta-analysis was not provided for continuous outcome data. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG- or ROTEM-guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA. MAIN RESULTS: We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta-analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I(2) = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I(2) = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta-analyses also showed fewer participants with dialysis-dependent renal failure.We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I(2) = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I(2) = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG- or ROTEM-guided transfusion in bleeding patients. AUTHORS' CONCLUSIONS: There is growing evidence that application of TEG- or ROTEM-guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.

Antithrombin III for critically ill patients.

BACKGROUND: Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown. This review was published in 2008 and updated in 2015. OBJECTIVES: To examine:1. The effect of AT III on mortality in critically ill participants.2. The benefits and harms of AT III.We investigated complications specific and not specific to the trial intervention, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general. SEARCH METHODS: We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP,), CAB, BIOSIS and CINAHL. We contacted the main authors of trials to ask for any missed, unreported or ongoing trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We contacted the investigators and the trial authors in order to retrieve missing data. In this updated review we include trials only published as abstracts. DATA COLLECTION AND ANALYSIS: Our primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetrics, and paediatrics), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed trial sequential analysis (TSA) to establish the implications for further research. MAIN RESULTS: We included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I² statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I² statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I² statistic = 0%, fixed-effect model, 20 trials, 967 participants).For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I² statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.Our secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I² statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I² statistic = 28%, random-effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I² statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I² statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was -2.18 (95% Cl -4.36 to -0.00, I² statistic = 0%, fixed-effect model, 3 trials, 102 participants, very low quality of evidence). The incidence of respiratory failure had a RR of 0.93 (95% Cl 0.76 to 1.14, I² statistic = 32%, random-effects model, 6 trials, 2591 participants, moderate quality of evidence). AT III had no statistically significant impact on the duration of mechanical ventilation (MD 2.20 days, 95% Cl -1.21 to 5.60, I² statistic = 0%, fixed-effect model, 3 trials, 190 participants, very low quality of evidence); on the length of stay in the ICU (MD 0.24, 95% Cl -1.34 to 1.83, I² statistic = 0%, fixed-effect model, 7 trials, 376 participants, very low quality of evidence) or on the length of stay in hospital in general (MD 1.10, 95% Cl -7.16 to 9.36), I² statistic = 74%, 4 trials, 202 participants, very low quality of evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support AT III substitution in any category of critically ill participants including the subset of patients with sepsis and DIC. We did not find a statistically significant effect of AT III on mortality, but AT III increased the risk of bleeding events. Subgroup analyses performed according to duration of intervention, length of follow-up, different patient groups, and use of adjuvant heparin did not show differences in the estimates of intervention effects. The majority of included trials were at high risk of bias (GRADE; very low quality of evidence for most of the analyses). Hence a large RCT of AT III is needed, without adjuvant heparin among critically ill patients such as those with severe sepsis and DIC, with prespecified inclusion criteria and good bias protection.

Melatonin for pre- and postoperative anxiety in adults.

BACKGROUND: Anxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre- and postoperative period. OBJECTIVES: To assess the effect of melatonin on pre- and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines. SEARCH METHODS: The following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review. SELECTION CRITERIA: Randomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures. MAIN RESULTS: This systematic review identified 12 randomized controlled trials (RCTs) including 774 patients that assessed melatonin for treating preoperative anxiety, postoperative anxiety or both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas the remaining eight studies compared melatonin and placebo only.The quality of the evidence for our primary outcome (melatonin versus placebo for preoperative anxiety) was high. More than half of the included studies had a low risk of selection bias and at least 75% of the included studies had a low risk of attrition, performance and detection bias. Most of the included studies had an unclear risk of reporting bias.Eight out the 10 studies that assessed the effect of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction compared to placebo. The reported estimate of effect (relative effect -13.36, 95% confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a meta-analysis of seven studies. Two studies did not show any difference between melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS found no evidence of a difference in preoperative anxiety between the two groups (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies assessed the effect of melatonin on postoperative anxiety. Four of these studies measuring postoperative anxiety 90 minutes postoperatively using a VAS did not find any evidence of a difference between melatonin and placebo (relative effect -3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect -5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing melatonin with midazolam using a VAS did not find any evidence of a difference between the two groups in postoperative anxiety (relative effect -2.02, 95% CI -5.82 to 1.78). AUTHORS' CONCLUSIONS: When compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90 minutes and 6 hours after surgery) in adults is mixed but suggests an overall attenuation of the effect compared to preoperatively.