Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour.

BACKGROUND: Multiple analgesic strategies for pain relief during labour are available. Recently remifentanil, a short-acting opioid, has recently been used as an alternative analgesic due to its unique pharmacological properties. OBJECTIVES: To systematically assess the effectiveness of remifentanil intravenous patient-controlled analgesia (PCA) for labour pain, along with any potential harms to the mother and the newborn. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 December 2015), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), handsearched congress abstracts (November 2015), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-randomised trials comparing remifentanil (PCA) with another opioid (intravenous (IV)/intramuscular (IM)), or with another opioid (PCA), or with epidural analgesia, or with remifentanil (continuous IV), or with remifentanil (PCA, different regimen), or with inhalational analgesia, or with placebo/no treatment in all women in labour including high-risk groups with planned vaginal delivery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data, and appraised study quality.We contacted study authors for additional information other than incomplete outcome data. We performed random-effects meta-analysis.To reduce the risk of random error in meta-analysis we performed trial sequential analysis. We included total zero event trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta-analysis. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: Twenty RCTs with 3569 women were included. Of those, 10 trials (2983 participants) compared remifentanil (PCA) to an epidural, four trials (216 participants) to another opioid (IV/IM), three trials (215 participants) to another opioid (PCA), two trials (135 participants) to remifentanil (continuous IV), and one trial (20 participants) to remifentanil (PCA, different regimen). No trials were identified for the remaining comparisons.Methodological quality of studies was moderate to poor. We assessed risk of bias as high for blinding issues and incomplete outcome data in 65% and 45% of the included studies, respectively.There is evidence of effect that women in the remifentanil (PCA) group were more satisfied with pain relief than women in the other opioids (IV/IM) group (standardised mean difference (SMD) 2.11, 95% confidence interval (CI) 0.72 to 3.49, four trials, very low-quality evidence), and that women were less satisfied compared to women in the epidural group (SMD -0.22, 95% CI -0.40 to -0.04, seven trials, very low-quality evidence).There is evidence of effect that remifentanil (PCA) provided stronger pain relief at one hour than other opioids administered IV/IM (SMD -1.58, 95% CI -2.69 to -0.48, three trials, very low-quality evidence) or via PCA (SMD -0.51, 95% CI -1.01 to -0.00, three trials, very low-quality evidence). Pain intensity was higher in the remifentanil (PCA) group compared to the epidural group (SMD 0.57, 95% CI 0.31 to 0.84, six trials, low-quality evidence).Data were limited on safety aspects for both the women and the newborns. Only one study analysed maternal apnoea in a comparison of remifentanil (PCA) versus epidural and reported that half of the women in the remifentanil and none in the epidural group had an apnoea (very low-quality evidence). There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for maternal respiratory depression when compared to epidural analgesia (RR 0.91, 95% CI 0.51 to 1.62, ccc 0.01, three trials, low-quality evidence) and no reliable conclusion might be reached compared to remifentanil (continuous IV) (all study arms included zero events, two trials, low-quality evidence). In one trial of remifentanil (PCA) versus another opioid (IM) three out of 18 women in the remifentanil and none out of 18 in the control group had a respiratory depression (very low-quality evidence).There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for newborns with Apgar scores less than seven at five minutes compared to epidural analgesia (RR 1.26, 95% CI 0.62 to 2.57, ccc 0.01, five trials, low-quality evidence) and no reliable conclusion might be reached compared to another opioid (IV) and compared to remifentanil (PCA, different regimen) both with zero events in all study arms (one trial, very-low quality evidence). In one trial of remifentanil (PCA) versus another opioid (PCA) none out of nine newborns in the remifentanil and three out of eight in the opioid (PCA) group had Apgar scores less than seven (very-low quality evidence).There is evidence that remifentanil (PCA) was associated with a lower risk for the requirement of additional analgesia when compared to other opioids (IV/IM) (RR 0.57, 95% CI 0.40 to 0.81, three trials, moderate-quality evidence) and that it was associated with a higher risk compared to epidural analgesia (RR 9.27, 95% CI 3.73 to 23.03, ccc 0.01, six trials, moderate-quality evidence). There is no evidence of effect that remifentanil (PCA) reduced the requirement for additional analgesia compared to other opioids (PCA) (RR 0.76, 95% CI 0.45 to 1.28, three trials, low-quality evidence).There is evidence that there was no difference in the risk for caesarean delivery between remifentanil (PCA) and other opioids (IV/IM) (RR 0.63, 95% CI 0.30 to 1.32, ccc 0.01, four trials, low-quality evidence) and epidural analgesia (RR 1.0, 95% CI 0.82 to 1.22, ccc 0.01, nine trials, moderate-quality evidence), respectively. Pooled meta-analysis revealed an increased risk for caesarean section under remifentanil (PCA) compared to other opioids (PCA) (RR 2.78, 95% CI 0.99 to 7.82, two trials, very low-quality evidence). However, a wide range of clinically relevant and non-relevant treatment effects is compatible with this result. AUTHORS' CONCLUSIONS: Based on the current systematic review, there is mostly low-quality evidence to inform practice and future research may significantly alter the current situation. The quality of evidence is mainly limited by poor quality of the studies, inconsistency, and imprecision. More research is needed on maternal and neonatal safety outcomes (maternal apnoea and respiratory depression, Apgar score) and on the optimal mode and regimen of remifentanil administration to provide highest efficacy with reasonable adverse effects for mothers and their newborns.

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions.

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews.

Vasopressors for hypotensive shock.

BACKGROUND: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016. OBJECTIVES: Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data. MAIN RESULTS: We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.

Anaesthetic interventions for prevention of awareness during surgery.

BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. OBJECTIVES: To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness:- anaesthetic drug regimens; and- intraoperative anaesthetic depth monitors. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, ISSUE 4 2016); PubMed from 1950 to April 2016; MEDLINE from 1950 to April 2016; and Embase from 1980 to April 2016. We contacted experts to identify additional studies. We performed a handsearch of the citations in the review. We did not search trial registries. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of either anaesthetic regimens or anaesthetic depth monitors. We excluded volunteer studies, studies of patients prior to skin incision, intensive care unit studies, and studies that only randomized different word presentations for memory tests (not anaesthetic interventions).Anaesthetic drug regimens included studies of induction or maintenance, or both. Anaesthetic depth monitors included the Bispectral Index monitor, M-Entropy, Narcotrend monitor, cerebral function monitor, cerebral state monitor, patient state index, and lower oesophageal contractility monitor. The use of anaesthetic depth monitors allows the titration of anaesthetic drugs to maintain unconsciousness. DATA COLLECTION AND ANALYSIS: At least two authors independently scanned abstracts, extracted data from the studies, and evaluated studies for risk of bias. We made attempts to contact all authors for additional clarification. We performed meta-analysis statistics in packages of the R language. MAIN RESULTS: We included 160 studies with 54,109 enrolled participants; 53,713 participants started the studies and 50,034 completed the studies or data analysis (or both). We could not use 115 RCTs in meta-analytic comparisons because they had zero awareness events. We did not merge 27 of the remaining 45 studies because they had excessive clinical and methodological heterogeneity. We pooled the remaining 18 eligible RCTs in meta-analysis. There are 10 studies awaiting classification which we will process when we update the review.The meta-analyses included 18 trials with 36,034 participants. In the analysis of anaesthetic depth monitoring (either Bispectral Index or M-entropy) versus standard clinical and electronic monitoring, there were nine trials with 34,744 participants. The overall event rate was 0.5%. The effect favoured neither anaesthetic depth monitoring nor standard clinical and electronic monitoring, with little precision in the odds ratio (OR) estimate (OR 0.98, 95% confidence interval (CI) 0.59 to 1.62).In a five-study subset of Bispectral Index monitoring versus standard clinical and electronic monitoring, with 34,181 participants, 503 participants gave awareness reports to a blinded, expert panel who adjudicated or judged the outcome for each patient after reviewing the questionnaires: no awareness, possible awareness, or definite awareness. Experts judged 351 patient awareness reports to have no awareness, 87 to have possible awareness, and 65 to have definite awareness. The effect size favoured neither Bispectral Index monitoring nor standard clinical and electronic monitoring, with little precision in the OR estimate for the combination of definite and possible awareness (OR 0.96, 95% CI 0.35 to 2.65). The effect size favoured Bispectral Index monitoring for definite awareness, but with little precision in the OR estimate (OR 0.60, 95% CI 0.13 to 2.75).We performed three smaller meta-analyses of anaesthetic drugs. There were nine studies with 1290 participants. Wakefulness was reduced by ketamine and etomidate compared to thiopental. Wakefulness was more frequent than awareness. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo., Also, higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness.We graded the quality of the evidence as low or very low in the 'Summary of findings' tables for the five comparisons.Most of the secondary outcomes in this review were not reported in the included RCTs. AUTHORS' CONCLUSIONS: Anaesthetic depth monitors may have similar effects to standard clinical and electrical monitoring on the risk of awareness during surgery. In older studies comparing anaesthetics in a smaller portion of the patient sample, wakefulness occurred more frequently than awareness. Use of etomidate and ketamine lowered the risk of wakefulness compared to thiopental. Benzodiazepines compared to thiopental and ketamine, or higher doses of inhaled anaesthetics versus lower doses, reduced the risk of awareness.

Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery.

BACKGROUND: The management of postoperative pain and recovery is still unsatisfactory in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects including nausea and constipation. These adverse effects prevent smooth postoperative recovery. On the other hand not all patients may be suited to, and take benefit from, epidural analgesia used to enhance postoperative recovery. The non-opioid lidocaine was investigated in several studies for its use in multi-modal management strategies to reduce postoperative pain and enhance recovery. OBJECTIVES: The aim of this review was to assess the effects (benefits and risks) of perioperative intravenous lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5 2014), MEDLINE (January 1966 to May 2014), EMBASE (1980 to May 2014), CINAHL (1982 to May 2014), and reference lists of articles. We searched the trial registry database ClinicalTrials.gov, contacted researchers in the field, and handsearched journals and congress proceedings. We did not apply any language restrictions. SELECTION CRITERIA: We included randomized controlled trials comparing the effect of continuous perioperative intravenous lidocaine infusion either with placebo, or no treatment, or with epidural analgesia in adults undergoing elective or urgent surgery under general anaesthesia. The intravenous lidocaine infusion must have been started intraoperatively prior to incision and continued at least until the end of surgery. DATA COLLECTION AND ANALYSIS: Trial quality was independently assessed by two authors according to the methodological procedures specified by the Cochrane Collaboration. Data were extracted by two independent authors. We collected trial data on postoperative pain, recovery of gastrointestinal function, length of hospital stay, postoperative nausea and vomiting (PONV), opioid consumption, patient satisfaction, surgical complication rates, and adverse effects of the intervention. MAIN RESULTS: We included 45 trials involving 2802 participants. Two trials compared intravenous lidocaine versus epidural analgesia. In all the remaining trials placebo or no treatment was used as a comparator. Trials involved participants undergoing open abdominal (12), laparoscopic abdominal (13), or various other surgical procedures (20).The risk of bias was low with respect to selection bias (random sequence generation), performance bias, attrition bias, and detection bias in more than 50% of the included studies. For allocation concealment and selective reporting the quality assessment yielded low risk of bias for only approximately 20% of the included studies.We found evidence of effect for intravenous lidocaine on the reduction of postoperative pain (visual analogue scale, 0 to 10 cm) compared to placebo or no treatment at 'early time points (one to four hours)' (mean difference (MD) -0.84 cm, 95% confidence interval (CI) -1.10 to -0.59; low-quality evidence) and at 'intermediate time points (24 hours)' (MD -0.34 cm, 95% CI -0.57 to -0.11; low-quality evidence) after surgery. However, no evidence of effect was found for lidocaine to reduce pain at 'late time points (48 hours)' (MD -0.22 cm, 95% CI -0.47 to 0.03; low-quality evidence). Pain reduction was most obvious at 'early time points' in participants undergoing laparoscopic abdominal surgery (MD -1.14, 95% CI -1.51 to -0.78; low-quality evidence) and open abdominal surgery (MD -0.72, 95% CI -0.96 to -0.47; moderate-quality evidence). No evidence of effect was found for lidocaine to reduce pain in participants undergoing all other surgeries (MD -0.30, 95% CI -0.89 to 0.28; low-quality evidence). Quality of evidence is limited due to inconsistency and indirectness (small trial sizes).Evidence of effect was found for lidocaine on gastrointestinal recovery regarding the reduction of the time to first flatus (MD -5.49 hours, 95% CI -7.97 to -3.00; low-quality evidence), time to first bowel movement (MD -6.12 hours, 95% CI -7.36 to -4.89; low-quality evidence), and the risk of paralytic ileus (risk ratio (RR) 0.38, 95% CI 0.15 to 0.99; low-quality evidence). However, no evidence of effect was found for lidocaine on shortening the time to first defaecation (MD -9.52 hours, 95% CI -23.24 to 4.19; very low-quality evidence).Furthermore, we found evidence of positive effects for lidocaine administration on secondary outcomes such as reduction of length of hospital stay, postoperative nausea, intraoperative and postoperative opioid requirements. There was limited data on the effect of IV lidocaine on adverse effects (e.g. death, arrhythmias, other heart rate disorders or signs of lidocaine toxicity) compared to placebo treatment as only a limited number of studies systematically analysed the occurrence of adverse effects of the lidocaine intervention.The comparison of intravenous lidocaine versus epidural analgesia revealed no evidence of effect for lidocaine on relevant outcomes. However, the results have to be considered with caution due to imprecision of the effect estimates. AUTHORS' CONCLUSIONS: There is low to moderate evidence that this intervention, when compared to placebo, has an impact on pain scores, especially in the early postoperative phase, and on postoperative nausea. There is limited evidence that this has further impact on other relevant clinical outcomes, such as gastrointestinal recovery, length of hospital stay, and opioid requirements. So far there is a scarcity of studies that have systematically assessed the incidence of adverse effects; the optimal dose; timing (including the duration of the administration); and the effects when compared with epidural anaesthesia.

Neuraxial anesthesia for the prevention of postoperative mortality and major morbidity: an overview of cochrane systematic reviews.

BACKGROUND: This analysis summarized Cochrane reviews that assess the effects of neuraxial anesthesia on perioperative rates of death, chest infections, and myocardial infarction. METHODS: A search was performed in the Cochrane Database of Systematic Reviews on July 13, 2012. We have included all Cochrane systematic reviews that examined subjects of any age undergoing any type of surgical (open or endoscopic) procedure, compared neuraxial anesthesia to general anesthesia alone for the surgical anesthesia, or neuraxial anesthesia plus general anesthesia to general anesthesia alone for the surgical anesthesia, and included death, chest infections, myocardial infarction, and/or serious adverse events as outcomes. Studies included in these reviews were selected on the same criteria. RESULTS: Nine Cochrane reviews were selected for this overview. Their scores on the Overview Quality Assessment Questionnaire varied from 4 to 6 of a maximal possible score of 7. Compared with general anesthesia, neuraxial anesthesia reduced the 0- to-30-day mortality (risk ratio [RR] 0.71; 95% confidence interval [CI], 0.53-0.94; I = 0%) based on 20 studies that included 3006 participants. Neuraxial anesthesia also decreased the risk of pneumonia (RR 0.45; 95% CI, 0.26-0.79; I = 0%) based on 5 studies that included 400 participants. No difference was detected in the risk of myocardial infarction between the 2 techniques (RR 1.17; 95% CI, 0.57-2.37; I = 0%) based on 6 studies with 849 participants. Compared with general anesthesia alone, adding neuraxial anesthesia to general anesthesia did not affect the 0- to-30-day mortality (RR 1.07; 95% CI, 0.76-1.51; I = 0%) based on 18 studies with 3228 participants. No difference was detected in the risk of myocardial infarction between combined neuraxial anesthesia-general anesthesia and general anesthesia alone (RR 0.69; 95% CI, 0.44-1.09; I = 0%) based on 8 studies that included 1580 participants. Adding a neuraxial anesthesia to general anesthesia reduced the risk of pneumonia (RR 0.69; 95% CI, 0.49-0.98; I = 9%) after adjustment for publication bias and based on 9 studies that included 2433 participants. The quality of the evidence was judged as moderate for all 6 comparisons. The quality of the reporting score of complications related to neuraxial blocks was 9 (4 to 12 [median {range}]) for a possible maximum score of 14. CONCLUSIONS: Compared with general anesthesia, neuraxial anesthesia may reduce the 0-to-30-day mortality for patients undergoing a surgery with an intermediate-to-high cardiac risk (level of evidence moderate). Large randomized controlled trials on the difference in death and major outcomes between regional and general anesthesia are required.

Anaesthetic techniques for risk of malignant tumour recurrence.

BACKGROUND: Surgery remains a mainstay of treatment for malignant tumours; however, surgical manipulation leads to a significant systemic release of tumour cells. Whether these cells lead to metastases is largely dependent on the balance between aggressiveness of the tumour cells and resilience of the body. Surgical stress per se, anaesthetic agents and administration of opioid analgesics perioperatively can compromise immune function and might shift the balance towards progression of minimal residual disease. Regional anaesthesia techniques provide perioperative pain relief; they therefore reduce the quantity of systemic opioids and of anaesthetic agents used. Additionally, regional anaesthesia techniques are known to prevent or attenuate the surgical stress response. In recent years, the potential benefit of regional anaesthesia techniques for tumour recurrence has received major attention and has been discussed many times in the literature. In preparing this review, we aimed to summarize the current evidence systematically and comprehensively. OBJECTIVES: To establish whether anaesthetic technique (general anaesthesia versus regional anaesthesia or a combination of the two techniques) influences the long-term prognosis for individuals with malignant tumours. SEARCH METHODS: We searched The Cochrane Library (2013, Issue 12), PubMed (1950 to 15 December 2013), EMBASE (1974 to 15 December 2013), BIOSIS (1926 to 15 December 2013) and Web of Science (1965 to 15 December 2013). We handsearched relevant websites and conference proceedings and reference lists of cited articles. We applied no language restrictions. SELECTION CRITERIA: We included all randomized controlled trials or controlled clinical trials that investigated the effects of general versus regional anaesthesia on the risk of malignant tumour recurrence in patients undergoing resection of primary malignant tumours. Comparisons of interventions consisted of (1) general anaesthesia alone versus general anaesthesia combined with one or more regional anaesthetic techniques; (2) general anaesthesia combined with one or more regional anaesthetic techniques versus one or more regional anaesthetic techniques; and (3) general anaesthesia alone versus one or more regional anaesthetic techniques. Primary outcomes included (1) overall survival, (2) progression-free survival and (3) time to tumour progression. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the titles and abstracts of identified reports and extracted study data.All primary outcome variables are time-to-event data. If the individual trial report provided summary statistics with odds ratios, relative risks or Kaplan-Meier curves, extracted data enabled us to calculate the hazard ratio using the hazard ratio calculating spreadsheet. To assess risk of bias, we used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included four studies with a total of 746 participants. All studies included adult patients undergoing surgery for primary tumour resection. Two studies enrolled male and female participants undergoing major abdominal surgery for cancer. One study enrolled male participants undergoing surgery for prostate cancer, and one study male participants undergoing surgery for colon cancer. Follow-up time ranged from nine to 17 years. All four studies compared general anaesthesia alone versus general anaesthesia combined with epidural anaesthesia and analgesia. All four studies are secondary data analyses of previously conducted prospective randomized controlled trials.Of the four included studies, only three contributed to the outcome of overall survival, and two each to the outcomes of progression-free survival and time to tumour progression. In our meta-analysis, we could not find an advantage for either study group for the outcomes of overall survival (hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.86 to 1.24) and progression-free survival (HR 0.88, 95% CI 0.56 to 1.38). For progression-free survival, the level of inconsistency was high. Pooled data for time to tumour progression showed a slightly favourable outcome for the control group (general anaesthesia alone) compared with the intervention group (epidural and general anaesthesia) (HR 1.50, 95% CI 1.00 to 2.25).Quality of evidence was graded low for overall survival and very low for progression-free survival and time to tumour progression. The outcome of overall survival was downgraded for serious imprecision and serious indirectness. The outcomes of progression-free survival and time to tumour progression were also downgraded for serious inconsistency and serious risk of bias, respectively.Reporting of adverse events was sparse, and data could not be analysed. AUTHORS' CONCLUSIONS: Currently, evidence for the benefit of regional anaesthesia techniques on tumour recurrence is inadequate. An encouraging number of prospective randomized controlled trials are ongoing, and it is hoped that their results, when reported, will add evidence for this topic in the near future.

Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death.

BACKGROUND: The diagnosis of death using neurological criteria (brain death) has profound social, legal and ethical implications. The diagnosis can be made using standard clinical tests examining for brain function, but in some patient populations and in some countries additional tests may be required. Computed tomography (CT) angiography, which is currently in wide clinical use, has been identified as one such test. OBJECTIVES: To assess from the current literature the sensitivity of CT cerebral angiography as an additional confirmatory test for diagnosing death using neurological criteria, following satisfaction of clinical neurological criteria for brain death. SEARCH METHODS: We performed comprehensive literature searches to identify studies that would assess the diagnostic accuracy of CT angiography (the index test) in cohorts of adult patients, using the diagnosis of brain death according to neurological criteria as the target condition. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and the following databases from January 1992 to August 2012: MEDLINE; EMBASE; BNI; CINAHL; ISI Web of Science; BioMed Central. We also conducted searches in regional electronic bibliographic databases and subject-specific databases (MEDION; IndMed; African Index Medicus). A search was also conducted in Google Scholar where we reviewed the first 100 results only. We handsearched reference lists and conference proceedings to identify primary studies and review articles. Abstracts were identified by two authors. Methodological assessment of studies using the QUADAS-2 tool and further data extraction for re-analysis were performed by three authors. SELECTION CRITERIA: We included in this review all large case series and cohort studies that compared the results of CT angiography with the diagnosis of brain death according to neurological criteria. Uniquely, the reference standard was the same as the target condition in this review. DATA COLLECTION AND ANALYSIS: We reviewed all included studies for methodological quality according to the QUADAS-2 criteria. We encountered significant heterogeneity in methods used to interpret CT angiography studies and therefore, where possible, we re-analysed the published data to conform to a standard radiological interpretation model. The majority of studies (with one exception) were not designed to include patients who were not brain dead, and therefore overall specificity was not estimable as part of a meta-analysis. Sensitivity, confidence and prediction intervals were calculated for both as-published data and as re-analysed to a standardized interpretation model. MAIN RESULTS: Ten studies were found including 366 patients in total. We included eight studies in the as-published data analysis, comprising 337 patients . The methodological quality of the studies was overall satisfactory, however there was potential for introduction of significant bias in several specific areas relating to performance of the index test and to the timing of index versus reference tests. Results demonstrated a sensitivity estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate prediction interval was very wide (0.34 to 0.98). Data in three studies were available as a four-vessel interpretation model and the data could be re-analysed to a four-vessel interpretation model in a further five studies, comprising 314 patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95% CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56 to 0.96). AUTHORS' CONCLUSIONS: The available evidence cannot support the use of CT angiography as a mandatory test, or as a complete replacement for neurological testing, in the management pathway of patients who are suspected to be clinically brain dead. CT angiography may be useful as a confirmatory or add-on test following a clinical diagnosis of death, assuming that clinicians are aware of the relatively low overall sensitivity. Consensus on a standard radiological interpretation protocol for future published studies would facilitate further meta-analysis.

Neuraxial blockade for the prevention of postoperative mortality and major morbidity: an overview of Cochrane systematic reviews.

BACKGROUND: Various beneficial effects derived from neuraxial blocks have been reported. However, it is unclear whether these effects have an influence on perioperative mortality and major pulmonary/cardiovascular complications. OBJECTIVES: Our primary objective was to summarize Cochrane systematic reviews that assess the effects of neuraxial blockade on perioperative rates of death, chest infection and myocardial infarction by integrating the evidence from all such reviews that have compared neuraxial blockade with or without general anaesthesia versus general anaesthesia alone for different types of surgery in various populations. Our secondary objective was to summarize the evidence on adverse effects (an adverse event for which a causal relation between the intervention and the event is at least a reasonable possibility) of neuraxial blockade. Within the reviews, studies were selected using the same criteria. METHODS: A search was performed in the Cochrane Database of Systematic Reviews on July 13, 2012. We have (1) included all Cochrane systematic reviews that examined participants of any age undergoing any type of surgical (open or endoscopic) procedure, (2) compared neuraxial blockade versus general anaesthesia alone for surgical anaesthesia or neuraxial blockade plus general anaesthesia versus general anaesthesia alone for surgical anaesthesia and (3) included death, chest infection, myocardial infarction and/or serious adverse events as outcomes. Neuraxial blockade could consist of epidural, caudal, spinal or combined spinal-epidural techniques administered as a bolus or by continuous infusion. Studies included in these reviews were selected on the basis of the same criteria. Reviews and studies were selected independently by two review authors, who independently performed data extraction when data differed from one of the selected reviews. Data were analysed by using Review Manager Version 5.1 and Comprehensive Meta Analysis Version 2.2.044. MAIN RESULTS: Nine Cochrane reviews were selected for this overview. Their scores on the Overview Quality Assessment Questionnaire varied from four to six of a maximal possible score of seven. Compared with general anaesthesia, neuraxial blockade reduced the zero to 30-day mortality (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53 to 0.94; I(2) = 0%) based on 20 studies that included 3006 participants. Neuraxial blockade also decreased the risk of pneumonia (RR 0.45, 95% CI 0.26 to 0.79; I(2) = 0%) based on five studies that included 400 participants. No difference was detected in the risk of myocardial infarction between the two techniques (RR 1.17, 95% CI 0.57 to 2.37; I(2) = 0%) based on six studies with 849 participants. Compared with general anaesthesia alone, the addition of a neuraxial block to general anaesthesia did not affect the zero to 30-day mortality (RR 1.07, 95% CI 0.76 to 1.51; I(2) = 0%) based on 18 studies with 3228 participants. No difference was detected in the risk of myocardial infarction between combined neuraxial blockade-general anaesthesia and general anaesthesia alone (RR 0.69, 95% CI 0.44 to 1.09; I(2) = 0%) based on eight studies that included 1580 participants. The addition of a neuraxial block to general anaesthesia reduced the risk of pneumonia (RR 0.69, 95% CI 0.49 to 0.98; I(2) = 9%) after adjustment for publication bias and based on nine studies that included 2433 participants. The quality of the evidence was judged as moderate for all six comparisons.No serious adverse events (seizure or cardiac arrest related to local anaesthetic toxicity, prolonged central or peripheral neurological injury lasting longer than one month or infection secondary to neuraxial blockade) were reported. The quality of the reporting score of complications related to neuraxial blocks was nine (four to 12 (median range)) of a possible maximum score of 14. AUTHORS' CONCLUSIONS: Compared with general anaesthesia, a central neuraxial block may reduce the zero to 30-day mortality for patients undergoing surgery with intermediate to high cardiac risk (level of evidence, moderate). Further research is required.

Positive end-expiratory pressure (PEEP) during anaesthesia for the prevention of mortality and postoperative pulmonary complications.

BACKGROUND: General anaesthesia causes atelectasis which can lead to impaired respiratory function. Positive end-expiratory pressure (PEEP) is a mechanical manoeuvre which increases functional residual capacity (FRC) and prevents collapse of the airways thereby reducing atelectasis. It is not known whether intra-operative PEEP alters the risk of postoperative mortality and pulmonary complications. OBJECTIVES: To assess the benefits and harms of intraoperative PEEP, for all adult surgical patients, on postoperative mortality and pulmonary outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (via Ovid) (1966 to January 2010), EMBASE (via Ovid) (1980 to January 2010), CINAHL (via EBSCOhost) (1982 to January 2010), ISI Web of Science (1945 to January 2010) and LILACS (via BIREME interface) (1982 to January 2010). SELECTION CRITERIA: We included randomized clinical trials that evaluated the effect of PEEP versus no PEEP, during general anaesthesia, on postoperative mortality and postoperative respiratory complications. We included studies irrespective of language and publication status. DATA COLLECTION AND ANALYSIS: Two investigators independently selected papers, extracted data that fulfilled our outcome criteria and assessed the quality of all included trials. We undertook pooled analyses, where appropriate. For our primary outcome (mortality) and two secondary outcomes (respiratory failure and pneumonia), we calculated the number of further patients needed (information size) in order to make reliable conclusions. MAIN RESULTS: We included eight randomized trials with a total of 330 patients. Two trials had a low risk of bias. There was no difference demonstrated for mortality (relative risk (RR) 0.95, 95% CI 0.14 to 6.39). Two statistically significant results were found: the PEEP group had a higher PaO(2)/FiO(2) on day 1 postoperatively (mean difference (MD) 22.98, 95% CI 4.40 to 41.55) and postoperative atelectasis (defined as an area of collapsed lung, quantified by computerized tomography (CT) scan) was less in the PEEP group (SMD -1.2, 95% CI -1.78 to -0.79). There were no adverse events reported in the three trials that adequately measured these outcomes (barotrauma and cardiac complications). Using information size calculations, we estimated that a further 21,200 patients would need to be randomized in order to make a reliable conclusion about PEEP and mortality. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to make conclusions about whether intraoperative PEEP alters the risk of postoperative mortality and respiratory complications among undifferentiated surgical patients.

Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics.

BACKGROUND: Spinal anaesthesia has been in use since 1898. During the last decade there has been an increase in the number of reports implicating lidocaine as a possible cause of temporary and permanent neurologic complications after spinal anaesthesia. Follow up of patients who received uncomplicated spinal anaesthesia revealed that some of them developed pain in the lower extremities after an initial full recovery. This painful condition that occurs in the immediate postoperative period was named 'transient neurologic symptoms' (TNS). OBJECTIVES: To study the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine compared to other local anaesthetics. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials Register (CENTRAL) (The Cochrane Library, Issue 4, 2008); MEDLINE (1966 to August 2008); EMBASE (1980 to week 35, 2008); LILACS (August 2008); and handsearched the reference lists of trials and review articles. SELECTION CRITERIA: We included all randomized and quasi-randomized studies comparing the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine as compared to other local anaesthetics. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Sixteen trials reporting on 1467 patients, 125 of whom developed TNS, were included in the analysis. The use of lidocaine for spinal anaesthesia increased the risk of developing TNS. There was no evidence that this painful condition was associated with any neurologic pathology; the symptoms disappeared spontaneously by the fifth postoperative day. The relative risk (RR) for developing TNS after spinal anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine, prilocaine, procaine, levobupivacaine, ropivacaine, and 2-chloroprocaine) was 7.31 (95% confidence interval (CI) 4.16 to 12.86). Mepivacaine was found to give similar results as lidocaine and was therefor omitted from the overall comparison to diminish the heterogeneity. AUTHORS' CONCLUSIONS: The risk of developing TNS after spinal anaesthesia with lidocaine was significantly higher than when bupivacaine, prilocaine, or procaine were used. The term 'transient neurological symptoms' implies neurologic pathology. Failing identification of the pathogenesis of TNS, consideration should be given to choosing a neutral descriptive term which does not imply a particular causation. One study about the impact of TNS on patient satisfaction and functional impairment demonstrated that non-TNS patients were more satisfied and had less functional impairment after surgery than TNS patients, but this did not influence their willingness to recommend spinal anaesthesia.

Research methods for meta-analyses.

Meta-analysis uses numerical tools to pool data and to estimate a summary effect size for the comparison of two interventions from a set of randomised controlled trials identified in a systematic review. An effect size is a single number that expresses the difference in outcome from the interventions. The most commonly used effect sizes for dichotomous outcomes, for example, mortality, are the odds ratio and the relative risk. The results of a meta-analysis are usually presented in a complex figure, known as a forest plot, which shows both the individual studies and the summary statistics. Sensitivity analyses are performed to clarify the effect of the experimental design bias on the effect size. Clinical and statistical heterogeneity of the included studies are explored by the additional tools of fixed effect versus random effects models and subgroup analyses.