Background
Operations on structures in the chest (usually the lungs) involve cutting between the ribs (thoracotomy). Severe post‐thoracotomy pain can result from pleural (lung lining) and muscular ...damage, costovertebral joint (ribcage) disruption and intercostal nerve (nerves that run along the ribs) damage during surgery. Poor pain relief after surgery can impede recovery and increase the risks of developing complications such as lung collapse, chest infections and blood clots due to ineffective breathing and clearing of secretions. Effective management of acute pain following thoracotomy may prevent these complications and reduce the likelihood of developing chronic pain. A multi‐modal approach to analgesia is widely employed by thoracic anaesthetists using a combination of regional anaesthetic blockade and systemic analgesia, with both non‐opioid and opioid medications and local anaesthesia blockade.
There is some evidence that blocking the nerves as they emerge from the spinal column (paravertebral block, PVB) may be associated with a lower risk of major complications in thoracic surgery but the majority of thoracic anaesthetists still prefer to use a thoracic epidural blockade (TEB) as analgesia for their patients undergoing thoracotomy. In order to bring about a change in practice, anaesthetists need a review that evaluates the risk of all major complications associated with thoracic epidural and paravertebral block in thoracotomy.
Objectives
To compare the two regional techniques of TEB and PVB in adults undergoing elective thoracotomy with respect to:
1. analgesic efficacy;
2. the incidence of major complications (including mortality);
3. the incidence of minor complications;
4. length of hospital stay;
5. cost effectiveness.
Search methods
We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 9); MEDLINE via Ovid (1966 to 16 October 2013); EMBASE via Ovid (1980 to 16 October 2013); CINAHL via EBSCO host (1982 to 16 October 2013); and reference lists of retrieved studies. We handsearched the Journal of Cardiothoracic Surgery and Journal of Cardiothoracic and Vascular Anesthesia (16 October 2013). We reran the search on 31st January 2015. We found one additional study which is awaiting classification and will be addressed when we update the review.
Selection criteria
We included all randomized controlled trials (RCTs) comparing PVB with TEB in thoracotomy, including upper gastrointestinal surgery.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. Two review authors (JY and SG) independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta‐analysis).
Main results
We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real‐world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low‐quality evidence that showed no significant difference in 30‐day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate‐quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate‐quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs.
Authors' conclusions
Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30‐day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well‐conducted, adequately‐powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs.
Background
The number of visits for antenatal (prenatal) care developed without evidence of how many visits are necessary. The content of each visit also needs evaluation.
Objectives
To compare the ...effects of antenatal care programmes with reduced visits for low‐risk women with standard care.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2015), reference lists of articles and contacted researchers in the field.
Selection criteria
Randomised trials comparing a reduced number of antenatal visits, with or without goal‐oriented care, versus standard care.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. We assessed studies for risk of bias and graded the quality of the evidence.
Main results
We included seven trials (more than 60,000 women): four in high‐income countries with individual randomisation; three in low‐ and middle‐income countries with cluster randomisation (clinics as the unit of randomisation). Most of the data included in the review came from the three large, well‐designed cluster‐randomised trials that took place in Argentina, Cuba, Saudi Arabia, Thailand and Zimbabwe. All results have been adjusted for the cluster design effect. All of the trials were at some risk of bias as blinding of women and staff was not feasible with this type of intervention. For primary outcomes, evidence was graded as being of moderate or low quality, with downgrading decisions due to risks of bias and imprecision of effects.
The number of visits for standard care varied, with fewer visits in low‐ and middle‐ income country trials. In studies in high‐income countries, women in the reduced visits groups, on average, attended between 8.2 and 12 times. In low‐ and middle‐ income country trials, many women in the reduced visits group attended on fewer than five occasions, although in these trials the content as well as the number of visits was changed, so as to be more 'goal‐oriented'.
Perinatal mortality was increased for those randomised to reduced visits rather than standard care, and this difference was borderline for statistical significance (risk ratio (RR) 1.14; 95% confidence interval (CI) 1.00 to 1.31; five trials, 56,431 babies; moderate‐quality evidence). In the subgroup analysis, for high‐income countries the number of deaths was small (32/5108), and there was no clear difference between the groups (RR 0.90; 95% CI 0.45 to 1.80, two trials); for low‐ and middle‐income countries perinatal mortality was significantly higher in the reduced visits group (RR 1.15; 95% CI 1.01 to 1.32, three trials).
There was no clear difference between groups for our other primary outcomes: maternal death (RR 1.13, 95%CI 0.50 to 2.57, three cluster‐randomised trials, 51,504 women, low‐quality evidence); hypertensive disorders of pregnancy (various definitions including pre‐eclampsia) (RR 0.95, 95% CI 0.80 to 1.12, six studies, 54,108 women, low‐quality evidence); preterm birth (RR 1.02, 95% CI 0.94 to 1.11; seven studies, 53,661 women, moderate‐quality evidence); and small‐for‐gestational age (RR 0.99, 95% CI 0.91 to 1.09, four studies 43,045 babies, moderate‐quality evidence).
Reduced visits were associated with a reduction in admission to neonatal intensive care that was borderline for significance (RR 0.89; 95% CI 0.79 to 1.02, five studies, 43,048 babies, moderate quality evidence). There were no clear differences between the groups for the other secondary clinical outcomes.
Women in all settings were less satisfied with the reduced visits schedule and perceived the gap between visits as too long. Reduced visits may be associated with lower costs.
Authors' conclusions
In settings with limited resources where the number of visits is already low, reduced visits programmes of antenatal care are associated with an increase in perinatal mortality compared to standard care, although admission to neonatal intensive care may be reduced. Women prefer the standard visits schedule. Where the standard number of visits is low, visits should not be reduced without close monitoring of fetal and neonatal outcome.
Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine ...whether the use of epinephrine is safe and effective in such patients.
In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 no symptoms to 6 death).
At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval CI, 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients 2.2% vs. 74 of 3994 patients 1.9%; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients 31.0% vs. 16 of 90 patients 17.8%).
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024 .).
Summary Background Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists ...for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest. Methods The pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942. Findings We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (<1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30 day survival was similar in the LUCAS-2 group (104 6% of 1652 patients) and in the manual CPR group (193 7% of 2819 patients; adjusted odds ratio OR 0·86, 95% CI 0·64–1·15). No serious adverse events were noted. Seven clinical adverse events were reported in the LUCAS-2 group (three patients with chest bruising, two with chest lacerations, and two with blood in mouth). 15 device incidents occurred during operational use. No adverse or serious adverse events were reported in the manual group. Interpretation We noted no evidence of improvement in 30 day survival with LUCAS-2 compared with manual compressions. On the basis of ours and other recent randomised trials, widespread adoption of mechanical CPR devices for routine use does not improve survival. Funding National Institute for Health Research HTA – 07/37/69.
Abstract Aim To summarise the evidence from randomised controlled trials of mechanical chest compression devices used during resuscitation after out of hospital cardiac arrest. Methods Systematic ...review of studies evaluating the effectiveness of mechanical chest compression. We included randomised controlled trials or cluster randomised trials that compared mechanical chest compression (using any device) with manual chest compression for adult patients following out-of-hospital cardiac arrest. Outcome measures were return of spontaneous circulation, survival of event, overall survival, survival with good neurological outcome. Results were combined using random-effects meta-analysis. Data sources Studies were identified by searches of electronic databases, reference lists of other studies and review articles. Results Five trials were included, of which three evaluated the LUCAS or LUCAS-2 device and two evaluated the AutoPulse device. The results did not show an advantage to the use of mechanical chest compression devices for survival to discharge/30 days (average OR 0.89, 95% CI 0.77, 1.02) and survival with good neurological outcome (average OR 0.76, 95% CI 0.53, 1.11). Conclusions Existing studies do not suggest that mechanical chest compression devices are superior to manual chest compression, when used during resuscitation after out of hospital cardiac arrest.
Summary Background In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced ...extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS. Methods We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2 /FI O2 ) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86. Findings We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 34% of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio RR 1·47, 95% CI 1·03–2·08). Interpretation Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended. Funding UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.
There is a growing interest in the use of Bayesian adaptive designs in late-phase clinical trials. This includes the use of stopping rules based on Bayesian analyses in which the frequentist type I ...error rate is controlled as in frequentist group-sequential designs.
This paper presents a practical comparison of Bayesian and frequentist group-sequential tests. Focussing on the setting in which data can be summarised by normally distributed test statistics, we evaluate and compare boundary values and operating characteristics.
Although Bayesian and frequentist group-sequential approaches are based on fundamentally different paradigms, in a single arm trial or two-arm comparative trial with a prior distribution specified for the treatment difference, Bayesian and frequentist group-sequential tests can have identical stopping rules if particular critical values with which the posterior probability is compared or particular spending function values are chosen. If the Bayesian critical values at different looks are restricted to be equal, O'Brien and Fleming's design corresponds to a Bayesian design with an exceptionally informative negative prior, Pocock's design to a Bayesian design with a non-informative prior and frequentist designs with a linear alpha spending function are very similar to Bayesian designs with slightly informative priors.This contrasts with the setting of a comparative trial with independent prior distributions specified for treatment effects in different groups. In this case Bayesian and frequentist group-sequential tests cannot have the same stopping rule as the Bayesian stopping rule depends on the observed means in the two groups and not just on their difference. In this setting the Bayesian test can only be guaranteed to control the type I error for a specified range of values of the control group treatment effect.
Comparison of frequentist and Bayesian designs can encourage careful thought about design parameters and help to ensure appropriate design choices are made.
Abstract Background Bayesian adaptive methods are increasingly being used to design clinical trials and offer several advantages over traditional approaches. Decisions at analysis points are usually ...based on the posterior distribution of the treatment effect. However, there is some confusion as to whether control of type I error is required for Bayesian designs as this is a frequentist concept. Methods We discuss the arguments for and against adjusting for multiplicities in Bayesian trials with interim analyses. With two case studies we illustrate the effect of including interim analyses on type I/II error rates in Bayesian clinical trials where no adjustments for multiplicities are made. We propose several approaches to control type I error, and also alternative methods for decision-making in Bayesian clinical trials. Results In both case studies we demonstrated that the type I error was inflated in the Bayesian adaptive designs through incorporation of interim analyses that allowed early stopping for efficacy and without adjustments to account for multiplicity. Incorporation of early stopping for efficacy also increased the power in some instances. An increase in the number of interim analyses that only allowed early stopping for futility decreased the type I error, but also decreased power. An increase in the number of interim analyses that allowed for either early stopping for efficacy or futility generally increased type I error and decreased power. Conclusions Currently, regulators require demonstration of control of type I error for both frequentist and Bayesian adaptive designs, particularly for late-phase trials. To demonstrate control of type I error in Bayesian adaptive designs, adjustments to the stopping boundaries are usually required for designs that allow for early stopping for efficacy as the number of analyses increase. If the designs only allow for early stopping for futility then adjustments to the stopping boundaries are not needed to control type I error. If one instead uses a strict Bayesian approach, which is currently more accepted in the design and analysis of exploratory trials, then type I errors could be ignored and the designs could instead focus on the posterior probabilities of treatment effects of clinically-relevant values.
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