A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain

We searched MEDLINE, Embase, CINAHL, AMED and CENTRAL databases until December 2014 and included 133 randomised controlled trials of peri-operative gabapentin vs placebo. Gabapentin reduced mean (95% CI) 24-h morphine-equivalent consumption by 8.44 (7.26–9.62) mg, p < 0.001, whereas more specific reductions in morphine equivalents were predicted (R2 = 90%, p < 0.001) by the meta-regression equation: 3.73 + (−0.378 × control morphine consumption (mg)) + (−0.0023 × gabapentin dose (mg)) + (−1.917 × anaesthetic type), where ‘anaesthetic type’ is ‘1’ for general anaesthesia and ‘0’ for spinal anaesthesia. The type of surgery was not independently associated with gabapentin effect. Gabapentin reduced postoperative pain scores on a 10-point scale at 1 h, 2 h, 6 h, 12 h and 24 h by a mean (95% CI) of: 1.68 (1.35–2.01); 1.21 (0.88–1.55); 1.28 (0.98–1.57); 1.12 (0.91–1.33); and 0.71 (0.56–0.87), respectively, p < 0.001 for all. The risk ratios (95% CI) for postoperative nausea, vomiting, pruritus and sedation with gabapentin were: 0.78 (0.69–0.87), 0.67 (0.59–0.76), 0.64 (0.51–0.80) and 1.18 (1.09–1.28), respectively, p < 0.001 for all. Gabapentin reduced pre-operative anxiety and increased patient satisfaction on a 10-point scale by a mean (95% CI) of 1.52 (0.78–2.26) points and 0.89 (0.22–1.57) points, p < 0.001 and p = 0.01, respectively. All the effects of gabapentin may have been overestimated by statistically significant small study effects

A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection

BackgroundResection of colorectal cancer (CRC) initiates inflammation, mediated at least partly by NFĸB (nuclear factor kappa-light-chain-enhancer of activated B-cells), leading to muscle catabolism and reduced physical performance. Eicosapentaenoic acid (EPA) has been shown to modulate NFĸB, but evidence for its benefit around the time of surgery is limited.ObjectiveTo assess the effect of EPA supplementation on muscle inflammation and physical function around the time of major surgery.DesignIn a double-blind randomized control trial, 61 patients (age: 68.3 ± 0.95 y; 42 male) scheduled for CRC resection, received 3 g per day of EPA (n = 32) or placebo (n = 29) for 5-days before and 21-days after operation. Lean muscle mass (LMM) (via dual energy X-ray absorptiometry (DXA)), anaerobic threshold (AT) (via cardiopulmonary exercise testing (CPET)) and hand-grip strength (HG) were assessed before and 4-weeks after surgery, with muscle biopsies (m. vastus lateralis) obtained for the assessment of NF-ĸB protein expression.ResultsThere were no differences in muscle NFĸB between EPA and placebo groups (mean difference (MD) −0.002; 95% confidence interval (CI) −0.19 to 0.19); p = 0.98). There was no difference in LMM (MD 704.77 g; 95% CI -1045.6 g–2455.13 g; p = 0.42) or AT (MD 1.11 mls/kg/min; 95% CI -0.52 mls/kg/min to 2.74 mls/kg/min; p = 0.18) between the groups. Similarly, there was no difference between the groups in HG at follow up (MD 0.1; 95% CI -1.88 to 2.08; p = 0.81). Results were similar when missing data was imputed.ConclusionEPA supplementation confers no benefit in terms of inflammatory status, as judged by NFĸB, or preservation of LMM, aerobic capacity or physical function following major colorectal surgery

Baseline morphine consumption may explain between-study heterogeneity in meta-analyses of adjuvant analgesics and improve precision and accuracy of effect estimates

BACKGROUND: Statistical heterogeneity can increase the uncertainty of results and reduce the quality of evidence derived from systematic reviews. At present, it is uncertain what the major factors are that account for heterogeneity in meta-analyses of analgesic adjuncts. Therefore, the aim of this review was to identify whether various covariates could explain statistical heterogeneity and use this to improve accuracy when reporting the efficacy of analgesics. METHODS: We searched for reviews using MEDLINE, EMBASE, CINAHL, AMED, and the Cochrane Database of Systematic Reviews. First, we identified the existence of considerable statistical heterogeneity (I2 > 75%). Second, we conducted meta-regression analysis for the outcome of 24-hour morphine consumption using baseline risk (control group morphine consumption) and other clinical and methodological covariates. Finally, we constructed a league table of adjuvant analgesics using a novel method of reporting effect estimates assuming a fixed consumption of 50 mg postoperative morphine. RESULTS: We included 344 randomized controlled trials with 28,130 participants. Ninety-one percent of analyses showed considerable statistical heterogeneity. Baseline risk was a significant cause of between-study heterogeneity for acetaminophen, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, tramadol, ketamine, [alpha]2-agonists, gabapentin, pregabalin, lidocaine, magnesium, and dexamethasone (R2 = 21%-100%; P 10 mg). We could not exclude a moderate clinically significant effect with ketamine. Dexamethasone demonstrated a small clinical benefit (>5 mg). CONCLUSIONS: We empirically identified baseline morphine consumption as the major source of heterogeneity in meta-analyses of adjuvant analgesics across all surgical interventions. Controlling for baseline morphine consumption, clinicians can use audit data to estimate the morphine-reducing effect of adding any adjuvant for their local population, regardless which surgery they undergo. Moreover, we have utilized these findings to present a novel method of reporting and an amended method of graphically displaying effect estimates, which both reduces confounding from variable baseline risk in included trials and is able to adjust for other clinical and methodological confounding variables. We recommend use of these methods in clinical practice and future reviews of analgesics for postoperative pain

Pre‐emptive and preventive opioids for postoperative pain in adults undergoing all types of surgery

Background: Postoperative pain is a common consequence of surgery and can have deleterious effects. It has been suggested that the administration of opioid analgesia before a painful stimulus may improve pain control. This can be done in two ways. We defined 'preventive opioids' as opioids administered before incision and continued postoperatively, and 'pre‐emptive opioids' as opioids given before incision but not continued postoperatively. Both pre‐emptive and preventive analgesia involve the initiation of an analgesic agent prior to surgical incision with the aim of reducing intraoperative nociception and therefore postoperative pain.Objectives: To assess the efficacy of preventive and pre‐emptive opioids for reducing postoperative pain in adults undergoing all types of surgery.Search methods: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED, and CINAHL (up to 18 March 2018). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication.Selection criteria: We included parallel‐group randomized controlled trials (RCTs) only. We included participants aged over 15 years old undergoing any type of surgery. We defined postincision opioids as the same intervention administered after incision whether single dose (as comparator with pre‐emptive analgesia) or continued postoperatively (as comparator with preventive analgesia) (control group). We considered studies that did and did not use a double‐dummy placebo (e.g. intervention group received active drug before incision and placebo after incision; control group received placebo before incision and active drug after incision).Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: early acute postoperative pain (measured within six hours and reported on a 0‐to‐10 scale) and respiratory depression. Our secondary outcomes included: late acute postoperative pain (24 to 48 hours and reported on a 0‐to‐10 scale), 24‐hour morphine consumption, and adverse events (intraoperative bradycardia and hypotension). We used GRADE to assess the quality of the evidence for each outcome.Main results: We included 20 RCTs, including one unpublished study with 1343 participants. Two studies were awaiting classification as the full text for these studies was not available. One study evaluated pre‐emptive opioids, and 19 studies evaluated preventive opioids. We considered only one study to be at low risk of bias for most domains. The surgeries and opioids used varied, although roughly half of the included studies were conducted in abdominal hysterectomy, and around a quarter used morphine as the intervention. All studies were conducted in secondary care.Pre‐emptive opioids compared to postincision opioidsFor pre‐emptive opioids in dental surgery, there may be a reduction in early acute postoperative pain (mean difference (MD) ‐1.20, 95% confidence interval (CI) ‐1.75 to ‐0.65; 40 participants; 1 study; low‐quality evidence). This study did not report on adverse events (respiratory depression, bradycardia, or hypotension). There may be a reduction in late acute postoperative pain (MD ‐2.10, 95% CI ‐2.57 to ‐1.63; 40 participants; 1 study; low‐quality evidence). This study did not report 24‐hour morphine consumption.Preventive opioids compared to postincision opioidsFor preventive opioids, there was probably no reduction in early acute postoperative pain (MD 0.11, 95% CI ‐0.32 to 0.53; 706 participants; 10 studies; I2 = 61%; moderate‐quality evidence). There were no events of respiratory depression in four studies (433 participants). There was no important reduction in late acute postoperative pain (MD ‐0.06, 95% CI ‐0.13 to 0.01; 668 participants; 9 studies; I2 = 0%; moderate‐quality evidence). There may be a small reduction in 24‐hour morphine consumption (MD ‐4.91 mg, 95% CI ‐9.39 mg to ‐0.44 mg; 526 participants; 11 studies; I2 = 82%; very low‐quality evidence). There may be similar rates of bradycardia (risk ratio (RR) 0.33, 95% CI 0.01 to 7.88; 112 participants; 2 studies; I2 = 0%; low‐quality evidence) and hypotension (RR 1.08, 95% CI 0.25 to 4.73; 88 participants; 2 studies; I2 = 0%; low‐quality evidence).Authors' conclusions: Due to the low quality of the evidence, we are uncertain whether pre‐emptive opioids reduce postoperative pain. Based on the trials conducted thus far, there was no clear evidence that preventive opioids result in reductions in pain scores. It was unclear if there was a reduction in morphine consumption due to very low‐quality of evidence. Too few studies reported adverse events to be able to draw any definitive conclusions. Once assessed, the two studies awaiting classification may alter the conclusions of the review

Preventive acetaminophen reduces postoperative opioid consumption, vomiting, and pain scores after surgery: systematic review and meta-analysis

Background and Objectives: Preventive analgesia has been proposed as a potential strategy to reduce postoperative pain. However, there is currently no review that focuses on acetaminophen for preventive analgesia. Methods: We conducted a search of MEDLINE, EMBASE, Cinahl, AMED, and CENTRAL databases identifying randomized controlled trials that compared preventive acetaminophen with postincision acetaminophen. Results: Seven studies with 544 participants were included. Overall, the studies showed a reduction in 24-hour opioid consumption (standardized mean difference [SMD] of -0.52; 95% confidence interval [95% CI], -0.98 to -0.06), lower pain scores at 1 hour (MD, -0.50; 95% CI, -0.98 to -0.02) and 2 hours (MD, -0.34; 95% CI, -0.67 to -0.01), and a lower incidence of postoperative vomiting (risk ratio, 0.50; 95% CI, 0.31-0.83) in the preventive acetaminophen group. Current studies are limited by a potential risk of bias. Conclusions: To our knowledge, this is the first review to describe a potential preventive effect of acetaminophen. However, well-conducted randomized controlled trials are necessary to substantiate the conclusions of this review

Botulism Type E Outbreak Associated with Eating a Beached Whale, Alaska

We report an outbreak of botulism that occurred in July 2002 in a group of 12 Alaskan Yu'pik Eskimos who ate blubber and skin from a beached beluga whale. Botulism death rates among Alaska Natives have declined in the last 20 years, yet incidence has increased

High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial

ObjectivesTo assess the efficacy of high-intensity interval training (HIIT) for improving cardiorespiratory fitness (CRF) in patients awaiting resection for urological malignancy within four weeks.Subjects/patients and methodsA randomised control trial of consecutive patients aged (>65 years) scheduled for major urological surgery in a large secondary referral centre in a UK hospital. The primary outcome is change in anaerobic threshold (VO2AT) following HIIT vs. standard care.ResultsForty patients were recruited (mean age 72 years, male (39): female (1)) with 34 completing the protocol. Intention to treat analysis showed significant improvements in anaerobic threshold (VO2AT; mean difference (MD) 2.26 ml/kg/min (95% CI 1.25–3.26)) following HIIT. Blood pressure (BP) also significantly reduced in following: HIIT (SBP: −8.2 mmHg (95% CI −16.09 to −0.29) and DBP: −6.47 mmHg (95% CI −12.56 to −0.38)). No reportable adverse safety events occurred during HIIT and all participants achieved >85% predicted maximum heart rate during sessions, with protocol adherence of 84%.ConclusionsHIIT can improve CRF and cardiovascular health, representing clinically meaningful and achievable pre-operative improvements. Larger randomised trials are required to investigate the efficacy of prehabilitation HIIT upon different cancer types, post-operative complications, socio-economic impact and long-term survival

Quick and simple: psoas density measurement is an independent predictor of anastomotic leak and other complications after colorectal resection

Purpose: Radiologically-defined sarcopenia has been shown to predict negative outcomes after cancer surgery, however radiological assessment of sarcopenia often requires additional software and standardisation against anthropomorphic data. Measuring psoas density using hospital Picture Archiving and Communication Systems, universally available in the UK, may have advantages over methods requiring the use of additional specialist and often costly software. This study aimed to assess the association between radiologically-defined sarcopenia measured by psoas density and postoperative outcome in patients having a colorectal cancer resectionMethods: All patients having a resection for colorectal cancer, discussed at the colorectal multi-disciplinary team in one institution between 1/1/15 and 31/12/15, were retrospectively identified. Mean psoas density at the level of the L3 vertebra were analysed from preoperative CT scans to define sarcopenia. Postoperative complications and mortality were recorded.Results: One hundred and sixty-nine patients had a colorectal resection for cancer and 140 of these had a primary anastomosis. Ninety-day mortality and 1-year mortality was 1.1% and 7.1% respectively. Eighteen(10.7%) patients suffered a Clavien-Dindo(CD) grade 3 or 4 complication of which 6(33%) were anastomotic leaks. In the whole cohort, sarcopenia was associated with an increased risk of CD3/4 complication(adjusted OR 6.33(1.65-24.23) p= 0.007). In those who had an anastomosis, sarcopenia was associated with an increased risk of anastomotic leak (adjusted OR 14.37(1.37-150.04) p=0.026).Conclusions: A quick and easy radiological assessment of sarcopenia using psoas density on standard hospital PACS is associated with a 6-fold increased risk of major post-operative complication and a 14-fold increase in anastomotic leak

Trainee-led emergency laparotomy operating

© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd Background: To achieve completion of training in general surgery, trainees are required to demonstrate competency in common procedures performed at emergency laparotomy. The aim of this study was to describe the patterns of trainee-led emergency laparotomy operating and the association between postoperative outcomes. Methods: Data on all patients who had an emergency laparotomy between December 2013 and November 2017 were extracted from the National Emergency Laparotomy Audit database. Patients were grouped by grade of operating surgeon: trainee (specialty registrar) or consultant (including post-Certificate of Completion of Training fellows). Trends in trainee operating by deanery, hospital size and time of day of surgery were investigated. Univariable and adjusted regression analyses were performed for the outcomes 90-day mortality and return to theatre, with analysis of patients in operative subgroups segmental colectomy, Hartmann's procedure, adhesiolysis and repair of perforated peptic ulcer disease. Results: The study cohort included 87 367 patients. The 90-day mortality rate was 15·1 per cent in the consultant group compared with 11·0 per cent in the trainee group. There were no increased odds of death by 90 days or of return to theatre across any of the operative groups when the operation was performed with a trainee listed as the most senior surgeon in theatre. Trainees were more likely to operate independently in high-volume centres (highest- versus lowest-volume centres: odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33) and at night (00.00 to 07.59 versus 08.00 to 11.59hours; OR 3·20, 2·95 to 3·48). Conclusion: There is significant variation in trainee-led operating in emergency laparotomy by geographical area, hospital size and by time of day. However, this does not appear to influence mortality or return to theatre

Anaesthetists stress is induced by patient ASA grade and may impair non-technical skills during intubation

BackgroundThe aims of this study were to determine if patient ASA grade was associated with increased stress in anaesthetists with a subsequent effect on non-technical skills.MethodsStress was measured using a validated objective (heart rate variability or heart rate) and subjective tool. We studied eight consultant anaesthetists at baseline (rest) and during 16 episodes of intubation with an ASA 1 or 2 patient vs. an ASA 3 or 4 patient. The primary outcome for the study was objective and subjective stress between both patient groups. Secondary outcomes were non-technical skill ratings and the association between stress measurements.ResultsASA 3 or 4 patients were associated with increases in objective stress when compared to baseline (mean 4.6 vs. 6.7; P = 0.004). However, ASA 1 or 2 patients were not associated with increases in stress when compared to baseline (mean 4.6 vs. 4.7; P = 1). There was no significant difference in subjective stress between the groups (P = 0.18). Objective stress negatively affected situational awareness (P = 0.03) and decision-making (P = 0.03); however, these did not decline to a clinically significant threshold. Heart rate variability (r = 0.60; P = 0.002) better correlated with subjective stress when compared to heart rate (r = 0.30; P = 0.15). Agreement between raters for Anaesthetic Non-Technical Skills (ANTS) scores was acceptable (ICC = 0.51; P = 0.003).ConclusionThis study suggests that higher patient ASA grade can increase stress in anaesthetists, which may impair non-technical skills