The impact of pre-operative depression on pain outcomes after major surgery: a systematic review and meta-analysis.

Symptoms of depression are common among patients before surgery. Depression may be associated with worse postoperative pain and other pain-related outcomes. This review aimed to characterise the impact of pre-operative depression on postoperative pain outcomes. We conducted a systematic review of observational studies that reported an association between pre-operative depression and pain outcomes after major surgery. Multilevel random effects meta-analyses were conducted to pool standardised mean differences and 95%CI for postoperative pain scores in patients with depression compared with those without depression, at different time intervals. A meta-analysis was performed for studies reporting change in pain scores from the pre-operative period to any time-point after surgery. Sixty studies (n = 501,962) were included in the overall review, of which 18 were eligible for meta-analysis. Pre-operative depression was associated with greater pain scores at < 72 h (standardised mean difference 0.97 (95%CI 0.37-1.56), p = 0.009, I2 = 41%; moderate certainty) and > 6 months (standardised mean difference 0.45 (95%CI 0.23-0.68), p < 0.001, I2 = 78%; low certainty) after surgery, but not at 3-6 months after surgery (standardised mean difference 0.54 (95%CI -0.06-1.15), p = 0.07, I2 = 83%; very low certainty). The change in pain scores from pre-operative baseline to 1-2 years after surgery was similar between patients with and without pre-operative depression (standardised mean difference 0.13 (95%CI -0.06-0.32), p = 0.15, I2 = 54%; very low certainty). Overall, pre-existing depression before surgery was associated with worse pain severity postoperatively. Our findings highlight the importance of incorporating psychological care into current postoperative pain management approaches in patients with depression.

Opioid Use After Nephrectomy for Kidney Cancer in Ontario: A Population-Based Study.

OBJECTIVE: To compare the odds of early and prolonged post-operative opioid use in patients undergoing minimally invasive surgery (MIS) vs open surgery for nephrectomy. METHODS: For opioid-naïve patients in Ontario who underwent nephrectomy for kidney cancer (1994-2017, n = 7900), post-discharge opioid use was determined by prescriptions in the Ontario Drug Benefit database (age ≥65 years) and the Narcotics Monitoring System (all patients from 2012). Early opioid use was defined as ≥1 prescription 1-90 days after surgery. Two separate definitions of prolonged opioid use were examined: (1) prescription(s) for ≥60 days during post-operative days 90-365; (2) ≥1 prescriptions between both of: 1-90 days AND 91-180 days after surgery. Predictors of opioid use were assessed using multivariable generalized estimating equation logistic regression, accounting for surgeon clustering. RESULTS: Overall, 67.4% of patients received early opioid prescriptions; however, prolonged use was low, ranging from 1.6 to 4.4% of patients depending on the definition. In multivariable analysis, open nephrectomy was associated with higher odds of early opioid use compared to MIS nephrectomy (Odds Ratio [OR] 1.36, 95% Confidence Interval [CI] 1.19-1.55). Surgery type was not significantly associated with prolonged opioid use for either definition (OR 1.22, CI 0.79-1.89 and OR 1.06, CI 0.83-1.35). CONCLUSIONS: In this population-level study of patients undergoing nephrectomy for kidney cancer, patients who received open surgery were at increased odds of receiving early post-operative opioids compared to MIS. Prolonged opioid use was low overall and was not significantly with associated with type of surgery.

A randomised controlled feasibility trial of a clinical protocol to manage hypotension during major non-cardiac surgery.

Intra-operative hypotension is a risk factor for postoperative morbidity and mortality. Minimally invasive monitors that derive other haemodynamic parameters, such as stroke volume, may better inform the management of hypotension. As a prelude to a multicentre randomised controlled trial, we conducted a single-centre feasibility trial of a protocol to treat hypotension as informed by minimally invasive haemodynamic monitoring during non-cardiac surgery. We recruited adults aged ≥40 years with cardiovascular risk factors who underwent non-cardiac surgery requiring invasive arterial pressure monitoring. Participants were randomly allocated to usual care, or a clinical protocol informed by an arterial waveform contour analysis monitor. Participants, outcome assessors, clinicians outside operating theatres and analysts were blinded to treatment allocation. Feasibility was evaluated based on: consent rate; recruitment rate; structured feedback from anaesthesia providers; and between-group differences in blood pressure, processes-of-care and outcomes. The consent rate among eligible patients was 33%, with 30 participants randomly allocated to the protocol and 30 to usual care. Anaesthesia providers rated the protocol to be feasible and acceptable. The protocol was associated with reduced fluid balance and hypotension exposure in the peri-operative setting. Postoperative complications included: acute myocardial injury in 18 (30%); acute kidney injury in 17 (28%); and surgical site infection in 7 (12%). The severity of complications was rated as moderate or severe in 25 (42%) participants. In summary, this single-centre study confirmed the feasibility of a multicentre trial to assess the efficacy and safety of a physiologically guided treatment protocol for intra-operative hypotension based on minimally invasive haemodynamic monitors.

Functional decline after major elective non-cardiac surgery: a multicentre prospective cohort study.

Self-reported postoperative functional recovery is an important patient-centred outcome that is rarely measured or considered in research and decision-making. We conducted a secondary analysis of the measurement of exercise tolerance before surgery (METS) study for associations of peri-operative variables with functional decline after major non-cardiac surgery. Patients who were at least 40 years old, had or were at risk of, coronary artery disease and who were scheduled for non-cardiac surgery were recruited. Primary outcome was a reduction in mobility, self-care or ability to conduct usual activities (EuroQol 5 dimension) from before surgery to 30 days and 1 year after surgery. A decline in at least one function was reported by 523/1309 (40%) participants at 30 days and 320/1309 (24%) participants at 1 year. Participants who reported higher pre-operative Duke Activity Status indices more often reported functional decline 30 days after surgery and less often reported functional decline 1 year after surgery. The odds ratios (95%CI) of functional decline 30 days and 1 year after surgery with moderate or severe postoperative complications were 1.46 (1.02-2.09), p = 0.037 and 1.44 (0.98-2.13), p = 0.066. Discrimination of participants who reported functional decline 30 days and 1 year after surgery were poor (c-statistic 0.61 and 0.63, respectively). In summary, one quarter of participants reported functional decline up to one postoperative year.

Role of patient-centred outcomes after hospital discharge: a state-of-the-art review.

The traditional approach for measuring outcomes after surgery involves ascertaining whether a patient survived surgery while avoiding major complications. This approach does not capture the full spectrum of events that are meaningful to patients, especially because mortality risks after elective surgery are relatively low, and different complication types vary considerably with respect to their impact on postoperative recovery. This review discusses the application, advantages, disadvantages and select examples of patient-centred outcomes in peri-operative medicine. When applied appropriately, these outcomes complement traditional clinical outcomes, identify important changes in postoperative function that impact patients without discernible complications and ensure that the definition of success after surgery is more meaningful to all relevant stakeholders.

Association of preoperative anaemia with cardiopulmonary exercise capacity and postoperative outcomes in noncardiac surgery: a substudy of the Measurement of Exercise Tolerance before Surgery (METS) Study.

BACKGROUND: Preoperative anaemia is associated with elevated risks of postoperative complications. This association may be explained by confounding related to poor cardiopulmonary fitness. We conducted a pre-specified substudy of the Measurement of Exercise Tolerance before Surgery (METS) study to examine the associations of preoperative haemoglobin concentration with preoperative cardiopulmonary exercise testing performance (peak oxygen consumption, anaerobic threshold) and postoperative complications. METHODS: The substudy included a nested cross-sectional analysis and nested cohort analysis. In the cross-sectional study (1279 participants), multivariate linear regression modelling was used to determine the adjusted association of haemoglobin concentration with peak oxygen consumption and anaerobic threshold. In the nested cohort study (1256 participants), multivariable logistic regression modelling was used to determine the adjusted association of haemoglobin concentration, peak oxygen consumption, and anaerobic threshold with the primary endpoint (composite outcome of death, cardiovascular complications, acute kidney injury, or surgical site infection) and secondary endpoint (moderate or severe complications). RESULTS: Haemoglobin concentration explained 3.8% of the variation in peak oxygen consumption and anaerobic threshold (P<0.001). Although not associated with the primary endpoint, haemoglobin concentration was associated with moderate or severe complications after adjustment for peak oxygen consumption (odds ratio=0.86 per 10 g L-1 increase; 95% confidence interval, 0.77-0.96) or anaerobic threshold (odds ratio=0.86; 95% confidence interval, 0.77-0.97). Lower peak oxygen consumption was associated with moderate or severe complications without effect modification by haemoglobin concentration (P=0.12). CONCLUSION: Haemoglobin concentration explains a small proportion of variation in exercise capacity. Both anaemia and poor functional capacity are associated with postoperative complications and may therefore be modifiable targets for preoperative optimisation.

Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study.

BACKGROUND: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury. METHODS: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)]. RESULTS: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001]. CONCLUSIONS: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.

Evaluation of validity of the STOP-BANG questionnaire in major elective noncardiac surgery.

BACKGROUND: The STOP-BANG questionnaire screens for obstructive sleep apnoea (OSA) in surgical patients. In prior research, the association of STOP-BANG scores with comorbidities and outcomes was inconsistent. The objective of this study was to evaluate the validity of the STOP-BANG score. METHODS: We conducted a retrospective cohort study of patients undergoing major elective noncardiac surgery at the University Health Network (Toronto, ON, Canada) between 2011 and 2015. Cross-sectional construct validity was evaluated based on proportions with diagnosed OSA across STOP-BANG strata. Concurrent construct validity was assessed based on the correlation of STOP-BANG with ASA Physical Status (ASA-PS), the Revised Cardiac Risk Index, and the Charlson Comorbidity Index. Predictive validity was assessed based on the adjusted associations of STOP-BANG risk with 30-day mortality (logistic regression), cardiac complications (logistic regression), and length-of-stay (negative binomial regression). RESULTS: Of 26 068 patients in the cohort, 58% were in the low-risk STOP-BANG stratum, 23% in the intermediate-risk stratum, and 19% in the high-risk stratum. The proportion with previously diagnosed OSA was 4% (n=615) in the low-risk stratum, 12% (n=740) in the intermediate-risk stratum, and 44% (n=2142) in the high-risk stratum. The correlations of STOP-BANG with ASA-PS (Spearman ρ=0.28), Revised Cardiac Risk Index (ρ=0.24), and Charlson Comorbidity Index (ρ=0.10) were weak, albeit statistically significant (P<0.001). After risk-adjustment, STOP-BANG risk strata were not associated with 30-day mortality, cardiac complications, or length-of-stay. CONCLUSIONS: The STOP-BANG questionnaire has modest construct validity but did not predict postoperative mortality, hospital length-of-stay, or cardiac complications.

Using the 6-minute walk test to predict disability-free survival after major surgery.

BACKGROUND: The 6-min walk test (6MWT) is a common means of functional assessment. Its relationship to disability-free survival (DFS) is uncertain. METHODS: This sub-study of the Measurement of Exercise Tolerance for Surgery study had co-primary outcome measures: correlation of the preoperative 6MWT distance with 30 day quality of recovery (15-item quality of recovery) and 12 month WHO Disability Assessment Schedule scores. The prognostic utility of the 6MWT and other risk assessment tools for 12 month DFS was assessed with logistic regression and receiver-operating-characteristic-curve analysis. RESULTS: Of 574 patients recruited, 567 (99%) completed the 6MWT. Twelve months after surgery, 16 (2.9%) patients had died and 444 (77%) had DFS. The 6MWT correlated weakly with 30 day 15-item quality of recovery (ρ=0.14; P=0.001) and 12 month WHO Disability Assessment Schedule (ρ=-0.23; P<0.0005) scores. When the cohort was split into 6MWT distance tertiles, the adjusted odds ratio of low vs high tertiles for DFS was 3.13 [95% confidence interval (CI): 1.54-6.35]. The only independent variable predictive of DFS was the Duke Activity Status Index (DASI) score (adjusted odds ratio: 1.06; P<0.0005). The area under the receiver-operating-characteristic curve for DFS was 0.63 (95% CI: 0.57-0.70) for the 6MWT, 0.60 (95% CI: 0.53-0.67) for cardiopulmonary-exercise-testing-derived peak oxygen consumption, and 0.70 (95% CI: 0.64-0.76) for the DASI score. CONCLUSIONS: Of the risk assessment tools analysed, the DASI was the most predictive of DFS. The 6MWT was safe and comparable with cardiopulmonary exercise testing for all predictive assessments. Future research should aim to determine the optimal 6MWT distance thresholds for risk prediction.

Association of preoperative anaemia with postoperative morbidity and mortality: an observational cohort study in low-, middle-, and high-income countries.

BACKGROUND: Anaemia is associated with poor postoperative outcomes, but few studies have described the impact of preoperative anaemia in low- and middle- (LMICs), and high-income countries (HICs). METHODS: This was a planned analysis of data collected during an international 7 day cohort study of adults undergoing elective inpatient surgery. The primary outcome was in-hospital death, and the secondary outcomes were in-hospital complications. Anaemia was defined as haemoglobin <12 g dl-1 for females and <13 g dl-1 for males. Hierarchical three-level mixed-effect logistic regression models were constructed to examine the associations between preoperative anaemia and outcomes. RESULTS: We included 38 770 patients from 474 hospitals in 27 countries of whom 11 675 (30.1%) were anaemic. Of these, 6886 (17.8%) patients suffered a complication and 198 (0.5%) died. Patients from LMICs were younger with lower ASA physical status scores, but a similar prevalence of anaemia [LMIC: 5072 (32.5%) of 15 585 vs HIC: 6603 (28.5%) of 23 185]. Patients with moderate [odds ratio (OR): 2.70; 95% confidence interval (CI): 1.88-3.87] and severe anaemia (OR: 4.09; 95% CI: 1.90-8.81) were at an increased risk of death in both HIC and LMICs. Complication rates increased with the severity of anaemia. Compared with patients in LMICs, those in HICs experienced fewer complications after an interaction term analysis [LMIC (OR: 0.92; 95% CI: 0.87-0.97) vs HIC (OR: 0.86; 95% CI: 0.84-0.87); P<0.01]. CONCLUSIONS: One-third of patients undergoing elective surgery are anaemic. These patients have an increased risk of complications and death. The prevalence of anaemia is similar amongst patients in LMICs despite their younger age and lower risk profile. CLINICAL TRIAL REGISTRATION: ISRCTN51817007.

Association between preoperative ambulatory heart rate and postoperative myocardial injury: a retrospective cohort study.

BACKGROUND: Resting heart rate is well established as a predictor of morbidity and mortality in the general population. However, the relationship between preoperative heart rate and perioperative outcomes, specifically myocardial injury, is unclear. METHODS: This retrospective cohort study included patients undergoing elective major non-cardiac surgery from 2008 to 2014 at a multisite healthcare system. The exposure was ambulatory heart rate measured during the outpatient preoperative clinic visit, whereas the outcome of interest was myocardial injury (peak postoperative troponin I concentration >30 ng L-1). Covariates included patient characteristics, comorbidities, and preoperative medications. We constructed several multivariable regression models that each modelled heart rate in a different manner, including as a simple continuous variable, categories, and fractional polynomials. RESULTS: The cohort included 41 140 patients, of whom 4857 (11.8%) experienced myocardial injury. Based on pre-specified heart categories thresholds, a heart rate ≥90 beats min-1 was associated with an elevated odds of myocardial injury compared with a heart rate <60 beats min-1 (adjusted odds ratio, 1.22; 95% confidence interval, 1.06-1.39; P=0.005). This result was consistent regardless of the method used for categorisation. When fractional polynomials were used to model heart rate, a 'J-shaped' relationship between heart rate and odds of myocardial injury was observed. CONCLUSIONS: This cohort study found that both very high preoperative heart rates, and possibly also very low heart rates, are associated with increased risk of myocardial injury. Whether heart rate is a modifiable risk factor, or rather simply a marker of underlying cardiac pathology, needs to be determined in further research.

Effectiveness of platelet inhibition on major adverse cardiac events in non-cardiac surgery after percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: Platelet inhibition is mandatory therapy after percutaneous coronary intervention (PCI). Withdrawal of oral antiplatelet agents has been linked to increased incidence of postoperative adverse cardiac events in post-PCI patients having non-cardiac surgery (NCS). There is limited knowledge of temporal changes in platelet inhibition in this high-risk surgical population. We therefore performed a multicentre prospective cohort study evaluating perioperative platelet function and its association with postoperative major adverse cardiac events (MACE). METHODS: In 201 post-PCI patients having NCS, we assessed the association between platelet function and postoperative MACE. We performed perioperative platelet function testing using a platelet mapping assay (PMA). Troponin-I was measured every 8 h for 2 days, then daily until day 5. Myocardial infarction was assessed using the third universal definition. We used multivariable logistic regression to assess the association between platelet inhibition and MACE. RESULTS: Major adverse cardiac events occurred in 40 patients within 30 days of surgery. Thirty-two of these events were non-ST-elevation myocardial infarction, four ST-elevation myocardial infarction, and four exacerbation of congestive heart failure. We were unable to show an association between platelet inhibition and MACE. The PMA showed declining levels of platelet inhibition the longer the antiplatelet therapy was withheld before surgery. Logistic regression did not show an association between preoperative platelet function or the type of stent and MACE. We found an increased cardiac risk of MACE after surgery within 6 weeks of PCI. CONCLUSIONS: The incidence of MACE in patients undergoing NCS after previous PCI is high in spite of adequate perioperative antiplatelet therapy. CLINICAL TRIAL REGISTRATION: NCT 01707459 (registered at http://www.clinicaltrials.gov).

Modern hydroxyethyl starch and acute kidney injury after cardiac surgery: a prospective multicentre cohort.

BACKGROUND: Recent trials have shown hydroxyethyl starch (HES) solutions increase the risk of acute kidney injury (AKI) in critically ill patients. It is uncertain whether these adverse effects also affect surgical patients. We sought to determine the renal safety of modern tetrastarch (6% HES 130/0.4) use in cardiac surgical patients. METHODS: In this multicentre prospective cohort study, 1058 consecutive patients who underwent cardiac surgery from 15th September 2012 to 15th December 2012 were recruited in 23 Spanish hospitals. RESULTS: We identified 350 patients (33%) administered 6% HES 130/0.4 intraoperatively and postoperatively, and 377 (36%) experienced postoperative AKI (AKI Network criteria). In-hospital death occurred in 45 (4.2%) patients. Patients in the non-HES group had higher Euroscore and more comorbidities including unstable angina, preoperative cardiogenic shock, preoperative intra-aortic balloon pump use, peripheral arterial disease, and pulmonary hypertension. The non-HES group received more intraoperative vasopressors and had longer cardiopulmonary bypass times. After multivariable risk-adjustment, 6% HES 130/0.4 use was not associated with significantly increased risks of AKI (adjusted odds ratio 1.01, 95% CI 0.71-1.46, P=0.91). These results were confirmed by propensity score-matched pairs analyses. CONCLUSIONS: The intraoperative and postoperative use of modern hydroxyethyl starch 6% HES 130/0.4 was not associated with increased risks of AKI and dialysis after cardiac surgery in our multicentre cohort.

Reliability of the American Society of Anesthesiologists physical status scale in clinical practice.

BACKGROUND: Previous studies, which relied on hypothetical cases and chart reviews, have questioned the inter-rater reliability of the ASA physical status (ASA-PS) scale. We therefore conducted a retrospective cohort study to evaluate its inter-rater reliability and validity in clinical practice. METHODS: The cohort included all adult patients (≥18 yr) who underwent elective non-cardiac surgery at a quaternary-care teaching institution in Toronto, Ontario, Canada, from March 2010 to December 2011. We assessed inter-rater reliability by comparing ASA-PS scores assigned at the preoperative assessment clinic vs the operating theatre. We also assessed the validity of the ASA-PS scale by measuring its association with patients' preoperative characteristics and postoperative outcomes. RESULTS: The cohort included 10 864 patients, of whom 5.5% were classified as ASA I, 42.0% as ASA II, 46.7% as ASA III, and 5.8% as ASA IV. The ASA-PS score had moderate inter-rater reliability (κ 0.61), with 67.0% of patients (n=7279) being assigned to the same ASA-PS class in the clinic and operating theatre, and 98.6% (n=10 712) of paired assessments being within one class of each other. The ASA-PS scale was correlated with patients' age (Spearman's ρ, 0.23), Charlson comorbidity index (ρ=0.24), revised cardiac risk index (ρ=0.40), and hospital length of stay (ρ=0.16). It had moderate ability to predict in-hospital mortality (receiver-operating characteristic curve area 0.69) and cardiac complications (receiver-operating characteristic curve area 0.70). CONCLUSIONS: Consistent with its inherent subjectivity, the ASA-PS scale has moderate inter-rater reliability in clinical practice. It also demonstrates validity as a marker of patients' preoperative health status.

Proportion of surgical patients with undiagnosed obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) affects ~9-24% of the general population, and 90% remain undiagnosed. Those patients with undiagnosed moderate-to-severe OSA may be associated with an increased risk of perioperative complications. Our objective was to evaluate the proportion of surgical patients with undiagnosed moderate-to-severe OSA. METHODS: After research ethics board approval, patients visiting preoperative clinics were recruited over 4 yr and screened with the STOP-BANG questionnaire. The 1085 patients, who consented, subsequently underwent polysomnography (PSG) (laboratory or portable) before operation. Chart review was conducted in this historical cohort to ascertain the clinical diagnosis of OSA by surgeons and anaesthetists, blinded to the PSG results. The PSG study-identified OSA patients were further classified based on severity using the apnoea-hypopnoea index (AHI) cut-offs. RESULTS: Of 819 patients, 111 patients had pre-existing OSA and 58% (64/111) were not diagnosed by the surgeons and 15% (17/111) were not diagnosed by the anaesthetists. Among the 708 study patients, PSG showed that 233 (31%) had no OSA, 218 (31%) patients had mild OSA (AHI: 5-15); 148 (21%) had moderate OSA (AHI: 15-30), and 119 (17%) had severe OSA (AHI>30). Before operation, of the 267 patients with moderate-to-severe OSA, 92% (n=245) and 60% (n=159) were not diagnosed by the surgeons and the anaesthetists, respectively. CONCLUSIONS: We found that anaesthetists and surgeons failed to identify a significant number of patients with pre-existing OSA and symptomatic undiagnosed OSA, before operation. This study may provide an impetus for more diligent case finding of OSA before operation.

Use of gabapentin for perioperative pain control -- a meta-analysis.

BACKGROUND: Gabapentin, an anticonvulsant, has recently been suggested as an effective postoperative 'analgesic' agent. The objective of the present study was to examine the analgesic effectiveness, opioid-sparing effects and side effects associated with the use of gabapentin in a perioperative setting. METHODS: Following the Quality of Reporting of Meta-analyses recommendations, nine electronic databases until February 2006 were searched, without language restriction, for randomized controlled trials comparing gabapentin with control for postoperative pain control. Outcome measures, namely, 24 h cumulative opioid consumption, visual analogue scale pain scores and adverse effects, were expressed as odds ratios, ratio of means or weighted mean differences (as appropriate), which were aggregated under the fixed or random effects models. RESULTS: Gabapentin caused a 35% reduction in total opioid consumption over the first 24 h following surgery (ratio of means 0.65, 95% CI 0.59 to 0.72), a significant reduction in postoperative pain at rest (in the first 24 h) and with movement (at 2 h, 4 h and 12 h), regardless of whether treatment effects were expressed as ratios of means or weighted mean differences, and a reduction of vomiting (relative risk [RR] 0.73, 95% CI 0.56 to 0.95) and pruritus (RR 0.30, 95% CI 0.13 to 0.70). It was associated with a significant increase in dizziness (RR 1.40, 95% CI 1.06 to 1.84) and an increase in sedation of borderline significance (RR 1.65, 95% CI 1.00 to 2.74). CONCLUSION: Gabapentin improves the analgesic efficacy of opioids both at rest and with movement, reduces analgesic consumption and opioid-related adverse effects, but is associated with an increased incidence of sedation and dizziness.