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 In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles.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 We used GRADE to assess the quality of the evidence for each outcome.Main results: We included 20 RCTs, including one unpublished study with 1343 participants.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

An evaluation of POSSUM and P-POSSUM scoring in predicting post-operative mortality in a level 1 critical care setting

Background POSSUM and P-POSSUM are used in the assessment of outcomes in surgical patients. Neither scoring systems’ accuracy has been established where a level 1 critical care facility (level 1 care ward) is available for perioperative care. We compared POSSUM and P-POSSUM predicted with observed mortality on a level 1 care ward. Methods A prospective, observational study was performed between May 2000 and June 2008. POSSUM and P-POSSUM scores were calculated for all postoperative patients who were admitted to the level 1 care ward. Data for post-operative mortality were obtained from hospital records for 2552 episodes of patient care. Observed vs expected mortality was compared using receiver operating characteristic (ROC) curves and the goodness of fit assessed using the Hosmer-Lemeshow equation. Results ROC curves show good discriminative ability between survivors and non-survivors for POSSUM and P-POSSUM. Physiological score had far higher discrimination than operative score. Both models showed poor calibration and poor goodness of fit (Hosmer-Lemeshow). Observed to expected (O:E) mortality ratio for POSSUM and P-POSSUM indicated significantly fewer than expected deaths in all deciles of risk. Conclusions Our data suggest a 30-60% reduction in O:E mortality. We suggest that the use of POSSUM models to predict mortality in patients admitted to level 1 care ward is inappropriate or that a recalibration of POSSUM is required to make it useful in a level 1 care ward setting

Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery

BackgroundPostoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre‐emptive nonsteroidal anti‐inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery.ObjectivesTo assess the efficacy of preventive and pre‐emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery.Search methodsWe searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). 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 criteriaWe included parallel‐group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre‐emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin.Data collection and analysisWe used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0‐10 scale), adverse events of NSAIDs, nausea and vomiting, 24‐hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours).Main resultsWe included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre‐emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low‐risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain.Pre‐emptive NSAIDs compared to post‐incision NSAIDsFor pre‐emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD ‐0.69, 95% CI ‐0.97 to ‐0.41; studies = 36; participants = 2032; I2 = 96%; moderate‐certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short‐term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I2 = 0%; low‐certainty evidence) or long‐term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I2 = 29%; low‐certainty evidence). There may be a reduction in late acute postoperative pain (MD ‐0.22, 95% CI ‐0.44 to 0.00; studies = 28; participants = 1645; I2 = 97%; low‐certainty evidence). There may be a reduction in 24‐hour morphine consumption with pre‐emptive NSAIDs (MD ‐5.62 mg, 95% CI ‐9.00 mg to ‐2.24 mg; studies = 16; participants = 854; I2 = 99%; low‐certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I2 = 95%; low‐certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I2 = 0%; low‐certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I2 = 0%; low‐certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre‐emptive NSAIDs.Preventive NSAIDs compared to post‐incision NSAIDsFor preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD ‐0.14, 95% CI ‐0.39 to 0.12; studies = 18; participants = 1140; I2 = 75%; low‐certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short‐term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low‐certainty evidence) or long‐term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I2 = 29%; low‐certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD ‐0.33, 95% CI ‐0.59 to ‐0.07; studies = 21; participants = 1441; I2 = 81%; low‐certainty evidence). There is probably a reduction in 24‐hour morphine consumption (MD ‐1.93 mg, 95% CI ‐3.55 mg to ‐0.32 mg; studies = 16; participants = 1323; I2 = 49%; moderate‐certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI ‐31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I2 = 98%; very low‐certainty evidence). As with pre‐emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I2 = 0%; low‐certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I2 = 0%; low‐certainty evidence). There is probably little or no difference in patient satisfaction (MD ‐0.42; 95% CI ‐1.09 to 0.25; studies = 1; participants = 72; moderate‐certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI ‐15.99 to 15.99; studies = 1; participants = 76; moderate‐certainty evidence).Authors' conclusionsThere was some evidence that pre‐emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre‐emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events