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

BACKGROUND: Postoperative 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. OBJECTIVES: To assess the efficacy of preventive and pre-emptive NSAIDs 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 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 In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles.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 CRITERIA: We 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 ANALYSIS: We 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 RESULTS: We 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 NSAIDs For 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 NSAIDs For 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' CONCLUSIONS: There 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.

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.

Oesophageal Doppler guided optimization of cardiac output does not increase visceral microvascular blood flow in healthy volunteers.

BACKGROUND: Oesophageal Doppler monitoring (ODM) is used clinically to optimize cardiac output (CO) and guide fluid therapy. Despite limited experimental evidence, it is assumed that increasing CO increases visceral microvascular blood flow (MBF). We used contrast-enhanced ultrasound (CEUS) to assess whether ODM-guided optimization of CO altered MBF. METHODS: Sixteen healthy male volunteers (62 ± 3·4 years) were studied. Baseline measurements of CO were recorded via ODM. Hepatic and renal MBF was assessed via CEUS. Saline 0·9% was administered to optimize CO according to a standard protocol and repeat CEUS performed. Time-intensity curves were constructed, allowing organ perfusion calculation via time to 5% perfusion (TT5). MBF was assessed via organ perfusion rise time (RT) (5-95%). RESULTS: CO increased (4535 ± 241 ml/min versus 5442 ± 329 ml/min, P<0·0001) following fluid administration, whilst time to renal (22·48 ± 1·19 s versus 20·79 ± 1·31 s; P = 0·03), but not hepatic (28·13 ± 4·48 s versus 26·83 ± 1·53 s; P = 0·15) perfusion decreased. Time to renal perfusion was related to CO (renal: r = -0·43, P = 0·01). Hepatic nor renal RT altered following fluid administration (renal: 9·03 ± 0·86 versus 8·93 ± 0·85 s P = 0·86; hepatic: 27·86 ± 1·60 s versus 30·71 ± 2·19 s, P = 0·13). No relationship was observed between changes in CO and MBF in either organ (renal: r = -0·17, P = 0·54; hepatic: r = -0·07, P = 0·80). CONCLUSIONS: ODM-optimized CO reduces time to renal perfusion but does not alter renal or hepatic MBF. A lack of relationship between microvascular visceral perfusion and CO following ODM-guided optimization may explain the absence of improved clinical outcome with ODM monitoring.

The effect of anaesthetist grade and frequency of insertion on epidural failure: a service evaluation in a United Kingdom teaching hospital.

BACKGROUND: Despite being a commonly performed procedure, epidural catheter insertion has a significant failure rate. There is a lack of guidance as to how regularly the procedure should be performed in order to maintain competence. This study aimed to quantify whether increasing frequency of practice is associated with a reduction in failure rates. METHODS: Data were collected prospectively on all patients undergoing intra-abdominal or thoraco-abdominal surgery who received epidural analgesia as part of their post-operative analgesic regimen over a 36 month period. Records were examined to identify the reason for epidural catheter removal, classified according to standardised definitions, the seniority of the inserting anaesthetist, and whether or not they were a permanent member of the anaesthetic department. Data were analysed using independent t tests, Mann-Whitney tests and Fisher's test. RESULTS: 881 epidurals were inserted during the study period. 48 hour failure rate was 27.2%, whilst by 96 hours 33.9% of epidurals had failed. Increasing frequency of epidural insertion did not show a significant decrease in failure rate at either 48 (p = 0.36) or 96 hours (p = 0.28). However, long-term survival of epidurals at 96 hours was greater if inserted by permanent rather than temporary members of staff (non-permanent 60/141, 42.6% vs permanent 228/715, 31.9%, OR 1.58 (CI 1.09-2.29) p = 0.02). CONCLUSION: This study demonstrates that failure rates for postoperative epidural analgesia in major surgery are not dependent upon the frequency with which practitioners insert epidural catheters. However, failure rates are dependent on permanency of anaesthetic staff. These findings are significant when placed in the context of the General Medical Council's requirements for clinicians to maintain competence in their clinical practice, suggesting that institutional factors may have greater bearing on epidural success or failure than frequency of task performance.

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.