Abdominal Hysterectomy 2006

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively. However, a previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). Nevertheless, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

ABDOMINAL HYSTERECTOMY-SPECIFIC EVIDENCE – STUDY INFORMATION

Arguments for…

• Three out of five studies demonstrated that pre- and postoperative oral gabapentin was superior compared with placebo for reducing pain scores Gilron et al 2005 Click here for more information
• Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005 Click here for more information
• Four out of five studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004 Click here for more information
• Two out of two studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo Gilron et al 2005  Click here for more information
• Qualitative analysis demonstrated that in three out of four studies there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004
• Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information
• The incidence of side effects following pre- and postoperative oral gabapentin + rofecoxib was significantly lower in two studies out of two when compared with placebo Gilron et al 2005 Click here for more information
• Patient satisfaction with postoperative pain management was significantly higher at 24 h following pre- and postoperative oral gabapentin compared with placebo (p<0.001) Turan et al 2006
• Patient satisfaction with postoperative pain management was significantly higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with placebo at 24 (p<0.01), 48 (p<0.01) and 72 h (p value not stated) postoperatively Turan et al 2006
• There was a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0–4 h postoperatively (R²=0.30, p=0.003, and R²=0.24, p=0.008, respectively), compared with placebo Dierking et al 2004
• Peak expiratory flow was higher in the pre- and postoperative oral gabapentin group compared with the placebo group throughout postoperative days 1 and 2 (p=0.002-0.0032) Gilron et al 2005
• Peak expiratory flow was higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with the placebo group throughout postoperative days 1 and 2 (p<0.001) Gilron et al 2005

TRANSFERABLE EVIDENCE FROM OTHER PROCEDURES

Arguments for…

• Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
• One systematic review Ho et al 2006

Arguments for…

• One systematic review Ho et al 2006

PROSPECT RECOMMENDATIONS

• Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea
• Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)
• Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

ABDOMINAL HYSTERECTOMY-SPECIFIC EVIDENCE – STUDY INFORMATION

  Arguments for…

• A pre-operative single bolus of IV parecoxib was superior to placebo for postoperative pain scores on sitting up over 24 h (p=0.02), providing a mean drop of 14 mm in VAS scores on a 100-mm scale (n=36) Ng et al 2003
• A pre-operative single bolus of IV parecoxib or oral rofecoxib reduced morphine consumption over 24 h compared with placebo Ng et al 2003 Click here for more information
• Pre-operative oral rofecoxib was associated with a lower incidence of PONV compared with placebo in one study (p<0.05; n=40) Celik et al 2003
• Pre-operative oral COX-2-selective inhibitors were as effective as oral conventional NSAIDs for reducing postoperative pain scores in two studies (n=25; n=40) Celik et al 2003
• COX-2-selective inhibitors are similarly effective compared with conventional NSAIDs for reducing postoperative opioid consumption Celik et al 2003 Click here for more information
• Compared with the conventional NSAID diclofenac, pre-operative rofecoxib was associated with significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) in a group of patients undergoing abdominal or vaginal hysterectomy (n=25) Hegi et al 2004

  Arguments against…

• A pre-operative single bolus of rofecoxib or parecoxib did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies (n=40; n=36) Celik et al 2003

TRANSFERABLE EVIDENCE FROM OTHER PROCEDURES

Arguments for…

• Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
• Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
• Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
• A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)

Arguments against…

• Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
• Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
• Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O’Connor et al 2003
• Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
• COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
• Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

CLINICAL PRACTICE

• Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

PROSPECT RECOMMENDATIONS

• Pre-operative COX-2-selective inhibitors for hysterectomy are recommended because they have an analgesic effect postoperatively (grade A). However, there is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration
• The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

ABDOMINAL HYSTERECTOMY-SPECIFIC EVIDENCE – STUDY INFORMATION

Arguments for…

• Pre-operative conventional NSAIDs significantly reduced postoperative pain scores compared with placebo, but a significant clinical benefit was only evident for up to 4 h Scott et al 1994 Click here for more information
• The combination of paracetamol with a conventional NSAID was superior to a higher dose of paracetamol alone, administered as a single pre-operative rectal dose for VAS pain scores at rest at 4 h (p<0.05), but there was no significant difference at 2 h and 6–24 h (n=46) Beck et al 2000b
• Conventional NSAIDs were equally as effective as COX-2-selective inhibitors for reducing postoperative pain scores in two studies Celik et al 2003

Arguments against…

• Pre-operative conventional NSAIDs showed no significant or clinically meaningful benefit over placebo in reducing supplementary analgesic consumption Beck et al 2000b Click here for more information
• Pre-operative conventional NSAIDs provided no significant benefit over placebo for extending the time to first analgesic request in two out of the three studies that reported this parameter Scott et al 1994 Click here for more information
• Pre-operative conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all studies used postoperative PCA strong opioids) Beck et al 2000a Click here for more information
• Conventional NSAIDs and COX-2-selective inhibitors similarly reduce the use of supplementary analgesics Celik et al 2003 Click here for more information
• Compared with diclofenac, pre-operative rofecoxib caused significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) following abdominal hysterectomy (n=25) Hegi et al 2004
• There was no significant benefit of pre-incisional conventional NSAIDs over post-incisional conventional NSAIDs in two of three studies for reducing postoperative pain scores Nakayama et al 2001b Click here for more information
• Of three studies, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=77; n=30) Gabbott et al 1997
• Pre-incisional administration of flurbiprofen was associated with a shorter time to first analgesic request compared with post-incisional administration of a conventional NSAID, in one study (p<0.05; n=30) Nakayama et al 2001b
• Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for the incidence of PONV in two studies (n=65, n=30) Gabbott et al 1997

TRANSFERABLE EVIDENCE FROM OTHER PROCEDURES

Arguments for…

• One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987

Arguments against…

• Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
• Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
• Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
• A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
• A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
• Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
• Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O’Connor et al 2003
• Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
• Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

PROSPECT RECOMMENDATIONS

• Pre-operative conventional NSAIDs are not recommended because there is evidence that pre-operative administration of conventional NSAIDs is no more effective than postoperative administration (grade A). Moreover, pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (grade A)

ABDOMINAL HYSTERECTOMY-SPECIFIC EVIDENCE – STUDY INFORMATION

Arguments for…

• Pre-operative rectal morphine was superior to placebo for reducing postoperative pain scores compared with placebo in one study Pitschas et al 2000 Click here for more information
• Pre-operative rectal morphine was superior to placebo for reducing supplementary analgesic consumption for 0–4 h in one study (p=0.002; n=78) Pitschas et al 2000

Arguments against…

• Pre-operative oral or IV strong opioids provided no significant benefit over placebo for the reduction of postoperative pain scores Cruickshank et al 1996 Click here for more information
• Three studies showed no significant benefit of pre-operative oral or IV strong opioids over placebo for reducing supplementary analgesic consumption Cruickshank et al 1996
• Pre-incisional strong opioids showed no significant benefit over post-incisional strong opioids for reducing postoperative pain scores – and post-incisional strong opioids were significantly more effective for reducing postoperative pain scores at rest and on movement Fassoulaki et al 1995 Click here for more information
• Pre-incisional strong opioids did not confer a significant benefit over post-incisional strong opioids for reducing supplementary analgesic consumption Kilickan et al 2001 Click here for more information
• Pre-incisional strong opioids provided no significant benefit over post-incisional strong opioids for reducing the time to first analgesic request Fassoulaki et al 1995 Click here for more information
• Pre-incisional strong opioids were associated with a similar incidence of PONV as post-incisional strong opioids Griffin et al 1997 Click here for more information

PROSPECT RECOMMENDATIONS

• Pre-incisional administration of strong opioids is not recommended because of the lack of effect in reducing postoperative pain and supplementary analgesic consumption compared with placebo, and the lack of benefit over post-incisional administration of strong opioids (grade A). Moreover, post-incisional strong opioids are significantly more effective for reducing postoperative pain compared with a similar dose of pre-incisional strong opioids (grade A)

ABDOMINAL HYSTERECTOMY-SPECIFIC EVIDENCE

Arguments against..

• Pre-operative clonidine provided no consistent significant benefit over placebo for reducing postoperative pain scores; and other postoperative pain outcomes were mixed Dimou et al 2003 Click here for more information
• Pre-operative benzodiazepines provided no significant benefit in reducing postoperative pain scores, and there is evidence that they have a limited effect on reducing supplementary analgesic consumption Caumo et al 2002 Click here for more information
• NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

CLINICAL PRACTICE

Arguments against..

• Clonidine is not used routinely for postoperative analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia
•  NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

PROSPECT RECOMMENDATIONS

• Pre-operative clonidine is not recommended based on its limited analgesic efficacy (grade A) and risk of side effects (grade D)
• NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side effects (grade D)
• Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)