Department of Surgical Gastroenterology, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark*Corresponding author
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Abstract |
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Keywords: anaesthesia, regional; pain, postoperative; analgesia, patient-controlled NSAIDs; postoperative morbidity
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Introduction |
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Effect of postoperative pain relief on surgical stress responses |
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Effect of patient-controlled analgesia on postoperative outcome |
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Non-steroidal anti-inflammatory agents |
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Epidural analgesic techniques |
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However, the literature has been confounded by many misunderstandings in different narrative reviews and meta-analyses. Studies with different types of epidural analgesic techniques have been combined. This is not rational as opioid-based regimens have less or no effect on stress responses and organ dysfunction compared with local anaesthetic-based regimens.40 Furthermore, a variety of surgical procedures have been included in these studies, which may limit interpretation of the findings as the effects on stress responses and organ dysfunction are less pronounced in major abdominal and thoracic procedures compared with lower body procedures.40 Thus, the level of epidural blockade is of major importance, in particular the distinction between thoracic and lumbar blockade. Also, definitions of adverse outcomes have varied. Finally, outcome effects have to be distinguished for single-dose and continuous regional anaesthetic/analgesic techniques.
The outcome of intra- and early postoperative analgesia by single-dose regional anaesthetic techniques (epidural and spinal anaesthesia) has been discussed for decades. A recent meta-analysis of all randomized studies,65 including 141 trials in a total of 9559 patients, concluded that central neuraxial blockade reduces the risk of deep venous thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, respiratory depression by 59% and myocardial infarction by 30%. Mortality was reduced by 30%. These positive findings were obtained predominantly after major orthopaedic procedures, whereas no significant effects were found in other procedures (urological, abdominal and thoracic). Because most studies involved single-dose regimens, the data did not allow any conclusions about the effect of continuous regional anaesthetic techniques on postoperative morbidity.65 In this article, an updated review of the effect on continuous epidural techniques (including local anaesthetics, local anaestheticopioid combinations and opioids) compared with opioid techniques as assessed in randomized, controlled studies is presented with respect to postoperative complications/morbidity. The data focus primarily on pulmonary and cardiac complications, postoperative paralytic ileus, thromboembolic and cerebral complications, and hospital stay.
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Pulmonary complications |
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In conclusion, continuous epidural local anaesthetic or local anaestheticopioid mixtures have only been demonstrated to provide a reduction in postoperative pulmonary morbidity in major abdominal procedures. Epidural opioid-based regimens also reduced pulmonary morbidity in abdominal (non-significantly) and thoracic procedures (significantly), but these results were largely influenced by a few studies. More work is required to validate these conclusions, as the number of patients studied was very limited and there was considerable variation in pulmonary morbidity in the individual studies. Furthermore, definitions of pulmonary outcome often differed between these studies, which further limits interpretation and a formal meta-analysis.
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Cardiac morbidity |
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In lower extremity procedures (Table 3), the only study available has shown a reduction in cardiac complications with epidural opioid.15 However, intraoperative epidural local anaesthetic was also used, which may have contributed to the reduced risk of myocardial infarction.65 The data from major abdominal surgery (Table 3) derive mostly from the use of epidural local anaesthetic techniques, while the regimen used in the study by Yeager and colleagues83 was predominantly based on epidural opioid analgesia (but with intra-operative local anaesthetics). However, this study is controversial as the patient population was not well defined (underlying disease and type of surgery). In another, often-cited study in a high-risk population scheduled for major surgery,8 the group receiving postoperative epidural opioid analgesia had a lower incidence of ventricular tachycardia than the group receiving systemic opioid analgesia. However, as this study was not randomized, it was excluded from the final data analysis. The epidural regimens based on local anaesthetics led to a non-significant reduction in postoperative cardiac morbidity from 24.5% to 16.4% in major abdominal procedures. When the two studies22 32 with inappropriate use of lumbar epidural local anaesthetic for abdominal procedures were excluded, the conclusion was not altered (non-significant reduction with thoracic epidural from 23.2% to 13.4%). The two opioid-based epidural regimens in the lower extremity and in mixed surgical procedures also led to a reduction in cardiac morbidity.15 83 The cumulative data may therefore suggest a clinically relevant reduction in cardiac morbidity, but further data are required from well-defined surgical procedures and patients, preferably including cardiac high-risk patients, in order to reach useful and statistically valid conclusions.
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Gastrointestinal complications (paralytic ileus)
Postoperative paralytic ileus (PI) may last for days and prolong hospitalization and convalescence.34 The main pathogenic factor of PI is activation of inhibitory splanchnic reflexes, which are subject to modification by thoracic epidural local anaesthetics.34 48 Accordingly, six of eight randomized clinical trials demonstrated that continuous thoracic epidural local anaesthetics reduced PI (Fig. 1).2 11 46 58 64 69 77 78 In the two negative studies,58 77 lack of effect was probably due to their small size, too short duration of block (24 h), or low epidural catheter insertion. In two of the three studies with inappropriate use of lumbar epidural analgesia for abdominal surgery,2 32 64 a significant reduction in postoperative ileus was nevertheless demonstrated. When epidural local anaestheticopioid mixtures were compared with systemic opioid analgesia, an ileus-reducing effect was also seen in four of seven studies (Fig. 1).13 32 36 46 51 70 71 In contrast, randomized studies have not demonstrated any reduction in ileus with an epidural opioid technique.34
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Postoperative cognitive dysfunction |
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Five randomized, controlled clinical trials have examined the role of continuous postoperative epidural analgesia versus systemic opioid-based analgesia.3 51 63 72 81 In all these studies, epidural analgesia was administered intra-operatively as an adjunct to general anaesthesia. In the largest study, in 262 patients undergoing knee surgery,81 postoperative analgesia was not adequately standardized or described, which prevented further analysis. However, no differences were demonstrated between epidural analgesia and systemic analgesia. After prostatectomy3 and hip surgery,63 continuous epidural analgesia with local anaesthetic had no effect on cognitive dysfunction. Furthermore, in 51 patients undergoing knee replacement surgery, no difference in the incidence of acute delirium was found between the group receiving epidural local anaestheticopioid mixture and the systemic opioid group.72 In contrast, a recent study investigating epidural low-dose bupivacaine morphine demonstrated improved postoperative cognitive function, measured in a limited number of assessments in elderly patients after major abdominal surgery.51
In conclusion, the effect of postoperative continuous epidural analgesic on cognitive dysfunction is unclear. Further studies are required that also control for other pathogenic factors, such as concomitant medication, sleep disturbances and early mobilization.
Mobilization and hospital stay
The effects of epidural analgesia on postoperative mobilization have been investigated only sporadically, usually with a negative result. In one study, epidural opioid analgesia improved mobilization in obese patients undergoing gastroplasty.62 The data from the use of continuous epidural local anaesthetic techniques in major orthopaedic procedures are controversial. Although one study demonstrated limited improvement in rehabilitation after knee replacement, hospital stay was not improved.80 However, postoperative analgesia was not standardized in this study, although most patients randomized to epidural anaesthesia also received postoperative epidural analgesia. In one study,12 the stay in the rehabilitation centre was reduced after continuous epidural analgesia, but the length of stay was substantial (about 40 days in total), which is different from common practice in most studies. In another study in knee and hip surgery, no difference was found in hours of daily mobilization between epidural local anaesthetic opioid mixture and systemic opioid.56 Furthermore, low-dose local anaestheticopioid epidural analgesia did not result in any improvement in rehabilitation measures in 51 patients scheduled for knee replacement surgery.72
The effect of epidural analgesic techniques on postoperative hospital stay, as a general indication of morbidity and mobilization is shown in Table 5. It appears that the improved pain relief given by epidural analgesic techniques (local anaesthetics, local anaestheticopioid mixtures, opioids alone) has no significant effect on hospital stay. These findings differ from the demonstrated positive effects in some procedures on paralytic ileus, pulmonary, cardiac and thromboembolic outcome after the use of epidural analgesia. However, as discussed below, it should be emphasized that hospital stay may be a poor outcome measure as it depends on many factors other than pain relief (e.g. use of drains, catheters, traditions, restrictions, reimbursement policy). The effect of improved pain relief by epidural analgesia may be obtunded by such factors.39 This is supported by the finding that discharge criteria were obtained earlier in patients receiving epidural analgesia46 but were not translated into a shorter hospital stay. Also, other studies have shown a discrepancy between achievement of discharge criteria and actual hospital stay.47 82 Therefore, in order to demonstrate a potential reduction in hospital stay by the more costly continuous epidural analgesic techniques, the improved pain relief has to be integrated into a multimodal rehabilitation programme.39
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Although the concept of multimodal postoperative rehabilitation seems rational and simple, progress has been slow.39 41 The most plausible explanation is that a successful multimodal rehabilitation programme requires the reorganization of peri-operative care, with increased collaboration between the patient, anaesthetist (acute pain service), surgical nurse and surgeon. Furthermore, major efforts must be made for educational programmes, with emphasis on peri-operative pathophysiology, as well as a revision of traditional postoperative care programmes with drains, gastrointestinal tubes, catheters, restrictions, etc. So far, preliminary experience from a variety of surgical procedures has shown such a collaborative effort to be extremely successful in reducing hospital stay and morbidity.7 39 41 To improve the rate of progress and to quantify the potential advantageous effects of analgesic techniques on postoperative outcome, a detailed analysis must be made of the various factors that may limit early recovery after each individual procedure, and be responsible for hospitalization on a given day. A key factor in the success of a multimodal rehabilitation programme is the development of daily nurse care programmes with an emphasis on rehabilitation7 and the expansion of the traditional acute pain service into a collaborative effort in functional recovery.
In summary, postoperative pain relief continues to demand our attention, but further progress is needed if we are to optimize functional (dynamic) pain relief and to demonstrate clinically significant advantages of pain relief for surgical outcome. The concept of a multimodal postoperative rehabilitation programme in which pain relief is a key factor is a major task for the future. However, such efforts will undoubtedly lead to major improvements in outcome, provided that perioperative care is adjusted to derive the benefits of the physiological effects of good pain relief.
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