1Department of Anaesthesiology and Intensive Care and 2Department of Obstetrics and Gynaecology, Herlev University Hospital, Copenhagen County, Denmark*Corresponding author
Accepted for publication: June 12, 2001
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Br J Anaesth 2001; 87: 72732
Keywords: anaesthetic techniques, epidural; anaesthetics local, bupivacaine; analgesics local, bupivacaine; pain, postoperative; surgery, gynaecological
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Administration of epidural local anaesthetics results in effective pain relief and improved gastrointestinal motility compared with opioid-based analgesia after hysterectomy.5 6 In healthy volunteers, epidural bupivacaine alone does not affect gastric emptying or bowel function,9 10 whereas addition of epidural opioid delays gastric emptying and prolongs orocaecal transit time.11
Only two randomized studies comparing postoperative epidural local anaesthetic with combined local anaesthetic and opioid have evaluated both gastrointestinal recovery and postoperative pain after laparotomy.12 13 In the study by Asantila and colleagues,12 analgesia with the combination of bupivacaine and morphine was superior to that with bupivacaine alone. However, gastrointestinal recovery was delayed in patients receiving the combination. In the study by Liu and colleagues,13 no significant differences in either analgesia or time to first postoperative flatus was observed between patients receiving bupivacaine and those receiving bupivacaine combined with morphine.
The aim of this study was to investigate the effect of continuous thoracic epidural bupivacaine alone vs combined epidural bupivacaine and morphine on postoperative gastrointestinal function and pain after radical hysterectomy and pelvic lymphadenectomy.
![]() |
Patients and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The study was double-blind and randomized with a computer program. The study drugs (bupivacaine 2 mg ml1 and bupivacaine 2 mg ml1/morphine 50 µg ml1) were prepared by the hospital pharmacy in identical containers marked with the name of the project, the investigators name and consecutive numbers. One hour before surgery, patients received sublingual triazolam 0.125 mg. Before induction of general anaesthesia, an 18-gauge epidural catheter was inserted through a Touhy needle and advanced 45 cm into the epidural space at the T1011 level and a 4-ml test dose of lidocaine 20 mg ml1 with epinephrine was administered. A bolus dose of 16 ml of lidocaine 20 mg ml1 with epinephrine was administered, followed by continuous infusion of lidocaine 20 mg ml1 at 8 ml h1 throughout the operation.
General anaesthesia was induced with propofol 1.5 2.5 mg kg1, alfentanil 1.0 mg and rocuronium 0.6 mg kg1, and an endotracheal tube was passed. Propofol without nitrous oxide was given for maintenance of anaesthesia. Further alfentanil 1.0 mg was administered at the discretion of the anaesthetist. Hypotension was treated by i.v. infusion of isotonic sodium chloride, HAES 6% or ephedrine 5 mg i.v. in incremental doses when systolic blood pressure was below 90 mm Hg. Fluid and blood losses were replaced according to the prescriptions of the department.
At skin closure, patients were randomized to receive an epidural bolus dose of 8 ml bupivacaine 2 mg ml1 followed by a continuous epidural infusion of bupivacaine 2 mg ml1 at 8 ml h1 for 48 h (bupi group) or 4 ml bupivacaine 2 mg ml1/morphine 50 µg ml1 followed by a continuous epidural infusion of bupivacaine 2 mg ml1/morphine 50 µg ml1 at 4 ml h1 for 48 h (bupi/morph group). Administration of the epidural bolus dose and initiation of the Deltec pump (Pharmacia) for the postoperative epidural infusion were performed by a person not involved in postoperative data collection or pain assessment. During the 48 h of infusion, the Deltec pump was covered by a box, so blinding the patient and assessors. For the first 48 h after surgery, all patients received paracetamol 2 g rectally every 8 h. For the first 72 h after surgery, ketorolac 15 mg was administered i.m. with a minimum interval of 8 h, on patient demand. If additional analgesic was required before another dose of ketorolac could be administered, morphine 0.125 mg kg1 was given i.m. In the recovery ward, morphine 0.0625 mg kg1 i.v. was administered on patient demand.
Patients were given ondansetron 4 mg i.v. with a lockout period of 8 h if they required an antiemetic. If additional antiemetic was required before another dose of ondansetron could be administered, metoclopramide 10 mg i.v. was given.
Before surgery, all patients were instructed in the use of the visual analogue scale (VAS) pain score, and to request supplementary analgesics and antiemetics if needed. VAS pain scores (0 mm = no pain, 100 = worst pain imaginable) at rest, on coughing and at mobilization from the supine to the sitting position were assessed by the patients 4, 6, 24, 48, 50, 54, 72 and 96 h after surgery. The numbers of ketorolac and morphine doses were recorded at the same intervals. Levels of sensory block to pinprick bilaterally were assessed 6, 24, 48, 50 and 54 h after surgery. In the event of asymmetrical blockade, the greater spread was recorded. Motor block was assessed using a four-point modified Bromage scale (0 = no motor block, 1 = inability to raise extended legs, 2 = inability to flex knees, 3 = inability to flex ankle joints) 6, 24, 48, 50 and 54 h after operation. Ability to walk (0 = no difficulty, 1 = little difficulty, 2 = very difficult, 3 = impossible, 4 = difficult or impossible for other reasons than motor block) was assessed 6, 24, 48, 50 and 54 h after surgery. The actual duration of mobilization (<1, 14 or >4 h) during the 2448 and 4872 h intervals was assessed 48 and 72 h after surgery. Patients who were not able to mobilize after >4 h were asked the primary reason for this.
At all visits, gastrointestinal function was assessed by asking the patients if and when they noted first flatus and stool, and if they had experienced nausea (0 = no, 1 = light, 2 = moderate, 3 = severe) and/or vomiting since the last assessment. Patients were encouraged to eat and drink whenever possible after the operation. Ingestion of predefined quantities of food and beverages was assessed at 24, 48 and 72 h.
Every 24 h after surgery, patients were assessed as ready or not ready for discharge from hospital by four discharge criteria: (1) normal defaecation and no urinary retention; (2) able to mobilize and dress; (3) need for opioid; (4) surgical complication requiring hospitalization. When the patient replied yes to the first two and no to the last two questions, he or she was declared ready for discharge from hospital.
The primary end-point of this study was time to first postoperative defaecation. Calculation of sample size was based on an unpublished pilot study performed at our institution and a previous study of postoperative gastrointestinal function after hysterectomy.12 For calculation, the following variables were used: type 1 error 5%; type 2 error 20%; minimal difference not to be overlooked, 24 h reduction in time to first postoperative stool in the bupi group; standard deviation of mean time to first postoperative defaecation, 24 h. The sample size needed to demonstrate this difference was 15 in each group. Statistical analyses were performed using the MannWhitney rank sum test for unpaired data, the Wilcoxon signed rank sum test for paired data and Fishers exact test for dichotomous data, where appropriate. A Cox regression analysis with time to first postoperative flatus and defaecation as dependent variable was performed. Independent covariates chosen beforehand were treatment group, duration of operation, dose of supplementary morphine administered before the event, and age of the patient. If multiple testing was performed, significant P values were corrected with a Bonferroni factor for multiple comparisons. P<0.05 was considered statistically significant. Calculations were performed using SPSS 9.5 for Windows.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
There were no significant differences between groups with respect to patient or operative characteristics (Table 1). In particular, intraoperative hypotension was not a problem and only nine and six patients in the bupi and the bupi/morph groups respectively needed i.v. ephedrine.
|
|
|
|
|
|
|
There was no difference between groups in mobilization time 2448, 4872 or 7296 h after surgery. At 2448 h, 11 and 16% of patients in the bupi group and bupi/morph groups respectively mobilized for more than 4 h. At 4872 h the corresponding numbers were 29 and 21% and those at 7296 h were 59 and 58%.
The two groups had similar incidences of nausea and vomiting (Table 78). There were no significant differences in the number of patients requesting antiemetics or the number of doses (Table 8). Nausea was mild in most patients; however, nine patients (five in the bupi group and four in the bupi/morph group) experienced severe nausea. Nine patients reported nausea of very short duration (minutes) during attempts to mobilize. The incidence of itching was significantly different in the two groups. At 24 h, one patient in the bupi group compared with nine in the bupi/morph group suffered itching (P=0.008) and at 48 h the corresponding numbers were one and eight (P=0.02) (Table 7). Furthermore, 24 h after surgery one patient in the bupi/morph group withdrew consent because of intolerable itching.
|
|
There were no significant differences between groups with respect to amount and time to ingestion of food and beverages. Patients fulfilled discharge criteria a median of 5 (quartiles 47) days and 6 (57) days after operation in the bupi and bupi/morph groups respectively (not significant).
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This study was designed to compare the effects of postoperative epidural bupivacaine 2 mg ml1/morphine 50 µg ml1 with the effects of the double dose and volume of epidural bupivacaine alone, on pain and gastrointestinal function. Because of the lack of doseresponse data for epidural bupivacaine, the dose administered to patients receiving epidural bupivacaine alone was chosen on the basis of a previous study conducted at our institution.19 Intra- and postoperative administration of opioids was restricted and standardized to reduce gastrointestinal paralysis and PONV. Thus, paracetamol was administered to all patients and ketorolac was the first-choice escape analgesic. Morphine was administered after surgery only if ketorolac was insufficient.
We showed no differences in VAS pain scores at rest, or during cough and ambulation between the study groups at any time, but a significantly increased need for both ketorolac and morphine in patients receiving bupivacaine alone. This is a clear indication that the combination of epidural local anaesthetic and opioid provides superior analgesia compared with the double dose of epidural local anaesthetic alone.
Regression analysis showed a reduction in time to restoration of gastrointestinal function in the bupi group compared with the bupi/morph group; there was a mean difference of 3 h to first postoperative flatus and 18 h to first postoperative defaecation. These results are in accordance with the findings by Asantila and colleagues12 and demonstrate that either omitting a small dose of epidural morphine or an increased dose of bupivacaine may improve the restoration of gastrointestinal function. Furthermore, regression analysis indicated that prolongation of time to first defaecation was associated with administration of supplementary systemic morphine.
As in previous studies,20 administration of epidural morphine was associated with itching in almost 50% of patients and one patient withdrew from the study because of this side-effect. A high incidence of this relatively minor side-effect may be acceptable if the patients get clear benefits. In this study, however, the benefit of the epidural combination of local anaesthetic and opioid was restricted to a reduced need for supplementary analgesics. Gastro intestinal function was impaired, itching was a significant problem and no other differences in side-effects were demonstrated. However, we studied a small number of patients, so conclusions should be guarded.
In summary, in patients undergoing major gynaecological surgery with free access to postoperative ketorolac and systemic morphine, epidural bupivacaine alone resulted in reduced gastrointestinal paralysis and itching, but similar pain relief and PONV, when compared with epidural bupivacaine and morphine. Under the conditions of this study, no effect on recovery or time to discharge from hospital was observed.
![]() |
Acknowledgements |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Hovorka J, Korttila K, Erkola O. Nausea and vomiting after general anaesthesia with isoflurane, enflurane or fentanyl in combination with nitrous oxide and oxygen. Eur J Anaesthesiol 1988; 5: 17782[ISI][Medline]
3 Madej TH, Simpson KH. Comparison of the use of domperidone, droperidol and metoclopramide in the prevention of nausea and vomiting following major gynaecological surgery. Br J Anaesth 1986; 58: 8847[Abstract]
4 Tsui SL, Ng KF, Wong LC, Tang GW, Pun TC, Yang JC. Prevention of postoperative nausea and vomiting in gynaecological laparotomies: a comparison of tropisetron and ondansetron. Anaesth Intens Care 1999; 27: 4716[ISI][Medline]
5 Jorgensen H, Wetterslev J, Moiniche S, Dahl JB. Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery (Cochrane Review). In: The Cochrane Library, Issue 3. Oxford: Update Software, 2001
6 Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg 2000; 87: 148093[ISI][Medline]
7 Livingston EH, Passaro EP Jr. Postoperative ileus. Digestion Dig Sci 1990; 35: 12132
8 Glise H, Abrahamsson H. Reflex inhibition of gastric motility pathophysiological aspects. Scand J Gastroenterol 1984; 89 Suppl: 7782
9 Thoren T, Tanghoj H, Mattwil M, Jarnerot G. Epidural morphine delays gastric emptying and small intestinal transit in volunteers. Acta Anaesthesiol Scand 1989; 33: 17480[ISI][Medline]
10 Thoren T, Wattwil M. Effects on gastric emptying of thoracic epidural analgesia with morphine or bupivacaine. Anesth Analg 1988; 67: 68794[Abstract]
11 Thorn SE, Wattwil M, Kallander A. Effects of epidural morphine and epidural bupivacaine on gastroduodenal motility during the fasted state and after food intake. Acta Anaesthesiol Scand 1994; 38: 5762[ISI][Medline]
12 Asantila R, Eklund P, Rosenberg PH. Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy. Acta Anaesthesiol Scand 1991; 35: 5137[ISI][Medline]
13 Liu SS, Carpenter RL, Mackey DC et al. Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology 1995; 83: 75765[ISI][Medline]
14 Scott DA, Beilby DS, McClymont C. Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1,014 patients. Anesthesiology 1995; 83: 72737[ISI][Medline]
15 Cooper DW, Ryall DM, McHardy FE, Lindsay SL, Eldabe SS. Patient-controlled extradural analgesia with bupivacaine, fentanyl, or a mixture of both, after Caesarean section. Br J Anaesth 1996; 76: 6115
16 George KA, Chisakuta AM, Gamble JA, Browne GA. Thoracic epidural infusion for postoperative pain relief following abdominal aortic surgery: bupivacaine, fentanyl or a mixture of both? Anaesthesia 1992; 47: 38894[ISI][Medline]
17 Lee A, Simpson D, Whitfield A, Scott DB. Postoperative analgesia by continuous extradural infusion of bupivacaine and diamorphine. Br J Anaesth 1988; 60: 84550[Abstract]
18 Scott DA, Blake D, Buckland M, Etches R, Halliwell R, Marsland C et al. A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 µg/mL fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery. Anesth Analg 1999; 88: 85764
19 Jorgensen H, Fomsgaard JS, Dirks J, Wetterslev J, Dahl JB. Effect of continuous epidural 0.2% ropivacaine vs 0.2% bupivacaine on postoperative pain, motor block and gastrointestinal function after abdominal hysterectomy. Br J Anaesth 2000; 84: 14450
20 Gedney JA, Liu EH. Side-effects of epidural infusions of opioid bupivacaine mixtures. Anaesthesia 1998; 53: 114855[ISI][Medline]