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From the *Department of Anesthesiology, Faculty of Medicine, University of Yamanashi; Department of Pharmacy, University of Yamanashi Hospital, Yamanashi, Japan; and School of Nursing, Faculty of Healthcare, Tokyo Healthcare University, Tokyo, Japan.
Address correspondence and reprint requests to Tadahiko Ishiyama, MD, PhD, Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. Address e-mail to ishiyama{at}yamanashi.ac.jp.
Abstract
BACKGROUND: The optimal concentration of ropivacaine in combination with fentanyl for patient-controlled epidural analgesia focusing on preservation of bowel function, analgesia, and motor function remains unclear.
METHODS: Three hundred-twelve women scheduled to undergo gynecologic lower abdominal surgery, were randomly allocated to receive ropivacaine 0.05, 0.075, or 0.1% in combination with fentanyl 4 µg/mL and droperidol 25 µg/mL. The settings of patient-controlled epidural analgesia were as follows: initial loading volume 5 mL, background infusion 2 mL/h during night-time, no background infusion during daytime, bolus volume 2 mL, and lockout interval 10 min. Bowel function was evaluated by the first passage of flatus and feces. Pain was assessed with a visual analog scale, and motor function was examined by modified Bromage scale. Data were collected in the evening on the day of surgery, in the morning and in the evening on the first postoperative day, and in the morning on the second postoperative day.
RESULTS: Gastrointestinal motility was not different among the three groups. All three solutions produced equivalent analgesia and no motor blockade.
CONCLUSION: We conclude that ropivacaine 0.05% is sufficient to preserve gastrointestinal motility, and provides excellent postoperative pain relief without motor blockade.
Epidural analgesia provides better postoperative analgesia for thoracic, abdominal, and upper and lower extremity surgery compared to parenteral opioids (1). The combination of local anesthetic and opioid is popular for patient-controlled epidural analgesia (PCEA) (2). Although epidurally administered local anesthetics promote gastrointestinal tract motility by blocking sympathetic nerves (3), fentanyl is commonly used in PCEA, and it can produce bowel dysfunction (4,5). Ropivacaine is widely used for PCEA, because it provides less motor blockade and cardiotoxicity than other long-lasting local anesthetic agents (6–8). However, the optimal concentration of ropivacaine for analgesia and motor function remains unclear. Furthermore, the suitable concentration of ropivacaine focusing on preservation of bowel function after gynecologic surgery has not been determined.
Thus, the current, prospective, double-blind, randomized, controlled study was conducted to compare the effects of three different concentrations (0.05, 0.075, and 0.1%) of ropivacaine with fentanyl on postoperative bowel function, quality of analgesia, motor blockade, and side effects.
METHODS
With local IRB approval, and written informed consent, 312 ASA physical status I or II female patients scheduled to undergo gynecological surgeries with midline lower-abdominal surgical incision were enrolled in the study. Exclusion criteria included a history of adverse events to amide local anesthetics or fentanyl, a history of ileus after abdominal surgery, current opioid use, inability to use the PCEA device, QT elongation (QT interval >470 ms)on preoperative electrocardiogram (ECG) assessment, Parkinson’s disease, and a history of bowel resection.
Preoperatively, all patients were randomized in a double-blind manner to receive one of three epidural infusions; ropivacaine 0.05% group, 0.075% group, or 0.1% group in combination with fentanyl 4 µg/mL and droperidol 25 µg/mL. All study personnel and participants were blinded to treatment assignment for the duration of the study. Study solutions were prepared by our investigational pharmacy. All patients were premedicated with atropine (<0.01 mg/kg) and midazolam (<0.05 mg/kg) IM. Before induction of general anesthesia, an epidural catheter was inserted 5 cm into the epidural space at L1–2 interspace. Aspiration and administration of a 5 mL test dose of mepivacaine 1.5% without epinephrine were performed to exclude accidental intravascular or subarachnoidal catheter position. General anesthesia was induced with propofol 2 mg/kg and vecuronium 0.1 mg/kg followed by tracheal intubation. Anesthesia was maintained with sevoflurane 1%–2% in nitrous oxide 67% and oxygen 33%. Opioids were not administered intraoperatively. Intraoperative epidural analgesia was achieved with 1, 1.5, or 2% mepivacaine 5 mL bolus injection followed by continuous infusion at 5 mL/h.
On initiation of wound closure, the epidural catheter was connected to a PCEA pump (Baxter 6060 multi-therapy pump, Baxter, Tokyo, Japan) that was set for a fixed bolus dose of 2 mL, with a 10-min lockout interval, and a background infusion of 2 mL/h. Background infusion was stopped in the morning (7:00–9:00) on the first postoperative day (POD), and was resumed in the evening (17:00–19:00) after data collection. PCEA was continued to at least the second POD. A blinded investigator visited patients repeatedly to assure adequate analgesia, proper equipment function, and stable vital signs. Patients with inadequate analgesia, defined as visual analog scale (range from 0 = no pain to 100 mm = worst pain) score at rest more than 50 mm despite two boluses from the PCEA pump, received pentazocine 15–30 mg IM, or diclofenac 25 mg suppository. Metoclopramide 10 mg was administered for nausea and vomiting. Severe pruritus was treated with diphenhydramine. Postoperative oral intake was allowed to start after the passage of flatus.
Data collections were made by a blinded investigator at 1–5 h after the completion of surgery (POD0), in the first postoperative morning (7:00–9:00) (POD1M) and in the evening (5:00–7:00) (POD1E), and in the second postoperative morning (7:00–9:00) (POD2M). Bowel function was assessed by the presence of the first passage of flatus or feces after the surgery. Pain at rest, on moving, and on coughing were evaluated with a visual analog scale. The use of supplemental analgesics was also recorded. Motor block on lower extremities was defined by using the modified Bromage scale (0 = no motor block, 1 = able to move knees, 2 = able to move feet only, 3 = unable to move feet or knees). Postoperative nausea and vomiting (PONV) were assessed with 4-point scale (0 = no nausea, 1 = slight nausea, 2 = moderate nausea, 3 = severe nausea with vomiting) and the use of antiemetics. Pruritus and drowsiness were defined by patient complaint. Respiratory depression was defined as the respiratory rate <8 breaths/min and hypotension was determined with systolic blood pressure <90 mm Hg. The sensory block level was detected by a pinprick test at POD1M. The QT interval was assessed with ECG monitoring at POD1M.
The sample size of this study was calculated with the significance level of 0.05 and the power of 0.8, at first flatus until POD2M in 0.05% and 0.1% groups was estimated to be 80% and 95% of patients. The result of this calculation showed that each group sample size was 80.
Data are presented as mean ± sd or number. Demographic data and pain scores were analyzed by analysis of variance. The incidence of PONV among groups was analyzed by 
2 test. Time to the first passage of the flatus, and to first feces were evaluated with Kaplan–Meier plots, and were compared with the log-rank test. A value of P < 0.05 was considered statistically significant.
RESULTS
In 312 patients enrolled in the study, 40 were excluded because of the following reasons: bowel resection during the surgery (2 cases), errors in setting the PCA pump (1 case), reoperation during the study period (2 cases), reduction of PCEA basal infusion for severe PONV (6 cases) and for hypotension (1 case), incomplete data collection (14 cases), running-out of the study solution (9 cases), intolerable pain at the insertion site of the epidural catheter (3 cases), and extrapyramidal effects (2 cases). Therefore, 93, 87, and 92 patients in the 0.05, 0.075, and 0.1% groups completed the study protocol, respectively.
No differences were noted with respect to age, height, weight, duration of operation, type of surgical procedure, and concentration of mepivacaine used during the surgery among the three groups (Table 1). The sensory block level detected by pinprick test, reached Th6-7 in. all patients in the morning on POD1.
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Cumulative consumption, in volume of the study solution, was similar among the three groups. Although background infusion was stopped during the daytime, consumption rates of study solutions were similar between POD1M to POD1E (continuous infusion was stopped, PCEA boluses only) and POD1E to POD2M (infusion was resumed) (Fig. 1). The first passage of flatus and feces was not different among the three groups (Fig. 2). Pain scores were similar at rest, on moving, and on coughing (Fig. 3). Need for supplemental analgesics, presence of motor blockade, severity of PONV, and use of antiemetics were comparable among the three groups (Table 2). One patient in the 0.075% group complained of severe pruritus, which was treated with diphenhydramine (Table 2). There were no cases of severe drowsiness, respiratory depression, hypotension, and QT prolongation on ECG (Table 2).
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DISCUSSION
The main finding of the current study was that three different concentrations (0.05, 0.075, and 0.1%) of ropivacaine with fentanyl 4 µg/mL for PCEA produced comparable postoperative resolution of gastrointestinal motility, pain relief and motor blockade. The results of this study suggest that a ropivacaine concentration of 0.05% is satisfactory for PCEA.
The incidence of postoperative ileus after major gynecologic surgery has been reported to range from 4.4% to 26.8% (9,10). Motility of the gastrointestinal tract is sometimes impaired after gynecologic surgery. Gastrointestinal motility is regulated by sympathetic fibers in the thoracic and lumber regions of the spinal cord (between T5 and L2). The return of gastric function is facilitated with thoracic epidural catheter placement using a local anesthetic-based regimen for analgesia (3,11). However, epidurally administered opioids can impair bowel function after hysterectomy (12). In the present study, using lumber epidural placement, all three doses of ropivacaine exerted similar sensory block levels up to Th6 or Th7, and solutions of 0.05, 0.075, and 0.1% ropivacaine produced comparable passage of first flatus and feces. Thus, regarding postoperative resolution of gastrointestinal motility, a ropivacaine concentration of 0.05% should be sufficient for PCEA.
A high concentration of ropivacaine produced superior analgesic effects and less opioid consumption (13). However, our study demonstrated that 0.05, 0.075, and 0.1% solution exerted an equivalent analgesic effect, and that higher concentrations did not cause a fentanyl-sparing effect. Furthermore, lumber epidural analgesia may provoke motor blockade of the lower extremities. Compared with 0.05% and 0.1% ropivacaine, 0.2% ropivacaine increased the frequency and severity of lower-extremity motor block (14). We showed that 0.05, 0.075, and 0.1% ropivacaine did not cause clinically significant motor blockade of the lower extremities. Regarding such blockade, a ropivacaine concentration of <0.1% may be favorable for PCEA. Based on local anesthetic consumption and motor blockade, 0.05% ropivacaine is our preferred concentration.
IV injection of droperidol at the end of surgery has been used for the prevention of PONV (15). Nevertheless, the duration of the antiemetic action of IV droperidol is limited, and PONV can last beyond 24 postoperative hours (16). On the other hand, epidural droperidol could exert its antiemetic action during the infusion period (17). Therefore, we chose epidural administration of droperidol. In addition, epidurally administered droperidol may act synergistically to the local anesthetic solution and/or fentanyl, and could have affected postoperative analgesia.
The potential major adverse effects of epidural droperidol are extrapyramidal symptoms and QT prolongation, symptoms which can develop after IV droperidol administration (18,19). In the present study, extrapyramidal symptoms occurred during epidural droperidol infusion at an incidence of 0.64%. Discontinuation of droperidol is the most effective treatment (20). On the other hand, although QT prolongation is a serious adverse event, it is very rare (21). QT prolongation has not been reported during epidural droperidol infusion, and we did not observe it in the present study. The United States Food and Drug Administration recommends continuous ECG monitoring for 3 h after a bolus of IV droperidol. There are no recommendations for epidural administration, as it is not an approved application. Although epidural infusion of droperidol is useful for the prevention of PONV, and may enhance analgesic effects, its safety has not been determined.
In the present study, the background infusion was stopped during the daytime, when patients could easily medicate themselves. Study solution consumption rates were actually similar between day and night in the three groups. A discontinuation of the background infusion may have affected the incidence of motor blockade among the three different concentrations of ropivacaine; however, the effect would have been small.
In conclusion, 0.05, 0.075, and 0.1% ropivacaine with 4 µg/mL fentanyl for PCEA produced comparable degrees of bowel motility, postoperative analgesia and motor blockade with minimal adverse events. We recommend a ropivacaine concentration at 0.05% in combination with 4 µg/mL fentanyl for postoperative PCEA. However, our results apply only to gynecologic surgery with an infra-umbilical incision.
ACKNOWLEDGMENTS
The authors thank Ms. Kaori Takahashi for her help with this study.
Footnotes
Accepted for publication April 23, 2007.
REFERENCES
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