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Comparison of Three Different Concentrations of Ropivacaine for Postoperative Patient-controlled Thoracic Epidural Analgesia After Upper Abdominal Surgery
Acta Anaesthesiol Taiwan 2008;46(3):100−105
O R IGINAL ART I CL E
Comparison of Three Different Concentrations of Ropivacaine for Postoperative Patient-controlled Thoracic Epidural Analgesia After Upper Abdominal Surgery Shen-Chih Wang, Ya-Ying Chang, Kuang-Yi Chang, Jenkin S. Hu, Kwok-Hon Chan, Mei-Yung Tsou* Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
Received: May 26, 2008 Revised: Jul 7, 2008 Accepted: Jul 10, 2008 KEY WORDS: analgesia, epidural; anesthetics, local: ropivacaine; surgery, upper abdominal
Background: Previous studies have reported the comparable efficacy of ropivacaine/ fentanyl for patient-controlled epidural analgesia (PCEA). In our hospital, three different concentrations of ropivacaine solution (0.1%, 0.15%, 0.2%) in combination with 1 μg/mL fentanyl were available for PCEA. As some studies have reported a much higher incidence of motor block and opioid-related side effects with 0.2% ropivacaine in combination with 4 μg/mL fentanyl, it was our intent to analyze the data of our patients who had received PCEA after upper abdominal surgery. In addition to comparing the analgesic effects and the incidence of motor block and opioidrelated side effects of these three different ropivacaine/fentanyl solutions, we also evaluated the workload of our pain staff. The main purpose of our study was to determine which of these three regimens of ropivacaine was most satisfactory with the least workload for the pain service staff. Methods: In total, 33 patients who had received PCEA after upper abdominal surgery were included in the analysis. The number of patients in each ropivacaine/ fentanyl group was 11 (group 1, 0.1% ropivacaine; group 2, 0.15%; group 3, 0.2%). The PCEA device was programmed to deliver a patient-controlled bolus of 2 mL with a lockout time of 20 minutes and background infusion of 5 mL/hr for 72 hours. Visual analog scale (VAS) pain scores, adverse events and the extent of sensory or motor block were recorded 12, 36 and 60 hours after surgery. The total volume of analgesic solution consumed and the frequency of requisite attendance by pain service staff were also recorded. Results: There were no differences among the three groups regarding total consumption. In group 1, VAS scores during ambulation and cough 12 hours postoperatively were significantly higher than in the other two groups (p < 0.05). There was no motor block. Four patients in group 3 suffered from loss of temperature sensation. The overall incidence of adverse events was less than 40%. Conclusion: Both thoracic epidural 0.15% and 0.2% ropivacaine provide effective postoperative pain control in combination with fentanyl without motor block. A 0.15% ropivacaine−1 μg/mL fentanyl solution is preferable considering the lower incidence of adverse events.
Dr Shen-Chih Wang and Dr Ya-Ying Chang made equal contributions to this manuscript. *Corresponding author. Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C. E-mail: [email protected] ©2008 Taiwan Society of Anesthesiologists
Thoracic epidural ropivacaine for postoperative analgesia
1. Introduction Ropivacaine is a long-acting amide local anesthetic that is structurally related to bupivacaine. It is a pure S(-)-enantiomer of propivacaine developed specifically to reduce potential toxicity and improve the relative sensory and motor block profiles.1 The relative analgesic potencies of ropivacaine and bupivacaine are 0.6 for epidural minimum local analgesic concentration.2,3 Ropivacaine has been proven to be effective for labor pain and a good choice for postoperative pain control.4−10 The addition of 4 μg/mL fentanyl to 0.2% ropivacaine resulted in significantly better analgesia.11 Comparisons of the analgesic effect and motor block of 0.1% and 0.2% ropivacaine in patient-controlled epidural analgesia (PCEA) have been made in several studies.6,12 Liu et al showed a 30% incidence of motor block and a high incidence of opioid-related adverse effects with 0.2% ropivacaine−4 μg/mL fentanyl solution for PCEA after lower abdominal surgery.12 They concluded that weaker concentrations of ropivacaine with fentanyl could provide comparable analgesia but with less motor block for similar amounts of ropivacaine and fentanyl. The conclusion was in agreement with a later study revealing that increasing the ropivacaine concentration did not improve analgesic efficacy after major abdominal surgery.6 In our hospital, an adjustable background infusion rate with bolus administration was adopted for PCEA, and our pain service staff was on duty aroundthe-clock to guard against inadequate analgesia and adverse events. Our study was instituted to examine the analgesic effect, motor block and opioidrelated adverse effects in patients who received one of the three different strengths of ropivacaine (0.1%, 0.15%, 0.2%) in combination with fentanyl 1 μg/mL. The purpose of our study was to determine which of these three concentrations of ropivacaine is most satisfactory for our PCEA infusion protocol, with the lowest workload for pain service staff.
2. Methods After institutional review board approval (IRB approval number, VGH 96-10-07A), 33 patients undergoing major upper abdominal surgery between December 2004 and March 2006 were included in the analysis. They were between 41 and 75 years of age, weighed 45−80 kg and were of ASA status I−II. Patients were excluded if they had contraindications for epidural catheter placement, concomitant disease interfering with postoperative assessment, pregnancy, drug abuse or a history of allergic reaction to local amide anesthetic or fentanyl.
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After the patient was sent to the operation room, an intravenous line was set up. Before induction of general anesthesia, epidural catheterization was performed via the T8−11 interspace with the patient lying in the left decubitus position. The epidural space was detected by the “loss of resistance” technique, and a 19-gauge epidural catheter was introduced through the 17-gauge Touhy needle and advanced cephalad for a length of 5 cm. After a test dose of 2 mL, 0.2% lidocaine with 1:200,000 epinephrine was given to ensure appropriate placement of the epidural catheter, general anesthesia was induced with atropine 0.5 mg, fentanyl 5 μg/ kg and thiopental 5 mg/kg under surveillance with electrocardiography, pulse oximetry and direct arterial pressure. Rocuronium 0.6 mg/kg was administered to facilitate tracheal intubation. Endtidal carbon dioxide concentration was kept at 35−40 mmHg and anesthesia was maintained with isoflurane in oxygen with rocuronium for surgical muscle relaxation. An initial dose of 10 mL 0.25% epidural bupivacaine was given during skin preparation followed by continuous infusion of 0.25% bupivacaine at 5 mL/hr until the end of the operation. The residual effect of rocuronium was reversed with neostigmine and atropine at the end of surgery, and all patients were extubated within 12 hours postoperatively. After surgery, the PCA machine (Abbott AIM Plus) was connected to the epidural catheter on arrival at the post-anesthesia care unit. Patients were classified into three groups: group 1, 0.1% ropivacaine with 1 μg/mL fentanyl; group 2, 0.15% ropivacaine with 1 μg/mL fentanyl; and group 3, 0.2% ropivacaine with 1 μg/mL fentanyl. The PCEA device was programmed to deliver a patient-controlled bolus of 2 mL with a lockout time of 20 minutes. The background infusion was set to run for 72 hours at a rate of 5 mL/hr. Postoperative pain assessments were made by the pain service staff at 12, 36 and 60 hours, designated as T1, T2 and T3, respectively, after the start of epidural solution infusion. We assessed the surgical wound pain at rest, during ambulation and during coughing using a visual analog scale (VAS). Sensory and motor block of the lower limbs were assessed with loss of temperature sensation and the Bromag scale. Adverse events including nausea, vomiting, dizziness and pruritus were recorded. The Bromag scale, loss of temperature sensation, and scores for adverse events are shown in Table 1. The staff of the anesthesia pain service were on duty around-the-clock for management of inadequate pain control and adverse events. If VAS pain scores at rest were > 50, our staff would give a 5 mL loading dose. The background infusion rate would be accordingly increased by 0.5 mL/hr. When the VAS pain score at rest was
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30−50, and in the case of adverse events occurring, the background infusion rate would be reduced by 0.5 mL/hr. Metoclopramide 10 mg for nausea or vomiting, and chlorpheniramine 5 mg for pruritus were administered intravenously if the patient was not satisfied after dose adjustment. If adverse events persisted, then the PCA program would be stopped and the patient would be withdrawn from the study. Demographic data of patients including age, gender, weight, height and surgical procedures were recorded. Total quantities of analgesic solution administered were obtained from the data registered in the Abbott pump, and the number of times of requirement for pain service was recorded on the chart. All of the data were collated with Microsoft Excel 2003 and analyzed with SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). Demographic and parametric data were expressed as mean ± standard deviation. Table 1
Scales of pain, motor block, and other side effects
Visual analog scale 0 mm = no pain 100 mm = worst pain possible Bromage scale 0 = no motor block 1 = inability to raise extended leg 2 = inability to flex knee 3 = inability to flex ankle Nausea/vomiting/dizziness/pruritus 0 = none 1 = mild 2 = moderate 3 = severe
Table 2
Parametric data were analyzed with one-way ANOVA, and non-parametric data with the χ2 test or Fisher’s exact test. A p value of less than 0.05 was considered to be statistically significant.
3. Results A total of 33 patients was enrolled in this study, with 11 patients in each of the three groups. There were no differences in age, gender, weight, height, ASA status and surgical procedures between groups (Table 2). No patient was withdrawn from the study due to persistent adverse events. There were no differences among the three study groups regarding total volume consumption of ropivacaine-fentanyl solution after a 72-hour infusion (Table 3). The total dose of ropivacaine in group 1 was significantly lower than that in group 3 (p = 0.001). VAS pain scores at rest, during ambulation and during coughing are shown in Figure 1. The VAS scores at rest, during ambulation and during coughing were higher in group 1 than in the other two groups after a 12-hour infusion (p < 0.05). There was no difference among the three groups in VAS scores at 36 and 60 hours after surgery. Loss of temperature sensation was only observed in four patients in group 3. No patient experienced motor block. Although the severity of adverse events, including nausea, vomiting, dizziness and pruritus, was recorded in grades from 0 to 3, only patients with grade 1−3 adverse events were taken into account. The incidence of adverse events is shown in Figure 2. There was no difference in adverse effects among the three groups. Table 4 shows the number of patients in each group who needed management by pain service staff.
Demographic characteristics of the three groups* Group
Age (yr) Gender (male/female) Height (cm) Weight (kg) Surgical procedure Radical subtotal gastrectomy Liver lobectomy Whipple’s operation Open cholecystectomy Nephrectomy *Data presented as mean ± standard deviation or n.
1
2
3
64 ± 12
58 ± 15
58 ± 15
9/2 165 ± 6
8/3 163 ± 8
9/2 163 ± 8
65 ± 10
60 ± 12
66 ± 12
5 2 2 1 1
3 7 1 0 0
5 2 2 2 0
Thoracic epidural ropivacaine for postoperative analgesia
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Table 3 Total local anesthetic and opioid requirements recorded from the PCA machine* Group
p†
1
2
3
Solution volume (mL)
559 ± 86
516 ± 86
477 ± 177
0.32
Dose Fentanyl (μg) Ropivacaine (mg)
559 ± 86 559 ± 86
516 ± 86 774 ± 129
477 ± 177 955 ± 354
0.32 0.001
VAS pain scores at rest
A
100 90 80 70 60 50 40 30 20 10 0
B Group 1 Group 2 Group 3
*
12
VAS pain scores with cough
C
100 90 80 70 60 50 40 30 20 10 0
36 60 Hours from start of infusion
Group 1 Group 2 Group 3
*
12
36 60 Hours from start of infusion
*
36 60 Hours from start of infusion
Group 1
Group 2
Group 3
40 Percentage of cases
100 90 80 70 60 50 40 30 20 10 0
Group 1 Group 2 Group 3
12
30 20 10 0 Nausea
VAS pain scores during ambulation
*Data presented as mean ± standard deviation; †p indicates the significance level of one-way ANOVA.
Dizziness Vomiting Adverse events
Pruritus
Figure 2 Incidence of opioid-related adverse events. There was no difference in the proportion of adverse effects among the three study groups.
Figure 1 Pain scores on a 100 mm visual analog scale (VAS): (A) at rest; (B) during ambulation; (C) with cough. The pain scores of the three groups at rest, during ambulation, and with cough were only significantly different in the first 12 hours. *p < 0.05.
4. Discussion Our study showed that the ropivacaine-fentanyl solution in thoracic epidural analgesia for postoperative pain control after upper abdominal surgery was efficacious. Although previous studies showed the same analgesic effect with 0.1% and 0.2% ropivacaine in combination with fentanyl or morphine,6,12 higher VAS pain scores at rest and during coughing and ambulation were observed in our group 1 patients in the first 12 hours after surgery. This might be explained by differences between PCEA infusion protocols. In the report by Liu et al, the background infusion rate, bolus, loading dose and adjustments were devised such that each study
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Table 4 The number of patients in each group who needed management by the anesthesia pain service Group Management by anesthesia pain service Infusion rate adjustment 5 mL loading dose Chlorpheniramine administration
group received the same dose of ropivacaine and fentanyl.12 In our study, the background infusion rate was 5 mL/hr in each patient group. Group 3 patients received twice as high a dose of ropivacaine as group 1 patients in the background infusion in the same period of time. This might also explain why more adjustments in the loading dose were observed in our group 1 patients. The PCEA infusion protocol in the report by Senard et al stipulated that only a bolus was given.7,8 The bolus was fixed at 5 mL in spite of different ropivacaine concentrations and the lockout interval was 10 minutes. In the first 12 hours after surgery, the demand was greater in patients receiving 0.1% ropivacaine than in patients receiving 0.2% ropivacaine (93 ± 44 mL vs. 78 ± 36 mL). The difference in demand between the 0.1% and 0.2% ropivacaine patient groups became much less 12 hours after surgery. This might indicate that 0.1% ropivacaine provided less effective analgesia in the first 12 hours after upper abdominal surgery. In our study, 0.1% ropivacaine also failed to offer adequate postoperative pain relief for ambulation or coughing in the first 12 hours after surgery. From a clinical point of view, this is crucial, as ambulation and coughing play a particularly important role in recovery of intestinal movement and respiratory function after abdominal surgery.13−15 In this study, the VAS pain scores during ambulation and coughing in group 1 patients 12 hours after surgery were much higher (p < 0.05). These patients obviously needed more additional loading doses than the other two groups. Therefore, it appeared to us that a background infusion at a rate of 5 mL/hr could offer good analgesia during ambulation or coughing for either 0.15% or 0.2% ropivacaine, but not for 0.1%. There was no observable motor block in our study. We owe this success to placement of the epidural catheter far beyond the lumbar spinal segments, and adjustment of the background infusion rate to avoid over-delivery of local anesthetic. In contrast to the report of Liu et al,12 we are of the opinion that placement of epidural catheters more cephalic can reduce the incidence of motor block, which is in accordance with the observation of Berti et al.16
1
2
3
9 6 1
6 2 1
7 2 0
The incidence of dizziness and pruritus, the two most frequent adverse events in our study, reached 36%. In comparison to the report of Scott et al,11 the incidence was not very high. However, we cannot explain the high incidence of dizziness and pruritus in group 1, whose consumption of fentanyl was the least, because these adverse events are related to the use of opioids. Sensory block as assessed by loss of temperature sensation only occurred in the group with the highest concentration (0.2%) of ropivacaine. Though physically it was not harmful at all, the reduced sensitivity of the lower limbs to temperature caused unease for some patients in group 3. In our study, group 2 patients needed the least adjustment of infusion rate and additional loading doses, which reflected greater satisfaction in the patients. In conclusion, the results of this study showed that thoracic epidural administration of ropivacainefentanyl solution provides good postoperative pain control with no motor block and few adverse events. Both 0.15% and 0.2% ropivacaine are effective choices. Considering the avoidance of troublesome sensations as a consequence of sensory block and a reduction in the workload of pain service staff, the use of 0.15% ropivacaine−1 μg/mL fentanyl solution for PCEA after major upper abdominal surgery is preferable.
Acknowledgments This study was supported in part by grant V97-B1013 from Taipei Veterans General Hospital.
References 1.
2.
3.
Simpson D, Curran MP, Oldfield V, Keating GM. Ropivacaine: a review of its use in regional anaesthesia and acute pain management. Drugs 2005;65:2675−717. Polley LS, Columb MO, Naughton NN, Wagner DS, van de Ven CJ, Goralski KH. Relative analgesic potencies of levobupivacaine and ropivacaine for epidural analgesia in labor. Anesthesiology 2003;99:1354−8. Capogna G, Celleno D, Fusco P, Lyons G, Columb M. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999;82:371−3.
Thoracic epidural ropivacaine for postoperative analgesia 4.
Cascio MG, Gaiser RR, Camann WR, Venkateswaran P, Hawkins J, McCarthy D. Comparative evaluation of four different infusion rates of ropivacaine (2 mg/mL) for epidural labor analgesia. Reg Aneth Pain Med 1998;23: 548−53. 5. Dresner M, Freeman J, Calow C, Quinn A, Bamber J. Ropivacaine 0.2% versus bupivacaine 0.1% with fentanyl: a double blind comparison for analgesia during labour. Br J Anaesth 2000;85:826−9. 6. Hofmann-Kiefer K, Saran K, Brederode A, Bernasconi H, Zwissler B, Schwender D. Ropivacaine 2 mg/ml vs. bupivacaine 1.25 mg/ml with sufentanil using patient-controlled epidural analgesia in labour. Acta Anaesthesiol Scand 2002; 46:316−21. 7. Senard M, Joris JL, Ledoux D, Toussaint PJ, Lahaye-Goffart B, Lamy ML. A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery. Anesth Analg 2002;95:444−9. 8. Senard M, Kaba A, Jacquemin MJ, Maquoi LM, Geortay MP, Honore PD, Lamy ML, et al. Epidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery. Anesth Analg 2004;98:389−94. 9. Cheng CR, Su TH, Hung YC, Wang PT. A comparative study of the safety and efficacy of 0.5% levobupivacaine and 0.5% bupivacaine for epidural anesthesia in subjects undergoing elective caesarean section. Acta Anaesthesiol Sin 2002;40:13−20. 10. Wong JO, Tan TD, Leung PO, Tseng KF, Cheu NW. Spinal anesthesia with two different dosages of 0.75% glucose-free
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15.
16.
105 ropivacaine: a comparison of efficacy and safety in Chinese parturients undergoing cesarean section. Acta Anaesthesiol Sin 2003;41:131−8. Scott DA, Blake D, Buckland M, Etches R, Halliwell R, Marsland C, Merridew G, 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; 88:857−64. Liu SS, Moore JM, Luo AM, Trautman WJ, Carpenter RL. Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 1999;90:727−33. Danelli G, Berti M, Perotti V, Albertin A, Baccari P, Deni F, Fanelli G, et al. Temperature control and recovery of bowel function after laparoscopic or laparotomic colorectal surgery in patients receiving combined epidural/general anesthesia and postoperative epidural analgesia. Anesth Analg 2002;95:467−71. Yeh CC, Jao SW, Huh BK, Wong CS, Yang CP, White WD, Wu CT. Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improves postoperative pain and bowel function in patients undergoing colonic surgery. Anesth Analg 2005;100:1384−9. Hall JC, Tarala RA, Tapper J, Hall JL. Prevention of respiratory complications after abdominal surgery: a randomised clinical trial. BMJ 1996;312:148−53. Berti M, Fanelli G, Casati A, Albertin A, Palmisano S, Deni F, Perotti V, et al. Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl. Can J Anesth 2000;47:27−32.
O R IGINAL ART I CL E
Comparison of Three Different Concentrations of Ropivacaine for Postoperative Patient-controlled Thoracic Epidural Analgesia After Upper Abdominal Surgery Shen-Chih Wang, Ya-Ying Chang, Kuang-Yi Chang, Jenkin S. Hu, Kwok-Hon Chan, Mei-Yung Tsou* Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
Received: May 26, 2008 Revised: Jul 7, 2008 Accepted: Jul 10, 2008 KEY WORDS: analgesia, epidural; anesthetics, local: ropivacaine; surgery, upper abdominal
Background: Previous studies have reported the comparable efficacy of ropivacaine/ fentanyl for patient-controlled epidural analgesia (PCEA). In our hospital, three different concentrations of ropivacaine solution (0.1%, 0.15%, 0.2%) in combination with 1 μg/mL fentanyl were available for PCEA. As some studies have reported a much higher incidence of motor block and opioid-related side effects with 0.2% ropivacaine in combination with 4 μg/mL fentanyl, it was our intent to analyze the data of our patients who had received PCEA after upper abdominal surgery. In addition to comparing the analgesic effects and the incidence of motor block and opioidrelated side effects of these three different ropivacaine/fentanyl solutions, we also evaluated the workload of our pain staff. The main purpose of our study was to determine which of these three regimens of ropivacaine was most satisfactory with the least workload for the pain service staff. Methods: In total, 33 patients who had received PCEA after upper abdominal surgery were included in the analysis. The number of patients in each ropivacaine/ fentanyl group was 11 (group 1, 0.1% ropivacaine; group 2, 0.15%; group 3, 0.2%). The PCEA device was programmed to deliver a patient-controlled bolus of 2 mL with a lockout time of 20 minutes and background infusion of 5 mL/hr for 72 hours. Visual analog scale (VAS) pain scores, adverse events and the extent of sensory or motor block were recorded 12, 36 and 60 hours after surgery. The total volume of analgesic solution consumed and the frequency of requisite attendance by pain service staff were also recorded. Results: There were no differences among the three groups regarding total consumption. In group 1, VAS scores during ambulation and cough 12 hours postoperatively were significantly higher than in the other two groups (p < 0.05). There was no motor block. Four patients in group 3 suffered from loss of temperature sensation. The overall incidence of adverse events was less than 40%. Conclusion: Both thoracic epidural 0.15% and 0.2% ropivacaine provide effective postoperative pain control in combination with fentanyl without motor block. A 0.15% ropivacaine−1 μg/mL fentanyl solution is preferable considering the lower incidence of adverse events.
Dr Shen-Chih Wang and Dr Ya-Ying Chang made equal contributions to this manuscript. *Corresponding author. Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C. E-mail: [email protected] ©2008 Taiwan Society of Anesthesiologists
Thoracic epidural ropivacaine for postoperative analgesia
1. Introduction Ropivacaine is a long-acting amide local anesthetic that is structurally related to bupivacaine. It is a pure S(-)-enantiomer of propivacaine developed specifically to reduce potential toxicity and improve the relative sensory and motor block profiles.1 The relative analgesic potencies of ropivacaine and bupivacaine are 0.6 for epidural minimum local analgesic concentration.2,3 Ropivacaine has been proven to be effective for labor pain and a good choice for postoperative pain control.4−10 The addition of 4 μg/mL fentanyl to 0.2% ropivacaine resulted in significantly better analgesia.11 Comparisons of the analgesic effect and motor block of 0.1% and 0.2% ropivacaine in patient-controlled epidural analgesia (PCEA) have been made in several studies.6,12 Liu et al showed a 30% incidence of motor block and a high incidence of opioid-related adverse effects with 0.2% ropivacaine−4 μg/mL fentanyl solution for PCEA after lower abdominal surgery.12 They concluded that weaker concentrations of ropivacaine with fentanyl could provide comparable analgesia but with less motor block for similar amounts of ropivacaine and fentanyl. The conclusion was in agreement with a later study revealing that increasing the ropivacaine concentration did not improve analgesic efficacy after major abdominal surgery.6 In our hospital, an adjustable background infusion rate with bolus administration was adopted for PCEA, and our pain service staff was on duty aroundthe-clock to guard against inadequate analgesia and adverse events. Our study was instituted to examine the analgesic effect, motor block and opioidrelated adverse effects in patients who received one of the three different strengths of ropivacaine (0.1%, 0.15%, 0.2%) in combination with fentanyl 1 μg/mL. The purpose of our study was to determine which of these three concentrations of ropivacaine is most satisfactory for our PCEA infusion protocol, with the lowest workload for pain service staff.
2. Methods After institutional review board approval (IRB approval number, VGH 96-10-07A), 33 patients undergoing major upper abdominal surgery between December 2004 and March 2006 were included in the analysis. They were between 41 and 75 years of age, weighed 45−80 kg and were of ASA status I−II. Patients were excluded if they had contraindications for epidural catheter placement, concomitant disease interfering with postoperative assessment, pregnancy, drug abuse or a history of allergic reaction to local amide anesthetic or fentanyl.
101
After the patient was sent to the operation room, an intravenous line was set up. Before induction of general anesthesia, epidural catheterization was performed via the T8−11 interspace with the patient lying in the left decubitus position. The epidural space was detected by the “loss of resistance” technique, and a 19-gauge epidural catheter was introduced through the 17-gauge Touhy needle and advanced cephalad for a length of 5 cm. After a test dose of 2 mL, 0.2% lidocaine with 1:200,000 epinephrine was given to ensure appropriate placement of the epidural catheter, general anesthesia was induced with atropine 0.5 mg, fentanyl 5 μg/ kg and thiopental 5 mg/kg under surveillance with electrocardiography, pulse oximetry and direct arterial pressure. Rocuronium 0.6 mg/kg was administered to facilitate tracheal intubation. Endtidal carbon dioxide concentration was kept at 35−40 mmHg and anesthesia was maintained with isoflurane in oxygen with rocuronium for surgical muscle relaxation. An initial dose of 10 mL 0.25% epidural bupivacaine was given during skin preparation followed by continuous infusion of 0.25% bupivacaine at 5 mL/hr until the end of the operation. The residual effect of rocuronium was reversed with neostigmine and atropine at the end of surgery, and all patients were extubated within 12 hours postoperatively. After surgery, the PCA machine (Abbott AIM Plus) was connected to the epidural catheter on arrival at the post-anesthesia care unit. Patients were classified into three groups: group 1, 0.1% ropivacaine with 1 μg/mL fentanyl; group 2, 0.15% ropivacaine with 1 μg/mL fentanyl; and group 3, 0.2% ropivacaine with 1 μg/mL fentanyl. The PCEA device was programmed to deliver a patient-controlled bolus of 2 mL with a lockout time of 20 minutes. The background infusion was set to run for 72 hours at a rate of 5 mL/hr. Postoperative pain assessments were made by the pain service staff at 12, 36 and 60 hours, designated as T1, T2 and T3, respectively, after the start of epidural solution infusion. We assessed the surgical wound pain at rest, during ambulation and during coughing using a visual analog scale (VAS). Sensory and motor block of the lower limbs were assessed with loss of temperature sensation and the Bromag scale. Adverse events including nausea, vomiting, dizziness and pruritus were recorded. The Bromag scale, loss of temperature sensation, and scores for adverse events are shown in Table 1. The staff of the anesthesia pain service were on duty around-the-clock for management of inadequate pain control and adverse events. If VAS pain scores at rest were > 50, our staff would give a 5 mL loading dose. The background infusion rate would be accordingly increased by 0.5 mL/hr. When the VAS pain score at rest was
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30−50, and in the case of adverse events occurring, the background infusion rate would be reduced by 0.5 mL/hr. Metoclopramide 10 mg for nausea or vomiting, and chlorpheniramine 5 mg for pruritus were administered intravenously if the patient was not satisfied after dose adjustment. If adverse events persisted, then the PCA program would be stopped and the patient would be withdrawn from the study. Demographic data of patients including age, gender, weight, height and surgical procedures were recorded. Total quantities of analgesic solution administered were obtained from the data registered in the Abbott pump, and the number of times of requirement for pain service was recorded on the chart. All of the data were collated with Microsoft Excel 2003 and analyzed with SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). Demographic and parametric data were expressed as mean ± standard deviation. Table 1
Scales of pain, motor block, and other side effects
Visual analog scale 0 mm = no pain 100 mm = worst pain possible Bromage scale 0 = no motor block 1 = inability to raise extended leg 2 = inability to flex knee 3 = inability to flex ankle Nausea/vomiting/dizziness/pruritus 0 = none 1 = mild 2 = moderate 3 = severe
Table 2
Parametric data were analyzed with one-way ANOVA, and non-parametric data with the χ2 test or Fisher’s exact test. A p value of less than 0.05 was considered to be statistically significant.
3. Results A total of 33 patients was enrolled in this study, with 11 patients in each of the three groups. There were no differences in age, gender, weight, height, ASA status and surgical procedures between groups (Table 2). No patient was withdrawn from the study due to persistent adverse events. There were no differences among the three study groups regarding total volume consumption of ropivacaine-fentanyl solution after a 72-hour infusion (Table 3). The total dose of ropivacaine in group 1 was significantly lower than that in group 3 (p = 0.001). VAS pain scores at rest, during ambulation and during coughing are shown in Figure 1. The VAS scores at rest, during ambulation and during coughing were higher in group 1 than in the other two groups after a 12-hour infusion (p < 0.05). There was no difference among the three groups in VAS scores at 36 and 60 hours after surgery. Loss of temperature sensation was only observed in four patients in group 3. No patient experienced motor block. Although the severity of adverse events, including nausea, vomiting, dizziness and pruritus, was recorded in grades from 0 to 3, only patients with grade 1−3 adverse events were taken into account. The incidence of adverse events is shown in Figure 2. There was no difference in adverse effects among the three groups. Table 4 shows the number of patients in each group who needed management by pain service staff.
Demographic characteristics of the three groups* Group
Age (yr) Gender (male/female) Height (cm) Weight (kg) Surgical procedure Radical subtotal gastrectomy Liver lobectomy Whipple’s operation Open cholecystectomy Nephrectomy *Data presented as mean ± standard deviation or n.
1
2
3
64 ± 12
58 ± 15
58 ± 15
9/2 165 ± 6
8/3 163 ± 8
9/2 163 ± 8
65 ± 10
60 ± 12
66 ± 12
5 2 2 1 1
3 7 1 0 0
5 2 2 2 0
Thoracic epidural ropivacaine for postoperative analgesia
103
Table 3 Total local anesthetic and opioid requirements recorded from the PCA machine* Group
p†
1
2
3
Solution volume (mL)
559 ± 86
516 ± 86
477 ± 177
0.32
Dose Fentanyl (μg) Ropivacaine (mg)
559 ± 86 559 ± 86
516 ± 86 774 ± 129
477 ± 177 955 ± 354
0.32 0.001
VAS pain scores at rest
A
100 90 80 70 60 50 40 30 20 10 0
B Group 1 Group 2 Group 3
*
12
VAS pain scores with cough
C
100 90 80 70 60 50 40 30 20 10 0
36 60 Hours from start of infusion
Group 1 Group 2 Group 3
*
12
36 60 Hours from start of infusion
*
36 60 Hours from start of infusion
Group 1
Group 2
Group 3
40 Percentage of cases
100 90 80 70 60 50 40 30 20 10 0
Group 1 Group 2 Group 3
12
30 20 10 0 Nausea
VAS pain scores during ambulation
*Data presented as mean ± standard deviation; †p indicates the significance level of one-way ANOVA.
Dizziness Vomiting Adverse events
Pruritus
Figure 2 Incidence of opioid-related adverse events. There was no difference in the proportion of adverse effects among the three study groups.
Figure 1 Pain scores on a 100 mm visual analog scale (VAS): (A) at rest; (B) during ambulation; (C) with cough. The pain scores of the three groups at rest, during ambulation, and with cough were only significantly different in the first 12 hours. *p < 0.05.
4. Discussion Our study showed that the ropivacaine-fentanyl solution in thoracic epidural analgesia for postoperative pain control after upper abdominal surgery was efficacious. Although previous studies showed the same analgesic effect with 0.1% and 0.2% ropivacaine in combination with fentanyl or morphine,6,12 higher VAS pain scores at rest and during coughing and ambulation were observed in our group 1 patients in the first 12 hours after surgery. This might be explained by differences between PCEA infusion protocols. In the report by Liu et al, the background infusion rate, bolus, loading dose and adjustments were devised such that each study
104
S.C. Wang et al
Table 4 The number of patients in each group who needed management by the anesthesia pain service Group Management by anesthesia pain service Infusion rate adjustment 5 mL loading dose Chlorpheniramine administration
group received the same dose of ropivacaine and fentanyl.12 In our study, the background infusion rate was 5 mL/hr in each patient group. Group 3 patients received twice as high a dose of ropivacaine as group 1 patients in the background infusion in the same period of time. This might also explain why more adjustments in the loading dose were observed in our group 1 patients. The PCEA infusion protocol in the report by Senard et al stipulated that only a bolus was given.7,8 The bolus was fixed at 5 mL in spite of different ropivacaine concentrations and the lockout interval was 10 minutes. In the first 12 hours after surgery, the demand was greater in patients receiving 0.1% ropivacaine than in patients receiving 0.2% ropivacaine (93 ± 44 mL vs. 78 ± 36 mL). The difference in demand between the 0.1% and 0.2% ropivacaine patient groups became much less 12 hours after surgery. This might indicate that 0.1% ropivacaine provided less effective analgesia in the first 12 hours after upper abdominal surgery. In our study, 0.1% ropivacaine also failed to offer adequate postoperative pain relief for ambulation or coughing in the first 12 hours after surgery. From a clinical point of view, this is crucial, as ambulation and coughing play a particularly important role in recovery of intestinal movement and respiratory function after abdominal surgery.13−15 In this study, the VAS pain scores during ambulation and coughing in group 1 patients 12 hours after surgery were much higher (p < 0.05). These patients obviously needed more additional loading doses than the other two groups. Therefore, it appeared to us that a background infusion at a rate of 5 mL/hr could offer good analgesia during ambulation or coughing for either 0.15% or 0.2% ropivacaine, but not for 0.1%. There was no observable motor block in our study. We owe this success to placement of the epidural catheter far beyond the lumbar spinal segments, and adjustment of the background infusion rate to avoid over-delivery of local anesthetic. In contrast to the report of Liu et al,12 we are of the opinion that placement of epidural catheters more cephalic can reduce the incidence of motor block, which is in accordance with the observation of Berti et al.16
1
2
3
9 6 1
6 2 1
7 2 0
The incidence of dizziness and pruritus, the two most frequent adverse events in our study, reached 36%. In comparison to the report of Scott et al,11 the incidence was not very high. However, we cannot explain the high incidence of dizziness and pruritus in group 1, whose consumption of fentanyl was the least, because these adverse events are related to the use of opioids. Sensory block as assessed by loss of temperature sensation only occurred in the group with the highest concentration (0.2%) of ropivacaine. Though physically it was not harmful at all, the reduced sensitivity of the lower limbs to temperature caused unease for some patients in group 3. In our study, group 2 patients needed the least adjustment of infusion rate and additional loading doses, which reflected greater satisfaction in the patients. In conclusion, the results of this study showed that thoracic epidural administration of ropivacainefentanyl solution provides good postoperative pain control with no motor block and few adverse events. Both 0.15% and 0.2% ropivacaine are effective choices. Considering the avoidance of troublesome sensations as a consequence of sensory block and a reduction in the workload of pain service staff, the use of 0.15% ropivacaine−1 μg/mL fentanyl solution for PCEA after major upper abdominal surgery is preferable.
Acknowledgments This study was supported in part by grant V97-B1013 from Taipei Veterans General Hospital.
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