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Comparison of the analgesic effects of intrabursal oxycodone and bupivacaine after acromioplasty
Original Contributions Comparison of the Analgesic Effects of Intrabursal Oxycodone and Bupivacaine After Acromioplasty Pasi A. Muittari, MD,* Olavi Nelimarkka, MD, PhD,† Timo Seppa¨la¨, MD, PhD,‡ Jussi H. Kanto, MD, PhD,§ Olli A. Kirvela¨, MD, PhD| Department of Anesthesiology, Turku University Hospital, Turku, Finland
*Staff Anesthesiologist †Assistant Professor of Surgery ‡Head of Laboratory, National Health Institute, Helsinki, Finland §Professor and Chairman, Department of Anesthesiology \
Assistant Professor of Anesthesiology
Address correspondence to Dr. Muittari at the Department of Anesthesiology, Turku University Hospital, P.O. Box 52, SF-20521, Turku, Finland. Received for publication September 10, 1998; revised manuscript revised and accepted for publication November 3, 1998.
Study Objectives: To compare the peripheral analgesic effect of oxycodone, an opioid agonist, to the effect of bupivacaine infiltration and parenteral oxycodone administration in conjunction with shoulder surgery. Design: Prospective, randomized, double-blind study. Setting: University teaching hospital. Patients: 42 ASA physical status I and II patients scheduled for shoulder surgery with general anesthesia. Interventions: Patients were randomized to three study groups: at the end of the surgery patients received either 10 ml of 0.5% bupivacaine (group BIB) or 5 mg of oxycodone in 10 ml of saline (group OIB) in the subacromial bursa; or 5 mg of oxycodone intramuscularly (group OIM). Postoperative analgesia was provided by patient-controlled analgesia (PCA). Measurements and Main Results: The fentanyl requirements were recorded for the 24-hour postoperative period and the total perioperative period. Postoperative pain was assessed by visual analog scale for pain (VASP). Plasma oxycodone concentrations were measured in groups OIB and OIM. The total perioperative fentanyl consumption was significantly lower in groups BIB (0.97 6 0.09 mg) and OIB (1.23 6 0.12 mg) than in group OIM (1.61 6 0.12 mg) (p 5 0.01 and 0.048, respectively). Groups BIB and OIB were similar (p 5 0.34). The absorption of oxycodone was significantly lower after subacromial than after intramuscular administration. Conclusion: Intrabursal oxycodone and intrabursal bupivacaine reduced perioperative analgesic requirements similarly. Intrabursal oxycodone may offer an effective, simple, and safe method for postoperative analgesia after shoulder surgery. © 1999 by Elsevier Science Inc.
Keywords: Acromioplasty; analgesia: patient-controlled, peripheral opioid, postoperative; oxycodone; surgery: shoulder.
Journal of Clinical Anesthesia 11:11–16, 1999 © 1999 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/99/$–see front matter PII S0952-8180(98)00122-6
Original Contributions
Introduction Acute postoperative pain after shoulder surgery varies from moderate to severe,1 and it can be managed using interscalene brachial plexus block or supraclavicular block.2 However, the use of these techniques may be limited by adverse effects.The incidence of hemidiaphragmatic paresis is 100% with interscalene block3 and 50% with supraclavicular block.4 Other possible major complications include high spinal or epidural anesthesia, inadvertent intravasal injection, and neural damage.2 Suprascapular nerve block is safer than either technique and has been shown to be effective in analgesia after arthroscopic shoulder surgery.5 After shoulder arthroscopy both intraarticular1 and subacromial6 injection of bupivacaine have been shown to be ineffective in reducing postoperative analgesic requirements. However, pain after manipulation of frozen shoulder has been treated succesfully with intraarticular injection of morphine and bupivacaine into the shoulder joint.7 In our previous study,8 we were able to show that the analgesic effect of infiltration of the subacromial bursa with a combination of bupivacaine and oxycodone is comparable to the effect of interscalene brachial plexus blockade, when comparing the perioperative analgesic requirements in conjunction to shoulder surgery. Additionally, the effect of a combination of bupivacaine and oxycodone 5 mg was superior to that of infiltration with plain 0.5% bupivacaine. However, the analgesic efficacy of intrabursal oxycodone alone was not investigated. The aim of the present study was to compare the local analgesic effect of intrabursally administered oxycodone to the effect of intrabursally administered bupivacaine and conventional intramuscular (IM) administration of oxycodone after elective shoulder surgery.
Materials and Methods The study protocol was approved by the Ethical Committee of Turku University Central Hospital and Turku University, and written informed consent was obtained from each patient on the day before surgery. Forty-two ASA physical status I and II patients scheduled for shoulder surgery were included in the study.The surgical procedures included the Neer acromioplasty for impingement syndrome (rotator cuff tendinitis) with possible repair of the rotator cuff rupture. The Neer acromioplasty consists of removal of the frontal lower part of the acromion and coracoacromial ligament, and resection of subacromial bursa, with subsequent decompression of the impingement.9 All procedures were performed by the same surgeon using conventional open technique. The criteria for exclusion from the study were severe cardiovascular, respiratory, metabolic, or neurologic disease, the use of oral or parenteral opioids preoperatively, history of allergy to any study medication, and the need for drainage after surgery. 1
Moote C: Random double-blind comparison of intra-articular bupivacaine and placebo for analgesia after outpatient shoulder arthroscopy [Abstract]. Anesthesiology 1994;81:A49. 12
J. Clin. Anesth., vol. 11, February 1999
Patients were given no opioid narcotic or antiinflammatory drugs 24 hours before operation. Premedication consisted of 10 mg of diazepam perorally 1 hour before arrival to the operating room. Anesthesia was induced with intravenous (IV) fentanyl 3 mg/kg and thiopental 4 mg/ kg, and maintained with 70% nitrous oxide in oxygen and isoflurane. Tracheal intubation was facilitated with vecuronium 0.08 mg/kg and ventilation controlled mechanically. Adequate anesthesia was maintained with isoflurane and supplementary doses of fentanyl 1 mg/kg when the patient’s blood pressure (BP) exceeded preoperative values by 25%. Monitoring included ECG, pulse oximetry, end-tidal CO2, and noninvasive BP measurement. All anesthetics were given by either of the two co-author anesthesiologists (O.K. or P.M.). Patients were randomly allocated, via sealed envelope assignment, to one of the three groups: at the conclusion of surgery, group BIB (n 5 14) received a 10-ml injection of 0.5% bupivacaine in subacromial bursa before skin closure; group OIB (n 5 14) received 5 mg of oxycodone (Oxanest, Leiras Medica, Turku, Finland) in 10 ml of normal saline, respectively; and group OIM (n 5 14) received 5 mg of oxycodone in the deltoid muscle of the opposite arm. The drug solutions were drawn into syringes by an independent nurse and administered by the surgeon who was blinded s to the contents of the syringes. The patients were under general anesthesia at the time of study drug administration and blinded as to which group they were assigned. After extubation the patients were moved to recovery room, and BP, heart rate, respiratory rate and peripheral oxygen saturation were monitored every 5 minutes for 2 to 3 hours. Immediately after arrival to the recovery room, patientcontrolled analgesia (PCA) with IV fentanyl was commenced to provide postoperative analgesia. PCA-device (Simms Deltec, Inc., St. Paul, MN) was programmed to give a 25-mg bolus of fentanyl without basal infusion. The lockout period was 7 minutes and the maximal fentanyl dose 200 mg/hr.The amount of fentanyl used over the 24-hour postoperative period and the total amount of fentanyl used perioperatively were documented and used for statistical analysis to avoid possible bias caused by different doses of fentanyl administered intraoperatively. Adverse effects such as nausea or drowsiness were recorded when reported spontaneously. Nausea and vomiting were treated with droperidol 1.25 mg IV as needed. Antiinflammatory drugs (NSAIDs) were not given. Patients were asked to mark the intensity of their shoulder pain in rest on a 100-mm visual analog scale for pain (VASP) ranging from 0 (no pain) to 100 mm (unbearable pain). Pain was first assessed just prior to the induction of the anesthesia and then postoperatively at 1, 2, 3, 6, and 24 hours after the study drug injection. Pain assesments were made by an independent nurse who was blinded as to patients’ study group assignment. The plasma concentrations of oxycodone were measured to compare drug absorption after IM administration and absorption from subacromial bursa. For blood sampling, an IV cannula was inserted during general anesthesia into a large antecubital vein to patients in groups OIB
Peripheral opiod analgesia: Muittari et al.
Table 1. Demographic and Clinical Data of Patients Undergoing Elective Shoulder Surgery
Age (yrs) Weight (kg) Gender (M:F) ASA physical status (I:II) Duration of surgery (min) Type of surgery: (acromioplasty:rotator cuff reconstruction)
Group BIB
Group OIB
Group OIM
51 6 2 83 6 3 9:5 8:6 44 6 4 8:6
48 6 3 78 6 5 7:7 10:4 43 6 2 7:7
51 6 2 79 6 4 8:6 12:2 42 6 4 8:6
Note: Values are means 6 SEM. BIB 5 intrabursal bupivacaine; OIB 5 intrabursal oxycodone; OIM 5 intramuscular oxycodone.
and OIM. Blood samples were drawn before administration of oxycodone and thereafter at 10, 20, 30, and 60 minutes and at 2, 3, and 6 hours. For oxycodone assay, the 10-ml samples were immediately centrifuged, and the obtained plasma was stored at 220°C until analyzed. Plasma oxycodone concentrations were determined in duplicate by gas chromatography as described by Kalso et al.10
Statistical Analysis The data were analyzed using a commercial statistical software package (SYSTAT, Systat, Inc., Evanston, IL). Patient age, weight, and duration of surgery were compared between groups using one-way analysis of variance
(ANOVA). Differences between groups in the VASP scores were tested by ANOVA for repeated measures. The amount of fentanyl administered from PCA-device during the 24-hour postoperative period and the total perioperative period were compared between the groups using ANOVA, and Tukey’s test was applied for post hoc analysis. Differences of plasma oxycodone consentrations in groups OIB and OIM were analyzed by t-test. Results are presented as means (standard error of mean). A p-value less than 0.05 was considered statistically significant.
Results Demographic and clinical data are presented in Table 1. There were no significant differences among the study groups with regard to age, weight, gender, ASA physical status, duration or surgery, or type of surgery performed. The study groups differed with regard to the amount of fentanyl administered from PCA-device during the 24hour postoperative period and the total amount of fentanyl required perioperatively (Figure 1). The postoperative fentanyl consumption was significantly (p 5 0.002) lower in group BIB (0.59 6 0.09 mg) than in group OIM (1.17 6 0.12 mg). Group BIB did not differ from group OIB with regard to fentanyl consumption (0.59 6 0.09 mg vs. 0.80 6 0.12 mg, respectively; p 5 0.33). The difference in fentanyl requirements between groups OIB and OIM did not reach statistical significance (p 5 0.057). The total fentanyl consumption was significantly lower in groups BIB (1.02 6 0.08 mg) and OIB (1.24 6 0.12 mg) than in group OIM (1.61 6 0.12 mg), and the difference reached statistical significance for both groups (p 5 0.001
Figure 1. Postoperative and total perioperative fentanyl consumption in the study groups. Values are given as means (SEM). * indicates a statistically significant difference: the postoperative fentanyl consumption in group BIB (intrabursal bupivacaine) was significantly lower (p 5 0.002) than in group OIM (intramuscular oxycodone), and the total fentanyl consumption was significantly lower in groups BIB (p 5 0.001) and OIB (intrabursal oxycodone) (p 5 0.048) than in group OIM. J. Clin. Anesth., vol. 11, February 1999
13
Original Contributions
Figure 2. Plasma oxycodone concentrations after intrabursal (OIB) and intramuscular (OIM) administration. Values are given as means (SEM). * indicates a statistically significant difference (p 5 0.041).
and 0.048, respectively). Groups OIB and BIB did not differ in their fentanyl requirements (p 5 0.34). Plasma oxycodone concentrations generally were lower after intrabursal injection (group OIB) than after IM injection (group OIM) (Figure 2). The difference reached statistical significance 20 minutes after oxycodone injection (p 5 0.041), when the plasma concentrations were
12.3 (1.3) and 24.1 (4.8) ng/ml in groups OIB and OIM, respectively. VASP scores were lowest in group BIB and highest in group OIM , but the differences did not reach statistical significance at any time points (Figure 3). In each group, pain was worst at 1 hour postoperatively, and then gradually diminished.
Figure 3. Visual analog scale for pain (VASP) scores at various times after study drug injection. Values are given as means (SEM). BIB 5 intrabursal bupivacaine; OIB 5 intrabursal oxycodone; OIM 5 intramuscular oxycodone. 14
J. Clin. Anesth., vol. 11, February 1999
Peripheral opiod analgesia: Muittari et al.
Postoperative analgesia provided by the PCA-device was well tolerated. Fentanyl caused only minor adverse effects in the study patients. During the 24 postoperative hours, 35% of patients complained of mild drowsiness and 29% of nausea; one patient in group BIB vomited. The number of nauseated patients who were treated with droperidol 1.25 mg IV were 3, 3, and 6 in groups BIB, OIB, and OIM, respectively.The incidence of these adverse effects did not differ among the study groups.
Discussion The results of the present study suggest that intrabursally administered oxycodone in conjunction with shoulder surgery may effectively alleviate postoperative pain and reduce consumption of analgesics. In reducing the need for perioperative fentanyl consumption, the efficacy of intrabursal oxycodone equals that of bupivacaine and is superior to IM oxycodone administration, despite lower plasma oxycodone concentrations. In our earlier study, intrabursally administered combination of oxycodone and bupivacaine did not differ in efficacy from interscalene brachial plexus block.9 Based on these two studies, one can assume that the combination of oxycodone and bupivacaine administered intrabursally is more effective than either of them alone in analgesia in conjunction with shoulder surgery. In the present study, groups OIB and OIM did not differ significantly in postoperative fentanyl requirements (p 5 0.057), but when the total perioperative consumption was compared, the difference reached statistical significancy (p 5 0.048). The amount of fentanyl administered intraoperatively did not differ among the study groups. Thus, the difference in significance level may reflect smaller interindividual variability within the study groups, when the total perioperative fentanyl requirements are accounted for. The half-life of fentanyl is relatively long, and intraoperatively administered fentanyl consequently has an effect on the postoperative needs of analgesics.11 Thus, in this setting, the total perioperative fentanyl consumption best reflects differences between pain treatment modalities. Additionally, this type of surgery is associated with considerable postoperative pain, and balanced anesthesia with perioperative fentanyl was considered necessary, even though the experimental design might have been simplified with the use of plain inhalation anesthesia. Plasma oxycodone concentrations after intrabursal administration proved to be lower than after IM administration. This finding, together with the fact that the concentrations generally were very low, rules out any longstanding central antinociceptive effect of oxycodone. Thus, comparison among groups for perioperative analgesic requirements is relevant, and group OIM (IM oxycodone) was used as a reference group instead of an actual placebo group. Oxycodone, or 14-hydroxy-7,8-dihydrocodeinone, is a synthetic thebain derivate and its pharmacokinetic characteristics10,12–14 and pharmacodynamic features14 –16 are closely related to those of morphine.
Surprisingly, the peak oxycodone plasma concentration occurred at 20 minutes after IM injection, earlier than the time of 60 minutes reported by Po¨yhia¨ et al.12. This may reflect more active circulation in deltoid than in vastus lateralis muscle.17 Patient-controlled analgesia is an established method in pain treatment, even after shoulder surgery.18 That there were only insignificant differences between groups in VASP scores indicates that the method worked properly: each patient received the amount of fentanyl needed to control the pain at an acceptable level. Moreover, PCA offers a valuable tool for pain research: a computerderived PCA-device records the precise amount of analgesic consumed and the delivery time. Kalso et al.19 reviewed studies on peripheral analgesic action of morphine in conjunction with arthroscopic knee surgery. They concluded that intraarticular morphine does induce analgesia. However, several questions remain to be addressed: the influence of tourniquet release time or the use of regional anesthesia, and variability of the tissue injury caused by surgical intervention. Thus, shoulder surgery may offer some advantages over knee surgery to elucidate the issue. First, pain after shoulder surgery varies from moderate to severe,1 and most patients need considerable amounts of analgesics to control their pain. By contrast, pain after minor arthroscopic operation often varies from minor to moderate.19 This fact may explain why many trials failed to show any differences between treatments. Second, subacromial bursa offers a suitable compartment for drug injection and for the spread of a drug to the injured area. Additionally, in acromioplasty, tissue injury is relatively standard in extent. Thus, shoulder surgery may offer a better model for studies on peripheral antinociceptive effects of opioids than knee arthroscopy. In conclusion, the results of the present study may support the concept of peripheral opioid analgesia: oxycodone administered intrabursally produced better analgesia than after IM administration, despite lower serum oxycodone concentrations. However, the analgesic effect of intrabursal oxycodone did not exceed that of intrabursal bupivacaine. The technique of peripherally administered opioids, alone or in combination with local anesthetics, may offer promising results in pain therapy after shoulder surgery: the technique seems effective, simple, and safe.
References 1. Bonica JJ: Postoperative pain. In: Bonica J, (ed): The Management of Pain, 2d ed. Philadelphia: Lea & Febiger, 1990;462. 2. Bridenbaugh LD: The upper extremity: somatic blockade. In: Cousins MJ, Bridenbaugh LD (eds): Neural Blockade in Clinical Anesthesia and Management of Pain, 2d ed. Philadelphia: J.B.Lippincott Co., 1988:387– 416. 3. Urmey WF, Talts KH, Sharrock NE: One hundred percent incidence of hemidiaphragmatic paresis associated with interscalene brachial plexus anesthesia as diagnosed by ultrasonography. Anesth Analg 1991;72:498 –503. 4. Neal JM, Moore JM, Kopacz DJ, Liu SS, Kramer DJ, Plorde JJ: Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block. Anesth Analg 1998;86:1239 – 44. J. Clin. Anesth., vol. 11, February 1999
15
Original Contributions 5. Ritchie ED, Tong D, Chung F, Norris AM, Miniaci A, Vairavanathan SD: Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: a new modality? Anesth Analg 1997;84:1306 –12. 6. de Nadal M, Agreda G, Massenet S, Salgado I, Lacasta A, Cabre B, Gancedo VA: Efficacy of bupivacaine infiltration upon postoperative pain after ambulatory shoulder arthroscopy under general anaesthesia. Br J Anaesth 1998;80 (Suppl 1):A595. 7. Joshi GP, McCarroll SM: Intra-articular morphine for the management of frozen shoulder [Letter]. Anaesthesia 1992;47:627. 8. Muittari P, Kirvela¨ O: The safety and efficacy of intrabursal oxycodone and bupivacaine in analgesia after shoulder surgery. Reg Anesth Pain Med 1998;23:474 – 8. 9. Neer CS II: Anterior acromioplasty for the chronic impingement syndrome of the shoulder. A preliminary report. J Bone Joint Surg Am 1972;54:41–50. 10. Kalso E, Vainio A, Mattila MJ, Rosenberg PH, Seppa¨la¨ T: Morphine and oxycodone in the management of cancer pain: plasma levels determined by chemical and radioreceptor assays. Pharmacol Toxicol 1990;67:322– 8. 11. Shafer SL, Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology 1991;74:53– 63. 12. Po¨yhia¨ R, Seppa¨la¨ T, Olkkola KT, Kalso E: The pharmacokinetics
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13.
14.
15.
16.
17. 18. 19.
and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol 1992;33: 617–21. Leow KP, Wright AW, Cramond T, Smith MT: Determination of the serum protein binding of oxycodone and morphine using ultrafiltration. Ther Drug Monit 1993;15:440 –7. Po¨yhia¨ R, Vainio A, Kalso E: A review of oxycodone9s clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manage 1993;8:63–7. Kalso E, Po¨yhia¨ R, Onnela P, Linko K, Tigerstedt I, Tammisto T: Intravenous morphine and oxycodone for pain after abdominal surgery. Acta Anaesthesiol Scand 1991;35:642– 6. Kalso E, Vainio A: Morphine and oxycodone hydrochloride in the management of cancer pain. Clin Pharmacol Ther 1990;47: 639 – 46. Evans EF, Proctor JD, Fratkin MJ, et al: Blood flow in muscle groups and drug absorption. Clin Pharmacol Ther 1975;17:44 –7. Harmer M, Rosen M, Vickers MD (eds): Patient-Controlled Analgesia. Oxford, UK: Blackwell Scientific Publications, 1985. Kalso E, Tramer MR, Carroll D, McQuay HJ, Moore RA: Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Pain 1997;71:127–34.
*Staff Anesthesiologist †Assistant Professor of Surgery ‡Head of Laboratory, National Health Institute, Helsinki, Finland §Professor and Chairman, Department of Anesthesiology \
Assistant Professor of Anesthesiology
Address correspondence to Dr. Muittari at the Department of Anesthesiology, Turku University Hospital, P.O. Box 52, SF-20521, Turku, Finland. Received for publication September 10, 1998; revised manuscript revised and accepted for publication November 3, 1998.
Study Objectives: To compare the peripheral analgesic effect of oxycodone, an opioid agonist, to the effect of bupivacaine infiltration and parenteral oxycodone administration in conjunction with shoulder surgery. Design: Prospective, randomized, double-blind study. Setting: University teaching hospital. Patients: 42 ASA physical status I and II patients scheduled for shoulder surgery with general anesthesia. Interventions: Patients were randomized to three study groups: at the end of the surgery patients received either 10 ml of 0.5% bupivacaine (group BIB) or 5 mg of oxycodone in 10 ml of saline (group OIB) in the subacromial bursa; or 5 mg of oxycodone intramuscularly (group OIM). Postoperative analgesia was provided by patient-controlled analgesia (PCA). Measurements and Main Results: The fentanyl requirements were recorded for the 24-hour postoperative period and the total perioperative period. Postoperative pain was assessed by visual analog scale for pain (VASP). Plasma oxycodone concentrations were measured in groups OIB and OIM. The total perioperative fentanyl consumption was significantly lower in groups BIB (0.97 6 0.09 mg) and OIB (1.23 6 0.12 mg) than in group OIM (1.61 6 0.12 mg) (p 5 0.01 and 0.048, respectively). Groups BIB and OIB were similar (p 5 0.34). The absorption of oxycodone was significantly lower after subacromial than after intramuscular administration. Conclusion: Intrabursal oxycodone and intrabursal bupivacaine reduced perioperative analgesic requirements similarly. Intrabursal oxycodone may offer an effective, simple, and safe method for postoperative analgesia after shoulder surgery. © 1999 by Elsevier Science Inc.
Keywords: Acromioplasty; analgesia: patient-controlled, peripheral opioid, postoperative; oxycodone; surgery: shoulder.
Journal of Clinical Anesthesia 11:11–16, 1999 © 1999 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/99/$–see front matter PII S0952-8180(98)00122-6
Original Contributions
Introduction Acute postoperative pain after shoulder surgery varies from moderate to severe,1 and it can be managed using interscalene brachial plexus block or supraclavicular block.2 However, the use of these techniques may be limited by adverse effects.The incidence of hemidiaphragmatic paresis is 100% with interscalene block3 and 50% with supraclavicular block.4 Other possible major complications include high spinal or epidural anesthesia, inadvertent intravasal injection, and neural damage.2 Suprascapular nerve block is safer than either technique and has been shown to be effective in analgesia after arthroscopic shoulder surgery.5 After shoulder arthroscopy both intraarticular1 and subacromial6 injection of bupivacaine have been shown to be ineffective in reducing postoperative analgesic requirements. However, pain after manipulation of frozen shoulder has been treated succesfully with intraarticular injection of morphine and bupivacaine into the shoulder joint.7 In our previous study,8 we were able to show that the analgesic effect of infiltration of the subacromial bursa with a combination of bupivacaine and oxycodone is comparable to the effect of interscalene brachial plexus blockade, when comparing the perioperative analgesic requirements in conjunction to shoulder surgery. Additionally, the effect of a combination of bupivacaine and oxycodone 5 mg was superior to that of infiltration with plain 0.5% bupivacaine. However, the analgesic efficacy of intrabursal oxycodone alone was not investigated. The aim of the present study was to compare the local analgesic effect of intrabursally administered oxycodone to the effect of intrabursally administered bupivacaine and conventional intramuscular (IM) administration of oxycodone after elective shoulder surgery.
Materials and Methods The study protocol was approved by the Ethical Committee of Turku University Central Hospital and Turku University, and written informed consent was obtained from each patient on the day before surgery. Forty-two ASA physical status I and II patients scheduled for shoulder surgery were included in the study.The surgical procedures included the Neer acromioplasty for impingement syndrome (rotator cuff tendinitis) with possible repair of the rotator cuff rupture. The Neer acromioplasty consists of removal of the frontal lower part of the acromion and coracoacromial ligament, and resection of subacromial bursa, with subsequent decompression of the impingement.9 All procedures were performed by the same surgeon using conventional open technique. The criteria for exclusion from the study were severe cardiovascular, respiratory, metabolic, or neurologic disease, the use of oral or parenteral opioids preoperatively, history of allergy to any study medication, and the need for drainage after surgery. 1
Moote C: Random double-blind comparison of intra-articular bupivacaine and placebo for analgesia after outpatient shoulder arthroscopy [Abstract]. Anesthesiology 1994;81:A49. 12
J. Clin. Anesth., vol. 11, February 1999
Patients were given no opioid narcotic or antiinflammatory drugs 24 hours before operation. Premedication consisted of 10 mg of diazepam perorally 1 hour before arrival to the operating room. Anesthesia was induced with intravenous (IV) fentanyl 3 mg/kg and thiopental 4 mg/ kg, and maintained with 70% nitrous oxide in oxygen and isoflurane. Tracheal intubation was facilitated with vecuronium 0.08 mg/kg and ventilation controlled mechanically. Adequate anesthesia was maintained with isoflurane and supplementary doses of fentanyl 1 mg/kg when the patient’s blood pressure (BP) exceeded preoperative values by 25%. Monitoring included ECG, pulse oximetry, end-tidal CO2, and noninvasive BP measurement. All anesthetics were given by either of the two co-author anesthesiologists (O.K. or P.M.). Patients were randomly allocated, via sealed envelope assignment, to one of the three groups: at the conclusion of surgery, group BIB (n 5 14) received a 10-ml injection of 0.5% bupivacaine in subacromial bursa before skin closure; group OIB (n 5 14) received 5 mg of oxycodone (Oxanest, Leiras Medica, Turku, Finland) in 10 ml of normal saline, respectively; and group OIM (n 5 14) received 5 mg of oxycodone in the deltoid muscle of the opposite arm. The drug solutions were drawn into syringes by an independent nurse and administered by the surgeon who was blinded s to the contents of the syringes. The patients were under general anesthesia at the time of study drug administration and blinded as to which group they were assigned. After extubation the patients were moved to recovery room, and BP, heart rate, respiratory rate and peripheral oxygen saturation were monitored every 5 minutes for 2 to 3 hours. Immediately after arrival to the recovery room, patientcontrolled analgesia (PCA) with IV fentanyl was commenced to provide postoperative analgesia. PCA-device (Simms Deltec, Inc., St. Paul, MN) was programmed to give a 25-mg bolus of fentanyl without basal infusion. The lockout period was 7 minutes and the maximal fentanyl dose 200 mg/hr.The amount of fentanyl used over the 24-hour postoperative period and the total amount of fentanyl used perioperatively were documented and used for statistical analysis to avoid possible bias caused by different doses of fentanyl administered intraoperatively. Adverse effects such as nausea or drowsiness were recorded when reported spontaneously. Nausea and vomiting were treated with droperidol 1.25 mg IV as needed. Antiinflammatory drugs (NSAIDs) were not given. Patients were asked to mark the intensity of their shoulder pain in rest on a 100-mm visual analog scale for pain (VASP) ranging from 0 (no pain) to 100 mm (unbearable pain). Pain was first assessed just prior to the induction of the anesthesia and then postoperatively at 1, 2, 3, 6, and 24 hours after the study drug injection. Pain assesments were made by an independent nurse who was blinded as to patients’ study group assignment. The plasma concentrations of oxycodone were measured to compare drug absorption after IM administration and absorption from subacromial bursa. For blood sampling, an IV cannula was inserted during general anesthesia into a large antecubital vein to patients in groups OIB
Peripheral opiod analgesia: Muittari et al.
Table 1. Demographic and Clinical Data of Patients Undergoing Elective Shoulder Surgery
Age (yrs) Weight (kg) Gender (M:F) ASA physical status (I:II) Duration of surgery (min) Type of surgery: (acromioplasty:rotator cuff reconstruction)
Group BIB
Group OIB
Group OIM
51 6 2 83 6 3 9:5 8:6 44 6 4 8:6
48 6 3 78 6 5 7:7 10:4 43 6 2 7:7
51 6 2 79 6 4 8:6 12:2 42 6 4 8:6
Note: Values are means 6 SEM. BIB 5 intrabursal bupivacaine; OIB 5 intrabursal oxycodone; OIM 5 intramuscular oxycodone.
and OIM. Blood samples were drawn before administration of oxycodone and thereafter at 10, 20, 30, and 60 minutes and at 2, 3, and 6 hours. For oxycodone assay, the 10-ml samples were immediately centrifuged, and the obtained plasma was stored at 220°C until analyzed. Plasma oxycodone concentrations were determined in duplicate by gas chromatography as described by Kalso et al.10
Statistical Analysis The data were analyzed using a commercial statistical software package (SYSTAT, Systat, Inc., Evanston, IL). Patient age, weight, and duration of surgery were compared between groups using one-way analysis of variance
(ANOVA). Differences between groups in the VASP scores were tested by ANOVA for repeated measures. The amount of fentanyl administered from PCA-device during the 24-hour postoperative period and the total perioperative period were compared between the groups using ANOVA, and Tukey’s test was applied for post hoc analysis. Differences of plasma oxycodone consentrations in groups OIB and OIM were analyzed by t-test. Results are presented as means (standard error of mean). A p-value less than 0.05 was considered statistically significant.
Results Demographic and clinical data are presented in Table 1. There were no significant differences among the study groups with regard to age, weight, gender, ASA physical status, duration or surgery, or type of surgery performed. The study groups differed with regard to the amount of fentanyl administered from PCA-device during the 24hour postoperative period and the total amount of fentanyl required perioperatively (Figure 1). The postoperative fentanyl consumption was significantly (p 5 0.002) lower in group BIB (0.59 6 0.09 mg) than in group OIM (1.17 6 0.12 mg). Group BIB did not differ from group OIB with regard to fentanyl consumption (0.59 6 0.09 mg vs. 0.80 6 0.12 mg, respectively; p 5 0.33). The difference in fentanyl requirements between groups OIB and OIM did not reach statistical significance (p 5 0.057). The total fentanyl consumption was significantly lower in groups BIB (1.02 6 0.08 mg) and OIB (1.24 6 0.12 mg) than in group OIM (1.61 6 0.12 mg), and the difference reached statistical significance for both groups (p 5 0.001
Figure 1. Postoperative and total perioperative fentanyl consumption in the study groups. Values are given as means (SEM). * indicates a statistically significant difference: the postoperative fentanyl consumption in group BIB (intrabursal bupivacaine) was significantly lower (p 5 0.002) than in group OIM (intramuscular oxycodone), and the total fentanyl consumption was significantly lower in groups BIB (p 5 0.001) and OIB (intrabursal oxycodone) (p 5 0.048) than in group OIM. J. Clin. Anesth., vol. 11, February 1999
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Original Contributions
Figure 2. Plasma oxycodone concentrations after intrabursal (OIB) and intramuscular (OIM) administration. Values are given as means (SEM). * indicates a statistically significant difference (p 5 0.041).
and 0.048, respectively). Groups OIB and BIB did not differ in their fentanyl requirements (p 5 0.34). Plasma oxycodone concentrations generally were lower after intrabursal injection (group OIB) than after IM injection (group OIM) (Figure 2). The difference reached statistical significance 20 minutes after oxycodone injection (p 5 0.041), when the plasma concentrations were
12.3 (1.3) and 24.1 (4.8) ng/ml in groups OIB and OIM, respectively. VASP scores were lowest in group BIB and highest in group OIM , but the differences did not reach statistical significance at any time points (Figure 3). In each group, pain was worst at 1 hour postoperatively, and then gradually diminished.
Figure 3. Visual analog scale for pain (VASP) scores at various times after study drug injection. Values are given as means (SEM). BIB 5 intrabursal bupivacaine; OIB 5 intrabursal oxycodone; OIM 5 intramuscular oxycodone. 14
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Peripheral opiod analgesia: Muittari et al.
Postoperative analgesia provided by the PCA-device was well tolerated. Fentanyl caused only minor adverse effects in the study patients. During the 24 postoperative hours, 35% of patients complained of mild drowsiness and 29% of nausea; one patient in group BIB vomited. The number of nauseated patients who were treated with droperidol 1.25 mg IV were 3, 3, and 6 in groups BIB, OIB, and OIM, respectively.The incidence of these adverse effects did not differ among the study groups.
Discussion The results of the present study suggest that intrabursally administered oxycodone in conjunction with shoulder surgery may effectively alleviate postoperative pain and reduce consumption of analgesics. In reducing the need for perioperative fentanyl consumption, the efficacy of intrabursal oxycodone equals that of bupivacaine and is superior to IM oxycodone administration, despite lower plasma oxycodone concentrations. In our earlier study, intrabursally administered combination of oxycodone and bupivacaine did not differ in efficacy from interscalene brachial plexus block.9 Based on these two studies, one can assume that the combination of oxycodone and bupivacaine administered intrabursally is more effective than either of them alone in analgesia in conjunction with shoulder surgery. In the present study, groups OIB and OIM did not differ significantly in postoperative fentanyl requirements (p 5 0.057), but when the total perioperative consumption was compared, the difference reached statistical significancy (p 5 0.048). The amount of fentanyl administered intraoperatively did not differ among the study groups. Thus, the difference in significance level may reflect smaller interindividual variability within the study groups, when the total perioperative fentanyl requirements are accounted for. The half-life of fentanyl is relatively long, and intraoperatively administered fentanyl consequently has an effect on the postoperative needs of analgesics.11 Thus, in this setting, the total perioperative fentanyl consumption best reflects differences between pain treatment modalities. Additionally, this type of surgery is associated with considerable postoperative pain, and balanced anesthesia with perioperative fentanyl was considered necessary, even though the experimental design might have been simplified with the use of plain inhalation anesthesia. Plasma oxycodone concentrations after intrabursal administration proved to be lower than after IM administration. This finding, together with the fact that the concentrations generally were very low, rules out any longstanding central antinociceptive effect of oxycodone. Thus, comparison among groups for perioperative analgesic requirements is relevant, and group OIM (IM oxycodone) was used as a reference group instead of an actual placebo group. Oxycodone, or 14-hydroxy-7,8-dihydrocodeinone, is a synthetic thebain derivate and its pharmacokinetic characteristics10,12–14 and pharmacodynamic features14 –16 are closely related to those of morphine.
Surprisingly, the peak oxycodone plasma concentration occurred at 20 minutes after IM injection, earlier than the time of 60 minutes reported by Po¨yhia¨ et al.12. This may reflect more active circulation in deltoid than in vastus lateralis muscle.17 Patient-controlled analgesia is an established method in pain treatment, even after shoulder surgery.18 That there were only insignificant differences between groups in VASP scores indicates that the method worked properly: each patient received the amount of fentanyl needed to control the pain at an acceptable level. Moreover, PCA offers a valuable tool for pain research: a computerderived PCA-device records the precise amount of analgesic consumed and the delivery time. Kalso et al.19 reviewed studies on peripheral analgesic action of morphine in conjunction with arthroscopic knee surgery. They concluded that intraarticular morphine does induce analgesia. However, several questions remain to be addressed: the influence of tourniquet release time or the use of regional anesthesia, and variability of the tissue injury caused by surgical intervention. Thus, shoulder surgery may offer some advantages over knee surgery to elucidate the issue. First, pain after shoulder surgery varies from moderate to severe,1 and most patients need considerable amounts of analgesics to control their pain. By contrast, pain after minor arthroscopic operation often varies from minor to moderate.19 This fact may explain why many trials failed to show any differences between treatments. Second, subacromial bursa offers a suitable compartment for drug injection and for the spread of a drug to the injured area. Additionally, in acromioplasty, tissue injury is relatively standard in extent. Thus, shoulder surgery may offer a better model for studies on peripheral antinociceptive effects of opioids than knee arthroscopy. In conclusion, the results of the present study may support the concept of peripheral opioid analgesia: oxycodone administered intrabursally produced better analgesia than after IM administration, despite lower serum oxycodone concentrations. However, the analgesic effect of intrabursal oxycodone did not exceed that of intrabursal bupivacaine. The technique of peripherally administered opioids, alone or in combination with local anesthetics, may offer promising results in pain therapy after shoulder surgery: the technique seems effective, simple, and safe.
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