Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine-butorphanol mixtures for postoperative analgesia

British Journal of Anaesthesia 1995; 75: 548–551

Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine–butorphanol mixtures for postoperative analgesia Z. WAJIMA, T. SHITARA, Y. NAKAJIMA, C. KIM, N. KOBAYASHI, H. KADOTANI, H. ADACHI, G. ISHIKAWA, K. KANEKO, T. INOUE AND R. OGAWA

Summary We have reported recently that continuous administration of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v. administration. In the present study, we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath: opioid alone, local anaesthetic alone or a mixture of local anaesthetic and opioid. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, we injected one of the three solutions into the axillary neurovascular sheath: butorphanol 2 mg (group B), 0.5 % mepivacaine alone (group M) and 0.5 % mepivacaine–butorphanol (group MB); the volume of each solution was 50 ml, administered at a rate of 50 ml per 24 h. At 3 h after operation, visual analogue scale (VAS) scores were significantly higher in group M than in group MB (P : 0.01), and higher in group B than in group MB (P ⬍ 0.05). (Br. J. Anaesth. 1995; 75: 548–551) Key words Analgesia, postoperative. Analgesic techniques, regional, brachial plexus. Analgesics opioid, butorphanol. Anaesthetics, local, mepivacaine.

Continuous brachial plexus block is a valuable technique for prolonged surgery of the upper extremity, provision of continuous postoperative analgesia and production of sympathectomy leading to increased blood flow in the upper extremity [1]. We have reported recently a randomized, doubleblind, controlled study comparing patients receiving continuous systemic i.v. infusion and those receiving a continuous local brachial plexus infusion of butorphanol for analgesia after surgery on the upper extremities [2]. We observed that continuous administration of butorphanol into the brachial plexus sheath at a dose of 83.3 ␮g h⫺1 provided analgesia of a quality superior to that of continuous i.v. injection. In the present study, we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath: butorphanol alone, 0.5 % mepivacaine alone or 0.5 % mepivacaine–butorphanol.

Patients and methods With the approval of our institutional Ethics Committee and written informed consent of the patients, we studied prospectively 33 patients undergoing elective upper extremity surgery. All patients were ASA I or II and aged 10–82 yr. The operations varied from open reduction of fractures to tendon transfer. Similar surgical procedures were performed in the three groups and surgery was performed by the same surgeon. Patients received 75 mg of oral roxatidine acetate hydrochloride, an H2 antagonist, the night before operation and 2 h before arrival in the operating theatre. For the operative procedure, a continuous axillary brachial plexus block was established with 30 ml of 1.5 % mepivacaine using the method of Sada, Kobayashi and Murakami [3]. The operation was started after complete analgesia at the operative area was established. Mepivacaine 1.5 % (10 ml) was injected every 90 min. Sedation was provided with midazolam in i.v. boluses at the discretion of the anaesthetist. Patients were excluded if complete analgesia at the operative area was not achieved by the initial block. Just after the end of operation, 1.5 % mepivacaine 10 ml was given into the brachial plexus sheath and patients were allocated randomly to one of three groups. The butorphanol group (group B) received a continuous brachial plexus infusion of butorphanol 83.3 ␮g h91 (2 mg per 24 h) using a disposable type continuous microinfuser (Surefuser-A 1D, Nipro, Osaka). The concentration of the butorphanol solution was 2 mg per 50 ml. The mepivacaine group (group M) received a continuous brachial plexus infusion of 0.5 % mepivacaine 50 ml per 24 h. The mepivacaine–butorphanol group (group MB) ZEN’ICHIRO WAJIMA*, MD, TOSHIRO SHITARA*, MD, YUSHI NAKAJIMA†, MD, CHOL KIM*, MD, NORIYUKI KOBAYASHI*, MD, HITOSHI KADOTANI*, MD, HITOSHI ADACHI*, MD, GEN ISHIKAWA*, MD, KATSUTOSHI KANEKO*, MD, TETSUO INOUE‡, MD, RYO OGAWA*, MD, Kitamurayama Kohritsu Hospital. Accepted for publication: June 12, 1995. Present addresses: * Department of Anaesthesiology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113 Japan. † Department of Anaesthesiology, National Cardiovascular Centre, 5-7-1, Fujishirodai, Suita-shi, Osaka, 565 Japan. ‡ Department of Anaesthesia, Chiba Hokusoh Hospital, Nippon Medical School, 1715, Kamakari, Inba-mura, Inba-gun, Chiba, 270-16 Japan.

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received a continuous brachial plexus infusion of 0.5 % mepivacaine with butorphanol 2 mg at 50 ml per 24 h; 24 and 48 h after operation, the same solution was added to the microinfuser. A supplementary analgesic drug, diclofenac suppository 50 mg, was available as needed for each patient to establish comfort at rest. No other opioids or sedatives were administered. Patients rated their pain at rest on a 10-cm unmarked linear visual analogue scale (VAS) [4, 5], ranging from “no pain” to “unbearable pain”. Scores were obtained 3, 6, 9, 12, 18, 24, 36 and 60 h after surgery. The observers were blinded to the analgesic solutions. The time and dose of supplementary analgesic medication were recorded. Arterial pressure, heart rate and ventilatory frequency were monitored. If side effects such as respiratory depression, nausea, vomiting and drowsiness occurred, the time was recorded. Quantitative data are expressed as mean (SD). Patient characteristics and duration of operation were analysed statistically by one-way analysis of variance (ANOVA). The dose of mepivacaine, pain scores and consumption of supplementary analgesic drugs were compared using the Kruskal–Wallis test and Dunn’s procedure for post hoc evaluation. The incidence of side effects was analysed by Fisher’s exact probability tests with Bonferroni’s correction. P ⬍ 0.05 was considered significant.

Results There were 14 patients in group B, nine in group M and 10 in group MB. There were no significant differences between the three groups in sex distribution, age, weight, height, dose of mepivacaine or duration of surgery (table 1).

At 3 h after operation, VAS scores were significantly higher in group M than in group MB (P ⬍ 0.01), and higher in group B than in group MB (P ⬍ 0.05). At 9 and 18 h after operation, VAS scores were significantly higher in group M than in group MB (P ⬍ 0.05). At 12 h after operation, VAS scores were significantly higher in group M than in group B (P ⬍ 0.05), while at 24 h, VAS scores were significantly higher in group M than in both groups MB and B (P ⬍ 0.05). However, VAS scores in the three groups did not differ at 6, 36 or 48 h after operation (table 2). At 4 h after operation, cumulative diclofenac analgesic consumption was significantly higher in group M than in group MB (P ⬍ 0.05). There were no significant differences between the three groups in supplementary analgesic consumption at 8 h or later (table 3). Respiratory depression (ventilatory frequency ⬍8 b.p.m.) did not occur. There were no significant differences in the incidence of vomiting, slight drowsiness and dizziness between the three groups, but there was a significant difference in the incidence of nausea in group B compared with group M (P ⫽ 0.014) (table 4).

Discussion We found that analgesia was most pronounced in group MB and that group B ranked next. Various investigators have studied continuous local anaesthetic infusion into the brachial plexus sheath by the axillary or interscalene approach for relief of postoperative pain [6–10]. While some investigators administered systemic opioids, none tried continuous opioid infusion into the brachial plexus sheath. It may be difficult sometimes to

Table 1 Patient characteristics (mean (SD) [range])

Sex (M : F) Group B (n ⫽ 14) Group M (n ⫽ 9) Group MB (n ⫽ 10)

Age (yr)

9:5

47.1 [10–68] 35.7 [13–55] 33.8 [13–82]

6:3 7:3

Weight (kg) 50.9 (11.2) [26–65] 57.9 (11.8) [43–78] 58.2 (11.8) [46–78]

Height (cm)

Dose of 1.5 % mepivacaine (ml)

Duration of surgery (min)

154.6 (10.8) [140–170] 161.2 (11.3) [140–172] 161.2 (13.8) [143–184]

44.3 (9.3) [40–70] 42.2 (4.4) [40–50] 42.0 (4.2) [40–50]

62.6 (23.9) [34–98] 64.4 (22.8) [40–94] 53.7 (13.2) [35–75]

Table 2 Visual analogue scale scores after operation (mean (SD) [range]). Data were analysed by Kruskal–Wallis’ and Dunn’s procedures Time (h)

Group B (n ⫽ 14) Group M (n ⫽ 9) Group MB (n ⫽ 10) Kruskal– Wallis test Post hoc comparison

3

6

9

12

18

24

36

60

2.5 (2.1) [0–6.2] 5.0 (2.4) [0–8.1] 0.3 (0.6) [0–1.9] H ⫽ 15.5 (P ⬍ 0.0005) M ⬎ MB (P ⬍ 0.01) B ⬎ MB (P ⬍ 0.05)

2.3 (2.5) [0–8.3] 4.1 (2.0) [0–7.1] 1.6 (2.1) [0–6.4] H ⫽ 6.3 (P ⬍ 0.05) ns

1.5 (1.8) [0–5.1] 3.6 (1.8) [0–6.5] 1.1 (1.5) [0–4.4] H ⫽ 7.8 (P ⬍ 0.05) M ⬎ MB (P ⬍ 0.05)

1.0 (1.6) [0–5.2] 3.2 (1.8) [0–6.1] 1.0 (1.2) [0–3.0] H ⫽ 9.6 (P ⬍ 0.01) M⬎B (P ⬍ 0.05)

1.5 (2.3) [0–7.5] 2.9 (1.2) [0–4.0] 1.1 (1.2) [0–2.5] H ⫽ 7.8 (P ⬍ 0.05) M ⬎ MB (P ⬍ 0.05)

0.7 (1.2) [0–3.6] 3.1 (1.5) [0–5.5] 1.0 (1.1) [0–2.9] H ⫽ 11.5 (P ⬍ 0.005) M ⬎ MB (P ⬍ 0.05) M⬎B (P ⬍ 0.05)

1.0 (1.8) [0–5.2] 2.7 (2.5) [0–8.2] 1.5 (1.9) [0–4.9] H ⫽ 5.8 (ns)

1.2 (2.5) [0–9.1] 1.6 (1.6) [0–4.0] 0.2 (0.6) [0–1.8] H ⫽ 4.0 (ns)

550

British Journal of Anaesthesia Table 3 Cumulative diclofenac suppository requirements (mean (SD)) in the three groups for the first 48 h after operation. Data were analysed by Kruskal–Wallis’s and Dunn’s procedures. The dose of diclofenac in group M at 4 h was significantly higher than in group MB Requirement for diclofenac (mg)

Group B (n ⫽ 14) Group M (n ⫽ 9) Group MB (n ⫽ 10) Kruskal– Wallis test Post hoc comparison

4h

8h

12 h

18 h

24 h

48 h

17.9 (31.7)

21.4 (37.8)

25.0 (38.0)

28.6 (46.9)

28.6 (46.9)

35.7 (69.1)

33.3 (25.0)

33.3 (25.0)

38.9 (33.3)

38.9 (33.3)

38.9 (33.3)

44.4 (46.4)

0.0 (0.0)

5.0 (15.8)

5.0 (15.8)

5.0 (15.8)

5.0 (15.8)

10.0 (21.1)

H ⫽ 9.0 (P ⬍ 0.05) M ⬎ MB (P ⬍ 0.05)

H ⫽ 5.7 (ns)

H ⫽ 5.9 (ns)

Table 4 Number of patients who required supplementary analgesia and who showed side effects in the three groups after operation. There was a significant difference between the three groups in the incidence of nausea (P ⬍ 0.05) (group B had a higher incidence than group M). * P ⫽ 0.05 compared with group M

Required supplementary analgesia Nausea Vomiting Slight drowsiness Dizziness

Group B (n ⫽ 14)

Group M (n ⫽ 9)

Group MB (n ⫽ 10)

5

6

2

7* 4 3 2

0 0 0 0

3 1 1 1

relieve postoperative pain by continuous infusion of a local anaesthetic alone, which may possibly induce local anaesthetic toxicity. Haynsworth, Heavner and Racz [9] measured plasma concentrations of bupivacaine after 8, 9 and 10 days of continuous infusion of a 0.125 % solution. Concentrations reported were 0.24, 0.40 and 0.54 ␮g ml⫺1, respectively. Such concentrations are well below the toxic concentration of 4 ␮g ml⫺1 for bupivacaine in humans [11]. Other studies, however, found significantly higher plasma concentrations during continuous infusion. Tuominen, Rosenberg and Kalso [8] reported a mean concentration of 1.03 ␮g ml⫺1 after only 16 h of infusion, while Rosenblatt, Pepitone-Rockwell and McKillop [6] reported a gradual increase in bupivacaine concentrations with levels greater than 1 ␮g ml⫺1 after 48 h. Both authors administered 0.25 % bupivacaine at a rate of 10 ml h⫺1. Thus systemic drug accumulation may occur when the rate of infusion exceeds clearance by metabolism and excretion. Potential systemic toxicity must be considered if long-term continuous infusions are used [12]. We reported recently that continuous infusion of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v. injection [2]. Consequently, we believe that continuous infusion of a mixture of local anaesthetic and opioid is preferable to infusion of a local anaesthetic alone into the neurovascular sheath, with systemic opioid administration. If sympathectomy is the prime aim, a high rate of infusion of local anaesthetic alone must be chosen, but for postoperative pain management, infusion of a local

H ⫽ 5.8 (ns)

H ⫽ 5.8 (ns)

H ⫽ 4.0 (ns)

anaesthetic combined with opioids may avoid local anaesthetic toxicity. There is evidence that concomitant use of an extradural opioid with a local anaesthetic may have additive effects that achieve control of postoperative and obstetric pain in smaller doses than those necessary with single-drug therapy [13–17]. With reduced drug doses, side effects are minimized and tolerance may be decreased. A similar effect has been demonstrated here with continuous brachial plexus infusion. Although group MB showed the most effective analgesia of the three groups in the first 3 h after operation, there were no significant differences between group MB and group B at or more than 6 h after operation. Further investigation is needed. It may be possible to potentiate postoperative pain relief by increasing the concentration of local anaesthetic, increasing the rate of administration of local anaesthetic or increasing the dose of opioid. The incidence of nausea was higher in group B than in group M. This may be caused by butorphanol administration [18, 19], but although the dose of butorphanol in group B was the same as in group MB, the incidence of nausea in group MB did not differ significantly from that of group M. In addition to being a side effect of opioids, nausea may also result from postoperative nociceptive impulses arising in the viscera and somatic structures. Studies have demonstrated the presence of powerful cutaneovisceral and viscerovisceral reflexes, resulting in segmental sympathetic hyperactivity and consequent inhibition of gastrointestinal function. These were shown to be produced by reflex responses initiated not only in the thoracic and abdominal viscera but in the extremities and elsewhere [20]. Presumably postoperative nociceptive impulses were not great in group MB. As we have reported that brachial plexus infusion of butorphanol had a more potent analgesic effect than systemic administration [2], a lower dose of butorphanol infused into the neurovascular sheath rather than systemic administration should be chosen to prevent side effects such as nausea.

Acknowledgements We are indebted to Takuya Sawaizumi, MD, Department of Orthopaedics, Nippon Medical School, Tokyo, Japan, for helpful comment.

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