1 Department of Anesthesiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. 2 Department of Anesthesiology, National Defense Medical College, Saitama, Japan
Corresponding author. E-mail: nitahara@fukuoka-u.ac.jp
Accepted for publication: December 2, 2002
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Abstract |
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Methods. After elective lower abdominal gynaecological surgery, 30 patients were randomized to receive continuous i.v. diltiazem 1 µg kg1 min1 (diltiazem group) or the same volume of saline (control group) for 24 h. Cumulative postoperative epidural fentanyl consumption, visual analogue scale (VAS) scores and verbal rating scores (VRS) at rest and during mobilization, sedation scores, incidence of side-effects and overall patient satisfaction were assessed.
Results. There was no significant difference in cumulative epidural fentanyl consumption between the groups at any period. Although there were no statistically significant differences in VAS scores, VRS, sedation scores, incidence of side-effects and overall patient satisfaction, there was a trend to an increased incidence of nausea in the diltiazem group.
Conclusions. Continuous i.v. infusion of diltiazem did not reduce epidural fentanyl consumption when administered at dosages having minimal haemodynamic depressant effects.
Br J Anaesth 2003; 90: 5079
Keywords: analgesic techniques, epidural; analgesics opioid, fentanyl; heart, antiarrhythmics, diltiazem; heart block, calcium channel blockers; pain, postoperative
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Introduction |
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Methods and results |
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Patients were premedicated with oral diazepam 10 mg. An epidural catheter was inserted at the T12L2 interspace. Epidural anaesthesia to achieve T46 sensory block (to cold) was established by injecting mepivacaine 2% via the catheter. General anaesthesia was induced and maintained with propofol.
In the postanaesthesia care unit (PACU), patients were randomized to receive continuous i.v. diltiazem 1 µg kg1 min1 (diltiazem group) or the same volume of saline (control group) for 24 h. At the same time, each patient received fentanyl 50 µg plus mepivacaine 0.25% 5 ml epidurally. The patient-controlled analgesia pump was set to deliver an epidural background infusion of fentanyl solution 3 µg ml1 at 4 ml h1 and a 4 ml bolus of the same solution on demand with a lockout time of 10 min and a maximum dose of 20 ml h1.
Data were collected from the PACU 3 and 6 h after surgery and then three times a day between 8:00 and 10:00 a.m., 0:00 and 2:00 p.m., and 6:00 and 8:00 p.m. until the morning of the second day after surgery. Data collection included visual analogue scale (VAS) scores for pain at rest and during mobilization (0=no pain, 100=worst imaginable pain), verbal rating scores (VRS) for pain at rest and during mobilization (0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain), and sedation scores (0=alert, 1=drowsy, 2=sleeping but easily arousable by calling, 3=awakened only by shaking, 4=unarousable). Overall satisfaction was assessed at the discontinuation of treatment (0=no satisfaction, 3=best satisfaction). Consumption of patient-controlled epidural fentanyl was recorded 3, 6, 12, 24, 36 and 48 h after operation.
Differences between the groups were analysed using the unpaired t-test, the MannWhitney U-test and the 2-test. P<0.05 was considered statistically significant.
Epidural analgesia was not established sufficiently in two patients and data from these patients were not included in the analysis. There were no statistically significant differences between the groups with respect to patient characteristics, duration of surgery and anaesthetic requirements.
VAS scores were similar, being <40 at rest and <50 at mobilization in both groups at any time. VRS were also similar and <2 in both groups at any period. VAS scores and VRS in the PACU were <10 and <0.5 in the two groups respectively. There was no significant difference in cumulative epidural fentanyl consumption between the groups at any time (Fig. 1). There were no significant differences between the groups in sedation scores and in the incidence of side-effects, including pruritus, nausea, vomiting, headache and dizziness. However, there was a trend towards an increase in the incidence of nausea in diltiazem group. Nausea occurred in 40% of the diltiazem group (6 of 15) and 13% of the control group (2 of 15) (P=0.09) and was observed only within the first 24 h. Overall patient satisfaction was also similar between the groups.
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Comment |
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The vasodilating effects of diltiazem are present at plasma concentrations above 100 ng ml1.5 The plasma diltiazem concentrations associated with a 20% prolongation of atrioventricular conduction time range from 65 to 250 ng ml1.6 We gave diltiazem at an infusion rate of 1 µg kg1 min1. Katori and colleagues7 showed that diltiazem 1 µg kg1 min1 stabilizes the plasma concentration at 4060 ng ml1 24 h after the start of the infusion. Although we did not measure the plasma diltiazem concentration, no patient developed clinically significant hypotension or bradycardia during the study.
Naito and colleagues8 showed in rabbits that diltiazem penetrated rapidly into the cerebrospinal fluid (CSF) through the bloodbrain barrier after i.v. administration, and the concentration in CSF reached a peak 5 min after the injection.8 The CSF/plasma ratio of diltiazem was 0.050.2, which is similar to that of nimodipine.9
It is probable that L-type calcium-channel blockers act more effectively by the epidural route. However, Koh and Cotman10 showed that verapamil and diltiazem 3 µM produced an increase in lactate dehydrogenase, released by damaged or destroyed cells. The migration of epidural catheters into the subarachnoid space is a well-documented complication. Although the toxicity of L-type calcium-channel blockers in the spinal cord is not clear, we selected the systemic route for the use of diltiazem.
In conclusion, low-dose diltiazem administered as an adjunct to epidural fentanyl offered no advantages in either pain relief or epidural fentanyl consumption after lower abdominal gynaecological surgery.
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References |
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