Department of Anaesthesia, The Cardiothoracic Centre, Liverpool, Thomas Drive, Liverpool L14 3PE, UK 1 Present address: Department of Anaesthesia, University Hospitals of Wales, Heath Park, Cardiff CF14 4WX, UK 2 Present address: Department of Anaesthesia, University Hospital Aintree, Longmoor Lane, Liverpool L9 7A, UK
*Corresponding author. E-mail: stephen.pennefather{at}ctc.nhs.uk
Accepted for publication: December 13, 2003
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. We studied 99 patients who were randomized to receive fentanyl 2 µg ml1 (group 2), fentanyl 5 µg ml1 (group 5) and fentanyl 10 µg ml1 (group 10) in bupivacaine 0.1% via a thoracic epidural. Postoperatively, pain on coughing was assessed using a visual analogue scale (VAS) and an observer verbal rating score (OVRS) at 2, 8, 16 and 24 h. At the same times, sedation, pruritus and nausea were assessed.
Results. Of 29, 28 and 32 patients who completed the study in groups 2, 5 and 10 respectively, there was no significant difference in baseline characteristics between the three groups. The number of patients with episodes of unsatisfactory pain, i.e. VAS scores >30 mm and OVRS >1, at each of the four assessments postoperatively was significantly (P<0.01) higher in group 2 than in groups 5 and 10. In group 10, 16 patients had sedation scores >1 compared with 10 each in groups 2 and 5. In addition, 19 patients in group 10 experienced pruritus compared with 12 each, in groups 2 and 5. These differences were not significant. Nausea was not significantly different between the three groups.
Conclusion. We conclude that thoracic epidural fentanyl 5 µg ml1 with bupivacaine 0.1% provides the optimum balance between pain relief and side effects following thoracotomy.
Br J Anaesth 2004: 92: 6704
Keywords: anaesthesia, regional; anaesthetic techniques, thoracic epidural; analgesics opioid, fentanyl; surgery, thoracotomy
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Epidural bupivacaine 0.1% is commonly used with a wide range of fentanyl concentrations (1 to 15 µg ml1).3 The important clinical question is what concentration of fentanyl in bupivacaine 0.1% will provide effective analgesia with minimal adverse effects after invasive thoracic surgery. The aim of this study was to investigate the analgesic and adverse effects of three concentrations of epidural fentanyl (2, 5 and 10 µg ml1) in bupivacaine 0.1%.
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
All patients received a standardized anaesthetic comprising diazepam 10 mg po, propofol 12 mg kg1 i.v., fentanyl 1.5 µg kg1 i.v. and atracurium 0.5 mg kg1 i.v. Their lungs were ventilated with isoflurane 12% in oxygen enriched air via a double lumen endobronchial tube. Blood pressure was monitored invasively and hypotension was treated with incremental doses of ephedrine and intravenous fluids as required. Surgical incisions were made through the bed of the 6th rib on the appropriate side. At the end of the procedure after reversal of residual neuromuscular blockade with neostigmine 2.5 mg and glycopyrolate 500 µg, patients were extubated and nursed in a high dependency unit.
In the postoperative period, assessments were made at 2, 8, 16 and 24 h, by one of the authors or nursing staff, blinded to the treatment. Pain on coughing was assessed using a visual analogue scale (VAS) comprising a horizontal 100 mm line representing no pain on the left and worst pain imaginable on the right. In addition, the observer verbal response score (OVRS) scale was used to demonstrate practical endpoints relating to the ability to cooperate with physiotherapy (Table 1).
|
At the same postoperative times, patients were assessed for adverse effects. Sedation was measured on a scale of 0, 1, 2, 3 and 4 representing: awake, not sedated; mild sedation; moderate sedation easily arousable; heavily sedated difficult to rouse; over sedated unarousable, respectively. Also, the presence of nausea and pruritus were assessed at 2, 8, 16 and 24 h postoperatively. Arterial blood gases breathing room air were measured prior to induction and at 2 h postoperatively. The total volume of epidural solution was noted at the end of the 24 h period.
From a pilot study, we showed that 20% of patients receiving bupivacaine 0.1% with fentanyl 5 µg ml1 for post-thoracotomy pain had no episodes when their pain VAS exceeded 30 mm. A clinically important result was judged to be when this proportion was at least 50%. In order to detect the difference with 80% power at the 5% significance level, we estimated that we had to study 30 patients per group.
Data were tabulated in Excel 2000 and analysed using SPSS v.10 for Windows. They were tested for normality using the KolmogorovSmirnov test. One-way ANOVA with Bonferroni correction for multiple comparisons was used to test normally distributed data for significance. We considered that patients were comfortable when their pain VAS scores were 30 mm and OVRS
1. Thus, over the four assessments postoperatively, we noted the number of times when the VAS scores were >30 mm and OVRS>1, for each patient. These frequencies were compared using Chi-squared or Fishers Exact tests, as appropriate.
Similarly, a sedation score of >1 was deemed unsatisfactory and the numbers of patients in each treatment group exceeding this score were compared. A similar analysis was performed for nausea and pruritus using the Chi-squared test. A value of P<0.05 was taken to be significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our results concur with those of a randomized controlled trial (RCT) of thoracic epidural fentanyl 2.5, 5, 10 and 20 µg ml1 with no local anaesthetic.9 It was shown that there was a concentration-dependent reduction in pain intensity in patients undergoing thoracotomy for lung resection. With fentanyl 2.5 µg ml1, there was a significant decrease in proportion of patients with >50% reduction in pain scores, compared with higher concentrations (fentanyl 5, 10 and 20 µg ml1). In another RCT comparing thoracic epidural fentanyl 1, 2 and 4 µg ml1 in ropivacaine 0.2% in patients undergoing major abdominal surgery, it was shown that pain intensity was significantly greater in patients receiving fentanyl 1 to 2 µg ml1 than in those having fentanyl 4 µg ml1.10 In addition, our results are in agreement with another double-blind RCT involving 66 patients undergoing thoracotomy. It was shown that lumbar epidural fentanyl 5 and 10 µg ml1 with no local anaesthetic provided equally effective analgesia.11
Epidural opioids can be associated with dose-dependent adverse effects e.g. sedation, pruritus, nausea and respiratory depression.7 Our study in which there was a tendency to increased sedation in patients receiving epidural fentanyl 10 µg ml1, concurs with a study by Welchew and colleagues.9 He showed that increased sedation occurred at fentanyl 10, 20 µg ml1 but not at fentanyl 2.5 µg ml1. In two other RCTs of patients receiving thoracic epidural fentanyl 1, 2 and 4 µg ml1 in ropivacaine 0.2%, sedation scores were low and no significant difference in sedation was detected.10 12
In our study, there appeared to be an increased incidence of pruritus in patients receiving epidural fentanyl 10 µg ml1. This trend is consistent with a RCT in which the incidence of pruritus increased from 17% at fentanyl 10 µg ml1, to 36% at fentanyl 20 µg ml1.9 In other studies of lower fentanyl concentrations, this concentration-dependent effect was also demonstrable. For instance, the incidence of pruritus was 23%, 8%, 4% and 4% in obstetric patients receiving epidural fentanyl of concentrations 4, 3, 2 and 1 µg ml1, respectively.13 Furthermore, in a RCT of 244 patients undergoing major abdominal surgery, thoracic epidural fentanyl 4 µg ml1 was associated with a significantly (P<0.02) higher incidence of pruritus than fentanyl 1 µg ml1 to 2 µg ml1.10
No significant difference in nausea was found between the three treatment groups in our study. This concurs with Welchews study showing that there was no concentration-dependent nausea between the groups with epidural fentanyl 2.5, 5, 10 and 20 µg ml1.9 In another RCT, no significant difference in nausea was shown between groups receiving epidural fentanyl at 1, 2 and 4 µg ml1.10
In our study, assessments were made in the first 24 h postoperatively, and so our results are applicable to this period. After thoracotomy for lung resection, patients may have an epidural in situ for 5 days. Analgesic requirements are expected to be much reduced on day 5 compared with the immediate postoperative period. Thus if this study was extended beyond the first 24 h, then it is likely that we would have recorded a progressive reduction in opioid consumption in all treatment groups. By day 5, opioid consumption would be low; any possible differences in pain scores and opioid related adverse effects would not be detectable between groups 2, 5 and 10.
Patients who are listed for a thoracotomy may have underlying lung pathology such as chronic obstructive pulmonary disease and pleural disease. Their surgery may involve lung collapse and re-expansion as well as lung resection. In the postoperative period, there is a high risk of sputum retention, pneumonia and pulmonary oedema.2 Consequently, provision of high quality analgesia following thoractomy is essential. From the above discussion and our results, it would appear that higher concentrations of epidural fentanyl may increase the likelihood of opioid-related adverse effects such as sedation and pruritus. On the other hand, lower concentrations of epidural fentanyl do not provide analgesia of high quality following thoracic surgery; they appear to be more appropriate for non-incisional pain e.g. pain during labour.13 14 In patients who receive insufficient analgesia, an alternative method to increasing the concentration of epidural opioid is to consider an additional drug e.g. clonidine. Epidural clonidine prolongs analgesia,15 and by minimizing opioid administration and hence opioid-related adverse effects, it may be useful as an analgesic adjunct after major surgery.16
In conclusion, our study has shown that thoracic epidural fentanyl 5 or 10 µg ml1 in bupivacaine 0.1% is associated with superior analgesia after thoracotomy compared with fentanyl 2 µg ml1 in bupivacaine 0.1% in the immediate postoperative period. However, the use of fentanyl at 10 µg ml1 does not improve analgesia compared with fentanyl 5 µg ml1 and may increase the tendency to excessive sedation and pruritus. Therefore, epidural fentanyl 5 µg ml1 in bupivacaine 0.1% would appear to provide the optimal balance between pain relief and adverse effects following thoracic surgery.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Conacher ID. Pain relief after thoracotomy. Br J Anaesth 1990; 65: 80612[ISI][Medline]
3 Romer HC, Russell GN. A survey of the practice of thoracic epidural analgesia in the United Kingdom. Anaesthesia 1998; 53: 101622[CrossRef][ISI][Medline]
4 Mahon SV, Berry PD, Jackson M, Russell GN, Pennefather SH. Thoracic epidural for post-thoracotomy pain: a comparison of fentanyl-bupivacaine mixtures vs fentanyl alone. Anaesthesia 1999; 54: 6416[CrossRef][ISI][Medline]
5 Liu S, Angel JM, Owen BD, Carpenter RL, Isabel L. Effects of epidural bupivacaine after thoracotomy. Reg Anesth 1995; 20: 30310[ISI][Medline]
6 De Leon-Casasola OA, Lema MJ. Postoperative epidural opioid analgesia: what are the choices? Anesth Analg 1996; 83: 86775[Abstract]
7 Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995; 42: 891903[Abstract]
8 Mourisse J, Hasenbos MA, Gielen MJ, et al. Epidural bupivacaine, sufentanil or the combination for post-thoracotomy pain. Acta Anaesthesiol Scand 1992; 36: 704[ISI][Medline]
9 Welchew EA. The optimal concentration for epidural fentanyl. Anaesthesia 1983; 38: 103741[ISI][Medline]
10 Scott D, Blake D, Buckland M, Etches R, et al. A comparison of epidural ropivacaine alone and in combination with 1, 2, and 4 µg ml1 fentanyl for 72 hrs of postoperative analgesia after major abdominal surgery. Anesth Analg 1999; 88: 85764
11 Thomson C, Becker D, Messick J, de Castro M, et al. Analgesia after thoracotomy: effects of epidural fentanyl concentration/ infusion rate. Anesth Analg 1995; 81: 97381[Abstract]
12 Liu SS, Moore JM, Luo AM, Trautman W, et al. Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 1999; 90: 72732[CrossRef][ISI][Medline]
13 Lyons G, Columb M, Hawthorne L, Dresner M. Extradural pain relief in labour: bupivacaine sparing by extradural fentanyl is dose dependent. Br J Anaesth 1997; 78: 4937
14 Comparative Obstetric Mobile Epidural Trial (COMET) study group UK. Effect of low dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet 2001; 358: 1923[CrossRef][ISI][Medline]
15 Eisenach J, De Kock M, Klimscha W. Alpha-2 adrenergic agonists for regional anesthesia: A clinical review of clonidine (19841995). Anesthesiology 1996; 85: 65574[ISI][Medline]
16 Curatolo M, Schnider T, Petersen-Felix S, et al. A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl and clonidine for postoperative analgesia. Anesthesiology 2000; 92: 32537[ISI][Medline]
|