BJA Advance Access originally published online on November 27, 2007
British Journal of Anaesthesia 2008 100(1):36-41; doi:10.1093/bja/aem338
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Pre-incisional epidural ropivacaine, sufentanil, clonidine, and (S)+-ketamine does not provide pre-emptive analgesia in patients undergoing major pancreatic surgery 
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1 Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Knappschaftskrankenhaus Bochum Langendreer, University Hospital Bochum, In der Schornau 23-25, 44892 Bochum, Germany
2 Department of Anaesthesiology
3 Department of Surgery, and
4 Pharmacy, University Hospital Hamburg Eppendorf, Hamburg, Germany
5 Department of Anaesthesiology and Critical Care Medicine, Academic Hospital Solingen, Germany
* Corresponding author: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Knappschaftskrankenhaus Bochum Langendreer, University Hospital Bochum, In der Schornau 23-25, 44892 Bochum, Germany. E-mail: gottschalk.andre{at}gmx.de
Background: The concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml–1, sufentanil 0.5 µg ml–1, clonidine 3 µg ml–1, and S(+)-ketamine 0.25 mg ml–1 (study solution) given before incision with the same combination started at the end of the operation.
Methods: After testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml–1 and sufentanil 0.5 µg ml–1, 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6–8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h–1) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects.
Results: Visual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (SD 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups.
Conclusions: Pre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.
Keywords: anaesthetics local, ropivacaine; analgesia, pre-emptive; analgesic techniques, extradural; analgesics non-opioid, clonidine; analgesics opioid, sufentanil
Results of this study were presented, in part, at meetings of the European Society of Regional Anaesthesia (ESRA) in Athens 2004 and in Monaco 2006, and at the meetings of the German Society of Anaesthesiology in Nürnberg 2004 and in Leipzig 2006.
Declaration of interest. The study was carried out at the Department of Anaesthesiology, University Hospital Hamburg Eppendorf, and received financial support from AstraZeneca, Wedel, Germany. This consisted of payment of the local ethics committee fee and insurance for the patients.
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