◊ BACKGROUND:
Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy.
◊ METHODS:
One hundred and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexa-methasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation, dizziness, number of vomits and consumption of ondansetron were recorded 2, 4 and 24 h after the operation. P<0.05 was considered statistically significant.
◊ RESULTS:
The 24-h morphine consumption and pain score, both at rest and during mobilization, were not significantly different between treatment groups. The mean nausea score (P=0.002) was reduced in group C vs. A. The number of vomits was significantly reduced in both group B (P=0.041) and C (P=0.001) vs. A. Consumption of ondansetron was reduced in group C vs. A and B (P<0.001). Other side effects were not different between groups.
◊ CONCLUSION:
Combinations of paracetamol and pregabalin, or paracetamol, pregabalin and dexamethasone did not reduce morphine consumption and pain score compared with paracetamol alone for patients undergoing abdominal hysterectomy. Dexamethasone reduced nausea, vomiting and use of ondansetron.
◊ Reviewed by S. Schug, MD, PhD
Chair of Anesthesiology,
Pharmacology and Anesthesiology Unit, Royal Perth Hospital, Perth, Australia
Multimodal analgesia is a concept, by which a combination of medications with different mechanism of action leads to reduced pain scores, reduced consumption of opioids and of their adverse effects. This study examines the multimodal analgesia achieved by combining paracetamol, pregabalin and dexamethasone. The results are disappointing insofar as the addition of neither pregabalin nor the combination of pregabalin and dexamethasone to paracetamol did improve pain scores or reduce opioid consumption. Not unexpectedly, dexamethasone had an antiemetic effect.
In view of the large number of studies which show gabapentin to provide significant benefits when used perioperatively (1) and the similarity of pregabalin and gabapentin effects in general, this is rather surprising. Indeed, pregabalin with better absorption kinetics and a longer half-life, should have even been the better choice in this setting.
However, the authors correctly commented, that in trials with gabapentin, patients gained more benefits after spinal surgery than after hysterectomy. This made them speculate, that gabapentinoids are perhaps more effective in somatic than in visceral pain and that hysterectomy might be the wrong model to show a benefit of this class of drugs.
Again, it becomes obvious, that postoperative pain is not always the same and that a procedure-specific approach is needed to assess risks and benefits of analgesic interventions (2). Furthermore, in view of the recent retraction of a large number of clinical trial publications on multimodal analgesia due to fraud (3), there is an urgent need for further trials to assess the benefits of various components of multimodal analgesia in a variety of operations.
◊ References:
1. Tiippana EM, Hamunen K, Kontinen VK, Kalso E.
Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesth Analg 2007 Jun;104(6):1545-56.
2. Kehlet H, Wilkinson RC, Fischer HB, Camu F.
PROSPECT: evidence-based, procedure-specific postoperative pain management. Best Pract Res Clin Anaesthesiol 2007 Mar;21(1):149-59.
3. http://www.aaeditor.org/HWP/Retraction.Notice.pdf
(accessed 23 March 2009)
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