Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia.
Information source: University Hospital, Lille
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Interaction Between Antiemetic Drugs and Paracetamol
Intervention: ondansetron (Drug); Droperidol (Drug); Dexamethasone (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: University Hospital, Lille
Summary
The purpose of our study is to determine if there is an antagonism between drugs used in the
prevention of postoperative nausea and vomiting (PONV) on the analgesia led by acetaminophen
after thyroidectomy.
Clinical Details
Official title: Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: "electric nociception threshold" measured by PainMatcher
Secondary outcome: numeric rating scale scoreneed in rescue analgesia with nefopam in case of numeric rating scale score > 4 presence of postoperative nausea and vomiting
Detailed description:
It was shown that there was an antagonism of the ondansetron on the analgesia led by
acetaminophen in a model of nociception by electrical stimulation using the PainMatcher in
healthy volunteers. Our study try to determinate if a such antagonism exist in clinical
conditions : 66 patients with an Apfel-score II undergoing thyroidectomy were randomized in
3 equal groups. Each group received an antiemetic (ondansetron, droperidol or dexamethasone)
at the begining of the intervention and paracetamol at the end of the intervention for the
postoperative analgesia. During 2 hours in the postoperative unit, we raised : the
electrical pain's threshold with the PainMatcher, the numeric pain intensity scale and the
presence of nausea or vomiting. For each patients we determined the cytochrome P450 2D6
activity that should have been able to explain a diminution of ondansetron's efficiency.
Paracetamol blood levels were also raised in the postoperative unit.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- patients undergoing thyroidectomy without lymph node dissection
- American Society of Anesthesiologists physical status from I to III
- Apfel-score equal to 2
- informed consent signed
Exclusion Criteria:
- pregnant and breast-feeding women
- addictive disorders
- psychic diseases
- allergy or contra-indication to a drug used in the study
- presence of postoperative nausea or vomiting
- administration of glucocorticoid for protecting recurent laryngeal nerve.
- protocol not respected
- protocol refused by the patient
- intellectual handicap
Locations and Contacts
Hospital and university center, Lille 59000, France
Additional Information
Related publications: Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006 Apr;79(4):371-8. Girard P, Pansart Y, Coppé MC, Niedergang B, Gillardin JM. Modulation of paracetamol and nefopam antinociception by serotonin 5-HT(3) receptor antagonists in mice. Pharmacology. 2009;83(4):243-6. doi: 10.1159/000207448. Epub 2009 Mar 9. Courade JP, Chassaing C, Bardin L, Alloui A, Eschalier A. 5-HT receptor subtypes involved in the spinal antinociceptive effect of acetaminophen in rats. Eur J Pharmacol. 2001 Nov 30;432(1):1-7. Pickering G, Estève V, Loriot MA, Eschalier A, Dubray C. Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther. 2008 Jul;84(1):47-51. Epub 2007 Oct 24. Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 Jun 10;350(24):2441-51. Apfel CC, Bacher A, Biedler A, Danner K, Danzeisen O, Eberhart LH, Forst H, Fritz G, Hergert M, Frings G, Goebel A, Hopf HB, Kerger H, Kranke P, Lange M, Mertzlufft F, Motsch J, Paura A, Roewer N, Schneider E, Stoecklein K, Wermelt J, Zernak C. [A factorial trial of six interventions for the prevention of postoperative nausea and vomiting]. Anaesthesist. 2005 Mar;54(3):201-9. German. Kaiser R, Sezer O, Papies A, Bauer S, Schelenz C, Tremblay PB, Possinger K, Roots I, Brockmöller J. Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol. 2002 Jun 15;20(12):2805-11. Nielsen M, Olsen NV. Genetic polymorphisms in the cytochrome P450 system and efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Br J Anaesth. 2008 Oct;101(4):441-5. doi: 10.1093/bja/aen246. Candiotti KA, Birnbach DJ, Lubarsky DA, Nhuch F, Kamat A, Koch WH, Nikoloff M, Wu L, Andrews D. The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis? Anesthesiology. 2005 Mar;102(3):543-9. Pelissier T, Alloui A, Paeile C, Eschalier A. Evidence of a central antinociceptive effect of paracetamol involving spinal 5HT3 receptors. Neuroreport. 1995 Jul 31;6(11):1546-8. Pelissier T, Alloui A, Caussade F, Dubray C, Cloarec A, Lavarenne J, Eschalier A. Paracetamol exerts a spinal antinociceptive effect involving an indirect interaction with 5-hydroxytryptamine3 receptors: in vivo and in vitro evidence. J Pharmacol Exp Ther. 1996 Jul;278(1):8-14. Alloui A, Chassaing C, Schmidt J, Ardid D, Dubray C, Cloarec A, Eschalier A. Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats. Eur J Pharmacol. 2002 May 17;443(1-3):71-7. Lund I, Lundeberg T, Kowalski J, Sandberg L, Budh CN, Svensson E. Evaluation of variations in sensory and pain threshold assessments by electrocutaneous stimulation. Physiother Theory Pract. 2005 Apr-Jun;21(2):81-92. Nielsen PR, Nørgaard L, Rasmussen LS, Kehlet H. Prediction of post-operative pain by an electrical pain stimulus. Acta Anaesthesiol Scand. 2007 May;51(5):582-6. Fujii Y, Nakayama M. Efficacy of dexamethasone for reducing postoperative nausea and vomiting and analgesic requirements after thyroidectomy. Otolaryngol Head Neck Surg. 2007 Feb;136(2):274-7. Samer CF, Piguet V, Dayer P, Desmeules JA. [Genetic polymorphism and drug interactions: their importance in the treatment of pain]. Can J Anaesth. 2005 Oct;52(8):806-21. Review. French. Lo Y, Chia YY, Liu K, Ko NH. Morphine sparing with droperidol in patient-controlled analgesia. J Clin Anesth. 2005 Jun;17(4):271-5. McCleane GJ, Suzuki R, Dickenson AH. Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled cross-over study. Anesth Analg. 2003 Nov;97(5):1474-8. Andrieu G, Amrouni H, Robin E, Carnaille B, Wattier JM, Pattou F, Vallet B, Lebuffe G. Analgesic efficacy of bilateral superficial cervical plexus block administered before thyroid surgery under general anaesthesia. Br J Anaesth. 2007 Oct;99(4):561-6. Epub 2007 Aug 6.
Starting date: June 2009
Last updated: August 31, 2012
|