Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia. - Full Text View

Purpose

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.

Condition	Intervention	Phase
Interaction Between Antiemetic Drugs and Paracetamol	Drug: ondansetron Drug: Droperidol Drug: Dexamethasone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia.

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Dexamethasone Acetaminophen Droperidol Dexamethasone acetate Dexamethasone sodium phosphate Ondansetron hydrochloride Ondansetron

U.S. FDA Resources

Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:

"electric nociception threshold" measured by PainMatcher [ Time Frame: during 2 hours after thyroidectomy in the postoperative care unit ] [ Designated as safety issue: Yes ]
The PainMatcher is a pain self-assessment device using the electric stimulation of the median nerve. The patient maintains a pressure on an electrode box between the thumb and the index finger, creating a current of increasing intensity. The threshold of pain sensation is obtained when the patient releases his fingers from the electrode box. So whe raise the electric nociceptive threshold showned by the PainMatcher. We realize two measures and consider the second one.

objective measure.

Secondary Outcome Measures:

numeric rating scale score [ Time Frame: during 2 hours after thyroidectomy in the postoperative care unit ] [ Designated as safety issue: Yes ]
to evaluate the sensation of pain with a 11 levels going from 0 ( no pain) to 10 ( worst pain imaginable).

subjective measure.
need in rescue analgesia with nefopam in case of numeric rating scale score > 4 [ Time Frame: during 2 hours after thyroidectomy in the postoperative care unit ] [ Designated as safety issue: Yes ]
presence of postoperative nausea and vomiting [ Time Frame: during the 2 hours after thyroidectomy in the postoperative care unit ] [ Designated as safety issue: Yes ]

Enrollment:	66
Study Start Date:	June 2009
Study Completion Date:	June 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: ONDANSETRON (OS) patients receiving ondansetron at the begining of the surgery to prevent postoperative nausea and vomiting (PONV); and paracetamol at the end of the surgery for postoperative analgesia.	Drug: ondansetron ondansetron: 4 mg intraveinous administration afer the induction of anesthesia.
Active Comparator: DROPERIDOL (DRO) patients receiving droperidol at the begining of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia.	Drug: Droperidol droperidol: 1.25 mg intraveinous administration after the induction of anesthesia.
Active Comparator: DEXAMETHASONE (DEXA) patients receiving dexamethasone at the begining of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia.	Drug: Dexamethasone dexametasone: 4 mg intraveinous administration after the induction of anesthesia.

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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679093

Locations

France
Hospital and university center
Lille, France, 59000

Sponsors and Collaborators

University Hospital, Lille

More Information

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. 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.

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, Norgaard 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.

Responsible Party:	University Hospital, Lille
ClinicalTrials.gov Identifier:	NCT01679093 History of Changes
Other Study ID Numbers:	2008-002701-40
Study First Received:	August 31, 2012
Last Updated:	August 31, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:

postoperative analgesia
paracetamol
5-HT3 antagonist
ondansetron
PainMatcher

Additional relevant MeSH terms:

Acetaminophen
Dexamethasone
Droperidol
Ondansetron
Antiemetics
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

Central Nervous System Agents
Therapeutic Uses
Autonomic Agents
Gastrointestinal Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Antipsychotic Agents

ClinicalTrials.gov processed this record on May 19, 2013

Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia. (ANPATHY)