advances in pharmacology applied to maxillofacial anaesthesia

1. Advances in pharmacology applied to maxillofacial anaesthesia

Postoperative nausea and vomiting (PONV) and Anti-emetics

Pain and Analgesics

Future developments

Incidence approximately 25%, (5-75%)

Medical impact minor

Patients impactHUGE

Requires treatment

Patient characteristics

Female>male (x3). Incidence increases during menstruation and decreases after the menopause.after 70 years of age,both sexes are equally affected. Obese (has been suggested, although there is currently insufficient evidence to conclude an association). Young. Risk of PONV is almost twice that for adults. Equal distribution between boys and girls until puberty. Previous history of PONV/motion sickness Early ambulation, early postoperative eating and drinking.

SurgeryIntra-abdominal-laparoscopic Intracranial, middle ear Squint surgery (highest incidence of PONV in children) Gynaecological, especially ovarian Head and neck, especially tonsillectomy and adenoidectomy (suggested due to blood in upper gastrointestinal tract (GIT),stimulation of trigeminal nerve afferents and peroperative opioids). Prolonged surgery Painful

Anaesthesia/drugs Opioids (NB untreated pain is also emetogenic) Sympathomimetics Inhalational agents (Isoflurane++) Etomidate, ketamine, methohexitone (compared with propofol and thiopentone) Neostigmine (recent work suggests that this is not associated with PONV) Nitrous oxide (GIT distension/expansion of middle ear cavities). Prolonged anaesthesia Spinal anaesthesia (blocks above T5), hypotension. Intraoperative dehydration Inexperienced bag and mask ventilation (gastric dilatation).

Intercurrent Disease Intestinal obstruction Metabolic, e.g. hypoglycaemia, uraemia Hypoxia

Tramr MR . A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues. Acta Anaesthesiol Scand. 2001 Jan;45(1):4-13.

Tramr MR . A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda. Acta Anaesthesiol Scand. 2001 Jan;45(1):14-9 .

Tramr MR.(Editorial) Rational control of PONV the rule of three/Le contrle rationnel des NVPO la rgle de trios. Canadian Journal of Anesthesia. 2004 51:283-285

1. Reduce the baseline risk by such measures as reducing nitrous oxide use, avoiding neostigmine, using localanaestheticswherever possible instead of opiates and using propofol for induction and maintenance of anaesthesia.

2. Do not use routine preventative treatment as it does not work well, is less cost effective and unnecessarily exposes patients to the drugs.

3. Identify the high risk patients and then use aneffectivedrug combination.

Apfel CC, Lr E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers.Anesthesiology.1990; 91:693-700.

Koivuranta M, Lr E, Snare L, Alahunta S. A survey of postoperative nausea and vomiting.

Anesthesia.1997; 52:443-449.

Major Proven Risk factors

Female gender

P/H of PONV or motion sickness

Non smokers

Opiates

Surgery duration >60 mins

Cumulative risk %ApfelKoivuranta

Background risk 10 17

Plus1 risk factor21 18

2 39 42

3 61 54

4 79 74

Major Proven Risk factors

Female gender

P/H of PONV or motion sickness

Non smokers

Opiates

Surgery duration >60 mins

For an effective drug combination:

It has been shown that both dexamethasone and droperidol increase the efficacy of setrons and it is more effective to give a cocktail of prophylaxis.

For example: steroid (dexamethasone 8mg) at induction and a 5-HT3 antagonist, good for treating vomiting, (ondansetron 4mg) with a D2 antagonist, good for treating nausea, (droperidol 0.75mg) at the end of the procedure .

There isnoevidence for an effect greater than placebo for metoclopramide.

Conclusion 1

MORE IS BETTER !

Prospective randomized, double-blind comparative study of dexamethasone, ondansetron, and ondansetron plus dexamethasone as prophylactic antiemetic therapy in patients undergoing day-case gynaecological surgery. Thomas R, Jones N. Br JAnaesth2001; 87(4): 588-92 .

Prevention of vomiting after strabismus surgery in children: dexamethasone alone versus dexamethasone plus low-dose ondansetron. Splinter WM. Paediatr Anaesth2001; 11(5): 591-5 .

Conclusion 2

The best setron is the cheapest setron.

(Remember oral formulations are available)

Williams DG ,Patel A ,Howard RF .

Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002 Dec;89(6):839-45.

Codeine analgesia is wholly or mostly due to its metabolism to morphine by the cytochrome P450 enzyme CYP2D6

Forty-seven per cent of children had genotypes associated with reduced enzyme activity.

Morphine and its metabolites were not detected in 36% of children given codeine

Intra-venous paracetamol

PERFALGAN Bristol-Meyers Squibb

1gm infusion equivalent to 10mg Morphine IMI

Tramadol

Karen Kaye ,

Executive Officer, NSW Therapeutic Advisory Group (formerly NSW Therapeutic Assessment Group), Sydney

Trouble with tramadol

Key words: analgesia, drug interactions, serotonin.

Aust Prescr 2004;27:267

As of March 2004 the Australian Adverse Drug Reactions Advisory Committee (ADRAC) has received 726 reports of adverse events associated with tramadol, detailing 1922 reactions

Nausea, vomiting, dizziness, confusion and seizures.The potential for serious drug-drug interactions should not be underestimated.

Like codeine, tramadol is metabolised via the CYP2D6 isoenzyme of cytochrome P450to an active metabolite which binds to receptors

For most patients, a combination of paracetamol and codeine will be equally effective and possibly better tolerated than tramadol

COX 2 Inhibitors

COX2 inhibitors

can also increase blood pressure, induce or worsen cardiac failure and impair kidney function to the point of renal failure

but, no significant effect on platelets or bleeding time, no opioid side effects and highly rated by the patients

PARECOXIB,DYNASTSAT Pharmacia

in combination with morphine provides significant opioid-sparing effects

improved pain management and patient satisfaction, in two major surgical pain models, compared with morphine alone.

T. Philip Malan, Jr, MD, PhD, Stephen Gordon, MD , Richard Hubbard, MD , and Michael Snabes, MD

The Cyclooxygenase-2-Specific Inhibitor Parecoxib Sodium Is as Effective as 12 mg of Morphine Administered Intramuscularly for Treating Pain After Gynecologic Laparotomy Surgery

Anesth Analg 2005;100:454-460

Chemical structure of remifentanil

C.-S. Degoute, M.-J. Ray, M. Manchon, C. Dubreuil, and V. Banssillon

Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty Can J Anesth, January1,2001; 48(1): 20 - 27.

Caverni, Valentina PhD; Rosa, Giovanni; Pinto, Giovanni; Tordiglione, Paolo PhD; Favaro, Roberto

Hypotensive Anesthesia and Recovery of Cognitive Function in Long-term Craniofacial Surgery.

Journal of Craniofacial Surgery. 16(4):531-536, July 2005 .

Org 25969

Fentanyl PCTS

Iontophoretic patient controlled transdermal system

Analgesics, anxiolytics, antiemetics

(Competing Interests: Shareholder)

New antiemetics

AntineurokininsAntiNK1

CannabinoidsNabilone

a safe substitute for propofol,with many propofol like properties, is expected to be approved by the FDA fornon-anesthesiologists use in the next year or two.

Fechner, Jorg M.D. ; Ihmsen, Harald Ph.D. ; Hatterscheid, Dirk M.D. ; Jeleazcov, Christian M.D. ; Schiessl, Christine M.D. ; Vornov, James J. M.D., Ph.D. ; Schwilden, Helmut M.D., Ph.D.; Schuttler, Jurgen M.D.

Comparative Pharmacokinetics and Pharmacodynamics of the New Propofol Prodrug GPI 15715 and Propofol Emulsion.

Anesthesiology. 101(3):626-639, September 2004.

THE END

advances in pharmacology applied to maxillofacial anaesthesia

Education

risk of ponv

vomiting ponv

ponv incidence

ponv conclusion

ponv cumulative risk

ponv tramr mr

ponv apfel cc

baseline risk