Advances in pharmacology applied to maxillofacial anaesthesia

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Advances in pharmacology applied to maxillofacial
anaesthesia

• Dr Patrick Hughes
• Victorian Anaesthetic Group
• Melbourne
• OMAX 2005

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• Postoperative nausea and vomiting (PONV) and
  Anti-emetics
• Pain and Analgesics
• Future developments

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PONV

• Incidence approximately 25, (5-75)
• Medical impact minor
• Patients impact HUGE
• Requires treatment

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PONV

• Patient characteristics
• Femalegtmale (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.
• Surgery Intra-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

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PONV
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PONV

• Tramèr 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
  Jan45(1)4-13.
• Tramèr 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
  Jan45(1)14-9.
• Tramèr MR. (Editorial) Rational control of PONV
  the rule of three/Le contrôle rationnel des NVPO
  la règle de trios. Canadian Journal of
  Anesthesia. 2004 51283-285

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PONV

• 1. Reduce the baseline risk by such measures as
  reducing nitrous oxide use, avoiding neostigmine,
  using local anaesthetics wherever 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
  an effective drug combination.

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PONV

• Apfel CC, Läärä 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 91693-700.
• Koivuranta M, Läärä E, Snare L, Alahunta S. A
  survey of postoperative nausea and vomiting.
• Anesthesia. 1997 52443-449.

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PONV

• Major Proven Risk factors
• Female gender
• P/H of PONV or motion sickness
• Non smokers
• Opiates
• Surgery duration gt60 mins

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PONV

• Cumulative risk Apfel Koivuranta
• Background risk 10 17
• Plus 1 risk factor 21 18
• 2 39 42
• 3 61 54
• 4 79 74
• 5 87

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PONV

• Major Proven Risk factors
• Female gender
• P/H of PONV or motion sickness
• Non smokers
• Opiates
• Surgery duration gt60 mins

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PONV

• 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 is no evidence for an effect greater than
  placebo for metoclopramide.

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PONV

• 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 J Anaesth 2001
  87(4) 588-92.
• Prevention of vomiting after strabismus surgery
  in children dexamethasone alone versus
  dexamethasone plus low-dose ondansetron.Splinter
  WM.Paediatr Anaesth 2001 11(5) 591-5.

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PONV

• Conclusion 2
• The best setron is the cheapest setron.
• (Remember oral formulations are available)

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ANALGESICS

• 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
  Dec89(6)839-45.

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ANALGESICS

• 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

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ANALGESICS

• Intra-venous paracetamol
• PERFALGAN Bristol-Meyers Squibb
• 1gm infusion equivalent to 10mg Morphine IMI

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ANALGESICS

• 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 200427267

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ANALGESICS

• 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 P450 to an active
  metabolite which binds to µ receptors
• For most patients, a combination of paracetamol
  and codeine will be equally effective and
  possibly better tolerated than tramadol

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ANALGESICS

• COX 2 Inhibitors

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ANALGESICS

• 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

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ANALGESICS

• 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 2005100454-460

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ANALGESICS

• Chemical structure of remifentanil

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ANALGESICS

• C.-S. Degoute, M.-J. Ray, M. Manchon, C.
  Dubreuil, and V. Banssillon
• Remifentanil and controlled hypotension
  comparison with nitroprusside or esmolol during
  tympanoplastyCan J Anesth, January 1, 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.

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THE FUTURE

• Org 25969

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THE FUTURE

• Fentanyl PCTS
• Iontophoretic patient controlled transdermal
  system

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THE FUTURE

• ACRUX
• Analgesics, anxiolytics, antiemetics
• (Competing Interests Shareholder)

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THE FUTURE

• New antiemetics
• Antineurokinins AntiNK1
• Cannabinoids Nabilone

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The Future

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

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THE FUTURE

• 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.

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• THE END