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The Treatment of Postoperative Nausea and Vomiting. C. M. Prada, MD August 4 th 2005. Nausea. by Jean-Paul Sartre. Muscular contractions associated with nausea and vomiting. Chemoreceptor Trigger Center (CTZ).
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The Treatment of Postoperative Nausea and Vomiting C. M. Prada, MD August 4th 2005
Nausea • by Jean-Paul Sartre
Chemoreceptor Trigger Center(CTZ) • “Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004
Anatomy and physiology of the vomiting centre and the chemoreceptor trigger zone World Federation of Societies of AnaesthesiologistsWWW implementation by the NDA Web Team, Oxford Issue 17 (2003) Article 2: Page 1 of 1
5HT-Receptor and PONV Pathophysiology • “Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004
Chemoreceptor Trigger Zone and Emetic Center Antagonist 5-HT3 RAs Droperidol Promethazine Atropine NK-1 RA Agonist Dopamine (D2) 5-HT3 Muscarinic Histamine Substance P Receptor Site • Nitrogen mustard • Cisplatin • Digoxin glycoside • Opioid, analgesics • Vestibular portion • of 8th nerve • N2O • GI tract distension • Higher centers (vision, taste) • Pharynx Chemoreceptor Trigger Zone (CTZ) Area Postrema Mediastinum Parvicellular Reticular Formation Emetic Center ? Vagus Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. Watcha MF, White PF. Anesthesiology. 1992;77:162–184.
Schematic representation of the factors influencing nausea and vomiting
A final pathway for nausea http://www.mywhatever.com/cifwriter/library/70/4938.html
PONV Impact • Incidence of PONV: varies with age, surgical procedure, anesthetic technique • Emesis frequently occurs after D/C from PACU = incidence lower in PACU than over 24 – 48 h • Delayed emesis: timing of oral intake or waning effects of perioperative antiemetics • Vomiting - unpleasant and medical risks: aspiration of gastric content; jeopardizes abdominal or inguinal closures; increased IV pressure: increase morbidity after ocular, tympanic, intracranial procedures; elevate HR and BP: risk for MI and dysrhythmias; gagging and retching: parasympathetic response: bradycardia and hypotension.
Demographic Factors for PONV • Study of 17,638 ambulatory patients: increased risk in younger pts.: PONVdecreasing13% per decade of age. (“Anesthesiology” – 1999;91:109, Sinclair DR, Chung F, Mezei G) • Women: 3 times higher incidence than men • Increased with GA and duration of GA • ENT and dental had higher incidence (14.3%), followed by orthopedic shoulder and plastic • Hx. of preop. emesis or motion sickness • GA near menses (increase E2) • High: procedures of extraocular muscles or middle ear, peritoneal or intestinal irritation, testicular traction • Smokers: lower risk
Contributing Factors • Risk of PONV: increased by starvation, gastricirritation, effects of anesthetics on chemotactic centers, autonomic imbalance, postoperative pain • Swallowed blood or tissue, gas in the stomach • General Anesthesia more than regional, although vomiting frequently when parenteralnarcotics.
Major Risk Factors for PONV in Adults • Patient-specific Risk Factors - Age (adult) - Non-smoking status - History of PONV / motion sickness - Predisposing gastric disorders - Low threshold for nausea - Preoperative anxiety - Obesity (disputed in recent studies) - Gastric distension (disputed in recent studies) • Anesthetic Risk Factors - Pre-anestheticmedications (opioids, atropine) - Volatile anesthetics - Nitrous Oxide - Intraoperative or postoperative use of opioids - Duration of anesthesia (> 120 min) • Surgical Risk Factors - Duration of surgery (each 30 min increases PONV risk by 60%) - Type of surgery (craniotomy; ear, nose, throat procedures; major breast procedures; strabismus surgery; laparoscopy; laparotomy). - Intubation (disputed in recent studies) - Early oral intake Am J Health Syst Pharm 1999;56:729-764
Specific factors increasing risk of nausea and vomiting - PONV • adults have more PONV than children • women • obesity • delayed gastric emptying disorders (GERD, GI obstruction, & neuromuscular disorders) • history of motion sickness (which can cause movement-induced PONV when patient is moved or turned) and/or history of PONV • history of smoking decreases risk • anxious person • emotogenic factors of anaesthetic • etomidate(Amidate),ketamine, and gaseous general anaesthesia, including nitrous oxide have higher risk • atropine decreases risk because it is a vagolytic • propofol (Diprivan) also decreases risk, probably because has slightly anti-serotonergic properties; but, is indicated only as a sedative-hypnotic; it has anti-emetic properties, but is not currently indicated solely for that use • longer procedures with general anaesthesia Garrett, K., Tsuruta, K., Walker, S., Jackson, S., & Sweat, M. (2003) http://www.eddyelmer.com/tools/aemetic.htm
Risk Score for Predicting PONV Apfel CC et al – “A simplified risk score for predicting postoperative nausea and vomiting” – Anesth; 91:693-700, 1999.
Anesthetic Agents • Exclusion of Nitrous Oxide reduces the incidence of PONV • PONV not different among potent inhalation anesthetics: except sevoflurane (marginally higher incidence) • Barbiturate induction less offensive than ketamine or etomidate; propofol induction lowest incidence • Narcotic analgesics: increase PONV • Ketorolac with small doses of narcotics: reduce severity of PONV • Neostigmine, physostigmine: increase the incidence of PONV
PONV Prevention and Treatment • Adequate postop. analgesia • Limit postoperative vestibular stimulation (minimize brisk head movement) • Avoid gastric distension (OG tube?) • Adequate hydration (Anesth Analg 1995;80:682; Yogendran S, Kumar B, Cheng D), but initiation of postop drinking is frequently a triggering event • Sometimes D/C children or high-risk patients before they take oral fluids • Nausea and Vomiting: also signs of serious underlying physiologic abnormalities – evaluate hypotension, increased ICP, hypoxemia, hypoglycemia, gastric bleeding.
Strategies to Reduce Baseline Risk • Use Regional Anesthesia • Use of Propofol for induction and maintenance • Use of intraoperative supplemental oxygen • Hydration • Avoid Nitrous Oxide and Volatile Anesthetics • Minimize intraoperative and postoperative opioids • Minimize the use of Neostigmine Anesth Analg 2004; 99;77-81.
“Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341
Effect of intraoperative intravenous crystalloid infusion on PONV • IV administration of CSL 30 ml/kg to healthy women undergoing day-case gynecological laparoscopy reduced the incidence of vomiting, nausea and anti-emetic use when compared with CSL 10 ml/kg. Br J Anaesth. 2004 Sep;93(3):381-5. Epub 2004 Jun 25
Phenothiazines Chlorpromazine, prochlorperazine, promethazine Butyrophenones Droperidol (haloperidol) Benzamides Metoclopramide Anticholinergics Scopolamine Antihistamines Dimenhydrinate, hydroxyzine, cyclizine 5-HT3 antagonists Dolasetron, granisetron, ondansetron Others Dexamethasone Dronabinol (9THC) Antiemetics—Members by Class • Upcoming class for PONV already approved for CINV • NK1-receptor antagonists Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
“Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004
Main classes of anti-emetic drugs Source: British National Formulary, March 2002
Agonists and Antagonists Associated with Nausea and Vomiting
Clinical Aspects in Selecting Antiemetics for Prevention of PONV
“Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341
Antiemetic treatment for PONV Patients with No Prophylaxis or Failed Prophylaxis Agent from a different class. When PONV occurs <6h after surgery: use agent from different class or Propofol 20 mg in PACU (adults). When PONV occurs >6h after surgery: repeat 5-HT3-receptor antagonist and droperidol (except dexamethasone or scopolamine) Use agents from a different class. Anesth Analg 2003;97:62-71
Standard Dosages of Antiemetics for the Prophylaxis of PONV in Adults Am J Health Syst Pharm 1999;56:729-764
Standard Dosages of Antiemetics for the Treatment of PONV in AdultsAm J Health Syst Pharm 1999;56:729-764
Standard Dosages of Antiemetics for the Management of POV in Pediatric Patients Am J Health Syst Pharm 1999;56:729-764
Phenothiazines • Chlorpromazine, Prochlorperazine, Promethazine • Antipsychotic agents • Blocks D2 receptors in CTZ and CNS • SIDE EFFECTS: EPS, sedation, dizziness, blurred vision, skin reactions, orthostatic hypotension chlorpromazine Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. • Prochlorperazine-heterocyclic side chain
Butyrophenones • Droperidol • α blocker, D2 receptor antagonist (binds to D2 receptor) • Acts at both CTZ and area postrema • 1.25 mg droperidol given at the beginning of surgery is as effective as 4 mg dexamethasone or 4 mg ondansetron ( Apfel et al. New Engl J Med 2004 ). • SIDE EFFECTS: EPS, sedation, QTc prolongation with torsade de pointes (there is little evidence that antiemetic doses trigger this condition - Gan et al. Anesthesiology 2002). - high doses: hypotension (a blockade) - low-dose droperidol may cause dysphoria (Melnick et al. Anesth Analg 1989, Lim et al. Anaesth Intensive Care 1999) EPS = extrapyramidal symptoms Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
Benzamide • Metoclopramide • Specific dopamine D2 antagonist • LES tone which enhances gastric motility • Short (1 to 2 hours) duration of action. • SIDE EFFECTS: EPS, restlessness, drowsiness, fatigue, agranulocytosis, methemoglobinemia, hypotension and bradycardia (or tachycardia) • Cisapride (removed from use – cardiac side effects) EPS = extrapyramidal symptoms Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
Anticholinergics • Scopolamine • Inhibit cholinergic and muscarinic CNS receptors. • Crosses the blood-brain barrier. • More effective against motion-induced emesis than against motion-induced nausea. • SIDE EFFECTS: sedation, CNS excitation, dry mouth, urinary retention, blurred vision, confusion, disorientation, hallucinations Night Shade = Atropa belladonna Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
Antihistamines • Dimenhydrinate, Hydroxyzine, Cyclizine • Block acetylcholine in the vestibular apparatus and histamine H1 receptors in the nucleus of the solitary tract. • SIDE EFFECTS: blurred vision, urinary retention, dry mouth, and sedation Cyclizine has similar efficacy to ondansetron; side effects: sedation and dry mouth (anticholinergic). Br J Anaesth 2000; 85(5):678-682/ Ahmed AB, Hobbs GJ, Curran JP: “Randomized, placebo-controlled trial of combination antiemetic prophylaxis for day-case gynaecological laparoscopic surgery”. Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
5-HT3 Antagonists • (Ondansetron (Zofran®), Granisetron (Kytril®), Tropisetron (Navoban®), and Dolasetron (Anzemet®) • - No difference in efficacy • No sedation, extrapyramidal reactions, adverse effects on vital signs or laboratory tests, or drug interactions with other anesthetic medications. • Because repeating ondansetron is of limited effectiveness (Kovac et al. J Clin Anesth 1999) - reasonable to use ondansetron predominantly as a rescue treatment ( White PF, New Engl J Med 2004) • SIDE EFFECTS: Headache, dizziness, flushing, elevated liver enzymes,constipation Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341
“Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341
Dexamethasone Synthetic steroid Hypotheses • inhibition of prostaglandin syn. • tryptophan • release of endorphins • change in CSF opening pressure • + psychological effects of steroids ACUTE SIDE EFFECTS: flushing and perineal itching. - Wang et al. Anesth Analg 2000 and the IMPACT data (unpublished observation) - dexamethasone has a delayed onset of antiemetic actions which might need a few hours to work. Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.
Dexamethasone (contin.) “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341
“Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341