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Unformatted text preview: The Treatment of Postoperative Nausea and Vomiting C. M. Prada, MD August 4th 2005 1 Nausea • by Jean­Paul Sartre 2 3 Muscular contractions associated with nausea and vomiting 4 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 Maze, 5 Anatomy and physiology of the vomiting centre and Anatomy and physiology of the vomiting centre and the chemoreceptor trigger zone World Federation of Societies of Anaesthesiologists WWW implementation by the NDA Web Team, Oxford Issue 17 (2003) Article 2: Page 1 of 1 6 5HT­Receptor 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 Pharmacology, 7 Chemoreceptor Trigger Zone and Emetic Center Antagonist 5-HT3 RAs Promethazine 5-HT3 Histamine Droperidol Atropine NK-1 RA Agonist Muscarinic Dopamine (D2) Substance P A r ea Postrema Receptor Site Parvicellular Reticular Formation Nitrogen mustard Cisplatin Digoxin glycoside Chemoreceptor Trigger Zone (CTZ) Opioid, analgesics Vestibular portion of 8th nerve Mediastinum Emetic Center N2O ? Vag us Watcha MF, White PF. Anesthesiology. 1992;77:162–184. GI tract distension Higher centers (vision, taste) Pharynx Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. 8 Schematic representation of the factors influencing nausea and vomiting 9 www.marinol.com/images/graphic-cancer.gif 10 11 A final pathway for nausea http://www.mywhatever.com/cifwriter/library/70/4938.html 12 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. 13 Demographic Factors for PONV • Study of 17,638 ambulatory patients: increased risk in younger pts.: PONV decreasing 13% 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 14 Contributing Factors • Risk of PONV: increased by starvation, gastric irritation, 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 parenteral narcotics. 15 Major causes of nausea and vomiting Drug/treatment - induced Cancer chemotherapy Opiates Nicotine Antibiotics Radiotherapy Labyrinth disorders Motion Meniere's disease Endocrine causes Pregnancy Infectious causes Gastroenteritis Viral labyrinthitis Increased intracranial pressure Haemorrhage Meningitis Post-operative Anaesthetics Analgesics Procedural CNS causes Anticipatory Migraine Bulimia nervosa 16 Major Risk Factors for PONV in Adults • • • Patient­specific Risk Factors ­ Age (adult) ­ Non­smoking 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 ­ Pre­anesthetic medications (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 17 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 movement­induced 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 sedative­hypnotic; 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 18 Risk Score for Predicting PONV RISK FACTORS: 1 -Female sex 2 - Hx. of motion sickness or PONV 3 - Nonsmoking status 4 - Use of Postoperative Opioids NONE 1 Factor 2 Factors 3 Factors 4 Factors 10 % 21 % 39 % 61 % 79 % Apfel CC et al – “A simplified risk score for predicting postoperative nausea and vomiting” – Anesth; 91:693-700, 1999. 19 20 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 21 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 high­risk patients before they take oral fluids • Nausea and Vomiting: also signs of serious underlying physiologic abnormalities – evaluate hypotension, increased ICP, hypoxemia, hypoglycemia, gastric bleeding. 22 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. 23 “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341 24 Effect of intraoperative intravenous crystalloid infusion on PONV • IV administration of CSL 30 ml/kg to healthy women undergoing day­case gynecological laparoscopy reduced the incidence of vomiting, nausea and anti­emetic use when compared with CSL 10 ml/kg. Br J Anaesth. 2004 Sep;93(3):381-5. Epub 2004 Jun 25 25 Antiemetics—Members by Class Phenothiazines – Chlorpromazine, prochlorperazine, promethazine Butyrophenones – Droperidol (haloperidol) Benzamides – Metoclopramide Anticholinergics – Scopolamine Antihistamines – Dimenhydrinate, hydroxyzine, cyclizine 5­HT3 antagonists – Dolasetron, granisetron, ondansetron Others – Dexamethasone – Dronabinol (9THC) Upcoming class for PONV already approved for CINV NK1-receptor antagonists Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. 26 •“Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004 Pharmacology, 27 Main classes of anti­emetic drugs Class Drug Anti-cholinergic scopolamine (L-hyoscine) Anti-histamine cinnarizine cyclizine promethazine (?) Dopamine antagonists metoclopramide domperidone droperidol (withdrawn 2001) haloperidol Cannabinoid nabilone Corticosteroid dexamethasone Histamine analogue betahistine 5HT3-receptor antagonist granisetron ondansetron tropisetron Source: British National Formulary, March 2002 28 29 Agonists and Antagonists Associated with Nausea and Vomiting 30 Clinical Aspects in Selecting Antiemetics for Prevention of PONV 31 32 “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341 33 Antiemetic treatment for PONV Patients with No Prophylaxis or Failed Prophylaxis If Initial Tx. Was: No prophylaxis or dexamethasone. 5­HT3­receptor antagonist plus 2nd agent (droperidol 0.625 mg IV, dexamethasone 2 – 4 mg IV, promethazine 12.5 mg IV). Triple therapy with 5­HT3­receptor antagonist plus 2 other agents. Then Treat With: Low­dose 5­HT3­receptor antagonist (Ondansetron 1 mg, Dolasetron 12.5 mg, Granisetron 0.1 mg, Tropisetron 0.5 mg). 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 5-HT droperidol (except dexamethasone or scopolamine) Use agents from a different class. Anesth Analg 2003;97:62-71 34 Standard Dosages of Antiemetics for the Prophylaxis of PONV in Adults Am J Health Syst Pharm 1999;56:729­764 Droperidol Agent Ondansetron Dosage 0.625 – 1.25 mg Iv 5 min before termination of 0.625 anesthesia anesthesia 4 mg IV immediately before induction 8 mg PO 1 h before induction Recent data: more effective- end of anesthesia Dolasetron 12.5 mg IV intraoperatively 100 mg PO 1 h before induction Metoclopramide 10 (20) mg IV near the end (not effective when 10 used alone) used Promethazine 25 mg PO 1 h before induction 12.5 – 25 mg IV immediately before ind. Prochlorperazine 5 – 15 mg PO 1 h before induction 5 – 10 mg IM 1 – 2 h before ind.; repeat once in 10 30 min, prn 30 5 – 10 mg IV 15 – 30 min before ind; x1 Granisetron 20 – 40 mcg/kg IV 35 Standard Dosages of Antiemetics for the Treatment of PONV in Adults Am J Health Syst Pharm 1999;56:729­764 Ondansetron Agent Dosage 1 – 4 mg IV postoperatively Metoclopramide 10 mg IV q 4–6 h prn post-operatively Promethazine 10 – 25 mg PO prn post-operatively 12.5 – 25 mg IM or IV q4h prn post-operatively Prochlorperazine 5 – 15 mg PO post-op. 5 – 10 mg IM; repeat once in 30 min prn 5 – 10 mg IV; may repeat once prn Chlorpromazine 10 – 25 mg PO q4-6h prn 12.5 – 25 mg IM if no hypotension; repeat in 1h Droperidol 0.625 – 1.25 mg IV prn Dolasetron 12.5 mg IV post-operatively 36 Standard Dosages of Antiemetics for the Management of POV in Pediatric Patients Agent Prophylaxis Dosage Dolasetron Age >2y: 1.8 mg/kg IV immediately before ind. Ondansetron 0.05 mg/kg IV (range: 0.05 – 0.15 mg/kg) Droperidol 0.015 – 0.075 mg/kg per dose IV Treatment Chlorpromazine 0.55 mg/kg PO or IM Droperidol 0.1 mg/kg per dose IV Ondansetron 0.05 mg/kg per dose IV Am J Health Syst Pharm 1999;56:729-764 37 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 Prochlorperazine-heterocyclic side chain Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. 38 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 (α blockade) ­ low­dose 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. 39 Anesthesiology, Vol.102, Number 6, June 2005 40 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) Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. 41 • Scopolamine Anticholinergics – Inhibit cholinergic and muscarinic CNS receptors. – Crosses the blood­brain barrier. – More effective against motion­induced emesis than against motion­induced nausea. – SIDE EFFECTS: sedation, CNS excitation, dry mouth, urinary retention, blurred vision, confusion, disorientation, hallucinations Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. Night Shade = Atropa belladonna 42 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):678­682/ Ahmed AB, Hobbs GJ, Curran JP: “Randomized, placebo­controlled trial of combination antiemetic prophylaxis for day­case gynaecological laparoscopic surgery”. Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. 43 5­HT3 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 44 Ondansetron Pharmacokinetics 45 www.anzemet.com/images/chart_c_pharmacology.jpg 46 “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341 47 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. 48 Dexamethasone (contin.) “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341 49 “Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341 50 NK1 Antagonists • Future development in anti­emesis is looking at the neurokinin 1 (NK­1) receptor, where substance P is the natural ligand. This receptor is found in the nucleus tractus solitarius and the area postrema, as well as the peripheral nervous system. Early studies of NK­1 antagonists have been promising, especially in combination with ondansetron. (World Federation of Societies of Anaesthesiologists WWW implementation by the NDA Web Team, Oxford ; Issue 17 (2003) Article 2: Page 1 ) • Neurokinine (substance P, NK1) antagonists ­ impressive antiemetic in the animal model. However, early clinical data have been disappointing, except for aprepitant (Emend®) ­ has demonstrated superiority over ondansetron in chemotherapy induced nausea and vomiting. http:// www.ponv.org/Knowledge.htm 51 DRONABINOL Marinol® – 9THC – Unknown mechanism involves inhibition of CTZ – SIDE EFFECTS: dizziness, drowsiness, nausea (not emesis) – Schedule II drug Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D. www.marinol.com/images/chart-clinical1.gif References: 1. Beal JE, et al. J Pain Symptom Manage. 1995;10(2):89-97. 2. Beal JE, et al. J Pain Symptom Manage. 1997;14(1):7-14. 52 Nonpharmacological Methods (TENS) for Prevention of PONV C K. Sim http://www.iars.org/abstracts/abstracts/S160/s180.htm 53 Accupressure Wristbands for PONV Accupressure Wristbands do not Prevent PONV after Urological Endoscopic Surgery – A. Agarwal et al. – Can J Anesth 2000/ 47:4/ p319324 54 Ginger root • Ginger root (Zingiber officinale Roscoe., Zingiberaceae) • "In summary, we found that ginger is a promising antiemetic herbal remedy, but the clinical data to date are insufficient to draw firm conclusions.“ Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (Ginger) - an antiemetic for day case surgery. Anaesthesia 1993; 48: 715-717 Postoperative nausea (Bone et al., 1990; Phillips et al., 1993; Arfeen et al., 1995) 55 • Aromatherapy With Peppermint , Isopropyl Alcohol or Placebo is Equally Effective in Relieving Postoperative Nausea Lynn AA, Jeffrey GB (2004) www.safehomeproducts.com/SHP/HH/ReliefBand.asp 56 Vestis K is a vestibular stimulator specially designed for clinical use, integrating current display and separate current monitoring with alarm functions for both electrodes. INDICATIONS Hyperemesis gravidarum postoperative Nausea Nausea after Chemo- and Radiotherapy Travel Sickness im.edirectory.co.uk/products/1816/i/6601042.jpg www.biegler.com/vestis.en.html 57 Noni CAPSULE Item Code : c017 Morinda citrifolia Linn. Morinda CAPSULE Each : 500 mg. Indication : for symptomatic relief of nausea and vomiting Dosage : 1-2 capsules each time , 3 times a day , before meal Packing : 50 Vcaps.Contained in Plant product qualified capsules. Passed national GMP evaluation. PRICE US$ 9.60 (excl. shipping) 58 HANUMAN PRASANKAI TEA Item Code : h011 Schefflera leucantha Vig. Herbal Tea for Health Each : Hanuman prasankai 100 % Indication : Relieves cough and nausea, Used as bronchodilator Content : 20 sachets. Net. weight 20 g. Price : US$ 2.90 (excl. shipping 59 Enterra Therapy Gastric Electrical Stimulation (GES) The implantable stimulation system for Enterra Therapy is shown in Figure 1 and is comprised of the following: Medtronic ITREL 3 Model 7425G Neurostimulator The ITREL 3 is a battery powered implantable device that is commercially available in the U.S. Medtronic Model 4351 Lead The new 4351 Intramuscular Lead is a unipolar lead intended for use with an implantable neurostimulator. The 4351 lead has a ski needle design for easier use with laparoscopic procedures. It is also designed with a fixed electrode length of 1 cm. The 4351 lead connects directly to the neurostimulator and is available in 35 cm length. Two leads are used in each patient. www.medtronic.com/.../images/chart_study.gif 60 The main sites of action of drugs affecting nausea and vomiting 61 Summary table Relating Type of Nausea, Receptor, Drug Class, and Example of Drug of Choice Type of Nausea Receptors Causing Nausea Drug Class Useful Examples of DOC Vestibular Cholinergic, histaminic Anticholinergic, antihistaminic Scopolamine patch, promethazine Obstruction of bowel caused by constipation Cholinergic, histaminic, ? 5HT3 Stimulate myenteric plexus Senna products DysMotility of upper gut Cholinergic, histaminic, ? 5HT3 Prokinetics stimulate 5HT4...
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