1 the treatment of postoperative nausea and vomiting c. m. prada, md august 4 th 2005

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The Treatment of The Treatment of Postoperative Nausea Postoperative Nausea

and Vomitingand Vomiting

C. M. Prada, MDC. M. Prada, MDAugust 4August 4thth 2005 2005

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NauseaNausea• by Jean-Paul by Jean-Paul

SartreSartre

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Muscular contractions Muscular contractions associated with nausea and associated with nausea and

vomitingvomiting

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Chemoreceptor Trigger Chemoreceptor Trigger CenterCenter (CTZ)(CTZ)

•““Antiemetics”Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004Maze, 2004

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World Federation of Societies of AnaesthesiologistsWWW implementation by the NDA Web Team, Oxford

Issue 17 (2003) Article 2: Page 1 of 1

Anatomy and physiology of the vomiting Anatomy and physiology of the vomiting centre and the chemoreceptor trigger centre and the chemoreceptor trigger

zonezone

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5HT-Receptor and PONV 5HT-Receptor and PONV PathophysiologyPathophysiology

•““Antiemetics”Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004Pharmacology, AS Evers and M Maze, 2004

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Chemoreceptor Trigger Zone Chemoreceptor Trigger Zone

and Emetic Centerand Emetic Center

Watcha MF, White PF. Anesthesiology. 1992;77:162–184.

AntagonistAntagonist

AgonistAgonist

Receptor SiteReceptor Site

Are

aA

rea

Po

stre

ma

Po

stre

ma ChemoreceptorChemoreceptor

TriggerTriggerZoneZone(CTZ)(CTZ)

EmeticCenter

5-HT5-HT33 RAs RAs

5-HT5-HT33

PromethazinePromethazine

HistamineHistamine

AtropineAtropine

MuscarinicMuscarinic

DroperidolDroperidol

Dopamine (DDopamine (D22))

Nitrogen mustardNitrogen mustard

CisplatinCisplatin

Digoxin glycosideDigoxin glycoside

Opioid, analgesicsOpioid, analgesics

Vestibular portionVestibular portionof 8th nerveof 8th nerve

NN22OO

GI tract distensionGI tract distension

Higher centers (vision, taste)Higher centers (vision, taste)

PharynxPharynx

ParvicellularParvicellularReticularReticular

FormationFormation

MediastinumMediastinum

??

VagusVagus

NK-1 RANK-1 RA

Substance PSubstance P

Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.

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Schematic representation of Schematic representation of the factors influencing nausea the factors influencing nausea

and vomitingand vomiting

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www.marinol.com/images/graphic-cancer.gif

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A final pathway for A final pathway for nausea nausea

http://www.mywhatever.com/cifwriter/library/70/4938.html

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PONV ImpactPONV Impact• Incidence of PONV: varies with age, surgical Incidence of PONV: varies with age, surgical

procedure, anesthetic techniqueprocedure, anesthetic technique• Emesis frequently occurs after D/C from PACU = Emesis frequently occurs after D/C from PACU =

incidence lower in PACU than over 24 – 48 hincidence lower in PACU than over 24 – 48 h• Delayed emesisDelayed emesis: timing of oral intake or waning : timing of oral intake or waning

effects of perioperative antiemeticseffects of perioperative antiemetics• Vomiting - Vomiting - unpleasantunpleasant and and medical risksmedical risks: :

aspirationaspiration of gastric content; jeopardizes of gastric content; jeopardizes abdominal or inguinalabdominal or inguinal closures; increased IV closures; increased IV pressure: increase morbidity after pressure: increase morbidity after ocularocular, , tympanictympanic, , intracranial proceduresintracranial procedures; elevate HR ; elevate HR and BP: risk for and BP: risk for MIMI and and dysrhythmiasdysrhythmias; gagging ; gagging and retching: and retching: parasympatheticparasympathetic response: response: bradycardiabradycardia and and hypotensionhypotension..

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Demographic Factors for Demographic Factors for PONVPONV

• Study of Study of 17,63817,638 ambulatory patients: increased ambulatory patients: increased risk in younger pts.: risk in younger pts.: PONVPONV decreasingdecreasing 13%13% per per decadedecade of age. (“Anesthesiology” – 1999;91:109, of age. (“Anesthesiology” – 1999;91:109, Sinclair DR, Chung F, Mezei G)Sinclair DR, Chung F, Mezei G)

• WomenWomen: : 3 times3 times higher incidence than men higher incidence than men• Increased with Increased with GAGA and and durationduration of GA of GA• ENTENT and and dentaldental had higher incidence (14.3%), had higher incidence (14.3%),

followed by followed by orthopedic shoulderorthopedic shoulder and and plasticplastic• Hx. of preop. Hx. of preop. emesisemesis or or motion sicknessmotion sickness• GA near GA near mensesmenses (increase E (increase E22))• High: procedures of High: procedures of extraocular musclesextraocular muscles or or

middle earmiddle ear, , peritoneal or intestinal peritoneal or intestinal irritationirritation, , testicular tractiontesticular traction

• SmokersSmokers: : lowerlower risk risk

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Contributing FactorsContributing Factors• Risk of PONV: Risk of PONV: increasedincreased by by

starvationstarvation, , gastricgastric irritationirritation, , effects of effects of anestheticsanesthetics on on chemotacticchemotactic centers, centers, autonomic autonomic imbalanceimbalance, postoperative , postoperative painpain

• Swallowed Swallowed bloodblood or or tissuetissue, , gasgas in the stomachin the stomach

• General AnesthesiaGeneral Anesthesia more than more than regional, although vomiting regional, although vomiting frequently when frequently when parenteralparenteral narcoticsnarcotics..

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Major causes of nausea and Major causes of nausea and vomitingvomiting

Drug/treatment - induced Cancer chemotherapyOpiatesNicotineAntibioticsRadiotherapy

Labyrinth disorders MotionMeniere's disease

Endocrine causes Pregnancy

Infectious causes GastroenteritisViral labyrinthitis

Increased intracranial pressure HaemorrhageMeningitis

Post-operative AnaestheticsAnalgesicsProcedural

CNS causes Anticipatory Migraine Bulimia nervosa

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Major Risk Factors for PONV Major Risk Factors for PONV in Adultsin Adults

• Patient-specific Risk FactorsPatient-specific Risk Factors- Age (adult)- Age (adult)- Non-smoking status- Non-smoking status- History of PONV / motion sickness- History of PONV / motion sickness- Predisposing gastric disorders- Predisposing gastric disorders- Low threshold for nausea- Low threshold for nausea- Preoperative anxiety- Preoperative anxiety- Obesity (disputed in recent studies)- Obesity (disputed in recent studies)- Gastric distension (disputed in recent studies)- Gastric distension (disputed in recent studies)

• Anesthetic Risk FactorsAnesthetic Risk Factors- Pre-anesthetic- Pre-anesthetic medications (opioids, atropine)medications (opioids, atropine)- Volatile anesthetics- Volatile anesthetics- Nitrous Oxide- Nitrous Oxide- Intraoperative or postoperative use of opioids- Intraoperative or postoperative use of opioids- Duration of anesthesia (> 120 min)- Duration of anesthesia (> 120 min)

• Surgical Risk FactorsSurgical Risk Factors- Duration of surgery (each 30 min increases PONV risk by 60%)- Duration of surgery (each 30 min increases PONV risk by 60%)- Type of surgery (craniotomy; ear, nose, throat procedures; - Type of surgery (craniotomy; ear, nose, throat procedures;

major breast procedures; strabismus surgery; laparoscopy; laparotomy).major breast procedures; strabismus surgery; laparoscopy; laparotomy).- Intubation (disputed in recent studies)- Intubation (disputed in recent studies)- Early oral intake- Early oral intake

Am J Health Syst Pharm 1999;56:729-764

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Specific factors increasing risk Specific factors increasing risk of nausea and vomiting - of nausea and vomiting -

PONVPONV• adultsadults have more PONV than children have more PONV than children• womenwomen• obesityobesity• delayed gastric emptying disorders (delayed gastric emptying disorders (GERDGERD, , GI obstructionGI obstruction, & , &

neuromuscular neuromuscular disorders)disorders)• history of history of motion sicknessmotion sickness (which can cause movement-induced (which can cause movement-induced

PONV when patient is moved or turned) and/or PONV when patient is moved or turned) and/or history of PONVhistory of PONV• history of history of smoking smoking decreasesdecreases risk risk• anxiousanxious person person• emotogenic factors of emotogenic factors of anaestheticanaesthetic• etomidateetomidate (Amidate(Amidate)),, ketamineketamine, and , and gaseous general gaseous general

anaesthesiaanaesthesia, including , including nitrous oxidenitrous oxide have higher risk have higher risk• atropine decreasesatropine decreases risk because it is a vagolytic risk because it is a vagolytic• propofol propofol ((DiprivanDiprivan) also ) also decreasesdecreases risk, probably because has risk, probably because has

slightly anti-serotonergicslightly anti-serotonergic properties; but, is indicated only as a properties; but, is indicated only as a sedative-hypnotic; it has anti-emetic properties, but is not sedative-hypnotic; it has anti-emetic properties, but is not currently indicated solely for that usecurrently indicated solely for that use

• longer procedureslonger procedures with with general anaesthesiageneral anaesthesiaGarrett, K., Tsuruta, K., Walker, S., Jackson, S., & Sweat, M. (2003)

http://www.eddyelmer.com/tools/aemetic.htm

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Risk Score for Predicting Risk Score for Predicting PONVPONV

RISK FACTORS: 1 -Female sex

2 - Hx. of motion sickness or PONV

3 - Nonsmoking status4 - Use of Postoperative

Opioids

NONE 1 Factor 2 Factors 3 Factors 4 Factors

79 %61 %39 %21 %10 %

Apfel CC et al – “A simplified risk score for predicting postoperative nausea and vomiting” – Anesth; 91:693-700, 1999.

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Anesthetic AgentsAnesthetic Agents• Exclusion of Exclusion of Nitrous OxideNitrous Oxide reduces the incidence reduces the incidence

of PONVof PONV• PONV not different among potent inhalation PONV not different among potent inhalation

anesthetics: except anesthetics: except sevofluranesevoflurane (marginally (marginally higherhigher incidence) incidence)

• BarbiturateBarbiturate induction less offensive than induction less offensive than ketamineketamine or or etomidateetomidate; ; propofolpropofol induction induction lowest incidencelowest incidence

• NarcoticNarcotic analgesics: increase PONV analgesics: increase PONV• KetorolacKetorolac with small doses of narcotics: reduce with small doses of narcotics: reduce

severity of PONVseverity of PONV• NeostigmineNeostigmine, , physostigminephysostigmine: increase the : increase the

incidence of PONVincidence of PONV

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PONV Prevention and PONV Prevention and TreatmentTreatment

• Adequate postop. Adequate postop. analgesiaanalgesia• Limit postoperative Limit postoperative vestibular stimulationvestibular stimulation

(minimize brisk head movement)(minimize brisk head movement)• Avoid Avoid gastric distensiongastric distension (OG tube?) (OG tube?)• Adequate Adequate hydrationhydration ( (Anesth AnalgAnesth Analg

1995;80:682; Yogendran S, Kumar B, 1995;80:682; Yogendran S, Kumar B, Cheng D), but initiation of postop Cheng D), but initiation of postop drinking is frequently a triggering eventdrinking is frequently a triggering event

• Sometimes D/C children or high-risk Sometimes D/C children or high-risk patients patients beforebefore they take they take oral fluidsoral fluids

• Nausea and Vomiting: also signs of Nausea and Vomiting: also signs of serious underlying physiologic serious underlying physiologic abnormalities – evaluate abnormalities – evaluate hypotensionhypotension, , increased increased ICPICP, , hypoxemiahypoxemia, , hypoglycemiahypoglycemia, , gastric bleedinggastric bleeding..

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Strategies to Reduce Strategies to Reduce Baseline RiskBaseline Risk

• Use Use RegionalRegional Anesthesia Anesthesia• Use of Use of PropofolPropofol for induction and for induction and

maintenancemaintenance• Use of intraoperative Use of intraoperative supplemental supplemental

oxygenoxygen• HydrationHydration• Avoid Avoid Nitrous OxideNitrous Oxide and and Volatile Volatile

AnestheticsAnesthetics• Minimize intraoperative and postoperative Minimize intraoperative and postoperative

opioidsopioids• Minimize the use of Minimize the use of NeostigmineNeostigmine

Anesth Analg 2004; 99;77-81.

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“Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341

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Effect of intraoperative Effect of intraoperative intravenous crystalloid intravenous crystalloid

infusion on PONVinfusion on PONV• IV administration of CSL IV administration of CSL 30 ml/kg30 ml/kg

to healthy women undergoing day-to healthy women undergoing day-case gynecological laparoscopy case gynecological laparoscopy reduced the incidence of vomiting, reduced the incidence of vomiting, nausea and anti-emetic use when nausea and anti-emetic use when compared with CSL compared with CSL 10 ml/kg10 ml/kg..

Br J Anaesth. 2004 Sep;93(3):381-5. Epub 2004 Jun 25

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Antiemetics—Members by Antiemetics—Members by ClassClass

PhenothiazinesPhenothiazines– Chlorpromazine, Chlorpromazine,

prochlorperazine, prochlorperazine, promethazinepromethazine

ButyrophenonesButyrophenones– Droperidol Droperidol

(haloperidol)(haloperidol)

BenzamidesBenzamides– MetoclopramideMetoclopramide

AnticholinergicsAnticholinergics– ScopolamineScopolamine

AntihistaminesAntihistamines– Dimenhydrinate, Dimenhydrinate,

hydroxyzine, cyclizinehydroxyzine, cyclizine

5-HT5-HT33 antagonists antagonists– Dolasetron, granisetron, Dolasetron, granisetron,

ondansetronondansetron

OthersOthers– DexamethasoneDexamethasone– Dronabinol (9THC)Dronabinol (9THC)

Upcoming class for PONV already approved for CINV NK1-receptor antagonists


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•““Antiemetics”Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS Evers and M Maze, 2004Pharmacology, AS Evers and M Maze, 2004

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Main classes of anti-Main classes of anti-emetic drugsemetic drugs

Class Drug

Anti-cholinergic scopolamine (L-hyoscine)

Anti-histamine cinnarizine cyclizine promethazine (?)

Dopamine antagonists metoclopramide domperidonedroperidol (withdrawn 2001)haloperidol

Cannabinoid nabilone

Corticosteroid dexamethasone

Histamine analogue betahistine

5HT3-receptor antagonist granisetronondansetrontropisetron

Source: British National Formulary, March 2002

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Agonists and Antagonists Agonists and Antagonists Associated with Nausea and Associated with Nausea and

VomitingVomiting

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Clinical Aspects in Clinical Aspects in Selecting Antiemetics for Selecting Antiemetics for

Prevention of PONVPrevention of PONV

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Antiemetic treatment for Antiemetic treatment for PONV Patients with No PONV Patients with No Prophylaxis or Failed Prophylaxis or Failed

ProphylaxisProphylaxisIf Initial Tx. Was:If Initial Tx. Was: Then Treat With:Then Treat With:No prophylaxis or No prophylaxis or dexamethasone.dexamethasone.

Low-dose 5-HTLow-dose 5-HT33-receptor -receptor antagonist antagonist (Ondansetron 1 mg, (Ondansetron 1 mg, Dolasetron 12.5 mg, Granisetron Dolasetron 12.5 mg, Granisetron 0.1 mg, Tropisetron 0.5 mg).0.1 mg, Tropisetron 0.5 mg).

5-HT5-HT33-receptor antagonist -receptor antagonist plus 2plus 2ndnd agent agent (droperidol 0.625 (droperidol 0.625 mg IV, dexamethasone 2 – 4 mg IV, mg IV, dexamethasone 2 – 4 mg IV, promethazine 12.5 mg IV).promethazine 12.5 mg IV).

Triple therapy with 5-HTTriple therapy with 5-HT33--receptor antagonist plus 2 receptor antagonist plus 2 other agents.other agents.

When PONV occurs <6h after surgery: use agent from different class or Propofol 20 mg in PACU (adults).

Agent from a different class.Agent from a different class.

When PONV occurs >6h after surgery: repeat 5-HT5-HT33-receptor antagonist-receptor antagonist and droperidol (except dexamethasone or scopolamine)

Use agents from a different class.

Anesth Analg 2003;97:62-71

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Standard Dosages of Standard Dosages of Antiemetics for the Antiemetics for the

Prophylaxis of PONV in Adults Prophylaxis of PONV in Adults Am J Health Syst PharmAm J Health Syst Pharm 1999;56:729-764 1999;56:729-764

AgentAgent DosageDosageDroperidolDroperidol 0.625 – 1.25 mg Iv 5 min before termination of 0.625 – 1.25 mg Iv 5 min before termination of

anesthesiaanesthesia

OndansetronOndansetron 4 mg IV immediately before induction4 mg IV immediately before induction

8 mg PO 1 h before induction8 mg PO 1 h before inductionRecent data: more effective- end of anesthesiaRecent data: more effective- end of anesthesia

DolasetronDolasetron 12.5 mg IV intraoperatively12.5 mg IV intraoperatively

100 mg PO 1 h before induction100 mg PO 1 h before induction

MetoclopramideMetoclopramide 10 (20) mg IV near the end (not effective when 10 (20) mg IV near the end (not effective when used alone)used alone)

PromethazinePromethazine 25 mg PO 1 h before induction25 mg PO 1 h before induction

12.5 – 25 mg IV immediately before ind.12.5 – 25 mg IV immediately before ind.

ProchlorperazineProchlorperazine 5 – 15 mg PO 1 h before induction5 – 15 mg PO 1 h before induction

5 – 10 mg IM 1 – 2 h before ind.; repeat once in 5 – 10 mg IM 1 – 2 h before ind.; repeat once in 30 min, prn30 min, prn

5 – 10 mg IV 15 – 30 min before ind; x15 – 10 mg IV 15 – 30 min before ind; x1

GranisetronGranisetron 20 – 40 mcg/kg IV20 – 40 mcg/kg IV

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Treatment of PONV in Treatment of PONV in AdultsAdults

Am J Health Syst PharmAm J Health Syst Pharm 1999;56:729-764 1999;56:729-764AgentAgent DosageDosageOndansetronOndansetron 1 – 4 mg IV postoperatively1 – 4 mg IV postoperatively

MetoclopramideMetoclopramide 10 mg IV q 4–6 h prn post-operatively10 mg IV q 4–6 h prn post-operatively

PromethazinePromethazine 10 – 25 mg PO prn post-operatively10 – 25 mg PO prn post-operatively

12.5 – 25 mg IM or IV q4h prn post-operatively12.5 – 25 mg IM or IV q4h prn post-operatively

ProchlorperazineProchlorperazine 5 – 15 mg PO post-op.5 – 15 mg PO post-op.

5 – 10 mg IM; repeat once in 30 min prn5 – 10 mg IM; repeat once in 30 min prn

5 – 10 mg IV; may repeat once prn5 – 10 mg IV; may repeat once prn

ChlorpromazineChlorpromazine 10 – 25 mg PO q4-6h prn10 – 25 mg PO q4-6h prn

12.5 – 25 mg IM if no hypotension; repeat in 1h12.5 – 25 mg IM if no hypotension; repeat in 1h

DroperidolDroperidol 0.625 – 1.25 mg IV prn0.625 – 1.25 mg IV prn

DolasetronDolasetron 12.5 mg IV post-operatively12.5 mg IV post-operatively

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Management of POV in Management of POV in PediatricPediatric Patients PatientsAgentAgent DosageDosage

ProphylaxisProphylaxisDolasetronDolasetron Age >2y: 1.8 mg/kg IV immediately before ind.Age >2y: 1.8 mg/kg IV immediately before ind.

OndansetronOndansetron 0.05 mg/kg IV (range: 0.05 – 0.15 mg/kg)0.05 mg/kg IV (range: 0.05 – 0.15 mg/kg)

DroperidolDroperidol 0.015 – 0.075 mg/kg per dose IV0.015 – 0.075 mg/kg per dose IV

TreatmentTreatmentChlorpromazineChlorpromazine 0.55 mg/kg PO or IM0.55 mg/kg PO or IM

DroperidolDroperidol 0.1 mg/kg per dose IV0.1 mg/kg per dose IV

OndansetronOndansetron 0.05 mg/kg per dose IV0.05 mg/kg per dose IV

Am J Health Syst Pharm 1999;56:729-764

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PhenothiazinesPhenothiazines• Chlorpromazine, Chlorpromazine,

Prochlorperazine, Prochlorperazine, PromethazinePromethazine

– Antipsychotic agentsAntipsychotic agents

– Blocks DBlocks D22 receptors in CTZ receptors in CTZ and CNSand CNS

– SIDE EFFECTSSIDE EFFECTS: EPS, : EPS, sedationsedation, dizziness, , dizziness, blurred vision, skin blurred vision, skin reactions, orthostatic reactions, orthostatic hypotensionhypotension

chlorpromazine

Prochlorperazine-heterocyclic side chain Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.

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ButyrophenonesButyrophenones

• DroperidolDroperidol– αα blocker, D blocker, D22 receptor antagonist (binds to D receptor antagonist (binds to D22 receptor) receptor)– Acts at both CTZ and area postremaActs at both CTZ and area postrema– 1.25 mg droperidol given at the beginning of surgery is as 1.25 mg droperidol given at the beginning of surgery is as

effective as 4 mg dexamethasone or 4 mg ondansetron effective as 4 mg dexamethasone or 4 mg ondansetron ( Apfel et al. New Engl J Med 2004 ). ( Apfel et al. New Engl J Med 2004 ).

– SIDE EFFECTSSIDE EFFECTS: EPS, sedation, : EPS, sedation, QTc prolongation with QTc prolongation with torsade de pointes torsade de pointes (there is little evidence that antiemetic (there is little evidence that antiemetic doses trigger this condition - Gan et al. Anesthesiology doses trigger this condition - Gan et al. Anesthesiology 2002). 2002).

- high doses: hypotension (- high doses: hypotension ( blockade) blockade)

- low-dose droperidol may cause dysphoria (Melnick - low-dose droperidol may cause dysphoria (Melnick et al. Anesth Analg 1989, Lim et al. Anaesth Intensive Care et al. Anesth Analg 1989, Lim et al. Anaesth Intensive Care 1999) 1999)

EPS = extrapyramidal symptomsEPS = extrapyramidal symptoms Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.

40Anesthesiology, Vol.102, Number 6, June 2005

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BenzamideBenzamide

• MetoclopramideMetoclopramide– Specific dopamine DSpecific dopamine D22 antagonist antagonist LES tone which enhances gastric motilityLES tone which enhances gastric motility– Short (1 to 2 hours) duration of action.Short (1 to 2 hours) duration of action.– SIDE EFFECTSSIDE EFFECTS: EPS: EPS, restlessness, drowsiness, , restlessness, drowsiness,

fatigue, agranulocytosis, methemoglobinemia, fatigue, agranulocytosis, methemoglobinemia, hypotension and bradycardia (or tachycardia)hypotension and bradycardia (or tachycardia)

• Cisapride (Cisapride (removed from use – cardiac removed from use – cardiac side effectsside effects))

EPS = extrapyramidal symptomsEPS = extrapyramidal symptoms


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AnticholinergicsAnticholinergics• ScopolamineScopolamine

– Inhibit cholinergic and muscarinic CNS Inhibit cholinergic and muscarinic CNS receptors. receptors.

– Crosses the blood-brain barrier. Crosses the blood-brain barrier. – More effective against motion-induced More effective against motion-induced

emesis than against motion-induced emesis than against motion-induced nausea. nausea.

– SIDE EFFECTSSIDE EFFECTS: : sedationsedation, CNS , CNS excitation, excitation, dry mouthdry mouth, urinary retention, , urinary retention, blurred vision, confusion, disorientation, blurred vision, confusion, disorientation, hallucinationshallucinations

Night Shade = Atropa belladonnaPost Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.

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AntihistaminesAntihistamines

• DimenhydrinateDimenhydrinate, , HydroxyzineHydroxyzine, , CyclizineCyclizine– Block acetylcholine in the vestibular Block acetylcholine in the vestibular

apparatus and histamine Happaratus and histamine H11 receptors in receptors in the nucleus of the solitary tract. the nucleus of the solitary tract.

– SIDE EFFECTSSIDE EFFECTS: blurred vision, urinary : blurred vision, urinary retention, dry mouth, and retention, dry mouth, and sedationsedation

CyclizineCyclizine has similar efficacy to has similar efficacy to ondansetronondansetron; side effects: sedation ; side effects: sedation and dry mouth (anticholinergic). and dry mouth (anticholinergic). Br J AnaesthBr J Anaesth

2000; 85(5):678-682/ Ahmed AB, Hobbs GJ, Curran JP: “Randomized, placebo-controlled trial of 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”.combination antiemetic prophylaxis for day-case gynaecological laparoscopic surgery”.


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5-HT5-HT33 Antagonists Antagonists • ((OOndansetronndansetron (Zofran®), (Zofran®),

GranisetronGranisetron (Kytril®), (Kytril®), TTropisetron ropisetron (Navoban®),(Navoban®), and and Dolasetron Dolasetron (Anzemet®)(Anzemet®)

• - No difference in efficacy- No difference in efficacy– No sedation, extrapyramidal reactions, No sedation, extrapyramidal reactions,

adverse effects on vital signs or laboratory adverse effects on vital signs or laboratory tests, or drug interactions with other tests, or drug interactions with other anesthetic medications. anesthetic medications.

– Because Because repeating ondansetronrepeating ondansetron is of is of limited limited effectivenesseffectiveness (Kovac et al. J Clin Anesth 1999) - (Kovac et al. J Clin Anesth 1999) - reasonable to use ondansetron predominantly as a reasonable to use ondansetron predominantly as a rescue rescue treatmenttreatment ( White PF, New Engl J Med 2004) ( White PF, New Engl J Med 2004)

– SIDE EFFECTSSIDE EFFECTS: : HeadacheHeadache, , dizzinessdizziness, , flushing, elevated liver flushing, elevated liver enzymes,enzymes, constipationconstipation


Management of PONV’ – Habib et al / CAN J ANESTH; 2004; 51:4; pp 326 - 341

45

Ondansetron Ondansetron PharmacokineticsPharmacokinetics

46

www.anzemet.com/images/chart_c_pharmacology.jpg

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48

Synthetic steroid Synthetic steroid

HypothesesHypotheses• inhibition of prostaglandin syn.inhibition of prostaglandin syn. tryptophantryptophan• release of endorphinsrelease of endorphins• change in CSF opening pressurechange in CSF opening pressure• + psychological effects of steroids + psychological effects of steroids

ACUTE SIDE EFFECTSACUTE SIDE EFFECTS: flushing : flushing and perineal itching. and perineal itching.

- Wang et al. Anesth Analg 2000 and the IMPACT data - Wang et al. Anesth Analg 2000 and the IMPACT data (unpublished observation) - dexamethasone has a (unpublished observation) - dexamethasone has a delayed onset of antiemetic actions which might need delayed onset of antiemetic actions which might need a a few hours to workfew hours to work..

DexamethasoneDexamethasone


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Dexamethasone (contin.)Dexamethasone (contin.)


50


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NK1 AntagonistsNK1 Antagonists

• Future development in anti-emesis is looking at the Future development in anti-emesis is looking at the neurokinin 1 (NK-1) receptorneurokinin 1 (NK-1) receptor, where , where substance substance PP is the is the natural ligandnatural ligand. This receptor is found in the . This receptor is found in the nucleus tractus solitariusnucleus tractus solitarius and the and the area area postremapostrema, as well as the , as well as the peripheralperipheral nervous nervous systemsystem. Early studies of NK-1 antagonists have been . Early studies of NK-1 antagonists have been promising, especially in combination with promising, especially in combination with ondansetron.ondansetron. ( (World Federation of Societies of AnaesthesiologistsWorld Federation of Societies of Anaesthesiologists

WWW implementation by the NDA Web Team, OxfordWWW implementation by the NDA Web Team, Oxford ; ; Issue 17 (2003) Article 2: Page 1Issue 17 (2003) Article 2: Page 1 ) )

• Neurokinine (substance P, NK1) antagonistsNeurokinine (substance P, NK1) antagonists - - impressive antiemetic in the animal model. However, impressive antiemetic in the animal model. However, early clinical data have been disappointing, except early clinical data have been disappointing, except for for aprepitant (Emendaprepitant (Emend®) - has demonstrated ®) - has demonstrated superiority over ondansetronsuperiority over ondansetron in in chemotherapychemotherapy

induced nausea and vomiting.induced nausea and vomiting. http://http://www.ponv.org/Knowledge.htmwww.ponv.org/Knowledge.htm

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DRONABINOL MarinolDRONABINOL Marinol®®

– 9THC9THC– Unknown Unknown

mechanism mechanism involves inhibition involves inhibition of CTZof CTZ

– SIDE EFFECTSSIDE EFFECTS: : dizziness, dizziness, drowsiness, nausea drowsiness, nausea (not emesis)(not emesis)

– Schedule II drugSchedule II drugPost Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.

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.

www.marinol.com/images/chart-clinical1.gif

53

Nonpharmacological Nonpharmacological Methods (TENS) for Methods (TENS) for Prevention of PONV Prevention of PONV

C K. Sim http://www.iars.org/abstracts/abstracts/S160/s180.htm

54

Accupressure Wristbands do not Prevent PONV after Urological Endoscopic Surgery – A. Agarwal et al. – Can J Anesth 2000/ 47:4/ p319-324

Accupressure Wristbands for PONV

55

Ginger rootGinger root• Ginger root (Ginger root (Zingiber Zingiber

officinaleofficinale Roscoe., Roscoe., Zingiberaceae)Zingiberaceae)

• "In summary, we found "In summary, we found that ginger is a that ginger is a promising antiemetic promising antiemetic herbal remedy, but the herbal remedy, but the clinical data to date are clinical data to date are insufficient to draw firm insufficient to draw firm conclusions.“conclusions.“

Postoperative nausea (Bone Postoperative nausea (Bone et alet al., 1990; Phillips ., 1990; Phillips et al.et al., 1993; Arfeen , 1993; Arfeen et al.,et al., 1995) 1995)

Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (Ginger) - an antiemetic for day case surgery. Anaesthesia 1993; 48: 715-717

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• 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

57www.biegler.com/vestis.en.html

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

58

Noni CAPSULEItem Code : c017 Morinda citrifolia Linn.Morinda CAPSULEEach : 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)

59

HANUMAN PRASANKAI TEAItem Code : h011 Schefflera leucantha Vig. Herbal Tea for HealthEach : Hanuman prasankai 100 %Indication : Relieves cough and nausea, Used as bronchodilator Content : 20 sachets. Net. weight 20 g.Price : US$ 2.90 (excl. shipping

60

Enterra TherapyGastric 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

61

The main sites of action of The main sites of action of drugs affecting nausea and drugs affecting nausea and

vomitingvomiting

62

Summary table Relating Type of Summary table Relating Type of Nausea, Receptor, Drug Class, and Nausea, Receptor, Drug Class, and

Example of Drug of ChoiceExample of Drug of Choice Type of Nausea

Receptors Causing Nausea

Drug Class Useful Examples of DOC

VestibularCholinergic, histaminic

Anticholinergic, antihistaminic

Scopolamine patch, promethazine

Obstruction of bowel caused by constipation

Cholinergic, histaminic, ? 5HT3

Stimulate myenteric plexus

Senna products

DysMotility of upper gutCholinergic, histaminic, ? 5HT3

Prokinetics stimulate 5HT4

receptorsMetoclopramide

Infection, InflammationCholinergic, histaminic, ? 5HT3

Anticholinergic, antihistaminic

Promethazine, prochlorperazine

Toxins stimulating the CTZ in the brain such as opioids

Dopamine 2, 5HT3

Antidopaminergic, 5HT3 antagonist

Prochlorperazine, haloperidol, ondansetron

http://www.mywhatever.com/cifwriter/library/70/4938.html

63www.uspharmacist.com/index.asp?show=article&p...

64

Individual Risk Factors for Individual Risk Factors for PONVPONV

65

Algorithm for PONV Algorithm for PONV ProphylaxisProphylaxis

Consider regionalanesthesia

Low

No prophylaxis unless there is medical risk of sequelae from

vomiting Not indicated

Patients at moderate risk

Consider antiemetic prophylaxiswith monotherapy (adults) or

combination therapy (children and adults)

Patients at high risk

Initiate combination therapy with 2 or 3 prophylactic

agents from different classes

HighModerate

Evaluate risk of PONVin surgical patient

If general anesthesia is used, reduce baseline risk factors when clinically practical & consider using nonpharmacologic therapies

Gan TJ et al. Anesth Analg. 2003;97:62–71.

66

www.allaboutpharmacy.co.uk/Formulary/ponv.jpg

67

PONV Treatment Pathway PONV Treatment Pathway --Mass. GeneralMass. General Protocol for PONV Protocol for PONV

• Step 1.Step 1.• Ondansetron 2 mg IV Ondansetron 2 mg IV andand dexamethasone 4 mg IV as a single dose dexamethasone 4 mg IV as a single dose

If nausea and vomiting continues to be problematic after 30 minutes, proceed to step 2:If nausea and vomiting continues to be problematic after 30 minutes, proceed to step 2:• Step 2.Step 2.• For the MGH only:For the MGH only:• Haloperidol 0.25mg IV, may repeat times one in 30 minutes, orHaloperidol 0.25mg IV, may repeat times one in 30 minutes, or

Ephedrine 50 mg IM (35 mg for patients < 50 Kg). May be repeated x1 in 4 hoursEphedrine 50 mg IM (35 mg for patients < 50 Kg). May be repeated x1 in 4 hours**contraindicated in patients with cardiovascular or hypertensive disease*contraindicated in patients with cardiovascular or hypertensive disease*

• and and • Metoclopramide 20 mg IV. May be repeated x1 in 4 hoursMetoclopramide 20 mg IV. May be repeated x1 in 4 hours• If nausea and vomiting continues to be problematic after 30 minutes, proceed to step 3:If nausea and vomiting continues to be problematic after 30 minutes, proceed to step 3:• Step 3.Step 3.• Promethazine 12.5 -25 mg IV q 4 h. Promethazine 12.5 -25 mg IV q 4 h. oror

Meclizine 25mg orally q 8 h. Meclizine 25mg orally q 8 h. ororProchlorperazine suppository 25 mg per rectum q 12 h.Prochlorperazine suppository 25 mg per rectum q 12 h.

• If nausea and vomiting continues to be problematic, proceed to step 4:If nausea and vomiting continues to be problematic, proceed to step 4:• Step 4.Step 4.• DroperidolDroperidol

Prior to prescribing droperidol, physician must determine that pre-administration EKG Prior to prescribing droperidol, physician must determine that pre-administration EKG QTc interval is < 440 msec [males] or <450 msec [females]. If within guidelines, thenQTc interval is < 440 msec [males] or <450 msec [females]. If within guidelines, then*Give droperidol 1.25 mg IV x 1 dose only*Give droperidol 1.25 mg IV x 1 dose only*Patient's EKG must be monitored for 2-3 hr post-dose. *Patient's EKG must be monitored for 2-3 hr post-dose.

• Note: These guidelines were developed by an interdisciplinary group of clinicians from Note: These guidelines were developed by an interdisciplinary group of clinicians from the BWH and MGH Pharmacy and Anesthesia Departments.the BWH and MGH Pharmacy and Anesthesia Departments.

• http://www.massgeneral.org/pharmacy/Newsletters/2002/March%202002/Postoperative%20Nauseahttp://www.massgeneral.org/pharmacy/Newsletters/2002/March%202002/Postoperative%20Nausea%20and%20Vomiting.htm%20and%20Vomiting.htm

68

Treatment of Established Treatment of Established PONVPONV

69

What is the Best Strategy to Prevent PONV?” – A.S. Habib and T.J. Gan; Chapter pp130-135; in Evidence-based Practice of Anesthesiology – Lee A. Fleisher, 2004

70


71

BibliographyBibliography• http://www.nauseaandvomiting.co.uk/NAVRES001-2-NandV-general.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-2-NandV-general.htm• Maddali MM, Mathew J, Fahr J, Zarroug AW. Postoperative Nausea and Vomiting in Diagnostic Maddali MM, Mathew J, Fahr J, Zarroug AW. Postoperative Nausea and Vomiting in Diagnostic

Gynaecological Laparoscopic Procedures: Comparison of the Efficacy of the Combination of Gynaecological Laparoscopic Procedures: Comparison of the Efficacy of the Combination of Dexamethasone and Metoclopramide with that of Dexamethasone and Ondansetron .J Postgrad Med Dexamethasone and Metoclopramide with that of Dexamethasone and Ondansetron .J Postgrad Med 2003;49:302-3062003;49:302-306

• http://faq.emetophobia.net/http://faq.emetophobia.net/• http://http://www.eddyelmer.com/tools/aemetic.htmwww.eddyelmer.com/tools/aemetic.htm • ““Clinical Anesthesia Practice” – R. R. Kirby, N. Gravenstein, E. B. Lobato, J. S. Gravenstein; 2Clinical Anesthesia Practice” – R. R. Kirby, N. Gravenstein, E. B. Lobato, J. S. Gravenstein; 2 ndnd edition edition

2002, p.114 2002, p.114 • ““Strategies for Maximizing The Efficacy of Antiemetics In PONV Therapy” - Special Report – May 01, Strategies for Maximizing The Efficacy of Antiemetics In PONV Therapy” - Special Report – May 01,

20052005• Post Operative Nausea & Vomiting: The Role of Antiemetics - Post Operative Nausea & Vomiting: The Role of Antiemetics - Cedric Dupont-Eisner M.D.Cedric Dupont-Eisner M.D.• Evidence-based management of PONV: a reviewEvidence-based management of PONV: a review – – A.S. Habib, T.J. Gan – CAN J ANESTH 2004 / 51:4 / pp326 – 341A.S. Habib, T.J. Gan – CAN J ANESTH 2004 / 51:4 / pp326 – 341• ““Antiemetics”Antiemetics” , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS , J Scholz, MD, PhD, M Steinfath, MD, PhD, PT Tonner, MD, Phd p777 – 791; in Anesthetic Pharmacology, AS

Evers and M Maze, 2004Evers and M Maze, 2004

Further Readings:Further Readings:• In In EnglishEnglish::

• Watcha MF. Postoperative nausea and vomiting. Anesthesiol Clin N Am 2002; 20: 709-20. • Watcha MF. Postoperative nausea and vomiting. Anesthesiol Clin N Am 2002; 20: 709-20. • Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59: 213-43. • Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59: 213-43. • Gan TJ et al. Consensus guidelines for management of postoperative nausea and vomiting. Anesth • Gan TJ et al. Consensus guidelines for management of postoperative nausea and vomiting. Anesth Analg 2003; 97:62-71. Analg 2003; 97:62-71.

• In In DeutschDeutsch: : • Apfel CC, Roewer: Postoperative Uebelkeit und Erbrechen. Anaesthesist 2004; 53:377-391. • Apfel CC, Roewer: Postoperative Uebelkeit und Erbrechen. Anaesthesist 2004; 53:377-391. PDF-FilePDF-File• Eberhart LHJ et al.: Minimierung von Uebelkeit und Erbrechen in der postoperativen Phase. Dtsch • Eberhart LHJ et al.: Minimierung von Uebelkeit und Erbrechen in der postoperativen Phase. Dtsch Arztebl 2003; 1000: A 2584-2591 [Heft 40]. Arztebl 2003; 1000: A 2584-2591 [Heft 40].

• En En FrancaisFrancais: : Pierre S, Corno G: Nausees et vomissements postoperatoires de l'adulte. Ann Fr Anesth Reanim Pierre S, Corno G: Nausees et vomissements postoperatoires de l'adulte. Ann Fr Anesth Reanim 2003;22:119-129. 2003;22:119-129.

1 the treatment of postoperative nausea and vomiting c. m. prada, md august 4 th 2005

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nausea http

phd p777

impactincidence of ponv

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major causes of nausea

major risk factors

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