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SAEEDA, JAIN : PONV : A REVIEW 253 Indian J. Anaesth. 2004 ; 48 (4) : 253-258

POST-OPERATIVE NAUSEA AND VOMITING (PONV) :

A REVIEW ARTICLEDr. Saeeda Islam 1 Dr. P. N. Jain 2

SUMMARYPONV still remains a problem, despite an evident clinical perception that its severity has diminished. Patients who have past history of vomiting, now simply experience nausea. However for many patients, persistent nausea may be more distressing than a single vomit.Several factors may account for perceived decrease in severity of PONV viz. an increase in day care surgery where opioids are beenavoided, wide spread use of propofol, an I.V. anaesthetic with antiemetic property, the greater awareness of risk of PONV and alower threshold to start its prophylaxis. Further fast progress must be made towards eradicating the occurrence of PONV. A product or method that merely provides statistical significance over placebo is just insufficient. As a first step, studies should be directed towards patients with a quantified risk of PONV. This should be followed by an exploration of the efficacy of multiple antiemetic regimens in susceptible individuals. It is clear that, as yet there is no magic bullet for the complete control or treatment of PONV.Once the efficacy of agents or their combination have been established against stratified risk groups, it would then be appropriateto explore the risk benefit of routine prophylactic antiemetic therapy.

Keyword : Post operative, Nausea and Vomiting.

1. M.D., DNB, Former Senior Registrar 2. M.D., Additional Professor

Dept. of Anaesthesiology, Critical Care and PainTata memorial Hospital, Parel, Mumbai 400 012.Correspond to :Dr. P. N. JainE-mail : pnj5@hotmail.com, pnj@bom7.vsnl.net.in(Accepted for publication on 13-05-2004)

IntroductionThe most common and distressing symptoms, which

follow anaesthesia and surgery, are pain and emesis. Sometimes nausea and vomiting may be more distressingespecially after minor and ambulatory surgery, delayingthe hospital discharge. Pathophysiology and pharmacology 1

of postoperative nausea and vomiting is quite complex(Fig. 1). A detailed history, physical examination of the

patient is required for the correct diagnosis and proper treatment. Nausea and vomiting have been associated for many years with the use of general anaesthetics i.e. ether and chloroform. One of the first extensive descriptions of this phenomenon was by Sir John Snow in 1848, within18 months of chloroform introduction in anaesthesia.Historical treatment included wine (which he consideredmore beneficial than smelling salts!) and Battleys solutionof opium. 2

During ether era, reported incidence of PONV wasas high as 7580%. Various techniques, including oliveoil and insulin glucose infusion, were reported to be effective.

Robert Ferguson described the use of olive oil in 1912. Theoil was administered by mouth immediately after partialrestoration of consciousness and he postulated that oil in

the stomach absorbed any residual ether that might bethere. 3 The effect of atropine was appreciated by BrownSequard as early as 1883, when he wrote in a greatmajority of cases, the addition of atropine to the morphineprevents the nausea and vomiting occurring with morphinealone. 3

In the second half of century, the incidence of PONVdecreased by almost 50%. This is largely because of a

change in anaesthesia practice from opioids and deepether anaesthesia to non opioid or supplemented opioidpremedication, lighter and non ether anaesthesia, refinementof operative technique and identification of patientspredictive emetogenic factors. Seventy five years ago, Flaggsuggested that PONV may result from causes other thananaesthetics : there are atleast three kinds of vomiting,the first of which has been attributed to anaesthetics suchas ether, the second to reflex responses, the last to opioids.Subsequent investigation unfolded a spectrum of nonanaesthetics factors in the pathogenesis of PONV. 4

Over years, numerous drugs have been used in the

management of PONV. Phenothiazines were synthesizedoriginally in the late 19 th century by chemists working inthe dye industry. Promethazines synthesized in 1930 wasfound to have profound antiemetic property. However,its sedative action limited its use. Charpentier synthesizedchlorpromazine and it was introduced in1949, but sedationand hypotension were limiting side effect. Prochlorperazineand perphenazine are phenothiazine derivatives have beenused extensively in the management of PONV. 3

Prevalence of PONV is unacceptably high, and isdistressing to patients and potentially detrimental to their

REVIEW ARTICLE253

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postoperative recovery. 2 The incidence of postoperativeemesis in some large studies 4 has been reported to be in therange of 2030 % (table-1). 5,6 In an editorial, Kapur describedPONV as the big little problem following ambulatorysurgery. 7 There have been a volley of systemic reviews inthe world literature on PONV. 8,9,10 However there is noconsensus on the specific treatment of PONV. IntractablePONV is the most frequent anaesthetic related cause for unexpected hospital admission of surgical out patients. 11

There has been a little change in the incidence of PONVsince the introduction of halothane in to clinical practicein 1956. However, newer anaesthetic agent like propofolhave contributed to a recent decline in incidence of PONV. 12

More recently, propofol in sub hypnotic doses has beenshown to be effective anti-emetic against chemotherapy 13

and PONV. 14 There are new antiemetics like neurokinin-1(Substance-P antagonist) in the development. 15

Table - 1 : Reports (1936-1990) on the incidence of postoperative emesis. 5,6

Investigators Year Study Population Incidence CommentsPublished Size of Emesis

Waters et al 1936 10,000 41% Follow up periodunknown

Bellville et al 1959 748 19% Follow up for only2.5 hour

Adriani J et al 1961 2,230 23% Average follow up6 hour

Rowley et al 1982 1,183 43% Limited to children;lower incidence ininfants

Stark RD et al 1985 200 1-3% High risk womenreceiving propofol

Gold et al 1989 9,616 Severe emesis Outpatients with0.2% severe emesis

requiring hospitalization

Patel et al 1989 9,910 9% Limited to ambulatorysurgery in children

Forrest et al 1990 16,000 Over all Multi center trial with

incidence halothane, enflurane,18-25%;severe isoflurane andemesis 0.15% fentanyl.

Karlsson et al 1990 485 25% Study limited to children;highest incidence after strabismus surgery

Cohen et al 1990 29,220 25% Study limited to children;highest incidence in 6-10years age range

Why is the mechanism of nausea and vomiting notknown for almost 150 years? Four factors need to beconsidered to answer this million dollar question.

1. Complexity of the problem : The variables are somany that it becomes difficult to identify themechanism to assess the effects of an intervention,

as it requires a considerable number of patients inwell controlled trials.

2. Inadequate quantification of the phenomena : Thoughthere have been a huge number of clinical trials, thephenomena have been poorly quantified i.e. nausea,retching, vomiting etc.

3. Inadequate anti-emetic regimen : Although emesis isa common symptom of disease, a side effect of many therapies (e.g. cytotoxic chemotherapy,radiotherapy, L-dopa) and a result of natural stimuli(e.g. motion sickness, pregnancy), the physiology

of the emetic mechanism has not been an area of particularly intense research. If 5HT 3 receptor antagonists are found as effective against PONV asagainst anticancer therapy then this may help toidentify the predominant mechanisms involved.

4. Animal model : A lack of animal model to study thephysiology and pharmacology of the mechanism of PONV. Many species of rat and rabbit do not vomitirrespective of stimulus. Though, monkeys and dogsrespond to the same range of emetic stimuli as manwith cytotoxic drugs and radiation, they do not suffer from pregnancy and motion sickness and post

operative and post anaesthetic emesis.DefinitionsNausea : It is an unpleasant sensation referred to a

desire to vomit, not associated with expulsivemuscular movement.

Retching : When no stomach contents are expelled evenwith expulsive muscular efforts.

Vomiting : It is the forceful expulsion of even a smallamount of upper gastrointestinal contentsthrough mouth.

Physiology of vomitingThere are three major components of vomit reflex-

emetic detectors, integrative mechanism and motor output(Fig. 1).

The main sensors of somatic stimuli are located inthe gut and chemo-receptor trigger zone (CTZ). The emeticstimuli in gut are detected by two types of vagal afferentfibres.

(a) Mechanoreceptors : They are located in the muscular wall of the gut and are activated by contraction anddistension of the gut, on physical damage and

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manipulation during surgery. Distension of the proximalgut may induce vomiting such as in overeating.

(b) Chemoreceptors : They are located in the mucosa of the upper gut and sensitive to noxious chemical stimuli.

CTZ (chemoreceptor trigger zone) lies withinthe portion of brain stem. The area postrema is able todetect the circulating toxins in the CSF and activates the

vomiting centre in the medulla. Afferent impulses fromother areas can also influence the vomiting centre (Vestibular labyrinthine e.g. morning sickness, input from higher centresuch as limbic system and visual cortex). Vestibular cardiacafferent may induce nausea and vomiting as in MI.

The vomiting centre in medulla oblongata is inthe close proximity to other visceral centres like therespiratory and vasomotor centres. Four types of receptorsare involved cholinergic, dopaminergic, histaminic andserotonergic.

Integrative mechanism : It is a motor programmeinvolving coordination between many physiological systemsand autonomic and somatic components of the nervoussystem. These occur in brain stem.

The motor component of vomiting reflex is mediatedby both autonomic and somatic senses, and is coordinatedby the vomiting system in the brainstem. The vagal motor neurons supplying the gut and the heart originate in dorsalmotor vagal nucleus and nucleus ambiguous. The dorsaland ventral respiratory groups regulating phrenic nerveoutput from the cervical spine, located in the brainstem,are parasympathetic neurons (which also maintainsympathetic tone to heart and blood vessels). The output of

these neuclei is coordinated to produce the physiologicalpattern associated with vomiting.

The vomiting reflex is divided into two phases.

1. Pre-ejection phase : This is characterized by asensation of nausea associated with cold, sweating,pupil dilatation, salivation and tachycardia mediatedby sympathetic and parasympathetic nerves.

2. Ejection phase : This comprises of retching andvomiting with expulsion of gastric contents.

Causes of vomiting1. Pharyngeal stimulation.2. Gastrointestinal distension.3. Abdominal surgery.

4. Anaesthetic agents.5. Pain.6. Opioid medication.7. Hypoxia.8. Hypertension.9. Vestibular disturbances.10. Psychological factors.

Factors influencing post operative emesisThe etiology of emesis is multifactorial. The factors

could be classified in the appropriate temporal sequence

in which the patient is exposed.1. Patient factors.2. Preoperative factors.3. Intraoperative factors : Anaesthetic factors

Anaesthesia techniquesSurgical factors

4. Post operative factors

Patient factorsa) Age : The incidence of PONV is 5% in infants, 25%

below 5 years, 42-51% in the 6-16 age group and14-40% in adults.

b) Gender : Adult women are 2-4 times likely to suffer from PONV than men, may be because of femalehormones.

c) Obesity : These patients are reported to have morePONV probably because either the excessive adiposetissue serves as storage for anaesthetic agents or because of excessive production of estrogen byadipose tissue.

d) H/O motion sickness : Patients who are susceptible tomotion sickness are predisposed to PONV.

Fig. 1 : Pharmacologist view of emetic stimuli

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SAEEDA, JAIN : PONV : A REVIEW 257

Manual electrical stimulation of the P-6 acupuncturepoint (Neiguan) by needle results in decrease in incidenceof PONV upto 6 hours. Application of pressure on P-6

point every 2 hours is reported to produce effect for 24 hours.

Key points for clinical practice Establish which patients are at high risk for PONV

or in whom PONV would compromise the outcome.Provide optimum prophylaxis.

Use of propofol, an I.V. anaesthetic with intrinsicantiemetic activity.

Avoid opioid if possible by liberal use of NSAIDSand local anaesthetic techniques.

Avoid sudden movements and change of posture

during recovery. Early intake of food and drink postoperatively should

be discouraged. If emesis dose occur rescue therapy with an antiemetic

and attention should be given to hydration and painmanagement.

If one antiemetic is unsuccessful a multimodal drugregime with different mechanisms of action shouldbe tried.

At all times the patients should be reassured.

References1. Brunton LL . Agents effecting gastrointestinal water influx and

motility. In: Hardman JG, Limbird LE, Molinoff PB, ReddonRW, editors. Goodman and Gillmans The pharmacological basisof therapeutics. 9 th eds. New York McGraw-Hill, 1996; 917-36.

2. Andrew PLR. Physiology of nausea and vomiting. Br J Anaesth1992; 69: 2-19.

3. Rowbotham J : Current management of postoperative nauseaand vomiting. Br J Anaesth 1992; 46-59.

4. Lerman J : Surgical and patient factors involved in postoperative nausea and vomiting. Br J Anaesth 1992; 69:24-32.

5. Palazzo MGA,Strumin A : Anaesthesia and emesis : Etiology.Can Anaesth Soc J 1984; 31: 178-187.

6. Maddali MM, Mathew J, Fahr J et al . A prospective studyof postoperative nausea and vomiting in a tertiary care hospitalin Oman. Middle East J Anaesthesiol 2003; 17(1): 131-41.

7. Kapur P A : The big little problem. Anesth Analg 1991; 73:243-245.

8. McKay WP, Yip RW . Distribution of randomised controlledtrials of drugs for postoperative nausea and vomiting. Can JAnaesth 2000; 47(5): 421-26.

9. Watcha MF . Postoperative nausea and emesis : Anesth Clin North America 2002; 20(3): 471-84.

Table - 2 : Receptor specific antiemetic effects.

Group and drugs Mechanisms of action Side effects

D2 M H2 5HT PHENOTHIAZINES

1. Fluphenazine + + + + + + + - Sedation2. Chlorpromazine + + + + + + + + + + + Extrapyramidal side

effects3. Prochlorperazine + + + + Cholestatic jaundice4. Promethazine Hemolytic abnormalities5. Perphenazine Skin sensitization6. Trifluperazine Hypotension

ANTIHISTAMINICS1. Diphenydramine + + + + + + + - Sedation2. Dimenhydrinate Drowsiness3. Promethazine + + + + + + + + - Depression4. Cyclizine Dry mouth5. Meclizine6. Hydroxyzine

BUTYROPHENONES1. Haloperidol + + + + - + + Drowsiness2. Droperidol + + + + - + - Restlessness,

hallucinations3. Domperidone + + + + - Extrapyramidal side effects

ANTICHOLINERGICS Hyoscine / scopolamine + + + + + + - Dryness of mouth,

/atropine tachycardia, mydriasis,retention of urine,somnolence

PROKINETICS1. Benzamides

Metoclopramide + + + - + + +2. Thiobenzamides Dysrrhythmias,

galactorrhoea3. Benzimidazole Gynaecomastia

derivative AmenorrhoeaDomperidone Constipation/Diarrhoea

4. Benzamide derivatives Extrapyramidal sideCisapride/Alizapride/ effects DrowsinessClebopride Hypertensive crisis

5. Substituted BenzamideBatanopride/Zacropride

5-HT 3 ANTAGONISTS Ondansetron - - - + + + + Allergic reactions Granisetron Dysarrhythmia Tropisetron Bronchospasm Dolasetron Blurred vision

OTHERS1. Corticosteroids

Dexamethasone and They enhances the anti-emetic Hyperglycaemia and m ethylprednisolone e ffic acy o f o th er d ru gs p sychotic rea ction etc.

2. Cannabinoids D 9 tetrohydro- Hallucination cannabinoid Dronabidol Disorientation Nabilone Vertigo

3. Benzodiazepins Lorazepam Sedative, anxiolytics Sedative Alprazo lam Amnesia, enhance e ffectiveness

of antiemetic regiments4. Clonidine and ephedrine

Abbreviations: D 2;Dopamine type 2 receptor, M; Muscarinic, H 2; Histamine type 2 receptor 5-HT 3; serotonin type 3 receptor

2. Non-pharmacological approachv Acupuncture 17

v Acupressure 18

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10. Kazemi-Kjellberg F, Henzi I, Tramer MR . Treatment of established postoperative nausea and vomiting. A quantitativesystemic review. BMC Anaesthesiol 2001; 1(1): 2.

11. Gold BS, Kitz DS, Lecky JH, Neuhans JM . Unanticipatedadmission to hospital following ambulatory surgery. JSMA1989; 262: 3008-10.

12. Raftery S, Sherry E . Total intravenous anesthesia with propofoland alfentanyl protects against postoperative nausea andvomiting. Can J Anaesth 1992; 39: 37-40.

13. Borgeat A, Wilder Smith OH, Wilder Smith CH, Forni Sukr PM : Propofol improves patients comfort during cisplatinchemotherapy. A pilot study. Oncology 1993; 50: 456-59.

14. Schulman ST, Rockett CB, Canada AT, Glass PS . Long term propofol infusion for refractory postoperative nausea. casereport with quantitative propofol analysis. Anesth Analg 1995;

80: 636-637.15. Loewen PS . Antiemetics in development. Expert opin investig

Drugs 2002; 11(6): 801-805.

16. Ison PJ, Perontka SJ. Neurotransmitter receptor bindingstudies predict antiemetic efficacy and side effects. Cancer treatment reports.1986; 70: 637-41.

17. Sinclair DR, Chung F, Mezei G. Can postoperative nausea andvomiting be predicted. Anesthesiology 1999; 91: 109-118.

18. Fry ENJ. Acupressure and postoperative vomiting (letter).Anaesthesia 1986; 41: 661-62.

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