PERIOPERATIVE CARE

© 2003 The Medicine Publishing Company Ltd335ANAESTHESIA AND INTENSIVE CARE MEDICINE

Postoperative nausea and vomiting (PONV) was recognized and described in 1848 by John Snow and remains a common post-operative complaint. It has an incidence of about 25% in adults, with a published range of 5–75%. PONV is distressing for the patient, can delay recovery from surgery, causes dehydration, electrolyte imbalance and wound dehiscence, interferes with oraltherapies and delays discharge from hospital, with associated costs.

Physiology of nausea and vomiting: nausea is often a precursor to vomiting and may be accompanied by sweating, salivation and pallor. The mechanism of action for this subjective symptom is unknown, though it has been suggested that a low level of sensory input to the emetic centres is responsible. Vomiting is co-ordinated by the vomiting centre, which lies in the dorsolateral reticular formation of the medulla, within the blood–brain barrier. It receives a multitude of afferents from the oropharynx, gastrointestinal tract, mediastinum, higher cognit-ive centres (visual, olfactory, vestibular and gustatory), and the chemoreceptor trigger zone (CTZ) (Figure 1). The main receptors

in the vomiting centre are acetylcholine (ACh), histamine- 1 (H1), opioid and neurokinin-1 (NK-1).The gastrointestinal tract is an important source of afferent input. The abdominal vagi conduct information to the vomiting centre from mechanoreceptors (gut distension and contractility) and chemoreceptors (pH and osmolar-ity). Stimulation of these nerves causes local serotonin (5-HT) and cholecystokinin (CCK) release, which may also stimulate the CTZ. The CTZ is in the area postrema in the lateral wall of the fourth ventricle. This is a very vascular region lying outside the blood–brain barrier, making it sensitive to any circulating emetic substances. The main receptors are dopamine-2 (D2), opioid and serotonin-3 (5-HT3). The vomiting reflex is controlled by efferents (V, VII, IX, XI and XII cranial nerves and some spinal nerves) from the vomiting centre. These cause the diaphragm to be fixed in mid-inspiration, the glottis to close and the abdominal wall muscles to contract. This raises intragastric pressure, the pylorus closes and the oesophageal sphincter opens, allowing food to be expelled into the oesophagus and pharynx. The soft palate contracts when the food reaches it, and rises so that food may be expelled through the mouth.

Treatment: the aetiology of PONV is multifactorial (Figure 2), and its management reflects this. Prophylaxis is preferable to treatment, because vomiting may be difficult to control once established. Care should be taken to ensure adequate intravenous hydration and oxygenation, and to avoid hypotension. Regional techniques may provide excellent analgesia while avoiding the use of opioids. Total intravenous anaesthesia using propofol and avoiding nitrous oxide gives good results.

Anti-emetic drugs: multiple neurotransmitters are involved in the stimuli for PONV and therefore no one anti-emetic is effective for all patients. Knowledge of the physiology of vomiting allows specific targeting of those receptors likely to be involved.Anti-emetic drugs can be classified pharmacologically as:• antidopaminergic drugs (D2-receptor antagonists)• antimuscarinic drugs

Ruth Taylor is Anaesthetic SpR on the South West Rotation. She qualifi ed

from Charing Cross and Westminster Medical School, London. Her

interests include thoracic anaesthesia and diffi cult airway management.

Alison Pickford is Consultant in Anaesthesia and Intensive Care at the

Royal Cornwall Hospital, Truro. She qualifi ed from University College

Hospital, London. Her interests include ENT and paediatric anaesthesia.

Postoperative Nausea and VomitingRuth Taylor

Alison Pickford

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Physiology of nausea and vomiting

Sensory input (pain, smell, sight) Memory, fear, anticipation

Higher cortical centres

LabyrinthsGastrointestinal tract

AnaestheticsOpioids

Chemoreceptortrigger zone

Vomiting centre

Vomiting reflex

Neuronal pathways

Site of action of drugs

5-HT3

antagonist

H1 antagonistACh antagonistD2 antagonistCannabinoids

NK-1 antagonist

H1 antagonistACh antagonist

Receptor typesHistamine 1 (H1)Muscarinic (ACh)Dopamine 2 (D2)Neurokinin (NK-1)5 Hydroxytryptamine 3 (5-HT3)

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PERIOPERATIVE CARE

© 2003 The Medicine Publishing Company Ltd336ANAESTHESIA AND INTENSIVE CARE MEDICINE

• antiserotonergic drugs (5-HT3 receptor antagonists)• neurokinin-1 (NK-1) receptor antagonists• other (e.g. dexamethasone, cannabinoids, ginger root). D2-receptor antagonists include butyrophenones (e.g. droperi-dol), phenothiazines (e.g. prochlorperazine) and metoclopramide. They act predominantly on the CTZ. Metoclopramide also has pro-kinetic properties. They all have reasonable efficacy, but clinical use is limited by the extrapyramidal side-effects (tremors, dyskinesia,dystonia, occulogyric crisis) especially in children and young adults. Antimuscarinic drugs (e.g. atropine, hyoscine) cross the blood–brain barrier to act on the vomiting centre. Both drugs produce autonomic side-effects and reduce lower oesophageal sphincter opening pressure, predisposing to gastro-oesophageal regurgitation. Hyoscine also has sedative properties. Antihistamines (e.g. cyclizine) cross the blood–brain barrier to block H1 receptors competitively in the vomiting centre. Many also have significant antimuscarinic activity, which accounts for their side-effects (sedation, dry mouth). They are useful in motion sickness and labyrinthine disorders. Antiserotonergic drugs (e.g. ondansetron, granisetron) block 5-HT3 receptors throughout the gut and in the CTZ. They are useful in the prevention and treatment of PONV, but are relatively expensive. They have a good side-effect profile (i.e. headache, light-headed sensation, constipation) though there are concerns about arrhythmias and prolonged QTc with their use. NK-1 receptor antagonists (e.g. aprepitant) are the latest class of drugs being investigated. NK-1 receptors are in abundance in the brainstem close to the emetic centres and are stimulated by substance P. NK-1 receptor antagonists are thought to prevent vomiting itself rather than block afferent inputs to the vomiting centre. To date, their use in humans has been limited to patients receiving chemotherapy. They have been well tolerated and are particularly effective when used in combination with other anti-emetics, and in the treatment of delayed vomiting. Dexamethasone has useful anti-emetic properties, particularly when used in combination with other drugs. Its exact mechanism of action remains unknown. Nabilone is a synthetic cannabinoid, which has been used to prevent nausea and vomiting from chemotherapy. Its perioperative use has yet to be evaluated but may be limited by its side-effectprofile (sedation, euphoria, dysphoria, hallucinations, paranoia). Powdered ginger root (active component 6-gingerol) has been used medicinally since the 9th century and in trials had some anti-emetic effect when compared with metoclopramide. However, its mechanism of action and usefulness in modern practice need further investigation.

Choice of drug: comparative studies have shown similar efficacy for ondansetron, cyclizine, dexamethasone and droperidol, though their side-effects and expense differ. Combinations (balanced anti-emesis)have superior efficacy to single agents. Scoring systems allow identification and prophylactic targeting of patients at high risk of PONV. The Apfel score highlights the risk factors for PONV (female patients, history of PONV, non-smokers and the use of postoperative opioids), with each additional factor increasing the risk of PONV by about 20%. All patients, except those at low risk, should receive a single anti-emetic agent, those at moderate and high risk of developing PONV should receive two agents, and those with a very high risk (all four factors present) three agents. All patients should be prescribed rescue anti-emetics.

Timing of treatment: there is a rapid increase in emetogenic chemi-cal and physical stimulation leading to PONV during emergence from general anaesthesia. Administration of ondansetron at the end of anaesthesia (as opposed to the beginning) achieves effective drug levels during emergence, whereas dexamethasone is more effective given before induction of anaesthesia..

Physical treatment methods: acupuncture, acupressure and tran-scutaneous electrical nerve stimulation (TENS) techniques remain popular with some physicians though their exact mechanism of action remains unclear. They are a useful adjuvant in the treatment of PONV, especially when administered to conscious patients.

FURTHER READINGApfel C C, Kranke P, Eberhart L H et al. Comparison of predictive models

for postoperative nausea and vomiting. Br J Anaesth 2002; 88(2): 39–40.

Rittenberg C N. A new class of antiemetic agents on the horizon.

Clin J Oncol Nurs 2002; 6: 103–4.

Rowbotham D J. Post-operative nausea and vomiting – time for

balanced antiemesis? Br J Anaesth 2000; 85: 6675–6.

Strunin L, Rowbotham D, Miles A. The effective management of

postoperative nausea and vomiting. London: Aesculapius Medical

Press, 1999.

Sun R, Klein K W, White P F. The effective timing of ondansetron

administration in outpatients undergoing otolaryngologic surgery.

Anesth Analg 1997; 84(2): 331–6.

Wang J J, Ho S T, Tzeng J I, Tang C S. The effective timing of

dexamethasone administration on its efficacy as a prophylactic

antiemetic for postoperative nausea and vomiting. Anesth Analg

2000; 91(1): 136–9.

Factors affecting incidence of postoperative nausea and vomiting (PONV)

Patient Surgical Anaesthetic Postoperative

Age (peak 11–14 years) Gynaecological Opioids PainSex (F:M 3:1 from puberty to 70 years) ENT Inhalational agents Opioid analgesiaObesity Gastrointestinal surgery Nitrous oxide Early oral intakeHistory of PONV Laparoscopic surgery Induction agent (etomidate, thiopental) MovementHistory of motion sickness/migraine Ophthalmic surgery Hypoxia HypotensionNon-smoking history Testicular surgery Hypotension HypoxiaMenstrual cycle (luteal phase) Lengthy surgery Dose and duration of anaesthesia DehydrationAnxiety Insufflation of stomach PsychologicalFed/over-fasted state Anticholinesterases

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