Postoperative nausea and vomiting (PONV) is a common issue, affecting approximately 35% of patients. It can decrease patient satisfaction and potentially increase recovery time. Several risk factors are identified, including female sex, history of motion sickness, nonsmoking status, and opioid use. Guidelines recommend stratifying patients into low, moderate, and high risk to guide appropriate prophylaxis and treatment. Common prophylactic medications include 5-HT3 antagonists, dexamethasone, droperidol, and anticholinergics. For high risk patients, combination therapy is more effective than single agents. Treatment focuses on 5-HT3 antagonists like ondansetron if prophylaxis fails. Multimodal prevent

1. Post Operative Nausea & Vomiting John Zois 2005

2. PONV Why is it Important? A very common problem in the ambulatory surgery patient population, occurring in an estimated 35% of all patients. If high-risk patients are considered as a separate group, then as much as 70% of these patients will experience PONV. Before the 1960s, when older inhalational anesthetic agents such as ether and cyclopropane were widely used, the incidence of vomiting in general population was as high as 60%. Patients rank PONV as one of the most unpleasant memories associated with their hospital stay. Patient satisfaction with their anaesthetic is highly linked to their experience (or lack of ) of PONV. In surveys, many state they prefer to experience pain than N&V. When severe it can lead to increased length of hospital stay, increased bleeding, incisional hernias and even life threatening aspiration pneumonia. Despite decades of progress in surgical and anaesthetic techniques, effective prevention and Tx of PONV has been elusive.

3. Physiology of PONV N + V can be induced by many factors (physiological, pathological and even psychological), as well as drugs or toxins. The part of the brain related to emesis is an ill-defined area located in the lateral reticular formation of the medulla. Afferent stimuli arrive from chemoreceptors and pressure receptors in the gut and CNS, as well as peripheral pain receptors. Other sites of input in the CNS include the cerebral cortex (pain, fear and anxiety), vestibular and cerebellar nuclei and the Chemoreceptor Trigger Zone (CTZ). The CTZ is outside the blood-brain barrier and is extremely sensitive to emetic stimuli. The neurotransmitters implicated in the control of nausea and vomiting include acetylcholine, dopamine and 5-HT. Hence anti-emetics have been targeted to antagonise one or more of these neurotransmitters.

4. Physiology of PONV

5. Consensus Guidelines Multidisciplinary panel of experts convened to review med literature on PONV (published till Feb 2002) Developed guidelines in risk stratification and treatment

6. Risk Stratification Postoperative nausea and vomiting is a multifactorial entity, comprising patient, surgical, and anesthetic factors. Due to the cost of pharmacological Tx of emesis, risk stratification is important. By focusing attention (and resources) on those groups of patients most likely to develop PONV, the overall cost of dealing with PONV is reduced. A number of studies have looked into PONV risk factors and risk stratification.

7. Risk Stratification Patient characteristics Female>male (x3) Incidence increases during menstruation and decreases after the menopause. After 70 years of age, both sexes are equally affected. Obese (suggested but no strong evidence). Age . POV in under 2yr olds is rare. From >3yrs to puberty, risk is higher than adults. Previous history of PONV/motion sickness Early ambulation, early postoperative eating and drinking. Anxiety

8. Risk Stratification Type of Surgery Intra-abdominal-laparoscopic Intracranial, middle ear Squint surgery The highest PONV risk surgery in children Gynaecological Esp ovarian ENT Especially T & As (? due to blood in upper GIT) Prolonged surgery Significant surgical pain

9. Risk Stratification Anaesthesia/drugs Opioids Well known for emetogenic potential but remember untreated pain can also be emetogenic Sympathomimetics Inhalational agents Isoflurane++, Etomidate, ketamine, methohexitone. Propofol considered one of the least emetogenic Nitrous oxide Prolonged anaesthesia Spinal anaesthesia (blocks above T5), hypotension. Intraoperative & Preoperative dehydration Gastric dilatation Eg aggressive mask ventilation

10. Risk Stratification Pathology Intestinal obstruction Metabolic, e.g. hypoglycaemia Hypoxia Uraemia

11. Quick Risk Factor Chart Four primary Risk Factors Female Non Smoker History of PONV Opiod use No of Risk Factors vs Risk % None= 10% 2RF=40% 4RF=80% 1 RF= 20% 3RF=60%

12. Risk Stratification Low Risk of PONV pts No prophylaxis or minimal prophylaxis is likely the best choice Moderate Risk of PONV pts Prophylaxis followed by aggressive treatment if nausea and vomiting develop.

13. Risk Stratification High Risk of PONV pts Aggressive prophylaxis + treatment. Expensive but becomes cost-effective when the issues of patients satisfaction and avoidance of unplanned admission are considered. Multi-modal therapy widely accepted as providing the best results

14. Treatment Modalities Some of the treatments used around the world include: metoclopramide domperidone droperidol Dopamine antagonists dexamethasone Corticosteroid scopolamine (L-hyoscine) Anti-cholinergic promethazine Anti-histamine ondansetron , tropiseron, granisetron 5HT3-receptor antagonist

15. Pharmacology 5-HT3 antagonists ONDANSETRON Four types of serotonergic (5-HT) receptors (5-HT1-4). 5-HT1 receptors are subdivided further (5-HT1A etc). Ondansetron is a highly selective antagonist at 5-HT3 receptors; it has an affinity 250-1000 times greater for the 5-HT3 receptor than for any other receptor. The drug antagonises 5-HT3 receptors both centrally and peripherally. Emetogenic stimuli result in the release of 5-HT in the small intestine and initiate a vomiting reflex (via vagal afferents, via 5-HT3 receptors). Thus, Ondansetron blocks the initiation of this reflex. Drug of choice in children. Dose =350mcg/kg

16. Pharmacology Dexamethasone Recent evidence has shown that dexamethasone is effective prophylaxis for PONV, at least as effective as droperidol and the serotonin antagonists when used as a single agent. It is orders of magnitude cheaper than the 5HT3 anatagonists. Dose required for this effect is very low (eg 2.5-5 mg IV and as such it causes no significant side effects) given early during the anesthetic. However has no role in the treament of established PONV, thus serotonin antagonists remain the mainstay in such circumstances.

17. Pharmacology Droperidol (butyrophenone) For many years, droperidol (in very small doses) was very popular in any strategy against PONV. Droperidol is very effective in small doses (0.625-1.25mg) for the prevention and treatment of PONV and was once considered almost as a gold standard when it came to comparing the efficacy of other medications. Being very inexpensive also further added to its popularity. Unfortunatey its use has declined after its association with rare fatal arrythmias (although at higher doses)

18. Pharmacology Anticholinergics Used in the prophylaxis of motion sickness and as an antispasmodic. Competitive antagonism of acetylcholine at muscarinic receptors. Hyoscine has been shown to reduce postoperative nausea and vomiting related to opiods. It also decreases muscle tone and secretions in the gut, which may contribute to its antiemetic properties. Hyoscine

19. Pharmacology Metoclopramide Antagonism of peripheral dopaminergic D2 receptors. Results in increased gastrointestinal motility and tone. Although metoclopramide has prokinetic effects that enhance gastric and upper intestinal motility, it is no more effective as an antiemetic than a placebo according to some trials.

20. Combination Therapy If a dose of a single agent is ineffective, additional dose of same agent is unlikely to increase efficacy. In fact it is likely to increase the risk of side effects

21. Non Pharmacological Therapy Acupuncture, TENS, accupressure, hypnosis Have shown quite significant efficacy when used before surgery. Obviously cost and effort of administering is a big drawback

22. In Summary.. STEP ONE Identify Pts at risk Attempt to stratify in low, moderate and high risk group

23. In Summary.. STEP TWO Reduce Baseline Risk Factors Use Regional anaesthesia when possible Use propofol for induction and maintenance Use intra-operative supplemental oxygen Use hydration Avoid Nitrous oxide, volatiles Minimise opiod use Minimise neostigmine use

24. In Summary.. STEP THREE Prophylaxis for moderate & high risk Multimodal drug prophylaxis

25. In Summary.. STEP FOUR Aggressively Tx PONV For pts where prophylaxis failed or was not used Ondansetron as first line Tx Add additional agents if PONV continues

26. Remember… PONV is one of the most distressing aspects of an anaesthetic for a patient. Be aware of Risk Factors and give pre-emptive prophylaxis if suitable. It’s best (and easier) to prevent than to treat. Combination therapy is much more effective and associated with less risk than repeat doses of same agent.