Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist, and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

The physiology of nausea and vomiting is poorly understood. The initiation of vomiting varies and may be due to motion, pregnancy, chemotherapy, gastric irritation or postoperative causes. Once initiated, vomiting occurs in two stages, retching and expulsion. The muscles responsible for this sequence of events are controlled by either a vomiting centre or a central pattern generator, probably in the area postrema and the nearby nucleus tractus solitarius. Drugs which induce vomiting include ipecacuanha, a gastric irritant, and apomorphine, a dopamine-receptor agonist. Opioid drugs also induce vomiting, but opioid antagonists are not useful to treat nausea and vomiting. Anti-emetic drugs consist of a variety of neurotransmitter antagonists and may act in the periphery, the central nervous system or both sites. The most important drugs are antagonists at muscarinic, dopamine D₂, 5-HT₃, histamine H₁ and neurokinin NK₁ receptors. These drugs are discussed with particular attention to post-operative nausea and vomiting (PONV).     

Postoperative nausea and vomiting

Despite many medical advances, the incidence of postoperative nausea and vomiting (PONV) and postdischarge nausea and vomit-ing (PDNV) remains high. Sequelae such as dehydration, wound dehiscence, bleeding and others, contributed to increased healthcare costs and patient dissatisfaction. This article reviews the literature regarding the anatomy of emesis, the predictors of PONV and various treatments.     

Postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) remains a common clinical problem that increases patient morbidity, healthcare costs and affects patient satisfaction. This article outlines the physiology, reviews the available drugs and suggests a structure using risk stratification that helps to plan sensible clinical management.     

Postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) is a major cause of morbidity and patient discomfort. Many patients fear vomiting as much as, if not more than pain.PONV may also have an economic impact. In day-case surgery, PONV may result in delayed discharge or even overnight admission. On average, 30% of surgical patients suffer PONV symptoms but after day-case gynaecological laparoscopic surgery the incidence exceeds 50%.In the last decades, a vast amount of research has been performed in this area and new antiemetic drugs and interventions have been introduced. However, no ‘gold standard’ antiemetic intervention has been found and the incidence of PONV is still significant. The mechanism of stimulation of emesis and the factors incriminated in the development of PONV are discussed. The impact of these factors on PONV and the calculation of risk scores are presented. The antiemetic drugs as well as the non-pharmacological techniques used for prophylaxis and treatment of PONV are also reviewed.     

Postoperative nausea and vomiting

Worldwide, approximately 80-100 million surgical procedures are performed under general anaesthesia each year. Despite major advances in surgical techniques and the introduction of new anaesthetic agents with reduced emetogenicity, the incidence of postoperative nausea and vomiting (20-30%) has remained largely unchanged over the past few decades. Postoperative nausea and vomiting are of greatest concern after ambulatory surgical procedures because they may delay discharge and result in unanticipated hospital admission, thus increasing the cost of the procedure by a large margin. This review discusses the current status of the antiemetic therapy of postoperative nausea and vomiting.     

Postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) is a prevalent side effect following general anaesthetic and surgery. Areas of the brainstem that coordinate the process of vomiting receive inputs from a number of areas, including high cortical areas and, importantly, the chemoreceptor trigger zone of the area postrema in the medulla oblongata of the brainstem, which can be affected directly by anaesthetic agents. A number of risk factors for PONV have been identified, and scores developed to help stratify risk. Based on this stratified risk pharmacological therapy can be given prophylactically intraoperatively, or as rescue postoperatively. The mechanisms and side effects of these drugs is discussed alongside a recent review of efficacy, and some potential future developments.     

Postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) remains a common clinical problem that increases healthcare costs and affects patient satisfaction and morbidity. This article outlines the physiology, reviews the available drugs and suggests a structure using risk stratification that helps to plan sensible clinical management.     

Postoperative nausea and vomiting

Numerous pathophysiological mechanisms are known to cause nausea or vomiting but their role for postoperative nausea and vomiting (PONV) is not quite clear. Volatile anesthetics, nitrous oxide and opioids appear to be the most important causes for PONV. Female gender, non-smoking and a history of motion sickness and PONV are the most important patient specific risk factors. With these risk factors an objective risks assessment is achievable as a good rational basis for a risk dependent antiemetic approach: When the risk is low, moderate, or high, the use of none, a single or a combination of prophylactic antiemetic interventions seems to be justified. Performing a total intravenous anesthesia (Ti.v.A) with propofol is a reasonable prophylactic approach, but does not solve the problem satisfactorily alone if the risk is very high, reducing the risk of PONV only by 30%. This is comparable to the reduction rate of antiemetics, such as serotonin antagonist, dexamethasone and droperidol. It must be stressed that metoclopramide is ineffective. Data from IMPACT indicate that prophylaxis is not very effective if the patients risk is low. At a moderate risk the use of Ti.v.A or an antiemetic is reasonable and only a (very) high risk justifies the combination of several prophylactic antiemetic interventions. For the treatment of PONV an antiemetic should be chosen which has not been used prophylactically. The necessary doses are usually a quarter of those needed for prophylaxis.     

Post-operative nausea and vomiting

Post-operative nausea and vomiting (PONV) is a common clinical problem with widespread effects on morbidity, patient satisfaction and cost. Although a myriad of risk factors have been postulated as having the potential to increase its incidence, a risk scoring system using four factors – female sex, non-smoking status, past history of PONV and use of post-operative opioids – identifies most at-risk individuals. Prevention and treatment is multi-factorial and aimed at risk-reduction, pharmacological and non-pharmacological techniques.     

Controlling postoperative nausea and vomiting

Postoperative nausea and vomiting (PNV) in the ambulatory surgical unit is a continuing and vexing problem. Delayed discharges and patient discomfort have major impact in an outpatient setting. An understanding of the causes and aetiologies of PNV including anaesthetic, surgical and patient factors is critically important in the management of these patients. Therapy begins with a good history, identification of patients at risk, and the use of appropriate anaesthetic technique and agents, as well as prophylactic treatment. Aggressive postoperative treatment is also a necessity and good communication between the staff, and the patient and their family, is essential. Postoperative nausea and vomiting can be controlled in the outpatient setting, leading to better patient outcome and satisfaction, as well as a smoother and more efficiently functioning ambulatory unit.     

Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment

Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Espa?ola de Anestesiología y Reanimación. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol.