Postoperative Nausea and Vomiting

Published on 27/02/2015 by admin

Filed under Anesthesiology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 4 (1 votes)

This article have been viewed 2774 times

Postoperative Nausea and Vomiting

It is estimated that up to 80% of patients experience postoperative nausea and/or vomiting (PONV) within the first 24 h after surgery. For most, PONV is easily manageable but for a smaller, ‘high risk’ cohort, symptoms can be distressing and disabling and, in some cases, have been described as worse than the pain of surgery. It is a common misconception that general anaesthetics are solely responsible for PONV because it is often forgotten that surgical procedures under anaesthesia involve not only a pharmacological but also a physical ‘assault’ on the patient. Fortunately, the multifactorial aetiology of PONV lends itself to interventions using a variety of different treatment options. Prevention, along with prompt and effective treatment of PONV, decreases the risk of adverse effects, limits the length of inpatient stay and reduces hospital costs. More importantly, successful prevention of PONV greatly improves patient satisfaction.

DEFINITIONS

Nausea is derived from the Greek word naus denoting ‘ship’ and was used originally to describe the feeling of seasickness. Nausea is an unpleasant sensation referred to the upper gastrointestinal tract and pharynx. It is associated with dizziness and a strong urge to vomit. Assessment of nausea is extremely difficult because symptoms are subjective, entirely patient-dependent and often difficult to quantify. For this reason, the incidence of postoperative nausea is frequently underestimated. Retching is the involuntary process of ‘unproductive vomiting’. It is characterized by the synchronous contraction of diaphragmatic and abdominal muscles against a closed mouth and glottis. Retching is extremely distressing and is usually accompanied by feelings of intense nausea. Vomiting represents the final common pathway of a highly coordinated sequence of events involving gastrointestinal, abdominal, respiratory and pharyngeal muscles which results in the active and rapid expulsion of contents from the stomach and upper intestine. In contrast to the rather subjective assessment of nausea, vomiting is easily identifiable and measurable!

MECHANISMS OF NAUSEA AND VOMITING

Vomiting Centre

The vomiting reflex probably developed as an evolutionary protective mechanism against ingestion of harmful substances or toxins. However, vomiting also occurs in response to a wide range of pathological and environmental triggers including sight, smell, motion and gastrointestinal disturbances. Afferent signals mediated by the vagus, vestibular and higher cortical nerves are carried to discrete areas within the brainstem collectively known as the ‘vomiting centre’ (Fig. 42.1). Traditionally, the vomiting centre was thought to be a single anatomical entity but there is increasing evidence that it is made up of a disparate group of interconnected cells and nuclei located in the lateral reticular formation of the medulla and the nucleus tractus solitarius (NTS). All information entering the vomiting centre is processed and co-ordinated (via autonomic and motor nerves) into a highly complex series of neuronal signals to initiate the three phases of the vomiting reflex.

Chemoreceptor Trigger Zone (CTZ)

The so-called ‘chemoreceptor trigger zone’ consists of several nuclei found within the area postrema at the caudal end of the fourth ventricle. Although the CTZ is anatomically located within the central nervous system, its unusual pattern of endothelial fenestrations allows it to ‘sense’ chemicals not only within cerebrospinal fluid, but also within circulating peripheral blood. In simple terms, the highly vascularized CTZ utilizes its defective blood brain barrier to detect potentially harmful substances present within the circulation. The CTZ contains an abundance of cholinergic, dopaminergic, histaminergic, serotinergic (5-HT) and opioid receptors which send afferent projections to the vomiting centre. Stimulation of the CTZ contributes significantly to the nausea and vomiting experienced by surgical patients, and pharmacological antagonism of receptor signalling within this important area represents a key strategy in the prevention and treatment of PONV.

Stimulation of the Vomiting Centre

Figure 42.1 outlines the various triggers and neural connections involved in the initiation of the vomiting reflex. The vomiting centre acts as the final processor for all sensory information received from central and peripheral receptors. Although the majority of afferent information from the periphery is relayed through the CTZ, other important causes of emesis are described below.

Gastrointestinal Tract

The normal functioning of the gastrointestinal (GI) tract is dependent on fully integrated neural feedback mechanisms. As part of this dynamic process, numerous mechano- and chemo-receptors send information to the central nervous system via the vagal nerve afferents. Any threat to the integrity of the GI system, e.g. gastric distension, irritation, damage or toxins, triggers an increase in ascending vagal activity which relays directly or indirectly to the vomiting centre. Cholinergic M1, serotoninergic 5-HT3 and dopaminergic D2 receptors are the principal mediators of signal transduction within the gut mucosa. Stimulation of one or all of these key receptors initiates a key step in the vomiting reflex and pharmacological antagonism at these sites represents a logical approach in the management of nausea and vomiting.

ADVERSE EFFECTS

Some clinicians dismiss PONV as an inevitable consequence of surgery but from the patients perspective PONV is almost always associated with distress and dissatisfaction. Importantly, if nausea or vomiting persist there is a risk of rare, but potentially serious, perioperative morbidity. These complications are summarized in Table 42.1.

TABLE 42.1

Adverse Affects of PONV

Patient distress and dissatisfaction

Pulmonary aspiration

Postoperative pain

Wound dehiscence/haemorrhage

 Eyes

 Head and neck

 Oesophageal

 Abdominal

Dehydration, electrolyte disturbance and/or requirement for intravenous fluids

Delayed oral input

 Drugs

 Nutrition

 Fluids

Delayed mobilization

Delayed discharge

Intact laryngeal reflexes ensure glottic closure during vomiting, but in the immediate postoperative phase, laryngeal reflexes may be obtunded due to residual effects of general anaesthesia and centrally acting analgesics. Vomiting can result in aspiration of gastric contents if the upper airway is not protected. The physical act of vomiting may lead to pain, wound dehiscence, haemorrhage, haematoma or possibly oesophageal rupture. If PONV persists, dehydration, reduced oral intake, electrolyte imbalance and delayed mobilization can result in serious medical complications and significantly increased healthcare costs associated with delayed discharge and unplanned admissions.

IDENTIFYING PATIENTS AT RISK

Many different approaches have been adopted in an attempt to stratify patients according to their individual risk of PONV. Risk stratification allows clinicians to optimize prevention and treatment strategies while minimizing the incidence of adverse drug reactions in patients at lower risk of PONV. Indiscriminate use of antiemetics in surgical patients is ill-advised and not cost-effective. A more logical and evidence-based approach involves identifying patients at moderate to high risk of PONV and prescribing appropriately.

Patient Factors

Although it is not possible to identify every patient at risk of PONV, a number of factors contribute to the incidence of nausea and vomiting in the postoperative period. The main factors are shown in Table 42.2. Numerous studies report that smoking habits, female patients and those with a history of PONV or motion sickness are all strong independent predictors for PONV. Delayed gastric emptying, anxiety and obesity may increase the risk of PONV but the evidence for a statistically significant association is currently lacking. Children over the age of 3 years are also at high risk of developing PONV in comparison to adults. Vomiting, rather than nausea, is often used as an outcome measure in paediatric studies because of the difficulty in assessing and quantifying nausea in young children. Fortunately, the risk of PONV decreases as children reach adolescence.

TABLE 42.2

Factors Which Increase the Risk of PONV

Patient

Female

Non-smoker

History of PONV or motion sickness

Children (age > 3 years)

Anaesthetic

Volatile anaesthetics

Opioids

Nitrous oxide

Postoperative pain

Hypotension

Neostigmine > 2.5 mg

Surgical

Duration

Type

 Gynaecological

 Squint

 ENT

 Head and neck

Anaesthetic Factors

Identifying specific anaesthetic triggers of PONV is difficult because of the large number of drugs given as part of a ‘standard’ general anaesthetic technique. However, the evidence for opioids and volatile agents inducing PONV is incontrovertible. Opioid administration by whatever route (oral, intramuscular, intravenous, epidural or spinal) is associated with a high incidence of PONV. Activation of peripheral and central opioid receptors by exogenous opioids leads to stimulation of the CTZ, direct activation of the vomiting centre and reduced gastric emptying. Increased sensitivity of the vestibular nerve (possibly as a result of activation of histaminergic H1 and muscarinic M1 receptors) may also play a role in the genesis of PONV. This is particularly prevalent during movement in the immediate postoperative phase. Preoperative opioids contribute towards a higher prevalence of PONV, but opioid-based premedication has largely been superseded by the use of non-opioid anxiolytic agents, e.g. benzodiazepines. Ineffective postoperative analgesia and pain can induce significant nausea and vomiting in susceptible individuals. In this situation, a non-opioid based analgesic approach is justified (e.g. simple analgesics and nerve blocks). Alternatively, careful titration of opioids may be appropriate.

Most intravenous anaesthetic induction agents induce PONV, but at subhypnotic concentrations, propofol exhibits some antiemetic activity. It is thought that this beneficial pharmacodynamic action is due to antagonism of dopaminergic D2 receptors. The increasing popularity of total intravenous anaesthesia (TIVA) techniques exploits the intrinsic antiemetic activity of propofol while avoiding the strong emetogenic stimuli from the volatile agents.

Evidence for the much-maligned nitrous oxide is less compelling. If used as part of a gas and oxygen mixture (e.g. Entonox), nitrous oxide has been shown to induce nausea and vomiting. However, studies using a combination of nitrous oxide with volatile agents do not report a consistently increased incidence of nausea and vomiting, particularly in patients at high risk of PONV.

The nondepolarizing neuromuscular reversal agent neostigmine has been implicated as a possible trigger for PONV. Anticholinesterase activity increases gastrointestinal motility and retrograde vagal nerve activity by activation of M1 receptors in the gut. However, these effects are normally antagonized by the co-administration of antimuscarinic agents, e.g. glycopyrrolate. It is only when higher doses of neostigmine are required (> 2.5 mg) that PONV becomes problematical.

Surgical Factors

Numerous studies have concluded that the type of surgery influences the risk of developing PONV. For example, stimulation of vestibular or pharyngeal nerves after ENT surgery is associated with an increased prevalence of emesis. Similarly, squint correction surgery (usually carried out in children) is reported to have a disproportionately high incidence of PONV. Patients undergoing gynaecological procedures are often recruited into studies to assess the efficacy of antiemetic drugs. However, it has been argued that many female patients are already at high risk of PONV, which places some doubt as to whether gynaecological surgery is an independent risk factor for PONV.

The cumulative doses of volatile agents and opioids are greater after lengthy surgical procedures, and therefore it is not surprising that the duration of surgery directly influences the number of patients experiencing PONV.

Post-Discharge Nausea and Vomiting (PDNV)

Increasing numbers of surgical procedures are now carried out on a day-case basis. Despite meeting strict discharge criteria, many patients experience PDNV after leaving hospital. Of those, up to 35% do not have any symptoms prior to discharge. One reason for this discrepancy relates to the relatively short half-lives of current antiemetic agents. Unfortunately, most patients have limited or no access to antiemetic treatment after discharge, which leads to delayed recovery and patient dissatisfaction. Prescribing antiemetic prophylaxis to every patient is neither beneficial nor cost-effective. Prophylaxis is best targeted towards patients at moderate to high risk of PONV, who should be offered oral antiemetics as part of their ‘take home’ prescription.

MANAGEMENT

Prevention

Prevention is the key to effective management of PONV. Identifying patients who are at risk of developing symptoms following surgery is the first step in this process. In simple terms, patients can be divided into three groups: low, moderate or high risk. Those at low risk do not require pharmacological intervention. Simply reducing or avoiding key triggers, e.g. opioids and/or volatile agents, may be sufficient to prevent the onset of PONV. Furthermore, prophylaxis for every patient is not necessary and adopting such a blanket approach may lead to adverse drug effects. For those at moderate to high risk, adopting a multimodal strategy, i.e. avoiding key triggers whilst giving one or more antiemetic, helps to reduce the risk of developing symptoms of PONV. For patients at highest risk, a combined approach usually works best, e.g. risk reduction measures in conjunction with increasing number of antiemetics.

Treatment

Despite careful planning and risk reduction, some patients still experience troublesome PONV. If so, it is vital that all possible causes of PONV are ruled out to avoid missing important signs of serious underlying pathology. The commonest causes of PONV are highlighted in Table 42.3. Each patient should be thoroughly assessed to exclude other treatable causes. Only when these have been excluded is it appropriate to consider an antiemetic treatment strategy. If antiemetic prophylaxis has already been given, repeat dosing may be required depending on the pharmacokinetic profile of the initial prophylactic agent(s), while bearing in mind that a second dose may be ineffective and might simply increase the risk of an adverse drug effect.

TABLE 42.3

Important Causes of PONV

Hypotension

Hypoxaemia

Drugs

Opioids

Antibiotics

Intra-abdominal pathology

Psychological factors e.g. anticipation/anxiety

Early mobilization

Fluid intake

Nasogastric tube

Pain

The next stage in treatment involves the use of various classes of drug targeting a range of different receptors. This logical approach maximizes pharmacodynamic efficacy whilst minimizing the risk of adverse drug events. For example, PONV prophylaxis using a glucocorticoid can be supplemented using one or more of the available D2, M1, H1 or 5-HT3 receptor antagonists.

PHARMACOLOGY

From an anaesthetist’s perspective, the numerous afferent and efferent components of the vomiting reflex lend themselves to pharmacological manipulation at multiple receptor sites within the peripheral and central nervous systems. Antagonism of one or more of the four key neurotransmitters involved in the vomiting reflex (dopamine, histamine, acetylcholine or 5-HT3) forms the basis of established treatment of PONV. Table 42.4 gives examples of the main classes of drug used worldwide for the treatment of nausea and vomiting. Not all are suitable or have been licensed for the treatment of PONV in the UK but are included in the table to indicate current or potential drug development strategies.

Dopamine D2 Receptor Antagonists

Peripheral and central dopaminergic D2 receptors are located within the gastrointestinal tract and the CTZ, respectively. D2 receptors mediate gastrointestinal activity and dopaminergic neurotransmission within the CTZ. The antiemetic efficacy of D2 receptor antagonists relates to a combination of increased gut motility and raising the emetogenic threshold within the CTZ. Butyrophenones, phenothiazines and benzamides act primarily as D2 receptor antagonists although most harbour cross-sensitivity with other receptor systems as shown in Table 42.5.

Butyrophenones

Droperidol was withdrawn from clinical practice in 2001 due to concerns over QTc prolongation following chronic treatment. After successful campaigning (mainly by anaesthetists), droperidol was reintroduced specifically for the acute management of PONV. It acts mainly as a D2 antagonist but it also has weak α1-adrenergic blocking activity. Intravenous droperidol administered 30 min before the end of surgery is economical and generally effective at reducing PONV and it can be co-administered with opioids using patient-controlled analgesia (PCA) pumps. Side-effects may limit treatment. These include sedation, extrapyramidal effects and gastrointestinal upset. Droperidol is contraindicated in patients with long QT syndrome.

Although not used routinely, oral domperidone may be prescribed to assist with the management of PONV. It is generally well tolerated and causes less central effects (mainly sedation) than many of the phenothiazines. Side-effects and contraindications are similar to those for droperidol although galactorrhoea and gynaecomastia can occur after chronic administration.

Phenothiazines

Phenothiazines were introduced originally to treat psychotic states including mania and schizophrenia. Subsequently, many were found to have useful antiemetic properties and are now used routinely during treatment of neoplastic disease. The main mechanism of action of the phenothiazines is via antagonism of the D2 receptor, but it is possible that some of their clinical effects are derived from blockade of other neurotransmitters involved in the vomiting reflex (Table 42.5). Prochlorperazine is used routinely in the treatment of PONV and labyrinthine disorders. It can be administered via intramuscular, oral or buccal routes. Side-effects include sedation, hypotension and extrapyramidal features.

Perphenazine is not licensed for treatment of PONV in the UK, but has proved to be useful as an oral antiemetic preparation.

Histamine H1 Receptor Antagonists

H1 receptors are located in the CTZ, vomiting centre and possibly the vestibular apparatus. Most antihistamine drugs display dual activity at histaminergic H1 and cholinergic M1 receptors. Increasing doses lead to D2 receptor blockade. Combined activity at H1 and M1 receptors makes antihistamines particularly useful in the treatment of motion sickness. Cyclizine is used routinely for PONV because it has less central sedating effect in comparison with other drugs in its class. It can be administered via oral, intramuscular and intravenous routes. Side-effects include dry mouth, sedation and blurred vision, all of which are related to inherent anticholinergic activity. Rapid intravenous injection of cyclizine induces tachycardia and it should be used with caution in patients with heart failure.

Serotonin 5-HT3 Receptor Antagonists

5-HT3 antagonists are indicated for use in the management of PONV and in the management of nausea and vomiting induced by chemo-radiotherapy. 5-HT3 receptors are located in the CTZ, vomiting centre and the gastrointestinal tract. 5-HT3 plays an important role in detecting and transmitting emetogenic signals from the CTZ to the vomiting centre whereas peripheral 5-HT receptors stimulate vagal afferents in response to damaging stimuli within the gut mucosa. 5-HT is also released in the area postrema in response to increased vagal activity. Therefore, it is likely that the efficacy of 5-HT3 antagonists is due to a combination of central and peripheral effects.

Ondansetron and granisetron are both licensed for treatment of PONV in the UK. Ondansetron has a shorter half-life than granisetron and can be administered via oral, intramuscular, intravenous or rectal routes. Although other 5-HT3 receptor antagonists (including topisetron and dolasetron) exist, they are not currently available in the UK. Ondansetron and granisetron are free from sedative and extrapyramidal side-effects, but in susceptible individuals they may induce QTc prolongation and abnormal liver function tests.

Substance P (NK1) Antagonists

Substance P, neurokinin A (NKA) and neurokinin B (NKB) are genetically related neuropeptides (tachykinins) which activate G-protein-coupled NK1, NK2 and NK3 receptors within peripheral and central compartments. Substance P is thought to play a key role in the generation of emetogenic stimuli by binding to NK1 receptors in the gut and also centrally within the nucleus tractus solitarius and area postrema. In theory, blocking substance P activity should be highly effective in the treatment of PONV but NK1 antagonists are no better (i.e. non-inferior) at reducing postoperative nausea than standard ondansetron therapy. In contrast, they can significantly reduce the incidence of postoperative vomiting. Further investigation of NK1 antagonists is needed to determine whether they have a place in the management of PONV. Two NK1 antagonists (aprepitant and its i.v. formulation, fosaprepitant) are licensed for use in the UK, but both are currently restricted to treatment of chemotherapy-induced nausea and vomiting (CINV). To date, no serious adverse effects have been attributed to the use of NK1 antagonists.

Related posts:

Anaesthesia for ENT, Maxillofacial and Dental Surgery Complications During Anaesthesia Preoperative Assessment and Premedication Basic Physics for the Anaesthetist Management of the Difficult Airway Anaesthesia Outside the Operating Theatre