Postoperative nausea and vomiting is a well recognised adverse effect of surgery and anaesthesia. It is invariably rated as the most unpleasant adverse effect experienced by patients. As well as being unpleasant for the patient (and caregivers) there can be a number of adverse effects arising from it:
Strain on suture lines
Prolonged hospital stay
Although the incidence will vary between groups, vomiting is quoted as occurring in around 30% of anaesthetics, with nausea in 50%.
The specific antiemetic agents are discussed elsewhere.
The full physiology of nausea and vomiting is complex and not completely understood. A vomiting centre can be considered to exist within the medulla. Although not a specific anatomical area, it can be considered as a collection of neurons with the function of triggering vomiting. This vomiting centre has a number of important afferent connections:
Chemoreceptor trigger zone
Vagal nerve - cardiovascular and abdominal afferent fibres, via the nucleus tractus solitarius (NTS)
Peripheral pain pathways
Higher cortical centres e.g. Limbic system
The chemoreceptor trigger zone (CTZ) is a particularly important afferent. This is found in the area postrema on the floor of the 4th ventricle, which is functionally outside of the blood brain barrier, and thus exposed to circulating chemicals (endogenous or otherwise).
The vomiting centre serves to coordinate these inputs into the vomiting reflex. These are enacted via the efferent fibres:
Abdominal wall muscles
This results in a characteristic chain of events, resulting in vomiting:
General relaxation of the stomach
Increased tone of upper jejunum and duodenum
Relaxation of upper part of the stomach
Organised contraction of the abdominal and respiratory muscles
There are a number of important neurotransmitters involved in this process. These are often a target for antiemetic therapy:
Serotonin (particularly via the 5HT3 receptor) acts as an important neurotransmitter in the pathways from the GI tract via the CTZ and NTS. Dopamine (via the D2 receptors) is an important neurotransmitter with many of the neurons in the brain e.g. neurons from the CTZ. Histamine (via the H1 receptors) has an association with emetic pathways from the vestibular systems, as does acetylcholine (via muscarinic receptors). Other molecules that are recognised as being involved in this signal transmission include substance P and neurokinin.
There are a number of known contributing factors to the risk of PONV. Patient factors
Gender (female RR 3)
Smoking status (non smoker RR 2)
History of PONV (RR 2)
Motion sickness (RR 2)
Volatile anaesthesia (RR 2)
Nitrous oxide (RR 1.4)
Duration of surgery
Surgical related (perhaps more controversial)
Gynaecological surgery (RR 1.2)
Laparoscopic surgery (RR 1.4)
Cholecystectomy (RR 1.9)
Strabismus surgery (in children)
Patient Factors The risk of PONV decreases with age. Being below the age of 50 has a RR of 1.79. Children are at particularly high risk, with the incidence peaking in the pre adolescent age group. Being female is associated with the strongest risk ratio for for PONV, with a risk ratio of about 3. This is suggested to be linked to the effects of oestrogen, as the effect is also related to the reproductive cycle. Being a non-smoker approximately doubles the risk of PONV. The reason behind this isn’t known, but one theory suggests that smoking induces the cytochrome p450 enzymes and thus results in faster clearance of emetogenic anaesthetic agents. Being susceptible to motion sickness is also associated with an odds ratio of around 2 for PONV.
Anaesthetic Factors Whilst it was previously thought that the benefits of TIVA were solely due to an antiemetic effect of propofol, volatile anaesthetic agents are well recognised as being emetogenic. The risk ratio is approximately 2, and is the most notable factor for PONV in the first 2 hours. In a similar way, nitrous oxide is well recognised for its emetogenic potential. This is quoted as a risk ratio of around 1.4, which is less than previously thought. This may be related to its central pharmacodynamic effects, as well as the physical effects of increasing the volumes of gas in the bowel and ear. An interesting paper reviewed here (http://www.rapidsequence.org.uk/blog/nitrous-nausea) suggests that this RR is duration based and that there is perhaps not a very high risk if the duration remains below an hour. As is well recognised, perioperative opioid use is associated with an increased PONV rate. This is quoted at around a RR of 1.5, is independent of the type of opioid but increases in a dose dependent manner. The recent consensus guidance suggested that it was primarily the postoperative opioid use that was important here.
Surgical Factors Although there has been some dispute about the impact of surgical factors on PONV, perhaps because of the presence of confounding factors e.g. being female for gynaecological surgery, there are some clear surgical risks outlined in recent guidance. Cholecystectomy is associated with a RR of around 1.9. Other laparoscopy surgery also has an increased association with a RR of about 1.4. As has been well recognised, gynaecological surgery has an increased risk, but only with a RR of around 1.2. Of particular note in children is strabismus surgery, which appears to be independelty related to PONV.
Disproved Factors A number of factors that were previously thought to contribute have since been disproved:
Use of supplemental oxygen
The aforementioned consensus statement on PONV assessment recommends using a risk stratification tool to provide a useful clinical application of these risk factors. The most common ones are:
Apfel Score 1 point for the following:
History of motion sickness or PONV
Postoperative opioids planned
An accumulated score provides the following approximated risk of PONV: 0 Points - 10% 1 Point - 21% 2 Points - 39% 3 Points - 61% 4 Points - 78%
The consensus guideline on PONV by the Society for Ambulatory Anesthesia is a very useful starting point for applying these aspects to clinical practice. (http://journals.lww.com/anesthesia-analgesia/Fulltext/2014/01000/Consensus_Guidelines_for_the_Management_of.13.aspx) Although not UK based, they provide a good overview for approaching the topic. There will of course need to be appropriate clinical adjustment based on the specific scenario, but this provides a good overall structure.
They suggest a structured approach to:
Assess the PONV risk
Reduce baseline risk factors.
Administer prophylaxis in patients at risk
Provide new agent treatment for patients with PONV
Assess the PONV risk They advise using the simple Apfel score to do this. This provides an easy to use rough appreciation of risk. The presence of other risk factors mentioned above will also clearly impact on this.
Reduce the baseline risk factors Although many factors are non-modifiable e.g. patient factors, nature of surgery, there are a number of factors which are. They advise:
Regional anaesthesia where possible
Use of propofol (as induction and maintenance agent i.e. TIVA)
Avoidance of volatile anaesthetic agents (as above)
Avoidance of nitrous oxide
Minimisation of opioid use - multimodal analgesia
Optimise hydration status
The use of propofol for maintenance of anaesthesia has a NNT to avoid PONV of around 5. Although nitrous does have some emetogenic effect, this is probably minimal in low risk patients, but should be considered. Because of the impact of opioid on PONV, a multimodal analgesia approach that can minimise (or avoid) their use is better. This might include the use of NSAIDs or other more novel analgesic agents.
Administer prophylaxis to at risk patients They recommend 1 to 2 prophylactic antiemetic agents being given to patients at moderate risk of PONV. They do go as far as to recommend all patients get prophylaxis, and suggest that low risk patients may benefit from a watch and see approach. Common first line agents are:
The effects of drug working at different receptors is additive and so combination prophylaxis is recommended.
Higher risk patients should receive at least 2 or more prophylactic measure.
Treat patients with PONV Patients with PONV should receive treatment, even if they received prophylactic measures. If they have received prophylaxis, then the drug should be from a different class of antiemetic Otherwise the first line agent is a 5HT3 antagonist.