Post-operative Nausea And Vomiting
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Postoperative nausea and vomiting (PONV) is the common complication of nausea, vomiting, or retching experienced by a person within the first 24 hours following a surgical procedure. Untreated, PONV affects about 30% of people undergoing
general anesthesia General anaesthesia (UK) or general anesthesia (US) is medically induced loss of consciousness that renders a patient unarousable even by painful stimuli. It is achieved through medications, which can be injected or inhaled, often with an analgesi ...
each year, with rates rising to 70–80% among those considered high-risk. Postoperative nausea and vomiting can be highly distressing for people undergoing surgery and may pose significant barriers towards recovery, cause surgical complications, and result in delayed discharge from the surgical center if not managed properly.


Cause


Risk factors

Risk factors for PONV can be classified into three main categories: patient-related, surgical, and anesthetic-related.


Patient-related

Patient factors that confer increased risk for PONV include female gender, younger age (<16 years old),
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
, non-smoking status, high levels of preoperative
anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, and prior history of PONV,
motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...
, or chemotherapy-induced nausea. The Apfel risk-scoring system is commonly used to sensitively and specifically determine the risk of PONV in adults. This simplified scoring system considers four primary predictors: # Female sex (most reliable) # Non-smoking status # History of PONV or motion sickness # Post-operative opioid use The presence of 0, 1, 2, 3, or 4 factors corresponds to PONV risks of approximately 10%, 20%, 40%, 70%, and 80%, respectively. Research has also shown a genetic disposition towards PONV. Certain procedure types such as gynecological, abdominal, laparoscopic, ENT surgeries, and
strabismus Strabismus is an eye disorder in which the eyes do not properly align with each other when looking at an object. The eye that is pointed at an object can alternate. The condition may be present occasionally or constantly. If present during a ...
surgery in children are associated with a modestly increased risk of PONV versus other general surgical procedures.


Anesthetic-related

The type of anesthetic medication plays a role in the risk for nausea and vomiting after surgery. Several medications routinely used in anesthesiology are believed to contribute to nausea and vomiting by acting on the highly sensitive chemoreceptor trigger zone (CTZ) located in the
area postrema The area postrema, a paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its role to detect circulating chemical messengers in the blood and tra ...
in the medulla oblangata, although the exact mechanisms remain poorly understood. Prolonged exposure to these drugs, namely volatile anesthetics,
nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or factitious air, among others, is a chemical compound, an Nitrogen oxide, oxide of nitrogen with the Chemical formula, formula . At room te ...
(N2O),
physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...
, and
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s has been found to be correlated with increased PONV risk. The approach taken to anesthesia may also play a role in the risk of nausea and vomiting post-operatively. A significant body of evidence indicates that
total intravenous anesthesia Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic age ...
(TIVA) using
propofol Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Nu ...
for induction and maintenance can reduce the incidence of postoperative nausea and vomiting significantly in both adults and children (3.5-fold vs. 5.7-fold reduction respectively) in comparison to volatile-anesthetic based techniques. Regional anesthesia has also demonstrated better outcomes for patients when compared to its general counterpart.


Mechanism

The pathophysiology of PONV is mediated by several key neurotransmitters, including
histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
,
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
,
serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
,
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
, and the more recently recognized neurokinin-1 (
substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a type of neuropeptide, belonging to the tachykinin family of neuropeptides. It acts as a neurotransmitter and a neuromodulator. Substance P ...
). Pharmacologic stimulation of different chemoreceptors in the brain trigger different pathways that can result in PONV. Additionally, direct surgical manipulation of the vestibular system (
cranial nerve VIII The vestibulocochlear nerve or auditory vestibular nerve, also known as the eighth cranial nerve, cranial nerve VIII, or simply CN VIII, is a cranial nerve that transmits sound and equilibrium (balance) information from the inner ear to the bra ...
) or gastrointestinal structures innervated by the vagus nerve ( cranial nerve X) can further activate the neural pathways involved in precipitating nausea and vomiting.


Prevention

Key strategies in the prevention of postoperative nausea and vomiting include diligent risk assessment and stratification, use of non-volatile anesthetic techniques when feasible, provision of preventative medications based on risk, and employment of multimodal, opioid-sparing techniques for surgical pain control. Optimizing intravascular fluid volume during surgery is another strategy to reduce the risk of PONV, often achieved by administering additional IV fluids under general anesthesia. This approach addresses the fluid deficit caused by preoperative fasting, which typically restricts oral fluid intake for 2–6 hours before surgery. There is some evidence that providing the person undergoing anesthesia with supplemental perioperative intravenous crystalloids may reduce vomiting and/or nausea in patients with certain characteristics ( American Society of Anesthesiologists (ASA) class I and II patients). The potential risks and other adverse effects with this type of therapy are unknown. For minor surgical procedures, more research is needed to determine the risks and benefits of this approach.


Management

Commonly administered medications like serotonin receptor antagonists (
ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by chemotherapy, radiation therapy, migraines, or surgery. It is also effective for treating gastroenteritis. It can be giv ...
), corticosteroids (
dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...
), and neurokinin-1 receptor antagonists ( aprepitant) primarily act by modifying the release and activity of the aforementioned neurotransmitters involved in nausea and vomiting, effectively reducing the incidence of PONV. Using a multimodal approach by combining drugs targeting different receptors involved in PONV has been shown to be more efficacious than monotherapy. However, numerous patient factors, adverse side effects, and cost-effectiveness of these medications must be taken into consideration when selecting a treatment regimen. Recent evidence has shown that alternative therapies may also play a role in decreasing the incidence of PONV when used in conjunction with conventional treatment.


Medications

* Serotonin (5-HT3) receptor antagonists can be administered as a single dose at the end of surgery. Adverse effects include prolongation of the
QT interval The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...
on electrocardiogram (EKG). Medications include
ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by chemotherapy, radiation therapy, migraines, or surgery. It is also effective for treating gastroenteritis. It can be giv ...
,
granisetron Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the ...
, and dolasetron. * Anticholinergics can be used as a long-acting patch placed behind the patient's ear. Adverse effects include dry mouth and blurry vision. Care must be taken when handling the patch, as transfer of medication to the eye can induce pupillary dilation. Avoid use in elderly patients. Medications include
scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...
. * Glucocorticoids have direct antiemetic effects and can reduce need for postoperative opioids. Adverse effects include a transient increase in serum glucose level, and poor wound healing (controversial). Medications include
dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...
. * Butyrophenones are antipsychotic medications that are typically administered as a single injection at the end of surgery. Medications include
droperidol Droperidol (Inapsine, Droleptan, Dridol, Xomolix, Innovar fentanyl.html" ;"title="ombination with fentanyl">ombination with fentanyl is an antidopaminergic medication, drug used as an antiemetic (that is, to prevent or treat nausea) and as an ...
and
haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...
, although droperidol is less frequently used as it may cause QT prolongation on EKG. * Phenothiazines are particularly effective in treating opioid-induced PONV. Adverse effects are dose-dependent and include sedation and
extrapyramidal symptoms Extrapyramidal symptoms (EPS) are signs and symptoms, symptoms that are wikt:archetypical, archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they ...
. Medications include
promethazine Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold a ...
,
chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...
and prochlorperazine. * Neurokinin-1 (NK1) receptor antagonists prevent emetic signals from being transmitted to the
area postrema The area postrema, a paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its role to detect circulating chemical messengers in the blood and tra ...
. Medications include aprepitant and rolapitant. * Histamine receptor antagonists can be administered by multiple routes, including orally, intramuscularly, or rectally. Adverse effects include dry mouth, sedation, and urinary retention. Medications include
dimenhydrinate Dimenhydrinate, also known as diphenhydramine/8-chlorotheophylline salt and sold under the brand names Dramamine and Gravol, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theocl ...
and
diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...
. * Propofol, an anesthetic medication, confers its own antiemetic properties. Current research has demonstrated that a combination of dexamethasone and ondansetron is the most common, and effective anti-emetic therapy for PONV. The literature also adds robust evidence towards the efficacy of drugs in newer classes, such as aprepitant or fosapreitant, or newer agents in familiar classes, such as ramosetron. However, given the poor cost effectiveness of the agents included and, despite increased efficacy for said novel agents, this may preclude their immediate utilization in anesthetic practice.


Alternative therapies

The management of perioperative pain using opioid-sparing multimodal analgesic techniques is critically important for reducing PONV incidence and achieving enhanced recovery after surgery. In addition to incorporating non-opioid analgesics like NSAIDs and
acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
, at least one study has found that application to the pericardium meridian 6
acupressure Acupressure is an alternative medicine technique often used in conjunction with acupuncture or reflexology. It is based on the concept of "life energy" (qi), which purportedly flows through "meridians" in the body. There is no scientific evidenc ...
point produced a positive effect in relieving PONV. Another study found no statistically significant difference. The two general types of alternative pressure therapy are sham acupressure and the use of the P6 point. A 2015 study found no significant difference between the use of either therapy in the treatment or prevention of PONV. In a review of 59 studies, both therapies significantly affected the nausea aspect, but had no significant effect on vomiting. There is also some evidence suggesting that music interventions in the perioperative period can effectively reduce postoperative vomiting, although the impact of music therapy and interventions on nausea remains unclear. Oral ginger capsule consumption before surgery has also been shown to significantly reduced incidence of postoperative nausea and vomiting 6 hours following surgery when compared to placebo. However, further investigation evaluating ginger's efficacy against and with conventional anti-emetic prophylaxis is required to properly determine its use as a supplemental therapy. Cannabinoids have also been used for treatment of PONV, but its safety and efficacy are controversial.


Epidemiology

Typically, the incidence of nausea or vomiting after general anesthesia ranges between 25 and 30%. Nausea and vomiting can be extremely distressing for patients, and so is one of their major concerns. Vomiting has been associated with major complications, such as pulmonary aspiration of gastric content, and might endanger surgical outcomes after certain procedures, for example after maxillofacial surgery with wired jaws. Nausea and vomiting can delay discharge, and about 1% of patients scheduled for day surgery require unanticipated overnight admission because of uncontrolled PONV.


References


Further reading

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External links

{{Anesthesia Anesthesia Vomiting