Postoperative nausea and vomiting in neurosurgical patients: Current concepts and management
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.236970
Source of Support: None, Conflict of Interest: None
Keywords: Antiemetic agents, neurosurgery, postoperative nausea and vomiting, risk factors
Nausea and vomiting are common and distressing complications after anesthesia and surgery, especially after neurosurgical procedures. Nausea is defined as an unpleasant sensation with an urge to vomit, while vomiting is the event of forceful expulsion of stomach contents. Postoperative nausea and vomiting (PONV) can be classified as 'early' (occurring within 0–2 hours after surgery) and 'late' (occurring from 2 to 24 hours after surgery). 'Post-discharge' nausea and vomiting (PDNV) can be defined as the presence of symptoms from 24 hours following the discharge up to 72 hours. For neurosurgical patients, the incidence of PONV has been reported to be as high as 55–70%.,,
PONV leads to various complications including fluid and electrolyte imbalance, airway compromise, venous hypertension, wound dehiscence, and surgical site hematoma. The high intra-abdominal and intrathoracic pressures (>100 mmHg) generated during the ejection phase of vomiting is directly transmitted to the intracranial cavity, resulting in increased intracranial pressure. In addition to this, the risk of aspiration is also high in neurosurgical patients due to depressed neurological status or weakened airway reflexes. Thus, the increased risk in patients due to the presence of PONV should be identified and effort should be made to reduce its incidence by timely intervention.
Pathophysiology of nausea and vomiting
The vomiting center (VC) and chemoreceptor trigger zone (CTZ) are the prime centers in the brain that are involved in the genesis of PONV [Figure 1]. The VC is located in the lateral reticular formation of the brainstem. It receives afferent fibers from higher cortical centers, as well as the cerebellum, vestibular apparatus, and vagal and glossopharyngeal nerves. The efferent fibers from VC travel through glossopharyngeal, vagus, hypoglossal, trigeminal, facial, and spinal nerves to the gut, diaphragm, and abdominal muscles, with all of them coordinating to generate vomiting. The CTZ lies in the area postrema in the floor of the IV th ventricle, which is situated outside the blood–brain barrier, a location that renders it more sensitive to chemical stimuli such as drugs and toxins. Various neurotransmitters are known to participate in the genesis of PONV including histamine, serotonin, dopamine, acetylcholine, and the recently discovered, substance-P. These neurotransmitters act through various receptors such as H1-receptors, dopamine-D2 receptors, 5-HT3 receptors, muscarinic receptors, and neurokinin-1 receptors.
Risk factors for postoperative nausea and vomiting
Multiple risk factors have been described for the general surgical population, which can be categorized as patient factors, surgical factors, and anesthetic factors [Table 1]., A simplified score given by Apfel et al., describe four predictors for PONV including the female gender, the history of motion sickness or PONV, the use of postoperative opioids, and a nonsmoking status. In this score, each factor was given a score of 1. A total score of 0, 1, 2, 3, or 4 of these risk factors increases the risk of PONV by 10%, 20%, 40%, 60%, and 80%, respectively. The risk for PONV increases if neurosurgical patients also possess other established risk factors. A few risk factors described in various studies are enumerated in [Table 2].,,,,,,,
Various studies comparing the location of the surgical site with the incidence of PONV found that infratentorial surgeries are more at risk than supratentorial surgeries.,, This incidence increases manifolds during the Vth cranial nerve decompression as compared to decompression of the cranial nerves VII, IX, or X. The hypothesis that has been implicated in an increased incidence of vomiting following infratentorial surgeries was the direct manipulation of the vomiting center  during resection of infratentorial lesions. Resection of acoustic neuromas might manipulate the vestibular apparatus leading to the increased risk of PONV. A few studies  have reported that PONV is more common after spinal surgeries than intracranial surgeries while other studies , failed to cite such a difference. Various studies describe the incidence of PONV after spinal surgery ranging from 50–60% and mostly related to the use of infusion of opioids in patient-controlled pump systems., Additives such as ketamine and dexmedetomidine in the opioid infusion pumps are reported to decrease the incidence of PONV after spine surgery.,
Anesthetic techniques also affect the incidence of PONV. Manninen et al., observed a significantly lesser PONV after awake anesthesia as compared to general anaesthesia. This difference was sustained only during the first four hours postoperatively, and thereafter, no such difference was observed. They postulated that the patients undergoing awake craniotomy received more propofol, which has inherent antiemetic effects, while the patients in whom craniotomy was done under general anesthesia received more intraoperative opioids, nitrous oxide, and neostigmine. The latter medicines contributed to the higher incidence of PONV in this group.
During endonasal trans-sphenoidal procedures, patients requiring intraoperative fat graft or intraoperative lumbar drain as a prophylactic maneuver against the development of cerebrospinal fluid leak were found to have a higher risk of PONV. The role of low cerebrospinal fluid pressure or a change in cerebrospinal fluid (CSF) dynamics was suggested as the possible casual factors in triggering PONV.
The histopathological characteristics of intracranial tumors (benign versus malignant) and midline shifts were not found to determine the risk of PONV.,
Apfel et al., reported that total intravenous anesthesia (TIVA) reduces the risk of PONV by 18.9% in high-risk general surgical patients. However, since neurosurgical patients were not included in this trial, these findings cannot be extrapolated to this population. In another study, TIVA decreased the incidence of PONV only in patients who underwent supratentorial craniotomy but not in those who underwent infratentorial surgeries.
Management of postoperative nausea and vomiting
Antiemetic agents are associated with severe side-effects ranging from mild headache to severe QTc (QT interval corrected) prolongations or cardiac arrest. Hence, the risk of side-effects and unnecessary cost of antiemetic medications must be weighed against the harmful effects of vomiting in neurosurgical patients. The multidisciplinary international panel of the Society for Ambulatory Anaesthesia (SAMBA) updated their guidelines to successfully manage PONV. These guidelines provide up-to-date information about strategies for the prophylaxis and treatment of PONV.
Management of postoperative nausea and vomiting in neurosurgical patients
Identification of patients at high risk for the development of postoperative nausea and vomiting
To identify the risk of PONV, one should combine the general risk scores as well as neurosurgical risk factors, as described in previous sections.
Reduction in baseline risk factors for postoperative nausea and vomiting
The incidence of PONV can be significantly decreased by reducing the baseline risk factors, as advised by the expert panel recommendations [Table 3].,,,,,,,,, PONV is less commonly seen if propofol is used for both induction as well as maintenance of anesthesia, and if nitrous oxide is avoided. Perioperative hypotension might decrease cerebral blood flow, leading to brainstem (VC and CTZ) ischemia that induces nausea and vomiting. Hence, prevention of hypotension and maintenance of a good hydration has been shown to reduce the incidence of PONV. Pain itself increases the incidence of PONV and opioid analgesics multiply it further. An adequate control of pain using multimodal analgesics as well as techniques such as regional blocks, reduces the dose of perioperative opioids. Abrupt changes in head position, such as sudden head-up position or head rotations, might trigger vomiting by stimulation of the vestibular apparatus. A slow and controlled positioning as well as reduction in noise and brightness might reduce the risk of PONV.
Administration of postoperative nausea and vomiting prophylaxis using 1 to 2 interventions
In neurosurgical patients, the prevalence of PONV is reported to be more than 70% in the absence of a prophylactic agent. As we know that PONV is triggered through multiple pathways and receptor systems, a combination of drugs acting at different receptors would have a greater efficacy than a single drug. The multimodal technique offers the benefits of dose reduction of the antiemetic agents, rendering a lower incidence of side-effects and maintaining a superior efficacy. Various antiemetic agents for PONV prophylaxis in adults include 5-hydroxytryptamine (5-HT3) receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, corticosteroids, butyrophenones, antihistamines, and anticholinergics [transdermal scopolamine (TDS)]. A few studies have shown that gabapentin also has some role in refractory PONV. As a sole agent, none of the medications is efficacious in high-risk patients for the prophylaxis of PONV. Various antiemetic agents, their dosage, mechanism of action, timing of administration, and common side effects are mentioned in [Table 4].
5-HT3 receptor antagonists are the most commonly used first-line agents used in preventing PONV. These agents are devoid of sedative and extrapyramidal side effects that makes them a favorable option in neurosurgical patients. None of the 5-HT3 antagonists are found to be superior or possessing lesser side-effects than other drugs of this class., The corticosteroid, dexamethasone, is another drug that is widely used for PONV prophylaxis and is as efficacious as ondansetron. It is recommended that dexamethasone be administered after induction of anaesthesia as its onset of action is delayed but is prolonged. Dexamethasone-induced hyperglycemia might be deleterious to neurosurgical patients. Hence, it is recommended to closely monitor blood sugar levels while using this drug. The sedative side-effects of certain drugs (anticholinergics, antihistamines, benzamides, and butyrophenones) interfere with neurocognitive monitoring and preclude their use in neurosurgical patients.
A double-blind randomized controlled trial was conducted in our institute by Wig et al. In the study, 70 adult patients of either gender who received preoperative steroids (dexamethasone) for at least 24 hours and were scheduled to undergo a craniotomy for supratentorial tumors, were included. The patients were randomized either in group O, received ondansetron 4 mg intravenously, or group S, received 0.9% saline intravenously at the time of dural closure. The authors found that the 6-hour postoperative nausea score was significantly lower in group O [median, 0; interquartile range (IQR), 0–20] than that in group S (median, 20; IQR, 0–20) [P< 0.05]. The incidence of vomiting was lower in group O (23%) than that in group S (46%) [P< 0.05]. The total number of emetic episodes, the number of doses of rescue antiemetics given in the first 6 postoperative hours, and the total number of rescue antiemetics given were significantly lower in group O than that in group S (P< 0.05).
Jain et al., compared ondansetron and granisetron with a placebo and found that the incidence of emesis was significantly lower in the ondansetron group (14.8%) and granisetron group (10%) compared with the placebo group (53%, P < 0.001) for 24 hours following a craniotomy.
Kathirvel et al., also found that ondansetron reduces the incidence of both nausea and vomiting in neurosurgical patients compared to the placebo (39% in the ondansetron and 11% in placebo group, P = 0.001) during the first postoperative 24 hours. All these studies recommend the routine use of ondansetron prophylaxis in neurosurgical patients.
For moderate-to-high risk patients, a combination therapy is considered to be more efficacious for prophylaxis of PONV. The drugs used for combination therapy should have different mechanisms and sites of action. As neurosurgery is considered to be of moderate-to-high risk for the development of PONV, triple-drug combination regimes are used in various studies.,, Various antiemetic agents (anticholinergics, antihistamines, benzamides, and butyrophenones) might cause sedation that interferes with neurocognitive monitoring and this factor often precludes their use in neurosurgical patients.
One such combination studied in neurosurgical patients includes droperidol, promethazine, and dexamethasone, which allows for the use of reduced dosage of each individual agent, when all three of the medications are used together. This practice was reduced after the United States Food and Drug Administration warnings and the contraindications highlighted during the usage of droperidol. Even though a 'black box' warning is issued for droperidol, it has been shown that, in clinically relevant dosage, the QTc prolongation caused by droperidol is equal to that caused by ondansetron. Another study replaced droperidol by transdermal scopolamine (TDS) in the triple-agent combination regime along with dexamethasone and ondansetron. TDS was found to be equally or more effective and was associated with a few undesirable side effects such as dry mouth, dizziness, blurred vision, and disorientation.
Recently, NK-1 receptor inhibitors are also being studied in neurosurgical patients. They are found to be more efficacious than 5HT3 receptor antagonists in preventing PONV in neurosurgical patients., Atsuta et al., compared fosaprepitant with droperidol and found that the incidence as well as frequency of vomiting was significantly lower in the fosaprepitant group for over 72 hours postoperatively.
Bergese et al., studied aprepitant in combination with promethazine and dexamethasone, and compared it with ondansetron, promethazine, and dexamethasone combination. They did not find any differences between these groups and concluded that both treatments regimes are effective in preventing PONV in neurosurgical patients undergoing a craniotomy under general anaesthesia.
In another study, Bergese et al., evaluated the efficacy of a triple-drug regimen that included palonosetron, promethazine, and dexamethasone in patients undergoing a craniotomy under general anesthesia. They demonstrated that this regimen may be an adequate alternative for the management of PONV in these patients, but there was a pertinent suggestion to evaluate this regimen with the control group.
Various nonpharmacological techniques, such as P-6 point stimulation (by acupuncture, acupressure, or/and electrical stimulation), have been found to be good adjuvant techniques when used with the standard antiemetic regimes. P-6 stimulation acts through endogenous opioid (b-endorphin) release in the CSF or a change in the serotonin transmission via the serotonergic and noradrenergic fiber activation. The timing of stimulation has no bearing on its effectiveness in preventing PONV. The P6 point is located nearly 5 cm proximal to the ventral wrist crease between the tendons of palmaris longus and flexor carpi radialis [Figure 2]. A randomized placebo-controlled trial failed to demonstrate the efficacy of P6 acupressure in patients undergoing a craniotomy, while other studies showed it to be an effective adjunct to the conventional antiemetics in preventing postcraniotomy PONV.
Ascertaining the optimal approach to treatment of PONV and the management of patients with prophylaxis failure
If a patient develops PONV, all possible contributing factors should be excluded prior to initiating rescue treatment. Various contributing factors might include opioid based patient-controlled analgesia (PCA) pumps, blood trickling down the throat, intestinal obstruction/gastric distention, hypoxia, and hypotension. Anesthesia charts should be reviewed to find out whether or not antiemetic prophylaxis was given intraoperatively. If no prophylaxis had been given, a low dose of 5-HT3 antagonist should be used for the treatment of PONV., Various other treatment options include dexamethasone, droperidol, or promethazine 6.,, Propofol 20 mg as an intravenous bolus can be considered as a rescue therapy in post-anesthesia care unit (PACU), which is as effective as ondansetron.,, The use of propofol is associated with a few limitations such as brief duration of action and the occurrence of sedation that hampers neurological assessment.
Patients who developed PONV within the first 4 postoperative hours after receiving ondansetron prophylaxis did not respond to the second dose of ondansetron or other 5-HT3 antagonists., If PONV develops after 6 hours postoperatively, a second dose of 5-HT3 antagonist or butyrophenone (droperidol or haloperidol) can be effective. Long-acting antiemetic agents, including dexamethasone, TDS, aprepitant, and palonosetron should not be re-administered.
PONV causes discomfort to the patients and can lead to dreaded consequences in neurosurgical patients such as an increase in the intracranial pressure and the occurrence of intracranial hemorrhage, both of which are associated with an increased mortality and morbidity, and a prolonged hospital stay. We should try to evaluate the patients to identify the factors that increase the risk of PONV and try to minimize them. The mechanisms of PONV are varied and involve multiple receptors; hence, a multimodal protocol of management and a combination of drugs should be used for its prophylaxis. We should combine the agents that act on different receptors and possess different mechanisms of action. The antiemetic agents causing sedation should be avoided in neurosurgical patients. Patients who have not received PONV prophylaxis and have developed PONV within 6 postoperative hours are treated with 5-HT3 receptor antagonists. In patients who have received prophylaxis and yet have developed vomiting in less than 6 hours, drugs of different group should be considered. Vomiting occurring 6 hours later can be treated with a repeat dose of 5-HT3 receptor antagonist, but re-administration of the drugs having a longer duration of action is not recommended.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]