Abstract
Patients undergoing ambulatory surgery have similar, but also different nausea and vomiting stimuli and mechanisms than inpatients. As the emphasis on “street readiness” and discharge home is a unique and important concern for outpatients, various medications, formulations, techniques, risk scores, and guidelines have been introduced to help improve the care of patients having ambulatory surgery. Additional research and data have been obtained regarding the effects of postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) on ambulatory anesthesia. More effective antiemetic combination techniques and new long-acting antiemetics have been introduced for PONV and PDNV prevention. Antiemetic drug selection for ambulatory surgery depends on efficacy, cost, adverse effects, and ease of dosing. Safety concerns include adverse events such as the ECG QTc prolongation effects of antiemetics. To help guide antiemetic drug selection, techniques, and therapy, the PONV consensus guidelines were updated in 2014.
Similar content being viewed by others
Introduction
Healthcare costs of ambulatory surgery related to postoperative nausea and vomiting (PONV) occur due to surgical complications, unanticipated hospital inpatient admissions, prolonged nursing care, and delayed discharge from the phase one post-anesthesia care unit (PACU) or phase 2 ambulatory care stepdown unit [1••]. PONV occurs with an overall average incidence of approximately 30 % taking into account all patient types and surgeries [1••]. Nausea occurs with an incidence of approximately 40–50 % and vomiting 25–30 % [1••, 2]. PONV incidence has been reported to be as high as 80 % in some high risk groups, such as patients who did not receive prophylactic antiemetics undergoing tonsillectomy, strabismus repair, or laparoscopy [3, 4].
Postdischarge nausea and vomiting (PDNV) is important in ambulatory patients discharged home and occurs with an incidence of about 30 % [5, 6]. The 2nd generation 5-hydroxytryptamine-3 (5HT3) antagonist palonosetron (Aloxi®, Helsinn) [7] and the neurokinin-1 (NK-1) receptor antagonist aprepitant (Emend®, Merck) [8] both of which have long half-lives of 40 h, offer alternative therapy methods for the prophylaxis of PONV and PDNV in the ambulatory surgery patient. As dexamethasone and scopolamine patch have a prolonged duration of antiemetic effect, they are useful medications that can be used to help prevent PDNV.
The mechanisms and causes of PONV during ambulatory anesthesia are similar to those for inpatient surgery patients and are the result of anesthesia, surgical, and patient-related factors [9–11]. Anesthesia-related causes in the PACU are most commonly due to the intraoperative use of nitrous oxide and volatile anesthetics, as well as the postoperative use of oral and intravenous (IV) opioids [1••]. Many patients may or may not experience PONV due to their own individual PONV susceptibility and genetic makeup resulting in fast versus slow drug metabolism [9]. An important difference in the ambulatory surgery patient compared to inpatients is the impact of oral medications (especially opioids), early ambulation, and the advancement of food and liquids [1••, 12].
Estimating the Risk of PONV and PDNV
Four risk factors that have been identified to contribute to PONV are: (a) female gender; (b) history of PONV and/or motion sickness; (c) non-smoker; and (d) postoperative opioids [13]. Each factor contributes a 20 % risk for PONV. The PONV risk factors are additive with a risk of 20, 40, 60, and 80 % for 1, 2, 3, and 4 risk factors, respectively. Four pediatric risk factors contributing to postoperative vomiting (POV) [14] are: (a) strabismus surgery; (b) age ≥3 years; (c) surgery >30 min; and (d) history of POV or postoperative nausea and vomiting in relatives (father, mother, siblings). These POV risk factors are additive risks of 10, 30, 50, and 70 % for 1, 2, 3, and 4 risk factors, respectively. In spite of receiving prior antiemetic prophylaxis, Apfel and colleagues [15•] identified the incidence of PDNV as 37 % in the first 48 h after hospital discharge. Five independent risk factors were found to cause PDNV: (a) female gender; (b) age less than 50 years; (c) history of nausea and vomiting after previous anesthesia; (d) PACU opioids; and (e) PACU nausea. The risk of PDNV was approximately 10, 20, 30, 50, 60, or 80 %, respectively, when 0, 1, 2, 3, 4, or 5 of these risk factors were present.
Apfel’s “simplified” scores for PONV and PDNV have been used to estimate the degree of PONV and PDNV risk for ambulatory surgery patients. Improved cost-benefit and effective treatment measures occur in patients who have a PONV risk greater than 40 % (more than two Apfel PONV risk factors) [16••]. Use of simplified PONV and PDNV algorithms should allow for improved PONV prevention and treatment of ambulatory patients [17, 18]. Estimation of PONV and PDNV risk in the ambulatory patient population can help predict the chance of these patients having PONV and/or PDNV [14]. Use of risk scores can help predict which patients may have a low (10–20 %) or moderate to high risk (60–80 %) for PONV and PDNV [1••, 16••].
The “relatively” safe side-effect profile of the 5HT3 receptor antagonists and low cost of “generic” ondansetron has led to the practice by some anesthesia providers of giving antiemetics to all patients having ambulatory surgery. The real question is should one or two antiemetics with a low antiemetic side-effect profile be given universally to every ambulatory surgery patient in spite of these patients having a low PONV and/or PDNV risk? [19]. This approach of giving all patients antiemetic prophylaxis could cause low-risk patients to receive unneeded antiemetics and expose them to unnecessary risks for rare but possible side effects [1••]. However, most recent studies, including the 2014 PONV Consensus Guidelines indicate that routine use of 1–2 prophylactic antiemetics is beneficial with a superior risk : benefit ratio.
Antiemetic Receptors and Their Antagonists
The etiology and mechanisms responsible for PONV and PDNV are similar and have been previously reviewed [11]. Numerous different neurochemicals and receptors are involved leading to the use of multimodal therapy to target these different receptor areas. A pertinent question for this review is does the mechanisms and types of antiemetic receptors for PONV and PDNV that occur in ambulatory outpatients differ from inpatients? In both types of patient populations, similar antiemetic receptor and pathways are involved, but the type and degree of antiemetic stimuli appear to be different [6, 20]. The cerebellum and vestibular areas relate to balance and movement, as occur when ambulatory patients increase their activity, ambulate, and begin their ride home from the hospital. The degree and amount of patient movement following discharge home from the hospital or ambulatory surgery center is an important difference between inpatients and outpatients. Nitrous oxide and the volatile anesthetics contribute to early but not delayed PONV after surgery [21]. Other stimuli to the chemoreceptor trigger zone and vomiting center are stimulation from opioids and movement via the vestibular part of the glossopharyngeal (8th cranial) nerve [1••, 10, 22].
Pharmacogenetics
The human genome and genetic polymorphism influence an individual’s pharmacogenetics, which in turn help determine which patients may or may not be affected by a specific drug therapy. Different genes in different patients control proteins activating specific receptors involved in the metabolism of a particular drug via liver enzymes. In turn, these genes can change an individual patient’s response to a specific drug [9, 23]. Ultra-rapid metabolism results in lower blood levels with less drug effectiveness and increased antiemetic failure. Slower metabolism results in higher blood levels with possible drug toxicity [9, 23]. Ethnic genetic differences cause differences in enzyme metabolism due to genetic polymorphism [24]. The glycoprotein MDR1 is thought to affect drug metabolism and has genetic inter-individual variability [25].
PONV Prophylaxis
The ambulatory surgery patient presents a special challenge compared to inpatients, as these patients usually will have less intense medical and nursing observation after discharge home. Safe “fast track” discharge home with “street readiness” is of utmost importance and once again raises the question whether prophylactic antiemetics should be given routinely to all ambulatory patients even though there is the possibility of rare but unwanted side effects. Some practitioners argue that liberal use of low risk antiemetics for PONV prophylaxis is a viable option to help totally eliminate or reduce PONV in the ambulatory patient population. However, one should remember that side effects of these medications, even if low, may be a possibility. The pressure to safely discharge patients home following ambulatory surgery requires a multimodal therapeutic prophylactic approach in patients at moderate (>40 %) to high (>60 %) risk for PONV [1••, 16••]. This is where the inclusion of one to two prophylactic antiemetics can be useful.
Eight antiemetics (ondansetron, dolasetron, granisetron, tropisetron, dexamethasone, droperidol, cyclizine, and metoclopramide) were evaluated by the Cochrane review [26••]. Each antiemetic was determined to reliably prevent nausea or vomiting after surgery. Interestingly, no drug was found to be especially better than another. When combined, their antiemetic effects were additive. Adult and pediatric antiemetic dosing are listed in Table 1.
Metoclopramide
Metoclopramide is a weak antiemetic with a short half-life of 30 min to 1 h. Meta-analysis studies have determined that the 10 mg dose is ineffective and no better than placebo when given as PONV prophylaxis. Doses higher than 25 mg are needed for prophylactic PONV effectiveness, but extrapyramidal side effects occur at these higher doses. However, due to its prokinetic effects on the gastrointestinal system and increase of gastric emptying, metoclopramide is used by some clinicians as treatment for PONV post-surgery [1••, 27].
Dexamethasone
Dexamethasone’s minimum effective dose for PONV prophylaxis is 4 mg, with an increase in effectiveness occurring with an increase in dose [1••, 28]. The antiemetic mechanism of action of dexamethasone is not known, but is possibly related to its anti-inflammatory effect. As dexamethasone takes time to work, it should be given at the start of surgery. It is more effective preventing late versus early PONV. There is increased effectiveness when dexamethasone is combined with other antiemetics [29, 30]. Controversy exists regarding the steroid side effects of postoperative wound and bone healing, bleeding, perineal pain, infection, and hyperglycemia [31–35]. Caution should be exercised in the use of dexamethasone in diabetic patients. With the availability of alternative antiemetics, an individualized review of the risks and benefits of using dexamethasome in these patients should be made [36, 37].
Methylprednisolone 40 mg IV has been shown to be effective to prevent late PONV occurring more than 6 h postoperative [38, 39]. Being also a steroid medication, methylprednisolone has characteristics similar to dexamethasone such as cortisol equivalency and side-effects profile.
Transdermal Scopolamine
Because of its long duration of action given via the transdermal route, a useful antiemetic for ambulatory surgery and PDNV is transdermal scopolamine. Transdermal scopolamine has been found useful when used alone or in combination with other prophylactic antiemetics [40, 41]. Transderm scopolamine’s main side effects are dry mouth and blurred vision occurring on the first and second postoperative days, respectively [42]. A transderm scopolamine patch contains a total 3-day dose of 1.5 mg with 0.5 mg used as the priming dose and a dose of 0.33 mg released per day over a 3-day period. Transderm scopolamine is FDA approved for 24 h for PONV and 72 h for motion sickness. Contraindications to transdermal scopolamine include acute angle glaucoma and voiding problems [1••, 42].
As blurred vision and pupillary changes can be a side effect of the scopolamine patch, it is the practice of this author to inquire with the operative surgeon if they have any concerns or questions about the use of the patch in their patients. This is important especially in neurosurgery or ENT surgery in which a change in vision (blurred) or pupil changes could indicate a CNS change or event. Also, a common question involves timing of patch placement. Current clinical practice is to apply the patch 1–2 h prior to surgery as this is the approximate time period in which patients may experience an increase in mouth dryness indicating that the patch is beginning to be absorbed from the skin to the blood stream. However, it is the opinion of this author that patch placement can also be made intraoperatively after anesthesia induction to have some effect for PDNV.
Butyrophenones–Droperidol
Droperidol has been found to be more effective when given at the end of surgery [1••, 26••]. Droperidol has comparable effects against nausea and vomiting [43]. Droperidol doses of 0.625–1.25 mg IV have PONV efficacy equal to ondansetron [16••] and better effectiveness than metoclopramide [44]. It has been determined that, when given prophylactically at doses less than 1 mg (i.e., 0.625 mg) there was PONV efficacy with fewer side effects [45]. Following the FDA’s 2001 “black box” QTc warning [46], droperidol was replaced by other antiemetics as the first choice for PONV prophylaxis in the USA and other countries. Combining droperidol with ondansetron does not cause any increased effects on QT prolongation [47].
Haloperidol
Haloperidol, another medication in the butyrophenone drug class, has been suggested as an alternative antiemetic to droperidol but has a longer half-life. Haloperidol doses of 0.5 to 2 mg IV or intramuscular (IM) have been found to be effective in the prevention of PONV [1••]. Its administration at the start versus end of surgery showed no difference in PONV effect and equal efficacy compared to ondansetron [48–50]. When haloperidol was combined with other antiemetics it had a better effect compared to using one antiemetic alone [49]. Haloperidol has a similar effect on the QTc interval as droperidol, with similar QTc warnings issued by FDA in 2007 [48].
5HT3 Antagonists
Ondansetron
Ondansetron is the “gold standard” antiemetic for PONV prophylaxis and treatment, with a recommended dose of 4 mg IV. It is effective when administered either at induction or end of surgery [1••]. However, because of a plasma half-life of 4–6 h, ondansetron dosing immediately prior to induction was less effective for prevention of PDNV compared to administration at the end of surgery [51]. Ondansetron is equally as effective as haloperidol [52], promethazine [53], and ramosetron [54], but less effective than palonosetron [55] and aprepitant [56]. Ondansetron 4 mg IV is equivalent to the 8 mg ondansetron oral disintegrating tablet (ODT). Because of its effect on the QTc interval, the FDA removed the ondansetron 32 mg dose for chemotherapy-induced nausea and vomiting from the US market [1••].
Granisetron
Granisetron 0.35–3.0 mg IV has a similar antiemetic effectiveness compared to ondansetron, dolasetron and tropisetron [57, 58]. The combination of granisetron with another antiemetic is more effective than using only one antiemetic alone [59].
Palonosetron- 2nd Generation 5HT3 Antagonist
Palonosetron is a highly selective 5HT3 antagonist with a binding affinity stronger than the other 1st generation 5HT3 antagonists. It has a longer plasma half-life (40 h) than ondansetron, (4–6 h), dolasetron (7–9 h), granisetron (5–8 h), and tropisetron (7 h). Palonosetron has a chemical structure that is distinctly different from the 1st generation 5HT3 receptor antagonists. This structural difference allows palonosetron to have a unique and different molecular interaction with the 5HT3 receptor compared to 1st generation antagonists due to allosteric binding, positive cooperativity, and receptor internalization [60, 61]. Stronger binding and receptor internalization allow for easier attachment of subsequent palonosetron molecules after the first molecule attaches, resulting in a more prolonged inhibition of 5HT3 receptor function [61–63]. Due to its long half-life, the original early FDA new drug application studies chose to administer palonosetron at the start of surgery, similar to the new drug application for ondansetron. In an outpatient study, palonosetron 0.075 mg IV was the most effective dose for the 0- to 24-h postoperative time period [7]. Palonosetron 0.075 mg has greater PONV effectiveness compared to granisetron 1 mg [64] and ondansetron 4 mg [55]. Palonosetron is primarily metabolized by CYP2D6 and to a lesser extent by the CYP1A2 and CYP3A P450 liver enzymes. No dose adjustments are required regarding age, liver disease, or mild to moderate kidney disease. Palonosetron has no effect on the QTc interval [60, 62, 65].
Aprepitant-NK-1 Receptor Antagonist
Aprepitant is a NK-1 antagonist with a 40-h half-life that is given orally 1–2 h preoperatively for PONV prophylaxis. In a PONV prevention study, while ondansetron 4 mg IV and aprepitant 40 mg per oral (PO) had similar effectiveness for the first 24 h, aprepitant was more effective in the subsequent 24- to 48-h postoperative time period [8, 56] with an effect on vomiting greater than nausea. Aprepitant 80 mg PO was more effective than the 40 mg dose in patients undergoing laparoscopic gynecologic surgery. The combination of aprepitant plus dexamethasone was found to be more effective than ondansetron plus dexamethasone [66].
Midazolam
Midazolam’s mechanism of action is believed to work by decreasing dopamine input at the chemoreceptor trigger zone and decreasing serotonin release at the GABA benzodiazepine complex [67]. Midazolam 2 mg IV given 30 min before the end of surgery decreased PONV more than midazolam 35 mcg/kg IV given as premedication [68]. Midazolam 2 mg was more effective than metoclopramide 10 mg [69] with similar PONV effectiveness compared to ondansetron 4 mg [70]. Given at the end of surgery, midazolam 2 mg IV was equally as effective as a 1 mg/kg/hr infusion of propofol [68]. Caution should be used with midazolam in the ambulatory patient as postoperative sedation is a possibility.
Combination Antiemetic Therapy
Combination antiemetic therapy for PONV is more effective than giving a single drug alone [1••, 16••, 71, 72]. Drugs from different drug classes working at different antiemetic receptors should be combined to achieve the best effect. To decrease the incidence of side effects, the lowest effective dose of antiemetic should be used in the combination. The 5HT3 antagonists work best if they are used in combination with dexamethasone, transdermal scopolamine, or droperidol. However, because of additive side effects, the combined doses of these medications should not be more than ondansetron 4 mg, dexamethasone 10 mg or droperidol 1 mg [1••]. Examples of combination antiemetic therapy for PONV and PDNV are listed in Table 2.
Treatment of PONV
The 2014 PONV Consensus Guidelines [1••] recommend that for treatment of failed antiemetic prophylaxis, an antiemetic of a different drug class not previously administered should be given [73]. However, due to their relatively short half-lives of less than 6 h, prophylacticantiemetics from the same drug class given more than 6 h prior can be repeated. If no prior antiemetic was given for prophylaxis, a low-dose 5HT3 antagonist is recommended. Treatment of PONV has been shown to be effective with IV droperidol, promethazine, propofol, dexamethasone, or inhalation of isopropyl alcohol vapor. Treatment studies using long-acting antiemetics such as palonosetron, dexamethasone, aprepitant, or transderm scopolamine have not been conducted.
Pediatrics
Tonsillectomy and strabismus repair are two of the most common outpatient emetogenic surgeries in children. Several prophylactic antiemetics have been found to be useful in pediatric patients. Ondansetron 0.1 mg/kg is effective to decrease POV in children 1 month to 2 years [74]. Children who received ondansetron oral disintegrating tabled (ODT) had less emesis and required less PACU rescue antiemetics [75, 76]. Combination antiemetics with dexamethasone have been determined to be effective in children [71, 77].
Postdischarge Nausea and Vomiting (PDNV)
Multiple factors cause PDNV, and include the initiation of postoperative oral opioids, antibiotics, birth control pills, as well as increase in diet, movement, and ambulation. Some patients experiencing PDNV may not have received antiemetic prophylactic premedication or postoperative PONV treatment in the PACU. The perioperative time periods of PONV and PDNV overlap and are shown in Fig. 1 [78].
In outpatient surgery, PDNV occurs in approximately 30–40 % in patients who had or did not have PONV in the PACU [2, 5]. In a systematic review of PDNV in outpatient surgery patients, the nausea and vomiting incidence was 17 and 8 %, respectively [20]. Analysis of the simplified Apfel PDNV risk factors [15•] can help clinicians determine what patients may or may not have PDNV so that appropriate therapeutic measures can be undertaken [17, 79].
Additional prophylactic PO and IV antiemetics given at different times in the perioperative period may be necessary to prevent and/or treat patients for PDNV. Pan et al. [80•] determined that giving dexamethasone 8 mg IV at anesthesia induction, ondansetron 4 mg IV at the end of surgery and ondansetron 8 mg PO postoperatively was more effective to prevent PONV than giving ondansetron 8 mg IV alone at the end of surgery. A study [8] comparing the single prophylactic dosing of ondansetron 4 mg IV to aprepitant 40 mg PO determined that both drugs had similar effects on nausea and vomiting in the 0–24 h postoperative period, but for the 24–48 h postoperative period, aprepitant, with its longer 40 h half-life, had a greater anti-vomiting effect than ondansetron. When combining antiemetics for their effect on PDNV, haloperidol 2.5 mg IV plus dexamethasone 5 mg IV had more effectiveness than droperidol 1.25 mg IV, haloperidol 2 mg IV or dexamethasone 5 mg IV given alone [81]. Droperidol given at doses less than 1 mg (i.e., 0.625 mg) was found to be ineffective in preventing PDNV [82].
Possible useful approaches to help decrease the incidence of PDNV include: (a) combination prophylactic antiemetic therapy; (b) total intravenous anesthesia (TIVA); substituting propofol for inhalation anesthesia; (c) P6 acupoint stimulation; and (d) use of long-acting antiemetics, such as dexamethasone, transdermal scopolamine, aprepitant, palonosetron, or ondansetron ODT [1••].
Safety and Side Effects
The main side effects of antiemetics used for PONV and PDNV are sedation, hypotension, extrapyramidal and dystonic effects, restlessness, dry mouth, dysphoria, headache, lightheadedness, constipation, and ECG QTc prolongation [1••, 83–85]. See Table 3. Combining older antiemetics increases the likelihood of side effects. QTc prolongation is a side effect of droperidol, haloperidol, and the 1st generation 5HT3 receptor antagonists ondansetron, dolasetron and granisetron, but not the 2nd generation 5HT3 antagonist, palonosetron [65, 85, 86]. The newer antiemetics, such as palonosetron and aprepitant, do not have the side effects of the older antiemetics. Their own side effects include headache, constipation, and hunger [1••, 87–90].
During the trials of aprepitant for chemotherapy-induced nausea and vomiting (CINV), there was a clinical concern about the effect of aprepitant on female hormone levels as the efficacy of hormonal contraceptives, such as birth control pills, skin patches, implants, and IUDs, may be reduced during coadministration with and for 28 days after the administration of aprepitant. It was recommended that women should use a backup method of birth control during their treatment with aprepitant and up to 1 month after receiving aprepitant. The CINV dose of aprepitant is 125, 80, and 80 mg given on days one, two and three, respectively. The aprepitant PONV dose is a one time dose of 40 mg. While the hormonal effects of the CINV 125, 80, and 80 mg doses over 3 days have been studied, the hormonal effect of the reduced one time 40 mg PONV dose has not. As such, it is not known if these concerns for PONV are clinically relevant.
Metoclopramide administered in doses of 25–50 mg not only has prophylactic PONV effectiveness but also increased side effects of hypotension, tachycardia, and extrapyramidal symptoms [27]. Transderm scopolamine has side effects of dry mouth and blurred vision on the first and second postoperative days, respectively [42]. Case reports indicated the possible need for caution in children undergoing tonsillectomy due to an increased incidence of bleeding following dexamethasone [91–93]. In spite of this, ENT guidelines recommend the use of dexamethasone [94] and ondansetron [75] in tonsillectomy patients.
Conclusions
PONV may occur in up to 80 % of high risk patients who do not receive prophylactic antiemetics. Overall, PONV and PDNV occur in about 30 % of patients. PONV and PDNV can occur in ambulatory surgery patients and are associated with increased morbidity and healthcare costs. Patient-specific, anesthesia-, and surgery-related PONV and PDNV risk factors should be evaluated to help determine the appropriate antiemetic therapy for proper prophylaxis or treatment. Volatile inhalation agents, opioids, early ambulation, and increases in fluids and diet are specific PONV and PDNV stimuli factors and triggers in the ambulatory surgery patient. Reducing a patient’s risk for PONV or PDNV can decrease the probability of these patients having nausea and/or vomiting after surgery. PONV antiemetic drug selection depends on efficacy, cost, safety, and ease of dosing. The 2014 PONV consensus guidelines are useful when applied to the ambulatory surgery patient to help determine proper antiemetic therapy and improve patient outcomes.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
•• Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118(1):85–113. Third publication of a very useful, well referenced, evidence based, algorithm approach to the prevention and treatment of PONV for adult and pediatric patients.
Carroll NV, Miederhoff P, Cox FM, Hirsch JD. Postoperative nausea and vomiting after discharge from outpatient surgery centers. Anesth Analg. 1995;80(5):903–9.
Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, et al. Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2007;105(6):1615–28 table of contents.
Blacoe DA, Cunning E, Bell G. Paediatric day-case surgery: an audit of unplanned hospital admission Royal Hospital for Sick Children. Glasgow Anaesth. 2008;63(6):610–5.
Gupta A, Wu CL, Elkassabany N, Krug CE, Parker SD, Fleisher LA. Does the routine prophylactic use of antiemetics affect the incidence of postdischarge nausea and vomiting following ambulatory surgery? A systematic review of randomized controlled trials. Anesthesiology. 2003;99(2):488–95.
Mattila K, Toivonen J, Janhunen L, Rosenberg PH, Hynynen M. Postdischarge symptoms after ambulatory surgery: first-week incidence, intensity, and risk factors. Anesth Analg. 2005;101(6):1643–50.
Candiotti KA, Kovac AL, Melson TI, Clerici G, JooGan T, Palonosetron 04-06 Study G. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo for preventing postoperative nausea and vomiting. Anesth Analg. 2008;107(2):445–51.
Gan TJ, Apfel CC, Kovac A, Philip BK, Singla N, Minkowitz H, et al. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg. 2007;104(5):1082–9 tables of contents.
Choi EM, Lee MG, Lee SH, Choi KW, Choi SH. Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting. Anaesthesia. 2010;65(10):996–1000.
Gan TJ. Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. CNS Drugs. 2007;21(10):813–33.
Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology. 1992;77(1):162–84.
Kolodzie K, Apfel CC. Nausea and vomiting after office-based anesthesia. Curr Opin Anaesthesiol. 2009;22(4):532–8.
Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999;91(3):693–700.
Eberhart LH, Geldner G, Kranke P, Morin AM, Schauffelen A, Treiber H, et al. The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients. Anesth Analg. 2004;99(6):1630–7 table of contents.
• Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, et al. Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology. 2012;117(3):475–86. Well designed and researched study of a risk score to help predict the possibility of post-discharge nausea and vomiting (PDNV) in adults.
•• Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 10;350(24):2441–51. Landmark well designed study which showed that there was no difference in PONV efficacy between antiemetics such as ondansetron, droperidol and dexamethasone when used either alone or in combination with each other.
Pierre S, Corno G, Benais H, Apfel CC. A risk score-dependent antiemetic approach effectively reduces postoperative nausea and vomiting: a continuous quality improvement initiative. Canadian journal of anaesthesia. J Can Anesth. 2004;51(4):320–5.
Kranke P, Eberhart LH, Gan TJ, Roewer N, Tramer MR. Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and efficiency simulation. Eur J Anaesthesiol. 2007;24(10):856–67.
White PF, Glass PSA. Universal PONV prophylaxis in general anesthesia: should we consider its immediate implementation? Anesth Analg. 2008;106(6):1922–3.
Wu CL, Berenholtz SM, Pronovost PJ, Fleisher LA. Systematic review and analysis of postdischarge symptoms after outpatient surgery. Anesthesiology. 2002;96(4):994–1003.
Apfel CC, Kranke P, Katz MH, Goepfert C, Papenfuss T, Rauch S, et al. Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth. 2002;88(5):659–68.
Horn CC, Wallisch WJ, Homanics GE, Williams JP. Pathophysiological and neurochemical mechanisms of postoperative nausea and vomiting. Eur J Pharmacol. 2014;5(722):55–66.
Candiotti KA, Birnbach DJ, Lubarsky DA, Nhuch F, Kamat A, Koch WH, et al. The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis? Anesthesiology. 2005;102(3):543–9.
Ozawa S, Soyama A, Saeki M, Fukushima-Uesaka H, Itoda M, Koyano S, et al. Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1. Drug Metab Pharmacokinet. 2004;19(2):83–95.
Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004;75(1):13–33.
•• Carlisle J, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2009(1). Cochrane database of systematic review of numerous studies and antiemetic medications for PONV prevention and treatment.
Wallenborn J, Gelbrich G, Bulst D, Behrends K, Wallenborn H, Rohrbach A, et al. Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial. BMJ (Clinical research ed). 2006;333(7563):324.
Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2000;90(1):186–94.
Gan TJ, Coop A, Philip BK. A randomized, double-blind study of granisetron plus dexamethasone versus ondansetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing abdominal hysterectomy. Anesth Analg. 2005;101(5):1323–9.
Sodhi K, Mohindra BK, Sodhi GS, Kumar M. A comparative study of granisetron, dexamethasone, and granisetron plus dexamethasone as prophylactic antiemetic therapy in female patients undergoing breast surgery. J Anaesthesiol Clin Pharmacol. 2007;23(4):373–8.
Eberhart LHJ, Graf J, Morin AM, Stief T, Kalder M, Lattermann R, et al. Randomised controlled trial of the effect of oral premedication with dexamethasone on hyperglycaemic response to abdominal hysterectomy. Eur J Anaesthesiol. 2011;28(3):195–201.
Nazar C, Flores R, Lacassie H, Muoz H. Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on glycaemia in normal patients undergoing laparoscopic surgery. Eur J Anaesthesiol. 2009;26:130.
Nazar C, Flores R, Lacassie H, Muoz H. Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on glycaemia in patients with type II diabetes undergoing laparoscopic surgery. Eur J Anaesthesiol. 2009;26:128.
Nazar CE, Lacassie HJ, Lopez RA, Munoz HR. Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on glycaemia in obese patients with impaired glucose tolerance. Eur J Anaesthesiol. 2009;26(4):318–21.
Neff SP, Stapelberg F, Warmington A. Excruciating perineal pain after intravenous dexamethasone. Anaesth Intensive Care. 2002;30(3):370–1.
Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear T, Vender JS, et al. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients. Anesth Analg. 2014;118(6):1204–12.
Abdelmalak BB, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, et al. The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Anesth Analg. 2013;116(5):1116–22.
Weren M, Demeere JL. Methylprednisolone vs. dexamethasone in the prevention of postoperative nausea and vomiting: a prospective, randomised, double-blind, placebo-controlled trial. Acta Anaesthesiol Belg. 2008;59(1):1–5.
Miyagawa Y, Ejiri M, Kuzuya T, Osada T, Ishiguro N, Yamada K. Methylprednisolone reduces postoperative nausea in total knee and hip arthroplasty. J Clin Pharm Ther. 2010;35(6):679–84.
White PF, Tang J, Song D, Coleman JE, Wender RH, Ogunnaike B, et al. Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms. Anesth Analg. 2007;104(1):92–6.
Gan TJ, Sinha AC, Kovac AL, Jones RK, Cohen SA, Battikha JP, et al. A randomized, double-blind, multicenter trial comparing transdermal scopolamine plus ondansetron to ondansetron alone for the prevention of postoperative nausea and vomiting in the outpatient setting. Anesth Analg. 2009;108(5):1498–504.
Apfel CC, Zhang K, George E, Shi S, Jalota L, Hornuss C, et al. Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis. Clin Ther. 2010;32(12):1987–2002.
Apfel CC, Cakmakkaya OS, Frings G, Kranke P, Malhotra A, Stader A, et al. Droperidol has comparable clinical efficacy against both nausea and vomiting. Br J Anaesth. 2009;103(3):359–63.
Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg. 1999;88(6):1370–9.
Schaub I, Lysakowski C, Elia N, Tramer MR. Low-dose droperidol (≤1 mg or ≤15 mug kg−1) for the prevention of postoperative nausea and vomiting in adults: quantitative systematic review of randomised controlled trials. Eur J Anaesthesiol. 2012;29(6):286–94.
Gan TJ, White PF, Scuderi PE, Watcha MF, Kovac A. FDA “black box” warning regarding use of droperidol for postoperative nausea and vomiting: is it justified? Anesthesiology. 2002;97(1):287.
Chan MTV, Choi KC, Gin T, Chui PT, Short TG, Yuen PM, et al. The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting. Anesth Analg. 2006;103(5):1155–62.
Rosow CE, Haspel KL, Smith SE, Grecu L, Bittner EA. Haloperidol versus ondansetron for prophylaxis of postoperative nausea and vomiting. Anesth Analg. 2008;106(5):1407–9 table of contents.
Grecu L, Bittner EA, Kher J, Smith SE, Rosow CE. Haloperidol plus ondansetron versus ondansetron alone for prophylaxis of postoperative nausea and vomiting. Anesth Analg. 2008;106(5):1410–3 table of contents.
Yang YL, Lai HY, Wang JJ, Wang PK, Chen TY, Chu CC, et al. The timing of haloperidol administration does not affect its prophylactic antiemetic efficacy. Can J Anaesth. 2008;55(5):270–5.
Cruz NI, Portilla P, Vela RE. Timing of ondansetron administration to prevent postoperative nausea and vomiting. P R Health Sci J. 2008;27(1):43–7.
Aouad MT, Siddik-Sayyid SM, Taha SK, Azar MS, Nasr VG, Hakki MA, et al. Haloperidol vs. ondansetron for the prevention of postoperative nausea and vomiting following gynaecological surgery. Eur J Anaesthesiol. 2007;24(2):171–8.
Olatosi OJ, Kushimo O, Okeke C, Oriyomi O, Ajayi GO. Antiemetic prophylaxis with promethazine or ondansetron in major gynaecological surgery. South Afr J Anaesth Analg. 2008;14(6):39–42.
Do SH, Ryu J. Ramosetron versus ondansetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Surg Endosc Other Interven Tech. 2010;24(7):1798–9.
Park SK, Cho EJ. A randomized, double-blind trial of palonosetron compared with ondansetron in preventing postoperative nausea and vomiting after gynaecological laparoscopic surgery. J Int Med Res. 2011;39(2):399–407.
Diemunsch P, Gan TJ, Philip BK, Girao MJ, Eberhart L, Irwin MG, et al. Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery. Br J Anaesth. 2007;99(2):202–11.
Bhatia N, Katyal S, Grewal A, Kaul TK. Antiemetic prophylaxis with granisetron, ondansetron and metoclopramide in ambulatory gynaecological laparoscopic surgery: a comparison. J Anaesthesiol Clin Pharmacol. 2008;24(3):303–6.
Erhan Y, Erhan E, Aydede H, Yumus O, Yentur A. Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : a randomized placebo-controlled study. Surg Endosc. 2008;22(6):1487–92.
Johns RA, Hanousek J, Montgomery JE. A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting. Anaesthesia. 2006;61(11):1053–7.
Bajwa SS, Bajwa SK, Kaur J, Sharma V, Singh A, Singh A, et al. Palonosetron: a novel approach to control postoperative nausea and vomiting in day care surgery. Saudi J Anaesth. 2011;5(1):19–24.
Rojas C, Thomas AG, Alt J, Stathis M, Zhang J, Rubenstein EB, et al. Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol. 2010;626(2–3):193–9.
Navari RM. Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol. 2006;2(5):591–602.
Yang LPH, Scott LJ. Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009;69(16):2257–78.
Bhattacharjee DP, Dawn S, Nayak S, Roy PR, Acharya A, Dey R. A comparative study between palonosetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol. 2010;26(4):480–3.
Wallenborn J, Kranke P. Palonosetron hydrochloride in the prevention and treatment of postoperative nausea and vomiting. Clin Med Insights. 2010;2:387–99.
Habib AS, Keifer JC, Borel CO, White WD, Gan TJ. A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy. Anesth Analg. 2011;112(4):813–8.
Jung JSA, et al. Effect of midazolam upon the prevention of nausea and vomiting after middle ear surgery. Korean J Anesthesiol. 2007;52(5):550–5.
Tarhan O, Canbay O, Celebi N, Uzun S, Sahin A, Coskun F, et al. Subhypnotic doses of midazolam prevent nausea and vomiting during spinal anesthesia for cesarean section. Minerva Anestesiol. 2007;73(12):629–33.
Shahriari A, Khooshideh M, Heidari MH. Prevention of nausea and vomiting in caesarean section under spinal anaesthesia with midazolam or metoclopramide? JPMA. 2009;59(11):756–9.
Lee Y, Wang JJ, Yang YL, Chen A, Lai HY. Midazolam vs ondansetron for preventing postoperative nausea and vomiting: a randomised controlled trial. Anaesthesia. 2007;62(1):18–22.
Bhardwaj N, Bala I, Kaur C, Chari P. Comparison of ondansetron with ondansetron plus dexamethasone for antiemetic prophylaxis in children undergoing strabismus surgery. J Pediatr Ophthalmol Strabismus. 2004;41(2):100–4.
Habib AS, White WD, Eubanks S, Pappas TN, Gan TJ. A randomized comparison of a multimodal management strategy versus combination antiemetics for the prevention of postoperative nausea and vomiting. Anesth Analg. 2004;99(1):77–81.
Kovac AL, O’Connor TA, Pearman MH, Kekoler LJ, Edmondson D, Baughman VL, et al. Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin Anesth. 1999;11(6):453–9.
Khalil SN, Roth AG, Cohen IT, Simhi E, Ansermino JM, Bolos ME, et al. A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia. Anesth Analg. 2005;101(2):356–61.
Cohen IT. An overview of the clinical use of ondansetron in preschool age children. Ther Clin Risk Manag. 2007;3(2):333–9.
Cohen IT. Ondansetron for postoperative nausea and vomiting. Therapy. 2006;3(5):571–8.
Shende D, Bharti N, Kathirvel S, Madan R. Combination of droperidol and ondansetron reduces PONV after pediatric strabismus surgery more than single drug therapy. Acta Anaesthesiol Scand. 2001;45(6):756–60.
Kovac AL. Update on the management of postoperative nausea and vomiting. Drugs. 2013;73(14):1525–47.
Biedler A, Wermelt J, Kunitz O, Muller A, Wilhelm W, Dethling J, et al. A risk adapted approach reduces the overall institutional incidence of postoperative nausea and vomiting. J Can Anesth. 2004;51(1):13–9.
• Pan PH, Lee SC, Harris LC. Antiemetic prophylaxis for postdischarge nausea and vomiting and impact on functional quality of living during recovery in patients with high emetic risks: a prospective, randomized, double-blind comparison of two prophylactic antiemetic regimens. Anesth Analg. 2008 Aug;107(2):429–38. Well designed study showing the efficacy of a combination approach of antiemetics administered different times at the end of surgery and postoperatively for the prevention of post-discharge nausea and vomiting (PDNV).
Chu C-C, Shieh J-P, Tzeng J-I, Chen J-Y, Lee Y, Ho S-T, et al. The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesth Analg. 2008;106(5):1402–6 table of contents.
Le TP, Gan TJ. Update on the management of postoperative nausea and vomiting and postdischarge nausea and vomiting in ambulatory surgery. Anesthesiol Clin. 2010;28(2):225–49.
Tramer MR. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues. Acta Anaesthesiol Scand. 2001;45(1):4–13.
Tramer MR. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda. Acta Anaesthesiol Scand. 2001;45(1):14–9.
Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D. Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Pharmacol Exp Ther. 2000;295(2):614–20.
Kovac AL. Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists. J Clin Anesth. 2006;18(4):304–18.
Jain A. Palonosetron-induced migraine-type headache. Can J Anaesth. 2011;58(2):230–1.
Muchatuta NA, Paech MJ. Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009;5(1):21–34.
Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs. 2009;69(13):1853–78.
Gray H. Aprepitant for postoperative nausea and vomiting. Anaesth Intensive Care. 2009;37(1):135–6.
Brigger MT, Cunningham MJ, Hartnick CJ. Dexamethasone administration and postoperative bleeding risk in children undergoing tonsillectomy. Arch Otolaryngol. 2010;136(8):766–72.
Gunter JB, Willging JP, Myer CM 3rd. Dexamethasone and postoperative bleeding after tonsillectomy in children. JAMA. 2009;301(17):1764–5 author reply 5-6.
Stewart PC, Baines DB, Dalton C. Paediatric day stay tonsillectomy service: development and audit. Anaesth Intensive Care. 2002;30(5):641–6.
Engelman E, Salengros JC, Barvais L. How much does pharmacologic prophylaxis reduce postoperative vomiting in children?: Calculation of prophylaxis effectiveness and expected incidence of vomiting under treatment using Bayesian Meta-analysis. Anesthesiology. 2008;109(6):1023–35.
Compliance with Ethics Guidelines
Conflict of Interest
Anthony L. Kovac has received grant support, participated on speaker’s bureaus and served as an advisor for GlaxoSmithKline, Roche, Abbott, Merck, Baxter, Esiai, Hoechst Marion Roussel and Helsinn.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kovac, A.L. Postoperative and Postdischarge Nausea and Vomiting After Ambulatory Surgery: An Update. Curr Anesthesiol Rep 4, 316–325 (2014). https://doi.org/10.1007/s40140-014-0076-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40140-014-0076-3