Postoperative Nausea and Vomiting Management

Full update April 2023

Postoperative recovery is complicated by nausea and vomiting in up to 30% of patients.1,8 Postoperative nausea and vomiting (PONV) can lead to dehydration, wound dehiscence, or delay hospital discharge.Pharmacologic and non-pharmacologic options can be used to prevent and/or treat PONV. This chart reviews antiemetic dosing, administration timing, and other considerations for managing adults with PONV.

Drugs listed in alphabetical order; NOT order of preference. Many doses are from consensus statements and may differ from product labeling.

Drug/Drug Class/Costa

Adult PONV Dosing Regimens

Other Considerations

Amisulpride
Barhemsys

Dopamine antagonist

Injection: $45
(5 mg/2 mL vial)

Prevention:
5 mg IV x 1, at anesthesia induction8,13

Treatment:
5 or 10 mg IV x 18,13

Consider using a 10 mg dose instead of 5 mg for treatment of established PONV in patients who failed prevention with antiemetic meds with other mechanisms of action, as 5 mg may not be effective in these patients.8

Studies using antiemetic doses have not reported sedation, EPS, or QTc prolongation.8

May be associated with injection site pain and a slight increase in prolactin levels.8,13

Aprepitant
Emend, generic (PO)
Aponvie emulsion (IV)

Neurokinin-1 antagonist

Capsule:
~$88 (40 mg capsule)

Injection:
~$58 (32 mg/4.4 mL vial)

Prevention:
40 mg PO x 1, at anesthesia induction8

32 mg IV x 1, at anesthesia induction28

Treatment: No data for use to treat established PONV.8

Aprepitant 40 mg PO more effective than ondansetron for prevention of PONV, especially 24 to 48 hours postoperatively, which may be due to its half-life of nine to 13 hours.8,13

Headache and dizziness are common side effects.13

Aprepitant can reduce the efficacy of hormonal contraceptives. Patients should be advised
to use a back-up contraceptive for one month following the last dose of aprepitant.28,29

CYP3A4 substrate, inhibitor, and inducer; CYP2C9 inducer.13

Aprepitant 40 mg PO plus dexamethasone seems more effective than ondansetron plus dexamethasone at preventing vomiting in neurosurgery patients.8

FDA approval of IV emulsion was based on efficacy data from PO formulation.28

Dexamethasone

Corticosteroid

Injection:
~$1.20 (4 mg/1 mL vial)

Prevention:
4 to 8 mg IV x 1, at or shortly after anesthesia induction8,23

Treatment: NOT effective alone as rescue therapy for established PONV.1

As effective as ondansetron and granisetron for PONV prevention.8,12 Considered a first-line option for prevention.

Possible additional benefit may be dexamethasone’s opioid-sparing effects.8

Doses used for PONV:

  • may increase blood glucose levels by up to ~36 mg/dL in patients with diabetes.27 Risk increases with dose.Some centers avoid in patients with diabetes.23
  • do not seem to increase infection risk or anastomotic leaks.11,27

Dexamethasone 8 mg IV x 1 added to standard therapy (preop ondansetron and/or cyclizine) seems more effective than standard therapy alone at preventing PONV for the first 24 hours after gastrointestinal surgery[Evidence Level A-1] and may reduce the need for rescue antiemetics for up to 72 hours after surgery.11

Droperidol

Inapsine, generics

Butyrophenone

Injection:
~$4.50 (5 mg/2 mL vial)

Prevention:
0.625 mg IV x 1, at the end of surgery8,23

Treatment:
0.625 mg IV x 11,13

Evidence for PONV prevention is not as strong as for aprepitant, 5-HT3 antagonists, or dexamethasone.20 Combo with ondansetron seems more effective than either med alone.22

Side effects include sedation, dizziness, hallucinations, and EPS.1,13

“Black box” warning added due to reports of QTc prolongation, arrhythmias, and sudden cardiac death. However, for doses <2.5 mg IV/IM, electrocardiogram (ECG) monitoring is not recommended and the boxed warning about QTc prolongation/torsades risk does not apply.8,13,21 When QTc monitoring is performed, avoid droperidol if QTc >440 ms (men) or >450 ms (women).21,23

Granisetron

5-HT3 antagonist

Tablet: ~$8 (1 mg)

Injection: ~$10
(1 mg/1 mL vial)

Prevention:
0.35 to 3 mg IV x 1, given at the end of surgery (1 mg is commonly used)1,8,13

1 mg PO x 1, given
1 hour before surgery1

Treatment:
0.1 mg IV x 18,13

Appears equally effective as ondansetron for PONV prevention and treatment.1,8

Side effects include headaches, constipation (especially if given to a patient receiving opioids), and QTc prolongation.1,8

Granisetron 0.1 mg IV is a recommended option to treat established PONV in patients who did NOT receive any meds for prevention. Doses between 0.1 mg and 3 mg have been studied, without evidence of dose responsiveness, thus lower doses are recommended.8,13

May be the preferred 5-HT3 antagonist option (instead of ondansetron) for patients with a history of delayed PONV due to its longer half-life.13,23

CYP3A4 substrate.13

Haloperidol

Butyrophenone

Tablet: ~$0.50 (1 mg)

Injection: ~$2.80
(5 mg/1 mL vial)

Prevention:
0.5 to <2 mg IM or IV
x 1, given at induction or at the end of surgery8

Treatment:
1 mg IV x 11

Has been given as an alternative to droperidol, and is similarly effective for PONV prevention.8

Noninferior to ondansetron for PONV treatment, but is more sedating when given IV.1,8,14

Side effects include headache, sedation, dizziness, dry mouth, and EPS. EPS appears to be less common with IV than other routes of administration.13

Appears to have a similar risk for QTc prolongation as the 5-HT3 antagonists.9 QTc prolongation is more likely to occur with IV administration, but is rare at doses lower than 2 mg.17

Metoclopramide

Dopamine antagonist

Disintegrating tablet:
~$7.50 (5 mg)

Injection:
~$1 (10 mg/2 mL vial)

Prevention:
10 mg IM or 10 to
25 mg IV x 1, given 15 to 30 minutes before the end of surgery1,13

10 to 20 mg IM x 1, given before the end of surgery13

Treatment:
10 mg IV x 11

Not considered as effective as other PONV options.8

Combinations using metoclopramide are not usually more effective than monotherapy.1

Weakly effective for PONV prevention at usual doses.A 25 to 50 mg dose is needed to provide similar efficacy to ondansetron.8

Side effects include sedation, hypotension (with fast injection), and EPS (more likely with higher doses).1,10,13

Dose may need to be adjusted based on renal function.13

IV doses should be given over 1 to 2 minutes to prevent feelings of restlessness and anxiety.10 For IV doses >10 mg, dilute and infuse over at least 15 minutes.13

Naloxone, low-dose

Opioid receptor antagonist

Injection:
~$9.50 (0.4 mg/1 mL vial)

Prevention:
0.2 to 0.25 mcg/kg/hr by continuous infusion postoperatively8,15

0.001 to 0.061 mcg/kg/hr delivered via patient-controlled analgesia (PCA)15

Continuous infusion route of administration more effective for PONV prevention than when given via PCA.8,15

Reduced postoperative nausea and the need for rescue medications, but did not reduce postop vomiting [Evidence Level A-2].8,15

Ondansetron

5-HT3 antagonist

Tablet: <$1 (4 mg, 8 mg)

Disintegrating tablet:
<$1 (8 mg)

Injection:
<$1 (4 mg/2 mL vial)

Prevention:
4 mg IV x 1, given at the end of surgery8

8 mg disintegrating tablet PO x 1, given 30 minutes before surgery3

Treatment:
4 mg IV x 113

“Gold standard” antiemetic for prevention and treatment of PONV.8

Combo with droperidol seems more effective than either med alone.22

Ondansetron 4 mg IV is considered a first-line option to treat established PONV in patients who did NOT receive meds for prevention.8

Side effects include headache, diarrhea, and constipation.13

Higher doses are more likely to cause QTc prolongation; single doses should not exceed 16 mg.13

CYP3A4, CYP2D6, and CYP1A2 substrate.13

Palonosetron

5-HT3 antagonist

Injection:
~$15 (0.25 mg/5 mL)

Prevention:
0.075 mg IV x 1, given right before induction8,13

More effective than ondansetron or granisetron for PONV prevention and similar effectiveness as aprepitant.8

Especially helpful for prolonged PONV prevention (up to 72 hours), due to its long half-life (40 hours).10

Low risk for drug interactions, and does not prolong the QTc.13

Promethazine

Phenothiazine

Injection:
<$2 (25 mg/mL vial)

Prevention:
6.25 mg to 12.5 mg IM (preferred) or IV x 1
(at start of surgery)8,13

Treatment:
6.25 mg to 12.5 mg IM (preferred) or IV x 11,8

12.5 mg to 25 mg IM (preferred) or IV q 4 to
6 hours PRN10,13

Limited evidence for efficacy for prevention of PONV.8 However, consider for treatment of established PONV, only when other safer alternatives can’t be used.2,8

Deep IM injection is the preferred route of administration.10 Subcutaneous administration is contraindicated, and IV injection should be avoided, if possible.13 If given IV, avoid concentrations >25 mg/mL and avoid administration rates >25 mg/minute.13

“Black box” warning about tissue damage, including thrombophlebitis, gangrene, and amputation.13

Side effects include sedation and EPS.13 Anticholinergic.13 Beers List drug.13

CYP2D6 substrate and inhibitor; CYP2B6 substrate.10,13

Rolapitant

Varubi

Neurokinin-1 antagonist

Tablet:
~$330 (90 mg)

Prevention:
90 to 180 mg PO given at induction (doses used in studies: 70 to 200 mg)8

Similar efficacy to ondansetron during the first 24 hours postoperatively, and more effective for PONV prevention during postoperative days two and three.8

Half-life of 180 hours.8,18

CYP2D6 inhibitor; contraindicated with thioridazine or pimozide.18

Rolapitant currently only FDA-approved for prevention of chemo-induced nausea/vomiting.13

Scopolamine

Transderm Scop, generics

Anticholinergic

Transdermal patch:
~$15 (1 mg/72 hours)

Prevention:
1 patch, applied behind the ear two hours before induction or as early as the night before surgery8,13

As effective as ondansetron or droperidol for PONV prevention.1

Onset of action is as early as two to four hours after application, and effects last up to
72 hours.8,13

Not effective alone as rescue therapy for established PONV.1

Sedating.13 Anticholinergic. Beers List drug.

Remove patch 24 hours after surgery.13 If not removed prior to discharge, ensure patient counseling for proper removal and disposal.23

Non-Pharmacologic Management of PONV

Options listed in alphabetical order; NOT order of preference. Evidence is limited.

Intervention

Adult PONV Dosing Regimens

Therapeutic Considerations

IV hydration
Lactated Ringer’s (LR),
Dextrose 5% in water (D5W)/LR, Normal saline (NS)

Crystalloids

Prevention:
10 to 30 mL/kg IV infusion7,8

Reduces both early and late PONV.7,8

May reduce the need for rescue antiemetics.7,8

May be more effective for late onset PONV prevention, than for PONV in first 24 hours following surgery.19

Transdermal stimulation
ReliefBand, etc

Transcutaneous electrical acupoint stimulation

Cost:6 ~$100
(ReliefBand 50 Hours)

Prevention:
Follow product labeling for specific instructions.

Uses conductivity gel.6

Usually applied to acupoint P6.25

Stimulation level is adjusted per patient tolerability.25

May be covered by insurance.24

Reduces risk and severity of PONV and need for rescue antiemetics.25,26

Most studies have been done in China, as part of a multimodal antiemetic strategy in patients receiving general anesthesia25,26

Side effects may include redness, itching, and swelling at the application site.26

70% isopropyl alcohol
Kendall Webcol prep pad, etc

Aromatherapy

Treatment:
3 deep inhalations q 5 to 15 minutes PRN, repeated up to 3 times.4,5

Fold prep pad in half and hold 0.5 inches below patient nares.4

Is thought to act at multiple sites within the chemoreceptor trigger zone.4

Fast onset (~10 to 15 minutes), but short-lived.4,5

May reduce the use of rescue antiemetics
[Evidence Level B-2].16

  1. Pricing based on wholesale acquisition cost (WAC), for generic when available. Medication pricing by Elsevier, accessed March 2023.

Abbreviations: EPS = extrapyramidal symptoms; IV = intravenous; PO = oral; PONV = postoperative nausea and vomiting; PRN = as needed; QTc = corrected QT-interval.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]

References

  1. Cao X, White PF, Ma H. An update on the management of postoperative nausea and vomiting. J Anesth. 2017 Aug;31(4):617-626.
  2. ISMP. 2022-2023 targeted medication safety best practices for hospitals. https://www.ismp.org. (Accessed March 18, 2023).
  3. Grover VK, Mathew PJ, Hegde H. Efficacy of orally disintegrating ondansetron in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: a randomised, double-blind placebo controlled study. Anaesthesia. 2009 Jun;64(6):595-600.
  4. Pellegrini J, DeLoge J, Bennett J, Kelly J. Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified as at high risk for developing PONV. AANA J. 2009 Aug;77(4):293-9.
  5. Cotton JW, Rowell LR, Hood RR, Pellegrini JE. A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home. AANA J. 2007 Feb;75(1):21-6.
  6. ReliefBand 50 Hours. https://www.reliefband.com/collections/reliefband/products/reliefband%C2%AE-7-day. (Accessed March 18, 2023).
  7. Jewer JK, Wong MJ, Bird SJ, et al. Supplemental perioperative intravenous crystalloids for postoperative nausea and vomiting. Cochrane Database Syst Rev. 2019 Mar 29;3(3):CD012212.
  8. Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020 Aug;131(2):411-448. Erratum in: Anesth Analg. 2020 Nov;131(5):e241.
  9. Singh PM, Borle A, Makkar JK, et al. Haloperidol Versus 5-HT3 Receptor Antagonists for Postoperative Vomiting and QTc Prolongation: A Noninferiority Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials. J Clin Pharmacol. 2018 Feb;58(2):131-143 [abstract].
  10. Kaye AD, Cornett EM, Chalabi J, et al. Pharmacology of Antiemetics: Update and Current Considerations in Anesthesia Practice. Anesthesiol Clin. 2017 Jun;35(2):e41-e54.
  11. DREAMS Trial Collaborators and West Midlands Research Collaborative. Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial). BMJ. 2017 Apr 18;357:j1455.
  12. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2000 Jan;90(1):186-94.
  13. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2023. http://www.clinicalkey.com. (Accessed March 19, 2023).
  14. Yazbeck-Karam VG, Siddik-Sayyid SM, Barakat HB, et al. Haloperidol Versus Ondansetron for Treatment of Established Nausea and Vomiting Following General Anesthesia: A Randomized Clinical Trial. Anesth Analg. 2017 Feb;124(2):438-444.
  15. Barrons RW, Woods JA. Low-Dose Naloxone for Prophylaxis of Postoperative Nausea and Vomiting: A Systematic Review and Meta-analysis. Pharmacotherapy. 2017 May;37(5):546-554
  16. Hines S, Steels E, Chang A, Gibbons K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2018 Mar 10;3(3):CD007598.
  17. Meyer-Massetti C, Cheng CM, Sharpe BA, et al. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med. 2010 Apr;5(4):E8-16.
  18. Product information for Varubi. Tersera Therapeutics. Deerfield, IL 60015. August 2020.
  19. Apfel CC, Meyer A, Orhan-Sungur M, et al. Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review. Br J Anaesth. 2012 Jun;108(6):893-902.
  20. Weibel S, Rücker G, Eberhart LH, Pace NL, et al. Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis. Cochrane Database Syst Rev. 2020 Oct 19;10(10):CD012859.
  21. Perkins J, Ho JD, Vilke GM, DeMers G. American Academy of Emergency Medicine Position Statement: Safety of Droperidol Use in the Emergency Department. J Emerg Med. 2015 Jul;49(1):91-7.
  22. Matsota P, Angelidi M, Pandazi A, et al. Ondansetron-droperidol combination vs. ondansetron or droperidol monotherapy in the prevention of postoperative nausea and vomiting. Arch Med Sci. 2015 Apr 25;11(2):362-70.
  23. MD Anderson Cancer Center. Nausea/vomiting associated with surgery – adult. October 19, 2019. https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-management/clin-management-ponv-web-algorithm.pdf. (Accessed March 22, 2023).
  24. Aetna. Electrical stimulation for nausea, vomiting and motion sickness (PrimaBella and ReliefBand) and other selected indications. Reviewed November 1, 2022. http://www.aetna.com/cpb/medical/data/600_699/0676.html. (Accessed March 18, 2023).
  25. Gao W, Zhang L, Han X, et al. Transcutaneous Electrical Acupoint Stimulation Decreases the Incidence of Postoperative Nausea and Vomiting After Laparoscopic Non-gastrointestinal Surgery: A Multi-Center Randomized Controlled Trial. Front Med (Lausanne). 2022 Mar 14;9:766244.
  26. Chen J, Tu Q, Miao S, et al. Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials. Int J Surg. 2020 Jan;73:57-64.
  27. Pang QY, Wang JY, Liang XL, et al. The safety of perioperative dexamethasone with antiemetic dosage in surgical patients with diabetes mellitus: a systematic review and meta-analysis. Perioper Med (Lond). 2023 Mar 8;12(1):4.
  28. Product information for Aponvie. Heron Therapeutics. San Diego, CA 92121. March 2023.
  29. Product information for Emend. Merck Sharp & Dohme. Rahway, NJ 07065. May 2022

Cite this document as follows: Clinical Resource, Postoperative Nausea and Vomiting Management. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber’s Letter. April 2023. [390431]

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