Olanzapine as a prophylactic antiemetic for preventing postoperative nausea and vomiting after general anesthesia: A systematic review and metaanalysis

Grigio, Thiago Ramos; Timmerman, Hans; Sousa, Angela Maria; Wolff, André Paul

doi:10.1016/j.clinsp.2024.100345

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Original articles • Clinics 79 • 2024 • https://doi.org/10.1016/j.clinsp.2024.100345 copy

Olanzapine as a prophylactic antiemetic for preventing postoperative nausea and vomiting after general anesthesia: A systematic review and metaanalysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects.

Methods:

A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute.

Results:

Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I² = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I² = 31 %).

Conclusion:

This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.

Keywords:
Antipsychotic agent; Perioperative care; Postoperative emesis; Postoperative nausea and vomiting; Review; Surgical

HIGHLIGHTS

Olanzapine is identified as a potentially effective prophylactic antiemetic.

Olanzapine reduces the incidence of postoperative nausea and vomiting.

Olanzapine has few side effects.

Study	Year	Country	Sample size	Patients	Age (Mean)	Female Gender	Surgery	Number of groups	Interventions	Comparisons	Time of measurement	Type of anesthesia	Induction	Maintenance	Results^a a Only significant between-group differences (p < 0.05) are shown; ↑, Significantly increased; ↓, Significantly decreased; NA, Not Applicable.	Measured outcome	Adverse events reported
Grigio, T. R. et al.	2023	Brazil	96	Adult with oncological disease, age 18‒60y, high risk for PONV (3 or 4 risk factors), previous history of CINV	44.2	96.8 %	Medium or major surgery	2	Olanzapine 10 mg + dexamethasone 4 mg + ondansetron 4 mg	Dexamethasone 4 mg + ondansetron 4 mg	0‒6 h, 0‒24 h and 24‒48 h after surgery	General anesthesia + neuraxial anesthesia	Propofol	TIVA + fentanyl	↓ incidence of PONV (60 % less)	Postoperative nausea or vomiting (or retching), only nausea, only vomiting	Lightheadedness/dizziness, dry mouth, itching, sleepness, hypotension, headache, restless, anxiety, sleep disturbance
Hyman, J. B. et al.	2020	USA	140	Adult female, age 18‒50y	37	100 %	Ambulatory gynecologic or plastic surgery	2	Olanzapine 10 mg + dexamethasone 8 mg + ondansetron 4 mg	Dexamethasone 8 mg + ondansetron 4 mg	‒24 h postdischarge, 0‒ 24 h after surgery	General anesthesia	Midazolam 2 mg IV + Propofol 1.5 to 2.5 mg/kg + duccinylcholine 1 to 2 mg/kg or rocuronium 0.6 mg/kg	Sevoflurane + fentanyl	↓ incidence of PONV (39 % less)	Postoperative nausea and/or vomiting	Sedation, visual disturbance, urinary retension, lightheadedness/dizziness
Seki, H. et al	2022	Japan	210	Adult female, age 20‒65y, at least 2 factors for PONV	41.4	100 %	Laparoscopic gynecological surgery	2	Olanzapine 5 mg + dexamethasone 6.6 mg	Dexamethasone 6.6 mg	0.5‒2 h, 2‒6 h, 6‒24 h after surgery	General anesthesia	?	Fentanyl + remifentanyl	↓ incidence of PONV (21 % less)	Postoperative nausea, vomiting and use of metoclopramide	Hypotension, headache
Ibrahim, M. et al	2013	Egypt	82	Adult female, ASA I or II	42	100 %	Breast surgery (mastectomy, tumor biopsy, reductive mastoplasty and other plastic surgery)	3	Olanzapine 5 mg and olanzapine 10 mg	Ondansetron 16 mg orally and placebo	0‒2 h, 2‒6 h, 6‒12 hand 12‒24 h after surgery	General anesthesia	Midazolam1-2 mg + propofol 2‒3 mg/ kg + rocuronium 1 mg/kg	Sevoflurane + fentanyl 2‒5 mcg/kg + nitrous oxide	NA	Complete response (without nausea, and vomiting, no rescue therapy), “no nausea” and “noemesis/’	Headache, sedation, anxiety, restlessness, and abnormal muscle movements

Author Year	Hyman 2020	Ibrahim 2013	Seki 2022	Grigio 2023
Criteria
1. Was the study described as a randomized, a randomized trial, a randomized clinical trial, or an RCT?	Yes	Yes	Yes	Yes
2. Was the method of randomization adequate (i.e., use of randomly generated assignment)?	NR	CD	Yes	Yes
3. Was the treatment allocation concealed (so that assignments could not be predicted)?	CD	NR	Yes	Yes
4. Were study participants and providers blinded to treatment group assignment?	Yes	Yes	Yes	Yes
5. Were the people assessing the outcomes blinded to the participants’ group assignments?	Yes	No	Yes	Yes
6. Were the groups similar at baseline on important characteristics that could affect outcomes (e.g., demographics, risk factors, co-morbid conditions)?	Yes	Yes	Yes	Yes
7. Was the overall drop-out rate from the study at endpoint 20 % or lower of the number allocated to treatment?	Yes	Yes	Yes	Yes
8. Was the differential drop-out rate (between treatment groups) at endpoint 15 percentage points or lower?	Yes	Yes	Yes	Yes
9. Was there high adherence to the intervention protocols for each treatment group?	Yes	Yes	Yes	Yes
10. Were other interventions avoided or similar in the groups (e.g., similar background treatments)?	Yes	Yes	Yes	Yes
11. Were outcomes assessed using valid and reliable measures, implemented consistently across all study participants?	Yes	Yes	Yes	Yes
12. Did the authors report that the sample size was sufficiently large to be able to detect a difference in the main outcome between groups with at least 80 % power?	Yes	Yes	Yes	Yes
13. Were outcomes reported or subgroups analyzed pre-specified (i.e., identified before analyses were conducted)?	Yes	Yes	Yes	Yes
14. Were all randomized participants analyzed in the group to which they were originally assigned, i.e., did they use an intention-to-treat analysis?	Yes	Yes	No	Yes

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[1] *Corresponding author. E-mail address: t.r.grigio@umcg.nl (T.R. Grigio)