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Systematic Review • Rev. Bras. Anestesiol. 70 (5) • Sep-Oct 2020 • https://doi.org/10.1016/j.bjane.2020.06.015 copy

Neurokinin-1 receptor antagonists for postoperative nausea and vomiting: a systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

Postoperative Nausea and Vomiting (PONV) is a common complication of general anesthesia. Several kinds of antiemetics, including 5-Hydroxytryptamine3 (5-HT3) receptor antagonists, and Neurokinin-1 (NK-1) receptor antagonists have been used to treat PONV.

Objectives:

To compare the antiemetic effect of NK-1 receptor antagonists, including fosaprepitant.

Data sources:

Online databases (PubMed, MEDLINE, Scopus, The Cochrane Library databases) were used.

Study eligibility criteria, participants, and interventions:

Randomized Controlled Trials (RCTs) performed in patients over 18 years with ASA-PS of I‒III, aimed to assess the efficacy of antiemetics including NK-1 receptor antagonists and 5-HT3 receptor antagonists, and compared the incidence of PONV were included.

Study appraisal and synthesis methods:

All statistical assessments were conducted by a random effect approach, and odds ratios and 95% Confidence Intervals were calculated.

Results:

Aprepitant 40 mg and 80 mg significantly reduced the incidence of vomiting 0‒24 hours postoperatively (Odds Ratio [OR = 0.40]; 95% Confidence Interval [95% CI 0.30‒0.54]; p < 0.001, and OR = 0.32; 95% CI 0.19‒0.56; p < 0.001). Fosaprepitant could also reduce the incidence of vomiting significantly both 0‒24 and 0‒48 hours postoperatively (OR = 0.07; 95% CI 0.02‒0.24; p < 0.001 and OR = 0.07; 95% CI 0.02‒0.23; p < 0.001).

Limitations:

Risk factors for PONV are not considered, RCTs using multiple antiemetics are included, RCTs for fosaprepitant is small, and some bias may be present.

Conclusions and implications of key findings:

Aprepitant and fosaprepitant can be effective prophylactic antiemetics for postoperative vomiting. However, more studies are required for higher-quality meta-analyses.

Systematic review registration number:

CRD42019120188.

KEYWORDS
Postoperative nausea and vomiting; Prophylaxis; Treatment; NK-1 receptor antagonists

Author, year, country	Participants	Surgery	Anesthesia	Antiemetic prophylaxis	Patients	Female	Age (y, Mean ± SD or median)	Surgical Time (min, Mean ± SD or median)	Anesthesia time (min, Mean ± SD or median)	Postoperative analgesia	Multicenter study
Yoo et al.¹⁸18 Yoo JH, Kim SI, Chung JW, et al. Aprepitant in combination with palonosetron for the prevention of postoperative nausea and vomiting in female patients using intravenous patient-controlled analgesia. Korean J Anesthesiol. 2018;71:440-6. 2018 Korea	100	Elective surgery	Sevoflurane or desflurane	Ap 80 mg + Palono 0.075 mg vs. Palono 0.075 mg	41 vs. 44	41 vs. 44	52.4 ± 11.4 vs. 52.1 ± 12.0	86.2 ± 56.1 vs. 89.1 ± 60.0	128.5 ± 56.1 vs. 131.5 ± 65.9	Fentanyl-based IV-PCA	No
De Morais et al.¹⁹19 De Morais LC, Sousa AM, Flora GF, et al. Aprepitant as a fourth antiemetic prophylactic strategy in high-risk patients: a double-blind, randomized trial. Acta Anaesthesiol Scand. 2018;62:483-92. 2018 Brazil	66	Laparoscopic intermediate procedures to abdominal or pelvic cancer	Propofol epidural anesthesia	Ap 80 mg + Ondan 4-8 mg + dexamethasone 4-8 mg vs placebo + Ondan 4-8 mg + dexamethasone 4-8 mg	34 vs. 32	34 vs. 32	60.5 (31.87) Vs. 50.5 (19,77)	437.5 (131, 610) vs. 367.5 (145, 600)	N/A	Tramadol 50 mg + dipyrone 2g	No
Ham et al.²⁰20 Ham SY, Shim YH, Kim EH, et al. Aprepitant for antiemesis after laparoscopic gynaecological surgery: a randomised controlled trial. Eur J Anaesthesiol. 2016;33:90-5. 2016 Korea	110	Laparoscopic gynecological surgery	Sevoflurane	Ap 80 mg + Ondan 4 mg vs placebo + Ondan 4 mg	55 vs. 55	55 vs .55	40 (22-55) vs. 42 (23-61)	N/A	N/A	Fentanyl IV	No
Kakuta et al.¹⁰10 Kakuta N, Kume K, Hamaguchi E, et al. The effects of intravenous fosaprepitant and ondansetron in the prevention of postoperative nausea and vomiting in patients who underwent lower limb surgery: a prospective, randomized, double-blind study. J Anesth. 2015;29:836-41. 2015 Japan	38	Lower limb surgery	Sevoflurane or desflurane	Fosaprepitant 150 mg vs. Ondan 4 mg	19 vs. 19	11 vs. 13	61 ± 11 vs. 56 ± 16	171 ± 47 vs. 183 ± 67	242 ± 55 vs. 264 ± 72	Diclofenac sodium 25 mg pentazocine 15mg loxoprofen 60mg celecoxib 100 mg	No
Soga et al.⁹9 Soga T, Kume K, Kakuta N, et al. Fosaprepitant versus ondansetron for the prevention of postoperative nausea and vomiting in patients who undergo gynecologic abdominal surgery with patient-controlled epidural analgesia: a prospective, randomized, double-blind study. J Anesth. 2015;29:696-701. 2015 Japan	44	Gynecologic abdominal surgery	Sevoflurane, epidural anesthesia with fentanyl	Fosaprepitant 150 mg vs. Ondan 4 mg	24 vs. 20	24 vs. 20	52 ± 11 vs 52 ± 11	209 ± 96 vs. 198 ± 82	246 ± 94 vs. 239 ± 86	Epidural anesthesia with fentanyl	No
Long et al.²¹21 Long JB, Galdi L, Hentz JG, et al. Prevention of postoperative nausea and vomiting in elective hysterectomy: a prospective, randomized, placebo controlled outcomes trial of aprepitant NK-1 receptor antagonist. Open J Anesthesiol. 2014;4:301-7. 2014 USA	94	Elective hysterectomy	Sevoflurane	Ap 40 mg + dexamethasone 8 mg + Ondan 4 mg vs. placebo + dexamethasone 8 mg + Ondan 4 mg	35 vs. 59	35 vs. 59	60 ± 12 vs. 53 ± 12	153 ± 64 vs. 159 ± 81	N/A	N/A	No
Sinha et al.²²22 Sinha AC, Singh PM, Williams NW, et al. Aprepitant’s prophylactic efficacy in decreasing postoperative nausea and vomiting in morbidly obese patients undergoing bariatric surgery. Obes Surg. 2014;24:225-31. 2014 USA	124	Bariatric surgery	Sevoflurane or desflurane	Ap 80 mg + Ondan 4 mg vs. placebo + Ondan 4 mg	64 vs. 60	42 vs. 39	43.09 ± 12.45 vs. 43.20 ± 12.70	153.05 ± 43.82 vs. 141.97 ± 41.80	N/A	Fentanyl IV or morphine IV	No
Tsutsumi et al.⁸8 Tsutsumi YM, Kakuta N, Soga T, et al. The effects of intravenous fosaprepitant and ondansetron for the prevention of postoperative nausea and vomiting in neurosurgery patients: a prospective, randomized, double-blinded study. Biomed Res Int. 2014;2014:307025. 2014 Japan	64	Elective craniotomy	Propofol	fosaprepitant 150 mg vs. ondansetron 4 mg	32 vs. 32	17 vs. 21	62 ± 10 vs. 58 ± 14	366 ± 137 vs. 403 ± 197	460 ± 138 vs. 513 ± 166	Diclofenac sodium 25 mg pentazocine 15 mg loxoprofen 60mg	No
Moon et al.²³23 Moon HY, Baek CW, Choi GJ, et al. Palonosetron and aprepitant for the prevention of postoperative nausea and vomiting in patients indicated for laparoscopic gynaecologic surgery: a double-blind randomized trial. BMC Anesthesiol. 2014;14:68. 2014 Korea	93	Laparoscopic gynecologic surgery	Desflurane	Ap 40 mg vs. Palono 0.075 mg	46 vs. 47	46 vs. 47	37.9 ± 11.1 vs. 37.6 ± 8.0	71.5 ± 37.7 vs. 79.2 ± 42.2	N/A	Nefopam 20 mg and automated IV-PCA with fentanyl 20 µg.kg^-1	No
Lim et al.²⁴24 Lim CS, Ko YK, Kim YH, et al. Efficacy of the oral neurokinin-1 receptor antagonist aprepitant administered with ondansetron for the prevention of postoperative nausea and vomiting. Korean J Anesthesiol. 2013;64:212-7. 2013 Korea	90	Elective rhinolaryngo-logical surgery	Desflurane	Ap 125 mg + Ondan 4 mg vs. Ap 80 mg + Ondan 4 mg vs. Ondan 4mg	26 vs. 28 vs. 24	6 vs. 10 vs. 6	41 ± 12 vs. 45 ± 12 vs. 42 ± 12	55 ± 32 vs. 83 ± 72 vs. 62 ± 32	77 ± 31 vs. 105 ± 73 vs. 84 ± 33	Ketorolac 30 mg	No
Vallejo et al.²⁵25 Vallejo MC, Phelps AL, Ibinson JW, et al. Aprepitant plus ondansetron compared with ondansetron alone in reducing postoperative nausea and vomiting in ambulatory patients undergoing plastic surgery. Plast Reconstr Surg. 2012;129:519-26. 2012 USA	150	Ambulatory plastic surgery	Sevoflurane	Ap 40 mg + Ondan 4 mg vs. placebo + Ondan 4 mg	75 vs. 75	70 vs. 70	60.5 (31.87) vs. 50.5 (19,77)	122.9 ± 73.3 vs. 117.4 ± 65.4	164.3 ± 80.1 vs. 153.2 ± 70.1	Fentanyl, morphine hydromorohine, oxycodone ketorolac, meperidine acetaminophen, ibuprofen	No
Altorjay et al.²⁶26 Altorjay A, Melson T, Chinachoit T, et al. Casopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study. Arch Surg. 2011;146:201-6. 2011 USA	456	Laparoscopic gynecologi-cal surgery	Sevoflurane	Caso 50 mg + Ondan 4 mg vs. Placebo + Ondan 4 mg	227 vs. 229	227 vs. 229	44.4 ± 12.19 vs. 44.8 ± 12.44	87.7 ± 50.39 vs. 92.1 ± 56.96	N/A	N/A	Yes
Lee et al.²⁷27 Lee SJ, Lee SM, Kim SI, et al. The effect of aprepitant for the prevention of postoperative nausea and vomiting in patients undergoing gynecologic surgery with intravenous patient controlled analgesia using fentanyl: aprepitant plus ramosetron vs ramosetron alone. Korean J Anesthesiol. 2012;63:221-6. 2012 Korea	84	Gynecological surgery	Desflurane	Ap 80 mg + Ramo 0.3 mg vs. Ramo 0.3 mg	42 vs. 42	42 vs. 42	43.8 ± 8.2 vs. 43.6 ± 10.4	113.4 ± 61.6 vs. 124.1 ± 48.7	145.0 ± 62.3 vs. 158.8 ± 48.9	IV-PCA with fentanyl 21 µg.h^-1	No
Gan et al.²⁸28 Gan TJ, Gu J, Singla N, et al. Rolapitant Investigation Group. Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg. 2011;112:804-12. 2011 USA	619	Elective open abdominal surgery	Sevoflurane or desflurane or isoflurane	Placebo vs. Rola 5 mg vs. Rola 20 mg vs. Rola 70 mg vs. Rola 200 mg vs. Ondan 4 mg	103 vs. 103 vs. 102 vs. 103 vs. 104 vs. 104	103 vs. 103 vs. 102 vs. 103 vs. 104 vs. 104	45.8 ± 10.1 vs. 44.6 ± 10.1 vs. 47.1 ± 12.8 vs 44.1 ± 10.1 vs. 47.4 ± 10.9 vs. 47.9 ± 12.6	209 ± 96 vs. 198 ± 82	2.2 ± 1.0 vs. 2.2 ± 1.0 vs. 2.2 ± 1.1 vs 2.1 ± 1.9 vs. 2.0 ± 0.9 vs. 2.3 ± 1.1	N/A	Yes
Habib et al.²⁹29 Habib AS, Keifer JC, Borel CO, et al. 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;112:813-8. 2011 USA	104	Craniotomy	Isoflurane	Ap 40 mg + dexamethasone 10 mg vs. Ondan 4 mg + dexamethasone 10 mg	51 vs. 53	28 vs. 30	51 ± 13 vs. 48 ± 13	180 (130, 223) vs. 179 (128, 213)	N/A	Fentanyl IVoral oxycodone oral acetaminophen	No
Singla et al.³⁰30 Singla NK, Singla SK, Chung F, et al. Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients. Anesthesiology. 2010;113:74-82. 2010 USA	702	Laparotomic gynecologic surgical procedure or laparoscopic cholecyst-ectomy	Sevoflurane or desflurane	Caso 0 mg + Ondan 4 mg vs. Caso 50 mg + Ondan 4 mg vs. Caso 100 mg + Ondan 4 mg vs. Caso 150 mg + Ondan 4 mg vs. Caso 150 mg	140 vs. 140 vs. 140 vs. 140 vs. 142	140 vs. 140 vs. 140 vs. 140 vs. 142	39.3 ± 8.15 vs. 38.1 ± 8.24 vs. 39.5 ± 8.58 vs. 39.3 ± 7.84 vs. 38.5 ± 8.33	77.2 ± 43.28 vs. 77.0 ± 49.87 vs. 80.5 ± 47.92 vs. 77.8 ± 43.74 vs. 79.1 ± 51.76	N/A	N/A	Yes
Diemunsch et al.⁴4 Diemunsch P, Gan TJ, Philip BK, et al. Aprepitant-PONV Protocol 091 International Study Group. 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;99:202-11. 2007 USA	866	Open abdominal surgery	Volatile anesthesia	Ap 40 mg vs. Ap 125 mg vs. Ondan 4 mg	303 vs. 304 vs. 285	273 vs. 274 vs. 257	46 ± 11 vs. 46 ± 11 vs. 45 ± 11	N/A	2.0 ± 1.0 vs. 1.9 ± 1.0 vs. 1.8 ± 0.9 (h)	N/A	Yes
Gan et al.⁵5 Gan TJ, Apfel CC, Kovac A, et al. Aprepitant-PONV Study Group. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg. 2007;104:1082-9. 2007 USA	766	Open abdominal surgery	Volatile anesthesia	Ap 40 mg vs. Ap 125 mg vs. Ondan 4 mg	261 vs. 252 vs. 253	245 vs. 238 vs. 239	46 ± 11.2 vs. 44 ± 9.4 vs. 45 ± 11.2	N/A	2.0 ± 1.0 vs. 2.0 ± 1.0 vs. 2.2 ± 1.2 (h)	N/A	Yes

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