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October 21, 2008
3:00 PM - 4:30 PM
Room Room 230A
Aprepitant Versus Multimodal Antiemetic Prophylaxis Following Extended-Release Epidural Morphine
Yeong-Shiuh Tang, M.D., Craig T. Hartrick, M.D., David Hunstad, M.D., John Pappas, M.D., Daniel Silvasi, M.D.
Anesthesiology, Beaumont Hospitals, Troy, Michigan
Background: Extended-release epidural morphine (EREM) is effective for analgesia following major orthopedic surgery, however postoperative nausea/vomiting (PONV) is a limitation. The incidence of PONV following prophylactic aprepitant (AP), a neurokinin-1 antagonist (NK-1), was compared to prophylactic time-contingent multimodal antiemetics in patients receiving EREM for analgesia following unilateral primary total knee arthroplasty (TKA).

Methods: Prospectively collected quality assurance data were examined with IRB approval. A sequential, open-label, matched case-control study compared PONV following EREM in patients receiving a “cocktail” containing ondansetron and dexamethasone, and either metoclopramide, diphenhydramine, or prochlorperazine, maintained for the 48 hour study period, to patients receiving AP 40mg as a single preoperative oral dose. Cases were matched for procedure (TKA), age, EREM dose, and major risk factors (sex, smoking, previous PONV or motion sickness). Patients receiving both prophylactic AP and another prophylactic antiemetic were excluded. Odds ratio (OR) was computed using GraphPad (InStat). Non-parametric analyses were used as appropriate.

Results: Twelve consecutive patients (3 male; 9 female) receiving AP prior to EREM were matched to 12 patients of the same sex of similar age (range 51-84 yrs.) and EREM dose (range 5-10mg) receiving a time-contingent “cocktail” using 3 or 4 agents. Pairing for age, dose, and risks was highly effective (Table 1).[table1]The incidence of PONV was significantly less in the aprepitant group (p=0.039, Fisher's Exact Test; OR=0.11; 95%CI: 0.018 to 0.706, p=0.03; Figure 1).

Figure 1. Incidence of PONV[figure1]Discussion: Risk factors for PONV include non-smoking, female sex, history of motion sickness or previous PONV, and postoperative opioids (1). Multimodal prophylaxis is recommended for patients at high risk (2). EREM provides 48 hours of analgesia following TKA (3); the risk for PONV may be similarly prolonged. AP significantly reduced, but did not eliminate PONV compared to multimodal antiemetics. A prospective, randomized, blinded study is planned to examine the inclusion of a NK-1 antagonist to a standardized multimodal regime in this high risk population.


1. Pierre S, et al. A risk score-dependent antiemetic approach effectively reduces postoperative nausea and vomiting--a continuous quality improvement initiative. Can J Anesth. 2004;51:320-5.

2. Apfel CC, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441-51.

3. Hartrick CT, et al. Evaluation of a single-dose, extended-release epidural morphine formulation for pain after knee arthroplasty. J Bone Joint Surg Am. 2006;88:2535-6.

Anesthesiology 2008; 109 A1587
Table 1. Case Pairing
PairingsexageEREM dosePONV historysmoking
Spearman r1.00.8970.9200.6741.0
p valuep<0.0001p<0.0001p<0.0001p=0.016p<0.0001
Figure 1