Research

Original Investigation

Use of Aprepitant and Factors Associated With Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Facial Plastic Surgery Scott J. Trimas, MD; Morgan D. Trimas

IMPORTANCE Patients who experience immediate postoperative nausea and vomiting

Author Audio Interview at jamafacialplasticsurgery.com

(PONV) after their facial plastic surgery procedure have a higher incidence of complications and dissatisfaction. OBJECTIVES To determine whether a single dose of aprepitant administered preoperatively can decrease the incidence of immediate PONV in patients undergoing facial plastic surgery compared with patients who are administered ondansetron hydrochloride alone and whether patient-related factors pose a greater risk of developing immediate PONV after surgery. DESIGN, SETTING, AND PARTICIPANTS In this retrospective study, we reviewed 172 patients undergoing facial plastic surgery with general anesthesia at an accredited office-based surgery practice from January 1, 2012, through December 31, 2013. INTERVENTIONS All patients received prophylactic treatment to mitigate against immediate

PONV. Fifty-six patients received aprepitant in addition to ondansetron as prophylaxis for PONV. MAIN OUTCOMES AND MEASURES Patients undergoing facial plastic surgery were assessed during the immediate postoperative period for PONV. In addition, patient age, type of procedure, duration of surgery, and sex were reported. RESULTS The addition of aprepitant preoperatively effectively reduced the PONV rate from 15.5% to 1.8% (P = . 02). Logistic regression analysis revealed that duration of surgery longer than 90 minutes (odds ratio [OR], 2.936; 95% CI, 0.560-15.385; P = .20), female sex (OR, 1.893; 95% CI, 0.379-9.448; P = .44), and type of procedure increased the likelihood of PONV after facial plastic surgery with an odds ratio of greater than 1 in this sample population. However, the odds ratios were not statistically significantly greater than 1 for the 95% CIs. Of the 19 patients who experienced PONV, 17 were women, and 17 patients had a duration of surgery longer than 90 minutes. Patient age did not appear to affect the rate of PONV (P = .32). CONCLUSIONS AND RELEVANCE Preoperative aprepitant administered within 1 hour before facial plastic surgery in patients at risk of developing PONV effectively reduce the rate of immediate PONV. Female patients and patients with facial surgery duration of longer than 90 minutes might benefit from the added expense of aprepitant to further reduce the likelihood of PONV. LEVEL OF EVIDENCE 3.

Author Affiliations: Beaches Facial Plastic and Nasal Surgery Center, Jacksonville Beach, Florida (S. J. Trimas); Department of Biology, Washington and Lee University, Lexington, Virginia (M. D. Trimas).

JAMA Facial Plast Surg. 2015;17(4):251-255. doi:10.1001/jamafacial.2015.0307 Published online May 14, 2015.

Corresponding Author: Scott J. Trimas, MD, Beaches Facial Plastic and Nasal Surgery Center, 1361 13th Ave S, Ste 125, Jacksonville Beach, FL 32250 ([email protected]).

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Research Original Investigation

P

Aprepitant for Postoperative Nausea and Vomiting in Facial Plastic Surgery

ostoperative nausea and vomiting (PONV) is a common symptom reported on patient satisfaction surveys1 and affects nearly one-third of all surgical patients.2-4 It can lead to unattended surgical consequences, such as hematoma formation, wound and suture dehiscence, or wound contamination and aspiration.1-6 Reducing the incidence of PONV requires careful assessment of the patient preoperatively to reduce risk factors. In addition, it has been previously reported that patients undergoing surgery with volatile anesthetics and long operative duration have an increased incidence of PONV.2,7 Nausea and emesis after the surgical procedure are the most significant reasons described by patients as precipitating events for poor patient satisfaction postoperatively and are big factors in patients who elect to not undergo additional surgical procedures.1,5 The cause of PONV is believed to be multifactorial.4,8-10 Multiple anatomical sites are ultimately involved in the development of PONV. The vomiting center, which is the central control site of nausea and vomiting, is located within the lateral reticular formation of the brainstem.4 This control center receives input from the cerebral cortex, vestibular system, visceral afferents via the vagal and glossopharyngeal nerves, and the chemoreceptor trigger zone.4,10 All these sites have multiple receptors specific to the following neurotransmitters: acetylcholine, serotonin, dopamine, and histamine.4,10 Because no single treatment to date can affect all areas responsible for PONV, a single treatment approach has not been found to be efficacious.2,4,8,11 Therefore, a multitreatment modality is often described as being the most effective approach to PONV prophylaxis.8 In 2006, aprepitant (Merck Sharp & Dohme Corp),12 a new antiemetic medication, was approved by the US Food and Drug Administration. Aprepitant is a selective high-affinity antagonist of human substance P and neurokinin 1 (NK1) receptors. The primary approval was for use as an antiemetic in chemotherapy treatment when used with other antiemetic agents. However, unlike other antiemetic treatments, it has little or no affinity for serotonin, dopamine, and corticosteroid receptors. Animal and human studies12,14 using positron emission tomography have found that it crosses the blood-brain barrier and occupies brain NK1 receptors. Aprepitant also augments the activity of the serotonin receptor antagonist ondansetron and the corticosteroid dexamethasone sodium and inhibits the acute and delayed phases of cisplatin-induced emesis. Therefore, because of its synergetic effect and absence of direct effect on the neurotransmitters, it is recommended that treatment with aprepitant include the use of other known antiemetics, which target the primary neurotransmitters involved in the PONV cascade. The normal recommended dosage for surgical prophylaxis is 40 mg administered within 1 to 3 hours of the surgical procedure.12 Elective plastic surgery is not immune to the problems of PONV. In fact, reports have indicated that nearly one-third of all patients undergoing plastic surgery experience PONV.2,4,7 It is a widely held belief that patients undergoing facial plastic surgery are at a higher risk although no specific studies addressing PONV have been quantitated to this patient population.2,4 Furthermore, female sex and duration of surgery longer than 252

90 minutes have been ascribed to patients undergoing plastic surgery as being better predictors of PONV.2,4,8,13 The purposes of this retrospective study were to identify a treatment approach for patients undergoing facial plastic surgery and to demonstrate whether a multitherapy approach to the prevention of PONV was effective in reducing the incidence of immediate nausea and vomiting. In addition, it would be advantageous to identify those patients who are at an additional risk of PONV. Finally, for those patients who are at a greater risk of PONV, it would be beneficial to see whether the addition of aprepitant could further reduce the incidence of PONV in patients who receive a multimodality, prophylactic regimen of antiemetics.

Methods We retrospectively reviewed the medical records of 172 consecutive patients who underwent facial plastic surgery from January 1, 2012, through December 31, 2013. Only patients who received general anesthesia were included in the analysis. The following types of procedures were performed in this patient population: rhinoplasty, rhytidectomy, endoscopic browlift, carbon dioxide laser resurfacing, blepharoplasty, otoplasty, chin implant, and neck liposuction. A total of 66 (38.4%) of the 172 patients underwent multiple procedures. Patients undergoing concomitant body procedures were excluded from the analysis. Patients were stratified into 2 age groups for comparison: those younger than 60 years and those 60 years and older. Another group for comparison were those patients who underwent a surgical procedure with a duration of longer than 90 minutes and those patients who underwent a surgical procedure with a duration of 90 minutes or less. In addition, 56 patients received aprepitant within 1 hour of their surgical procedure. Aprepitant was primarily offered to those patients who were female, had a strong history of nausea and vomiting, or were thought to be at an increased risk of nausea and vomiting (eg, those with a history of PONV after surgery, those with motion sickness, and nonsmokers). All female patients, aged 25 to 65 years, were offered aprepitant preoperatively; however, many of those patients declined because of the added cost of the drug, or the patient declined for various other reasons, including self-reported lack of nausea history, noncoverage of drug by third-party payer, or the patient’s belief that the additional drug regimen was not necessary. All patients undergoing general anesthesia followed the same guidelines to minimize perioperative nausea and vomiting. Patients received intraoperative dexamethasone sodium, 8 to 12 mg dependent on their weight, ondansetron, 4 mg intravenously at the time of anesthetic induction, and fluid hydration. Intraoperative narcotics were avoided. Patients underwent induction of anesthesia with propofol, received inhalational sevoflurane on induction, and were maintained with isoflurane and nitrous oxide. Intermittent doses of propofol were also used during the surgery if additional relaxation of the patient was required during the procedure.

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Aprepitant for Postoperative Nausea and Vomiting in Facial Plastic Surgery

Original Investigation Research

Table 1. Patient Characteristics and Surgical Procedures

Table 2. Breakdown of Surgical Procedures

No. of Patients

Characteristic

With PONV

No. of Patients

Without PONV

Undergoing a Single Procedure

Undergoing Multiple Procedures

Age, y

Procedure Type

Total

Rhinoplasty

43

With PONV 5

Rhytidectomy

82

10 8

≥60

10

77

48

36

Blepharoplasty

73

90 min

Male patients not taking aprepitant

2 (9.1)

20 (90.9)

Type of procedure Rhinoplasty

3.687 (0.580-23.438)

.17

Rhytidectomy

4.176 (0.912-19.127)

.07

Female patients not taking aprepitant

16 (17.0)

78 (83.0)

Duration of procedure >90 min

17 (12.9)

115 (87.1)

Duration of procedure ≤90 min

2 (5.0)

38 (95.0)

Abbreviation: PONV, postoperative nausea and vomiting.

Logistic regression analysis was used to determine which variables were significant predictors of PONV. The predictors included were use of aprepitant, sex, duration of surgery (>90 vs ≤90 minutes), and 4 procedures. Four other procedures (browlift, chin implant, otoplasty, and neck liposuction) were excluded because there were too few cases in the study. Table 4 gives the results of the logistic regression analysis. Of the predictors, only use of aprepitant was a statistically significant predictor of postoperative nausea. The odds ratio of 0.039 indicates that patients who did not receive aprepitant were approximately 25 times more likely to have nausea than patients who received it. We determined that 1 patient (1.8%) of the 56 who took aprepitant still experienced postoperative nausea vs 18 (15.5%) of the 116 who did not take aprepitant. This observation indicated that the real proportion of patients who contracted postoperative nausea after taking aprepitant was 1.8% (P = .02).

Discussion Ondansetron is a known medication prescribed to prevent PONV in certain patients.2,4,11 In July 2006, a new antiemetic, aprepitant, was approved by the US Food and Drug Administration, which acts by a different mechanism. Aprepitant (Merck & Co) is a selective antagonist against human substance P and NK1 receptors.12 The NK1 receptors in the brainstem are thought to produce substance P, which is a potent inducer of emesis; therefore, a highly selective antagonist to this NK1 receptor would antagonize the central effects of substance P.14 The US Food and Drug Administration approved this drug based on 2 multicenter, randomized, and double-blind clinical trials of aprepitant against ondansetron. Both those studies12,14 revealed superior efficacy with aprepitant vs ondansetron in the prevention of PONV through 24 and 48 hours postoperatively. Because ondansetron lowers PONV in the patient undergoing plastic surgery, this study was performed to assess the known correlations that cause postoperative nausea in that of a less frequently used medication, aprepitant, and its effectiveness based on a study performed with ondansetron alone.2 An observational study was performed with 172 patients undergoing facial plastic surgery with general anesthesia to examine the correlation between certain factors and postoperative nausea symptoms. Again, all comparative statistics were 254

P Value

Predictor

Carbon dioxide laser resurfacing

2.243 (0.455-11.053)

.32

Blepharoplasty

2.668 (0.709-10.042)

.15

used based on known data from a similar study performed with ondansetron. 2 Logistic regression analysis was also performed to determine which of several variables may have been a predictor for PONV (Table 4). In previously reported studies,2,4 the incidence of PONV averages 33% and has been reported to be even higher in the plastic surgery literature. There currently are no specific studies related to facial plastic surgery; however, some of the previous studies and multivariate analyses2,4,11 have suggested that patients undergoing facial plastic surgery tend to have higher rates of PONV. Prevention of PONV is paramount in the perioperative period for patients undergoing facial plastic surgery. Higher incidences of hematoma formation, wound breakdown, and dehiscence and lower patient satisfaction rates have all been previously reported as associated with PONV.1,3,5,6 Various paradigms have also been espoused as being effective in lowering PONV levels. However, currently there is no generally accepted method other than using ondansetron and avoiding narcotics that is statistically effective in lowering nausea rates in patients undergoing plastic surgery.2,4 Our current regimen in preventing PONV includes a multimodality approach using preoperative ondansetron, intravenous dexamethasone, fluid hydration, and avoidance of intraoperative narcotics. Induction of all patients is performed with propofol, and patients undergoing general anesthesia are maintained with inhalational anesthetics and nitrous oxide. If additional anesthesia is required during the procedure, additional doses of propofol are given with supplementation of local anesthesia with lidocaine; narcotics are avoided intraoperatively. Aprepitant is offered to all nonsmoking female patients and those patients who are at an increased risk of PONV because of underlying patient-related factors. A single 40-mg dose is administered orally within 1 hour of the surgical procedure. In this comparative study, we looked at our current regimen of PONV suppression and various patient-related factors to determine whether there was any correlation as has been previously reported in other patient populations in regard to patient age, sex, and duration of surgery. We further looked to objectively determine whether the use of aprepitant in at risk patients could lead to an even lower rate of PONV. Solely looking at the occurrence of postoperative nausea in the 172 patients, 19 patients (11.0%) experienced nausea. Using the known statistic that approximately 33% of all patients undergoing surgery experience postoperative nausea,

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Aprepitant for Postoperative Nausea and Vomiting in Facial Plastic Surgery

Original Investigation Research

it was determined that there is sufficient evidence that our percentage was highly likely to be much lower than 33% by a factor other than chance (P < .001). Therefore, we have sufficient evidence that our current regimen of intraoperative ondansetron, fluid hydration, intravenous dexamethasone, and avoidance of narcotics is statistically lower than the current levels reported in the literature of PONV occurring in approximately 33% of patients. The addition of aprepitant further lowered the incidence of PONV to 1.8% in at risk women who received this medication within 1 hour of their surgical procedure. It has also been suggested that patients with surgery durations longer than 90 minutes are more likely to experience PONV than patients with surgery durations of 90 minutes or less. Of the 172 patients in this study, 19 experienced PONV, and of those patients, 17 had surgery durations longer than 90 minutes. Furthermore, women are more likely to contract PONV than men. Of the 19 patients who felt nauseated, 17 were women in this patient population. The odds ratios for female sex, duration of surgery longer than 90 minutes, and undergoing facial plastic surgery are greater than 1, indicating that there was a greater likelihood of PONV in the sample of patients participating in the study. However, the odds ratios were not statistically significantly greater than 1, indicating that there is not enough evidence to make the claim about the entire population of patients who might undergo facial plastic surgery (Table 4). Another claim is that age may have, at most, a minimal effect on the likelihood of PONV. In this study, the 19 patients who experienced PONV were split into 2 age groups (≤59 years and ≥60 years). We tested to see whether more than 50% of the nauseated patients were 60 years or older. With a test statistic greater than 0.05 (P = .32), we did not have significant evidence to support our alternative hypothesis and therefore must

support the claim that age has no or minimal effect on the likelihood of PONV. There is not enough evidence that the 10 patients who experienced PONV and were 60 years or older experienced the nausea because of some other chance or factor besides age. Finally, in the comparative study, 15.5% of the patients who took ondansetron alone still experienced PONV.2 We used this percentage as a comparison to our 1.8% of patients who took aprepitant and experienced PONV. Using logistic regression analysis, we found that patients who did not receive aprepitant were approximately 25 times more likely to have PONV than patients who received the medication. There is sufficient evidence in this observation that the real proportion of patients who contracted postoperative nausea after taking aprepitant was 1.8% (P = .02). Therefore, aprepitant appears to reduce PONV more frequently than ondansetron alone.

Conclusions After performing this observational study, we can state that based on these results aprepitant may potentially reduce the likelihood of postoperative nausea to a greater extent than ondansetron alone. Factors that can potentially affect the likelihood of PONV include sex, surgery duration, and facial plastic surgery. Therefore, because ondansetron is known to reduce the likelihood of these factors that lead to PONV and because this study found that aprepitant could further reduce nausea more frequently than ondansetron alone in which all the stated factors were involved, surgeons should consider recommending aprepitant more frequently for prevention of PONV, at least in the facial plastics realm.

ARTICLE INFORMATION

REFERENCES

Accepted for Publication: March 12, 2015.

1. Lehmann M, Monte K, Barach P, Kindler CH. Postoperative patient complaints: a prospective interview study of 12,276 patients. J Clin Anesth. 2010;22(1):13-21.

Published Online: May 14, 2015. doi:10.1001/jamafacial.2015.0307. Author Contributions: Drs S. J. Trimas and M. D. Trimas had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: S. J. Trimas. Acquisition, analysis, or interpretation of data: Both authors. Drafting of the manuscript: M. D. Trimas. Critical revision of the manuscript for important intellectual content: S. J. Trimas. Statistical analysis: M. D. Trimas. Administrative, technical, or material support: Both authors. Study supervision: S. J. Trimas. Conflict of Interest Disclosures: None reported. Additional Contributions: Statistical analysis was performed by Steven J. Naber, PhD, senior consulting research statistician, The Ohio State University, Columbus. The Department of Statistics was compensated for their statistical services.

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2. Marcus JR, Few JW, Chao JD, Fine NA, Mustoe TA. The prevention of emesis in plastic surgery: a randomized, prospective study. Plast Reconstr Surg. 2002;109(7):2487-2494. 3. Beer GM, Goldscheider E, Weber A, Lehmann K. Prevention of acute hematoma after face-lifts. Aesthetic Plast Surg. 2010;34(4):502-507.

8. Steely RL, Collins DR Jr, Cohen BE, Bass K. Postoperative nausea and vomiting in the plastic surgery patient. Aesthetic Plast Surg. 2004;28(1): 29-32. 9. Williams KS. Postoperative nausea and vomiting. Surg Clin North Am. 2005;85(6):1229-1241, xi. 10. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology. 1992;77(1):162-184. 11. Apfel CC, Korttila K, Abdalla M, et al; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350(24):2441-2451.

4. Buck DW, Mustoe TA, Kim JYS. Postoperative nausea and vomiting in plastic surgery. Semin Plast Surg. 2006;20(4):249-255.

12. Emend (Aprepitant) Prescribing Information. Whitehouse Station, NJ: Merck & Co; 2006:1-24.

5. Hirsch J. Impact of postoperative nausea and vomiting in the surgical setting. Anaesthesia. 1994; 49(suppl):30-33.

13. Apfel CC, Roewer N. Risk assessment of postoperative nausea and vomiting. Int Anesthesiol Clin. 2003;41(4):13-32.

6. Mustoe TA, Park E. Evidence-based medicine: face lift. Plast Reconstr Surg. 2014;133(5):1206-1213.

14. Diemunsch P, Joshi GP, Brichant JF. Neurokinin-1 receptor antagonists in the prevention of postoperative nausea and vomiting. Br J Anaesth. 2009;103(1):7-13.

7. Candiotti KA, Ahmed SR, Cox D, Gan TJ. Palonosetron versus ondansetron as rescue medication for postoperative nausea and vomiting: a randomized, multicenter, open-label study. BMC Pharmacol Toxicol. 2014;15(1):45-52.

(Reprinted) JAMA Facial Plastic Surgery July/August 2015 Volume 17, Number 4

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255

Use of Aprepitant and Factors Associated With Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Facial Plastic Surgery.

Patients who experience immediate postoperative nausea and vomiting (PONV) after their facial plastic surgery procedure have a higher incidence of com...
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