Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone

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Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2017.03.026, available online at http://www.sciencedirect.com

Clinical Paper Trauma

Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone

A. Haapanen1, H. Thore´n1, J. To¨rnwall1, A. L. Suominen2,3,4, J. Sna¨ll1 1

Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2 University of Eastern Finland, Institute of Dentistry, Kuopio, Finland; 3Department of Oral and Maxillofacial Surgery, Kuopio University Hospital, Kuopio, Finland; 4 Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland

A. Haapanen, H. Thore´n, J. To¨rnwall, A.L. Suominen, J. Sna¨ll: Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone. Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx. ã 2017 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.

Abstract. This study aimed to establish the incidence of postoperative nausea and vomiting (PONV) in facial fracture patients. The specific aim was to investigate the effect of perioperative dexamethasone on PONV. A total of 119 adult patients with facial fractures were analysed in this prospective study. Patients were randomized to receive perioperatively either a total dose of 30 mg of dexamethasone i.v. and i.m., or no glucocorticoid (control). PONV was evaluated every 6 hours during the first postoperative 24 hours and when pain medications were given. PONV occurred in 20 out of 119 patients (16.8%). The only significant (P = 0.016) association with PONV was postoperative administration of opioids. Slightly more cases of PONV occurred for patients who had not received dexamethasone (20%) compared to those who had (13.6%). PONV was also non-significantly more common in patients 40 years (21.3%) than in patients < 40 years (12.1%), after orbital floor reconstruction (28.0%) compared with mandibular (11.6%) and zygomatic (15.6%) fractures surgeries, and also after anaesthesia lasting >97 minutes (21.7%) compared with a shorter duration (11.3%). Alternative medications should be used for prevention of post-surgery nausea and vomiting in facial fracture patients.

Postoperative nausea and vomiting (PONV) is the most frequent side effect of general anaesthesia and a major cause of significant morbidity. It is known to 0901-5027/000001+04

cause dehydration and electrolyte imbalance. Vomiting also causes pressure on the sutured site, which can lead to further complications in wound healing, including

Key words: facial fracture; dexamethasone; postoperative nausea and vomiting. Accepted for publication 22 March 2017

dehiscence1. The incidence of PONV varies greatly. For example, it is often reported to be around 30%2 but some studies have reported PONV to be as high

ã 2017 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.

Please cite this article in press as: Haapanen A, et al. Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.03.026

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as 80% in high-risk patients, including females, history of motion sickness or PONV, non-smokers, use of postoperative opioids3. Patients find PONV highly unpleasant1 and it can lead to delayed discharge, which affects the total treatment costs4. Findings on the incidence rate of PONV in maxillofacial surgery also vary. Phillips et al.5 studied patients undergoing orthognatic surgery and reported a rate of 67% for postoperative nausea (PON) and nearly one-third of their patients suffered from postoperative vomiting (POV). Slightly lower rates were found after orthognathic surgery in the study by Silva et al.6, whereby 40% of patients experienced PONV. A study of facial fracture patients reported a lower incidence of PONV7. The overall incidence of PONV in was 12.5%. A total of 150 patients in that same study were randomized to receive metoclopramide, gabapentin, chlorpromazine, dexamethasone, or placebo. Patients given metoclopramide, gabapentin, or chlorpromazine medications had significantly reduced PONV. However, a dose of 5 mg of dexamethasone showed no significant effect in PONV reduction. There were only 30 patients in each group, so a broader conclusion needs to be made with larger number of patients.

Use of dexamethasone in preventing PONV

Among other anti-emetics, dexamethasone was shown to be effective for preventing PONV8. There is no clear guideline about the proper dose on dexamethasone in preventing PONV, although De Oliveira et al.9 showed that there is no effect for doses of dexamethasone between 4–5 mg i.v. and 8–10 mg i.v. The aims of the present study were to determine the rate of PONV after surgical treatment of facial fractures, investigate the effect of perioperatively administered dexamethasone on PONV and indicate any possible causes for the results.

Patients and methods Inclusion and exclusion criteria

Patients were recruited between June 1, 2006, and December 31, 2010. Patients who were included had to be aged at least 18 years and they also about to undergo one of the following three procedures: (1) surgical treatment of mandibular fracture (one or two fractures in the dentate area) with titanium miniplates, (2) open reduction and miniplate fixation of unilateral zygomatic complex fracture, and (3) reconstruction of orbital floor fracture

Table 1. Descriptive statistics of 119 patients with facial fracture. No. of patients

% of 119

Gender Male Female

96 23

80.7 19.3

Age (years) Range 18.1–82.4 Mean 39.1, median 40.6 40 or more Less than 40

61 58

51.3 48.7

Site of surgery Zygomatic complex Mandible Orbital floor

51 43 25

42.9 36.1 21

Surgical approach Intraoral or intra- and extraoral Extraoral

69 50

58 42

Duration of anaesthesia (minutes) Range 49–200 Mean 101, median 97 Less than 97 minutes 97 minutes or more

60 59

49.6 50.4

Postoperative administration of opioids Yes No

96 23

80,7 19.3

Administration of dexamethasone No Yes

60 59

50.4 49.6

PONV, postoperative nausea and/or vomiting.

(uni- or bilaterally). Patients with infected fractures, a history of liver or kidney dysfunction, a history of peptic ulcer, a history of psychosis because of steroid use, pregnancy, breastfeeding, or allergy to any constituent of the dexamethasone preparation used were excluded from the study. Study design

Patients were randomly assigned to one of two groups for each fracture type. Randomization between dexamethasone treatment and control was carried out at the time of recruitment and it was conducted with sealed envelopes. The patients in the study group received dexamethasone and patients in the control group received none. No placebo was used. The dexamethasone group received 10 mg of dexaintravenously during methasone anaesthesia induction and an additional 10 mg intramuscularly every 8 hours over 16 hours, up to a total dose of 30 mg of dexamethasone. Anaesthesia was initiated with propofol and maintained with sevo- or desflurane. Fentanyl was administered for pain during surgery. Patients received paracetamol 1,000 mg every 6 hours postoperatively for analgesia. Oxycodone-hydrochloride 0.2–0.4 mg per 10 kg was given intravenously in the recovery ward, followed by 1 mg per 10 kg intramuscularly in the inpatient ward when needed. A throat pack was used in patients with intraoral surgery to minimize blood leaking to digestive tract. PONV was evaluated regularly during the first postoperative 24 hours. Patients were asked if they had any nausea every 6 hours, and were administered ondansetron if needed. The enquiry was additionally performed when oxycodonehydrochloride was given. Retching and vomiting occurring on other occasions were registered. Study variables

The outcome variable was PONV. The primary predictor variable was the perioperative use of dexamethasone. Other predictor variables included in the analysis were age, sex, site of surgery, surgical approach, duration of surgery, and postoperative administration of opioids. The final analyses included the following outcomes, age categorized as (1) 40 years or more and(2) less than 40 years; site of surgery as (1) mandible, (2) zygomatic complex, and (3) orbital floor; surgical approach as (1) extraoral and (2)

Please cite this article in press as: Haapanen A, et al. Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.03.026

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Nausea and vomiting in facial fracture patients intraoral, or intra- and extraoral; and duration of anaesthesia as (1) less than 97 minutes and (2) 97 minutes or more Statistical analyses

x2 tests were used to analyse associations between occurrence of PONV for sex, age group, postoperative administration of opioids, perioperative use of dexamethasone, site of surgery, surgical approach, and categorized duration of anaesthesia. Results

A total of 129 patients fulfilled the inclusion criteria. Of these, seven refused to participate at all. Of the remaining 122 patients, three were excluded because they failed to complete all the scheduled dexamethasone doses. Thus, a total of 119 patients were included in the final analyses. Table 1 summarizes the descriptive statistics of the 119 patients. The great majority (80.7%) were male. The age ranged from 18.1 to 82.4 years (median 40.6 years). The duration of the anaesthesia ranged from 49 to 200 minutes (median 97 minutes). Ninety-six patients (80.7%) received opioids postoperatively. Fiftynine patients (50.4%) received dexamethasone and 60 did not. PONV occurred in 20 patients (16.8%) and 95% of the patients experienced it during the first 12 hours after the surgery. Vomiting occurred in four patients (3.4%) Table 2 shows the association between PONV and predictors. PONV was more frequent among the control patients (20%) than in the dexamethasone-treated group (13.6%) but the difference was not statistically significant. The only significant association with PONV as determined by the Chi-squared test was the postoperative administration of opioids (P = 0.016). PONV was also more common in patients aged 40 years or more (21.3%) than in their younger counterparts (12.1%), more common after orbital floor reconstruction (28.0%) than after surgery for mandibular (11.6%) and zygomatic (15.6%) fractures, and for patients after anaesthesia lasting more than 97 minutes (21.7%) than after a shorter duration (11.3%). None of these differences were statistically significant. Fourteen of the 20 patients with PONV (70%) had received opioids before PONV and 6 (30%) after PONV (P < 0.001) Discussion

The present study found that 20 out of 119 patients (16.8%) suffered from PONV,

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Table 2. Association between PONV and predictors. No. of patients with PONV

% of n

Gender Female (n = 23) Male (n = 96) P = 0.934

4 16

16.7 16.3

Age (years) 40 or more (n = 61) Less than 40 (n = 58) P = 0.178

13 7

21.3 12.1

Site of surgery Orbital floor (n = 25) Zygomatic complex (n = 51) Mandible (n = 43) P = 0.211

7 8 5

28 15.6 11.6

Surgical approach Extraoral (n = 50) Intraoral or intra- and extraoral (n = 69) P = 0.641

9 11

18 15.9

Duration of anaesthesia (minutes) 97 minutes or more (n = 59) Less than 97 minutes (n = 60) P = 0.153

13 7

22.4 11.5

Postoperative administration of opioids Yes (n = 96) No (n = 23) P = 0.016

20 0

100.0 0

Administration of dexamethasone No (n = 60) Yes (n = 59) P = 0.348

12 8

20 13.6

PONV, postoperative nausea and/or vomiting.

which is in line with a previous study on facial fracture patients. Jahromi et al.7 reported PONV in 12.5% of facial fracture patient population/group. However, these rates are considerably less than those reported for previous findings in orthognathic patients5,6. This difference can be explained by the fact that our study group consisted mostly of males (80.7%), and it almost entirely lacked young females The average age of females in this study was 50.9 years and only 8.7% (2/23) where under the age 30. Apfel et al.10 conducted a meta-analysis in 2012 in which they systematically reviewed 22 studies with a total of 95,154 patients and concluded that the strongest patient-specific predictor for PONV was the female sex. This verifies the previous findings on this matter. Dexamethasone did not significantly reduce PONV (P = 0.348) in the present study. This confirms previous observations made by Jahromi et al.7. This is a very important finding because one purpose in the perioperative use of dexamethasone is to reduce postoperative nausea. Therefore, the efficacy of dexamethasone for reducing PONV had to be determined. This study was done with proper random-

ization and thus the population and resulting dataset closely represent typical facial fracture patients whom are relatively young and mostly male. The treatment guidelines on PONV prevention for patients undergoing facial fractures should be based on studies with the representative population. This is especially important when taking into consideration the increased risk of short-term PONV on dehiscence of the surgical site in facial fractures11 and delayed union in mandibular fractures caused by any apparent lack of efficacy or ineffective timing of perioperative dexamethasone12. Another antiemetic medication should therefore be chosen for such patient groups. The statistically significant difference was observed between occurrence of PONV and perioperative use of dexamethasone. Because a small sample size can be considered as one of the weaknesses of the present study, we did a power analysis to evaluate the statistical reliability of the present study. The power of a statistical test is the probability of detecting a ‘‘true’’ effect when it exists. We used a two-sided Fisher exact test with a significance level of 0.05 for retrospective power analysis for a test of the two independent propor-

Please cite this article in press as: Haapanen A, et al. Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.03.026

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tions, namely occurrence of PONV and perioperative use of dexamethasone. With the slightly unbalanced design (n = 59 in the dexamethasone group and n = 60 in the control group) and the rates observed (13.56%/20.00%), we estimated a power of 0.66, which is somewhat below the commonly used standard (0.80  1 b  0.95). To get the recommended level, a sample size of n = 81 per group would have been needed. The dexamethasone patients in the present study received a dose of 10 mg of dexamethasone at induction and dosing was continued postoperatively up to a total dose of 30 mg. Wang et al.13 studied 120 women undergoing abdominal total hysterectomy and concluded that the optimal timing of dexamethasone administration is at induction, because under that dosing schedule dexamethasone provided an effective antiemetic effect during the first 24 hours. In that same study the authors also stated that when dexamethasone was administered at the end of anaesthesia, dexamethasone did not provide an effective antiemetic14 effect during the immediate postoperative period of 0 to 2 hours. Prolonged administration of dexamethasone in the present study similarly did not show the benefits for PONV. Thus, it is possible that dexamethasone is not an appropriate antiemetic option when administered postoperatively. Longer anaesthesia time did not significantly increase PONV, but there was a trend towards it. Previous studies have shown that longer anaesthesia time is a predictor for PONV but they have not been able to verify the causality because a longer anaesthesia time also often leads to excessive emetic drug administration during surgery. Phillips et al.5 concluded that the median length of surgery time was almost 35 minutes longer (P = 0.04) for those patients that suffered from postoperative nausea. The fact that opioid use was significantly associated to PONV in the present study confirms the results of previously published studies: opiates are known to have side effects that include, among others, nausea and vomiting15. The majority (80.7%) of the patients in this study received opiate-based analgesics after the surgery, and all of the patients that suffered from PONV had received one or more doses of opiates postoperatively. This clearly indicates that patients having undergone surgery for facial fractures more or less routinely need opiates, and it should be taken into consideration when

planning postoperative anti-emetic medications. Dexamethasone does not significantly reduce PONV in facial fracture patients. Dexamethasone should be used to target high-risk patients without risk of glucocorticoid related complications, but the routine use of dexamethasone as an antiemetic drug during facial trauma surgery cannot be recommended. There are other medication options without so many known disadvantages for the treatment of PONV in facial fracture patients (such as metoclopramide, ondansetron, and droperidol) and their use should be considered as an alternative to dexamethasone. Funding

None. Competing interests

None. Ethical approval

The Research Ethics Board of the Department of Surgery and the Internal Review Board of the Division of Musculoskeletal Surgery, Helsinki University Central Hospital, Finland, approved the study (Dno 33/E6/06) in accordance with the declaration of Helsinki 1975 and amendments thereafter. Patient consent

Informed written consent was obtained from all patients. References 1. Gan TJ. Risk factors for postoperative nauand vomiting. Anesth Analg sea 2006;102:1884–98. 2. Franck M, Radtke FM, Apfel CC, Kuhly R, Baumeyer A, Brandt C, Wernecke KD, Spies CD. Documentation of post-operative nausea and vomiting in routine clinical practice. J Int Med Res 2010;38:1034–41. 3. Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations betwo centers. Anesthesiology tween 1999;91:693–700. 4. Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ. Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis. Curr Med Res Opin 2006;22:1093–9.

5. Phillips C, Brookes CD, Rich J, Arbon J, Turvey TA. Postoperative nausea and vomiting following orthognathic surgery. Int J Oral Maxillofac Surg 2015;44:745–51. 6. Silva AC, O’Ryan F, Poor DB. Postoperative nausea and vomiting (PONV) after orthognathic surgery: a retrospective study and literature review. J Oral Maxillofac Surg 2006;64:1385–97. 7. Jahromi HE, Gholami M, Rezaei F. A randomized double-blinded placebo controlled study of four interventions for the prevention of postoperative nausea and vomiting in maxillofacial trauma surgery. J Craniofac Surg 2013;24:e623–627. 8. Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186–94. 9. De Oliveira Jr GS, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ. Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg 2013;116:58–74. 10. Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, Zhang K, Cakmakkaya OS. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth 2012;109:742–53. 11. Snall J, Kormi E, Koivusalo AM, Lindqvist C, Suominen AL, Tornwall J, Thoren H. Effects of perioperatively administered dexamethasone on surgical wound healing in patients undergoing surgery for zygomatic fracture: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:685–9. 12. Snall J, Apajalahti S, Suominen AL, Tornwall J, Thoren H. Influence of perioperative dexamethasone on delayed union in mandibular fractures: a clinical and radiological study. Med Oral Patol Oral Cir Bucal 2015;20:e621–626. 13. Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91:136–9. 14. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be predicted? Anesthesiology 1999;91:109–18. 15. Smith HS, Laufer A. Opioid induced nausea and vomiting. Eur J Pharmacol 2014;722:67–78.

Address: Aleksi Haapanen Department of Oral and Maxillofacial Diseases Helsinki University Hospital 00029 HUH Finland E-mail: [email protected]

Please cite this article in press as: Haapanen A, et al. Postoperative nausea and vomiting in facial fracture patients: A Randomized and controlled trial on the effect of dexamethasone, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.03.026