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Anesth Analg 2008; 107:429-438 © 2008 International Anesthesia Research Society doi: 10.1213/ane.0b013e318172f992
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Abstract |
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 Top Abstract IntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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BACKGROUND: We compared two antiemetic prophylaxis regimens, their efficacy for preventing postdischarge nausea and vomiting, and their impact on quality of living, during recovery.
METHODS: Sixty-four women undergoing outpatient gynecological surgery and at high risk for emesis were randomized into one of two groups. The study group received intraoperative IV dexamethasone 8 mg and ondansetron 4 mg, followed with an 8 mg oral disintegrating ondansetron tablet, to be taken on discharge and in the morning of postoperative days 1 and 2. The control group received only the IV ondansetron 4 mg intraoperatively. The incidence and severity of emetic symptoms and pain were assessed while patients were in the recovery room and via telephone and patient diary for 5 days after discharge. A modified functional living index of emesis was used to assess the impact on quality of living during recovery.
RESULTS: Sixty patients, 30 in each group, completed the study. The incidences for postdischarge nausea were 57% and 20%, and for postdischarge vomiting 20% and 3% in the control and study groups, respectively, for the period between the 8th and 120th hours postanesthesia (P < 0.05). Thirty-three percent of the study and 60% of the control group reported that emetic symptoms negatively affected their quality of living (P < 0.05).
CONCLUSIONS: When compared with a single dose of intraoperative IV ondansetron prophylaxis, our study regimen of additional intraoperative dexamethasone and once a day ondansetron significantly reduced the incidence of postdischarge nausea and vomiting and its negative impact on quality of living during the first 5 days of recovery.
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Introduction |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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Postoperative (PONV) and postdischarge (PDNV) nausea and vomiting are among the most common complications of ambulatory surgery. Apfel et al. evaluated a factorial trial of six interventions for prevention of PONV and showed that the average incidence of PONV was 34%, or as high as 70%–80% in high-risk patients without prophylactic antiemetics.1 Numerous studies and consensus guidelines have been published on prevention of PONV, but few have evaluated the efficacy of prophylaxis on PDNV or its impact on quality of living (QOL) during recovery.2–5 Gupta et al., in a systematic review on nausea and vomiting, found that only 19 articles had sufficient data on PDNV, and that most data were only on the first 24 postoperative hours.5 In the same meta-analysis review, the authors showed that one drug or combination antiemetic drug prophylaxis may only marginally change the incidence of PDNV.5 Other authors found similar results with reported postdischarge nausea (PDN) incidences that varied from 0% to 55% and postdischarge vomiting (PDV) incidences from 0% to 16%.5–8 Furthermore, it is not clear whether the risk factors for PDNV are the same as for PONV, or whether PONV in the postanesthesia care unit (PACU) predicts PDNV.6,8,9 Carroll et al. reported that outpatients who were discharged home often chose to wait for resolution of emetic symptoms rather than to contact their physicians for antiemetic treatment.7 Patients with PDNV are significantly more likely to have problems performing activities of daily living, have a lower satisfaction score, and higher negative economic impact than are those not experiencing PDNV.7 Therefore, the objective of this prospective, double-blind, randomized study was to evaluate two forms of antiemetic prophylaxis in high emetic risk outpatients on their efficacy for preventing PDNV and impact on QOL during recovery between 24 and 120 h postoperatively. The goal of this study was to compare the efficacy of preventing PDNV between a commonly used single drug prophylaxis regimen (intraoperative ondansetron alone) versus a more aggressive multidrug combination with sequential administration regimen [intraoperative dexamethasone and ondansetron, followed by oral disintegration tablet (ODT) ondansetron at discharge and postoperative days 1 and 2]. We hypothesized that IV dexamethasone and ondansetron followed by ODT ondansetron are more effective than IV ondansetron alone in preventing PDNV between 24 and 120 h postoperatively in high-risk patients having gynecological laparoscopic surgery.
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METHODS |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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After obtaining approval by IRBs at Forsyth Medical center and at Wake Forest University in Winston-Salem, North Carolina, written informed consent was obtained for this prospective double-blind, randomized control study from 64 healthy ASA physical status I or II women undergoing outpatient laparoscopic gynecological surgeries with general anesthesia. Other inclusion criteria were age
18-yr-old; having all three patient-specific emetic risk factors2 (female, nonsmoker, PONV history, or motion sickness); ability to follow study protocol instructions, and willing to complete the daily diary and be interviewed daily for five consecutive days after discharge. Exclusion criteria included a history of allergy to any study medications; pregnancy; having nausea or vomiting or receiving any drugs with antiemetic properties within 24 h before anesthetic induction; chronic opioid use; and body mass index >45 kg/m2. Patients were randomized in a double-blind fashion preoperatively to one of two prophylactic antiemetic treatment groups according to a computer-generated random-number table. The randomization was concealed before consent and remained double-blind and concealed until after completion of the study. The study treatment group (study group) received IV dexamethasone 8 mg in 2 mL volume immediately after successful intubation, and IV ondansetron 4 mg within 15 min before tracheal extubation at the end of anesthesia. They also received an ODT of ondansetron 8 mg, at the time of discharge from the PACU, and on the morning of postoperative day (POD) #1 and #2 at home. Patients in the comparator control treatment group (control group) received IV placebo of 2 mL normal saline (instead of dexamethasone) immediately after successful intubation, and IV ondansetron 4 mg within 15 min before tracheal extubation at end of anesthesia and then received placebo ODT (instead of ODT ondansetron) at discharge and on the morning of POD #1 and #2, as in the study group.
On the day of surgery while in the preoperative holding area, inclusion and exclusion criteria were reconfirmed. Negative urine pregnancy test was confirmed on those patients with child bearing potential. All patients were fasted for at least 6 h before induction of anesthesia. The anesthetic regimen was similar for both groups. Preoperative medication consisted of 0–2 mg IV midazolam and oral ibuprofen 800 mg or equivalent in the preoperative holding area. After arrival in the operating room, standard monitoring devices were applied and patients were administered oxygen and a standardized general anesthetic. Anesthesia was induced with propofol 1.5–2.5 mg/kg IV and fentanyl 1–2 µg/kg IV, and tracheal intubation was facilitated with succinylcholine, 1–2 mg/kg IV. Anesthesia was maintained with sevoflurane titrated between 1.5% and 2.5% end-tidal concentration in combination with oxygen and nitrous oxide at 50%– 60% as tolerated. Total intraoperative opioid used was limited to no more than 6 µg · kg–1 · h–1 of fentanyl IV. Rocuronium was titrated for neuromuscular blockade as needed during the maintenance period. At the end of the surgical procedure, sevoflurane was discontinued, and residual neuromuscular blockade was reversed with glycopyrrolate, up to 0.02 µg/kg, and neostigmine, up to 50 µg/kg IV, and the inspired oxygen was increased to 100%. Tracheal extubation was performed when the patients maintained adequate spontaneous tidal volume and respiratory rate and could follow simple commands such as opening eyes, squeezing hands, or head lifting. Vital signs and neuromuscular monitoring were recorded in 1–5 min intervals, whereas end-tidal concentrations of gases were continuously measured using a calibrated infrared gas analyzer.
Anesthesia time (defined as time from anesthetic induction to time of arrival at the PACU), surgical time (defined as time from skin incision to time of wound dressing placement), time for extubation, and the time interval between PACU arrival to discharge home from PACU (our standard institutional outpatient PACU discharge protocol using criteria with the Modified Aldrete score 18/20) were recorded. The use of Aldrete scores for PACU discharge is part of our normal clinical and institutional practice. It is not specific for PONV per se, but consists of evaluation on 10 categories, each with a score from 0 to 2 and a total maximum of 20. The 10 categories are: activity, respiration, circulation, consciousness, oxygen saturation, pain, dressing, ambulation, intake (includes evaluation of ability to drink fluid, nausea, and vomiting), and output. PONV is defined as emetic symptoms occurring after arrival to the PACU to the time ready for discharge home from the PACU. PDNV was defined as emetic symptoms occurring any time from ready for discharge home from PACU to 120 h after the end of anesthesia. Complete response in PDNV was defined as no emesis, no retching, and no rescue medication during the PDNV period studied. A complete response in PONV was defined the same as PDNV, except for applying it during the PONV period.
After patient arrival in the PACU, a research nurse monitored the antiemetic efficacy in the PACU by assessing the incidences of nausea, vomiting, or retching, the need for rescue medications and the intensity of average, current, and worst nausea (if present) graded verbally with an 11-point scale (from 0 to 10 with 0 being none and 10 being the most severe). A single vomiting episode was defined as expulsion of gastric contents, whereas retching was defined as an involuntary attempt to vomit but without expulsion of gastric contents. Vomiting or retching episodes occurring within 3 min were considered as single episodes. The first choice of rescue medication (promethazine 25–50 mg IV) was administered in the PACU if patients were experiencing vomiting lasting >3 min or more than one episode, moderate-to-severe nausea (>4/10) for >5 min, and/or patients requesting rescue antiemetic. If emetic symptoms recurred and required additional rescue antiemetic, the choice of such medication was administered at the discretion of the recovery room attending anesthesiologist. The patients, the investigators administering the medications, collecting data, or interviewing the patients, and all the health care providers involved in the direct care of the patients were blinded to the patient group assignment. Postoperative pain management in the PACU consisted of fentanyl 50 µg IV given as needed up to 250 µg. At discharge from the PACU, patients were given a prescription for ibuprofen 800 mg PO every 6 h, and/or oxycodone PO q 6–8 h as needed.
According to the patient's group assignment, an 8 mg ODT of ondansetron or identical placebo ODT was administered at discharge home from the PACU, and two 8 mg ODTs ondansetron each or ODT placebo were given to the patients with the instructions to take the ODT, one each on the first and second postoperative morning shortly after they woke-up, regardless of whether they had nausea or emetic symptoms or not. Patients were also instructed to complete a daily diary for the next five postoperative days to record the daily incidence and severity of emetic symptoms and pain, the need for antiemetic rescue and other medications, as well as to complete a daily questionnaire separately assessing the impact of emetic symptoms and pain on their functional daily activities. An investigator interviewed and assessed the patients at the 8th, 24th, 48th, 72nd, 96th, and 120th hour postanesthesia by telephone to go over their daily diary and questionnaire. On the last day of the study (120 h after end of anesthesia), an interview and a modified functional living index of emesis (FLIE) questionnaire were administered to assess the impact of emetic symptoms on the quality of their daily functional activities during recovery.10–14 The FLIE questionnaire is a nausea- and vomiting-specific patient-reported outcome tool that has been validated for assessing the impact of nausea or vomiting after chemotherapy on a patient's QOL.10–14 The tool comprises two domains (nausea and vomiting) with nine items for each domain in assessing the impact of nausea and vomiting separately on a patient's QOL. The nine items are: (1) amount of nausea or emesis; (2) ability to enjoy recreation/ leisure activities; (3) ability to make a meal or do minor household work; (4) ability to enjoy a meal; (5) ability to enjoy drinking liquid; (6) willingness to spend time with family and friends; (7) daily routine functioning; (8) imposing a personal hardship; and (9) imposing a hardship on those closest to them.7 With the modified FLIE, the patients then rated (with a 10 point scale, 1 being none and 10 being a great deal) each of the 9 items as to the impact on their QOL during the 5 days after surgery. A cumulative modified FLIE score (minimum of 9 and maximum of 90) for each domain (nausea or vomiting) was obtained by summation of the scores from the above nine items for the corresponding domain, with the lower score being less impact on QOL. The modified FLIE used in this study differs from the original FLIE in that the original FLIE uses a reverse and smaller rating scale ranging from 1 to 7, with 1 being a great deal and 7 being none.
For statistical analysis, SigmaStat for Windows version 3.01 (SPSS Inc., Chicago, IL) was used. On the basis of limited data in the literature on the PDNV period up to 120 h postanesthesia, we estimated our high emetic risk subjects to have a cumulative incidence of PDNV or an incidence of reporting PDNV negatively affecting QOL during the 24–120 h postanesthesia recovery period to be 70% in the control group and 40% in the investigation treatment group. The primary outcome measure was the cumulative incidence of PDNV between 24 and 120 h after administration of anesthesia (POD 1–4). Power analysis suggested that a sample size of 30 per group is needed to detect such differences in proportion with a power of 0.80 and an 
of 0.05. We chose the 24–120 h postanesthetic period as the primary outcome measure period to evaluate PDNV so as to allow more accurate data collection and interviews during this period concerning nausea and vomiting and their impact on quality of recovery. Our past experience suggested that many of our patients slept or rested shortly after they arrived home for most of the operative day. Nevertheless, information on the incidence of PONV during other postanesthetic periods, such as during the recovery room period and from discharge to 120 h after the end of anesthesia, was also collected and analyzed. Normally distributed continuous data (age, weight, height, amount of drug use, time duration, nausea scores, satisfaction scores, and FLIE scores) were analyzed using Student's t-test. If continuous data were not normally distributed, the Mann–Whitney U- test was used. Categorical data were analyzed using the 
2 test or Fisher's exact test as appropriate. A P value of <0.05 is considered statistically significant. Data are presented as mean values ± sd or median values, and percentages as appropriate.
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RESULTS |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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Demographics
Sixty-four patients were enrolled in the study. However, four patients (2 in the control group and 2 in the investigation treatment group) were excluded from final data analysis for the following reasons: 1 patient had a protocol violation due to difficult intubation, one had emetic symptoms within 24 h before surgery, and 2 had a change of surgical plan. Of the remaining 60 evaluable patients, each group had 30 patients. Data analysis was conducted and results reported were obtained from the full data set of all 60 evaluable patients without missing or excluded data. All patients in both groups had three patient-specific emetic risk factors and at least one major anesthesia-specific risk factor leading to a simplified Apfel emetic risk score of 4.2 The demographics, anesthetic management, perioperative and postdischarge opiate and analgesic requirement, pain scores, and emetic risk factors were all similar between groups (Table 1).
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PACU Period
The worst nausea intensity was scored significantly higher in the control group (6.7 ± 2.5) when compared with the study group (5.0 ± 2.4) (P < 0.01). The time to discharge from the PACU was longer in the control group (158 ± 62 min) than the study group (131 ± 40 min) (P < 0.05). The complete response rate in the PACU period was 53% for the control group and 70% in the study group. The incidence of being "very satisfy and willing to use the same antiemetic regimen in the future" was identical to the complete response rate for the corresponding group when evaluated at the time of discharge from the PACU. The satisfaction scores were similar between groups. The incidence of any nausea rated >3 of 10 in severity was 53% and 40%; for any vomiting or retching was 23% and 10%; and for rescue medication was 40% and 27%, in the control group and study group respectively without statistically significant differences between groups (Table 2).
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PDNV Period
The incidences of PDN and the number of patient days of emetic symptoms between 24 h postanesthesia and 120 h postanesthesia were both significantly higher in the control group when compared with the study group (P < 0.05) (Table 3). Five additional patients developed emesis in the control group and only one in the study group during the period from 24 to 120 h after end of anesthesia. The complete response rate for the whole PDNV period studied (from PACU discharge to 120th hour after end of anesthesia) was 80% for the control group and 90% for the study treatment group. The incidences of any PDN were 73% (control group) and 57% (study treatment group), whereas the incidences for PDV were 20% and 10% for the control and study groups, respectively. No patients received rescue medication in the PDNV period, even though some had actually obtained the prescribed medication from a local pharmacy when emetic symptoms occurred. For the group of patients with emetic symptoms, one cumulative patient-day of emetic symptoms is defined as one patient with emetic symptoms occurring within one day, whereas two cumulative patient-days indicate either only one patient with emetic symptoms occurring on two separate days, or two patients each with emetic symptoms occurring on only 1 day. Among those patients with emetic symptoms, the cumulative numbers of patient- days of nausea (and the average number of days with nausea per patient) for the whole PDNV studied period were 37 (average 2.2 days per patient) for the control group and 26 (average 0.6 day per patient) for the study group, whereas the cumulative numbers of patient-days of emesis (and the average number of days with emesis per patient) were 7 (average 3.5 days per patient) and 3 (average 1.5 days per patient) for the control and study group, respectively. The detailed daily incidences of emetic symptoms during the PDNV studied period are summarized in Table 3.
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Impact on QOL During Recovery
For the modified FLIE questionnaire, 33% of the study group reported nausea affecting their QOL during the PDNV period studied, whereas 60% reported the same in the control group (P < 0.04). Vomiting affecting the subjects' QOL in the PDNV period was reported in 3% of the study group and 20% of the control group (P < 0.04). The mean cumulative modified FLIE scores on nausea were 23.8 ± 16.8 (control group) and 15.2 ± 10.1 (study group) (P < 0.02), and on emesis were 14.0 ± 11.8 and 9.3 ± 1.8 for the control and study group, respectively (P < 0.04). The magnitude of emetic symptoms affecting the different aspects of the patients' QOL during the period from discharge to 120 h after end of anesthesia is shown by the FLIE subscores in Table 4.
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DISCUSSION |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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With increasing numbers of patients having ambulatory surgery, PDNV has become a growing problem that has not been fully recognized, in part, because the patients often choose to wait for resolution of emetic symptoms on their own rather than contacting their physician for interventions.15 In our study, we found that the overall incidence of PDNV on POD #0 remained high with either prophylaxis regimen studied, but that the incidences of PDN and PDV between POD #1 to POD #4 and between the 8 and 120 h after the end of anesthesia were significantly (P < 0.05) lower in the study group. The modified FLIE questionnaire also showed that significantly fewer patients (33%) in the study treatment group reported having emetic symptoms affecting their QOL during the PDNV studied period (60%) than in the control group(P < 0.05). The study treatment regimen seemed to have significantly reduced the incidence of PDNV and improved quality of functional living between POD #1 and #4, as well as between 8 and 120 hours after the end of anesthesia.
All our patients had high emetic risk with at least three risk factors according to a simplified emetic risk score.2 In addition, our patients underwent laparoscopic surgery and volatile inhaled anesthesia with more than 50% nitrous oxide and the use of opioids intraoperatively and postoperatively. The anesthesia is likely to have added to the risks and incidence of PONV and PDNV in these patients. In part, because of all these factors combined, the incidence (53%–73%) of PDNV (from discharge to 5 days after surgery) found in this study was relatively higher than some of the earlier studies reporting data on a PDNV incidence of 30%–55%. However, many of these previous studies enrolled patients from both genders with mixed emetic risks, and PDNV was often evaluated as a secondary outcome or only assessed for the first 24 h, in contrast to the 5 days after surgery in our study.5,7,16–21 More recently, White et al., in their PDNV study, evaluated patients from both genders and mixed emetic risks undergoing laparoscopic surgery. After having received prophylactic IV ondansetron or granisetron at the end of anesthesia, their patients had a PDN incidence of 38%–46% between 4 and 24 h postanesthesia and 12%–19% during 24–48 h postanesthesia.22 Our results with all high emetic risk female patients for a similar postdischarge interval showed a similar or slightly higher PDN incidence, when compared with White et al.'s study.
In our study, when compared with the control group, the absolute risk reduction of PDNV in our study treatment group for the period between POD #1 and POD #4 was 23% (reduction from 40% to 17%), which translates into a number-needed-to-treat of 4. For the interval between 8 and 120 h postanesthesia, the absolute risk reduction of PDNV was 37%, translating to a number-needed-to-treat of 3. From these results, it seems worthwhile to consider using the antiemetic prophylaxis used in our treatment group for populations having a high emetic risk to prevent PDNV and to improve QOL during recovery.23,24
For the immediate postdischarge period (first few hours after discharge), the antiemetic regimens studied in either group did not differ in preventing PDNV, and the PDNV incidence in this immediate discharge period remained high in the 50+%. For those patients reporting PDNV between discharge and the 8th hour postanesthesia, most emetic symptoms occurred between the time of discharge from the PACU to shortly after arriving home. It is possible that the acute ambulation and motion associated with a car ride shortly after surgery caused emetic symptoms severe enough to render the prophylaxis ineffective. Further studies are needed to address more effective prophylaxis for this immediate postdischarge period in ambulatory surgery patients.
Few studies have evaluated PDNV directly, and even fewer have reported the impact of emetic symptoms on QOL after discharge.7,22,25 The modified FLIE results suggested that more favorable functional QOL during recovery in our study treatment group than the control group, and that PDN had more negative impact than PDV on QOL during recovery. The modified FLIE uses a rating scale of 1–10, with the higher number being QOL more affected for each item measured in the FLIE. We felt this scale was easier for our patient population to understand than the original FLIE, which uses a reverse rating scale of 7–1. Furthermore, when we transformed and converted our data from the modified FLIE scores to the original FLIE scale and scores, the conclusion remained the same. The original FLIE with its modifications was the only validated nausea- and vomiting-specific assessment tool on QOL in patients with chemotherapy-induced nausea and vomiting.10–15 The FLIE originally developed by Lindley et al. and its modifications have been shown, in chemotherapy-induced nausea and vomiting studies, to have excellent internal consistency within FLIE nausea and vomiting domains with high Cronbach's , and acceptable convergent validity, as shown by moderate-to-strong correlations between FLIE domain scores and independent clinical end-points of emetic episodes, nausea ratings, and use of rescue medications.10–15 There is no "gold standard" for measuring QOL after PDNV, as it is a subjective measure, but the FLIE focuses on the impact of nausea and vomiting on QOL, and is often used as a secondary end-point to compare different antiemetic regimens or for comparing QOL before and after chemotherapy. PDNV is only one of several factors affecting overall QOL after surgery. The FLIE focuses only on emetic symptoms but does not incorporate other factors, such as pain, family support, and expectation, all of which may be equally or more important. Thus, 73% of the control group and 87% of the study group reported that they would be willing to use the same antiemetic in the future, whereas the overall satisfaction scores were high in both groups without statistical differences between groups. These findings are similar and consistent with a PDNV study using antiserotoninergic class antiemetic prophylaxis.22
In the PACU, our results are consistent with those reported by other authors using one or two antiemetic drugs for preventing PONV.1,3,18 Our study treatment group had a lower worst nausea scores (P < 0.05) in the PACU and a shorter PACU stay (P < 0.05) than the control group, which may be a reflection of a higher number of complete responses, a lower incidence of PONV and rescue medication required in the study group in the PACU even though these were not statistically different between groups. Our study was not aimed nor powered to show the relative 20% reduction in PONV with each additional antiemetic,which has been demonstrated in previous PONV studies.1,3,18 Our studies aimed at assessing PDNV between after discharge to 120 h after end of anesthesia rather than the PACU period before discharge. Nevertheless, the PONV results for the PACU period are consistent with other, larger PONV studies.1,3,18
Since PDNV may last more than the immediate few hours after anesthesia, we chose to study a combination antiemetic regimen with IV ondansetron and dexamethasone (with supposedly a longer duration of antiemetic effect) and an additional dose of ODT ondansetron at discharge to prevent emetic symptoms, especially during the first few hours after discharge while traveling home with all the ambulatory activities and motion involved with a car ride. We erred on the higher dose range of dexamethasone for maximizing and extending its duration and effect in combination with ODT ondansetron to provide prolonged efficacy for PDNV prevention. One additional dose of ODT ondansetron was administered on each morning of POD #1 and POD #2 immediately on awakening to prevent possible nausea or emetic symptoms associated with further ambulation during the day. ODT ondansetron was chosen because of the ease of use, and its not requiring water, especially if patients were nauseated and had no IV access. In comparison to just a single dose of intraoperative IV ondansetron, the study was under-powered to detect the possible small protective effect from dexamethasone during the first few hours after discharge and the first ODT ondansetron dose at discharge but, together with the added last two doses of ODT ondansetron, the regimen seemed to be significant in reducing the overall PDNV incidence and PDN incidence, respectively, between the 8 and 120 h and between 24 and 120 h after end of anesthesia, respectively. There were also no serious untoward side effects from the antiemetic regimen of either group.
There are a number of limitations in this study. The addition of dexamethasone in the treatment group prevented us from determining if adding only ODT ondansetron to the postanesthesia regimen would on its own provide similar results. We may also be criticized for using too high a dose of dexamethasone, especially when Paech et al. recently showed a dose as low as 2 mg dexamethasone in combination with 2 mg ondansetron was effective for PONV prophylaxis.26 However, the efficacy for preventing PDNV from small dose dexamethasone in combination with ondansetron is not known. Furthermore, Henzi et al. in a systematic review suggested that dexamethasone 8 mg was antiemetic without clinically relevant toxicity and that the late efficacy of dexamethasone seemed to be most pronounced when compared with ondansetron.27 In addition, a 2006 Cochrane analysis of PONV prophylaxis medications suggested that "risks for most outcomes were greater after smaller doses of dexamethasone."28 Therefore, we erred on the side of a higher dexamethasone dose with the goal of maximizing its effect and duration, especially for its late effect on PDNV protection together with IV and ODT ondansetron. Our clinical practice of using 25 mg promethazine as a rescue medication may also be criticized for using too high a dose, especially when recent retrospective data suggested a dose of 6.25 mg may be adequate. Observing our simple consciousness score that we routinely assess in the PACU, we did not observe any untoward events, and the consciousness scores were not significantly different between groups. We also did not prescribe a strict IV fluid regimen, but all our subjects on average received half of their fluid deficit replaced with lactated Ringer's solution by the end of anesthetic induction. The rest of the fluid deficit was replaced within the first hour of surgery as is our usual clinical practice and we found no significant difference between groups.
Other limitations in our study were that the sample size was relatively small and made it prone to type 1 and type 2 errors, and unable to detect differences smaller than the expected 30%, which may already be clinically significant and beneficial to patients. We also did not perform a preoperative FLIE assessment, which would have been useful as an individual baseline to allow a temporal comparison as well as to ensure no differences preoperatively between groups. However, with our exclusion criteria, we should have already excluded patients with any emetic symptoms within the 24 h before surgery, logically making them unlikely to have an abnormally low preoperative FLIE score. The FLIE is the only validated nausea- and vomiting-specific patient-reported tool for assessing impact on QOL in patients with chemotherapy-induced nausea and vomiting, but it has not been validated in postoperative patients or in PDNV studies. However, there are no significant facts to imply that it would behave differently when applied to postoperative patients to assess impact of emetic symptoms on QOL. Nevertheless, the results from the modified FLIE scores should be interpreted with caution and should be used to supplement the primary clinical outcome measures, such as incidence, duration, and severity of emetic symptoms.
In conclusion, PDNV incidence can be high and its impact on QOL may last up to 5 days after surgery. When compared with a single dose of intraoperative IV ondansetron prophylaxis, our study treatment regimen of intraoperative IV dexamethasone and ondansetron, followed by ODT ondansetron administered at discharge and on each morning of POD #1 and POD#2, significantly reduced the incidences of PDN and PDV for the period between the 8th and 120th hour after end of anesthesia and their negative impact on QOL during recovery. However, for the immediate postdischarge period (time of discharge to 8th hour after the end of anesthesia), the study regimen did not differ from the control regimen in reducing PDNV. Further research is needed to focus on means to prevent PDNV during this immediate postdischarge period.
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Footnotes |
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Accepted for publication February 11, 2008.
Presented, in part, as a poster presentation at American Society of Anesthesiology Annual Scientific Meeting on October 15–18, 2006 in Chicago, IL, and on October 15, 2007, in San Francisco, CA, at the 12th Asian-Australasian Congress of Anesthesiologists Scientific Meeting on November 6–10, 2006, in Singapore, and at Society of Obstetric Anesthesia and Perinatology 40th Annual Meeting on May 16–20, 2007, in Banff, Canada.
This research study is an investigator initiated research study. It is, in part, supported by a research grant from GlaxoSmithKline at 1250 Collegeville Road, Collegeville, Pennsylvania 19426.
The data, results, and conclusions are solely from the authors alone and have no direct or indirect input from anyone directly associated with GlaxoSmithKline.
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REFERENCES |
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- Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of post-operative nausea and vomiting. E Engl J Med 2004;350:2441–51
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- Odom-Forren J, Moser DK. Post discharge nausea and vomiting: a review of current literature. J Ambulatory Surg 2005;12:99–105
- Carroll NV, Miederhoff P, Cox FM, Hirsch JD. Postoperative nausea and vomiting after discharge from outpatient surgery centers. Anesth Analg 1995;80:903–9[Abstract]
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