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Comparison of Inhaled Isopropyl Alcohol and Intravenous Ondansetron for Treatment of Postoperative Nausea

Comparison of Inhaled Isopropyl Alcohol and Intravenous Ondansetron for Treatment of Postoperative Nausea

Comparison of inhaled isopropyl and intravenous for treatment of postoperative

LT Anthony W. Winston, CRNA, MS, NC, USN Bethesda, Maryland LT Robert S. Rinehart, CRNA, MS, NC, USN Portsmouth, Virginia LT George P. Riley, CRNA, MSN, NC, USN Bethesda, Maryland CAPT Charles A. Vacchiano, CRNA, PhD, NC, USN Pensacola, Florida CDR Joseph E. Pellegrini, CRNA, DNSc, NC, USN Bethesda, Maryland

Postoperative nausea, a common complication in patients rating scores between the ondansetron and alcohol receiving general anesthesia, was studied in this random- groups were 6.00 and 3.00, 5.00 and 3.00, and 5.00 and ized investigation to compare the efficacy of 70% inhaled 2.00, respectively (P = .002, .015, and .036, respectively). and intravenous ondansetron. No statistically significant differences were found at any For the study, 100 healthy women, ASA physical status other time interval. Mean times from initiation of therapy I or II, scheduled for outpatient gynecologic laparoscopic to a 50% reduction in nausea between the ondansetron procedures randomly received 4 mg of intravenous and alcohol groups were 6.3 minutes and 27.7 minutes, ondansetron or isopropyl alcohol for the treatment of respectively (P = 0 .022). postoperative nausea. Nausea was measured on arrival to Based on this study, it seems postoperative nausea can the postanesthesia care unit, at first complaint of nausea, be resolved quicker using 70% inhaled isopropyl alcohol compared with intravenous ondansetron in women under- every 5 minutes after initiation of therapy until nausea going outpatient gynecologic laparoscopic procedures. resolution, and every 15 minutes thereafter using a 0 to 10 verbal numerical rating scale. Key words: Antiemetics, inhaled isopropyl alcohol, At 5, 10, and 15 minutes, the median verbal numerical ondansetron, postoperative nausea.

ostoperative nausea and (PONV) additional supplies and antiemetics to treat PONV is a pervasive problem in patients who and in additional nursing care hours due to extended undergo general anesthesia. Its quick reso- postanesthesia care unit (PACU) stays of the patients. lution is important for optimizing the Patients with PONV spend an additional 47 to 61 safety and comfort of patients and for minutes in the PACU.2 Indirect costs for the institu- increasingP their overall satisfaction with the anesthe- tion are those associated with patient hospitalization sia and surgical experience. and PACU stays. In a typical same day surgery (SDS) The etiology of PONV is complex and dependent center, it was calculated that for every 5 patients who on many factors, such as the operative site, age, and experience PONV, an additional 2 patients could not sex of the patient. The incidence of PONV has been be scheduled for surgery due to lack of space for estimated to be 70% following intra-abdominal sur- recovery of these patients. The annual cost of PONV gery, 58% following major gynecological surgery, and in that typical SDS center was reported to be between 40% to 77% following laparoscopic surgery. Children $250,000 and $1,500,000.3 The direct costs to the are twice as likely as adults and women are 2 to 4 patient are those associated with their treatment and times as likely as men to experience PONV.1 hospitalization, while the indirect costs are those To gain a full understanding of the impact of involved with returning them back to their previous PONV, the direct and indirect costs to the institution functioning level. and patient should be examined. From the institu- There are several mechanisms that can lead to tion’s perspective, direct costs are seen in stocking PONV, although the exact pathophysiology is unclear.

AANA Journal/April 2003/Vol. 71, No. 2 127 The vomiting reflex is composed of peripheral mech- authors reported that 84% of the subjects treated with anisms in the and central mech- IPA for transport-related PONV experienced relief of anisms in the chemoreceptor trigger zone (CTZ) in their symptoms.15 The only formal study published the area postrema of the . Four neurotransmit- reported that 65% of the children treated with inhaled ters are involved in the activation of the vomiting IPA for PONV had a significant reduction in the sever- reflex: , , , and acetyl- ity of nausea or vomiting compared with placebo (P = . Release of these stimulates .03).16 However, this relief was transient. It is hypothe- receptors in the CTZ, which in turn stimulate the sized that the IPA may influence the neurotransmitters emetic center to produce nausea and vomiting.4 The that activate the CTZ. To our knowledge, there are no specific serotonin involved is the 5-HT3 published studies that have compared inhaled 70% IPA (hydroxytryptamine) subtype. Surgical manipulation with intravenous (IV) ondansetron for treatment of of the gut can cause the release of serotonin, leading postoperative nausea (PON). to emesis during the postoperative period.5 Inhaled The primary goal of this study was to compare the agents modulate the conductivity of ions efficacy of inhaled 70% IPA and IV ondansetron for through the 5-HT3 receptor, which suggests a possible the treatment and control of PON in groups of women mechanism for the nausea and vomiting these agents undergoing outpatient gynecological laparoscopic are known to produce.6 procedures. Many effective treatments are used to control PONV. Commonly used treatment regimens include a Materials and methods , such as or This was an investigational, randomized study. After , or a 5-HT3 (serotonin) receptor institutional review board approval, written, informed antagonist.7 Droperidol is a butyrophenone possess- consent was obtained from 100 women, ASA physical ing both tranquilizer and antiemetic effects. Control status I or II, older than 18 years scheduled to undergo of nausea is accomplished by producing an antago- diagnostic laparoscopy, operative laparoscopy, or 8 nism at the dopamine D2 receptor site. However, laparoscopic bilateral tubal occlusion. Subjects were droperidol is associated with some clinically signifi- excluded if they reported sensitivity to IPA or cant side effects, most notably extrapyramidal symp- ondansetron, had an impaired ability to breathe toms and .9,10 through the nose, were pregnant or using the medica- Ondansetron, a carbazole, produces antiemetic and tion , reported preexisting nausea, or antinauseant effects via competitive and selective reported any antiemetic use within 24 hours before antagonism of the serotonin receptor sites in the vagal surgery. In addition, patients who reported a history of afferent nerves in the gastrointestinal tract and block- significant PONV, defined as nausea or vomiting resist- ade of 5-HT3 binding sites in the CTZ and the nucleus ant to antiemetic therapy, or had a history of alco- tractus solitarius of the brainstem.11 Because of its holism were excluded from the study. Informed con- selectivity to the 5-HT3 receptor sites, ondansetron is sent was obtained on the day of surgery in the not associated with the side effects typically found preoperative holding area. Subjects were randomly with antagonism of the dopamine receptor. The side assigned to receive inhaled 70% IPA (experimental effects that most commonly are associated with group) or IV ondansetron (control group) for the treat- ondansetron include headache, , drowsiness, ment of PON. and sedation. For many practitioners, ondansetron’s A preoperative assessment for level of nausea was demonstrated efficacy and its low incidence of side conducted using a 0 to 10 verbal numeric rating scale effects have made it the “gold standard” antiemetic (NRS) for all subjects in the preoperative holding area treatment.12 However, despite the efficacy of to obtain a baseline score. Subjects were asked to rate ondansetron, some studies report that 45% of women their nausea on a 0- to 10-point scale with a score of undergoing outpatient laparoscopic procedures who 0 indicating no nausea and 10 indicating the worst received ondansetron prophylactically reported ongo- nausea imaginable. Subjects then were instructed that ing nausea during the postoperative period.13 this scale would be used to rate the level of nausea For reasons not clearly understood, the inhalation of during the postoperative period. isopropyl alcohol (IPA) seems to be effective for Upon arrival in the operating room, routine moni- treating PONV. In a published abstract, the authors toring devices were placed on all subjects, and base- reported that 80% of the subjects treated for PONV with line vital signs were recorded. General anesthesia was inhaled IPA had an almost complete resolution of symp- induced with , 2 mg/kg IV, and , 2.0 toms compared with placebo.14 In a published letter, the to 3.0 µg/kg IV. Tracheal intubation was facilitated

128 AANA Journal/April 2003/Vol. 71, No. 2 using rocuronium, 0.3 to 0.6 mg/kg IV. An oral gastric assignment. All nursing personnel in the PACU were tube was inserted to facilitate evacuation of instructed about the parameters of the study and contents and increase vision in the surgical field. became familiar with data collection tools before ini- Anesthesia was maintained with , 0.5% to tiation of the study. 1.0%, in combination with , 50%, and For the purposes of this study, an emetic event was oxygen, 50%. Fentanyl was administered on an as- considered vomiting or retching. Episodes must have needed basis up to a total of 5 µg/kg. Approximately been separated by at least 1 minute to constitute sep- 15 minutes before emergence, all subjects were given arate events. Nausea was defined as a subjective 30 mg of IV, and the oral gastric tube was unpleasant sensation associated with the awareness of removed. Neuromuscular blockade was antagonized the urge to vomit. Demographic data (age, height, using neostigmine, 0.05 mg/kg IV, and glycopyrrolate, weight, sex, and ASA physical status) were obtained 0.01 mg/kg IV, when necessary. All subjects then were during the preanesthesia interview and recorded. extubated and transported to the PACU. Additional data obtained included anesthesia time Assessment of nausea (using the 0-10 verbal NRS (arrival time in operating room until arrival time in scale) was performed on all subjects in the PACU PACU), surgery time (surgical incision until skin clo- when they were awake, on first request for treatment sure), PACU time (arrival until “fit for discharge” of PON, at 5-minute intervals until nausea resolved, from PACU), and SDS time (arrival until discharge and every 15 minutes thereafter until discharge from from SDS). Frequency data obtained in both the the PACU. At the first request for treatment, subjects PACU and the SDS included episodes of nausea, assigned to the control group received ondansetron, 4 episodes of emesis, and number of times were mg IV, to be repeated 1 time in 15 minutes if needed. administered. The type of , quantity adminis- Those assigned to the experimental group received tered at each request, and total amount administered 70% IPA to inhale, to be repeated 1 time in 15 minutes were recorded. All study subjects were sent home with if needed. Administration of IPA was accomplished a simple data collection form to use for tracking nau- using a standard, medium, 2-ply 70% isopropyl alco- sea and emetic events, subsequent treatment, and hol “prep pad” (The Kendall Company, Mansfield, overall satisfaction with anesthesia care. Twenty-four Mass). The package was opened and the pad removed hours after discharge, a follow-up telephone call was immediately before use. The pad was folded in half made to retrieve these data. and placed under the subject’s nose. The subjects were A power analysis was performed before initiation of instructed to take 3 consecutive deep breaths through the study and showed that a sample size of 50 subjects the nose to inhale the vapors, and the pad was then per group would be sufficient to provide 80% power to discarded. For subjects receiving supplemental oxy- detect a difference between the groups. This was based gen, it was removed during administration of the IPA. on the assumption that a mean verbal NRS score in Rescue treatment was provided at the subject’s request both groups would be 6 at complaint of postoperative or if nausea failed to resolve after 2 treatments. Rescue nausea and a reduction of this score by 3 (to 3) would treatment for failed IPA was provided with 4 mg of IV denote clinical effectiveness of each treatment using a ondansetron every 15 minutes for 2 doses. Rescue 2-tailed test at a 5% significance level. All data were treatment for failed IV ondansetron was at the discre- analyzed for entry errors, missing data, and consis- tion of the anesthesia provider. tency before statistical analysis. Statistical analysis was Before transport to the PACU from the operative performed using an SPSS statistical package (version suite, postoperative orders, which identified them as 8.0, SPSS, Chicago, Ill). Verbal NRS scores were ana- participants in the study, were written for all subjects. lyzed with a Mann-Whitney U test; demographic data These orders identified the treatment protocols to be and frequency data were analyzed using a c 2 test. A P followed by PACU nursing personnel based on the value of less than .05 was considered significant. Ver- group assignments (IPA or ondansetron). The bal NRS scores were expressed as median ± SD. All preprinted order forms allowed opioids for postoper- other data were expressed as mean ± SD. ative pain to be prescribed at the discretion of the individual anesthesia provider in each study case. Results However, 2 antiemetic regimens (standardized based For the study, 100 women were enrolled and equally on the study protocols) were printed on each form, randomized to the experimental IPA group or the con- allowing the providers to check only 1 of 2 blanks trol ondansetron group. When surgical procedures indicating which regimen was to be followed in case were analyzed, it was noted that 40 women under- of PONV based on each subject’s original group went laparoscopic bilateral tubal ligation, 41 under-

AANA Journal/April 2003/Vol. 71, No. 2 129 Table 1. Group comparison of means

Ondansetron group IPA group P value Intraoperative fentanyl (µg) 183.8 ± 68.2 195.1 ± 54.8 .364 Anesthesia time (min) 80.6 ± 29.3 74.6 ± 31.4 .326 Surgery time (min) 41.3 ± 19.0 40.7 ± 25.8 .895 PACU time (min) 60.3 ± 24.8 58.4 ± 26.5 .498 Total postoperative opioid use ( equivalent) 5.07 ± 2.0 4.79 ± 1.45 .826

IPA = inhaled isopropyl alcohol PACU = postanesthesia care unit went diagnostic laparoscopy, and 19 underwent oper- Table 2. Median verbal numeric rating scale scores ative laparoscopy. An equal distribution of surgical procedures was noted between groups. Demographic Relative Ondansetron IPA P characteristics with regard to age, weight, height, and time group group value ASA physical status were similar between groups. First complaint 8.00 8.00 .854 Anesthesia times, surgical times, PACU times, intra- operative fentanyl use, and total postoperative opioid 5 min 6.00 3.00 .002 use also were similar between groups (Table 1). The 10 min 5.00 3.00 .015 use of neuromuscular blockade reversal agents also 15 min 5.00 2.00 .036 was similar between groups. 30 min 0.00 1.50 .469 Of the 100 subjects, 41 experienced PON (29 in the experimental [IPA] group and 12 in the control 45 min 0.00 0.00 .522 [ondansetron] group). There were no statistically sig- 60 min 0.00 0.00 .871 nificant differences in median verbal NRS scores for PON at any time interval measured except at the 5-, IPA = inhaled isopropyl alcohol 10-, and 15-minute marks. Median verbal NRS scores were 6.00 and 3.00 (P = .002), 5.00 and 3.00 (P = While there were no differences noted in the NRS .015), and 5.00 and 2.00 (P = .036) in the scores in either group before discharge from the hos- ondansetron and IPA groups, respectively (Table 2). pital, except at the 5-, 10-, and 15-minute marks, the When the mean time from initiation of therapy to IPA group reported more episodes of nausea at home 50% relief of PON was analyzed, a mean time of 6.3 during the first 24 hours after discharge than did the minutes was required in the IPA group compared with ondansetron group. The reported mean incidence of a mean time of 27.7 minutes in the ondansetron group nausea events at home was 0.92 in the IPA group com- (maximum of 2 doses for each group). This was statis- pared with 0.40 in the ondansetron group (P = .035). tically significant (P = .022; Figure). Despite the dif- It is possible that subjects who received ondansetron ference in time to relief of symptoms noted between achieved a longer lasting antiemetic effect with their the groups, this did not have an impact on the mean therapy. stay times in the PACU and SDS units between groups (58.4 minutes for the IPA group compared with 60.3 Discussion minutes for the ondansetron group in the PACU; 139.2 PONV has been associated with recovery from general minutes for the IPA group compared with 124.12 min- anesthesia for many years. The general trend is toward utes in the ondansetron group in the SDS). a decrease in its incidence; however, it still occurs A total of 8 subjects in the IPA group did not expe- with unacceptable frequency. PONV not only is dis- rience relief after 3 treatments with IPA, and they sub- tressing to the patient, but it also can influence the sequently received ondansetron. Two subjects in the duration of recovery from anesthesia and the time ondansetron group did not experience relief after 2 needed for patients to return to their normal func- treatments with IV ondansetron and received meto- tional level. clopramide or at the discretion of the This study showed that PON can be resolved anesthesia provider. quicker using 70% inhaled IPA compared with IV

130 AANA Journal/April 2003/Vol. 71, No. 2 Figure. Time from initiation of antiemetic therapy to a the IPA .14 This method of blinding, while effec- 50% reduction of postoperative nausea (PON) for 41 tive in that pilot study, was deemed inappropriate for subjects undergoing laparoscopic tubal occlusion, the present study in which a direct comparison of diagnostic laparoscopy, or operative laparoscopy clinical effectiveness was performed between IV ondansetron and inhaled IPA. 50 Other benefits may be derived from the use of inhaled 70% IPA due to its ease of administration and 40 portability, allowing it to be used easily during patient transport or self-administered after patient discharge. 30 * These observations represent opportunities for further research. In addition, cost savings may be realized by 20 using the 70% IPA pads. At our institution, a single

10 70% IPA pad costs $0.01 compared with $17.00 for * one 4-mg IV dose of ondansetron. These costs repre-

me (min) to 50% reduction of PON me (min) to 50% reduction 0 sent the acquisition cost for our institution rather Ti than the charges to the patient. -10 12 29 REFERENCES Ondansetron IPA 1. Kenny G. Risk factors for postoperative nausea and vomiting. Anaesthesia. 1994;49:6-10. Twenty-nine subjects received inhaled 70% isopropyl 2. Metter S, Kitz D, Young M, Baldeck A, Apfelbaum J, Lecky J. Nau- alcohol (IPA), and 12 subjects received intravenous sea and vomiting after outpatient laparoscopy: incidence, impact, ondansetron for treatment of PON. Mean time to a 50% on recovery room stay and cost [abstract]. Anesth Analg. reduction of PON (represented by *) was 6.3 minutes in 1987;66(suppl):S116. the IPA group compared with 27.7 minutes in the 3. Sanches L, Hirsch J. Identification of cost consequences as the crit- ondansetron group. The difference was statistically ical step in a cost-of-illness study: post-operative nausea and vom- significant (P = .022). iting in an ambulatory surgery center example. J Res Pharm Eco- nomics. 1992;4:41-54. 4. Watcha M, White P. Postoperative nausea and vomiting: its etiol- ondansetron in groups of women undergoing outpa- ogy, treatment, and prevention. Anesthesiology. 1992;77:162-184. 5. Naylor R, Inall F. The physiology and pharmacology of postopera- tient laparoscopic procedures—a mean time of 6.3 tive nausea and vomiting. Anaesthesia. 1994;49(suppl):2-5. minutes compared with a mean time of 27.7 minutes 6. Machu T, Harris R. and enhance the function for the ondansetron to achieve a 50% reduction in of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis nausea. These data should prove useful to anesthesia oocytes. J Pharmacol Exp Ther. 1994;271:898-905. 7. Fujii Y, Saitoh Y, Tanaka H, Tayooka H. for prevent- providers since PONV is a pervasive problem follow- ing postoperative nausea and vomiting in women undergoing ing anesthesia. It should be noted that this study was gynecological surgery. Anesth Analg. 2002;90:472-475. conducted on a small portion of the population who 8. Tang J, Watcha M, White P. A comparison of costs and efficacy of undergoes surgery. ondansetron and droperidol as prophylactic antiemetic therapy for elective outpatient gynecological procedures. Anesth Analg. One unusual finding in this study was the dispro- 1996;83:304-313. portionate number of subjects in the IPA group who 9. Follet C, Farinotti R, Palmer J. Physiology of chemotherapy- reported nausea, 60% compared with 24% in the induced emesis and antiemetic therapy. . 1997;53:206-234. ondansetron group, despite the use of block random- 10. Sung Y. Risks and benefits of drugs used in management of post- ization. A possible explanation for this is respondent operative nausea and vomiting. Saf. 1996;14:181-197. 11. Markham A, Sorkin E. Ondansetron: an update of its therapeutic bias. We chose to administer the IPA by having the use in chemotherapy-induced and postoperative nausea and vom- subject inhale the IPA from a folded alcohol pad iting. Drugs. 1993;45:931-952. because it offered a simple, readily available method. 12. Splinter W, Rhine E. Prophylaxis for vomiting by children after However, we realized that this did not allow us to tonsillectomy: ondansetron compared with . Br J Anaesth. 1998;80:155-158. blind the study intervention. In fact, a pilot study that 13. Ahmed AB, Hobbs GJ, Curran JP. Randomized placebo-controlled investigated the effectiveness of inhaled IPA vs a trial of combination antiemetic prophylaxis for day-case gynaeco- placebo attempted to keep PACU personnel unaware logical laparoscopic surgery. Br J Anaesth. 2000;85:678-682. of the intervention used. That study required that 14. Langevin P, Brown M. A simple, innocuous, and inexpensive treat- ment for postoperative nausea and vomiting [abstract]. Anesth recovery room nurses apply bandages saturated with Analg. 1997;84(suppl):S15. IPA to their own upper lips before administering treat- 15. Smiler BG, Srock M. Isopropyl alcohol for transport-related nau- ment to study subjects to mask the investigators’ sea [letter]. Anesth Analg. 1998;87:1214. of smell, thus preventing them from detecting 16. Wang S, Hofstadter M, Zain A. An alternative method to alleviate

AANA Journal/April 2003/Vol. 71, No. 2 131 postoperative nausea and vomiting in children. J Clin Anesth. CAPT Charles A. Vacchiano, CRNA, PhD, NC, USN, is currently on 1999;11:231-234. staff at the Naval Aerospace Medical Research Laboratory, Pensacola, Fla. CDR Joseph E. Pellegrini, CRNA, DNSc, NC, USN, is director of AUTHORS Research, Navy Nurse Corps Anesthesia Program, Bethesda, Md. LT Anthony W. Winston, CRNA, MS, NC, USN, is currently a staff nurse anesthetist at the National Naval Medical Center, Bethesda, Md. ACKNOWLEDGMENTS We thank the following individuals for their contributions to this He is the principal author of this study. This study was conducted research: LT Mark Allen, RN, BSN, NC, USN; LT David Melvin, RN, while he was a nurse anesthesia student as part of the Master of Science BSN, NC, USN; CWO4 William Hohman, RN, NC, USN; and Christine degree requirements for the nurse anesthesia program at Georgetown Bundy, RN, BSN, CPAN, for assistance in data collection. We also thank University. the Anesthesia Department, Postanesthesia Care Unit, and Ambulatory LT Robert S. Rinehart, CRNA, MS, NC, USN, is currently a staff Procedures Department at Naval Medical Center Portsmouth, Va, for nurse anesthetist at the Naval Medical Center, Portsmouth, Va. He was assistance in data collection. an associate investigator and classmate of LT Winston at Georgetown University. DISCLAIMER The views expressed in this article are those of the authors and do not LT George P. Riley, CRNA, MSN, NC, USN, is currently a staff nurse reflect the official policy or position of the Department of the Navy, anesthetist at the National Naval Medical Center, Bethesda, Md. Department of Defense, or the US Government.

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