Interpretation of statistics

Nursing Research March/April 2002 Vol 51, No 2 125

� Background: The mechanisms for postoperative nausea and vomiting are numerous and pathways not well elucidated. Although many medications have been developed to help prevent postoperative nausea and vomiting, the search for better approaches to recovery treatment continues.

� Objective: The purpose of this study was to evaluate the effec- tiveness of isopropyl alcohol (IPA) inhalation for treatment of postoperative nausea and vomiting for patients who have general anesthesia for a surgical procedure.

� Method: Participants were recruited from an urban hospital on the East Coast of the United States. Participants were assigned to an experimental or control group and IPA inhala- tion was compared to the standard anti-emetic treatment for rescue treatment in the immediate postoperative period. Postoperative nausea and vomiting was rated using a descriptive ordinal scale.

� Results: The results of this study show IPA to be effective and that there was no significant difference between the stan- dard treatment protocol and treatment with IPA. Treatment with IPA was significantly more cost effective than standard drug treatment.

� Discussion: Further research is recommended to evaluate the length of effectiveness, standard dose needed, most effec- tive mode of inhalation, and factors blocking IPA effective- ness.

� Key Words: alternative treatment • IPA • nausea • postopera- tive • vomiting

oday’s healthcare concerns center on decreasing costs, shortening hospital stays, and facilitating a

quick return to normal activity for patients. Post-operative nausea and vomiting (PONV) is a major concern for patients having same-day surgery under general anesthesia as it causes increased complications and delays in dis- charge from the hospital (Hirsch, 1994). Approximately one-third of the 11 million patients under- going outpatient surgery under general anesthesia will

experience significant nausea or emesis in the postopera- tive period (Claybon, 1994). The mechanisms for PONV are numerous and the causative pathways not well eluci- dated. Many factors may play a role in an episode of nau- sea and vomiting, and despite advances in new drug thera- pies in minimizing the incidence, no ideal drug has been found to prevent all the causes of PONV.

Aromatherapy is a relatively new and under-researched alternative treatment that might hold promise in treating PONV. Isopropyl alcohol (IPA) is among several aromas displaying possible anti-emetic properties. Isopropyl alco- hol inhalation is a new treatment with only limited inves- tigations to date (Langevin & Brown, 1997).

Literature Review

Current PONV treatment strategies are based on the understanding of the vomiting reflex; however, the lack of well-elucidated pathways in the control of PONV has con- tributed to the problems with these treatment strategies and medications. It has been well documented that some patients are more susceptible to PONV indicating varia- tions in sensitivity of the vomiting reflex to stimuli. This complicates discovering how anesthesia and surgical pro- cedures might cause PONV (Naylor & Inall, 1994).

The vomiting reflex has two main detectors of the need to vomit: the gastrointestinal tract and the chemo receptor trigger zone (CTZ) in the nucleus tractus solitarius of the area postrema located in the brain stem. The vomiting reflex is triggered in the gastrointestinal tract by 5-HT chemoreceptors in the mucosa of the upper digestive tract, which leads to the activation of visceral vagal afferents and propagating of information to the CTZ. Stimulation of either the gastrointestinal tract or the CTZ pathway resultsT Donna M. Jasinski, CRNA, DNSc, is Assistant Professor, George- town University, Washington, DC. Bret A. Merritt, CRNA, MS, is a graduate of Georgetown Uni- versity, Washington, DC. Charles P. Okyere, MS, is a graduate of Georgetown University, Washington, DC.

Isopropyl Alcohol Inhalation

Alternative Treatment of Postoperative

Nausea and Vomiting

Bret A. Merritt � Charles P. Okyere � Donna M. Jasinski

Brief Report

126 Isopropyl Alcohol Inhalation Nursing Research March/April 2002 Vol 51, No 2

in activation of the vomiting episode (Naylor & Inall, 1994). It has been postulated that the motor component of the vomiting reflex is mediated by both the autonomic and somatic nervous system with the emetic center in the brain acting as the coordinating zone. However, at present there are no known anti-emetic drugs that act directly on the emetic zone (Andrews et al., 1990).

There is little doubt that the mechanisms underlying PONV are numerous. Factors which are likely to con- tribute or associate with increased inci- dence include (a) type of surgical proce- dure, (b) anesthetics used, (c) inadequate postoperative pain control, and (d) certain participant characteris- tics (e.g., sex, age, anxiety, previous his- tory of PONV) (Kenny, 1994).

Many drug therapies have been developed over the last 50 years in response to PONV either for prophylac- tic or rescue usage. All of these therapies have possible adverse reaction such as sedation, antihistamine actions, extrapyramidal reactions, and limited dosing abilities (Sung, 1996). The cost of prophylactic treatment can be rela- tively inexpensive as seen with the use of promethazine (Rodola et al., 1995) or relatively expensive as seen with the new HT-3 receptor antagonist like granisetron (Cieslak, Watcha, Phillips, & Pennant, 1996). Fujii, Tanaka, & Toyooka (1997) concluded that a combi- nation of dexamethazone and granisetron helped signifi- cantly reduce PONV in women after gynecologic surgery at a cost over $107 per dose. While the results are promising, the high cost may prevent its use in the cost conscience world of healthcare. Further, 20% of the participants treated with the combination treatment had some adverse effect including headache, drowsiness, and dizziness.

Alternative medicine treatments are now being used to help control PONV. These treatments include oral ginger as a prophylactic medicine and acupuncture as prophylac- tic and rescue treatment. Mixed results are reported for both (Sung, 1996). Aromatherapy is another alternative medical treatment that could be used to treat PONV. There are limited studies on aromatherapy or olfactory remedia- tion that consist mainly of qualitative data research with mixed anecdotal results (Martin, 1996). Despite the uncer- tain mechanism of action, aromatherapy has been used effectively in many types of treatments. The treatment of PONV could be considered. Recently, nasal inhalation of IPA has been considered as treatment for PONV (Langevin & Brown, 1997).

Isopropyl alcohol has been in use for many years as an antiseptic in hospitals and at home. The safety of IPA has been demonstrated and there are no warnings on the alco- hol pad other than that it is intended for external use only. Toxicity is seen in human adults only with oral ingestion. Studies in rats and mice in which the animals were exposed to inhalation of IPA vapor at 100, 500, 1500, or 5000 parts per million (ppm) for six hours a day, five days a week for 13 weeks, demonstrated organ and neurobehav-

ioral effects only at 5000 ppm (Burleigh-Flayer et al., 1995). There have been no reports of human toxicity due to inhalation.

Recently, nasal inhalation of IPA has been considered as treatment for PONV. A pilot study of IPA inhalation (N � 15) showed an 80% success rate in treating PONV (Langevin & Brown, 1997). Wang, Hofstadter and Kain (1999) evaluated IPA inhalation in 91 children ages 6–16. After three treatments, 65% of the children had a signifi-

cant reduction in the severity of either nausea or vomiting. The effect was transient however, and 54% had recur- rent symptoms. The mechanism of action related to prevention of nausea and vomiting with inhalation of IPA is unknown, but may be due to its depres- sant qualities on the central nervous system.

The purpose of the current study was to evaluate the effect of IPA inhala- tion for rescue treatment of PONV in adult same-day surgery patients who had general anesthesia for any type of surgical procedure. It was hypothesized that (a) patients treated with IPA inhala- tion would have decreased nausea and vomiting in the immediate postopera- tive period; (b) IPA inhalation treatment would be more effective in decreasing

nausea and vomiting in the immediate postoperative period than standard rescue treatment; and (c) IPA inhalation treatment would decrease postanesthesia care costs.

Methodology

This quasi-experimental study was conducted at a medium-sized urban teaching hospital on the East Coast of the United States. Following Institutional Review Board approval, a convenience sample was drawn from patients admitted for same-day surgery. Inclusion criteria were (a) requirements for general anesthesia, (b) ability to breathe through nose before and after procedure, (c) minimum of 18 years of age, (d) American Society of Anesthesiologists (ASA) physical status of I, II, or III, and (e) ability to read and write English. Exclusion criteria were (a) allergy to IPA, (b) alcohol abuse, (c) no recent history of nausea or vomiting within the last 8 hours, (d) no recent intake of cefoperazone, Antabuse, or metronidazole, (e) ability to communicate in recovery room, (f) regional anesthesia, and (g) monitored anesthesia care. When patients agreed to participate, written informed consent was obtained.

Sample size determined by power analysis was 64 to achieve an alpha of .05, critical effect of .30 and a beta/power of 80%. The actual number of participants enrolled in the study was 111. Of these 111 participants, 71 had no nausea or vomiting, thus a total of 40 were evaluated.

Participants were recruited in the preoperative waiting area on the day of the surgical procedure. Participants were blinded to which treatment they were to receive. Group assignment was alternated by day: experimental one day and control the next. This method was used instead of ran-

There have been no reports

of human toxicity due to

inhalation

Nursing Research March/April 2002 Vol 51, No 2 Isopropyl Alcohol Inhalation 127

dom assignment because the intervention took place in the post anesthesia care unit where control patients could potentially overhear the researchers explaining the interven- tion to the experimental group participants.

Many tools have been used to measure nausea and vomiting such as visual analog scales (VAS) and descriptive ordinal scales (DOS). For this study DOS scores were cho- sen over VAS because many patients cannot read without glasses in the recovery room due to the use of eye lubricant, which can blur vision. Each participant was given instruc- tions on how nausea and vomiting were to be measured via the DOS on a scale from 0 to 10, with 0 being no nausea or vomiting and 10 being the worst nausea and vomiting they could imagine.

If nausea or vomiting was present in control partici- pants, an appropriate anti-emetic was given. Experimental participants were given IPA via nasal inhalation using stan- dard hospital alcohol pads. The participant was instructed to take three deep sniffs with the pad one inch from the nose. This was repeated every five minutes for three doses or until nausea and vomiting was relieved. If nausea and vomiting continued after three doses of IPA, then an intra- venous drug was given.

Data analysis. Descriptive statistics were obtained on: (a) demographic data (age, weight, sex, smoking history, alco- hol use); (b) class of surgical procedure; (c) type of anes- thesia used for both induction and maintenance; and (d)

prophylactic medications given intra-operatively. Hypothe- ses were tested with t tests and a one-way analysis of vari- ance (ANOVA).

Results

Participants (N � 111) were enrolled in the study: (age: X � 43; range 19–80 years) 40 (36%) had PONV, 71 (64%) had no complaints of PONV, and 94 (84.6%) received pro- phylactic anti-emetics. Types of surgery included (a) intra- abdominal (29.7%), (b) orthopedic/extremity (23.4%), (c) perineal (19.8%), (d) neuro-skeletal (10.8%), (e) extra- thoracic (6.3%), (f) eyes, ear, nose, or throat (6.3%), and (g) neck (3.6%). The average length of surgical procedure was 90 minutes (range 30–180 minutes).

Of the 40 participants who had some form of PONV, one participant had spontaneous recovery before any treat- ment was given. Of the 39 participants remaining, 21 were in the experimental group and 18 were in the control group (Table 1). Anesthetic types and the surgical proce- dures of these 39 participants are presented in Table 2.

The first hypothesis of the study was that participants would have decreased PONV with the use of IPA. In the experimental group, 11 (52.4%) had relief of PONV after the first dose and 10 needed at least one medication from the standard regimen. Thirteen (72.2%) of the 18 control group participants had relief of nausea and vomiting after the first dose of anti-emetic, and five had no relief. The sec- ond hypothesis was that IPA treatment would be superior to standard anti-emetic treatment for relief of symptoms. A two-tailed t test was used to analyze the nausea change scores. The results were not significant (p � .21) (Table 3). The third hypothesis was that the cost of IPA treatment would be less than the cost of the standard treatment regi- men (see Table 3). The IPA group had a PONV average medication cost (IPA and other anti-emetics when necessary)

IPA Control n = 21 n = 18

Sex Male 10 (47.6%) 5 (27.7%) Female 11 (52.4%) 13 (72.3%)

Age (yrs) M 40 37 SD 12 14

Weight (Kg) M 72 77 SD 18 17

Smoking history Never 13 (61.9%) 16 (88.8%) Quit 3 (14.3%) 1 (5.6%) Current 5 (23.8%) 1 (5.6%)

Alcohol use Never 5 (23.8%) 5 (27.7%) Occasional 15 (71.4%) 13 (72.3%) Moderate 1 (4.8%) 0 Heavy 0 0

Note. IPA, isopropyl alcohol.

TABLE 1..Demographics: Control and Experimental Groups

IPA Control Inhalation agents n = 21 n = 18

Isoflurane/nitous oxide 14 10 Desflurane/nitrous oxide 6 7 Sevoflurane/nitrous oxide 1 1

Surgical procedures

Intra-abdominal 6 6 Orthopedic 4 4 Perineal 5 5 Neuroskeletal 1 2 Extrathoracic 2 2 Neck 1 0 Eye/ear/nose/throat 2 1

Note. IPA, isopropyl alcohol.

TABLE 2. Frequency of Surgical Procedures and Inhalation Agents Used

128 Isopropyl Alcohol Inhalation Nursing Research March/April 2002 Vol 51, No 2

of $9.75. The PONV average medication cost for the con- trol group was $17.08. A one-way ANOVA demonstrated a significant difference (F � 16.5, df � 38, p � .003)

Discussion

The groups are similar with respect to demographics, type of surgical procedures, anesthetics administered and postoperative analgesics given. Only 40 of the 111 par- ticipants recruited had PONV. This is explained by aggressive prophylactic treatment at the study facility where only 7 (6.3%) of 111 participants did not receive prophylactic medication and none of these 7 participants had PONV. Additionally, the researchers speculate that pain may have been a confounding factor in accurate assessment on the DOS. A landmark study by Anderson and Krogh (1976) identified pain as a major cause of postoperative nausea.

The findings of the present study parallel results obtained in a previous study (Langevin & Brown, 1997) and suggest that IPA is a clinically important treatment for PONV. The current results indicate no statistically sig- nificant difference in the recovery from PONV after stan- dard treatment and IPA treatment. Numerous factors play a role in PONV. A meta-analysis (Apfel & Roewer, 2000) revealed that female sex, a history of prior PONV, nitrous oxide, opioids, and inhalation agents are corre- lated with PONV. Isopropyl alcohol treatment is rela- tively inexpensive at $0.01 per alcohol pad and on hand anywhere in the hospital. The average cost of rescue treatment for the control group was significantly higher than with the IPA group. These results demonstrate the clinical effectiveness of IPA in a little over half the partic- ipants and its low cost.

Isopropyl alcohol can be administered quickly and eas- ily without going to the “drug cabinet.” Participants remarked favorably about such a simple method to control their nausea, and asked if IPA can be used for other types of nausea. More research is needed to evaluate the length

of effectiveness, standard dose needed, most effective mode of inhalation, and factors blocking IPA effectiveness.

Accepted for publication July 12, 2001.

Corresponding author: Donna M. Jasinski, CRNA, DNSc, George- town University SNHS, Box 571107, 3700 Reservoir Road, NW, Washington, DC 20057 (e-mail: [email protected]).

References Anderson, R. & Krohg, K. (1976). Pain as a major cause of post-

operative nausea. Canadian Anaesthetists Society Journal, 23, 366-379.

Andrews, P. L., Davis, C. J., Bingham, S., Davidson, H. I., Hawthorne, J., & Maskell, L. (1990). The abdominal visceral innervation and the emetic reflex: Pathways, pharmacology, and plasticity. Canadian Journal of Physiology and Pharma- cology, 68, 325-345.

Apfel, C. C. & Roewer, N. (2000). Risk factors for nausea and vomiting after general anesthesia: Fictions and facts. Anaes- thetist, 49, 629-642.

Burleigh-Flayer, H. D., Gill, M. W., Strother, D. E., Masten, L. W., McKee, R. H., Tyler, T. R., et al. (1994). Isopropanol 13 week vapor inhalation study in rats and mice with neurotoxi- city evaluation in rats. Fundamental and Applied Toxicology, 23, 421-428.

Cieslak, G. D., Watcha, M., Phillips, M. B., & Pennant, J. H. (1996). The dose-response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. Anesthesiology, 85, 1076-1085.

Claybon, L. (1994). Single dose intravenous ondansetron for the 24-hour treatment of postoperative nausea and vomiting. Anaesthesia, 49(Suppl.), 24-29.

Fujii, Y., Tanaka, H., & Toyooka, H. (1997). The effects of dex- amethasone on antiemetics in female patients undergoing gynecologic surgery. Anesthesia and Analgesia, 85, 913-917.

Hirsch, J. (1994). Impact of postoperative nausea and vomiting in the surgical setting. Anaesthesia, 49(Suppl.), 30-33.

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Langevin, P. B., & Brown, M. M. (1997). A simple, innocuous, and inexpensive treatment for postoperative nausea and vom- iting. Anesthesia and Analgesia, 84(Suppl.), 16.

Martin, G. N. (1996). Olfactory remediation: Current evidence and possible applications. Social and Scientific Medicine, 43, 63-70.

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Rodola, F., Cannelli, G., Barbi, S., Forte, E., Anastasio, S., & Vagnoni, S. (1995). Cost effective prophylaxys of postopera- tive nausea and vomiting by anesthetic premedication. Euro- pean Review for Medical and Pharmacological Sciences, 17, 243-246.

Sung, Y. (1996). Risks and benefits of drugs used in the manage- ment of postoperative nausea and vomiting. Drug Safety, 14, 182-193.

Wang, S. M., Hofstadter, M. B., & Kain, Z. N. (1999). An alter- native method to alleviate postoperative nausea and vomiting in children. Journal of Clinical Anesthesiology, 11, 231-234.

IPA (n = 21) Control (n = 18) Mean (SD) Mean (SD)

Pretreatment DOS 5.71 (2.10) 6.11 (2.32) Post-test DOS 2.7 (3.02) 1.94 (2.48) Cost (U.S. $) 9.75 (11.89) 17.08 (8.61)*

*One-way ANOVA f = 16.55; df = 38; p = .003. Note. IPA, isopropyl alcohol; DOS, descriptive ordinal scores.

TABLE 3. Results of Descriptive Ordinal Scores and Costs for Isopropyl Alcohol and Control Groups