“A Comparison of Two Differing Doses of Promethazine for the Treatment of Postoperative Nausea and Vomiting”

“A Comparison of Two Differing Doses of Promethazine for the Treatment of Postoperative Nausea and Vomiting”

Purpose: To compare the use of promethazine 6.25 mg intravenous (IV) (experimental group) with promethazine 12.5 mg IV (control group) among adult ambulatory surgery patients to control established postoperative nausea or vomiting (PONV).

Design/Methods: In a double-blind, randomized controlled trial (n5120), 59 subjects received promethazine 6.25 mg and 61 subjects received promethazine 12.5 mg to treat PONV. Study doses were administered postoperatively if the subject reported/exhibited nausea and/or vomiting. Outcomes for experimental and control groupswere compared on the basis of relief of PONV and sedation levels.

Findings: Ninety-seven percent of subjects reported total relief of nausea with a single administration of promethazine at either dose. Sedation levels differed between groups at 30 minutes post-medication administration and at the time of discharge to home.

Conclusions: Promethazine 6.25 mg is as effective in controlling PONVas promethazine 12.5 mg, while resulting in less sedation.

Keywords: ambulatory surgery, nausea and vomiting, promethazine, sedation, perianesthesia nursing, research, RCT.
2015 by American Society of PeriAnesthesia Nurses ONE OF THE MOST COMMON adverse effects of surgery and anesthesia is postoperative nausea and vomiting (PONV).1 These adverse effects may persist despite administration of intraoperative medications to prevent their occurrence.2-4 Various agents including 5-HT3 receptor antagonists (ondansetron, granisetron), glucocorticoids (dexamethasone), antihistamines (dimenhydrinate, cyclizine), cholinergic antagonists (scopolamine patch), dopamine antagonist (droperidol or haloperidol), metoclopramide, or neurokinin-1 receptor antagonists4 are used to prevent or treat PONV, as is intravenous (IV) promethazine.

Promethazine is a phenothiazine derivative that competitively blocks histamine (H [1]) receptors and exhibits anti-emetic and sedative properties.5 Relief of PONV typically is achieved within 5 minutes of IV infusion of promethazine6 and lasts for 2 to 6 hours.5 The major drawback to the use of promethazine for ambulatory surgery patients is its sedating effect.6 Any adverse reaction to medication, including sedation, delays patients’ postoperative recovery time,7 resulting in delayed ambulation and fluid intake, increasing the need for nursing intervention, and decreasing patient satisfaction. The possibility of delayed discharge is an added inconvenience for both the patient and their family.

Because of the sedating effect of promethazine, recommendations exist for the use of doses lower than the current standard (12.5 to 25 mg) to achieve antiemetic relief.8,9 Although limited research has been carried out related to promethazine dosing, some evidence exists for the administration of promethazine 6.25 mg in the presence of PONV. In a comparison of three IV doses (6.25, 12.5, and 25 mg), no differences were found in the effectiveness of promethazine doses in treating PONV among patients (n 5 330) in a post-anesthesia care unit (Phase I).10 In a similar comparison carried out among hospitalized elderly patients (n 5 26), no difference in relief of symptoms was observed with the lower dose of promethazine (6.25 mg IV) for the treatment of nausea and vomiting.11 Several investigators have examined the use of IV promethazine at doses of either 12.5 or 25 mg for treatment of PONV11-14; however, these studies compared IV promethazine with different classes of antiemetics or were carried out in settings other than perianesthesia. Moreover, a review of current literature revealed no studies that were focused on the use of promethazine 6.25 mg IV in the adult ambulatory surgery population.

Study Purpose

The purpose of this study was to compare two doses of IV promethazine (6.25 vs 12.5 mg) in a sample of adult ambulatory surgery subjects (n 5 120) who were expected to be discharged home after an elective surgical procedure. Based on direct clinical experience and direct observation of adult ambulatory surgery patients over
time by Phase I and Phase II (ambulatory surgical center) nurses, the following specific aims were
generated:
1. To compare the effects of two different doses of promethazine (6.25 mg IV vs 12.5 mg IV) on PONV in a sample of adult ambulatory surgery patients undergoing elective surgery.
2. To compare levels of postoperative sedation between adult ambulatory surgery patients who received promethazine 6.25 mg IV (experimental group) vs promethazine mg IV (control group).

Study Design

Between October 2008 and March 2011, a convenience sample of adult ambulatory surgical patients who were sent from the operating room (OR), per the determination of the anesthesiologist, to either Phase I or Phase II were randomized to receive promethazine 6.25 mg IV (experimental group) or promethazine 12.5 mg IV (control group) if PONV were to occur.

Setting

The study was conducted at a 750-bed teaching hospital in the Northeastern United States.

Preparation of Study Team

Phase I and Phase II nurses responsible for data collection were oriented to the study and subject enrollment procedures during educational sessions carried out by the investigators and supported by the institution’s Clinical Nursing Research Center. In these sessions, data collection instruments were reviewed and regulations concerning the protection of human subjects’ rights were discussed. Copies of the consent form, data collection tool, study design, study kits, and visual descriptive scale were provided and discussed in detail. Laminated cue cards were posted in each area for reference, and a nurse investigator was available to answer questions,
address concerns, and monitor inter-rater reliability during data collection in both Phase I and Phase II areas.
6 DEITRICK ET AL

Sample

The sample for this study was drawn from adult patients undergoing elective surgery and who were between the ages of 18 and 75 years. Study inclusion criteria were elective urologic, neurologic, general surgery, thoracic, vascular, otolaryngology, orthopedic, oral maxillofacial, gynecologic, or colorectal surgery; English speaking; and able to consent to participate. Exclusion criteria were less than 18 years or older than 75 years, pregnancy, breastfeeding, known allergy to promethazine, non-English speaking, and refusal or inability to sign study consent. Any prospective subject with a sedation level greater than ‘‘3’’ on the hospital’s internal sedation scale or who had limited IV access requiring IV placement in the lower extremities was excluded. Subjects also were excluded if the attending surgeon did not agree to enrollment of his or her patients or to the planned use of promethazine by either surgeon or anesthesiologist. No subject was excluded because of gender, income, race, or religion. Sample demographics are contained in Table 1.

Method Used for Randomization

Using a computer-generated random numbers table, each subject was randomized to receive either promethazine 6.25 mg IV or promethazine 12.5 mg IV. Drug preparation and subject randomization were performed by the pharmacist member of the study team. The nurses administering the promethazine dose and those collecting the study data were not aware of which dose was being administered to the subject. A safety measure was put in place so that in the case of an apparent adverse response to the promethazine dose, the investigators were able to break the code for an individual subject, determine the dose given, and provide reversal measures, per anesthesiologist order, if warranted. That subject would then be dropped from the study.

Protection of Subjects’ Rights

Approval to conduct the study was granted by the University’s institutional review board. Participation was voluntary, and all subjects received an explanation of the study, were given the opportunity to ask questions and receive answers, and signed a witnessed informed consent. Following consent, subjects were randomized to the experimental or control group. A pharmacist who was not involved with the study served as data safety monitor and conducted independent checks of data to monitor for evidence of unsafe or adverse events that would warrant discontinuation of the study.

Instruments
Nausea Scale

The investigators developed a verbal descriptive scale (VDS) to address subjects’ degree of PONV. The tool assessed degree of nausea, vomiting, or both, by the subject with or without the assistance of the bedside Registered Nurse (reviewing the scale or asking the patient). Response options ranged from 1 (none) to 6 (vomited repeatedly). Subjects were asked, by their bedside nurse, to state, point, or indicate the whole number or words that described their level of nausea or frequency of vomiting on the VDS scale. If, after one episode of vomiting, the nausea did not independently resolve without intervention, the subjects were asked if they would like treatment (promethazine study dose) for any residual nausea. Clinical nursing observation, over time, has revealed that PONV frequently resolves, without intervention, after a single episode of vomiting.

Sedation Scale
The investigators used the institution’s internal sedation scale, which has been used in both Phase I and Phase II settings. Options ranged from 0 (awake/alert) to 5 (unable to arouse), similar to other scales: Ramsay Scale and Sedation-Agitation Scale.15

When required, study doses were administered intravenously in 50 cc sterile normal saline and infused over 15 minutes. Subjects were evaluated at the time of admission to the Phase I or Phase II setting, 15 minutes after admission, or when the subject complained of nausea or demonstrated overt signs of nausea/vomiting. If PONV was described or observed, the study dose was administered at that time, and the subject was evaluated at 15 minutes and then again at 30 minutes from the time the medication infusion was completed.