Original Contributions
Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: A prospective, randomized, controlled trial*,**

Presented at the American College of Emergency Physicians Research Forum, Philadelphia, PA, October 2000.
https://doi.org/10.1067/mem.2001.119249Get rights and content

Abstract

Study Objective: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. Methods: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. Results: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Δ=–6.7%; 95% confidence interval [CI] –24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI –9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI –4.6% to 29.8%). Conclusion: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made. [Collins RW, Jones JB, Walthall JDH, Chisholm CD, Giles BK, Brizendine EJ, Cordell WH. Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial. Ann Emerg Med. November 2001;38:491-496.]

Introduction

Akathisia is an often distressing condition of restlessness that can include nervousness, a feeling that one's skin is “crawling,” and the inability to remain in a sitting position. After experiencing akathisia, Kendler wrote, “The intensity of the dysphoria was striking. With the possible exception of going on stage on an opening night, I cannot remember any feeling of anxiety so intense.”1 Anecdotally, this restlessness has been observed to be so intense that patients with drug-induced akathisia have been known to pull out their own intravenous lines and leave the emergency department.

Prochlorperazine, a phenothiazine used as an antiemetic for decades,2 is now also one of the mainstay therapies of acute cephalalgia in the ED.3, 4, 5, 6 As a phenothiazine, prochlorperazine displays extrapyramidal side effects that broadly fall into 4 categories: acute akathisia, acute dystonia, parkinsonism, and chronic tardive dyskinesia.7 Chronic use of phenothiazines has long been known to be associated with the development of akathisia and other movement disorders.8, 9, 10 However, single doses of a phenothiazine, including prochlorperazine, have also been reported to induce akathisia.4, 11

A study by Drotts and Vinson7 found a 44% incidence of akathisia in ED patients after a single intravenous bolus dose of prochlorperazine. Because akathisia is so common after even single intravenous doses of prochlorperazine and because the symptoms can be so distressing, methods of prophylaxis have been proposed. One strategy is to administer medications, including diphenydramine,12 benztropine, or lorazepam, with the prochlorperazine. Slowing the infusion rate of prochlorperazine has also been proposed.7 We conducted a study to test the latter strategy. We hypothesized that a 15-minute intravenous infusion would have a 50% lower incidence of akathisia than the label-recommended 2-minute intravenous bolus. The secondary objective was to evaluate whether the efficacy of prochlorperazine in treating headache and nausea was affected by the rate of administration.

Section snippets

Materials and methods

We conducted a prospective, randomized, double-blind study in the ED of Methodist Hospital, a teaching hospital located in central Indianapolis, IN. The annual ED census was 94,000 at the time of the study. The Clarian/Methodist Institutional Review Board approved the study. All study participants gave written informed consent before enrollment.

Patients aged 18 to 65 years were eligible for participation in this study if they were to receive intravenous prochlorperazine for the treatment of

Results

We enrolled 100 nonconsecutive study participants between July 7, 1999, and March 30, 2000. One study participant was excluded after a protocol violation (lorazepam was administered during the first 30 minutes) (Figure 1). Patient characteristics and baseline measures are presented in the Table.

Table. Demographic data and baseline measures.

CharacteristicTotal (n=99)2-Min Bolus (n=50)15-Min Infusion (n=49)
Female sex (%)65 (65.7)31 (62.0)34 (69.4)
White (%)50 (50.5)28 (56.0)22 (44.9)
Mean±SD age (y)

Discussion

The term “akathisia” is derived from the Greek words meaning inability to sit down. It was first coined in 1902 to describe restless patients with hysteria and neurasthenia.9 In the 1950s, some patients taking neuroleptic drugs were observed to manifest jittery, restless, or rhythmic movements, often of the feet, resembling those movements described by Haskovec.14 There is some debate whether akathisia is truly a movement disorder or an intense and uncomfortable mental state that leads to

Acknowledgements

Author contributions: JBJ, CDC, EJB, BKG, and WHC conceived the study and designed the trial. JBJ, BKG, and EJB supervised the conduct of the trial and all aspects of the data collection. RWC, JDHW, and BKG undertook the responsibility for patient recruitment including data management and entry. All statistical plans and analyses were supervised and performed by EJB. RWC and JDHW drafted the manuscript and all authors contributed extensively to its revision and final presentation. The paper was

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  • Cited by (23)

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      Of the 65 patients reporting nausea and/or vomiting on their VAS, 84.4% reported a decrease of at least 2 points (82% BG; 87% IG; P = not significant; Wilcoxon rank sum test). The incidence of akathisia varies widely in reports in the literature [13-15]. The emergency medicine literature on this topic begins in 1999, with a published incidence of prochlorperazine-induced akathisia of 44% as measured with the same modified PHH akathisia scale used for this study [13].

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    *

    Author contributions are provided at the end of this article.

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    Reprints not available from the authors.

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