Page 28 - Journal of Special Operations Medicine - Summer 2015

promethazine from the TCCC Guidelines and replace it extrapyramidal symptoms, neuroleptic malignant syn-
with ondansetron. drome, akathisia, and hypotension, although these
symptoms are less common. More concerning in the
11
combat casualty, metoclopramide is a prokinetic agent,
Background
stimulating upper gastrointestinal tract motility, and,
Nausea and vomiting are common side effects of opioid therefore, would be contraindicated in a casualty with
use. The incidence of nausea and vomiting in trauma is abdominal trauma. Droperidol use has been associated
also common but perhaps less well appreciated. Easton et with fatal dysrhythmias in patients with no preexisting
al. showed a larger-than-expected number of trauma pa- history or risk factors who received single therapeutic
5
tients with nausea (38%), a smaller-than-expected num- doses. Due to these concerns, neither drug will be
12
ber who were properly treated (40%), and a significant given consideration as a replacement for promethazine.
difference in nausea between the treated and untreated
groups (4 of 79 [5%] versus 71 of 117 [61%]; p < .0001).
Methods
Promethazine hydrochloride is a phenothiazine deriva- A PubMed search was performed for the keywords
tive that is structurally different from the neuroleptic “promethazine” and “ondansetron,” each using the
phenothiazines, resulting in a relative lack of dopamine following filters: English language journal articles pub-
antagonist properties. Promethazine is a competitive H1 lished after 1 January 1984; human subjects; and adults
receptor antagonist that possesses antihistaminic, seda- at least 19 years old. This produced 344 articles for pro-
tive, anti–motion-sickness, antiemetic, and anticholiner- methazine and 1,165 articles for ondansetron. An ad-
gic effects. Clinical effects are generally apparent within ditional filter to remove articles from cancer literature
6,7
5 minutes of an intravenous (IV) injection and within 20 produced 750 articles for ondansetron.
minutes of an intramuscular (IM) injection. Duration of
action is reliably 6 hours, although effects may persist up Searches were screened for titles that appeared relevant to
to 24 hours. Promethazine was introduced in the 1940s this topic. Specific exclusion criteria included the follow-
and is still used in contemporary medicine. 8 ing: combinations of promethazine or ondansetron with
any other drug; comparison of either agent against a cor-
Ondansetron is a selective serotonin 5-HT receptor an- ticosteroid; ondansetron use in cancer treatment–related
3
tagonist that does not have dopaminergic properties. Its nausea and vomiting (unless specifically reporting adverse
exact mechanism of action has not been precisely de- reactions or, for a subgroup analysis, comparing the ef-
fined. Serotonin receptors of the 5-HT type are present fectiveness of oral versus IV ondansetron); special topics
3
on vagus nerve terminals and in the chemoreceptor trig- in unique surgical populations (e.g., middle-ear surgery);
ger zone of the area postrema. It is not certain whether and non–clinically oriented research (e.g., “influence of
ondansetron’s antiemetic action is mediated centrally, ondansetron on gastric sensorimotor responses to short
peripherally, or both. 9 duodenal acid infusion”). Considering surgery from the
perspective of a planned, controlled, traumatic injury,
Ondansetron is increasingly becoming the antiemetic gynecologic, orthopedic, and general surgical titles were
of choice in the prehospital and ED settings, including also screened for inclusion. Abstracts were examined for
the combat operational environment. Between 1995 pertinent content and those articles were reviewed.
and 2009, ondansetron administration in US EDs in-
creased from 38,000 to 12.6 million doses annually. Data from a retrospective review and preliminary analy-
10
In a review of 13,863 patients given an antiemetic in sis were obtained from an ongoing, nonpublished study
the United States between 2006 and 2009, ondansetron on antiemetic use in Afghanistan being conducted by the
was the most prescribed agent, given 54.8% of the time. JTTS. This information is included to present recent ex-
Promethazine was the second most frequent agent used, perience with antiemetic use in the TCCC environment
at 50.3%. Data from the Joint Theater Trauma System (E. Burrell, personal communication, 17 June 2014).
2
(JTTS) show an even greater propensity for ondansetron
use (E. Burrell, personal communication, 17 June 2014). Additionally, information was obtained from the FDA
website and some general drug information was ob-
Two other commonly used agents were briefly consid- tained from open-source pharmacology websites.
ered: metoclopramide and droperidol. Each of these has
been issued FDA black box warnings—metoclopramide Discussion Points
for tardive dyskinesia, and droperidol for prolonged
11
QT intervals and torsades de pointes at doses at or The Case Against Promethazine
below recommended doses. Metoclopramide has a Promethazine is an H1-receptor–blocking agent that
12
side effect profile similar to promethazine, including also has sedative and antiemetic effects along with its

18 Journal of Special Operations Medicine Volume 15, Edition 2/Summer 2015