Page 29 - Journal of Special Operations Medicine - Summer 2015

antihistaminic properties. Its effectiveness as both an metoclopramide were equally effective and better than
antiemetic and a sedative are well established. 13–16 Even placebo in reducing nausea, but patients receiving meto-
at low doses of 6.25mg, parenteral promethazine is as clopramide or placebo had significantly better reduc-
effective of an antiemetic as parenteral ondansetron, tions in pain and significantly less sedation than patients
4mg. It is frequently used primarily for its antiemetic receiving promethazine. 29
16
effects and is often considered as an adjunct to analge-
sia or anesthesia because of the sedation it causes. It has Since 16 September 2009, there has been an FDA black
even been shown effective solely for use as a hypnotic box warning for the injectable form of promethazine,
sleep-induction agent. This sedative effect is concerning due to “the risk of serious tissue injury when this drug
17
when used in the acute trauma patient and particularly is administered incorrectly.” Foret et al. reported two
30
20
in patients with head injury and altered mental status. cases of accidental intra-arterial promethazine injec-
tion that led to necrosis, gangrene, and eventual upper
There are other significant side effects with prometha- extremity amputation. Keene et al. reported a case of
31
zine that may be particularly worrisome in the combat accidental intra-arterial injection in the dorsum of the
casualty. Promethazine has a well-documented history hand that ultimately resulted in complete amputation of
of undesired side effects relating to impairment and the thumb and distal index, ring, and little finger. Finally,
dysregulation of the central and autonomic nervous Paula et al. reported two cases of necrosis, one leading
32
systems. Of particular importance, promethazine may to gangrene and amputation, and one case of chronic
cause sedation and respiratory depression when used pain and hypersensitivity, with a permanent decrease in
independently and in conjunction with opioids. 4,18–20 range of motion, from promethazine IV injection.
Behrbalk et al. demonstrated that morphine with pro-
18
methazine, when compared with morphine alone, in- Although the published literature reports no incidents of
creased drowsiness by more than 70% and increased adverse events, such as those noted in the previous para-
ED stay times by 78 minutes in patients with acute low graph, in combat casualties in Afghanistan and Iraq,
back pain, with no discernible difference in analgesia. In the potential exists for these events to occur. Combined
a review of a hospital adverse drug event (ADE) data- with the more advantageous current pricing of generic
base, Sheth et al. found an increase in ADE rates for ondansetron, its potential benefits versus the risks of
19
promethazine when compared with all other antiemet- promethazine make this a good time to reevaluate the
ics combined, and they also found that concurrent use preferred medication for nausea and vomiting in com-
of opioids or other sedating drugs contributed to ADEs bat casualties.
with promethazine in 78.6% of patients.
The Case for Ondansetron
Additionally, promethazine has risks for extrapyramidal Ondansetron is used as an antiemetic with the FDA in-
symptoms, dystonia and other movement abnormali- dications for treatment of nausea from cancer-related
ties, impairment of psychomotor function, neuroleptic chemotherapy and radiation therapy and for post-
malignant syndrome, and hypotension. 1,21–27 Cowings et operative nausea and vomiting (PONV). It is very com-
al. demonstrated that therapeutic doses of prometha- monly used off-label for various other causes of nausea
22
zine cause significant impairment of operational task and vomiting, including opioid use, migraine headache,
performance in astronauts. Ridout and Hindmarch ob- and prepartum and intrapartum pregnancy-related
served similar results when promethazine was compared nausea and vomiting, as well as undifferentiated acute
to fexofenadine or placebo in healthy volunteers. 27 nausea. 4,13,33 It does not cause sedation or hypotension
and has a favorable safety profile. In comparison with
34
Although promethazine is effective as an antiemetic, other agents, ondansetron has performed at least as well
14
there are multiple agents that are equally or more effec- as droperidol, metoclopromide, prochloperazine, pro-
tive for the primary indication of nausea. Compared methazine, and other 5-HT receptor antagonists and
13
3
with prochlorperazine, for example, promethazine had is at least as safe. 1,4,33–39 This has been demonstrated in
slower onset, increased incidence of side effects, and less the prehospital, outpatient and inpatient settings, and in
benefit. There are multiple studies showing that on- gravid and laboring women.
28
dansetron is at least equivalent to promethazine as an
antiemetic. These will be discussed in detail in the fol- In 2008, Braude and Crandall demonstrated that on-
4
lowing section. dansetron was noninferior to promethazine as an anti-
emetic when treating undifferentiated nausea in the ED.
The well-designed and executed study by Vella et al. Ondansetron had antiemetic and anxiolytic effects that
29
compared promethazine, metoclopramide, and placebo were not significantly different than promethazine but
when given with pethidine (meperidine) in laboring caused significantly less sedation. Additionally, there
mothers. They demonstrated that promethazine and were no reports of akathisia in the ondansetron group

Replacement of Antiemetics in TCCC 19