Page 114 Acute Pain Management

differences between the groups (Chan et al, 2006 Level II). Another study showed that QT
prolongation occurred after 0.625 and 1.25 mg IV droperidol, but that this was not significantly
different from that seen with saline, indicating that other causes of mild QT prolongation
occur with anesthesia and surgery (White et al, 2005 Level II).
A large review (Nuttall et al, 2007 Level III‐3) of surgical patients in the periods 3 years before
(139 932 patients) and 3 years after (151 256 patients) the FDA ‘black box’ warning merged
anaesthesia database information with information from ECG and other databases as well as
patients’ case notes, and recorded all patients who had documented prolonged QT intervals,
TdP or death within 48 hours of their surgery. Despite a reduction in the use of droperidol
from 12% to 0% of patients following the warning, there was no difference in the incidence of
QT prolongation, ventricular tachycardia, or death within 48 hours of surgery and no clearly
identified case of TdP related to use of droperidol (Nuttall et al, 2007 Level III‐3). The authors
concluded that for low‐dose droperidol, the ‘black box’ warning was ‘excessive and
unnecessary’. Others have supported use of the warning but suggested it should be made
clear that the doses commonly used in the prevention and treatment of PONV are ‘off‐label’
and that the ‘FDA has no position on the safety and efficacy of doses below 2.5 mg’ (Ludwin &
Shafer, 2008).
The authors of recent guidelines for the management of PONV also expressed concerns about
CHAPTER 4 this warning, ‘droperidol would have been the panel’s overwhelming choice for PONV
the quality and validity of evidence that led to the FDA caution and concluded that without

prophylaxis’ (Gan, Meyer et al, 2007).
Haloperidol has also been associated with prolonged QT intervals and TdP (Habib & Gan, 2008b).
Using data from studies published up until 1988, a meta‐analysis showed that haloperidol was
also an effective antiemetic (Buttner et al, 2004 Level I). More recent studies have confirmed its
effectiveness compared with placebo (Aouad et al, 2007 Level II), ondansetron (no differences in
efficacy, side effects or QT intervals) (Aouad et al, 2007 Level II; Lee Y et al, 2007 Level II; Rosow et
al, 2008 Level II) and droperidol (as effective) (Wang et al, 2008 Level II). Combination of
haloperidol with ondansetron was more effective than ondansetron alone (Grecu et al, 2008
Level II) and haloperidol and dexamethasone also more effective than either drug given alone
(Chu CC et al, 2008 Level II), again with no difference in side effects or QT intervals. Compared
with droperidol, the only advantage of haloperidol may be ‘that there is no black box warning’
(Ludwin & Shafer, 2008).
Dolasetron (IV and oral formulations) is contraindicated by the Canadian authorities for any
therapeutic use in children and adolescents under 18 years of age and the prevention or
treatment of PONV in adults because of the risk of QT prolongation (Health Canada, 2006). The
age restriction is not limited to Canada, but valid in a number of countries including the United
Kingdom; cases of prolonged QT interval have also been reported after overdose (Rochford
et al, 2007).
NK1‐receptor antagonists may also be effective in the treatment of PONV. Aprepitant was
more effective than ondansetron for preventing vomiting at 24 and 48 hours after open
abdominal surgery, and in reducing the severity of nausea in the first 48 hours (Diemunsch et al,
2007 Level II). In a similar study with a slightly smaller number of patients after open abdominal
surgery, aprepitant was also found to be superior to ondansetron for prevention of vomiting in
the first 24 and 48 hours, but no difference was seen in the incidence of nausea (Gan, Apfel et
al, 2007 Level II).
P6 acupoint stimulation in patients with no antiemetic prophylaxis resulted in significant
reductions in the risks of nausea, vomiting and the need for rescue antiemetics; compared

66 Acute Pain Management: Scientific Evidence