Page 113 Acute Pain Management

Nausea and vomiting
PONV is common and related to opioid administration in a dose‐dependent manner (Marret et
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al, 2005 Level I ; Roberts et al, 2005 Level IV), although many other risk factors for PONV have also
been identified (Gan, 2006). Therefore, drugs used as components of multimodal analgesia and
which are opioid‐sparing may also reduce PONV. Opioid‐sparing and a reduction in PONV has
been shown with concurrent administration of gabapentin (Tiippana et al, 2007 Level I), non‐
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selective non‐steroidal anti‐inflammatory drugs (nsNSAIDs) (Elia et al, 2005 Level I ; Marret et al,
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2005 Level I ); and ketamine (Bell et al, 2006 Level I). Opioid‐sparing with no decrease in PONV
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was reported for paracetamol and coxibs (Elia et al, 2005 Level I ; Remy et al, 2005 Level I).
The risk of PONV is significantly reduced by the use of droperidol, dexamethasone and
ondansetron, which are equally effective (Tramer, 2001 Level I; Apfel et al, 2004 Level II); propofol
and omission of nitrous oxide (N 2O) are less effective (Apfel et al, 2004 Level II).
A Cochrane review identified eight drugs that effectively prevented PONV compared with
placebo: droperidol, metoclopramide, ondansetron, tropisetron, dolasetron, dexamethasone,
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cyclizine and granisetron (Carlisle & Stevenson, 2006 Level I ). The authors concluded that
evidence for differences between the drugs was unreliable due to publication bias. There were
few data to compare side effects, but droperidol was more sedative and headache was more
common after ondansetron.
Combinations of antiemetics may be more effective than one drug given alone. Prophylaxis
with the combination of a 5HT3‐receptor antagonist and dexamethasone was associated with
lower use of rescue antiemetics than 5HT3‐receptor antagonist or dexamethasone alone CHAPTER 4
(Kovac, 2006 Level I). Similarly, the combination of droperidol and ondansetron was additive
(Chan et al, 2006 Level I). Other combinations that were more effective than either drug given
alone were cyclizine and granisteron (Johns et al, 2006 Level II), dexamethasone and haloperidol
(Rusch et al, 2007 Level II; Chu CC et al, 2008 Level II), and dexamethasone and dolasetron (Rusch et
al, 2007 Level II). The addition of metoclopramide to dexamethasone also led to better PONV
prophylaxis but, compared with dexamethasone 8 mg alone, only if doses of 25 mg and 50 mg
metoclopramide were used and not 10 mg (Wallenborn et al, 2006 Level II).
Droperidol, and to a lesser extent, ondansetron, may lead to prolonged QT intervals. Concerns
about the potential for serious cardiac arrhythmias secondary to QT prolongation associated
with administration of droperidol led to a ‘black box’ warning by the United States Food and
Drug Administration (FDA) in 2001. Following this there has been a significant reduction in
the use of this drug, even though the warning was felt by many to be unwarranted (Habib
& Gan, 2008a).
In a study in healthy volunteers, QT prolongation with droperidol 1 mg IV was significantly
greater than following ondansetron 4 mg IV, but the effect of combining both drugs was no
worse than droperidol alone (Charbit et al, 2008 Level II). Significant but similar QT prolongation
(compared with pretreatment values) was also noted in patients given droperidol 0.75 mg IV
or ondansetron 4 mg IV after surgery (Charbit et al, 2005 Level II). However, QT interval was
already prolonged in 21% of these patients prior to administration of any antiemetic drug.
There was also a transient increase in QT interval after administration of ondansetron 4 mg IV,
droperidol 1.25 mg IV, or their combination given prior to surgery, but there were also no

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This meta‐analysis includes a study or studies that have since been withdrawn from publication. Please refer to the
Introduction at the beginning of this document for comments regarding the management of retracted articles.
Expert advice suggested that withdrawal of the retracted articles would not influence the conclusions but that
reanalysis would be required for this to be confirmed. Marret et al (Marret et al, Anesthesiology 2009; 111:1279–89)
reanalysed the data included in this meta‐analysis after excluding that obtained from the retracted publications.
They concluded that removal of this information did not significantly alter the results.
Acute pain management: scientific evidence 65