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patients’ (Weinger, 2007). This was despite recognising the limitations of currently available
monitors, and despite the low sensitivity of continuous pulse oximetry in patients given
supplemental oxygen (common in many countries). In contrast, the ASA publication (Horlocker
et al, 2009) stated that both the Task Force members and consultants ‘disagree that pulse
oximetry is more likely to detect respiratory depression than are clinical signs’.
Measuring haemoglobin oxygen saturation levels may not be a reliable method of detecting
respiratory depression in the postoperative setting. In addition to the use of supplemental
oxygen, there may be reasons other than opioids for hypoxaemia. For example, when
measurement of oxygen saturation was used as an indicator of respiratory depression, the
incidence was reported to be 11.5% in patients receiving PCA and 37% in those given IM
opioids (Cashman & Dolin, 2004 Level IV). However, the same authors showed that patients given
IM opioids reported significantly more pain (moderate–severe pain in 67.2% and severe pain
in 29.1% compared with 35.8% and 10.4% respectively in PCA patients), suggesting that these
patients received much lower doses of opioids (Dolin et al, 2002 Level IV).
Increases in PCO 2 are the most reliable way of detecting respiratory depression. Continuous
monitoring of transcutaneous CO 2 for 24 hours after major abdominal surgery showed that
patients given IV PCA morphine had significantly higher CO 2 levels that those receiving
epidural local anaesthetic/fentanyl infusions (Kopka et al, 2007 Level III‐2; McCormack et al, 2008
CHAPTER 4 Cardiac effects
Level III‐2).

The use of methadone has been linked to the development of prolonged QT interval with a
risk of TdP and cardiac arrest (Gupta et al, 2007). Most case reports of TdP in patients taking
methadone have identified the presence of at least one other risk factor in addition to
methadone (Justo et al, 2006; Fredheim et al, 2008). Risk factors include female sex, heart disease,
other drugs with effects on QT interval (eg tricyclic antidepressants, antipsychotics, diuretics)
or methadone metabolism, congenital or acquired prolonged QT syndromes, liver impairment
and hypokalaemia (Fredheim et al, 2008).
Of patients receiving 60 to 100 mg methadone per day, 23% developed prolonged QT intervals
during treatment compared with none of the buprenorphine patients taking 16 to 32 mg three
times a week (Wedam et al, 2007 Level II). In the methadone group, the QT interval continued to
increase over time, even with stable doses.
There is as yet no consensus regarding the benefits or otherwise of obtaining an
electrocardiogram (ECG) in patients prior to starting methadone, although it may be that the
threshold for doing so should be lower in patients with other concomitant risk factors,
including those receiving higher doses of methadone (Cruciani, 2008).
The use of dextropropoxyphene also carries a risk of TdP (Barkin et al, 2006).

64 Acute Pain Management: Scientific Evidence