Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

This survey represents the most recent analysis of drug combinations administered by CSCI in the UK. The most commonly prescribed drug administered by CSCI was midazolam, while the most commonly prescribed opioid was morphine. Diamorphine was identified as the least commonly prescribed opioid. The previous national survey, however, identified diamorphine as the opioid most commonly administered by CSCI [6]. The worldwide shortage of diamorphine during the winter of 2004 forced services to adopt morphine as the opioid of choice and it would appear that many have not reverted to diamorphine. In 2012, the National Institute for Health and Clinical Excellence recommended that the parenteral opioid with the lowest acquisition cost (i.e. morphine) should be used first-line [22]. Diamorphine, with its superior solubility, appears to be generally reserved for patients with a relatively high opioid requirement, as reflected by mean and median doses of 77 mg and 30 mg respectively (Table 1).

A previous literature review found that only 70 drug combinations suitable for administration by CSCI had been investigated for compatibility and stability. The majority of these (88.6%) referred to two-drug combinations [23]. Indeed, a review of the literature for the top 40 combinations identified by the national survey revealed that only 13 (32.5%) have been analysed at clinically relevant doses for compatibility and stability, the majority of which comprised two drugs. The five combinations identified by the Delphi study were those mainly associated with the management of difficult or recalcitrant symptoms. Such combinations were expected to occur infrequently, a supposition vindicated by the appearance of only one combination in the database derived from the survey. These combinations often reflect specialist practice. It was unclear from the survey which area of practice the data were collected. A survey of specialist palliative care inpatient services only would be expected to identify a different list of commonly used combinations. Indeed, analysis of practice at a specialist palliative care inpatient unit revealed that 70% of the combinations comprised three or more drugs (compared to 50.6% in this survey) [24]. Since the majority of currently available compatibility and stability data refer to two-drug combinations, there is a disparity between available evidence and clinical practice.

A limitation of the Delphi technique is the risk of selection bias often associated with the choice of expert panel. Indeed, there are no universally accepted criteria for the selection of experts using the Delphi technique [25]. Selecting panel members through methods other than acquaintance is believed to minimise bias [26, 27]. In an attempt to reduce the risk of researcher bias, experts were selected for the Delphi study through a mix of promptness of response to the call to participate and snowballing. Both methods, however, may be associated with a potential for bias. A promptness to respond to the invitation and a willingness to participate suggests the expert has an interest in the subject under scrutiny, which carries a risk of self-selection bias. It has been proposed that there is an inherent bias in Delphi studies because experts may volunteer to take part as they hold particular views about the subject matter, which could influence the consensus process [28]. Nonetheless, it has been shown that those who are willing to participate in expert panels are representative of their unwilling colleagues [29]. The ‘snowballing’ technique is a conventional recruitment method in Delphi research [30‐32]. This technique, however, could have led to selection bias because of its unrepresentative approach by potentially limiting the breadth of experience and geographical distribution of participants [33, 34].