A non-injected opioid analgesia protocol for acute pain crisis in adolescents and adults with sickle cell disease

Abstract

Initial management of the acute pain crisis (APC) of sickle cell disease (SCD) is often unsatisfactory, and might be improved by developing a standardised analgesia protocol. Here, we report the first stages in developing a standard oral protocol for adolescents and adults. Initially, we performed a dose finding study to determine the maximal tolerated dose of sublingual fentanyl (MTD SLF) given on arrival in the acute care facility, when combined with repeated doses of oral oxycodone. We used a dose escalation algorithm with two dosing ranges based on patient's weight (<50 kg or >50 kg). We also made a preliminary evaluation of the safety and efficacy of the protocol. The study took place in a large tertiary centre in London, UK. Ninety patients in the age range 14-60 years were pre-consented and 31 treatment episodes were evaluated. The first 21 episodes constituted the dose escalation study, establishing the MTD SLF at 600 mcg (>50 kg) or 400 mcg (<50 kg). Further evaluation of the protocol indicated no evidence of severe opioid toxicity, nor increased incidence of acute chest syndrome (ACS). Between 0 and 6 hours, the overall gradient of reduction of visual analogue pain score (visual analogue scale (VAS)) was 0.32 centimetres (cm) per hour (95% confidence interval (CI) = 0.20 to 0.44, p < 0.001). For episodes on MTD SLF, there was median (interquartile range (IQR)) reduction in VAS score of 2.8 cm (0-4.2) and 59% had at least a 2.6-cm reduction. These results are supportive of further evaluation of this protocol for acute analgesia of APC in a hospital setting and potentially for supervised home management.

Keywords: Sickle; VOC; analgesia; crisis; opioid; pain.

Figure 1.

Treatment and observation flow chart. PS: pain score, RR: respiratory rate, A: alert, V: responds to verbal commands, P: responds to painful stimuli, U: unresponsive, PCA: patient-controlled analgesia.

Figure 2.

Consort study diagram.

Figure 3.

Sublingual fentanyl dosing and opioid adverse events (during the first 6 hours of monitoring) are shown diagrammatically for each treatment episode. MTD episodes are episodes 10–31. In the top section, the black bar represents the dose of SFL given for the treatment episode. In the second and third sections, the most severe degree of respiratory depression and sedation, and in the lower sections, most severe grades of pruritis, nausea and dizziness for each episode are shown as grey bars. SLF: sublingual fentanyl (dose in micrograms); RR: respiratory rate; A: alert; V: responds to verbal commands; P: responds to painful stimuli; U: unresponsive.