Felix Anthony Lubega1, Mithrika Sureshi De silva2, Tonny Stone Luggya1, Deogratias Munube1
1) Uganda 2) Australia
Background:Ketamine is cheap, widely safe, readily available drug, with analgesic effects at sub-anaesthetic doses however literature concerning its use in sickle cell crises is still limited.
Objectives: To compare the maximum change in numeric rating scale (NRS) pain scores, in patients receiving low-dose ketamine (LDK) or morphine (MOR) for acute severe vaso occlusive crisis(VOC) pain at sickle cell day care center.
Methods: We performed a IRB approved, randomized, prospective, double-blinded, active-control, non-inferiority trial of children between 7 and 18 years of age with severe painful sickle cell crisis, at a tertiary resource limited Sickle Cell Clinic. Patients were consented and randomized to receive, either IV Ketamine(1mg/kg) or IV Morphine(0.1mg/kg) over 10 minutes. The primary endpoint is maximal change in NRS pain score. A clinically meaningful difference in validated pain scores was defined as 13mm.Assuming both treatments are on average equal, a sample size of 240 patients (120 per group) provided 95% power to demonstrate that IV LDK is non-inferior to IV morphine with a 0.05 level of significance.
Results: Two hundred forty patients were enrolled (LDK120, MOR120).Demographic variables and baseline NRS scores (8.9 vs 9.2) were similar. LDK was comparable to MOR in the maximum change in NRS scores, 66.4% vs 61.3% (MD5.5; 95%CI-2.2 to-13.2;p=0.18). Time to achieve maximum reduction in NRS pain scores was at 19.8 minutes for LDK and 34.1minutes for MOR. LDK patients were 11.3 times more likely to develop adverse effects, though were transient, mild and anticipated (37.5% vs 3.3%). MOR had more treatment failures 40% vs 28.3%. Vital signs and sedation scores were similar in both groups.
Conclusion: IV LDK at 1mg/kg provides comparable analgesic effectiveness as IV MOR for acute severe painful sickle cell crisis in children in the day case sickle cell centre. However is associated with high incidence of several transient, anticipated, mild adverse effects.
