Impact of oral L-arginine supplementation on blood pressure dynamics in children with severe sickle cell vaso-occlusive crisis

Abstract

Sickle cell anaemia (SCA) patients generally have lower blood pressures compared to those with the AA haemoglobin genotype. However, during vaso-occlusive crises (SCA-VOC), blood pressures (BP) may elevate transiently to levels beyond the 95^th percentile. The risk of stroke or even death increases with increasing systolic BP in SCA. Therefore, interventions targeted at BP reduction may be essential during severe vaso-occlusive episodes. Reduction in BP was achieved with arginine therapy in a meta-analysis of randomized controlled trials (RCT) in non-sickle cell adults. The impact of oral arginine (given for pain control) on the BP of children with SCA-VOC has not been documented.

Methods: A double-blind RCT of oral _L-arginine hydrochloride as adjuvant therapy for pain reduction was conducted in children with SCA-VOC, aged 5-17 years, over a 2-year period. The mean change in BP and the time to achieve BP <90^th percentile was added as part of the outcome variables. The anthropometry, pain scores and mercury sphygmomanometry were done following standard procedures. BP percentiles were generated using the Fourth Report guidelines. Differences in the time to normalization of BP in the treatment arms were tested with Kaplan-Meier analysis.

Results: Sixty-six children (57.6% male) were randomized into _L-arginine (35 patients) or placebo (31 patients) arm. The prevalence of hypertension (BP ≥95^th percentile) at presentation tended to increase as the pain scores increased, from a prevalence of 50% in patients with a score of 7 to 65% in those with score of 10 (systolic hypertension) and from 44.4% in patients with pain score of 7 to 50% in patients with pain score of 10 (diastolic hypertension). Patients that received arginine recorded a 12.8±3.2 mmHg decline in mean systolic BP compared to the placebo group, where a mean difference of 7.6±1.5 mmHg was observed, P<0.001. Similarly, the mean diastolic BP reduced by 13% in the arginine group and 7.5% in the placebo group, P<0.001. Children who received arginine tended to achieve BP normalization much faster than the placebo group (P=0.112), and no serious adverse events were documented related to the hypertension or arginine administration.

Conclusions: High blood pressure (≥95^th percentile) is common amongst children with SCA-VOC and are mostly asymptomatic. Administration of oral arginine given for pain control achieves a reduction of the BP at a faster rate in children compared to placebo and it is safe.

Keywords: Nigerian children; Oral arginine; blood pressure; sickle cell anemia.

Figure 1

Daily percentage decline in mean of systolic blood pressure (upper panel) and diastolic blood pressure (lower panel) from the baseline in the arginine and placebo groups, showing a steeper rate of decline in the arginine group than in the placebo, p value for trend <0.001.

Figure 2

Time-to-normalization of elevated systolic blood pressure (SBP <90^th percentile for age, gender and height), and elevated diastolic blood pressure (DBP <90^th percentile for age, gender and height). By 72 hours, 50% of patients that received arginine had achieved normalization of systolic blood pressure as against 25% in the placebo group, P=0.06 (upper panel). Similarly, higher proportion of patients (87.5%) in the arginine group than in the placebo group (62.5%) had achieved normalization of diastolic BP, P=0.112 (lower panel) by 72 hours.