Sickle cell disease (SCD) is the most common genetic disorder in the UK. Increasing evidence suggests that autonomic function is altered in SCD, and if sympathetic drive is increased, this might increase the vascular tone of the intracranial arteries, leading to narrowing and increased velocities. Deep inspiratory gasps generate a vasomotor reflex characterised by sympathetic mediated transient vasoconstriction of skin arterioles. The aim of this study was to assess the relationship between autonomic reactivity, oxygen saturation (SpO2) and cerebral blood flow velocity (CBFV) in children with SCD.
Methods Autonomic reactivity was assessed using the inspiratory gasp vascular responses (IGVR) in 71 children with SCD (median age 7.8, range 2.8–15.3) years and 26 controls (7.7, 3.2–12.8). Cutaneous blood flux was measured by laser Doppler fluximetry (VMS and VP1T probe, Moor Instruments UK) on the pulp of the index finger of the non-dominant hand at rest and during three deep inspiratory gasps. CBFV was measured in the middle cerebral artery (MCA) and basilar artery (BA) using transcranial Doppler (DopplerBox, ScanMed, UK); daytime and minimum nocturnal SpO2 using pulse oximetry (Masimo, Irvine CA).
Results Mean resting blood flux (MRBF), IGVR, CBFV in the right and left MCA and BA were all higher in SCD compared to controls (p=0.002, p=0.001, p<0.0001, p<0.0001, p<0.0001, respectively), while SPO2 and minimum nocturnal SpO2 were lower (p<0.0001, p=0.026). In an analysis including SCA patients and controls, MRBF and IGVR were inversely correlated with SPO2 (r=−0.286, −0.269; p=0.011, 0.019). Left and right MCA and BA velocities were correlated with MRBF (r=0.241, 0.364, 0.283; p=0.47, 0.002, 0.022, respectively) and IGVR (r=0.420, 0.307, 0.451; p<0.0001, p=0.011, p<0.0001). SpO2 was inversely correlated with maximum CBFV in MCA and BA (r= −0.223, −0.276; p=0.044, 0.015). In multiple linear regression, IGVR predicted maximum MCA CBFV (r2=0.097, p=0.011); SpO2 predicts IGVR (r2=0.058 p=0.037) but not CBFV. IGVR predicts CBFV independently of SpO2 in a stepwise model.
Conclusion The study provides evidence of increased MRBF, sympathetic tone and CBFV in children with SCD and low SpO2 which may improve understanding of the pathogenesis and prevention of cerebrovascular disease and neurological complications.