Impaired Skeletal Muscle Microvascular Function and Increased Skeletal Muscle Oxygen Consumption in Severe Falciparum Malaria

Abstract

Organ dysfunction and tissue hypoxia in severe falciparum malaria result from an imbalance between oxygen delivery and demand. In severe malaria, microvascular obstruction from parasite sequestration decreases oxygen delivery. However, host microvascular function (defined as the capacity to increase oxygen delivery in response to ischemia) and oxygen consumption have not been assessed. We used near-infrared resonance spectroscopy to measure thenar muscle microvascular function (StO(2)recov) and oxygen consumption (VO(2)) in 36 adults in Papua, Indonesia, with severe malaria, 33 with moderately severe malaria (MSM), 24 with severe sepsis, and 36 healthy controls. In the severe malaria group, the StO(2)recov of 2.7%/second was 16% and 22% lower than that in the MSM group (3.1%/second) and control group (3.5%/second), respectively (P < .001), and comparable to that in the severe sepsis group (2.5%/second). In the severe malaria group, StO(2)recov was inversely correlated with lactate level (r = -0.63; P < .001) and predicted death (area under the receiver operating characteristic curve, 0.71 [95% confidence interval {CI}, .51-.92]), with each percentage decrease associated with an increased odds of mortality (odds ratio, 2.49 [95% CI, 1.05-6.2]). Conversely, VO(2) increased in the severe malaria group by 18%, compared with levels in the control and severe sepsis groups (P < .001), and was associated with parasite biomass (r = 0.49; P = .04). Impaired microvascular function is associated with increased mortality among individuals with severe malaria, while oxygen consumption is increased. Tissue hypoxia may result not only from microvascular obstruction, but also from impaired ability of the microvasculature to match oxygen delivery to increased oxygen demand.