Abstract
In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria. Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The systemic vascular resistance index (SVRI) was estimated from the echocardiographic cardiac index and the mean arterial pressure. SVRI and hematocrit levels were lower and plasma CFH and asymmetric dimethylarginine levels were higher in patients with malaria, compared with healthy participants. In multivariate linear regression models for mean arterial pressure or SVRI in patients with severe malaria, hematocrit and CFH but not asymmetric dimethylarginine were significant predictors. The SVRI was lower in patients with suspected bacterial sepsis than in those with severe malaria, after adjustment for hematocrit and age. Plasma CFH levels correlated positively with the core-peripheral temperature gradient and plasma lactate levels and inversely with the perfusion index. Impaired peripheral perfusion, as reflected by a low perfusion index or a high core-peripheral temperature gradient, predicted mortality in patients with severe malaria. CFH is associated with mean arterial pressure, SVRI, and peripheral perfusion in patients with severe malaria. This may be mediated through the nitric oxide scavenging potency of CFH, increasing basal vascular tone and impairing tissue perfusion.
Highlights
In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon
Severe malaria is a multiorgan disease defined by the presence of 1 or more diverse syndromes, including coma, metabolic acidosis, hyperparasitemia, severe anemia, and renal failure
Hyperlactatemia was more frequent in the severe malaria group (54/119, 45%) than the suspected bacterial sepsis group (6/50, 12%; P < .001), whereas hypotension was more frequent in the suspected bacterial sepsis group (5/56; 9%) than the severe malaria group (2/119, 2%; P = .001)
Summary
Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The inclusion criteria for malaria was presence of asexual falciparum parasitemia on blood film examination. The only exclusion criteria was absence of consent for practical reasons only patients admitted to adult medical wards (which included children down to 10 years old) participated in hemodynamic studies. Patients with suspected bacterial sepsis were recruited during the same timeframe and from the same sites as the malaria patients. Blood films were checked for suspected bacterial sepsis patients to confirm they did not have malaria. Written consent was sought from participants or, in cases where they were unable to give consent or aged under 18, from a legally acceptable representative
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