Jul 8, 2009 - Josh Hanson,1,2 Sophia W. K. Lam,1 Kishore Chandra Mahanta,3 ...... Boyle, and Ms Sophie Cohen for valuable advice and support during the.
MAJOR ARTICLE
Relative Contributions of Macrovascular and Microvascular Dysfunction to Disease Severity in Falciparum Malaria Josh Hanson,1,2 Sophia W. K. Lam,1 Kishore Chandra Mahanta,3 Rajayabardhan Pattnaik,3 Shamsul Alam,4 Sanjib Mohanty,3 Mahatab Uddin Hasan,4 Amir Hossain,4 Prakaykaew Charunwatthana,2 Kesinee Chotivanich,2 Richard J. Maude,2,5 Hugh Kingston,2,5 Nicholas P. Day,2,5 Saroj Mishra,3 Nicholas J. White,2,5 and Arjen M. Dondorp2,5 1
Cairns Base Hospital, Queensland, Australia; 2Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Ispat General Hospital, Rourkela, Orissa, India; 4Chittagong Medical College Hospital, Chittagong, Bangladesh; and 5Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom
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Background. Sequestration of parasitized erythrocytes in the microcirculation is considered the central pathophysiological process in severe falciparum malaria. Hypovolemia with reduced oxygen delivery and microvascular obstruction have different implications for patient management; however, their relative contributions to disease severity are uncertain. Methods. Adult patients (n = 28) with severe Plasmodium falciparum malaria were enrolled in a prospective hemodynamic study. Volume status and oxygen delivery were assessed using transpulmonary thermodilution. Microvascular sequestration was measured using orthogonal polarized spectroscopy. Findings. Duration of therapy before study enrollment was correlated with the amount of directly visualized and quantitated microvascular sequestration (P = .03). The amount of sequestration correlated with plasma lactate (rs = 0.55; P = .003) and disease severity (rs = 0.41; P = .04). In patients who had received artesunate for 6 meq/L, blood urea nitrogen >60 mg/dL (21.4 mmol/L), or pulmonary edema (defined as oxygen saturation of less than 90% with bi-basal crepitations on respiratory examination). Patients were enrolled only after written informed consent was obtained from an accompanying relative via a local translator. Patients were excluded if they were
