N-acetylcysteine as adjunctive treatment in severe malaria: A randomized, double-blinded placebo-controlled clinical trial

被引:54
作者
Charunwatthana, Prakaykaew [1 ]
Faiz, M. Abul [2 ]
Ruangveerayut, Ronnatrai [3 ]
Maude, Richard J. [7 ]
Rahman, M. Ridwanur [4 ]
Roberts, L. Jackson, II [5 ]
Moore, Kevin [6 ]
Bin Yunus, Emran [4 ]
Hoque, M. Gofranul [4 ]
Hasan, Mahatab Uddin [4 ]
Lee, Sue J. [1 ,7 ]
Pukrittayakamee, Sasithon [1 ]
Newton, Paul N. [7 ]
White, Nicholas J. [1 ,7 ]
Day, Nicholas P. J. [1 ,7 ]
Dondorp, Arjen M. [1 ,7 ]
机构
[1] Mahidol Univ, Fac Trop Med, Bangkok, Thailand
[2] Dhaka Med Coll, Dhaka, Bangladesh
[3] Mae Sot Gen Hosp, Mae Sot, Tak Province, Thailand
[4] Chittagong Med Coll Hosp, Chittagong, Bangladesh
[5] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA
[6] UCL, Dept Med, Ctr Hepatol, London, England
[7] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX3 9DU, England
基金
英国惠康基金;
关键词
N-acetylcysteine; severe malaria; adjunctive treatment; ACETYL-L-CYSTEINE; OXIDATIVE STRESS; BLOOD-FLOW; FALCIPARUM-MALARIA; CELL DEFORMABILITY; CEREBRAL MALARIA; ORGAN FAILURE; PLASMODIUM; CHILDREN; F-2-ISOPROSTANES;
D O I
10.1097/CCM.0b013e3181958dfd
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objective: Markers of oxidative stress are reported to be increased in severe malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be beneficial in treatment. We studied the efficacy and safety of parenteral NAC as an adjunct to artesunate treatment of severe falciparum malaria. Design: A randomized, double-blind, placebo-controlled trial on the use of high-dose intravenous NAC as adjunctive treatment to artesunate. Setting: A provincial hospital in Western Thailand and a tertiary referral hospital in Chittagong, Bangladesh. Patients. One hundred eight adult patients with severe falciparum malaria. Interventions: Patients were randomized to receive NAC or placebo as an adjunctive treatment to intravenous artesunate. Measurements and Main Results. A total of 56 patients were treated with NAC and 52 received placebo. NAC had no significant effect on mortality, lactate clearance times (p = 0.74), or coma recovery times (p = 0.46). Parasite clearance time was increased from 30 hours (range, 6-144 hours) to 36 hours (range, 6-120 hours) (p = 0.03), but this could be explained by differences in admission parasitemia. Urinary F-2-isoprostane metabolites, measured as a marker of oxidative stress, were increased in severe malaria compared with patients with uncomplicated malaria and healthy volunteers. Admission red cell rigidity correlated with mortality, but did not improve with NAC. Conclusion: Systemic oxidative stress is increased in severe malaria. Treatment with NAC had no effect on outcome in patients with severe falciparum malaria in this setting. (Crit Care Med 2009; 37:516-522)
引用
收藏
页码:516 / 522
页数:7
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