Article type
Year
Abstract
Background: Malaria is an important cause of deaths worldwide. Quinine is either given as a series of uniform doses or with a high first (loading) dose followed by a series of uniform doses.
Objectives: To assess the clinical outcomes and adverse effects of a high first (loading) dose regimen of quinine with a uniform (no loading) dose regimen in patients with severe malaria.
Methods: We searched the Cochrane Infectious Diseases Group specialized trials register (May 2001) and, the Controlled Trials Register (Issue 2, 2001), MEDLINE (1966 to April 2001), EMBASE (1988 to March 2001), LILACS (La Literatura Latinoamericana y del Caribe de Informacion en Ciencias de Salud; 2000 39a Edition CD-ROM). We contacted researchers for unpublished and ongoing trials. Randomized controlled trials were selected. Patients were adults or children with any form of severe malaria treated with intravenous quinine. The intervention group had a loading dose of intravenous quinine (20 mg/kg as the first dose) while the control group had no loading (uniform) dose (10 mg/kg as the first dose). After the first dose, patients in both groups were given 10 mg/kg every 8 or 12 hours. The quality of trials included were independently assessed with regard to the allocation sequence, concealment of allocation, blinding, and completeness of the trial, using guidelines designed by the Cochrane Infectious Diseases Group. The data from the trials were extracted by one reviewer and independently cross checked by the second reviewer and analysed using Review Manager (Version 4.1). We contacted all the authors of the trials included for clarification where necessary. Binary data were combined using Relative Risk, and continuous data were combined using the weighted mean difference.
Results: Two trials involving 72 people (39 children and 33 adolescents and adults) were included. Regarding the primary outcome (death), there were fewer deaths in the high first (loading) dose group though it was not statistically significant (Relative Risk [RR] 0.43; 95% confidence interval [CI] 0.09 to 2.15). With the secondary outcomes, we found that while a high first (loading) dose did not hasten the recovery of consciousness (weighted mean difference [WMD] 1.0; 95% CI -10.63 to 12.63) it was associated with faster clearance of parasites (WMD -7.44; 95% CI -13.24 to -1.64) and resolution of fever (WMD -11.11; 95% CI -20.04 to -2.18). Concerning adverse effects, the high first (loading) dose was associated with deafness (RR 3.14; 95% CI 1.05 to 9.38) which was transient as it resolved within 2 weeks. Nevertheless the loading dose was not associated with more neurological sequelae (RR 0.58; 95% CI 0.06 to 5.91) or convulsions (RR 0.73; 95% CI 0.29 to 1.84).
Conclusion: Quinine loading dose reduced fever clearance time and parasite clearance time and was not associated with increased convulsions or an increased incidence of hypoglycaemia. For clinicians using quinine in severely ill children, this is probably sufficient evidence to use a loading dose, whilst monitoring carefully blood glucose for quinine induced hypoglycaemia.
Objectives: To assess the clinical outcomes and adverse effects of a high first (loading) dose regimen of quinine with a uniform (no loading) dose regimen in patients with severe malaria.
Methods: We searched the Cochrane Infectious Diseases Group specialized trials register (May 2001) and, the Controlled Trials Register (Issue 2, 2001), MEDLINE (1966 to April 2001), EMBASE (1988 to March 2001), LILACS (La Literatura Latinoamericana y del Caribe de Informacion en Ciencias de Salud; 2000 39a Edition CD-ROM). We contacted researchers for unpublished and ongoing trials. Randomized controlled trials were selected. Patients were adults or children with any form of severe malaria treated with intravenous quinine. The intervention group had a loading dose of intravenous quinine (20 mg/kg as the first dose) while the control group had no loading (uniform) dose (10 mg/kg as the first dose). After the first dose, patients in both groups were given 10 mg/kg every 8 or 12 hours. The quality of trials included were independently assessed with regard to the allocation sequence, concealment of allocation, blinding, and completeness of the trial, using guidelines designed by the Cochrane Infectious Diseases Group. The data from the trials were extracted by one reviewer and independently cross checked by the second reviewer and analysed using Review Manager (Version 4.1). We contacted all the authors of the trials included for clarification where necessary. Binary data were combined using Relative Risk, and continuous data were combined using the weighted mean difference.
Results: Two trials involving 72 people (39 children and 33 adolescents and adults) were included. Regarding the primary outcome (death), there were fewer deaths in the high first (loading) dose group though it was not statistically significant (Relative Risk [RR] 0.43; 95% confidence interval [CI] 0.09 to 2.15). With the secondary outcomes, we found that while a high first (loading) dose did not hasten the recovery of consciousness (weighted mean difference [WMD] 1.0; 95% CI -10.63 to 12.63) it was associated with faster clearance of parasites (WMD -7.44; 95% CI -13.24 to -1.64) and resolution of fever (WMD -11.11; 95% CI -20.04 to -2.18). Concerning adverse effects, the high first (loading) dose was associated with deafness (RR 3.14; 95% CI 1.05 to 9.38) which was transient as it resolved within 2 weeks. Nevertheless the loading dose was not associated with more neurological sequelae (RR 0.58; 95% CI 0.06 to 5.91) or convulsions (RR 0.73; 95% CI 0.29 to 1.84).
Conclusion: Quinine loading dose reduced fever clearance time and parasite clearance time and was not associated with increased convulsions or an increased incidence of hypoglycaemia. For clinicians using quinine in severely ill children, this is probably sufficient evidence to use a loading dose, whilst monitoring carefully blood glucose for quinine induced hypoglycaemia.