Page 172 - 80 guidelines for the treatment of malaria_opt

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Guidelines for the treatment of malaria – 2 edition

a8.2 Question:
Is a loading dose of quinine (20 mg/kg) superior to no loading dose?

summary
One systematic review, and one subsequent randomized controlled trial in children,
found no significant difference in mortality between quinine regimens with a high initial
quinine dose and those with no loading dose. However, parasite and fever clearance times
were reduced in the former.

Benefits
One systematic review (search date: 2002, three RCTs, 92 people) (2). One subsequent
RCT (3).

The systematic review found no significant difference in mortality between a group
receiving a high initial dose of quinine (20 mg salt/kg or 16 mg base/kg given by the
intramuscular route or by intravenous infusion) followed by a standard dose of quinine,
and one receiving the standard dose but no loading dose (two RCTs, 2/35 (5.7%) died in
the group receiving a high initial dose, 5/37 (13.5%) with no loading dose; relative risk:
0.43, 95% CI 0.09–2.15) (2). One of the RCTs (39 children) found no significant difference
between the two groups in mean time to recover consciousness (14 h with a high initial
dose, 13 h with no loading dose, weighted mean difference (WMD) 1.0 h, 95% CI −8.8 h
to +10.8 h) (4). Parasite clearance and fever clearance times were shorter for the high
initial dose group than for the group with no loading dose (parasite clearance time: two
RCTs, 67 people, WMD 7.4 h, 95% CI −13.2 h to −1.6 h; fever clearance time, two RCTs, 68
people, WMD −11.1 h, 95% CI −20.0 h to −2.2 h). The subsequent RCT (72 children aged 8
months–15 years in Togo, 1999–2000) found no significant difference between the group
receiving a high initial dose of IV quinine (20 mg salt/kg over 4 h, then 10 mg salt/kg every
12 h) and that receiving no loading dose (15 mg salt/kg every 12 h) in mortality (2/35 (6%)
with a high initial dose, 2/37 (5%) with no loading dose, RR 1.06, 95% CI 0.16–7.1) (3). It
also found no significant difference between the two groups for recovery of consciousness
(35.5 h with a high initial dose, 28.6 h with no loading dose, WMD +6.9 h, 95% CI −0.6 h
to +14.4 h) or time to 100% parasite clearance (48 h compared with 60 h).

Harms

The systematic review found no significant difference between the groups receiving a
high initial dose of quinine and no loading dose in rate of hypoglycaemia (two RCTs,
4/35 (11%) hypoglycaemia with a high initial dose, 3/37 (8%) with no loading dose, RR
1.39, 95% CI 0.32–6.00) (2). In one RCT (33 people) included in the review, transient
partial hearing loss was significantly increased in the group receiving a high initial dose
(10/17 (59%) compared with 3/16 (19%), RR 3.14, 95% CI 1.05–9.38) (5). In another RCT
(39 children), there was no significant difference between the two groups in neurological
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