SUPPORTIVE CARE AND MANAGEMENT
OF COMPLICATIONS
Good nursing care is essential in the management of severe
malaria, with particular attention to fluid balance, manage-
ment of the unconscious patient, and detection of potentially
lethal complications such as hypoglycemia.
Coma. In Western ICUs, mechanical ventilation is often
used in the unconscious cerebral malaria patient to protect
the airway, although its efficacy in terms of prevention of
mortality and sequelae has not been proven.29 In a small
study of Kenyan children with cerebral malaria and raised
intracranial pressures, mannitol, an anti-osmotic agent, was
successful in reducing intracranial pressure for short periods,30 but no convincing clinical evidence exists to support its
routine use.
Convulsions. Seizures in cerebral malaria should be treated
with rectal diazepam, intravenous lorazepam, paraldehyde, or
other standard anticonvulsants, after high-flow oxygen and
appropriate airway management have been initiated.31 Prophylactic phenobarbitone was shown to reduce seizure incidence in adult cerebral malaria, but a study in children using
a single intramuscular dose of 20 mg/kg reduced seizures but
increased mortality, possibly through respiratory depression
caused by an interaction with diazepam.32,33 Prophylactic anticonvulsive therapy is therefore currently not recommended.
Acute renal failure. Whereas in African children malariaassociated acute renal failure is extremely rare, it is a relatively common complication of severe malaria in nonimmune
adults and children. It has an untreated mortality of > 70%
and should be treated with adequate renal replacement
therapy—preferably by hemofiltration when available, as this
has been shown to be superior to peritoneal dialysis in terms
of mortality and cost-effectiveness.34,35 The role of hemodialysis has not been assessed in a randomized trial, but it is
likely to be superior to peritoneal dialysis in the hemodynamically stable patient.
Hemodynamic shock. Shock in severe malaria (“algid malaria”) carries a high mortality in both adults and children.29,36 It should be treated initially with oxygen and fluids
(with monitoring of central venous pressure if available),
though, as in children, it is unclear how aggressive the volume
expansion should be in terms of safety and effectiveness. Massive hemorrhage, from the gastrointestinal tract or rarely a
ruptured spleen, should be excluded. A septic screen including blood cultures should be performed and appropriate
broad-spectrum antibiotics administered to cover the possibility of bacterial sepsis. If inotropes are necessary, dopamine
has been used safely in malaria, and dobutamine and norepinephrine may also be used though there is little experience
with them in severe malaria.37 Epinephrine should be avoided
as it induces serious lactic acidosis.38
Fluid resuscitation. The role of aggressive fluid resuscitation in the management of severe malaria, particularly in children, is unclear and currently controversial. The debate centers around whether hypovolemia plays an important role in
the pathophysiology of severe malaria, causing poor tissue
perfusion, leading to anaerobic glycolysis and consequent acidosis. Advocates of aggressive fluid repletion suggest that the
standards of care applied in resource-rich settings for severely
ill children with bacterial sepsis should be extrapolated to
severe malaria, while those against argue that there is no
evidence that severe dehydration occurs in severe malaria and
are concerned that overzealous rehydration may lead to pulmonary and cerebral edema.39–41 There is at present insufficient evidence either way, as all clinical studies conducted so
far have been small and unsatisfactory.42 A large multicenter
clinical trial is planned that will hopefully provide some answers, but in the meantime, intravenous fluid regimens should
be guided by clinical judgment and, if available, by central
venous pressure monitoring.
Acidosis. Metabolic acidosis, a common complication of severe malaria, is strongly associated with fatal outcome in both
adults and children.43,44 Lactic acid is an important contributor, but impaired renal bicarbonate handling and the presence
of other as yet unidentified acids also play major roles.45
Dichloroacetate (which stimulates pyruvate dehydrogenase)
has been shown to reduce plasma lactate in severe malaria,
but to have no effect on pH, possibly because of the multifactorial etiology of the acidosis.46,47 Hemofiltration has been
shown to rapidly eliminate acidosis in malaria patients with
renal failure, even in the presence of lactic acidosis.35 Early
hemofiltration may be a useful strategy in patients with acidosis and renal impairment who have not yet developed established renal failure, but this has not yet been evaluated in
a clinical trial.
Anemia. This is present in almost all patients with severe
malaria but occurs most prominently in young children. Benefits of blood transfusion should outweigh the risks (especially of HIV and other pathogens). There is no clear evidence supporting specific hemoglobin cut-off levels, and a
number of figures are quoted in reviews and guidelines. In
adults, the threshold for blood transfusion is commonly set at
a hematocrit < 20%. Clinical evidence from Kenya has led to
proposed threshold hemoglobin levels for African children of
5 g/dL if there is co-existing respiratory distress, impaired
consciousness, or hyperparasitemia or at an absolute cut-off
of 4 g/dL.48
ARDS. This feared complication has a high mortality rate
and can develop several days after admission and onset of
treatment. Clinical research is needed into both the pathophysiology and treatment of this condition. The etiology is
poorly understood, and treatment in malaria is currently
based on expert opinion and extrapolation from studies on
ARDS associated with other conditions.