Page 994 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 78: Severe Malaria 725

the anti-inflammatory cytokines IL-1ra and IL-10 were detected in all it is associated with quinine use and particularly in the more susceptible
patients, including those with P vivax infection. 24 pregnant patient with malaria. Lactic acidosis, especially if sustained
after a patient has been admitted and treatment has begun, is one of the
■ CEREBRAL MALARIA best prognostic indicators of a fatal outcome. 35,36 In children, acidosis is
One of the most clinically discrete manifestations of severe disease associated with the syndrome of respiratory distress, 37,38 and in adults it
has been exacerbated by the use of epinephrine treatment as supportive
caused by P falciparum infections is coma in the absence of other intensive care therapy. Many of the neurological and metabolic features
39
causes. Investigations over the past three decades have established of severe malaria are mimicked by thiamine deficiency, which has been
25
that coma is associated with an increased density of parasitized eryth- unmasked by severe malaria in some southeast Asian adults. Plasma
40
rocytes in cerebral capillaries when compared with patients who died alanine levels like lactate are raised in severe malaria, consistent with
from severe malaria without coma. 26-28 There is no large increase in decreased gluconeogenesis. Lactate/pyruvate ratios are raised (to ~30)
blood-brain barrier permeability. Coma is also associated with increased and are much higher than values commonly seen in septic patients
anaerobic glycolysis, retinal hemorrhages and exudates and whiten- (~15). Plasma glutamine levels in children are lower in moderate than
29
ing of the retina, focal or generalized seizures, and clinical features of uncomplicated malaria, but are not significantly reduced in severe
30
a metabolic encephalopathy such as dysconjugate gaze, bruxism, and disease. Hypophosphatemia is associated with fever in malaria and
32
abnormal extensor or flexor posturing (Fig. 78-4). Deep tendon, plan- disease severity. There are increases in plasma triglyceride levels during
31
tar, and abdominal reflexes are variably altered and may be increased or acute infection in children and adults with malaria.
absent. These features are common to cerebral malaria in both African
some aspects. CSF opening pressures are usually normal in adults with ■ PULMONARY COMPLICATIONS
children and adults, but the syndromes in two age groups also differ in
cerebral malaria, and usually elevated in children. Coma often recovers Acute respiratory distress syndrome (ARDS) can be associated with
within a few hours in children and associated seizures (focal or general- several species of Plasmodium and often develops when parasitemia is
ized) are very common. Coma can take much longer (often 48-72 hours) clearing or has disappeared. It may be a manifestation of disease that is
to reverse in adults. Approximately 10 % of African children are left with less directly associated with cytoadherence of parasites to the pulmonary
significant neurological sequelae, whereas adults usually make a full microvasculature, and perhaps more associated with alterations in the
recovery. The radiological features of cerebral malaria may also differ patterns of circulating and local cytokines or other mediators. ARDS
31
between adults and children. is associated with a particularly high mortality, and often arises in the
■ METABOLIC COMPLICATIONS context of multiorgan failure. 41
Both children and adults with malaria show many metabolic derange- ■ ACUTE RENAL IMPAIRMENT
ments associated with severe malaria. Hypoglycemia may occur in up Renal impairment in severe malaria is of the acute tubular necrosis vari-
to a quarter of children with cerebral malaria and is associated with ety and probably arises as a consequence of microcirculatory obstruction
other complications such as seizures and neurological sequelae. It is complicated by prerenal causes. It can be precipitated by massive intra-
also associated with lactic acidosis and shares an underlying common vascular hemolysis, or “blackwater fever” that is variably due to infection,
mechanism of greatly increased anaerobic glycolysis from host tissues host red cell enzyme deficiency, and oxidant drugs used in treatment. 42
that have impaired microcirculation, as well as increased production
of lactic acid due to anemia, seizures, fever, and decreased clearance ■
of lactate by the liver. Acidosis may also interfere with compensatory HEMATOLOGICAL COMPLICATIONS
32
shifts in the hemoglobin oxygen dissociation curve toward the right Anemia in malaria is due to decreased erythropoiesis in acute infec-
(Bohr shift) associated with anemia, by decreasing relatively the red cell tion together with increased clearance of uninfected as well as infected
synthesis of 2,3-diphosphoglycerate. 33 erythrocytes. It can be exacerbated by acute intravascular hemolysis in a
Hypoglycemia is also associated with hyperinsulinemia due to qui- small percentage of patients, sometimes associated with the use of anti-
nine or quinidine as both antimalarial drugs exert direct effects on pan- malarial drugs. Direct destruction of red cells when parasites multiply
creatic beta cells. Hypoglycemia is less commonly seen in adults, unless and lyse them may be significant when a high proportion of cells are
34
infected, particularly bearing in mind that the number of infected cells
may be underestimated as the more mature parasites are largely absent
from the circulation.
Thrombocytopenia is common in all malarias and is usually due to
increased clearance by splenic mechanisms when it has been studied.
The degree of thrombocytopenia is inconsistently linked to disease
severity in falciparum infections. Thrombocytopenia is more marked
in P knowlesi compared with P vivax or P falciparum infections, and
is correlated with parasitemia. Despite frequent thrombocytopenia,
bleeding complications and features of florid disseminated intravascular
coagulation are relatively rare in severe malaria. Patients can occasionally
develop peripheral gangrene, sometimes in the absence of marked coag-
ulopathy or evidence for coincident bacterial sepsis or use of particular
antimalarial. This complication is then attributed to microcirculatory
abnormalities (sequestration of parasites) rather than vasculitis. 43
■ HEPATIC DYSFUNCTION

Jaundice of the conjugated bilirubin type can be marked in severe
infections although serum aminotransferases may not be markedly
elevated (beyond five times the upper limit of normal). Impaired syn-
thetic capacity is shown by falling albumin levels and prolongation in
FIGURE 78-4. Posturing in an African child with cerebral malaria. prothrombin times.

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