Page 995 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

726 PART 5: Infectious Disorders

■ CIRCULATORY CHANGES CSF examination in the absence of contraindications is advised

Shock is not a common complication of severe malaria in either in adults with cerebral symptoms to exclude coincident infections
(bacterial or viral, for example). In children, because of possible risks
children or adults. In children, there has been controversy about the
degree of intravascular volume depletion and the need for aggressive associated with raised intracranial pressure, some suggest delaying
CSF examination until antimalarial treatment has begun. A case can be
fluid administration. 44,45 A recent randomized study in African chil-
dren found that both normal saline and albumin fluid bolus strategies made for children and adults for starting empirical antibiotic therapies,
as about a quarter of adults in intensive care in France had coinfections
increased mortality compared to a no-bolus strategy. The study was
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conducted in the absence of intensive care unit facilities. In adults, the (both gram-positive and gram-negative and community acquired or
nosocomial) diagnosed during their admission, and these were signifi-
risk of pulmonary edema and the ability to monitor hemodynamic 50
status of patients comparatively easily guide implementation of the sug- cantly more common in fatal cases. The CSF shows little if any eleva-
tions in cell count (usually below 50 cells/μL) and protein content.
gestion that patients should not be “overhydrated.” In children, although
there is less risk of pulmonary edema, there is a potential increased DIFFERENTIAL DIAGNOSIS
risk of raised intracranial pressure and intracerebral displacement syn-
dromes, suggesting that decisions about volume replacement should be Malaria should be distinguished from other acute infections (bacterial
guided by real-time assessments of hemodynamic status (see Chap. 34 sepsis or meningitis), viral encephalitides (particularly dengue fever with
regarding hemodynamic assessment). thrombocytopenia), enteric fevers and leptospirosis, severe influenza,
viral hepatitis or hepatic failure due to other causes (Reye syndrome in
DIAGNOSIS children), intoxications, and other noninfective causes of coma.
The diagnosis of malaria should be considered in any traveler return-
ing from malaria-endemic areas even if they have adopted appropriate TREATMENT OF SEVERE FALCIPARUM MALARIA
malaria-prevention measures. In case patients have been pretreated with Severe falciparum malaria is a medical emergency with a high case
antimalarials, peripheral parasitemia may be very difficult to detect, fatality rate. In hospitalized African children with strictly defined severe
and the decision to begin antimalarial treatment becomes a clinical malaria, mortality is around 11%, but this increases to 20% if the child
one, although the presence of malaria pigment in leukocytes and a presents with cerebral malaria (coma) where supportive facilities may be
positive PfHRP2-based rapid test can confirm the recent presence of limited. Death occurs early after admission, with 65% of fatalities within
P falciparum. Malaria can occasionally arise in the vicinity of airports in the first 24 hours and 83% within the first 48 hours. In Asian adults
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nonendemic areas where infected mosquitoes are delivered by airplanes. overall inhospital mortality in low resource settings is higher, around
Headaches, myalgias, and fever are the commonest features of malaria. 24% in severe malaria and 34% in cerebral malaria; 50% of patients die
These symptoms can emerge many months after travel, and sometimes within the first 48 hours after admission. In high resource settings
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even longer if antimalarial prophylaxis was used. Most travelers (~80%) with state-of-the-art critical care facilities, mortality of imported severe
develop symptoms of malaria within a month of leaving endemic areas, malaria is around 11%. In this setting, higher parasitemia, increased
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and cannot develop symptoms earlier than 1 week after being bitten by age, and depth of coma independently predicted fatal outcome.
an infected mosquito. Other nonspecific symptoms such as diarrhea, Management of severe malaria consists of promptly starting adequate
vomiting, cough, fatigue, and weakness are also common. Periodicity of parenteral antimalarial treatment, treatment of concomitant diseases,
fever so well described in classical texts on malaria is not a diagnostically and supportive treatments. No adjuvant therapies have been proven to
useful sign for falciparum malaria as often fevers are irregular. be beneficial.
The onset of coma indicating cerebral involvement can be heralded Blood glucose (and lactate) should be monitored frequently and regu-
by seizures or confusion. Often there is biochemical evidence of other larly together with peripheral parasitemia and its response to treatment.
organ involvement, such as renal or hepatic impairment. Metabolic Hematological changes including worsening anemia should be detected
derangements and thrombocytopenia are also frequently observed. and corrected. Changes in the white count are variable, and phagocytic
Microscopic diagnosis is still the gold standard for confirming cells can be seen carrying malarial pigment in blood films. Electrolyte
malaria. Good quality thick and thin films stained conventionally examinations often show mild hyponatremia and hypophosphatemia.
should be examined by experienced microscopists. Thick films are Other abnormalities in electrolytes or biochemistry are indicative of
43
more sensitive at detecting parasites but thin films are better at reveal- specific organ involvement.
ing morphological details useful to speciate most parasites. P knowlesi
cannot be distinguished from P malariae or sometimes other species by ■ ANTIMALARIAL TREATMENT
microscopy. Rapid diagnostic tests available as kits that rely on detecting The available parenteral antimalarial drugs (see Table 78-2 for sum-
parasite antigens (lactate dehydrogenase or histidine rich protein 2) can maries of doses) include the artemisinin derivatives—artesunate and
be useful in confirming species. They are relatively insensitive at detec-
tion of low parasitemias, but they can increase confidence in a result if a
microscopist is inexperienced. One of the most sensitive ways to distin-
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guish species and detect parasites uses PCR, but this is not in routine use. TABLE 78-2 Dosing Schemes for Parenteral Antimalarials Used for the
PCR-based tests that have been used in research and epidemiological Treatment of Severe Malaria
studies can also identify mutations in genes associated with drug resis- Artesunate 2.4 mg/kg IV or IM stat, at 12 h, 24 h, then daily. Artesunic acid (60 mg) is
tance (eg, increased pfmdr1 copy number predisposes to failure after dissolved in 0.6 mL of 5% sodium bicarbonate and injected IV as a bolus, or
mefloquine+artesunate combination treatment). 48 diluted to 5 mL with 5% dextrose for IM injection. 1 ampule = 60 mg.
CT or MRI imaging in adults may not reveal major shifts or focal Artemether 3.2 mg/kg IM stat followed by 1.6 mg/kg daily. Not for IV administration.
defects in adults with cerebral malaria, beyond a degree of reversible 1 ampule = 80 mg.
swelling. There are, however, several case reports of variable focal
changes, subarachnoid hemorrhage, and infarction in thalamic and Quinine 20 mg/kg of dihydrochloride salt by intravenous infusion over 4 h followed
cerebellar structures in some patients with fatal disease. In African by 10 mg/kg infused over 2-8 h every 8 h.
children, there may be more marked abnormalities, with focal features. Quinidine 10 mg base/kg infused at constant rate over 1-2 h followed by 0.02 mg/kg/min
Susceptibility-weighted imaging with MR has recently shown diffuse as constant infusion, with electrocardiographic monitoring.
petechial hemorrhages in a case of cerebral malaria that may represent Parenteral artesunate is the drug of choice for the treatment of severe malaria in both adults and
in vivo findings hitherto seen only at postmortem. 49 children, irrespective of the endemic setting.

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