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142 Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002
Critical determinants : after fluid replacement, an intravenous diuretic
hypovolaemia and hypervolaemia,
challenge may be given.
hyperparasitaemia, Diuretic challenge: The loop diuretic (furosemide
haemoconcentration, or bumetanide) 40 mg is given initially and then
hyperbilirubinaemia, in incremental dose of 100, 200, and 400 mg at
hyperpyrexia half hourly intervals. If there is still no urine flow,
dopamine 2.5 - 5 g/kg/min may be tried.
Lab. investigations and monitoring Dopamine challenge: The use of dopamine for
In addition to the peripheral blood smear the prevention and treatment of acute renal
examination to establish the diagnosis and failure is not yet established. Its use is based on
parasite clearance, the following tests are needed the understanding that selective renal
for the management of the cases. vasodilatation will occur when it is infused at
low dose. A recent article compared the effects
Blood : Urea, creatinine, bilirubin, SGPT, Na+, K+,
of dopamine and epinephrine in various doses
HCO3, pH
on renal haemodynamics and oxygen transport
Urine : Specific gravity, renal failure index, in patients with severe malaria and severe
fractional excretion of Na+ sepsis19. In a prospective, controlled, crossover
ECG, Chest X-Ray when indicated trial in an intensive care unit of an infectious
diseases hospital in Vietnam, dopamine at a
Treatment renal dose (2.5 g/kg/min) was associated
The treatment guidelines include institution of with a mean (95% confidence interval) fractional
appropriate antimalarials, at the earliest, and increase in the absolute renal blood flow index
maintenance of fluid and electrolytes: recording (RBFI) of 37% (13% to 61%) and in RBF as a
of intake and output chart, prevention of fluid fraction of cardiac output (RBF/CO) of 35%
overload, and secondary infection including (10% to 59%; p = .007 and p = .014,
pneumonia. Treatment of acquired infection respectively). At higher doses (10 g/kg/min),
should be done at the earliest. both RBF and RBF/CO were not significantly
different from baseline values and decreased
Fluid and electrolytes: a meticulous record of fluid
further as the dose was reduced again. Neither
requirement and urinary output is needed. It helps
epinephrine, nor dopamine significantly
to guide the administration of fluid, monitoring
affected creatinine clearance or urine output.
the improvement, and most of all preventing fluid
There was no evidence that either drug
overload. This simple, albeit most important factor,
produced any beneficial effect on renal oxygen
is left to the nursing staff or the ignorant attendants
metabolism or function. A review article
of the patient, thus getting a confused or
analysed the available data on the clinical use
inadequate information. To prevent fluid overload
of dopamine. When used to prevent acute renal
a CVP line can be established.
failure in high-risk treatments there is no
Fluid challenge: If any patient is dehydrated, he evidence of benefit of dopamine. In treatment
should be given a fluid challenge of upto 20 ml/ of acute renal failure, the quality of the data is
kg of 0.9 % saline infused over 60 minutes. In poor. Except one small randomised trial of
order to prevent fluid overload, auscultation of moderate acute renal failure in patients with
lungs and JVP measurements (and if possible, CVP malaria showing clinically significant benefits
measurements) should be performed after every by use of dopamine, rest of the data, in the
200 ml of fluid. The CVP should always be kept form of case series, showed either minor or no
between 0 and +5. If there is no urine output benefit of clinical significance. Hence, its use
Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002 143
cannot be advised until trials examining should be taken to monitor cardiotoxicity as
clinically important endpoints in large numbers artemisinins are also known to cause
of patients have been performed 20. prolongation of QT interval.
Similarly, with use of diuretics, urinary output
Drugs to be avoided in malaria patients as they
increases in 75% of the oliguric patients and only
may impair renal function:
in 5% anuric patients. However, there may not be
associated improvement in the renal parameters. NSAID should not be given as they may
Rather it may lead to delay in initiating dialysis. precipitate pre-renal azotaemia to ischaemic
So use of diuretic challenge should be considered ARF.
with utmost caution. ACE inhibitors and cyclo-oxigenase inhibitors.
If fluid replacement with or without the above Nephrotoxic drugs should be avoided where
procedures are ineffective, it is critical that further ARF is suspected or anticipated, such as,
fluid should be restricted to keep the CVP between cephalosporins, aminoglycosides.
0 to +5 of H 2O, and monitored for need of Assessment of renal function using
dialysis. measurement of urine volume should not be
Antimalarials: Quinine, chloroquin, and done in patients receiving diuretics.
artemisinin are the mainstay of therapy. Even
Exchange transfusion: it is of use in patients with
in the presence of pregnancy and acute renal
severe haemolysis and hyperbilirubinaemia.
failure, quinine should not be withheld for fear
However, in other conditions it is of doubtful value.
of toxicity. Quinine should be given in a dose
of 10 mg/kg 8 hourly during the first 48 hours Dialysis: Dialysis has improved the survival of the
of treatment. However, when it needs to be given cases when instituted early in the course.
beyond this period, the dose should be reduced
to 2/3rd or . The dose should not be reduced Indications for dialysis include:
in the initial 48 hours 1.
a) Clinical indications:
Cardiotoxicity of quinine must be of concern in 1. Uraemic symptoms
malaria patients with ARF after 3 days of quinine
2. Symptomatic volume overload, e.g.,
therapy, and ECG monitoring during quinine
pulmonary oedema, congestive heart
infusion is recommended in all severe malaria
failure
patients with persistent ARF. If there is any
arrhythmia, the infusion should be discontinued. 3. Pericardial rub
However, in some hospitals where ECG facilities b) Laboratory indications:
are not available, reduction in quinine dosage
1. Severe metabolic acidosis (HCO3 < 15
in persistent ARF patients should be considered
mEq/1)
after the third day of therapy. The appropriate
dosage reduction should be further studied. 2. Hyperkalaemia (K+ > 6.5 mEq/1)
Monitoring of free rather than total plasma Clearance of urea and other molecular waste
quinine concentrations is of value for predicting products is much faster with haemodialysis (HD) as
the cardiotoxicity in ARF patients. However, ECG compared to peritoneal dialysis (PD). However, PD
seems to be the practical procedure to monitor has certain advantages such as: PD does not need
cardiotoxicity. It may be possible to use the QTc a special set up, it can be started immediately, it
interval for this purpose18. Artemisinin drugs do may prove to be life saving. Thus, in the absence of
not require any dose modification in the facilities for HD whenever indicated, PD should be
presence of acute renal failure. However, care started as early as possible.
144 Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002
Table I : Dosage and use of antimalarial drugs in severe malaria.
Agent Route of Dosage Duration Dose modification Special
administration of therapy in renal failure precaution
Quinine Intravenous 10 mg salt/kg body 7 days No modification of IV Pulmonary
dihydrochloride infusion weight, diluted in 10 quinine for first 48 hrs oedema
ml/kg body weight of even if renal (or hepatic)
5% dextrose or insufficiency is present.* Hypotension
dextrose saline infused If the drug is continued
over a period of 4 hours intravenously beyond Hypoglycaemia
and repeated every 48 hours, the dose is
8 hrs. halved in presence Prolonged QT
of renal failure.* interval
Artesunate Intravenous 2.4 mg/kg (loading 6 days No dose modification Safe drug.
dose) IV, followed by It can be used in
1.2 mg/kg at 12 hours, patients with fluid
then 1.2 mg/kg daily overload,
for 6 days, if the patient hypotension, or
is able to swallow, the shock.
daily dose can be given Does not cause
orally. hypoglycaemia
Artemether Intramuscular 3.2 mg/kg body wt stat, 5 days No dose modification
followed by 1.6 mg/kg Artemisinin drugs
daily are not yet
Arteether Intramuscular 2.4 mg/kg or 150 mg 3 days No dose modification approved (by Govt
of India) for use in
pregnant women
and children
Chloroquine** Intramuscular 10 mg base/kg bwt on 3 days No dose modification Daily dose must
day 1, day 2, and not exceed 15
5mg/kg bwt on day 3 mg/kg bwt. Total
dose not to exceed
25 mg/kg bwt
Mefloquin Oral No role in patients of severe malaria as parenteral preparation is not available.
Halofantrine
* If there is no clinical improvement after 48 hours of parenteral therapy, the maintenance dose of parenteral quinine should be reduced as follows (even without
any renal or hepatic involvement):
First 48 hours (two days) of treatment : 30 mg salt/kg of body weight per 24 hours.
Subsequently : 15-21 mg salt/kg of body weight per 24 hours.
** Widespread chloroquine resistance is reported from South-East Asia. It is therefore recommended to treat all patients of severe malaria with quinine or
appropriate artemisinin derivatives.
Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002 145
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