Biomedical subjects

Tim Planche

Publications and source records attributed to Tim Planche.

4 recordsLinked to original sources

PubMed2005

Malaria and fluids--balancing acts.

Severe malaria has many manifestations, of which coma and lactic acidosis are the best independent predictors of a fatal outcome. Most deaths from malaria occur within the first 24 h of admission, despite appropriate antimalarial chemotherapy. Adjunctive therapy for severe malaria has been seen as a way to improve survival by 'buying time' until antimalarials can act. Several adjunctive therapies have undergone clinical trials in the past 25 years but all of these trials showed worsened outcome or no benefit to patients receiving adjuncts compared with those receiving placebo. Although metabolic acidosis occurs in both hypovolaemia and malaria, the contribution of the former to the pathophysiology of severe malaria is unclear. I suggest that lactic acidosis due to malaria can be explained primarily by factors that are independent of volume depletion. Lactic acidosis in malaria can be treated safely with dichloroacetate. This intervention could prove useful as an adjunctive therapy aimed at reducing mortality rates in severe malaria.

Acidosis, Lactic↗

PubMed2005

The relevance of malaria pathophysiology to strategies of clinical management.

PURPOSE OF REVIEW: Malaria claims 1-2 million lives a year, mostly children in sub-Saharan Africa. The majority of hospital deaths occur within 24 h of admission despite adequate treatment with antimalarial chemotherapy. Understanding the pathophysiological disturbances of malaria should allow the development of supportive therapy to "buy time" for antimalarial chemotherapy to clear the infection. It is sobering, however, that despite many trials over the last quarter of a century all large trials of adjunctive therapy so far have resulted in either increased morbidity or mortality, or both. RECENT FINDINGS: Severe malaria may be divided broadly into neurological and metabolic complications. We review recent findings about the pathophysiology of these complications and the implications for future adjunctive therapy of malaria, including the proposed importance of fluid volume depletion and sequestration of parasitized red cells in severe malaria. We also consider other anaemia, hyperparasitaemia and renal failure, which also require urgent treatment in severe malaria. SUMMARY: We review the important pathophysiological features of severe malaria and promising adjunctive therapies such as dichloroacetate that warrant further larger trials to determine whether they improve the so-far intractable death rate of severe malaria.

Acidosis, Lactic↗

PubMed2003

A prospective comparison of malaria with other severe diseases in African children: prognosis and optimization of management.

The burden of malaria in regions of high endemicity frequently overwhelms hospitals' capacity to provide effective care. A rapid, simple method of identifying children who are at highest risk is vital to reduce mortality among hospitalized children. Multiple regression analysis identified prognostic variables predicting mortality in severely ill children admitted to a Ghanaian teaching hospital. These variables were compared in children with and without malaria. A total of 1492 (90.2%) of 1654 severely ill children referred for assessment had evaluable outcomes. Low Blantyre coma score (BCS), high blood lactate level, and high body mass index were independent predictors of mortality among children with malaria (area under the receiver operating characteristic curve [AUC/ROC], 0.84). In children without malaria, BCS and lactate level also predicted mortality, but the addition of respiratory distress and hematocrit improved the model (AUC/ROC, 0.77). Predictors of mortality in children with malaria differ from those for other severe illnesses and reflect differences in underlying pathophysiological processes.

Child↗

PubMed2003

Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children.

The authors conducted a randomized, double-blind, placebo-controlled trial of intravenous dichloroacetate (DCA) for the purpose of treating lactic acidosis in 124 West African children with severe Plasmodium falciparum malaria. Lactic acidosis independently predicts mortality in severe malaria, and DCA stimulates the oxidative removal of lactate in vivo. A single infusion of 50 mg/kg DCA was well tolerated. When administered at the same time as a dose of intravenous quinine, DCA significantly increased the initial rate and magnitude of fall in blood lactate levels and did not interfere with the plasma kinetics of quinine. The authors developed a novel population pharmacokinetic-pharmacodynamic indirect-response model for DCA that incorporated characteristics associated with disease reversal. The model describes the complex relationships among antimalarial treatment procedures, plasma DCA concentrations, and the drug's lactate-lowering effect. DCA significantly reduces the concentration of blood lactate, an independent predictor of mortality in malaria. Its prospective evaluation in affecting mortality in this disorder appears warranted.

Acidosis, Lactic↗