Fluid Resuscitation of Adults With Severe Falciparum Malaria

Hanson, Josh; Lam, Sophia W. K.; Mohanty, Sanjib; Alam, Shamshul; Pattnaik, Rajyabardhan; Mahanta, Kishore C; Hasan, Mohammad Rashedul; Charunwatthana, Prakaykaew; Mishra, Saroj K.; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

doi:10.1097/ccm.0b013e31827466d2

Cited by 78 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the relative contributions of different disease mechanisms to death from severe malaria are still debated [31, 32]. An important underlying pathophysiological mechanism involved in acidosis and coma, and to a lesser extent in renal failure, is microvascular sequestration of parasitized red blood cells causing a compromised microcirculation falciparum malaria [14, 31, 33]. If microcirculatory obstruction is one of the pivotal mechanisms, improvement of plasma lactate concentrations through improvement of the microcirculation will be associated with an improvement in mortality.…”

Section: Discussionmentioning

confidence: 99%

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundClinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria.MethodsThree datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures.ResultsImprovements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery.ConclusionsThe relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.

show abstract

Section: Discussionmentioning

confidence: 99%

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…However in severe malaria, even if rehydration improves systemic haemodynamics, there may be limited improvement in the microvascular obstruction, which makes a greater relative contribution to tissue hypoperfusion [1,8]. Adults with severe malaria also have a generalized increase in vascular permeability which is particularly important in the lungs where pulmonary oedema can occur rapidly, unpredictably, and is frequently fatal [8-10]. The hazards of fluid loading have also been demonstrated recently in African children with severe malaria, with mortality substantially higher in the patients receiving liberal resuscitation than in those receiving standard maintenance therapy [11].…”

Section: Introductionmentioning

confidence: 99%

The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study

Hanson

Lam

Alam

et al. 2013

Malar J

Self Cite

View full text Add to dashboard Cite

BackgroundAdults with severe malaria frequently require intravenous fluid therapy to restore their circulating volume. However, fluid must be delivered judiciously as both under- and over-hydration increase the risk of complications and, potentially, death. As most patients will be cared for in a resource-poor setting, management guidelines necessarily recommend that physical examination should guide fluid resuscitation. However, the reliability of this strategy is uncertain.MethodsTo determine the ability of physical examination to identify hypovolaemia, volume responsiveness, and pulmonary oedema, clinical signs and invasive measures of volume status were collected independently during an observational study of 28 adults with severe malaria.ResultsThe physical examination defined volume status poorly. Jugular venous pressure (JVP) did not correlate with intravascular volume as determined by global end diastolic volume index (GEDVI; rs = 0.07, p = 0.19), neither did dry mucous membranes (p = 0.85), or dry axillae (p = 0.09). GEDVI was actually higher in patients with decreased tissue turgor (p < 0.001). Poor capillary return correlated with GEDVI, but was present infrequently (7% of observations) and, therefore, insensitive. Mean arterial pressure (MAP) correlated with GEDVI (rs = 0.16, p = 0.002), but even before resuscitation patients with a low GEDVI had a preserved MAP. Anuria on admission was unrelated to GEDVI and although liberal fluid resuscitation led to a median hourly urine output of 100 ml in 19 patients who were not anuric on admission, four (21%) developed clinical pulmonary oedema subsequently. MAP was unrelated to volume responsiveness (p = 0.71), while a low JVP, dry mucous membranes, dry axillae, increased tissue turgor, prolonged capillary refill, and tachycardia all had a positive predictive value for volume responsiveness of ≤50%. Extravascular lung water ≥11 ml/kg indicating pulmonary oedema was present on 99 of the 353 times that it was assessed during the study, but was identified on less than half these occasions by tachypnoea, chest auscultation, or an elevated JVP. A clear chest on auscultation and a respiratory rate <30 breaths/minute could exclude pulmonary oedema on 82% and 72% of occasions respectively.ConclusionsFindings on physical examination correlate poorly with true volume status in adults with severe malaria and must be used with caution to guide fluid therapy.Trial registrationClinicaltrials.gov identifier: NCT00692627

show abstract

“…Taking into account that in these patients pulmonary edema secondary to increased pulmonary vascular permeability has been shown to be frequent, unpredictable and exacerbated by fluid loading, a conservative strategy of fluid management was followed in all three patients before and after ECMO initiation [20]. Moreover, a liberal strategy of fluid management in acute lung injury has been previously associated with prolonged duration of mechanical ventilation and intensive care [21].…”

Section: Discussionmentioning

confidence: 99%

Extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome in severe malaria

Alves

Chen

Patel

et al. 2013

Malar J

View full text Add to dashboard Cite

BackgroundSevere malaria may be complicated by the acute respiratory distress syndrome (ARDS), which is associated with a high mortality. In the present report, a series of three cases of imported malaria complicated by refractory severe ARDS supported with extracorporeal membrane oxygenation (ECMO) is presented.MethodsOne female and two male adult patients (ages 39 to 53) were included. Two patients had Plasmodium falciparum infection and one patient had Plasmodium vivax and Plasmodium ovale co-infection. Anti-malarial therapy consisted in intravenous quinine (in two patients) and intravenous quinidine (in one patient), plus clindamycin or doxycycline.ResultsDespite lung protective ventilation, a conservative strategy of fluid management, corticosteroids (two patients), prone position (two patients) and inhaled nitric oxide (one patient), refractory severe ARDS supervened (PaO2 to FiO2 ratio 68) and venovenous ECMO was then initiated. In one patient, a bicaval dual-lumen cannula was inserted; in the two other patients, a two-site configuration was used. Two patients survived to hospital-discharge (duration of ECMO support: 8.5 days) and one patient died from nosocomial sepsis and multi-organ failure after 40 days of ECMO support.ConclusionsECMO support allowed adequate oxygenation and correction of hypercapnia under lung protective ventilation, therefore reducing ventilator-induced lung injury. ECMO referral should be considered early in malaria complicated by severe ARDS refractory to conventional treatment.

show abstract

Fluid Resuscitation of Adults With Severe Falciparum Malaria

Cited by 78 publications

References 33 publications

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study

Extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome in severe malaria

Contact Info

Product

Resources

About