Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria*

Abstract

Objective: A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution (HAS) compared to other resuscitation fluids.HAS is expensive and not readily available in Africa. We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids, Dextran 70 and hydroxyethyl starch to inform future trial design.Design: An open-label randomised controlled, phase II safety and efficacy trial. 23/37 (62%) and 25/39 (64%) respectively (p=0.99). Acidosis resolution and respiratory distress was marginally superior in HES group: 3/39 (8%) remained acidotic at 8 hours versus 10/37 (27%) in Dextran arm (p=0.05). There were 4 deaths (5%), two per arm; including 3 deaths in the coma subgroup (3/39, 8%). No other new adverse event was reported. Conclusions:Correction of shock by volume expansion with either Dextran or HES in children with severe malaria acidosis is safe with low mortality, including the highest risk cases admitted in coma. Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria.3

Fluid Bolus Therapy-Based Resuscitation for Severe Sepsis in Hospitalized Children

“…Yet the scarce data from a broad hospitalized population with sepsis from resourcerich settings require attention-particularly in light of the FEAST trial which challenged current practice and triggered discussion and debate (28)(29)(30)(31)(32)(33)(34). Finally, our findings are coherent with a recent systematic review of fluid resuscitation in adults (34).…”

“…The majority of trials of FBT-based resuscitation in children with septic shock have occurred outside of Europe or North America in the context of dengue shock syndrome (24)(25)(26), malaria (27)(28)(29), or malnutrition (30), thus limiting their broader applicability to developed countries. We excluded these studies based on their focused populations and lack of advanced therapeutic interventions such as mechanical ventilation and vasoactive support.…”

Management of severe paediatric malaria in resource-limited settings

“…Fatal neurological events more common in gelatin arm.2. Gelofusin (N = 44)Akech et al [152]KenyaChildren >6 monthsSevere malaria (Hb > 5 g/dl) plus deep breathing and base deficit >8 N = 79RCT 20 ml/kg over the first hour, repeat x1 if shock persists1 0 resolution of shock over 8 hours.1 0 no difference in 8 hour shock resolution (D70: 23/37 (62%) vs HES: 25/39 (64%), respectively ( P  = .99).Fluid boluses with either Dextran or 6% HES lead shock and acidosis resolution without eividence of adverse outcome.Specifically, there was no evidence of a renal impairment with HES over 24 hrs of observation, its use was associated with falling creatinine levels and good urine output1. Dextran 70 (N = 39)2 0 resolution of acidosis, in-hospital mortality, SAEs (allergic reaction, pulmonary oedema, and neurologic sequelae)2 0 Acidosis and respiratory distress resolved better in HES: 3/39 (8%) remained acidotic at 8 hours vs D70 10/37 (27%) ( P  = .05).…”

“…In total, five Phase II trials were conducted in Kenyan children with severe malaria comparing different fluid types on physiological endpoints, including correction of metabolic acidosis (base excess) and haemodynamic parameters as well as mortality and neurological sequelae in survivors. The results of these trials are individually summarised in Table 2 [60,149-152] but have been formally collated (four of five) in a meta-analysis examining types of fluid resuscitation therapy published in 2010 [153]. This review compiled data from all published paediatric clinical trials of fluid resuscitation.…”

“…A further trial comparing Dextran 70 (D70) (n = 39) and 6% hydroxyethyl starch (HES) (n = 40) found no difference in the primary outcome (shock resolution at eight hours) (D70: 23/37 (62%) versus HES: 25/39 (64%)), although resolution of acidosis was better in the HES arm. Overall, case fatality (four in each arm, 5%) was similar [152]. …”