Trial results challenge the use of Fluid Resuscitation for African Children

The surprise findings of a landmark clinical trial show that a long-standing treatment, called Fluid Resuscitation, does not confer the expected benefits when given to African children suffering from severe infections including malaria and septicemia (bloodstream infection).

The UK and African scientists, who conducted the trial, are therefore urging the World Health Organization (WHO) to change the pediatric emergency guidelines for Africa and other regions where there is limited access to intensive care units. They also say that further research is needed to evaluate Fluid Resuscitation therapy in wealthy countries where it has been used for more than two decades as part of standard emergency practice.

The trial known as FEAST (Fluid Expansion as Supportive Therapy) set out to evaluate the impact of Fluid resuscitation, which consists of giving children large volumes or "boluses" of intravenous fluids through a drip to try to reverse the deadly effects of shock. It is estimated that one in ten children arriving in hospital in sub-Saharan Africa are in shock, a condition where the body restricts blood flow to vital organs in an effort to stave off death. A  Child in shock becomes pale, cold to the touch and has a weak pulse which often results in death within hours of admission and before effective medicines are administered.

The FEAST Trial studied 3170 critically ill children at six hospitals in Uganda, Kenya and Tanzania who were randomly divided into three equally sized groups. Two groups were given emergency doses of 20-40 mls per kilogram of bodyweight in the first hour of arriving in hospital; one group was given albumin, the other saline whereas the third group  did not receive a bolus but received fluids slowly, to replace the amounts needed by a sick child who cannot drink. After the first hour, children in all groups were then given replacement fluids slowly.                                

The trial results, published today in the New England Journal of Medicine, found no difference between children receiving Albumin and Saline. More surprisingly, the study found that the children given fluids slowly did better: 92.7% survived at 48 hours compared to the 89.4% of children who received boluses.  This means that the addition of Fluid Resuscitation to other emergency management led to an extra three child deaths out of every hundred treated. This is a statistically significant difference especially since Emergency Fluid Resuscitation has been the standard practice for children in shock for the last two decades in the United States, Europe and Australasia. 

"The results surprised me," said Professor Sarah Kiguli, Chief Principal Investigator in Uganda. "This was because I had seen some children getting better after being given large volumes of fluids. But more important the results went against the recommendations of the World Health Organization (WHO) and the normal practice in wealthy countries, and this surprised me greatly."

Prof Kathryn Maitland, the Chief Investigator for FEAST, Imperial College London and KEMRI-Wellcome Trust Programme, Kilifi said: “The FEAST trial was set up in Africa with the hope that Fluid Resuscitation would help prevent deaths in children with malaria and septicemia. Large-scale clinical trials of this nature carried out to a high standard are crucial to find new ways to improve the survival of these children.  Disappointingly, across all groups of children in the trial we found that Fluid Resuscitation had no benefit- our only conclusion is that boluses are harmful for African children when used for shock in the illnesses we studied."

The researchers however stress the need to continue to use Fluid Resuscitation to treat diarrhea and other conditions like burns and trauma, where children lose fluids. For these conditions, where Fluid Resuscitation will continue to be a vital lifesaving treatment, current WHO recommendations should stay the same. Children with acute malnutrition were also excluded from the trial, because fluids are not recommended in their treatment.

"Finding this out before we started to encourage the use of fluid resuscitation across Africa was incredibly important.  It will save many lives in future.  However it will not mean big changes in most African hospitals where fluid resuscitation has until now not normally been used for the conditions covered by FEAST," said Dr Sam Akech, FEAST Principal Investigator at KEMRI-Wellcome trust Programme, Kilifi, Kenya.

Dr Elizabeth Juma of the Division of Malaria Control (DOMC) in Kenya added that “Bolus fluid resuscitation has not been introduced into routine practice for in the management of severely ill children in Kenya and thus, the findings of this study mean that we should revisit the issue and discuss available evidence conclusively before making a recommendation.  Fluid therapy is important for children severely ill with infections and it is important to make a distinction between maintenance fluid and bolus fluid resuscitation. We do not want health workers to stop giving maintenance fluids and starve severely ill children of fluid. “

The FEAST Study also has some significant implications for pediatric emergency care guidelines in developed Western Countries. Professor Diana Gibb from the Medical Research Council Clinical Trials Unit said: "The treatment may not carry the same risks in wealthy countries because children are healthier, and in particular have few problems of underlying long-standing malnutrition or anemia. However the clear findings from the FEAST trial do question the use of boluses for severe infections even in wealthy countries and more research is needed’. 

"At present large numbers of sick children in wealthy countries are routinely given fluid boluses in emergency units and even ambulances before arriving in hospital. In the light of the results from FEAST"   said Dr Jennifer Evans, Consultant Paediatrician at the University Hospital of Wales in Cardiff, ‘it is imperative that we review our current practice and as clinical researchers decide how to evaluate its’ safety and ask whether it is indeed the best thing to do for our sick children."

This is the first time anywhere in the world that the emergency use of Fluid Resuscitation treatment has been compared for safety and effectiveness against control (i.e. a no bolus group) in a large clinical trial. The researchers are very confident that the results are correct and independent reviewers have praised the conduct of the study. The trial scored 99.5% on its adherence to the trial plan, or "protocol" and a similar amount for retention of patients, two key indicators of a good trial.