About the FEAST (Fluid Expansion as Supportive Therapy) Trial
The FEAST trial was a large randomised controlled trial examining the effectiveness of fluid resuscitation of children with severe infections in Africa. This treatment involves giving seriously ill children large volumes or ‘boluses’ of intravenous fluids quickly through a drip in their first hour at hospital to try to reverse the deadly effects of shock. The trial was carried out in six hospitals in Africa (in Kenya, Uganda and Tanzania). More than 3,000 children took part.
The trial looked at whether rapid fluid infusion (fluid resuscitation or expansion) at admission to hospital improves survival compared to standard management alone.
Why is this trial important?
In sub-Saharan Africa between 15-30% of children admitted to hospital because of severe infections die. Over a million children die of severe infection in hospital each year in sub-Saharan Africa. Currently, antimalarial and antimicrobial drugs are the mainstay of treatment, however most deaths occur early, before definitive treatments have time to act. In this situation doctors have to rely upon supportive therapies to treat complications to try to improve outcome. But there have not been enough clinical studies to determine which are the best life-saving treatments.
Rapid fluid infusion to correct fluid deficits is a standard supportive treatment. It is practised routinely in developed countries for the emergency management of children with severe illness. But there have been no large trials anywhere to evaluate the safety and effectiveness of this treatment. There were considerable doubts over whether such an approach would work in sub-Saharan Africa, where intensive care facilities to deal with any side-effects of the treatment do not exist.
What did the trial show?
The trial found that fluid resuscitation as an emergency treatment for African children suffering with shock from severe infections does not save lives. Giving children fluids slowly to maintain normal levels, rather than rapid fluid resuscitation, is safer and more effective in aiding recovery. 92.7% of children given fluids more slowly survived the first 48 hours in hospital, compared to 89.4% of those given boluses.
While fluid resuscitation did not help children in the trial, all those taking part were less likely to die than is usual in hospitals in sub-Saharan Africa. This may be because of the training that hospital staff were given on emergency triage and treatment of children. This meant staff could identify the sickest children and make sure they get treated first.
What do these results mean?
These findings challenge current WHO guidelines on how best to provide fluids to children in Africa with fever and shock caused by malaria, sepsis and other infections. Further research is needed in countries where fluid resuscitation is already standard practice, although the results in Africa may not be directly applicable to wealthy countries. One reason for this is that sophisticated life support equipment is available in wealthier countries and is available along with fluid resuscitation as part of a ‘package of care’.
It is important that fluid resuscitation is still used to treat diarrhoea and other conditions like burns and trauma, where children lose fluids. For these conditions, where fluid resuscitation will continue to be a vital life-saving treatment. Children with severe malnutrition were not included in the trial as fluids are not recommended as part of their treatment.
The results of the FEAST trial were published in the New England Journal of Medicine on 30th June 2011. They showed that giving fluids rapidly through a drip into a vein (fluid resuscitation) as an emergency treatment for African children suffering with shock from severe infections does not save lives. The trial showed that giving children fluids slowly to replace the needs of a sick child who cannot drink, rather than rapid fluid resuscitation, is safer and more effective in aiding recovery. These findings challenge current WHO guidelines on how best to provide fluids to children in Africa with fever and shock caused by malaria, sepsis and other infections.
The FEAST trial involved over 3000 children in six hospitals across Tanzania, Uganda & Kenya. It examined the effectiveness of a long-standing treatment used across the world called fluid resuscitation. This treatment involves giving seriously ill children large volumes or ‘boluses’ of intravenous fluids quickly through a drip in their first hour at hospital to try to reverse the deadly effects of shock.
The children on the trial were divided randomly into three equally sized groups. Two groups were given emergency boluses of either albumin or saline in the first hour of arriving in hospital. After the first hour, the children were then given fluids slowly, to replace the amounts a sick child should drink. The third group were given fluids slowly but no additional bolus treatment.
The trial results showed that children given fluids more slowly did better, with a 48 hour survival rate of 92.7%, compared with 89.4% of those children given boluses. Compared with giving children fluids slowly, fluid resuscitation caused three additional children to die out of every hundred treated.
The trial was stopped early because the independent committee overseeing safety saw that giving boluses was unsafe. However, all children who took part in FEAST had a better chance of survival than is normally the case in Africa, in part due to extra training given to hospital staff to give emergency treatments, such as oxygen and providing medicines for malaria and other infections.
Prof Kathryn Maitland, the Chief Investigator for FEAST, Imperial College London and KEMRI-Wellcome Trust Programme said:
“This is the first time anywhere in the world that fluid resuscitation has been evaluated for safety and effectiveness in such a large trial, even though it has been standard treatment for the last two decades in the United States, Europe and Australasia. The FEAST trial was set up with the hope that fluid resuscitation would help the many African children with malaria and septicemia. Around one in ten children in Africa admitted to hospital with these deadly infections are in a state of shock. Although there are effective medicines for these illnesses, too often children arrive in hospital already very sick, with many children dying within hours of admission. Large-scale clinical trials of this nature carried out to the highest levels are crucial if we are to find new ways to keep children alive when they come into hospital. Disappointingly, across all parts of the trial we found that fluid resuscitation had no benefit- our only conclusion is that boluses are harmful when used for shock in the illnesses we studied.”
Professor Sarah Kiguli, Chief Principal Investigator in Uganda said:
“The results have surprised me, particularly as I had seen some children getting better after being given large volumes of fluids. But more importantly the results went against the recommendations of the WHO and the normal practice in wealthy countries, and this surprised me greatly. Finding this out before we started to encourage the use of fluid resuscitation children with severe infections and shock across Africa was incredibly important. It will save many lives in future.” The study authors agree that further research is needed in countries where fluid resuscitation is already standard practice, although the results in Africa may not be directly applicable to wealthy countries. One reason for this is that sophisticated life support equipment is available in wealthier countries and is available along with fluid resuscitation as part of a ‘package of care’.
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 anaemia. 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.”
The researchers have stressed the need to continue to use fluid resuscitation to treat diarrhoea and other conditions like burns and trauma, where children lose fluids. For these conditions, where fluid resuscitation will continue to be a vital life-saving treatment, they advise that current WHO recommendations should stay the same. Children with severe malnutrition were not included in the trial as fluids are not recommended as part of their treatment.
Reaction to the FEAST trial results
The FEAST trial results have stimulated much interest and discussion. Links to some of the news coverage and comments on the trial can be found below.
The East African: WHO rules may be killing, not saving children in Africa
Wellcome Trust: African trial questions emergency treatment of children in shock
Malaria Consortium: Trial Results Show Error in Routine Practice for Critically Ill Children
Imperial college: African trial questions emergency treatment of children in shock
Global Health trials: A gold standard example of running a trial in Africa
Twitter Journal Club discussion of the results: