Evidence- Based Medicine Fluid Therapy Ndidi Musa M.D. Assosciate Professor of Pediatrics Medical College of Wisconsin/ Children s Hospital of Wisconsin
Disclosures A. I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. B. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.
Improved Survival and Quality of Life In The US 1950 s to 2008 Leukemia Pediatric Shock HIV Congenital Heart Disease 1950 1960 1970 1980 1990 2000 2010
What About Low Resource Settings? FEAST Trial the mortality was lower than expected because there was a high adherence to the protocol ETAT plus applied in Kenya has reduced their 48 hour in hospital mortality ETAT in Malawi decreased their hospital mortality
Goal Directed Therapies in Pediatrics Cardiac Arrest Resuscitation Guidelines Post-Resuscitation Brain support Hypothermia Mechanical Ventilation Barotrauma Weaning Extubation Sepsis Volume Endocrine Oxygen Saturation Monitoring Brain Trauma ICP control Hypothermia
Goal Directed Therapies: Is is applicable to children?
Capillary Refill Normal capillary refill is <2 seconds in a normal temperature environment
Limitations Of Physical Exam As A Shane Tibby s study Means of Monitoring Trevor Duke s comment about FEAST Trial itself
Perfusion Assessment In Infants Parameters HR BP clinical exam skin perfusion pulse amplitude organ function mental status urine output metabolic acidosis cardiac output Problems/assumptions sympathetic tone CO*SVR assumptions autoregulation normothermia late indicators multifactorial not quantitative other causes assumes VO 2 ; technically difficult
Golden Hour Compensated Shock Possibly Hours Hypotensive Shock Potentially minutes Cardiac Arrest
Golden Hour of Shock Management Recognition, oxygen, access 5 Rapid fluid boluses/ no bolus, glucose, antibiotics Additional IV/intraosseous access First Hour 15 Secure airway, central access Begin to titrate vasoactive agent Within first hour: Hydrocortisone if at risk for absolute or relative adrenal insufficiency Titrate fluid resuscitation, inotropes with serial exams 11
Early Resuscitation Hospital mortality lower in EGDT 28 and 60 day mortality also significantly lower in EGDT N Engl J Med 345:1368, November 8, 2001
Controversy of Fluid Resuscitation in Resource Limited Settings
The Fluid Expansion as Supportive Therapy (FEAST) study
Hypothesis NO FLUID Fluid resuscitation in children with severe febrile illness and impaired perfusion and tachycardia in resource-limited settings increases 48-hour mortality Samer Abu Sultaneh
Methods-Design Two-stratum, multicenter, open, randomized, controlled study in six clinical centers: Kenya (one center) Tanzania (one center) Uganda (four centers Stratum A: No severe hypotension Stratum B: Severe hypotension; systolic BP: a) <50 mm Hg in children <12 months of age b) <60 mm Hg in children 1-5 years of age c) <70 mm Hg in children > 5 years of age Samer Abu Sultaneh
Methods-Treatment Protocol Stratum A @ 1hr if impaired perfusion persisted +20 40 ml/kg NS +20 40 ml/kg 5% Alb No bolus If severe hypotension developed, the child was treated with 40-ml boluses of study fluid per kilogram (saline in the case of the control group). Samer Abu Sultaneh
Methods-Treatment Protocol Stratum B @ 1hr if impaired perfusion persisted +20 40 60 ml/kg NS +20 40 60 ml/kg 5% Alb If severe hypotension developed, the child was treated with 40-ml boluses of study fluid per kilogram.
Inclusion And Exclusion Criteria 60 days and 12 years of age Severe febrile illness complicated by impaired consciousness (prostration or coma), respiratory distress (increased work of breathing), or both, and with impaired perfusion Severe malnutrition Gastroenteritis Noninfectious causes of shock (e.g., trauma, surgery,or burns) Conditions for which volume expansion is contraindicated. 20
End Points Primary: Mortality at 48 hours after randomization Secondary: Mortality at 4 weeks Neurologic sequelae at 4 and 24 weeks Episodes of hypotensive shock within 48 hours Adverse events potentially related to fluid resuscitation: Pulmonary edema Increased intracranial pressure Severe allergic reaction Samer Abu Sultaneh
Study Procedures Training in triage and emergency pediatric life support given to participating providers throughout the trial to optimize case recognition, supportive management, and adherence to the protocol. Maintenance fluids (2.5 to 4.0 ml/kg/hr) Antibiotics, antimalarials, antipyretics Treatment for hypoglycemia (if <45 mg/dl) Whole blood transfusion (20 ml/kg over 4hrs if Hb <5 g/dl) Samer Abu Sultaneh
Strengths Large number of children enrolled Multinational Small loss to follow-up Concealment of treatment assignments High rate of adherence to the assigned treatment. Important survival gains, across all the groups, may have resulted from training and implementation of triage, basic life support measures, and regular observation
Limitations Setting No intensive care facilities? Management in pre hospital settings? Delay in seeking medical care and recognition Gastroenteritis, severe malnutrition, or noninfectious causes of shock were excluded. Few children were recruited to stratum B (no control group)
What the African fluid-bolus trial means Characteristics of population suggest many conditions that are likely to be adversely affected by over-hydration. 32% severe anemia (Hb<5g/dL)- dilute Hb tissue O2 delivery or cardiac failure. 25% hypoxemia-pneumonia 3% LP Bacterial meningitis Pneumonia and meningitis circulating ADH Trevor Duke :Lancet 06/11 26
Conclusion Fluid boluses are dangerous in children with malaria and other febrile illnes where ADH secretion is likely high Caution in transfer of fluid resuscitation guidelines from high to low resource settings. This trial does not inform about management of shock from dengue fever, hypovolemic shock from diarrhea and vomiting and bacterial septic shock. Trevor Duke :Lancet 06/11 27