Diarrhea is one of the leading causes of under-five childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. The coexistence of sepsis and hypovolemic shock in children with severe acute malnutrition (SAM) having diarrhea is common. At Dhaka hospital of icddr,b, the death rate is as high as 40% and 69% in children with severe sepsis and septic shock respectively with co-morbidities such as severe malnutrition. The conventional management of SAM children with features of severe sepsis recommended by WHO includes administration of boluses of isotonic saline followed by blood transfusion in unresponsive cases with septic shock; whereas the Surviving Sepsis Campaign (SSC) guideline recommends vasoactive support. To date, no study has evaluated systematically the effects of inotrope(s) and vasopressor or blood transfusion in children with dehydrating diarrhea (for example, in cholera) and SAM having shock and unresponsive to WHO standard fluid therapy. This randomized trial will generate evidence whether inotrope and vasopressor or blood transfusion should be selected for severely malnourished children having hypotensive shock and who failed to respond to WHO standard fluid bolus.
Background: 1. Burden: Burden: Diarrhea is one of the leading causes of under-five childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. Co-morbidity of severe acute malnutrition (SAM) and shock in children with diarrhea is associated with increased mortality. Nearly half of the patients admitted to the Intensive Care Unit (ICU) of Dhaka Hospital of icddr,b present with sepsis. Data demonstrates that about 43% of children progressed from severe sepsis to septic shock despite receiving recommended treatment. The death rate was found to be as high as 40% and 69% in children with severe sepsis and septic shock respectively with co-morbidities such as severe malnutrition. 2. Knowledge gap: The conventional management of SAM children with features of severe sepsis recommended by WHO include administration of boluses of isotonic saline followed by blood transfusion in unresponsive cases with septic shock. However, a recent African study reported significantly higher mortality among children with features of severe sepsis when they were treated with boluses. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhea (for example, in cholera) and SAM having shock and unresponsive to WHO standard fluid therapy. 3. Relevance: If this randomized trial signifies survival benefit from a blood transfusion, inotrope or vasopressor in the management of fluid refractory shock in children with severe acute malnutrition and cholera or other dehydrating diarrheas, then this approach would be a good candidate for implementation in the management of such children especially in developing countries Hypothesis: We hypothesize that the death rates will be significantly lower in children with SAM or severe underweight, dehydrating diarrhea and fluid refractory shock who will be treated with blood transfusion and adrenaline compared to blood transfusion and dopamine, after treatment failure with WHO standard bolus intravenous fluid therapy. Objectives: To reduce mortality of the SAM or severely underweight children presenting with diarrhea and fluid refractory shock who will receive WHO standard fluid therapy followed by blood transfusion with either dopamine or adrenaline. Methods: This will be a randomized, two-arm, controlled, non-masked clinical trial in children 1- 59 months old with SAM or severely underweight and fluid refractory shock. It will compare the efficacy of WHO-recommended fluid resuscitation followed by blood transfusion and dopamine versus blood transfusion and adrenaline. Children in both groups will also receive inj hydrocortisone. After parental written informed consent, children, in addition to usual supportive care, will be allocated to the study interventions following randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
135
Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also receive dopamine, 8 microgram/kg.min (increasing the dose after 15 minutes to 12 microgram/kg/min to a maximum of 15 microgram/kg/min)
Children in this group will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. They will also receive adrenaline, 0.1 microgram/kg/min (increasing the dose after 15 minutes to 0.2 microgram/kg.min to a maximum of 0.3 microgram/kg.min)
Icddr,B
Dhaka, Bangladesh
RECRUITINGCase fatality rate
Number of mortalities among acutely malnourished children presenting with diarrhea and fluid refractory shock who would receive WHO standard fluid therapy followed by blood transfusion with either dopamine or adrenaline.
Time frame: 28 days (± 3 days)
Treatment failure rates
Number of children where we failed to achieve the goal of resuscitation after starting any one of the interventions
Time frame: Through study completion, an average of 7 days
Need for mechanical ventilation
Number of children who would require mechanical ventilation
Time frame: Through study completion, an average of 7 days
Heart failure
Number of children who developed heart failure. Heart failure will be assessed on the basis of - age-specific tachypnea, tachycardia, enlarged tender liver, pedal edema, basal crackles and/or gallop and response to furosemide (combination of findings).
Time frame: Through study completion, an average of 7 days
Length of ICU stay
Time a child stays in ICU
Time frame: Through study completion, an average of 7 days
Time-to-achieve recovery
Required times (minutes) for resuscitation of a child after randomization to a specific arms
Time frame: 3-4 hours
Left ventricular function of the study participants
Evaluation of left ventricular function (hyperdynamic or normal) by cardiac USG at enrollment, at time of heart failure (if any)
Time frame: Through study completion, an average of 7 days
Right ventricular function of the study participants
Evaluation of right ventricular function (hyperdynamic or normal) by cardiac ultrasound at enrollment, at time of heart failure (if any)
Time frame: Through study completion, an average of 7 days
Inferior vena cava collapsibility of the study participants
Evaluation of Inferior vena cava collapsibility by cardiac ultrasound at enrollment, at time of heart failure (if any)
Time frame: Through study completion, an average of 7 days
Length of hospital stay
Time a child stays in the hospital
Time frame: variable (days to months)
Mean arterial pressure (MAP) stabilization at 48 hours
Number of children whose MAP was stabilized at 48 hours
Time frame: 48 hours from the point of inclusion in the study
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