Management of Shock in Children With SAM and Diarrhea
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Detailed Description
Background:
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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.
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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.
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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, dehydrating diarrhea and fluid refractory shock who will be treated with dopamine or adrenaline compared to blood transfusion, after treatment failure with WHO standard bolus intravenous fluid therapy.
Objectives: To reduce mortality of the SAM children presenting with diarrhea and fluid refractory shock who will receive WHO standard fluid therapy followed by dopamine or adrenaline, compared to those receiving blood transfusion after WHO standard fluid therapy.
Methods: This will be a randomized, three-arm, controlled, non-masked clinical trial in children 1- 59 months old with SAM and fluid refractory shock. It will compare the efficacy of WHO-recommended fluid resuscitation followed by dopamine or adrenaline administration versus WHO recommended fluid resuscitation followed by blood transfusion. After parental written informed consent, children, in addition to usual supportive care, will be allocated to the study interventions following randomization.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dopamine arm Children in the dopamine arm (Treatment plan A) will 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) |
Drug: Dopamine
Children will 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)
|
| Experimental: Adrenaline arm Children in the adrenaline arm (Treatment plan B) will 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) |
Drug: adrenaline
Children will 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)
Other Names:
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| Active Comparator: Blood transfusion arm Children in the blood transfusion arm (Treatment plan C) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. While the blood transfusion is being arranged, IV fluid would be given @ of 3 ml per kg per hour |
Drug: Blood Transfusion
Children will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. While the blood transfusion is being arranged, IV fluid would be given @ of 3 ml per kg per hour
Other Names:
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Outcome Measures
Primary Outcome Measures
- Case fatality rate [28 days]
Number of mortality among SAM children presenting with diarrhea and fluid refractory shock who would receive WHO standard fluid therapy followed by dopamine or adrenaline, compared to those receiving blood transfusion after WHO standard fluid therapy
Secondary Outcome Measures
- Treatment failure rates [Through study completion, an average of 7 days]
Number of children where we failed to achieve the goal of resuscitation after starting any one of the interventions
- Need for mechanical ventilation [Through study completion, an average of 7 days]
Number of children who would require mechanical ventilation
- Heart failure [Through study completion, an average of 7 days]
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).
- Length of ICU stay [Through study completion, an average of 7 days]
Time a child stays in ICU
- Time-to-achieve recovery [3-4 hours]
Required times (minutes) for resuscitation of a child after randomization to a specific arms
- Left ventricular function of the study participants [Through study completion, an average of 7 days]
Evaluation of left ventricular function (hyperdynamic or normal) by cardiac USG at enrollment, at time of heart failure (if any)
- Right ventricular function of the study participants [Through study completion, an average of 7 days]
Evaluation of right ventricular function (hyperdynamic or normal) by cardiac ultrasound at enrollment, at time of heart failure (if any)
- Inferior vena cava collapsibility of the study participants [Through study completion, an average of 7 days]
Evaluation of Inferior vena cava collapsibility by cardiac ultrasound at enrollment, at time of heart failure (if any)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Children of either sex with SAM and diarrhea
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Age: 1-59 months
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Fluid refractory shock
Exclusion Criteria:
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Severe anemia (hemoglobin< 5 gm/dl) who will require a blood transfusion
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Sclerema
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Congenital anomalies (TOF/ASD/VSD/Trisomy 21, etc.)
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Developmental delay (H/O perinatal asphyxia/cerebral palsy)
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Having a rare blood group
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Icddr,B | Dhaka | Bangladesh | 1000 |
Sponsors and Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- University of British Columbia
- Muhimbili University of Health and Allied Sciences
Investigators
- Principal Investigator: Tahmeed Ahmed, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh
Study Documents (Full-Text)
None provided.More Information
Publications
- AABB. Technical Manual. 19th ed. Fung MK, Eder AF, Spitalnik SL, Westhoff CM, editors. United States.
- Green REB, Klostermann DA. The Antiglobulin Test. In: Harmening D, editor. Modern Blood Banking & Transfusion Practices. 6th ed. Philadelphia: F.A. Davis. p. 107-10.
- Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses. 2nd edition. Geneva: World Health Organization; 2013.
- PR-20021