Randomized Controlled Trial of Dopamine, Adrenaline, and Blood Transfusion for Treatment of Fluid Refractory Shock in Children With Severe Acute Malnutrition or Severe Underweight and Cholera or Other Dehydrating Diarrheas
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Case fatality rate
研究概览
简要总结
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.
详细描述
Background:
- 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.
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children of either sex with acute malnutrition and diarrhea
- •Age: 1-59 months
- •Children with cerebral palsy (CP) and/or developmental delay, Down Syndrome with or without heart diseases
- •Fluid refractory shock
- •Consent from the caregivers/parents
排除标准
- •Having a rare blood group (Rh negative blood groups provided that donor is not available)
- •A child requiring cardio-pulmonary resuscitation during screening or having gasping respiration
研究组 & 干预措施
Blood Transfusion and Dopamine arm
Children in this group (Treatment plan A) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. In addition, they 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)
干预措施: Blood and Dopamine (Drug)
Blood Transfusion and Adrenaline arm
Children in this group (Treatment plan B) will receive a transfusion of whole human blood in a dose of 10 mL/kg over 2-3 hours. In addition, they 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)
干预措施: Blood and adrenaline (Drug)
结局指标
主要结局
Case fatality rate
时间窗: 28 days (± 3 days)
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.
次要结局
- Heart failure(Through study completion, an average of 7 days)
- Treatment failure rates(Through study completion, an average of 7 days)
- Need for mechanical ventilation(Through study completion, an average of 7 days)
- Length of ICU stay(Through study completion, an average of 7 days)
- Time-to-achieve recovery(3-4 hours)
- Mean arterial pressure (MAP) stabilization at 48 hours(48 hours from the point of inclusion in the study)
- Right ventricular function of the study participants(Through study completion, an average of 7 days)
- Inferior vena cava collapsibility of the study participants(Through study completion, an average of 7 days)
- Left ventricular function of the study participants(Through study completion, an average of 7 days)
- Length of hospital stay(variable (days to months))