Management of Shock in Children With SAM or Severe Underweight and Diarrhea

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Blood and Dopamine
  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)
• Препарат Blood and adrenaline
  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)

Первичные конечные точки

• Case fatality rate [Срок оценки: 28 days (± 3 days)]

Вторичные конечные точки (10)

• Treatment failure rates [Срок оценки: Through study completion, an average of 7 days]
• Need for mechanical ventilation [Срок оценки: Through study completion, an average of 7 days]
• Heart failure [Срок оценки: Through study completion, an average of 7 days]
• Length of ICU stay [Срок оценки: Through study completion, an average of 7 days]
• Time-to-achieve recovery [Срок оценки: 3-4 hours]
• Left ventricular function of the study participants [Срок оценки: Through study completion, an average of 7 days]
• Right ventricular function of the study participants [Срок оценки: Through study completion, an average of 7 days]
• Inferior vena cava collapsibility of the study participants [Срок оценки: Through study completion, an average of 7 days]
• Length of hospital stay [Срок оценки: variable (days to months)]
• Mean arterial pressure (MAP) stabilization at 48 hours [Срок оценки: 48 hours from the point of inclusion in the study]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Bangladesh · 1 центр

• Icddr,B — Dhaka

Публикации

• Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses. 2nd edition. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK154447/ PMID 24006557
• 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.
• Chisti MJ, Pietroni MA, Smith JH, Bardhan PK, Salam MA. Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh. Acta Paediatr. 2011 Dec;100(12):e275-9. doi: 10.1111/j.1651-2227.2011.02368.x. Epub 2011 Jun 21. PMID 21627690
• Sarmin M, Ahmed T, Bardhan PK, Chisti MJ. Specialist hospital study shows that septic shock and drowsiness predict mortality in children under five with diarrhoea. Acta Paediatr. 2014 Jul;103(7):e306-11. doi: 10.1111/apa.12640. Epub 2014 Apr 11. PMID 24661049
• Ahmed T, Ali M, Ullah MM, Choudhury IA, Haque ME, Salam MA, Rabbani GH, Suskind RM, Fuchs GJ. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet. 1999 Jun 5;353(9168):1919-22. doi: 10.1016/S0140-6736(98)07499-6. PMID 10371570
• Chisti MJ, Salam MA, Bardhan PK, Faruque AS, Shahid AS, Shahunja KM, Das SK, Hossain MI, Ahmed T. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study. PLoS One. 2015 Oct 6;10(10):e0139966. doi: 10.1371/journal.pone.0139966. eCollection 2015. PMID 26440279
• Sarker AR, Sultana M, Mahumud RA, Ali N, Huda TM, Salim Uzzaman M, Haider S, Rahman H, Islam Z, Khan JAM, Van Der Meer R, Morton A. Economic costs of hospitalized diarrheal disease in Bangladesh: a societal perspective. Glob Health Res Policy. 2018 Jan 5;3:1. doi: 10.1186/s41256-017-0056-5. eCollection 2018. PMID 29318195

Идентификаторы

NCT: NCT04750070 · PR-20021

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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