Multiple Electrolyte Solution vs. Saline in Pediatric Septic Shock
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 708
- 试验地点
- 4
- 主要终点
- New or progressive acute kidney injury defined as increase in serum creatinine by > 0.3mg/dL within 48 hours or to 1.5 times baseline or more within the last 7 days or urine output less than 0.5 mL/kg/h for 6 hours
研究概览
简要总结
Fluid resuscitation is the cornerstone of pediatric shock management; current practices of fluid resuscitation in children are not evidence based. Normal saline is the preferred crystalloid recommended during initial resuscitation in shock, as the incidence of hyponatremia is lower with normal saline compared to all other fluids available and commonly used. However, normal saline has its own set of undesired physicochemical actions. Emerging data strongly indicate the increased incidence of hyperchloremia, metabolic acidosis and consequently, acute kidney injury associated with infusion of large volumes of normal saline. Balanced salt solutions or crystalloids, which have composition resembling plasma but lower chloride concentrations than normal saline, clearly decrease the risk of hyperchloremia and metabolic acidosis in adult as well as pediatric studies when used during the peri-operative period. The results favored balanced solutions in comparison to normal saline. Recent systematic reviews comparing balanced or buffered versus non-buffered fluids for surgery in adults favored the former solution as the metabolic derangements were less with the use of this type of fluid. In adult patients, the two solutions have been compared in various other settings as well such as in traumatic brain injury and in shock. The results favored balanced solutions in comparison to normal saline. However, in the non-surgical setting there is a paucity of evidence on the use of these solutions in children with shock and more evidence needs to be generated to support or refute the use of this fluid as compared to normal saline.
Given this background, the investigators decided to compare the effect of two solutions on the incidence of acute kidney injury in children resuscitated with either of the two fluids. Children receiving at least one fluid bolus at 20 ml/kg in the first hour would be enrolled and followed up for the proposed outcome variables. The investigators plan to enroll 708 patients over a period of 3 years. The investigators believe that the proposed study will provide answer to the research question of which of the fluids could be preferred for resuscitation.
详细描述
Background
Fluid resuscitation is the cornerstone of pediatric shock management; current practices of fluid resuscitation in children are not evidence based. Emerging data strongly indicate the increased incidence of hyperchloremic metabolic acidosis and consequently, acute kidney injury associated with infusion of large volumes of normal saline in critically ill adults in shock. Balanced salt solutions or crystalloids, which have composition resembling plasma but lower chloride concentrations than normal saline, have shown to decrease the risk of hyperchloremia and metabolic acidosis in adult as well as pediatric studies when used during the peri-operative period. In adult patients, the two solutions have been compared in various other settings as well such as in traumatic brain injury and in shock. The results favored balanced solutions in comparison to normal saline. However, in the non-surgical setting there is a paucity of evidence on the use of these solutions in children with shock and more evidence needs to be generated to support or refute the use of this fluid as compared to normal saline.
Objectives
Primary To examine if use of 'balanced crystalloids (multiple electrolyte solution)" results in lower incidence of new or progressive Acute kidney injury (defined as increase in serum creatinine by > 0.3mg/dL within 48 hours or to 1.5 times baseline or more within the last 7 days or urine output less than 0.5 mL/kg/h for 6 hours) in the first seven days after initial fluid resuscitation as compared to saline.
Secondary
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Serially numbered, sealed, opaque pouches containing 10 bags of 500 ml of either MES or saline each will be kept at the study site. Each of the 500 ml bags will be packed in sealed opaque covers inside the pouches as well.The research staff will pick the bag of fluids kept as per allocation sequence and start the bolus in the patient.
入排标准
- 年龄范围
- 2 Months 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children 2 month to ≤ 15 years with features of septic shock - defined as children who have a suspected infection manifested by hypothermia or hyperthermia and have at least two clinical signs of decreased perfusion with or without hypotension
排除标准
- •Children receiving fluid boluses before enrollment
- •Children with cardiogenic shock
- •Known patient with chronic kidney disease with baseline deranged renal function (eGFR < 90 ml/1.73 m2/min)
- •Severe malnutrition
- •Children whose parents refuse to give an informed consent
研究组 & 干预措施
Balanced crystalloid or multiple electrolyte solution group
After enrollment, a fluid bolus comprising of 'multiple electrolyte solution (Plasma-Lyte P)' solution at a dose of 20 ml/kg over 15-20 minutes (recommended) with careful monitoring for features of fluid overload would be administered to each child. Fluid resuscitation will be targeted at achieving the therapeutic end points as given in study definitions. After this the management protocol will be as per recommendations of the American College of Critical Care Medicine 2017 for septic shock in children.
干预措施: Balanced crystalloid solution (Drug)
0.9% saline or saline group
After enrollment, a fluid bolus comprising of 'saline' solution at a dose of 20 ml/kg over 15-20 minutes (recommended) with careful monitoring for features of fluid overload would be administered to each child. Fluid resuscitation will be targeted at achieving the therapeutic end points as given in study definitions. After this the management protocol will be as per recommendations of the American College of Critical Care Medicine 2017 for septic shock in children.
干预措施: 0.9%sodium chloride (Drug)
结局指标
主要结局
New or progressive acute kidney injury defined as increase in serum creatinine by > 0.3mg/dL within 48 hours or to 1.5 times baseline or more within the last 7 days or urine output less than 0.5 mL/kg/h for 6 hours
时间窗: From the time of randomization/intervention to 7 days of admission
Incidence of new or progressive AKI in first 7 days after randomization/ intervention
次要结局
- Proportion of patients with serum chloride levels > 108 meq/L at admission, 6, 24, 48 and 72 hours(At 6, 24, 48 and 72 hours after randomization)
- Number of fluid boluses received in the first 6 hours after randomization(From the time of randomization to 6 hours)
- Incidence of metabolic acidosis at 6, 24, 48 and 72 hours after randomization(At admission and at 6, 24, 48 and 72 hours after randomization)
- Time to resolution of AKI(From the time of onset of AKI after randomization till death or discharge from hospital, whichever came first assessed upto 100 days)
- SOFA scores at 24 and 48 hours after randomization(At 24 and 48 hours after randomization)
- Total fluids received in the first 24 hours, 24-48 hours and 48-72hrs in ml/kg after randomization(From the time of randomization to 72 hours)
- Mortality (serious adverse event)(From the time of randomization till death or discharge from ICU, whichever came first assessed upto 100 days)
- PELOD scores at 24 and 48 hours after randomization(At 24 and 48 hours after randomization)
研究者
Jhuma Sankar
Additional Professor Pediatrics
All India Institute of Medical Sciences, New Delhi