A Prospective, Randomized, Controlled Trial of Combination Vasopressin and Epinephrine to Epinephrine Only for In-Intensive Care Unit Pediatric Cardiopulmonary Resuscitation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Combination vasopressin and epinephrine (CPA refractory to cardiopulmonary resuscitation and initial epinephrine dosing) will increase the proportion of patients surviving to hospital discharge by 25% compared to epinephrine alone.
研究概览
简要总结
Cardiac arrest has a very poor prognosis, especially with prolonged efforts at resuscitation, and unfortunately, survivors are often severely neurologically impaired. CPA in children is often the result of a prolonged illness rather than a sudden, primary cardiac event as is frequent in adults. This necessitates that resuscitation research must be conducted separately for pediatric and adult patients. Authorities currently endorse the use of epinephrine for restoring spontaneous circulation based on its ability to maintain diastolic blood pressure and subsequent blood flow to the heart during resuscitation. However, human studies have shown no clear survival benefit of epinephrine and have elucidated concerning adverse effects. Recently, both the European Resuscitation Council and the American Heart Association have recognized the use of vasopressin as a promising vasoconstrictor and an alternative or adjunct to epinephrine in the resuscitation of adults. Vasopressin causes profound vasoconstriction without the adverse effects of epinephrine and is associated with improved blood flow to the heart and brain. This increased cerebral blood flow has been associated with better neurologic outcome in animal studies. In light of compelling animal and human studies of combined vasopressin and epinephrine, pediatric trials are indicated for vasopressin usage in pediatric CPR. This study will evaluate the addition of the administration of vasopressin to standard advanced CPR therapy (epinephrine alone) for pediatric patients that experience in-intensive care unit CPA to assess for improved time to return of spontaneous circulation (ROSC), survival to 24 hours, survival to hospital discharge, and neurologic outcome. When a patient experiences a CPA, standard Pediatric Advanced Life Saving (PALS) protocols as endorsed by the American Heart Association will be initiated. This will include receiving epinephrine as the first vasopressor medication. Patients will then be randomized to receive vasopressin (treatment group) or epinephrine (control group) as the second vasopressor medication, if needed. If more then two doses of vasopressor medication is required in either group, epinephrine will be administered according to the PALS algorithm until the end of the event. All CPA events meeting inclusion criteria will be entered into the National Registry of Cardiopulmonary Resuscitation (NRCPR) Database, which tracts all CPA events at Children's Medical Center Dallas. Prior to commencement of the RCT, a pilot trial of 10 patients will be completed to assess preliminary safety, feasibility, and effectiveness of combination epinephrine-vasopressin for pediatric in-intensive care unit CPA refractory to initial epinephrine dosing. All pilot patients will receive vasopressin as the second vasopressor medication.
详细描述
CONCISE SUMMARY OF PROJECT:
The study design will be a prospective, randomized, controlled clinical trial to be conducted in the PICU of CMC Dallas (UT Southwestern Medical Center) following a pilot trial enrolling 10 patients. This study will be undertaken after consultation with and acceptance by the resuscitation committee and PICU at CMC. Pediatric patients that experience in-hospital CPA who remain in cardiac arrest despite CPR and an initial, standard dose of epinephrine (0.01 mg/kg), will be randomly assigned to receive either standard dose epinephrine (0.01 mg/kg) or vasopressin (0.8 units/kg) rescue as the second vasopressor medication.
SUMMARY OF STUDY PROCEDURES:
When a patient experiences a CPA, standard Pediatric Advanced Life Saving (PALS) protocols will be followed. This will include: establishment of an airway, support of breathing including supplemental oxygen, evaluation of cardiac rhythm, chest compressions, electrical defibrillation if appropriate, and administration of epinephrine as the first vasopressor medication. The quality of CPR will be monitored and reported by the documenting nurse for the event, to include rate of ventilation, rate and depth of chest compressions, and no-flow time (time without chest compressions). In addition, monitoring of end-tidal CO2, diastolic blood pressure via arterial line if present, and human observation and coaching will be employed to track CPR quality. The patient will then be randomized to receive either epinephrine (control group) or vasopressin (treatment group) as the second vasopressor medication if needed. If further doses of medication are required in either group, epinephrine will be administered according to the PALS algorithm until the end of the CPA event as defined below. Thus, the only difference between the groups will be the replacement of epinephrine with vasopressin as the second vasopressor medication in the algorithm. A total of 120 patients will be enrolled in the randomized, controlled trial portion of the study.
After completion of PICU staff training and prior to the randomized, controlled trial, a pilot trial of vasopressin resuscitation involving 10 patients will be conducted to test the feasibility and safety of study methodology. Pilot participants who meet inclusion criteria will be enrolled serially from the PICU at CMC. Study protocol for the treatment group of the randomized, control trial (vasopressin + epinephrine) will be followed. Collected information will be reviewed by members of a Data Safety and Monitoring Board (DSMB) before proceeding to the next phase of the trial. These patients will not be included in the final analysis.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children, ages 0 to 18 years, admitted to the PICU who experience CPA requiring either chest compressions and/or defibrillation. This will include males, females and Spanish speaking individuals.
- •Patients must require at least 2 doses of vasopressor medication during the CPA event (all patients would receive epinephrine as first dose, followed by either epinephrine or vasopressin as second dose depending on randomization, all subsequent doses required would be epinephrine) given via any route (intravenous, intraosseous, or endotracheal).
排除标准
- •Do Not Attempt Resuscitate (DNAR) patients
- •Chemical code only (i.e., no CPR/defibrillation)
- •Events not requiring chest compressions and/or defibrillation
- •Events with a pulse requiring synchronized or unsynchronized cardioversion
- •Successful internal cardiac device defibrillation of Vfib/pVT that initiates the resuscitation event
- •Defibrillation for Vfib/pVT without administration of a vasopressor
- •All patients in the custody of the State of Texas
- •Any patient whose parent or guardian "opts out" of the study
- •Any patient who is pregnant
- •Any patient whose attending physician "opts out" of the study
- •Any patient who does not consent to follow up data collection
研究组 & 干预措施
1
Pediatric patients that experience in-hospital CPA who remain in cardiac arrest despite CPR and an initial, standard dose of epinephrine (0.01 mg/kg), will be randomly assigned to receive vasopressin (0.8 units/kg) rescue as the second vasopressor medication.
干预措施: Vasopressin (Drug)
2
Pediatric patients that experience in-hospital CPA who remain in cardiac arrest despite CPR and an initial, standard dose of epinephrine (0.01 mg/kg), will be randomly assigned to receive standard dose epinephrine (0.01 mg/kg)rescue as the second vasopressor medication.
干预措施: Epinephrine (Drug)
结局指标
主要结局
Combination vasopressin and epinephrine (CPA refractory to cardiopulmonary resuscitation and initial epinephrine dosing) will increase the proportion of patients surviving to hospital discharge by 25% compared to epinephrine alone.
时间窗: Immediate
次要结局
- Combination vasopressin and epinephrine will decrease the time to ROSC(Immediate)
- Vasopressin and epinephrine will improve the proportion of CPA survivors with favorable neurologic outcome (short-term Pediatric Overall Performance Category) [POPC] score discharge of 1-3 or unchanged from hospital admission at the time of hospital .(Period of hospitalization)
- Vasopressin and epinephrine will improve the proportion of CPA survivors with favorable neurologic outcome (short-term Pediatric Cerebral Performance Category) [PCPC] score of 1-3 or unchanged from hospital admission at time of hospital discharge.(Period of Hospitalization)
- Combination vasopressin and epinephrine will decrease the proportion of patients who require prolonged CPR (CPR > 20minutes) to achieve sustained ROSC.(Immediate)
- Combination vasopressin and epinephrine will increase organ recovery in those patients who meet brain death criteria following the CPA event.(Period of hospitalization)
- Combination epinephrine and vasopressin will improve rates of return of spontaneous circulation (ROSC)(Immediate)
- Combination vasopressin and epinephrine will improve 24 hour survival.(24 hrs)