Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.
Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
JAMA. 2019 May 7;321(17):1677-1685. doi: 10.1001/jama.2019.4149.
Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is a method used to induce cooling, primarily of the brain, during cardiopulmonary resuscitation (ie, intra-arrest).
To determine whether prehospital trans-nasal evaporative intra-arrest cooling improves survival with good neurologic outcome compared with cooling initiated after hospital arrival.
DESIGN, SETTING, AND PARTICIPANTS: The PRINCESS trial was an investigator-initiated, randomized, clinical, international multicenter study with blinded assessment of the outcome, performed by emergency medical services in 7 European countries from July 2010 to January 2018, with final follow-up on April 29, 2018. In total, 677 patients with bystander-witnessed out-of-hospital cardiac arrest were enrolled.
Patients were randomly assigned to receive trans-nasal evaporative intra-arrest cooling (n = 343) or standard care (n = 334). Patients admitted to the hospital in both groups received systemic therapeutic hypothermia at 32°C to 34°C for 24 hours.
The primary outcome was survival with good neurologic outcome, defined as Cerebral Performance Category (CPC) 1-2, at 90 days. Secondary outcomes were survival at 90 days and time to reach core body temperature less than 34°C.
Among the 677 randomized patients (median age, 65 years; 172 [25%] women), 671 completed the trial. Median time to core temperature less than 34°C was 105 minutes in the intervention group vs 182 minutes in the control group (P < .001). The number of patients with CPC 1-2 at 90 days was 56 of 337 (16.6%) in the intervention cooling group vs 45 of 334 (13.5%) in the control group (difference, 3.1% [95% CI, -2.3% to 8.5%]; relative risk [RR], 1.23 [95% CI, 0.86-1.72]; P = .25). In the intervention group, 60 of 337 patients (17.8%) were alive at 90 days vs 52 of 334 (15.6%) in the control group (difference, 2.2% [95% CI, -3.4% to 7.9%]; RR, 1.14 [95% CI, 0.81-1.57]; P = .44). Minor nosebleed was the most common device-related adverse event, reported in 45 of 337 patients (13%) in the intervention group. The adverse event rate within 7 days was similar between groups.
Among patients with out-of-hospital cardiac arrest, trans-nasal evaporative intra-arrest cooling compared with usual care did not result in a statistically significant improvement in survival with good neurologic outcome at 90 days.
ClinicalTrials.gov Identifier: NCT01400373.
心脏骤停后，治疗性低温可能会增加存活并获得良好的神经功能结局。经鼻蒸发冷却法是一种在心肺复苏期间（即停搏期）用于诱导冷却的方法，主要是冷却大脑。
确定与入院后开始冷却相比，院前经鼻蒸发性停搏期内冷却是否能提高具有良好神经功能结局的存活率。
设计、设置和参与者：PRINCESS 试验是一项由研究人员发起的、随机的、国际性的多中心研究，由 7 个欧洲国家的紧急医疗服务机构进行，对结局进行盲法评估，从 2010 年 7 月至 2018 年 1 月进行，最终随访日期为 2018 年 4 月 29 日。共有 677 名有旁观者见证的院外心脏骤停患者入组。
患者被随机分配接受经鼻蒸发性停搏内冷却（n = 343）或标准护理（n = 334）。两组入院的患者均接受 32°C 至 34°C 的全身治疗性低温治疗 24 小时。
主要结局为 90 天时具有良好神经功能结局的存活率，定义为 CPCS 1-2。次要结局为 90 天时的存活率和达到核心体温低于 34°C 的时间。
在 677 名随机患者中（中位数年龄 65 岁；172 [25%] 名女性），671 名完成了试验。干预组达到核心体温低于 34°C 的中位时间为 105 分钟，对照组为 182 分钟（P < .001）。90 天时 CPCS 1-2 的患者数量在干预冷却组为 337 例中的 56 例（16.6%），在对照组为 334 例中的 45 例（13.5%）（差异，3.1%[95%CI，-2.3%至 8.5%]；相对风险 [RR]，1.23[95%CI，0.86-1.72]；P = .25）。在干预组中，60 名患者（17.8%）在 90 天时存活，而对照组为 52 名患者（15.6%）（差异，2.2%[95%CI，-3.4%至 7.9%]；RR，1.14[95%CI，0.81-1.57]；P = .44）。最常见的与器械相关的不良事件是轻微鼻出血，在干预组的 337 名患者中，有 45 名（13%）报告了该不良事件。两组在 7 天内的不良事件发生率相似。
在院外心脏骤停患者中，与常规护理相比，经鼻蒸发性停搏内冷却在 90 天时并未显著改善具有良好神经功能结局的存活率。
ClinicalTrials.gov 标识符：NCT01400373。
