Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Anesthesiology and Intensive care, Odense University Hospital, Odense, Denmark.
Crit Care Med. 2018 Oct;46(10):1626-1633. doi: 10.1097/CCM.0000000000003289.
No double-blinded clinical trials have investigated optimal mean arterial pressure targets in the ICU. The aim of this study was to develop and validate a method for blinded investigation of mean arterial pressure targets in patients monitored with arterial catheter in the ICU.
Prospective observational study (substudy A) and prospective, randomized, controlled clinical study (substudy B).
ICU, Department of Cardiology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Adult patients resuscitated from out-of-hospital cardiac arrest.
Standard blood pressure measuring modules were offset to display 10% lower or higher blood pressure values. We then: 1) confirmed this modification in vivo by comparing offset to standard modules in 22 patients admitted to the ICU. Thereafter we 2) verified the method in two randomized, clinical trials, each including 50 out-of-hospital cardiac arrest patients, where the offset of the blood pressure module was blinded to the treating staff.
Substudy A showed that the expected separation of blood pressure measurements was achieved with an excellent correlation of the offset and standard modules (R = 0.997). Bland-Altman plots showed no bias of modified modules over a clinically relevant range of mean arterial pressure. The primary endpoint of the clinical trials was between-group difference of norepinephrine dose needed to achieve target mean arterial pressure. Trial 1 aimed at a 10% difference between groups in mean arterial pressure (targets: 65 and 72 mm Hg, respectively) and demonstrated a separation of 5 ± 1 mm Hg (p < 0.001). The difference in norepinephrine dose was not significantly different (0.03 ± 0.03 µg/kg/min; p = 0.42). Trial 2 aimed at a 20% difference between groups in mean arterial pressure (targets: 63 and 77 mm Hg, respectively). Separation was 12 ± 1 mm Hg (p < 0.01) in mean arterial pressure and 0.07 ± 0.03 µg/kg/min (p < 0.01) in norepinephrine dose.
The present method is feasible and robust and provides a platform for double-blinded comparison of mean arterial pressure targets in critically ill patients.
尚无临床试验对 ICU 患者的最佳平均动脉压目标进行双盲研究。本研究旨在开发和验证一种在 ICU 中使用动脉导管监测的患者中对平均动脉压目标进行盲法研究的方法。
前瞻性观察性研究（子研究 A）和前瞻性、随机、对照临床试验（子研究 B）。
丹麦哥本哈根大学医院 Rigshospitalet 心内科 ICU。
院外心脏骤停复苏的成年患者。
标准血压测量模块被偏移，以显示低 10%或高 10%的血压值。我们随后：1）在 22 名入住 ICU 的患者中，通过比较偏移与标准模块来证实这一改变。此后，我们 2）在两项随机临床试验中验证了该方法，每项试验包括 50 名院外心脏骤停患者，其中血压模块的偏移对治疗人员是盲法的。
子研究 A 表明，预期的血压测量分离得以实现，偏移和标准模块具有极好的相关性（R=0.997）。Bland-Altman 图显示，在平均动脉压的临床相关范围内，修正模块没有偏差。临床试验的主要终点是组间去甲肾上腺素剂量差异，以达到目标平均动脉压。试验 1 旨在两组之间的平均动脉压有 10%的差异（目标分别为 65 和 72mmHg），并显示出 5±1mmHg 的分离（p<0.001）。去甲肾上腺素剂量的差异无显著性差异（0.03±0.03μg/kg/min；p=0.42）。试验 2 旨在两组之间的平均动脉压有 20%的差异（目标分别为 63 和 77mmHg）。平均动脉压分离为 12±1mmHg（p<0.01），去甲肾上腺素剂量分离为 0.07±0.03μg/kg/min（p<0.01）。
本方法可行且稳健，为在危重症患者中对平均动脉压目标进行双盲比较提供了一个平台。
