Devlin John W, Al-Qadheeb Nada S, Chi Amy, Roberts Russel J, Qawi Imrana, Garpestad Erik, Hill Nicholas S
School of Pharmacy, Northeastern University; Division of Pulmonary, Critical Care and Sleep Medicine.
School of Pharmacy, Northeastern University.
Chest. 2014 Jun;145(6):1204-1212. doi: 10.1378/chest.13-1448.
Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear.
Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 μg/kg/h titrated every 30 min to 0.7 μg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 μg, respectively, at a minimum interval of every 3 h.
The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar.
Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.
无创通气（NIV）成功应用于急性呼吸衰竭（ARF）需要患者的配合与舒适感。在按方案按需静脉注射咪达唑仑和芬太尼的基础上，早期静脉注射右美托咪定的疗效和安全性尚不清楚。
成年ARF患者在开始NIV的8小时内被随机双盲分为两组，分别接受静脉注射右美托咪定（0.2μg/kg/h，每30分钟滴定至0.7μg/kg/h，以维持镇静-躁动评分[SAS]为3至4分）或安慰剂，持续72小时，直至NIV停止≥2小时或直至插管。每次增加右美托咪定和安慰剂15分钟后出现躁动（SAS≥5）或疼痛（视觉模拟评分≥10cm中的5分）的患者，可分别接受静脉注射咪达唑仑0.5至1.0mg或静脉注射芬太尼25至50μg，最小间隔时间为每3小时一次。
右美托咪定组（n = 16）和安慰剂组（n = 17）在基线时相似。早期使用右美托咪定并未改善NIV耐受性（评分，4分中的1分；OR，1.44；95%CI，0.44 - 4.70；P = 0.54），与安慰剂相比，也未导致耐受NIV的中位（四分位间距）时间百分比更高（99%[61% - 100%]对67%[40% - 100%]，P = 0.56）或维持在所需镇静水平（SAS评分 = 3或4）的时间百分比更高（100%[86% - 100%]对100%[100% - 100%]），P = 0.28），插管次数也未减少（P = 0.79）。虽然与安慰剂相比，使用右美托咪定与NIV持续时间更长有关（37[16 - 72]对12[4 - 22]小时，P = 0.03），但总通气时间（NIV + 有创通气）相似（3.3[2 - 4]天对3.8[2 - 5]天，P = 0.52）。与安慰剂相比，接受右美托咪定的患者有更多人出现一次或多次深度镇静（SAS≤2，25%对0%，P = 0.04）。咪达唑仑的使用（P = 0.40）以及严重心动过缓（心率≤50次/分钟，P = 0.18）或低血压（收缩压≤90mmHg，P = 0.64）的发作情况相似。
在ARF患者开始NIV后不久开始使用右美托咪定既不能提高NIV耐受性，也无助于维持所需的镇静目标。需要针对初始不耐受患者进行随机、多中心试验，以进一步阐明右美托咪定在该人群中的作用。
