Martin Greg S, Moss Marc, Wheeler Arthur P, Mealer Meredith, Morris John A, Bernard Gordon R
Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Crit Care Med. 2005 Aug;33(8):1681-7. doi: 10.1097/01.ccm.0000171539.47006.02.
Hypoproteinemia is a common condition in critically ill patients, associated with the development of acute lung injury and acute respiratory distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide benefits lung physiology in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome, but the independent pharmacologic effects of these drugs are unknown.
Randomized, double-blinded, placebo-controlled multicentered trial.
Eleven medical, surgical, and trauma intensive care units including 190 beds within two university hospital systems.
Forty mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome, whose serum total protein concentrations were <6.0 g/dL were included. Patients were excluded for hemodynamic instability or significant renal or hepatic failure.
Subjects were equally randomly allocated to receive furosemide with albumin or furosemide with placebo for 72 hrs, titrated to fluid loss and normalization of serum total protein concentration.
The primary outcome was change in oxygenation from baseline to day 1, with secondary physiologic and clinical outcomes. There were no differences in baseline characteristics of the subjects in relation to group assignment. Albumin-treated patients had greater increases in oxygenation (mean change in Pao2/Fio2: +43 vs. -24 mm Hg at 24 hrs and +49 vs. -13 mm Hg at day 3), serum total protein (1.5 vs. 0.5 g/dL at day 3), and net fluid loss (-5480 vs. -1490 mL at day 3) throughout the study period (all p < .05). Fluid bolus administration to control patients reduced net negative fluid balance; control patients more frequently developed hypotension and had fewer shock-free days, which translated to differences in organ failure at study end.
The addition of albumin to furosemide therapy in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome significantly improves oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability. Additional randomized clinical trials are necessary to examine mechanisms and determine the effect on important clinical outcomes, such as the duration of mechanical ventilation.
低蛋白血症在重症患者中很常见,与急性肺损伤、急性呼吸窘迫综合征的发生及随后更差的临床结局相关。白蛋白联合呋塞米对急性肺损伤/急性呼吸窘迫综合征的低蛋白血症患者的肺生理功能有益,但这些药物的独立药理作用尚不清楚。
随机、双盲、安慰剂对照的多中心试验。
两个大学医院系统内的11个内科、外科和创伤重症监护病房,共190张床位。
纳入40例机械通气的急性肺损伤/急性呼吸窘迫综合征患者,其血清总蛋白浓度<6.0 g/dL。因血流动力学不稳定或严重肾或肝功能衰竭而排除患者。
受试者被随机平均分配接受白蛋白联合呋塞米或安慰剂联合呋塞米治疗72小时,根据液体丢失情况和血清总蛋白浓度正常化进行滴定。
主要结局是从基线到第1天氧合的变化,以及次要的生理和临床结局。受试者的基线特征在分组方面无差异。在整个研究期间,接受白蛋白治疗的患者氧合增加更多(24小时时动脉血氧分压/吸入氧分数值的平均变化:+43 vs. -24 mmHg,第3天时为+49 vs. -13 mmHg)、血清总蛋白增加更多(第3天时为1.5 vs. 0.5 g/dL)、净液体丢失更多(第3天时为-5480 vs. -1490 mL)(所有p<0.05)。对对照患者给予液体冲击治疗可减少净负液体平衡;对照患者更频繁地出现低血压且无休克天数更少,这导致研究结束时器官衰竭存在差异。
在急性肺损伤/急性呼吸窘迫综合征的低蛋白血症患者中,呋塞米治疗加用白蛋白可显著改善氧合,具有更大的净负液体平衡并更好地维持血流动力学稳定性。需要更多的随机临床试验来研究其机制并确定对重要临床结局的影响,如机械通气时间。