感染性休克患者不同时期液体负荷对机体影响的前瞻性临床研究

Influence of fluid loading in patients at different stages of septic shock： a prospective study

目的探讨感染性休克患者不同时期进行液体负荷试验对机体的影响。方法采用前瞻性研究方法，选择2010年3月至2014年3月沈阳市第四人民医院重症医学科收治42例接受机械通气治疗的感染性休克患者，在诊断感染性休克0、24、48、72h进行液体负荷试验，记录液体负荷试验前后采用脉搏指示连续心排血量仪（PiCCO）监测的心排血量（CO）、每搏量（SV）、血管外肺水指数（EVLWI），采血检测动脉血氧分压（PaO2）等指标。以液体负荷后SV增加值（△SV）≥15％定义为容量反应阳性；EVLWI增加且〉7mL／kg定义为肺水增加；氧合指数（PaO2/FiO2）较前下降定义为氧合下降。分析不同时间点感染性休克患者的容量反应性、血管外肺水及氧合情况。结果42例患者共进行168次液体负荷试验。与液体负荷试验前比较，确诊0、24、48h时液体负荷试验后患者心率（HR）明显下降，平均动脉压（MAP）、CO、SV均明显增加（均P〈0．01），72h时无明显变化。确诊各时间点EVLWI均增加，其中0h、24h时EVLWI〈7mL／kg，而48h、72h时EVLWI〉7mL／kg[EVLWI（mL／kg）0h：6．0±1．5比4．7±1．5，t=-4．183，P=0．000；24h：6．5±1．5比5．6±1．3，t=-6．000．P=0.000；48h：8．1±2．2比6．1±1．7，t=-7．246，P=0.000；72h：9．0±2．4比6．2±1．5，t=-7．524，P=0．000]；而PaO2/FiO2在0h、24h明显上升，48h无明显变化，72h明显下降[PaO2/FiO2（mmHg，1mmHg=O．133kPa）0h：189．6±34．5比183．2±36．6，t=-3．644，P=0．002；24h：194．6±35．7比190．7±37．5，t=-4．594，P=0．000；48h：201．8±30．2比200．8±33．0，t=-0．793，P=0．437；72h：201．7±24．8比206．2±26．9，t=2．243，P=0．036]。诊断0、24、48、72h时患者容量反应阳性率逐渐降低，分别为85．7％、80．9％、42．8％、28．6％；肺水增加发生率逐渐增高，分别为9．8％、14．3％、42．8％、61．9％；氧合下降发生率逐渐增高，分别为9．5％、11．9％、19．0％、33．3％。与0h相比，48h起容量反应阳性率减少、肺水增加发生率增高的差异即有统计学意义（P〈0．05或P〈0．01）。72h时氧合下降发生率增高差异有统计学意义（P〈0．01）。结论感染性休克患者发病48～72h可能是发生液体过负荷的关键时期，此时期限制液体输注可减少肺水肿发生。

Objective To explore the influence of fluid loading at different stages in patients with septic shock. Methods A prospective study was conducted. Forty-two mechanically ventilated patients in septic shock were enrolled in the Department of Critical Care Medicine of the Fourth People＇s Hospital of Shenyang from March 2010 to March 2014. Fluid loading was performed at 0, 24, 48 and 72 hours after the diagnosis of septic shock. The hemodynamic parameters including cardiac output （CO）, stroke volume （SV）, and extravascular lung water index （EVLWI） were measured by pulse indicator continuous cardiac output （PiCCO）, and arterial partial pressure （PaO2） was determined. Positive responders were defined as SV increased by more than 15% after fluid loading. Increase of lung water was defined as EVLWI increased after fluid loading and its value was more than 7 mL/kg. Oxygenation descend was defined when oxygenation index （PaO2/FiO2） lowered. Fluid responsiveness, extravascular lung water, and oxygenation were analyzed and recorded at different stages in patients with septic shock. Results Fluid loading test was conducted for a total of 168 times in 42 patients. Compared with those before fluid loading test, the heart rate （HR） was lowered, and mean arterial pressure （MAP）, CO, and SV were increased after fluid loading at 0, 24, 48 hours （all P 〈 0.01 ）, unchanged at 72 hours. EVLWI levels at all time points were increased including an increase of EVLWI less than 7 mL/kg at 0 hour and 24 hours, and higher than 7 mL/kg at 48 hours and 72 hours [EVLWI （mL/kg） at 0 hour： 6.0 ± 1.5 vs. 4.7 ± 1.5, t = -4.183, P = 0.000; 24 hours： 6.5 ± 1.5 vs. 5.6＋ 1.3, t = -6.000, P = 0.000; 48 hours： 8.1±2.2 vs. 6.1＋1.7, t = -7.246, P = 0.000; 72 hours： 9.0±2.4 vs. 6.2±1.5, t = -7.524, P = 0.000]. After fluid loading, PaO2/FiO2 was increased remarkably at 0 hour and 24 hours, unchanged at 48 hours, and decreased significantly at 72 hours [PaO2/FiO2 （mmHg, 1 mmHg = 0.133 kPa） at 0 hour： 189.6±34.5 vs. 183.2±36.6, t = -3.644, P = 0.002; 24 hours： 194.6＋35.7 vs. 190.7±37.5, t = -4.594, P = 0.000; 48 hours： 201.8±30.2 vs. 200.8 ± 33.0, t = -0.793, P=0.437; 72 hours： 201.7-4-24.8 vs. 206.2 ± 26.9, t = 2.243, P = 0.036]. The rate of positive response gradually decreased： 85.7%, 80.9%, 42.8%, 28.6% at 0, 24, 48, and 72 hours, the rate of lung water increased was gradually elevated： 9.8%, 14.3%, 42.8%, 61.9% at 0, 24, 48, and 72 hours, and there was an increase of rate of lowering oxygenation with elapse of time （9.5%, 11.9%, 19.0%, 33.3% at 0, 24, 48 and 72 hours）. Compared with 0 hour, the rate of positive response decreased and rate of lung water increased were increased from 48 hours on （P 〈 0.05 or P 〈 0.01 ）, and rate of lowering oxygenation was increased at 72 hours （P 〈 0.01 ）. Conclusions 48 to 72 hours might be the crucial period of occurrence of volume overload in patients with septic shock. Curtailing fluid infusion during this period might reduce the occurrence of pulmonary edema.