抑制一氧化氮合成对犬感染性休克的影响

目的：探讨一氧化氮（NO）在感染性休克中的作用机制,及抑制NO合成的治疗学意义。方法：10只健康杂种狗予戊巴比妥麻醉,大肠杆菌内毒素（LPS）60μg·kg-1·h-1×30min静脉滴注,继以生理盐水（NS）15ml·kg-1·h-1维持。随机分成两组。组Ⅰ、组Ⅱ在LPS开始注射后60min分别单剂注射NS30ml、NS30ml＋L-硝基精氨酸（LNNA）20mg·kg-1。观察血液动力学、氧动力学、尿NO3/NO2（NOx）、血浆内皮素（ET）变化。结果：LPS注射后60min两组动物均呈典型高动力状态,平均动脉压（MAP）、体循环阻力（SVRI）明显下降,心脏指数（CI）轻度增加。LPS使氧输送（DO2）、氧耗（VO2）增加。尿NOx升高。LNNA使MAP恢复至基础水平,SVRI、PVRI显著升高且超过基础值;CI下降,DO2、VO2减少,PvO2上升,尿NOx低于组Ⅰ,而ET明显高于组Ⅰ。结论：LPS诱导的犬感染性休克的血液动力学异常与NO过多释放有关,NO抑制LPS引起的ET释放。LNNA虽可逆转低血压,但对感染性休克的整体治疗不利。     

An extreme form of the hyperdynamic syndrome in septic shock

We classified 41 patients in septic shock on the basis of cardiac index (CI) after volume expansion with plasma protein solution, in order to obtain adequate filling pressures. Five had decreased CI (<3.5 l/min per m²), 31 had moderately increased CI (3.5–7.0 l/min per m²) and 5 had extreme hyperdynamic shock with CI superior to 7.0 l/min per m². Among the patients with increased CI, those with extreme hyperdynamic state (EHS) had lower total systemic and pulmonary arteriolar resistances (370 vs 658 and 52 vs 119 dynes·s·cm^-5, respectively) and a higher stroke index (67 vs 46 ml/m²), in spite of similar right atrial pressures. In this latter group, blood lactate was higher (6.5 vs 2.1 mmol/l), acidosis was more severe and coagulation disorders more pronounced; all five patients maintained an extremely high CI until death, which supervened after a brief episode of sinus bradycardia. A similar clinical course was rarely observed in the remaining moderately hyperdynamic group, in which mortality rate was significantly lower (35%). Three of five patients with EHS (compared to 2 of 31 in the moderately hyperdynamic group) had liver cirrhosis, the fourth died of fulminant meningococcemia and the fifth had prolonged polymicrobial bacteremia before adequate treatment was begun. Thus, underlying liver disease or particularly severe and uncontrolled infection seems to predispose to EHS. It is concluded that septic shock with extremely high cardiac output and excessively low peripheral resistances represents a distinct subset with more severe metabolic and coagulation disorders, an unusual hemodynamic evolution and a particularly poor prognosis.     

High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock

Objectives To evaluate the effect of short-term (12-h) high-volume hemofiltration (HVHF) in reversing progressive refractory hypotension and hypoperfusion in patients with severe hyperdynamic septic shock. To evaluate feasibility and tolerance and to compare observed vs. expected hospital mortality.Design and setting Prospective, interventional, nonrandomized study in the surgical-medical intensive care unit of an academic tertiary center.Patients Twenty patients with severe septic shock, previously unresponsive to a multi-intervention approach within a goal-directed, norepinephrine-based algorithm, with increasing norepinephrine (NE) requirements (> 0.3 μg kg^–1 min^–1) and lactic acidosis.Interventions Single session of 12-h HVHF.Measurements and results We measured changes in NE requirements and perfusion parameters every 4 h during HVHF and 6 h thereafter. Eleven patients showed decreased NE requirements and lactate levels (responders). Nine patients did not fulfill these criteria (nonresponders). The NE dose, lactate levels, and heart rates decreased and arterial pH increased significantly in responders. Hospital mortality (40%) was significantly lower than predicted (60%): 67% (6/9) in nonresponders vs. 18% (2/11) in responders. Of 12 survivors 7 required only a single 12-h HVHF session. On logistic regression analysis the only statistically significant predictor of survival was theresponse to HVHF (odds ratio 9).Conclusions A single session of HVHF as salvage therapy in the setting of a goal-directed hemodynamic management algorithm may be beneficial in severe refractory hyperdynamic septic-shock patients. This approach may improve hemodynamics and perfusion parameters, acid-base status, and ultimately hospital survival. Moreover, it is feasible, and safe.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

乌司他丁治疗感染性休克治疗体会

目的观察并探讨乌司他丁（UTI）对感染性休克患者的治疗效果。方法将80例感染性休克患者随机分为治疗组（40例）和对照组（40例）。对照组给予常规治疗,包括补充血容量、抗感染,必要时机械通气及使用血管活性药物;治疗组在此基础上加用UTI 30万U溶于30 ml生理盐水中静脉注射（约15 min）,3次/d,连续用药3 d。分别在治疗前和治疗3 d后检测血白细胞介素6（IL-6）、白细胞介素8（IL-8）、肿瘤坏死因子α（TNF-α）、C反应蛋白（CRP）和氧自由基丙二醛（MDA）含量及超氧化物歧化酶（SOD）活力,同时观察比较发生多器官功能障碍（MODS）的病例数、ICU的住院天数及病死率。结果与对照组比较,治疗组在治疗3 d后,患者的血IL-6、IL-8、TNF-α、CRP和MDA含量下降幅度均明显大于对照组（P均〈0.01~0.05）,而SOD活力增加幅度亦明显高于对照组（P〈0.05）;治疗组的病死率、MODS发生率和ICU的住院天数均少于对照组（P〈0.05）。结论 UTI对感染性休克致炎细胞因子IL-6、IL-8和TNF-α有明显的抑制作用,降低MDA含量,增强SOD活力,减轻组织器官损伤,缩短患者在ICU住院天数。     

High-mobility group box 1 protein plasma concentrations during septic shock

Objective To investigate plasma high-mobility group box 1 protein (HMGB1) concentration and its relationship with organ dysfunction and outcome in septic shock patients. Design and setting Prospective, noninterventional study. Medical adult intensive care unit at a university hospital in France. Patients 42 critically ill patients with septic shock. Methods Arterial blood was drawn within 12 h of admission for the measurement of plasma HMGB1 concentration by ELISA. Repeated sampling was performed on days 3, 7, and 14. Results Median HMGB1 concentration was 4.4 ng/ml (IQR 1.2–12.5) at admission, with no difference between survivors and nonsurvivors. A positive correlation was observed between HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a progressive but statistically nonsignificant decline in HMGB1 concentration among the survivors, while nonsurvivors showed an increase in HMGB1 level between days 1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated survivors from nonsurvivors with 66% sensitivity and 67% specificity, and concentration greater than 4 ng/ml was associated with an odds ratio of death of 5.5 (95% CI 1.3–23.6).     

Admission plasma vasopressin levels in children with meningococcal septic shock

Objective Vasopressin (AVP) response has been reported to be inappropriately low in adult established septic shock. We studied admission AVP levels in children with meningococcal septic shock (MSS).Patients and methods All children with meningococcal infection admitted to our PICU between May 2001 and August 2002 were classified as MSS (persistent hypotension despite fluid therapy, with perfusion abnormalities and the need for vasoactive drug infusion for at least 24 h or until death), or meningococal infection without shock (fever and purpura, with or without meningitis). Blood samples were collected at admission and AVP levels were subsequently determined using Nichols Institute Diagnostics vasopressin assay. Eighteen of 19 children with MSS (7 deaths) and 15 without shock (no death) were included.Results In children with MSS median admission AVP level was 41.6 pg/ml (1.4–498.9) and in those without 3.3 pg/ml (1.6–63.8). In children with MSS the AVP level was not correlated with duration of shock and fluid expansion prior to AVP sampling, or with age-adjusted blood pressure and natremia at the time of blood sampling. AVP levels were higher in nonsurvivors, but not significantly so. Only one nonsurvivor had an admission AVP level below 30 pg/ml.Conclusions In our children with established MSS who died the admission AVP level were not inappropriately low. Further studies including serial AVP level assessments are needed before concluding that AVP administration is of little interest in children with MSS.     

中药注射液血必净对感染性休克犬促凝物质的影响

目的 研究中药注射液血必净对感染性休克犬促凝物质的影响,探讨血必净治疗感染性休克作用机制.方法 在北京朝阳医院基础动物实验窜通过给健康杂种犬静脉内注射内毒素制?感染性休克的动物模型,以收缩压下降大于40 mmHs开始计时,持续稳定60 min,即视为模型成功.按照随机原则将制模的动物分为3组:多巴胺治疗组6只,血必净+多巴胺治疗组(简称血必净组)6只,另设对照组6只.分别按照实验设计的时间点即注射内毒素前(基础),模型成功后用药前,以及用药后3 h检测血管细胞黏附分子(vascular cell adhesion molecule,VCAM)、细胞间黏附分子(inter-cell adhesionmolecule,ICAM)、血管性血友病因子(vonwillibrand factor,VWT)和纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)血浆含鼍指标,采用SPSS 13.0统计软件进行统计分析.结果 犬机体促凝功能监测指标VCAM,ICAM,VWT以及PAI-1:血必净组与对照组、多巴胺组相比,在用药后3 h或7 h五项监测指标发生了具有统计学意义的变化(P<0.01或P<0.05),包括降低同观测点的峰值或者延迟峰值的出现;多巴胺组与对照组相比,ICAM,VWT,PAI-1在3 h或7 h也出现具有统计学意义的降低(P<0.01或P<0.05).结论 在应用多巴胺治疗感染性休克犬的基础上加用血必净可以更加有效地降低感染性休克犬体内的促凝物质血浆水平,是中药注射液血必净对感染性休克犬发挥治疗作用的机制之一.     

乳酸林格液与羟乙基淀粉溶液对感染性休克患者凝血及纤溶系统的影响

目的 观察应用不同液体复苏对感染性休克患者凝血及纤溶系统功能的影响.方法 选择2009年9月至2011年6月连续收治的感染性休克患者42例,其中应用乳酸林格液治疗者20例(RL组),应用羟乙基淀粉130/0.4治疗者22例(HES组).于患者治疗前及治疗后6、12、24h分别取血,测定凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、组织型纤溶酶原激活物及其抑制物(t-PA及PAI),同时记录患者住院及预后情况.结果 HES组患者住重症监护病房(ICU)时间(d)明显短于RL组(12.5±8.8比17.1±16.6,P＜0.01),且HES组复苏液体用量(L:2.77±0.59)及血管活性药物用量(μg·kg-1·min-1:0.56±0.15)明显少于RL组(3.46±0.73、0.81±0.41,均P＜0.01).RL组死亡12例、存活8例,HES组死亡7例、存活15例,两组间无差异.两组组内及组间各时间点PT、APTT及t-PA比较差异均无统计学意义,但HES组PAI( μg/L)逐渐降低,并在24h明显低于治疗前及同期RL组(41.76±25.95比89.11±14.27、55.08±35.43,均P＜0.05).结论 不同液体复苏对感染性休克患者预后无影响,但HES复苏效率明显好于RL.不同液体复苏对患者凝血功能没有明显影响,但应用胶体可能对血管内皮细胞有保护作用,减弱纤溶系统功能的抑制,从而缓解患者早期的高凝状态.     

连续性血液滤过救治脓毒性休克的临床评价

目的探讨连续性静脉—静脉血液滤过(CVVH)治疗脓毒性休克的临床疗效。方法回顾性分析76例严重脓毒症伴脓毒性休克患者,分为两组,常规综合治疗组32例,采用快速而充分的液体复苏、血管活性药物改善脏器灌注、早期肠道营养保护肠黏膜屏障等综合治疗;综合治疗 CVVH组44例,在常规综合治疗基础上加CVVH治疗。分别观察两组患者治疗前后APACHEⅡ评分、中心静脉压(CVP)、平均动脉压(MAP)、静脉血氧饱和度(SvO2)、氧合指数(PaO2/FiO2)、血乳酸水平的变化。结果44例脓毒性休克患者加用CVVH治疗后,APACHEⅡ评分、CVP、MAP、SvO2、PaO2/FiO2、血乳酸水平以及有效治愈率和死亡率与常规综合治疗组比较差异均有统计学意义(P<0·05)。结论在常规综合治疗的基础上加用连续性血液滤过治疗脓毒性休克,能有效清除患者致炎介质和毒素,维持内环境稳定,改善氧合功能,补充营养,提高抢救成功率。     

Haemodynamic effects of dopamine in septic shock

The Haemodynamic response to dopamine infusion has been assessed in 30 patients in septic shock with myocardial dysfunction. Dopamine infusion resulted in a haemodynamic improvement as indicated by significant increases in cardiac output of 38.4% (p>.001), stroke volume 18.7% (p<.001), and mean arterial pressure of 33% (p<.001). Despite the inotropic effect, left ventricular filling pressure did not change in 20 cases and increased in 10 cases. Mean peripheral resistance remained unchanged with a scatter of individual responses depending upon factors such as dopamine dose and initial vascular resistance.Dopamine increased intrapulmonary shunting by 48% (p<.001), insignificantly decreased PaO₂, increased mixed venous oxygen saturation by 16% (p<.02) and decreased pulmonary vascular resistance by 15% (p<.02).Both isoprenaline and dopamine improve stroke volume by an inotropic action, with an increase in venous return in the case of the latter and a reduction in afterload in the former.It is cocluded that the usefulness of dopamine in septic shock may be limited in patients with previous myocardial disease because of the risk of increasing preload and in hypoxaemic patients because of the risk of increasing intrapulmonary shunting.A preliminary report of this work was presented at the Fifth Annual Society of Critical Care Medicine meeting, Pittsburgh, PA, USA, May 1976     

Value of dynamic plasma cell-free DNA monitoring in septic shock syndrome: A case report

BACKGROUND Mortality due to septic shock is relatively high.The dynamic monitoring of plasma cell-free DNA(cfDNA)can guide the treatment of septic shock.CASE SUMMARY Herein,we present a typical case of septic shock syndrome caused by the bacilli Acinetobacter baumannii and Pantoea.The patient complained of abdominal pain,fever and chills upon admission to the Emergency Department.Marked decreases in white blood cells and procalcitonin(PCT)were observed after the patient received continuous renal replacement and extracorporeal membrane oxygenation.Plasma cfDNA levels were consistently high,peaking at 1366.40 ng/mL,as measured by a duplex real-time PCR assay with an internal control,which was developed as a novel method for the accurate quantification of cfDNA.The patient died of septic shock on HD 8,suggesting that cfDNA could be used to monitor disease progression more effectively than PCT and the other inflammatory factors measured in this case.CONCLUSION CfDNA may be a promising marker that complements other inflammatory factors to monitor disease progression in patients with septic shock.     

Steroid therapy of septic shock

Steroid therapy in patients with septic shock has been controversial for decades. Although treatment with high-doses of corticosteroids for patients with septic shock has been shown not to be beneficial, it was believed that therapy with low-doses would be helpful. Recent studies document that steroids are beneficial only in adult septic shock patients whose blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy. For the majority of septic shock patients, corticosteroids should not be used, as the benefit of reversing shock is not worth the complications of superinfection, new sepsis, and septic shock. Finally, steroid therapy should not be guided by corticotropin test results.     

感染性休克病人的血流动力学特点及意义

目的 了解感染性休克病人早期血流动力学改变的特点及预后关系。方法 临床前瞻性研究，监测感染性休克早期血流动力学改变并分析与预后的关系。结果 共连续观察48例病人，其中25例（52%）死亡。一些指标的水平在死亡者与生存者间差别较大，其中包括平均肺动脉压（MPAP)、肺动脉楔压（PAWP）、体/肺循环阻力指数（SVRI/PVRI）、左/右心做功（LCW/RCW）和左/右心每搏动（LCSW/RCSW）等血流动力学指标的氧合指数，动脉混合静脉血含氧量差（a-vDO2)、全身性为症反应综合征（SIRS）指标积分等。结论 感染性休克病情凶险，部分血流动力学指标对早期评估其预后有指标作用。     

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock

Objective To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock.Design Prospective study comparing a therapy group to a matched control group.Setting Medical intensive care unit at a university hospital.Patients Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group.Interventions Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group.Measurements ad results Cytokine levels [tumor necrosis factor- (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, -1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h later. After 24 h, TNF levels were significantly lower in the therapy group (p=0.013), while IL-6 levels were significantly higher in the therapy group (p=0.030). Within the 24 h TNF declined significantly in the therapy group (p=0.006), while IL-6 showed a significant increase (p=0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p=0.05), APACHE III score lower (p=0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p=0.0026) whereas the cardiac index declined (p=0.035).Conclusions PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.     

The pathophysiology of septic shock

Septic shock remains a significant challenge for clinicians. Recent advances in cellular and molecular biology have significantly improved our understanding of its pathogenetic mechanisms. These improvements in understanding should translate to better care and improved outcomes for these patients.     

Peripheral vascular resistance in septic shock: its relation to outcome

To support the concept that patients who die of septic shock have a persistent defect in peripheral vascular tone irrespective of cardiac index (CI), a retrospective study was undertaken of 42 patients with documented septic shock. From the patient records, the single lowest CI (t=2) measured after initial values (t=1) with concomitantly obtained haemodynamic and metabolic variables was taken. Group 1 consisted of 21 survivors and group 2 of 21 patients, who had died in shock. Initial haemodynamic and metabolic variables were comparable between the groups, reflecting shock with a hyperdynamic circulation and lactic acidemia. At t=2, median CI measured 3.21·min^-1·m^-2 in both groups, but mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were higher in group 1 than 2 (p<0.0005). Changes in arterial blood lactate levels also differed significantly. The rankcorrelation between CI and SVRI at t=2 was significant in group 1 (r _s=-0.69, p<0.005) but not in group 2 (r _s=-0.34). Our data suggest that when CI decreases in septic shock, patients with a fatal outcome have less capability to augment vascular resistance than survivors. Hence, peripheral vascular failure, even if complicated by inability to maintain an elevated CI, may be a major haemodynamic determinant of mortality in septic shock.     

Hemodynamic variables related to outcome in septic shock

Objective To assess the impact of hemodynamic variables on the outcome of critically ill patients in septic shock and to identify the optimal threshold values related to outcome with special reference to continuously monitored mean arterial pressure (MAP) and mixed venous oxygen saturation (SvO₂).Design and setting Retrospective cohort study in a university hospital intensive care unit (ICU).Patients All consecutive 111 patients with septic shock treated in our ICU between 1 Jan. 1999 and 30 Jan. 2002.Measurements and results The data on the hemodynamic and respiratory monitoring and circulation-related laboratory tests over the first 48 h of treatment in the ICU were collected from the clinical data management system. Data from 6 h and 48 h were analyzed separately. The 30-day mortality rate was 33% (36 of 111). Univariate analysis and forward stepwise logistic regression analysis were performed using the 30-day mortality as the primary endpoint. Mean MAP and lactate on arrival during 6 h, while mean MAP, the area of SvO₂ under 70%, and mean CVP during 48 h were independently associated with mortality. MAP level of 65 mmHg and SvO₂ of 70% had the highest areas under receiver characteristics curves.Conclusions MAP, SvO₂, CVP, and initial lactate were independently associated with mortality in septic shock, with threshold values supporting those published in recent guidelines.     

Effects of norepinephrine on right ventricular function in septic shock patients

Objective To study the effects of norepinephrine on right ventricular function in patients with hyperdynamic septic shock.Design Prospective, open study.Setting A 15 bed ICU in a university hospital.Patients 9 patients with hyperdynamic septic shock (SBP<90 mmHg, Cl4l·min^–1·m^–2, SVRI850 dynes·s·cm^–5m^–2 and oliguria).Interventions Plasma volume expansion was used to correct a suspected volume deficit and then, norepinephrine infusion was started and titrated to restore systemic blood pressure to the normal range (mean infusion rate: 1.1±0.2 mcg·kg^–1·min^–1). Norepinephrine was the only vasoactive agent used in these patients.Measurements and results A modified Swan-Ganz catheter mounted with a fast response thermistor was inserted in each patient, allowing repeated measurements of RVEDVI and RVEF. At time of inclusion to the study, all but one patient had elevated MPAP (23±4 mmHg) and RVEF50%, and all patients had RVEDVI90 ml·m^–2. During norepinephrine infusion, MAP increased from 51±9 to 89±10 mmHg (p<0.0001), PVRI increased from 204±35 to 286±63 dynes·s·cm^–5·m^–2 (p<0.05), and despite this increase in right ventricular afterload, no detrimental effect in RVEF (36±11 to 36±10%) or in RVEDVI (116±30 to 127±40 ml·m^–2) was observed. A Frank-Starling relationship for the right ventricle was constructed by plotting an index of ventricular performance (RVSWI) against an index of ventricular preload (RVEDVI). A significant upward shift to the right of the relationship was observed during norepinephrine infusion.Conclusion It was concluded that norepinephrine exerted a favourable effect on right ventricular function.Work done at Sainte Marguerite Hospital, Marseille, France     

不同剂量右美托咪定对脓毒症大鼠早期免疫调节的影响

目的通过对盲肠结扎穿孔（CLP）后的大鼠输注不同剂量右美托咪定来评估其免疫调节作用。方法48只盲肠结扎穿孔（CLP）后的 Wistar 大鼠随机（随机数字法）分为四组：（1）盲肠结扎穿孔组（CLP 组）;（2）2.5μg／（kg·h）右美托咪定治疗组（DEX2.5组）;（3）5μg／（kg·h）右美托咪定治疗组（DEX5.0组）;（4）10μg／（kg·h）右美托咪定治疗组（DEX10.0组）。监测 CLP 术后1 h、3 h 及5 h 的 HLA-DR 及细胞因子：IL-4、IL-6、IL-10及 TNF-α变化,同时监测平均动脉压（MAP）、心率（HR）,并计算24 h 病死率。结果右美托咪定治疗组（包括DEX2.5组,DEX5.0组,DEX10.0组）,各组间在 HLA-DR 水平、炎性介质水平、平均动脉压（MAP）及心率（HR）均无明显变化。与 CLP 组比较,右美托咪定治疗组（包括 DEX2.5组, DEX5.0组,DEX10.0组）的 HLA-DR 水平降低（P ＝0.020）,促炎介质 IL-6水平在 CLP 术后3 h时明显增加（P ＝0.011）,随后5 h 时下降,HR 明显下降（P ＜0.01）的同时 MAP 无明显变化（P ＝0.124）。与 CLP 组比较,右美托咪定治疗组的病死率的显著减少,且与剂量成正相关;CLP组,DEX2.5组,DEX5.0组,DEX10.0组病死率分别为91.7％,66.7％,25.0％和18.0％。结论右美托咪定在 CLP 脓毒症大鼠中持续输注5 h 内即开始诱导免疫调节,输注同时使 HR 显著下降并维持 MAP 稳定。随着右美托咪定输注剂量的增加,CLP 脓毒症大鼠的生存率显著改善。     

Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients

Objective Because recombinant human activated protein C (rhAPC) reduces NO production during sepsis, it could improve the vascular tone. We tested whether rhAPC reduces the dose of norepinephrine required to maintain mean arterial pressure (MAP) in septic shock patients.Design and setting Retrospective study in intensive care unit of two university hospitals.Patients Twenty-two septic shock patients with at least two organ failures were retrospectively investigated for MAP and the required dose of norepinephrine before and 24 h after rhAPC administration. A control group of 22 septic shock patients with at least two organ failures who did not receive rhAPC was matched on age, SAPS II, MAP, and norepinephrine dose at the time of the theoretical start of rhAPC.Measurements and results The MAP remained stable and similar in the two groups (86±16 vs. 89±9 mmHg at 24 h). The required dose of norepinephrine increased in the control group (+38%, from –41% to +38%) but decreased in the treated group (–33%, from –74% to +11%).Conclusions rhAPC rapidly improved the vascular tone in septic shock patients as assessed by a decrease in the norepinephrine dose required to maintain arterial pressure.