(2.1.1)--病理生理学病理生理学Intravenous+iloprost+to+recruit+.pdf

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1、Intensive Care MedDOI 10.1007/s00134-017-4935-5LETTERIntravenous iloprost torecruit the microcirculation inseptic shock patients?Franois Dpret1,2,Alexandre Sitbon1,Sabri Soussi1,Christian De Tymowski1,Alice Blet1,3,Alexandre Fratani1 and Matthieu Legrand1,2,3,4*2017 Springer-Verlag GmbH Germany and

2、ESICMDear Editor,Microcirculatory perfusion alterations have been associ-ated with poor outcome in septic shock patient.To date,there is no available treatment to improve the perfusion at the microcirculatory level with the ultimate goal to improve outcome in septic shock patients 1,2.Iloprost,an an

3、alogue of prostaglandin I2(PGI2),has been used in critical limb ischemia,intestinal critical ischemia,and frost bite to recruit the microcirculation and improve tis-sue perfusion.Iloprost acts as a vasodilator,inductor of fibrinolysis,inhibitor of leukocyte adhesion,and plate-let aggregation,all fac

4、tors contributing to microcircula-tory dysfunction in septic shock 3.Iloprost improved mesenteric or kidney perfusion in experimental sepsis but clinical data are lacking 4.In this proof-of-concept report we describe the utilization of iloprost as a compas-sionate salvage therapy in four septic shoc

5、k patients with multiple organ failure and apparition or persistent signs of hypoperfusion despite macrohemodynamics optimiza-tion.The delay between norepinephrine onset and start of iloprost infusion was 43(range 1797)h.Age was 775years,SAPS2 on admission was 583,and SOFA before iloprost infusion w

6、as 112.Three out of four patients had a history of hypertension,two of diabetes,and two had cancer.The source of sepsis was abdominal in three(biliary peritonitis,perforated sig-moiditis,stercoral peritonitis after Hartmann interven-tion)and urinary tract in one(obstructive pyelonephritis complicate

7、d by left ischemic colitis).All patients received broad spectrum antibiotic and norepinephrine;three received dobutamine,and two received renal replace-ment therapy before iloprost introduction.The maxi-mum dosage of iloprost used for the four patients was 1.250.28ng/kg/min.Even though we did not di

8、rectly assess the microcircu-lation,we used skin mottling as a surrogate of microcir-culation disorders 5.All patients presented persistent signs of hypoperfusion despite macrocirculation opti-mization with extensive skin mottling,cold extremities,and increased skin recoloration time.We noticed a cl

9、ini-cal improvement of hypoperfusion signs in all patients within 3h after iloprost infusion(Fig.1),arterial lactate dropped from 7.96.6 to 1.82.2mmol/L.Cardiac index significantly increased whereas mean arterial pres-sure,central venous pressure,and norepinephrine dosage were not significantly affe

10、cted(Table 1 supplementary material).Patients 1 and 3 were discharged alive from hospital.The results of this case series suggest that iloprost may recruit the microcirculation in septic shock refractory to macrohemodynamic optimization.Persistent microcir-culatory disorders are associated with very

11、 poor outcome in sepsis 5.Furthermore,clinical assessment of skin perfusion(using mottling score or capillary refill time)has been reported to accurately reflect microcirculatory disorders in critically ill patients and predict outcome 5.Strategies to recruit the microcirculation when resuscita-tion

12、 with fluid,vasopressors,and/or inotropes has failed remain,however,lacking.Accumulating preclinical and clinical data suggest that iloprost might fill this gap 3.*Correspondence:matthieu.legrandaphp.fr 1 GH St-Louis-Lariboisire,Department of Anesthesiology and Critical Care and Burn Unit,St-Louis H

13、ospital,Assistance Publique-Hopitaux de Paris(AP-HP),Paris,FranceFull author information is available at the end of the articleIn this series we observed a clear and sustained improvement of the peripheral perfusion.Iloprost appeared to be well tolerated with no side effects noticed and improvement

14、in macrohemodynamic.Prospective,observational,and randomized studies are now eagerly needed to confirm this hypothesis.Electronic supplementary materialThe online version of this article(doi:10.1007/s00134-017-4935-5)contains supplementary material,which is available to authorized users.Author detai

15、ls1 GH St-Louis-Lariboisire,Department of Anesthesiology and Critical Care and Burn Unit,St-Louis Hospital,Assistance Publique-Hopitaux de Paris(AP-HP),Paris,France.2 University Paris Diderot,Paris,France.3 UMR INSERM 942,Institut National de la Sant et de la Recherche Mdicale(INSERM),Lariboisire Ho

16、spital Univ Paris Diderot,75475 Paris,France.4 F-CRIN,INI-CRCT,Paris,France.Accepted:7 September 2017References 1.Perner A,Gordon AC,Angus DC et al(2017)The intensive care medicine research agenda on septic shock.Intensive Care Med.doi:10.1007/s00134-017-4821-1 2.Legrand M,Bezemer R,Kandil A et al(2

17、011)The role of renal hypop-erfusion in development of renal microcirculatory dysfunction in endotoxemic rats.Intensive Care Med 37:15341542.doi:10.1007/s00134-011-2267-4 3.Mller B,Schmidtke M(1987)Microvascular effects of iloprost in the hamster cheek pouch.Adv Prostaglandin Thromboxane Leukot Res

18、17A:455458 4.Johannes T,Ince C,Klingel K et al(2009)Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in the rat.Crit Care Med 37:14231432.doi:10.1097/CCM.0b013e31819b5f4e 5.Ait-Oufella H,Lemoinne S,Boelle PY et al(2011)Mottling score predicts survival in septic shock.Intensive Care Med 37:801807.doi:10.1007/s00134-011-2163-yFig.1 Effect of iloprost on mottling in three patients.Picture from the fourth patient could not be retrieved