This case describes the first reported use of human-derived synthetic angiotensin II (Ang-2) in a patient with decompensated cirrhosis and septic shock. The patient presented in vasodilatory shock from Enterobacter cloacae bacteremia with a Sequential Organ Failure Assessment Score of 14 and a Model for End-Stage Liver Disease score of 36. This case is significant because liver failure was an exclusion criterion in the Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) trial, but the liver produces angiotensinogen, which is key precursor to Ang-2 in the renin-angiotensin-aldosterone system. Resuscitation with Ang-2 is a potentially beneficial medication when conventional vasopressors have failed to control mean arterial pressure in this population.
NadimMKDurandFKellumJA, et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol. 2016;64:717-735.
2.
OlsonJCKarvellasCJ.Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit. Liver Transpl. 2017;23:1465-1476.
3.
AcevedoJFernándezJPradoV, et al. Relative adrenal insufficiency in decompensated cirrhosis: relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death. Hepatology. 2013;58:1757-1765.
4.
TrifanAChiriacSStanciuC.Update on adrenal insufficiency in patients with liver cirrhosis. World J Gastroenterol. 2013;19:445-456.
5.
WagenerGKovalevskayaGMinhazMMattisFEmondJCLandryDW.Vasopressin deficiency and vasodilatory state in end-stage liver disease. J Cardiothorac Vasc Anesth. 2011;25:665-670.
6.
KhaliqueSCFergusonN.Angiotensin II (Giapreza): a distinct mechanism for the treatment of vasodilatory shock. Cardiol Rev. 2019;27:167-169.
7.
KhannaAEnglishSWWangXS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419-430.
8.
ChawlaLSChenSBellomoRTidmarshGF.Angiotensin converting enzyme defects in shock: implications for future therapy. Crit Care. 2018;22:274.
9.
YiannikourisFWangYShoemakerR, et al. Deficiency of angiotensinogen in hepatocytes markedly decreases blood pressure in lean and obese male mice. Hypertension. 2015;66:836-842.
10.
BassoNTerragnoNA.History about the discovery of the renin-angiotensin system. Hypertension. 2001;38:1246-1249.
11.
FerrarioCMAhmadSVaragicJ, et al. Intracrine angiotensin II functions originate from noncanonical pathways in the human heart. Am J Physiol Heart Circ Physiol. 2016;311:H404-H414.
12.
SaidAWilliamsJHoldenJ, et al. Model for end stage liver disease score predicts mortality across a broad spectrum of liver disease. J Hepatol. 2004;40:897-903.
13.
FerreiraFLBotaDPBrossAMélotCVincentJL.Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286:1754-1758.
14.
VincentJLMorenoRTakalaJ, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707-710.
15.
MarikPEKhangooraVRiveraRHooperMHCatravasJ.Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151:1229-1238.
16.
ChawlaLSOstermannMForniLTidmarshGF.Broad spectrum vasopressors: a new approach to the initial management of septic shock?Crit Care. 2019;23:124.
17.
ArnalJFCudekPPlouinPFGuyenneTTMichelJBCorvolP.Low angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements. Am J Med. 1991;90:17-22.
MyburghJAHigginsAJovanovskaALipmanJRamakrishnanNSantamariaJ; CAT Study investigators. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med. 2008;34:2226-2234.
20.
RussellJAWalleyKRSingerJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877-887.
21.
ZhouFMaoZZengX, et al. Vasopressors in septic shock: a systematic review and network meta-analysis. Ther Clin Risk Manag. 2015;11:1047-1059.
22.
DunserMWMayrAJTürA, et al. Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med. 2003;31:1394-1398.
23.
RodriguezRCucciMKaneSFernandezEBenkenS. Novel vasopressors in the treatment of vasodilatory shock: a systematic review of angiotensin II, selepressin, and terlipressin [published online December 18, 2018]. J Intensive Care Med. doi:10.1177/0885066618818460
24.
WakefieldBJBusseLWKhannaAK.Angiotensin II in vasodilatory shock. Crit Care Clin. 2019;35:229-245.
25.
CorreaTDTakalaJJakobSM.Angiotensin II in septic shock. Crit Care. 2015;19:98.
ChowJHGalvagnoSMJrTanakaKA, et al. When all else fails: novel use of angiotensin II for vasodilatory shock: a case report. A A Pract. 2018;11:175-180.
28.
EvansAMcCurdyMTWeinerMZakuBChowJH.Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome. Ann Thorac Surg. 2019;108:e5-e7.
29.
BusseLWMcCurdyMTAliOHallAChenHOstermannM.The effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literature. Crit Care. 2017;21:324.
30.
MederleKSchwedaFKattlerV, et al. The angiotensin II AT1 receptor-associated protein Arap1 is involved in sepsis-induced hypotension. Crit Care. 2013;17:R130.
31.
LemarieCASchiffrinEL.The angiotensin II type 2 receptor in cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2010;11:19-31.
32.
AkinagaJLimaVKigutiLR, et al. Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline. Mol Pharmacol. 2013;83:870-881.
33.
LuHCassisLAKooiCWDaughertyA.Structure and functions of angiotensinogen. Hypertens Res. 2016;39:492-500.
34.
KashaniALandaverdeCMediciVRossaroL.Fluid retention in cirrhosis: pathophysiology and management. QJM. 2008;101:71-85.
35.
SilvaACSEMirandaASRochaNPTeixeiraAL. Renin angiotensin system in liver diseases: friend or foe?World J Gastroenterol. 2017;23:3396-3406.
36.
El-RazikyMSGoharNEl-RazikyM.Study of substance P, renin and aldosterone in chronic liver disease in Egyptian children. J Trop Pediatr. 2005;51:320-323.
37.
WongPYTalamoRCWilliamsGH.Kallikrein-kinin and renin-angiotensin systems in functional renal failure of cirrhosis of the liver. Gastroenterology. 1977;73:1114-1118.
38.
WunderinkRGAlbertsonTEBusseLW, et al. Baseline angiotensin levels and ACE effects in patients with vasodilatory shock treated with angiotensin II. Intensive Care Med Exp. 2017;5(suppl 2):0703.
39.
RochwergBOczkowskiSJSiemieniukRAC, et al. Corticosteroids in sepsis: an updated systematic review and meta-analysis. Crit Care Med. 2018;46:1411-1420.
40.
AnnaneDRenaultABrun-BuissonC, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378:809-818.
41.
VenkateshBFinferSCohenJ, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797-808.
42.
WoolumJAAbnerELKellyABastinMLTMorrisPEFlanneryAH.Effect of thiamine administration on lactate clearance and mortality in patients with septic shock. Crit Care Med. 2018;46:1747-1752.
43.
FowlerAA3rdSyedAAKnowlsonS, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32.
44.
MayJMHarrisonFE.Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013;19:2068-2083.
