Association between septic shock prehospital hemodynamic parameters improvement and 28-day mortality
Septic shock prehospital hemodynamic parameters improvement and 28-day mortality
Abstract
Objective:
The early hemodynamic optimization of septic shock patients is a cornerstone of care to hope for a better outcome, e.g., mortality decrease. However, in the prehospital setting, hemodynamic evaluation is restricted to micro and macrocirculatory clinical parameters.
This study aims to assess the relationship between micro and macrocirculatory hemodynamic parameters improvement and 30-days mortality among septic shock patients being taken care of for by a mobile intensive care unit (mICU) in the prehospital setting.
Methods: We performed a retrospective multicenter study, from January 2015 to November 2019 including septic shock patients requiring pre-hospital mICU intervention.
Results: Three hundred thirty-seven patients were analyzed. The mean age was 69 ± 15-years-old and 226 of which 67% were male patients. One hundred thirty-six patients (40%) had previous hypertension. Pulmonary infection was the main cause of septic shock (46%) and 30-days mortality reached 30%.
After propensity score analysis, for the macrocirculation: when systolic blood pressure increased by at least 30mmHg the odd ratio (OR) for 30-days mortality was 0.77 [0.65-0.84], when diastolic blood pressure increased by at least 5mmHg, the OR for 30-days mortality was 0.95 [0.88-0.99], when mean blood pressure increased by at least 30%, the OR for 30-days mortality was 0.88 [0.77-0.92] and when the heart rate decreased by at least 30 bpm, the OR for 30-days mortality was 0.62 [0.55-0.76]. For microcirculation, when the mottling score decreased by at least 2 points, the OR for 30-days mortality was 0.83 [0.75-0.91].
Conclusion: In this study, we report that prehospital improvement in micro and macrocirculatory parameters are associated with 30-days mortality rate decrease.
References
Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K; International Forum of Acute Care Trialists. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. doi: 10.1164/rccm.201504-0781OC. PMID: 26414292.
Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013 May;41(5):1167-74. doi: 10.1097/CCM.0b013e31827c09f8. PMID: 23442987.
Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7. PMID: 31954465; PMCID: PMC6970225.
Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, Iwashyna TJ. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014 Jul 2;312(1):90-2. doi: 10.1001/jama.2014.5804. PMID: 24838355.
Busani S, Damiani E, Cavazzuti I, Donati A, Girardis M. Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness. Minerva Anestesiol. 2016 May;82(5):559-72. Epub 2015 Oct 16. PMID: 26474267.
Luhr R, Cao Y, Söderquist B, Cajander S. Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002-2016. Crit Care. 2019 Jul 3;23(1):241. doi: 10.1186/s13054-019-2528-0. PMID: 31269976; PMCID: PMC6610784.
Sakr Y, Elia C, Mascia L, Barberis B, Cardellino S, Livigni S, Fiore G, Filippini C, Ranieri VM. Epidemiology and outcome of sepsis syndromes in Italian ICUs: a muticentre, observational cohort study in the region of Piedmont. Minerva Anestesiol. 2013 Sep;79(9):993-1002. Epub 2013 Jun 25. PMID: 23811620.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. PMID: 26903338; PMCID: PMC4968574.
Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Bounes V, Boularan J, Léguillier T, Gueye-Ngalgou P, Vivien B. Impact of Prehospital Antibiotic Therapy on Septic Shock Mortality. Prehosp Emerg Care. 2021 May-Jun;25(3):317-324. doi: 10.1080/10903127.2020.1763532. Epub 2020 May 15. PMID: 32352890.
Nauclér P, Huttner A, van Werkhoven CH, Singer M, Tattevin P, Einav S, Tängdén T. Impact of time to antibiotic therapy on clinical outcome in patients with bacterial infections in the emergency department: implications for antimicrobial stewardship. Clin Microbiol Infect. 2021 Feb;27(2):175-181. doi: 10.1016/j.cmi.2020.02.032. Epub 2020 Feb 29. PMID: 32120032.
Peltan ID, Brown SM, Bledsoe JR, Sorensen J, Samore MH, Allen TL, Hough CL. ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis. Chest. 2019 May;155(5):938-946. doi: 10.1016/j.chest.2019.02.008. Epub 2019 Feb 16. PMID: 30779916; PMCID: PMC6533450.
Timing of antibiotics in septic patients: a prospective cohort study - Clinical Microbiology and Infection [Internet]. 2020 Feb [cited 2020 June 6]. Available from: https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30089-6/pdf
Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017 Jun 8;376(23):2235-2244. doi: 10.1056/NEJMoa1703058. Epub 2017 May 21. PMID: 28528569; PMCID: PMC5538258.
Singer M. Antibiotics for Sepsis: Does Each Hour Really Count, or Is It Incestuous Amplification? [Internet]. American journal of respiratory and critical care medicine. 2017 [cited 2020 June 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/28504905/
Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis. Crit Care Med. 2015 Sep;43(9):1907-15. doi: 10.1097/CCM.0000000000001142. PMID: 26121073; PMCID: PMC4597314.
Leisman DE, Doerfler ME, Ward MF, et al. Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts. Critical Care Medicine. 2017 Mar;45(3):395-406. DOI: 10.1097/ccm.0000000000002184. PMID: 27941371.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18. PMID: 28101605.
Jouffroy R, Vivien B. Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: antibiotic action needs time and tissue perfusion to reach target. Crit Care. 2020 Jan 14;24(1):17. doi: 10.1186/s13054-020-2727-8. PMID: 31937340; PMCID: PMC6958718.
Brun-Buisson C, Meshaka P, Pinton P, Vallet B; EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004 Apr;30(4):580-8. doi: 10.1007/s00134-003-2121-4. Epub 2004 Mar 2. PMID: 14997295.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9. PMID: 16625125.
Kung HC, Xu J. Hypertension-related Mortality in the United States, 2000-2013. NCHS Data Brief. 2015 Mar;(193):1-8. PMID: 25932893.
Unal AU, Kostek O, Takir M, Caklili O, Uzunlulu M, Oguz A. Prognosis of patients in a medical intensive care unit. North Clin Istanb. 2015 Dec 31;2(3):189-195. doi: 10.14744/nci.2015.79188. PMID: 28058366; PMCID: PMC5175105.
Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Hervé F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18. PMID: 24635770.
Hylands M, Moller MH, Asfar P, Toma A, Frenette AJ, Beaudoin N, Belley-Côté É, D'Aragon F, Laake JH, Siemieniuk RA, Charbonney E, Lauzier F, Kwong J, Rochwerg B, Vandvik PO, Guyatt G, Lamontagne F. A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension. Can J Anaesth. 2017 Jul;64(7):703-715. English. doi: 10.1007/s12630-017-0877-1. Epub 2017 May 11. PMID: 28497426.
Lamontagne F, Meade MO, Hébert PC, Asfar P, Lauzier F, Seely AJE, Day AG, Mehta S, Muscedere J, Bagshaw SM, Ferguson ND, Cook DJ, Kanji S, Turgeon AF, Herridge MS, Subramanian S, Lacroix J, Adhikari NKJ, Scales DC, Fox-Robichaud A, Skrobik Y, Whitlock RP, Green RS, Koo KKY, Tanguay T, Magder S, Heyland DK; Canadian Critical Care Trials Group.. Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med. 2016 Apr;42(4):542-550. doi: 10.1007/s00134-016-4237-3. Epub 2016 Feb 18. PMID: 26891677.
Adnet F, Lapostolle F. International EMS systems: France. Resuscitation. 2004 Oct;63(1):7-9. doi: 10.1016/j.resuscitation.2004.04.001. PMID: 15451580.
Le Borgne P, Kam C, Bilbault P. Marbrures : expression clinique de la dysfonction microcirculatoire dans le choc septique. Ann. Fr. Med. Urgence. May 2016;6(3):212 3. https://doi.org/10.1007/s13341-016-0637-9
Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993 Dec 22-29;270(24):2957-63. doi: 10.1001/jama.270.24.2957. Erratum in: JAMA 1994 May 4;271(17):1321. PMID: 8254858.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG. 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 Jul;22(7):707-10. doi: 10.1007/BF01709751. PMID: 8844239.
Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8. PMID: 21818162; PMCID: PMC3144483.
Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009 Nov 10;28(25):3083-107. doi: 10.1002/sim.3697. PMID: 19757444; PMCID: PMC3472075.
Ait-Oufella H, Bige N, Boelle PY, Pichereau C, Alves M, Bertinchamp R, Baudel JL, Galbois A, Maury E, Guidet B. Capillary refill time exploration during septic shock. Intensive Care Med. 2014 Jul;40(7):958-64. doi: 10.1007/s00134-014-3326-4. Epub 2014 May 9. PMID: 24811942.
Ait-Oufella H, Lemoinne S, Boelle PY, Galbois A, Baudel JL, Lemant J, Joffre J, Margetis D, Guidet B, Maury E, Offenstadt G. Mottling score predicts survival in septic shock. Intensive Care Med. 2011 May;37(5):801-7. doi: 10.1007/s00134-011-2163-y. Epub 2011 Mar 4. PMID: 21373821.
Charlton M, Sims M, Coats T, Thompson JP. The microcirculation and its measurement in sepsis. J Intensive Care Soc. 2017 Aug;18(3):221-227. doi: 10.1177/1751143716678638. Epub 2016 Nov 10. PMID: 29118834; PMCID: PMC5665123.
De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002 Jul 1;166(1):98-104. doi: 10.1164/rccm.200109-016oc. PMID: 12091178.
Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004 Sep;32(9):1825-31. doi: 10.1097/01.ccm.0000138558.16257.3f. PMID: 15343008.
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. Erratum in: N Engl J Med. 2013 Nov 21;369(21):2069. PMID: 23984731.
Jouffroy R, Saade A, Tourtier JP, Gueye P, Bloch-Laine E, Ecollan P, Carli P, Vivien B. Skin mottling score and capillary refill time to assess mortality of septic shock since pre-hospital setting. Am J Emerg Med. 2019 Apr;37(4):664-671. doi: 10.1016/j.ajem.2018.07.010. Epub 2018 Jul 6. PMID: 30001815.
Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K, Dong Y, Xu L, Li N. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care. 2014 Oct 3;18(5):532. doi: 10.1186/s13054-014-0532-y. PMID: 25277635; PMCID: PMC4194405.
Hamzaoui O, Georger JF, Monnet X, Ksouri H, Maizel J, Richard C, Teboul JL. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Crit Care. 2010;14(4):R142. doi: 10.1186/cc9207. Epub 2010 Jul 29. PMID: 20670424; PMCID: PMC2945123.
Morimatsu H, Singh K, Uchino S, Bellomo R, Hart G. Early and exclusive use of norepinephrine in septic shock. Resuscitation. 2004 Aug;62(2):249-54. doi: 10.1016/j.resuscitation.2004.03.016. PMID: 15294412.
Dünser MW, Takala J, Ulmer H, Mayr VD, Luckner G, Jochberger S, Daudel F, Lepper P, Hasibeder WR, Jakob SM. Arterial blood pressure during early sepsis and outcome. Intensive Care Med. 2009 Jul;35(7):1225-33. doi: 10.1007/s00134-009-1427-2. Epub 2009 Feb 3. PMID: 19189077.
Immink RV, van den Born BJ, van Montfrans GA, Koopmans RP, Karemaker JM, van Lieshout JJ. Impaired cerebral autoregulation in patients with malignant hypertension. Circulation. 2004 Oct 12;110(15):2241-5. doi: 10.1161/01.CIR.0000144472.08647.40. Epub 2004 Oct 4. PMID: 15466625.
Autoregulation of Brain Circulation in Severe Arterial Hypertension | The BMJ [Internet]. 1973 March [cited 2020 June 6]. Available from: https://www.bmj.com/content/1/5852/507.short, doi: https://doi.org/10.1136/bmj.1.5852.507
Bourgoin A, Leone M, Delmas A, Garnier F, Albanèse J, Martin C. Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med. 2005 Apr;33(4):780-6. doi: 10.1097/01.ccm.0000157788.20591.23. PMID: 15818105.
LeDoux D, Astiz ME, Carpati CM, Rackow EC. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med. 2000 Aug;28(8):2729-32. doi: 10.1097/00003246-200008000-00007. PMID: 10966242.
Xu JY, Ma SQ, Pan C, He HL, Cai SX, Hu SL, Liu AR, Liu L, Huang YZ, Guo FM, Yang Y, Qiu HB. A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study. Crit Care. 2015 Mar 30;19(1):130. doi: 10.1186/s13054-015-0866-0. PMID: 25887027; PMCID: PMC4409762.
Thooft A, Favory R, Salgado DR, Taccone FS, Donadello K, De Backer D, Creteur J, Vincent JL. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care. 2011;15(5):R222. doi: 10.1186/cc10462. Epub 2011 Sep 21. PMID: 21936903; PMCID: PMC3334768.
Lee GT, Hwang SY, Jo IJ, Kim TR, Yoon H, Park JH, Cha WC, Sim MS, Shin TG. Associations between mean arterial pressure and 28-day mortality according to the presence of hypertension or previous blood pressure level in critically ill sepsis patients. J Thorac Dis. 2019 May;11(5):1980-1988. doi: 10.21037/jtd.2019.04.108. PMID: 31285891; PMCID: PMC6588786.
ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18. PMID: 24635773; PMCID: PMC4101700.
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Copyright (c) 2023 Romain Jouffroy, Basile Gilbert, Papa Gueye, Léa Thomas, Emmanuel Bloch Laine, Patrick Ecollan, Josiane Boularan, Vincent Bounes, Benoit Vivien
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