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Septic Shock

Date Last Search Run: Jan 14, 2025
Table last updated: Jan 28, 2025
Data last added: Jan 28, 2025

Recommendation RECOMMENDATION FOR INTERVENTION
STRENGTH OF EVIDENCE FOR INTERVENTION   SUPPORTIVE (Green) NEUTRAL (Yellow) AGAINST (Red) NOT YET GRADED (White)
1 (strong evidence exists)  
2 (fair evidence exists)    
3 (weak evidence exists)  


Interventions

Balanced crystalloids
Level Direction Primary Outcome Patient/Process Setting Reference
II Supportive (Green) 30-day mortality Patient Other Jouffroy R, Gilbert B, Gueye PN, Tourtier JP, Bloch-Laine E, Ecollan P, et al. Prehospital hemodynamic optimisation is associated with a 30-day mortality decrease in patients with septic shock. Am J Emerg Med 2021; 45:105-11. Medline
II Supportive (Green) In-hospital mortality Patient ED-MD Sethi M, Owyang CG, Meyers C, Parekh R, Shah KH, Manini AF. Choice of resuscitative fluids and mortality in emergency department patients with sepsis. Am J Emerg Med 2018; 36(4):625-9. Medline
II Supportive (Green) Mortality Patient In-Patient Winters ME, Sherwin R, Vilke GM, Wardi G. What is the Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock? J Emerg Med 2017; 53(6):928-39. Medline

Colloid Infusion
Level Direction Primary Outcome Patient/Process Setting Reference
I Neutral (Yellow) Mortality Patient Bunn F., Trivedi D., Ashraf S. Colloid solutions for fluid resuscitation. Cochrane Database of Systematic Reviews 2008; 1. Cochrane Library
I Neutral (Yellow) Mortality Patient Perel P., Roberts IG. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews 2007; (4). Cochrane Library
I Opposes (Red) 6 month mortality Patient Perner A., Haase N., Winkel P., et al. Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or ringer's acetate. Intensive Care Med 2014; 40(7):927-34. Medline
III Supportive (Green) Mortality Patient ED-MD Velanovich V. Crystalloid versus colloid fluid resuscitation: A meta-analysis of mortality. Surgery 1989; 105:65-71. Medline

Crystalloid Infusion
Level Direction Primary Outcome Patient/Process Setting Reference
I Neutral (Yellow) Mortality Patient PH-Paramedic & MD Ward MA, Kuttab HI, Tuck N, Taleb A, Okut H, Badgett RG. The Effect of Fluid Initiation Timing on Sepsis Mortality: A Meta-Analysis. J Intensive Care Med 2022; 8850666221118513. Medline
II Neutral (Yellow) In-hospital mortality Patient ED-MD Sethi M, Owyang CG, Meyers C, Parekh R, Shah KH, Manini AF. Choice of resuscitative fluids and mortality in emergency department patients with sepsis. Am J Emerg Med 2018; 36(4):625-9. Medline
II Neutral (Yellow) Goal MAP Process Seymour CW., Cooke CR., Mikkelsen ME., Hylton J., Rea TD., Goss CH., et al. Out-of-hospital fluid in severe sepsis: effect on early resuscitation in the emergency department. Prehosp Emerg Care 2010; 14(2):145-152. Medline
II Neutral (Yellow) Mortality Patient Winters ME, Sherwin R, Vilke GM, Wardi G. What is the Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock? J Emerg Med 2017; 53(6):928-39. Medline
II Neutral (Yellow) Time to treatment; mortality; length of stay Patient ED-MD Xantus GZ, Allen P, Norman S, Kanizsai PL. Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis. Emerg Med J 2021; 38(6):430-8. Medline
III Neutral (Yellow) Improvement of hypotension Patient Lipcsey M., Chiong J., Subiakto I., Kaufman MA., Schneider AG., Bellomo R. Primary fluid bolus therapy for infection-associated hypotension in the emergency department. Crit Care Resusc 2015; 17(1):6-11. Medline
III Neutral (Yellow) Mortality, length of stay due to sepsis Patient ED-Paramedic & CCP Xantus GZ, Allen P, Norman S, Kanizsai PL. Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis. Emerg Med J 2021; 38(6):430-8. Medline

Dobutamine
Level Direction Primary Outcome Patient/Process Setting Reference
III Supportive (Green) Oxygen delivery Patient Vincent JL., Roman A., Kahn RJ. Dobutamine administration in septic shock: Addition to standard protocol. Critical Care Med 1990; 18:689-693. Medline

Dopamine
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Death at 28 days Patient ICU De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar 4;362(9):779-89. doi: 10.1056/NEJMoa0907118. PMID: 20200382. Medline
I Supportive (Green) All-cause 28-day mortality. Patient ICU Patel GP, Grahe JS, Sperry M, Singla S, Elpern E, Lateef O, Balk RA. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock. 2010 Apr;33(4):375-80. doi: 10.1097/SHK.0b013e3181c6ba6f. PMID: 19851126. Medline
I Opposes (Red) Mortality Patient ED-MD De Backer D, Aldecoa C, Njimi H, Vincent JL. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis*. Crit Care Med. 2012 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee. PMID: 22036860. Medline

Epinephrine
Level Direction Primary Outcome Patient/Process Setting Reference
III Supportive (Green) Mortality Patient PH-MD & CCT Braham D, Adams DWS, Johnson R. Pre-hospital “dirty adrenaline”: A descriptive case series of patients receiving peripheral dilute adrenaline infusions in Central Australian remote nurse-led clinics prior to aeromedical retrieval. Emerg Med Australas Sept 2024. Medline
III Supportive (Green) Hemodynamic effect Patient ED-MD Nawrocki PS., Poremba M., Lawner BJ. Push Dose Epinephrine Use in the Management of Hypotension During Critical Care Transport. Prehospital emergency care 2019:1-8. Medline

Hypertonic Saline
Level Direction Primary Outcome Patient/Process Setting Reference

Liberal fluid management
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Survival Patient ED-MD & CCP Rajdev K, Leifer L, Sandhu G, Mann B, Pervaiz S, Lahan S, et al. Aggressive versus conservative fluid resuscitation in septic hemodialysis patients. Am J Emerg Med 2021; 46:416–9. Medline
I Supportive (Green) All cause mortality Patient ICU Silversides JA, Major E, Ferguson AJ, et al. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017;43(2):155–170. Medline
I Neutral (Yellow) Mortality Patient Other Xantus GZ, Allen P, Norman S, Kanizsai PL. Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis. Emerg Med J 2021; 38(6):430-8. Medline
II Supportive (Green) 30-Day Mortality attributable to sepsis Patient ED-MD Eisenberg MA, Riggs R, Paul R, Balamuth F, Richardson T, et al. Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock. Ann Emerg Med 2022; 80(3):213–24. Medline
II Supportive (Green) 30 day mortalitiy Patient ED-Paramedic & MD Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Pressat-Laffouilhère T, Gueye P. Prehospital Bundle of Care Based on Antibiotic Therapy and Hemodynamic Optimization Is Associated With a 30-Day Mortality Decrease in Patients With Septic Shock. Crit Care Med 2022; 50(10):1440–8. Medline
II Supportive (Green) 28 day mortality Patient PH-MD & CCT Jouffroy R., Saade A., Muret A., Philippe P., Michaloux M., Carli P., et al. Fluid resuscitation in pre-hospital management of septic shock. Am J Emerg Med 2018; 36(10):1754-8. Medline
II Supportive (Green) Detection and septic shock Patient ED-MD Leisman D., Wie B., Doerfler M., Bianculli A., Ward MF., Akerman M., et al. Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay. Ann Emerg Med 2016; 68(3):298-311. Medline
II Supportive (Green) In-hospital mortality Patient ED-MD Leisman DE., Goldman C., Doerfler ME., Masick KD., Dries S., Hamilton E., et al. Patterns and Outcomes Associated With Timeliness of Initial Crystalloid Resuscitation in a Prospective Sepsis and Septic Shock Cohort. Crit Care Med 2017; 45(10):1596-606. Medline
II Neutral (Yellow) Mortality Patient PH-Paramedic Femling J., Weiss S., Hauswald E., Tarby D. EMS patients and walk-in patients presenting with severe sepsis: Differences in management and outcome. South Med J 2014; 107(12):751-6. Medline
II Neutral (Yellow) Mortality Patient Other Xantus GZ, Allen P, Norman S, Kanizsai PL. Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis. Emerg Med J 2021; 38(6):430-8. Medline
II Opposes (Red) Mortality Patient PH-Paramedic Lane DJ., Wunsch H., Saskin R., Cheskes S., Lin S., Morrison LJ., et al. Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis. JAMA network open 2018; 1(8):e185845. Medline
III Supportive (Green) Volume of fluid administered Process ICU Chen C, Kollef MH. Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study. Chest. 2015;148(6):1462–1469. doi:10.1378/chest.15-1525 Medline
III Supportive (Green) Total fluid administered Process ICU Hjortrup PB, Haase N, Bundgaard H, et al. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med. 2016;42(11):1695–1705. Medline
III Supportive (Green) Feasibility Process ED-MD Macdonald SPJ., Keijzers G., Taylor DM., Kinnear F., Arendts G., Fatovich DM., et al. Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial. Intensive Care Med 2018; 44(12):2070-8. Medline
III Supportive (Green) Increased stroke volume Process ED-MD Oord M., Olgers TJ., Doff-Holman M., Harms MP., Ligtenberg JJ., Ter Maaten JC. Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild sepsis in the emergency department: a pilot study. BMJ Open 2017; 7(1):e013465. Medline
III Neutral (Yellow) Resolution of shock Patient ICU Richard JC, Bayle F, Bourdin G, et al. Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial. Crit Care. 2015;19(1):5. Published 2015 Jan 8. Medline

Norepinephrine
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Mortality Patient ED-MD De Backer D, Aldecoa C, Njimi H, Vincent JL. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis*. Crit Care Med. 2012 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee. PMID: 22036860. Medline
I Supportive (Green) Death at 28 days Patient ICU De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar 4;362(9):779-89. doi: 10.1056/NEJMoa0907118. PMID: 20200382. Medline
I Supportive (Green) All-cause 28-day mortality. Patient ICU Patel GP, Grahe JS, Sperry M, Singla S, Elpern E, Lateef O, Balk RA. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock. 2010 Apr;33(4):375-80. doi: 10.1097/SHK.0b013e3181c6ba6f. PMID: 19851126. Medline
I Supportive (Green) Shock control rate Patient ED-MD Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019; 199(9):1097-1105. Medline
II Supportive (Green) 30 day mortalitiy Patient ED-Paramedic & MD Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Pressat-Laffouilhère T, Gueye P. Prehospital Bundle of Care Based on Antibiotic Therapy and Hemodynamic Optimization Is Associated With a 30-Day Mortality Decrease in Patients With Septic Shock. Crit Care Med 2022; 50(10):1440–8. Medline
II Supportive (Green) 30-day mortality Patient PH-MD & CCT Jouffroy R, Hajjar A, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye PN. Prehospital norepinephrine administration reduces 30-day mortality among septic shock patients. BMC Infect Dis 2022; 22(1):345. Medline
II Supportive (Green) Complications Patient Other Ley Greaves R, Bolot R, Holgate A, Gibbs C. Safety of pre-hospital peripheral vasopressors: The SPOTLESS study (Safety of PrehOspiTaL pEripheral vaSopreSsors). Emerg Med Australas February 2024. Medline
III Supportive (Green) Adverse events incidence Patient ED-MD Messina A, Milani A, Morenghi E, Costantini E, Brusa S, Negri K, et al. Norepinephrine Infusion in the Emergency Department in Septic Shock Patients: A Retrospective 2-Years Safety Report and Outcome Analysis. Int J Environ Res Public Health 2021; 18(2). Medline

Shock Prediction Tool
Level Direction Primary Outcome Patient/Process Setting Reference
II Supportive (Green) Acuity prediction & progress of pediatric severe sepsis Patient ED-MD Gupta S, Alam A. Shock index is better than conventional vital signs for assessing higher level of care and mortality in severe sepsis or shock. Am J Emerg Med 2021; 46:545–9. Medline
II Supportive (Green) 28 day mortality Process PH-MD & CCT Jouffroy R, Gilbert B, Thomas L, Bloch-Laine E, Ecollan P, Boularan J, Gueye PN. Association between prehospital shock index variation and 28-day mortality among patients with septic shock. BMC Emerg Med 2022; 22(1):87. Medline
III Supportive (Green) 28-day mortality Process PH-MD & CCT Jouffroy R, Gille S, Gilbert B, et al. RELATIONSHIP BETWEEN SHOCK INDEX, MODIFIED SHOCK INDEX, AND AGE SHOCK INDEX AND 28-DAY MORTALITY AMONG PATIENTS WITH PREHOSPITAL SEPTIC SHOCK. J Emerg Med February 2024; 66(2):144-53. Medline

Titrated fluid management
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) All cause mortality Patient ICU Silversides JA, Major E, Ferguson AJ, et al. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017;43(2):155–170. Medline
II Supportive (Green) 30-day mortality Patient PH-Paramedic & MD Jouffroy R, Gilbert B, Gueye PN, Tourtier JP, Bloch-Laine E, Ecollan P, et al. Prehospital hemodynamic optimisation is associated with a 30-day mortality decrease in patients with septic shock. Am J Emerg Med 2021; 45:105-11. Medline
II Supportive (Green) Mortality Patient PH-Paramedic Lane DJ., Wunsch H., Saskin R., Cheskes S., Lin S., Morrison LJ., et al. Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis. JAMA network open 2018; 1(8):e185845. Medline
II Supportive (Green) Incidence of mechanical ventilation Patient ED-MD & CCP Rajdev K, Leifer L, Sandhu G, Mann B, Pervaiz S, Lahan S, et al. Aggressive versus conservative fluid resuscitation in septic hemodialysis patients. Am J Emerg Med 2021; 46:416–9. Medline
II Supportive (Green) Mortality Patient PH-Paramedic Seymour CW., Cooke CR., Heckbert SR., et al. Prehospital intravenous access and fluid resuscitation in severe sepsis: An observational cohort study. Crit Care 2014; 18(5):533-014-0533-x. Medline
II Neutral (Yellow) Mortality Patient PH-Paramedic Femling J., Weiss S., Hauswald E., Tarby D. EMS patients and walk-in patients presenting with severe sepsis: Differences in management and outcome. South Med J 2014; 107(12):751-6. Medline
II Opposes (Red) 28 day mortality Patient PH-MD & CCT Jouffroy R., Saade A., Muret A., Philippe P., Michaloux M., Carli P., et al. Fluid resuscitation in pre-hospital management of septic shock. Am J Emerg Med 2018; 36(10):1754-8. Medline
III Supportive (Green) Feasibility Process ED-MD Macdonald SPJ., Keijzers G., Taylor DM., Kinnear F., Arendts G., Fatovich DM., et al. Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial. Intensive Care Med 2018; 44(12):2070-8. Medline
III Neutral (Yellow) Volume of fluid administered Process ICU Chen C, Kollef MH. Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study. Chest. 2015;148(6):1462–1469. doi:10.1378/chest.15-1525 Medline
III Neutral (Yellow) Increased stroke volume Process ED-MD Oord M., Olgers TJ., Doff-Holman M., Harms MP., Ligtenberg JJ., Ter Maaten JC. Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild sepsis in the emergency department: a pilot study. BMJ Open 2017; 7(1):e013465. Medline

Trendelenburg
Level Direction Primary Outcome Patient/Process Setting Reference
III Neutral (Yellow) MAP increase Patient ICU Sing RF., O'Hara D., Sawyer MAJ., Marino PL. Trendelenburg position and oxygen transport in hypovolemic adults. Ann Emer Med 1994; 23:564-7. Medline
III Neutral (Yellow) Internal jugular vein flow Patient Terai C., Anada H., Matsushima S., Shimizu S., Okada Y. Effects of mild trendelenburg on central hemodynamics and internal jugular vein velocity, cross-sectional area and flow. Am J Emer Med 1995; 13:255-8. Medline


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