Reviewed and revised 15 November 2013
Early goal directed therapy (EGDT) was to decrease mortality and morbidity in the River’s trial (2001) – although this trial has been heavily criticised.
Resuscitation targets in severe sepsis include:
- preload, e.g. CVP
- afterload, e.g. MAP
- tissue oxygen delivery; end point controversial: ScvO2 vs lactate clearance
Continuous spectrophotometric ScVO2 monitoring was used in the Rivers trial but may not be needed if lactate clearance can be shown to be non-inferior.
CAUSES OF HYPERLACTEMIA IN SEPSIS
- Endogenous catecholamine release and use of adrenaline as an inotrope
- Circulatory failure due to hypoxia and hypotension
- Cytopathic hypoxia – widespread microvascular shunting and mitochondrial failure
- Inhibition of pyruvate dehydrogenase (PDH) by endotoxin
- Coexistent liver disease
THE JONES STUDY
Goal is to compare lactate clearance as non-inferior to ScVO2 as a resuscitation target in severe sepsis.
- prospective, randomized, parallel group, non-blinded
- January 2007 – 2009
- 3 US urban hospitals
- severe sepsis or septic shock admitted to ED
- > 17 years
- confirmed or presumed infection
- 2 or more SIRS criteria
- hypoperfusion (SBP < 90mmHg post 20mL/kg volume or a blood lactate of at least 4.0mmol/L
- Exclusion criteria: pregnancy, primary diagnosis other than sepsis, suspected requirement for immediate surgery within 6 hours of diagnosis, an absolute contraindication to chest or neck CVL, CPR, transfer from another institution with a sepsis-specific resuscitative therapy underway, advanced directive orders that would restrict the study procedure
-> ScvO2 group mortality rate = 23%
-> lactate clearance group mortality rate = 17%
-> patients with septic shock and resuscitated to a normal CVP and MAP when randomised to target SvO2 vs lactate clearance of 10% -> there was no difference in mortality.
-> lactate measurements in peripheral venous blood is as safe and efficacious as a computerised spectrophotometric catheter in sepsis resuscitation.
References and Links
- CCC — Lactate and lactic acidosis
- CCC — Sepsis Overview
- CCC — ScvO2 monitoring
- CCC — Early Goal Directed Therapy
- Fuller BM, Dellinger RP. Lactate as a hemodynamic marker in the critically ill. Curr Opin Crit Care. 2012 Jun;18(3):267-72. doi: 10.1097/MCC.0b013e3283532b8a. Review. PubMed PMID: 22517402; PubMed Central PMCID: PMC3608508.
- Gibot S. On the origins of lactate during sepsis. Crit Care. 2012 Sep 10;16(5):151. [Epub ahead of print] PubMed PMID: 22979942; PubMed Central PMCID: PMC3682245.
- Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. PubMed PMID: 20179283; PubMed Central PMCID: PMC2918907.
- Jones AE, Brown MD, Trzeciak S, Shapiro NI, Garrett JS, Heffner AC, Kline JA; Emergency Medicine Shock Research Network investigators. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis. Crit Care Med. 2008 Oct;36(10):2734-9. Review. PubMed PMID: 18766093; PubMed Central PMCID: PMC2737059.
- Marik PE, Bellomo R. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3. [Free Full Text]
- Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. PubMed PMID: 11794169. [Fulltext]
The paper that allowed us to start non-invasive protocols=gamechanger. [1. Jones AE, Shapiro NI, et al.; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb;303(8):739?46.]
Is septic shock without lactate elevation as sick as those with? This retrospective study would say they are not. Maybe the alactemic septic patient can just be fluid resuscitated and get their pressors without having to worry about going further. [2. J Crit Care 2011;26:435] [3. Crit Care Res Pract. 2012;2012:536852]
Additional evidence [2. Crit Care 2008;12:R33],[2. Crit Care 2006;10:R80]
Napoli AM, Seigel TA. The role of lactate clearance in the resuscitation bundle. Crit Care. 2011;15(5):199. Epub 2011 Oct 24. PubMed PMID: 22078132;
PubMed Central PMCID: PMC3334784.
Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. PubMed PMID: 20179283; PubMed Central PMCID: PMC2918907.
Nguyen HB, Kuan WS, Batech M, Shrikhande P, Mahadevan M, Li CH, Ray S, Dengel A; ATLAS (Asia Network to Regulate Sepsis care) Investigators. Outcome effectiveness of the severe sepsis resuscitation bundle with addition of lactate clearance as a bundle item: a multi-national evaluation. Crit Care. 2011;15(5):R229. Epub 2011 Sep 27. PubMed PMID: 21951322; PubMed Central PMCID:PMC3334775.
Rivers EP, Elkin R, Cannon CM. Counterpoint: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis
and septic shock therapy? No. Chest. 2011 Dec;140(6):1408-13; discussion 1413-9. PubMed PMID: 22147818; PubMed Central PMCID: PMC3244279.
Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes.
Chest. 2011 Dec;140(6):1406-8. PubMed PMID: 22147817; PubMed Central PMCID: PMC3244278.
Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J; LACTATE study group. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010 Sep 15;182(6):752-61. Epub 2010 May 12. PubMed PMID: 20463176.
Nguyen’s Asian quality improvement trial added lactate clearance to standard EGDT. These patients were hemodynamically stable with normal ScvO2 and good fluid loading before trial entrance. After multi-variate analysis, patients who cleared lactate had lower risk of death than those who did not. [2. Nguyen HB et al. Outcome Effectiveness of the severe sepsis resuscitation bundle with the addition of lactate clearance as a bundle item: a multi-national evaluation. Crit Care 2011;15:R229]
This flawed study question lactate non-expressors with septic shock. Unfortunately they looked at lactate level after initial resus [1. Dugas. J Crit Care 2012;27:344]
Lactate Non-Expressors are a distinct and less ill population [1. doi:10.1155/2012/536852]
Lactate predicts mortality all the way up to 20 mmol/L [1. Academic Emerg Med 2012;19:983]
Lactate normalization within 6 hours is the best predictor of survival [1. CHEST. 2012 doi:10.1378/chest.12-0878]
Even in the ICU lactate clearance was the best predictor of death [1. Annals of Intensive Care 2013, 3:3 ]
FOAM and web resources
- EMCrit — Severe Sepsis Resources
- EMCrit Podcast 22 – Non-Invasive Severe Sepsis Care with Alan Jones
- EMCrit Podcast 37 — Lactate in Sepsis and the Lactate Reference Sheet
- EMCrit — EMCrit Wee – Is Lactate Clearance a Flawed Paradigm?
- Free Emergency Talks — Emanuel Rivers (USA): Lactate Clearance in Severe Sepsis (2012)
- Free Emergency Talks — Alan Jones (North Carolina): Optimal Goals of Sepsis (2009)
- Free Emergency Talks — Peter Greenwald: Early Goal-Directed Therapy in the Community (2010)
- ICN — Podcast 33: Delaney on EGDT, Surviving sepsis and ARISE
- PulmCCM.org — Should lactate clearance replace SvO2 in sepsis protocols? (Pro/Con, CHEST)