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Evidence for the Protocols

Evidence for Non-Invasive Protocol

The paper that allowed us to start non-invasive protocols=gamechanger. 1

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

Additional evidence34

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. 5

Evidence for the Invasive Protocol (ScvO2 & Lactate Guided Resuscitation)

Meta-Analysis. 6

The original, the seminal ED sepsis work. 7

2nd RCT: A prospective, randomized controlled trial was performed involving 273 patients in the early stage of shock at risk of potential MODS development.

The incidence of MODS in the EGDT group was significantly lower than that in control group (P=0.002). The Lactate(2), Lactate(4), SOFA(T), SOFA(S), and the number of dysfunctional organs in EGDT group were also significantly lower (P=0.045, 0.016, 0.009, 0.010, 0.002). EGDT was associated with a significantly lower total mortality rate of MODS than the conventional therapy (P=0.007), and also with a significantly lower mortality rate of MODS after controlling for severe sepsis (P=0.047 and 0.044)8

A point counterpoint debate with Rivers from Chest. 9

Best Review Article on ScvO2 10

One argument to continue to use invasive strategy is that lactate may not detect low, but persistent levels of oxygen debt. 11

Reanalysis of the Jones trial shows ScvO2 clearance did not have as good a mortality benefit as lactate clearance, but remember; very view patients needed anything more that fluids/pressors in this trial 12

Sonography of the IVC for Prediction of Fluid Responsiveness

Fluid Assessment Conference Call Handout

Fluid Assessment Sheet

13,14,15,16,17,18,19,2021

Dialysis study shows IVCCI of >30% predicts hypotension and when it is safe to continue fluid removal 22

Lactate as a Marker for Adequate Resuscitation

Elevated lactate is a marker of severe sepsis

23|24|25|2627|28

|29|30|31

|32

Persistent elevation of lactate is associated with dismal outcome. Lactate clearance is associated with better outcome.

33‘34‘35‘36‘37‘38‘39

For more on Lactate, see the FAQ.

Alactemic Sepsis

In this study, 9.1% of the hypotensive patients had a lactate < 2 and 24.2% had a lactate < 4. 40

In this second study, 11.6% of the patients had the lactate <2 and 25% had lactates <4 41

Patients without lactate elevations don’t seem to be particularly sick 42

Cryptic (Occult) Sepsis

In abstract form, this demonstrated that the cryptic shock patients probably got the lion’s share of mortality benefit as opposed to the patients that were already on the downslope. 43

In a newly published study, they compared cryptic and overt shock patients; the mortality between the two groups was the same. This was a reanalysis of the Jones paper. Of interest, many of the patients in the Occult Shock group had lactates < 4; are these patients less sick? 44

Early Antibiotics

Kumar proved antibiotic timing is incredibly important in septic shock. 45

And it needs to be the correct antibiotic. 46

If antibiotics were delayed until after shock recognition, severe sepsis patients did markedly worse. Delay for patients not in shock did not seem to have an effect on mortality 47

Vasopressor Choice

De Backer’s Meta-Analysis of dopamine vs. norepi, may be the final piece in making norepi the 1st choice pressor for sepsis 48

Barriers to Implementation

Carlbom DJ, Rubenfeld GD. Barriers to implementing protocol?based sepsis resuscitation in the emergency department??results of a national survey. Crit Care Med. 2007 Nov; 35(11):2525?32.

Mikkelsen ME, Gaieski DF, et al. Factors associated with nonadherence to early goaldirected therapy in the ED. Chest. 2010 Sep;138(3):551?8. Epub 2010 Feb 19. Surviving Sepsis Campaign Guidelines

Dellinger RP, Levy MM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan; 36(1):296?327. Erratum in: Crit Care Med. 2008 Apr;36(4):1394?6. Normal Vital Signs do not predict adequate resuscitation

Rady MY, Rivers EP, Nowak RM. Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate. Am J Emerg Med. 1996 Mar; 14(2):218?25. Intubation will improve organ perfusion

Hernandez G, Peña H, et al. Impact of emergency intubation on central venous oxygen saturation in critically ill patients: a multicenter observational study. 49

In an ED study, placing A-line, CVP, or getting ScvO2 was v. hard 50

Misc.

Still patient benefit even if we miss the 6-hour time window for bundle completion 51

When we look at the microcirculation, some patients will actually benefit from MAPs of >65. They used NE and pushed MAP to 85 mm Hg and then checked micro-circ effects with NIRS and SDF 52

Meta-analysis shows norepi is better than dopamine for severe sepsis 53

Dopamine causes a-fib–If you wind up with new a-fib in severe sepsis, you have a higher risk of stroke and of death 54

Vasopressin even at the 0.4 u/hr dose may impair gastric perfusion 55

Classification of what sepsis, severe sepsis, and septic shock varies amongst different studies and affects predicted mortality 56

Excellent Reviews

Marik’s take on what to do with severe sepsis 57

Point/Counterpoint on Resuscitation Goals from Rivers and Jones

References

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  2. J Crit Care 2011;26:435 ↩
  3. Crit Care 2008;12:R33 ↩
  4. Crit Care 2006;10:R80 ↩
  5. 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 ↩
  6. Jones AE, Brown MD, et al.; 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. ↩
  7. Rivers, E, Nguyen, B, et al. (for the 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; 345(19):1368-77. ↩
  8. Chen ZQ, Jin YH, Chen H, Fu WJ, Yang H, Wang RT. Early goal-directed therapy lowers the incidence, severity and mortality of multiple organ dysfunction syndrome. Nan Fang Yi Ke Da Xue Xue Bao. 2007 Dec;27(12):1892-5. ↩
  9. Rivers EP. Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself. Chest. 2010 Sep;138(3):476?80;discussion 484-5. ↩
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  12. Puskarich et al. Prognostic Value and Agreement of Achieving Lactate Clearance or Central Venous Oxygen Saturation Goals During Early Sepsis Resuscitation. Acad Emerg Med 2012;19:252 ↩
  13. Brennan JM, Blair JE, et al. A comparison by medicine residents of physical examination versus hand?carried ultrasound for estimation of right atrial pressure. Am J Cardiol. 2007 Jun;99(11):1614-6. ↩
  14. Brennan JM, Ronan A, et al. Handcarried ultrasound measurement of the inferior vena cava for assessment of intravascular volume status in the outpatient hemodialysis clinic. Clin J Am Soc Nephrol. 2006 Jul;1(4):749?53. Epub 2006 May 24. ↩
  15. Carr, Brendan G., Dean, Anthony J., et al.; Intensivist Bedside Ultrasound (INBU) for Volume Assessment in the Intensive Care Unit: A Pilot Study. Journal of Trauma?Injury Infection & Critical Care. 2007 Sept: 63(3): 495?502. ↩
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  20. Yanagawa, Youichi; Sakamoto, Toshihisa; Okada, Yoshiaki. Hypovolemic Shock Evaluated by Sonographic Measurement of the Inferior Vena Cava During Resuscitation in Trauma Patients. Journal of Trauma?Injury Infection & Critical Care. 2007 Dec. 63(6):1245?1248. ↩
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  25. Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD: Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009, 37:1670-1677. ↩
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{ 1 comment… read it below or add one }

Brian Wieczorek May 8, 2012 at 10:56

Scott,

I am interested in any feedback you may have on the use of ketamine drips for sedation in the setting of severe sepsis. I have been using fentanyl drips for sedation in a variety of settings with success. I would think that ketamine would be an ideal sedative adjunct with severe sepsis. Any information or feedback to support the use of ketamine in this setting is appreciated.

Brian Wieczorek MD

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