Adam Drenzla wrote these excellent comments after listening to the Rivers' Podcasts. Adam's comments are in gray, my replies are in black.
Excellent sepsis talk, thanks Scott and Emanuel. A few points of discussion:
1. SVV and fluid. One important caution on the use of SVV and the like for assessment of preload responsivness seems to be in those patients with poor long compliance such as ARDS in which the cyclical changes in cardiac output induced by IPPV are a result not of preload changes to the right and left ventricles but rather of changes to afterload in a failing RV. See editorial – Preload responsivness or right ventricular dysfunction (Crit care med 2009;37(9):2662)
SVV has many false positives and negatives; the one you point out is absolutely correct. Fortunately, we rarely see patients at this stage of lung disease in the ED. More commonly people screw this up by keeping patients at low VT. When I want to look at SVV, I knock the patient up to 10 ml/kg Vt for the duration of the SVV check.
2. Echo and mycoardial dysfunction in sepsis. (a) The actual incidence of myocardial dysfunction in severe sepsis and septic shock is somehwat contentious, but the figure maybe as high as around 50%, (b) interestingly, there is a suggestion that the patients without myocardial dysfunction do worse, not better (c) I was recently at a talk in Australia given by Antoine Vieillard-Baron who presented as yet unpublished data comparing an egdt strategy based on early transesophageal echo versus a strategy advocated by the surviving sepsis guidelines based on Rivers’ trial including CVP/MAP/ScVo2 targets. There was a very significant decrease in IVF administration in the TEE group as well as a very significant increase in the use of inootropes in this group. By implication, the surviving sepsis guidelines and use of ScVO2 may miss many patients with myocardial suppression. My understanding is that this translated into outcome differences but publication is awaited. This was, i think, an ICU trial and so the stage of resucitation may be an important factor here.
Actual incidence of global left ventricular hypokinesia in adult septic shock. Antoine Vieillard-Baron, MD; Vincent Caille, Crit Care Med 2008 Vol. 36, No. 6
Fascinating, I can't wait to see the publication.
3. Differentiating causes of sepsis and use of activated protein C. Although there is now a heavy cloud over the benefits of APC its turbulent history has many important implications for how research is conducted in critical care. One of the most intriguing is what Neil Soni has termed the pinocchio effect. In short, the sepsis sydnrome has many causes; are the outcomes and response treatments really expected to be the same? Is lumping them all together in big trials always useful toward our understanding? As Dr. Rivers mentioned perhaps APC has some particularly beneficial effect in those suffering from strep pneumoniae related sepsis, but to my knowledge it has not been directly studied in this setting. The story is the same for TNF inhibitors which are harmful in this group of patients but potentialy of benefit in others. (Neil Soni, Anaesthesia 2010;65(10):976 ARDS, acronyms and the Pinocchio effect. Systemic Host Responses in Severe Sepsis Analyzed by Causative Microorganism and Treatment Effects of Drotrecogin Alfa (Activated) Clinical Infectious Diseases 2003; 37:50–8)
I don't think it has been prospectively studied; Dr. Rivers' comments emerged, I believe from the subgroup analysis of Prowess: (Crit Care Med 2005;33(5):952),
4. Cryptic septic shock. An interesting addit to the use of vasodilators in the River’s trial is the issue of cryptic septic shock. The post hoc analysis in this group of patients is only availbale in abstract form but it seems that those patients who arrive to emergency with sepsis who have MAP>100 but elevated lactates >4 do particularly well with EGDT. Indeed, although only accounting for around a fifth of the total numbers in that trial they account for about half of the total beneift of EGDT. This group of patients would not only have been missed without measuring lactate but would also have recevied the most vasodilator therapy as the MAP target in the trial was 65-90. Cryptic septic shock: A sub-analysis of early, goal-directed therapy Donnino, Michael W;Nguyen, Bryant;Jacobsen, Gordon;Tomlanovich, Michael;Rivers, Emanuel)