Should lactate clearance replace SvO2 in sepsis protocols? - PulmCCM
Jan 012013

It started with a friendly pro/con debate in the December 2011 Chest, about whether lactate clearance or mixed venous oxygen saturation is a better "goal" for early goal-directed therapy in severe sepsis and septic shock. It ended with Alan Jones reviving the rumors and innuendo that have swirled for years around Emanuel Rivers's body of work.

Continuous central venous oxygenation saturation monitoring (ScvO2), used in Rivers's 2001 NEJM landmark trial, requires a proprietary catheter (originally patented by Dr. Rivers and marketed by Edwards Lifesciences). Intermittently-obtained central venous oxygen saturation correlates well with mixed or continuous central venous oxygen saturation, and is considered a proper substitute for continuous central venous O2 saturation. Most intensivists use the less expensive intermittently collected ScvO2.

The randomized LACTATES trial compared early goal directed therapy using lactate clearance (change in lactate / original lactate / time elapsed) against a strategy using ScvO2, and showed equivalent outcomes (mortality) in the two groups. Alan Jones (PI of LACTATES) squares off against the threesome of Emanuel Rivers, Ronald Elkin and Chad Cannon to make the case that lactate clearance is more useful and should replace SvO2 in EGDT.

Jones's most compelling point is that either central or mixed venous O2 sats can be normal or high in severe sepsis, even in the presence of severe organ hypoperfusion, because if oxygen extraction varies throughout the body (as it does during sepsis), the mixed blood can "average out" to a misleadingly normal/high value. Therefore, following ScvO2 results in mismanagement. Also, lactate clearance has repeatedly been shown to independently predict survival from sepsis, whereas SvO2 (as a single variable) has not. 

Rivers and friends counter that ScvO2 is more sensitive as an early-warning system in sepsis than lactate (based on their own data), that lactate kinetics are too complex and variable between patients to use it as a standard, that lactate levels often don't rise even in life threatening sepsis, and that using percent lactate clearance is oversimplified (e.g., it considers a lactate going from 10 to 9 as being the same as one from 4 to 3.6: both are a 10% clearance). They also bemoan the fact that people have interpreted Jones's LACTATES to mean central lines are not needed at all in severe sepsis (although of course they are under current practice standards, to measure central venous pressures).

But in the rebuttals, things really heated up.

In response to criticism of LACTATES's methodology, Jones revives the persistent suspicions (by some) surrounding Dr. Rivers's original single center trial, even casting aspersions on the care delivered at Henry Ford, noting Rivers's original control group mortality was "20% higher than any septic shock mortality reported in the recent literature." Jones also suggests peculiarity of Dr. Rivers's data collected between 1997 and 2000, calling it "markedly different than any other septic shock population reported in the world’s literature" and wondering if "systematic selection bias was a significant problem in the their study."

As reported in the Wall Street Journal, prominent academics have wondered publicly about the dramatic benefit seen in Dr. Rivers's original study, particularly about the less-than-perfect clarity initially as to whether he included all patients properly according to intention-to-treat. Rivers has repeatedly assured everyone that no patients were cherry-picked or excluded. But a medical resident at Henry Ford doing a follow-up study raised a red flag as to the integrity of the original data, pointing out there were 25 patients who should have been included and had they been, would have reduced or eliminated the trial's findings. The hospital performed its own internal analysis of the data, and publicly announced everything was on the up-and-up -- but declined to share the primary data with anyone on the outside, the WSJ story says. Since Rivers and his hospital have had a longstanding complex relationship with Edwards Lifesciences, makers of the SvO2 monitoring catheter, the whole thing is redolent with intrigue.

I saw Dr. Rivers speak once. He gave a great presentation. The main thing I remember about it, though, was that he announced "nothing to disclose" and then showed several videos of his septic shock patients, during which he kept zooming in for tight shots on the Edwards Lifesciences logo on the ScvO2 monitor, holding focus for several suspenseful, brand-building seconds. (Wouldn't you know it, there was a 0% mortality for those three patients! I felt like I should be getting a free lunch, at least.)

Clinical Takeaway: All the combatants agree that ScvO2 and lactate provide complementary information. I'll keep checking both, and hope the forthcoming ProCESS study lights our way.

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;140:1406-1408.

Rivers EP et al. Counterpoint: Should Lactate Clearance Be Substituted for Central Venous Oxygen Saturation as Goals of Early Severe Sepsis and Septic Shock Therapy? No. CHEST 2011;140:1408-1413. 

Rebuttal from Alan Jones

Rebuttal from Manny Rivers

Thomas M. Burton, "New Therapy for Sepsis Infections Raises Hope but Many Questions," The Wall Street Journal, August 14, 2008.

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  3 Responses to “Should lactate clearance replace SvO2 in sepsis protocols?”

  1. Very interesting, but this makes matters worse for an exam-going candidate like me…

  2. Funny about the nothing to disclose as he holds a patent for a continuous oximetry catheter

    • No, he doesn’t — it’s more convoluted than that. According to the WSJ’s reporting, Dr. Rivers transferred the patent rights to Henry Ford Hospital prior to publication of the NEJM article. However, since that time (quoting the WSJ here):

      “Since the publication, catheter maker Edwards Lifesciences has made various payments to Dr. Rivers and his hospital. Such arrangements aren’t unusual in medicine, but their existence can raise doubts about findings.

      Dr. Rivers and the hospital over the years have received at least $404,000 from Edwards, the Irvine, Calif., company says.

      For instance, Edwards paid $150,000 between 2001 and 2003 to Henry Ford Hospital for what Edwards terms ‘nonexclusive patent rights [and] ongoing research’ into blood oxygen and the mechanism of shock. Dr. Rivers, in an interview, described this as ‘money I’ve gotten from the catheter…all for research.’

      In addition, Edwards said, it has paid Dr. Rivers $158,000 to make speeches about his research, $20,000 to reimburse him for patent legal fees, $36,000 in reimbursed expenses and $40,000 in consulting fees.” [end quote from WSJ]

      Nothing to disclose.

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