The PROCESS Trial: End of the Line for Central Lines?

A lot of things change for doctors once we’re done with training. Most of us leave behind the ivory tower that is the academic medical center to plow the common fields of private practice. We no longer have the weekly journal clubs, the Grand Rounds, the CME lectures. But what we gain is practical hands-on experience with what works, and what doesn’t. A nuanced knowledge of what’s accepted vs. what’s acceptable.

One such area has been the approach to sepsis. Manny Rivers et al published  their game changing study on early goal directed therapy (EGDT) in the treatment of septic shock in 2001, and the result became scripture in the field of Critical Care Medicine. The knowledge that tying sepsis resuscitation to the measurement of central venous oxygen saturation (ScvO2) and central venous pressure (CVP) using a central venous catheter, lead to a surge of recommendations.

The brain trust spewed forth these recommendations in various forms;  Surviving Sepsis Campaign, Sepsis guidelines, Sepsis bundles, Sepsis video games and Sepsis action figures. Somewhere in that sentence I may have transitioned to hyperbole.

Those of us in clinical practice didn’t always follow the drumbeat. Many of our patients with sepsis it seemed, did just fine without a routine central line or blood transfusions, or dobutamine drips. Why use invasive measures when we don’t really need them, and we’re not really sure that they’re helping? Still, when I talked to my ivory tower friends, the response was same, “We always use central lines and follow the EGDT”, they would say.

In case you’re thinking that I’m a maverick, well, it wasn’t just me. Surveys/studies that have looked at compliance with EGDT show compliance anywhere from as low as 0.1% to just above 50%. Clearly people were pushing back against the guidelines, and many began to publicly question whether results of EGDT could be generalized to the general population with sepsis.

Numerous studies showed that the overall mortality from sepsis appeared to be much lower than that in the original EGDT article. It began to become apparent that the patients in the original EGDT study were much sicker with higher lactic acid levels, lower ScvO2 levels, and higher mortality than in other studies. Possible explanations included selection bias, earlier presentation, or that they simply were sicker. Any of those explanations  however harmed  the external validity of the study.

The ProCESS trial aimed to answer the questions raised regarding EGDT. It randomized 1,351 patients at multiple sites to three different arms. One was EGDT which included placement of a central line to measure ScvO2, and CVP, as well treatment with dobutamine and blood transfusion if indicated by the protocol.

The second arm was protocolized therapy but without the EGDT protocol interventions. Patients had 2 large bore peripheral intravenous cathethers placed, and would receive a central venous catheter only if the former failed. Patients would then receive IV fluid boluses and pressors if required (this group most closely mirrors my own clinical practice as well as many other critical care physician colleagues in private practice) The third group was “usual care”, wherein critical care providers could treat as they would normally, without any recommendations from the study monitors.

The results of the study were quite illuminating. Overall mortality for the 3 groups was about 20%, in line with more recent studies on sepsis. More importantly, there was no significant difference in survival among the three groups. (Oddly, the “usual care” had the lowest incidence of renal replacement therapy (2.8%) vs. 6 % in the protocolized therapy arm, which was statistically significant). There were no significant differences among the three groups in survival,  length of stay in the hospital, or in the ICU.

And finally, to my point, among the patients in the protocolized therapy arm, only 56% of patients required a central line. Let me you remind you that the study was conducted only at academic centers which routinely adhere to the Surviving Sepsis Campaign Guidelines.

It was both intesting and telling that treatment in the “usual care” arm, in which the physicians were left to their own devices,  more closely mirrored the interventions in the protocolized arm than the care in the EGDT arm. Again, this at academic centers that adhere to the Surviving Sepsis Campaign recommendations.

So what can we take away from this? Was Early Goal Directly Therapy wrong? Was it simply an unneeded detour in the science of managing sepsis?

No, it was timely. There was a time when we needed a simple instruction manual, a “how-to” guide in resuscitating patients from septic shock. EGDT gave us that guide during a time when those of us in the medical community were still naive about the diagnosis and treatment of sepsis. But thanks to the study by Dr. Rivers and the efforts of our leadership, we’ve gotten better at finding and treating sepsis. We now have a better idea of what works, and what doesn’t. So now it’s time to remove the training wheels and discard the notion that we need to have static goals in the treatment of sepsis.

What else can we take away from this? That 20% of patient still die from sepsis, and that’s 20% too many. So for the time being I’ll keep working the fields of clinical practice, and continue to look to my ivory tower colleagues for the next innovation that will help my patients survive sepsis.

– Deep Ramachandran is a Pulmonary, Critical Care, Sleep Medicine physician and a Social Media Section Editor at Chest Journal.  I am on twitter @caduceusblogger.