Early Management Bundle for Severe Sepsis and Septic Shock

CMS … proposes the addition of NQF [National Quality Forum] #0500: Early Management Bundle for Severe Sepsis and Septic Shock, which mandates the invasive monitoring of CVP [central venous pressure] and ScVO2 [central venous oxygen saturation] via central line. With nearly two-thirds of all admitted septic patients presenting to the ED, and with the clear time sensitivity that exists between recognition, treatment, and outcomes, our members are on the “front lines” to save lives from this frequently fatal disease and promote the highest quality of sepsis care. Importantly, mortality is significantly reduced for septic patients who present to the ED compared to those who are admitted directly to the ICU or other inpatient floors, due to the timely, high quality care treatment they receive.¹ ACEP appreciates that CMS verified this in the proposed rule by citing research performed by the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP), which determined that patients admitted through the ED had a 17 percent lower likelihood of dying from sepsis than when directly admitted.²

As previously stated by ACEP in public comments to CMS, although early intervention does reduce mortality, not all elements of the composite 2012 NQF #0500 meet the criteria of being evidence-based. Specifically, we refer to the measurement of CVP and/or central oxygen saturation, both requiring placement of a central venous catheter. ACEP continues to have grave concerns about requiring the use of invasive monitoring of central venous pressure and oxygenation levels in patients with severe sepsis or septic shock, when less invasive methods of monitoring intravascular volume are equally effective.

On March 18, 2014, the Protocolized Care for Early Septic Shock (ProCESS) trial published its findings in the New England Journal of Medicine. The ProCESS Investigators published a large multi-center randomized trial of protocol-based care for early septic shock to address whether better outcomes would be realized using an invasive approach with central line and central venous oxygenation monitoring as compared to usual care or protocolized care without invasive monitoring. In the two non-invasive arms of the trial, it was left up to the clinician to decide whether a central venous catheter was necessary. In all three arms of the study, the cornerstones of sepsis management, including early recognition, antibiotics, and resuscitation were maintained. The ProCESS trial results showed no difference in the primary mortality outcome after enrolling 1,341 patients, having the power to detect a 6–7 percent difference in 60-day mortality for any reason as the primary outcome.³ In addition, there were no differences in 90-day mortality, one year mortality, or the need for organ support.³ The ProCESS trial is more powerful than the seminal Rivers trial⁴ from over a decade ago and reflects a change in basic care with respect to lactate clearance, blood cultures, antibiotics, fluids and vasopressors.

The results from the ProCESS trial reaffirmed that a mandate to measure central venous oxygenation and central venous pressure is not necessary in all patients with severe sepsis and septic shock. It should also be noted that the placement and use of use of central lines can add elements of risk to patients, including pneumothoraces and infections (HACs), suggesting a need for caution when considering whether the use of such lines should be mandated. This high-quality trial demonstrates that high quality resuscitation of patients with septic shock can happen without central venous access and deliver improved outcomes compared to years earlier. In fact, many studies have demonstrated dramatic improvements in sepsis-related mortality after the implementation of early interventions for septic patients, which included early antibiotic administration, source control, and aggressive fluid resuscitation without invasive monitoring of CVP and ScVO2.^5-9 Another trial addressing this same issue in JAMA, authored by Dr. Alan Jones and colleagues, was conducted at three EDs in the U.S., and compared two protocols that both included central venous pressure measurement; however, one used lactate clearance and the other used central venous oxygenation monitoring as a way to guide resuscitation.¹⁰ Dr. Jones’ study also found no differences in mortality, suggesting that using central venous oxygenation to guide resuscitation may not be necessary.

The results of these trials confirm the results of a number of earlier observational studies of thousands of patients, which showed no independent effect on the mortality of patients who achieved CVP targets versus patients who do not.^5-9 ACEP notes that in the observational trials cited as supporting full bundle implementation, many who benefitted from the protocol did not actually have the CVP or ScVO2 measured or monitored.⁹ This supports our view that the most important and valid mandates are the earlier steps: measure lactate, obtain blood cultures, administer broad spectrum antibiotics, administer fluids, and apply vasopressors for hypotension that does not respond to initial fluid resuscitation. In response to the results of the ProCESS trial, ACEP initiated an NQF ad hoc review of the evidence. Upon review, the NQF Patient Safety Committee recommended removal of the requirement for invasive monitoring from measure #0500. The Committee’s recommendation, in accordance with NQF’s Consensus Development Process, will be subject to public comment, review by the Consensus Standards Approval Committee and ratification by the NQF Board of Directors. Although ACEP is strongly supportive of a measure of early identification and resuscitation for sepsis and septic shock, ACEP will continue to strenuously object to requiring steps that deliver limited benefit without clear evidence that creates the opportunity for unintended patient harm and impedes real quality improvement.

References

1. Powell ES, Khare RK, Courtney DM, Feinglass J. Lower mortality in sepsis patients admitted through the ED vs direct admission. Am J Emerg Med. 2012;30:432-9.
2. HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2007-2009. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcupus.ahrq.gov/nisoverview.jsp
3. ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370:1683-93.
4. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
5. Jones AE1, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739-46.
6. Castellanos-Ortega A, Suberviola B, Garcia-Astudillo LA, et al. Impact of the surviving sepsis campaign protocols on hospital length of stay and mortality in septic shock patients: Results of a 3-year follow-up quasi-experimental study. Crit Care Med. 2010;38:1036-43.
7. Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. 2007; 35:1105-12.
8. Jeon K, Shin TG, Sim MS, et al. Improvements in compliance of resuscitation bundles and achievement of end points after an educational program on the management of severe sepsis and septic shock. Shock. 2012;37:463-7.
9. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38:367-374.
10. Cannon CM, for the Multicenter Severe S, Septic Shock Collaborative G. The GENESIS Project (Generalization of Early Sepsis Interventions): a multicenter quality improvement collaborative. Acad Emerg Med. 2010;17:1258.