Optimizing Outcomes for Potentially Septic Patients
Search Strategy: You conduct a PUBMED Clinical Queries (therapy, broad) search for “sepsis” yielding 46618 citations. Next, you combine the first search with the terms “implementation” (88670 citations) and “early goal directed therapy” (496 citations) yielding 13 citations. Reviewing these 13 citations and their bibliographies is all that you need to identify the selections below. (http://tinyurl.com/3e7ne33)
After 12 years of homework, studying, lectures, and long hours of training, you have finally reached the finished line and graduated from the wonderful world of residency and can now officially call yourself an Emergency Medicine Attending.
To become an indispensible colleague in your new Emergency Medicine group, you decide to join the sepsis quality improvement group of your group and hospital. However, you notice that there is sparse attendance to these meetings given the deleterious press that Early Goal Directed Therapy (EGDT) has received of late (Marik 2010, Klauer 2010– answer yes to the first question to see the 2010 article which the publisher has removed from their website)
Despite these counterarguments, your chair believes in strongly EGDT in the treatment of sepsis and wants to implement it as protocol. Since your résumé proudly boasts that you have graduated from the very prestigious Washington University Emergency Medicine Residency, where you have worked with such Emergency Medicine stars as Dr. Brian Fuller and Dr. Chris Holthaus, she has decided to make you the local “Sepsis Champion” leaving you with the responsibility of creating an Early Goal Directed Therapy (EGDT) protocol for the entire hospital.
Intimidated (yet excited!) at the chance to contribute immediately to your new job, you gladly accept this responsibility. Forced to rely on your own resources, you fortunately remember your excellent Evidence Based Medicine and Knowledge Translation training that you received at Washington University.
Population: Adults (over age 18) presenting to the ED with sepsis (>2 SIRS + source), severe sepsis (with lactate > 4), or septic shock.
Intervention: Early goal directed therapy (fluid resuscitation, crystalloid, Central venous pressure goals, MAP goal >65, ScvO2 goal > 70)
Comparison: Adults with sepsis treated in standard fasion (physician discretion)
Outcome: Mortality (28 day and in hospital), and Hospital Length of Stay
Third years: Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department, Chest 2006; 129: 225-32. (http://pmid.us/16478835)
Article 1: Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock, NEJM 2001; 345: 1368-1377
Article 2: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008, Crit Care Med 2008; 36: 296-327
Article 3: Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department, Chest 2006; 129: 225-232
Article 4: The costs and cost-effectiveness of an integrated sepsis treatment protocol, Crit Care Med 2008; 36: 1168-1174
Severe sepsis and septic shock are highly lethal, common, and expensive. Millions of people are affected each year worldwide, with a conservative mortality estimate of 25%. In the United States approximately 215 000 deaths are attributed to sepsis annually. More people die annually of sepsis than of lung and breast cancer combined, resulting in over 380,000 ICU admissions annually with an enormous economic burden of over $17 billion. The incidence of sepsis is estimated to be increasing steadily at 1.5% annually, with over 1.1 million cases per year by 2020. Unfortunately, the number of failed trials in sepsis therapy far outnumber those associated with a good outcome.
Early goal directed therapy is an algorithmic treated approach for patients with severe sepsis and septic shock presenting to the Emergency Department. In a 263 patient randomized study, Rivers et al. showed an absolute risk reduction for mortality of 16% (number needed to treat of 6). Similar results were reproduced by other investigators at different centers. Despite these findings, EGDT has not been without controversy and has been hotly debated in the literature. In addition, sepsis management in ED’s around the world remains highly variable.
From 37 respondents (36 from Barnes Jewish/Washington University – see attached results for more details), 95% believe sepsis is a common problem in emergency medicine. Despite this, 24% were unaware that an EGDT protocol even existed at their institution. One-in-three respondents stated they would forego EGDT if a patient clinically looked well (good mentation, feeling better). This is despite the inability of clinicians to accurately and reliably recognize occult hypoperfusion – not to mention the comparable mortality of cryptic shock patients compared to overt shock. Most (95%) respondents routinely check serum lactate levels on patients with systemic inflammatory response syndrome (SIRS).
Barriers to EGDT implementation identified by survey respondents:
- Too time consuming (66%)
- Lack of resource/staffing (54%)
- Lack of physician acceptance (34%)
- Insufficient nursing training (31%)
A clinician champion was viewed as the most important asset to the successful implementation of EGDT (82%), followed by and education program (76%), a quality feedback mechanism (55%), and the presence of a nurse educator (39%). A recurring theme in the survey seemed to be the need for floor-to-ceiling (entire hospital system) education at regular intervals.
When would individual physicians use EGDT? Some (37%) stated that it depends on the timing of ICU bed availability. This is also despite a known correlation of treatment and ICU transfer delays with worse mortality associated with sepsis management delays measured in minutes. Most (97%) respondents stated that if a “sepsis team” was available (combination of EM and ICU staff and pharmacist), they would use them.
Analysis of the Evidence
In hypotensive (systolic blood pressure < 90 mm Hg after initial volume resuscitation) or hypoperfused (Lactate > 4 mmol/L) adult patients with systemic inflammatory response syndrome, Rivers’ protocol EGDT [crystalloid and packed red blood cells as needed to maintain CVP ≥ 8-12 mm Hg, MAP ≥ 65, urine output > 0.5 cc/kg/hr and SVO2 ≥ 70%] the absolute risk reduction of mortality during hospitalization is 16% (NNT = 6 patients who need to be treated with EGDT to prevent one death) when compared with standard therapy. This contradicts earlier research conducted in ICU’s (Hayes 1994, Gattinoni 1995) which may have been too late in the “golden hour” of sepsis management. Rivers’ study is a landmark trial for sepsis care and EM research, but has generated a LOT of controversy since 2001 (see Marik 2010, Klauer 2010). However with the benefit of 10-years’ of subsequent trial sat different institutions, totaling thousands of patients, the bulk of research evidence still supports EGDT as the standard of care for emergency medicine sepsis management (Chen 2007, Puskarich 2009, Gaieski 2010, Xue 2010, Sivayoham 2011).
This is not a static argument: ProCESS is a large NIH-funded study to further evaluate EGDT currently under way. Another multicenter study of EGDT is being conducted in Australia. For now, there is no data to demonstrate that EGDT is or may be harmful. Evidence also supports that EGDT can be done at different institutions with different staffing model and approaches. The data we reviewed suggests that sepsis bundles like the MUST protocol do not save costs, but they do provide an increase in quality adjusted life years at a cost of ~$9000-$13,000 per quality adjusted life year gained. Future research should evaluate specific subgroups (source of infection, age extremes, severity of sepsis) in distinct settings to better understand the costs and benefits of the labor-intensive EGDT protocol in the ED. The primary challenge is the successful implementation and sustainability of EGDT which can consume many person-hours. Successful EGDT protocols at a local level will require continued re-education and feedback.
Translating the Evidence into Practice: Small Group Discussions
Group 1: Practical Considerations in EGDT implementation
Care of the septic patient in the ED must be de-individualized. Why? There is enough data to suggest that (similar to ACS, CVA, trauma) de-individualizing care of the septic patient, by following the EGDT protocol and guideline recommendations, emergency medicine providers can improve outcomes. The clinician must risk stratify infected patients, as the outcome and treatment is very different. A patient with SIRS is much different than a patient with severe sepsis with a lactate above 4 and/or a septic shock patient. This group also debated the issues regarding central venous access, such as ultrasound use, procedure resident, and time to do the procedure Ultimately, the work group concluded that the benefits of recommending wide-spread central venous access to fulfill the EGDT protocol was safer than not performing EGDT (the other alternative). The group also identified a treatment gap in monitoring response to therapy, on the physician and nurse level. Example- what has the CVP done over the past hour, or urine output, etc.?
Group 2: Developing a multidisciplinary team
This group consisted of EM residents, several EM attendings, and an EM/CCM attending. There was a general consensus that EGDT is used with wide variability. The residents stated there was a large practice variation amongst attending physicians. Some residents reported that they have been denied at times the ability to do EGDT by the attending. To eliminate heterogeneity within a group, wide spread acceptance of a treatment protocol will be essential.
Nurses are of utmost importance in the care of these patients. Continued nurse education and identifying motivators for success will be vital. The group did not perceive any barriers with respect to transition of care to the ICU, but acknowledge that this institution has long ICU wait times, perhaps making EGDT even more important to employ on an institutional level.
Group 3: Sepsis programs of care at the system/hospital level
Developing a successful EGDT protocol at the hospital level will require three considerations: education, resources, and sustainability (Trzeciak 2006, Jones 2007, Nguyen 2007, Casserly 2011). In the realm of education, considerations for policy makers will include who to educate (ICU + ED, MD + RN, others?), how to best educate them (simulation? Small-group sessions? Didactics?), and how often to re-educate. Resources ultimately come down to profit margins. Since hospitals often operate on a 1-2% profit margin, how will policy makers decide upon which therapy to invest capital on new equipment and personnel. One supporting argument in favor of funding EGDT costs within an institution would be that in our current U.S. funding system, hospitals begin to lose money after 10-12 days of ICU care since the DRG reimbursement is capped at that time. EGDT can reduce ICU length of stay thereby alleviating this monetary loss to institutions. To sustain EGDT a local opinion leader is essential to identify early. And this opinion leader must be retained. In addition, nurses and physicians must receive regular audit-and-feedback for their sepsis management monitoring accepted and reliable metrics of EGDT. It would be helpful if bonus structures could be tied to the efficient delivery of EGDT, too. On a legislative level, having EGDT not delivered defined as a “never event” for which CMS would not reimburse hospitals for the cost of sepsis-related care would be the ultimate “hammer” to ensure implementation and sustainability at a national level.