From the Editor: Paul Marik has been attempting to bring SEP-1 (the United States Sepsis Core Measure) closer in line to good clinical practice. He asked me to post his emails here on EMCrit. The views expressed by Dr. Marik do not necessarily represent the views of EMCrit or its editorial staff:

Emails to CMS from Paul Marik

From: Marik, Paul E.

Sent: Friday, April 28, 2017 12:15 PM

Subject: RE: CMS SEP-1 “Quality”” mandate is harmful to patients; An update

Dear Dr Lemeneh and Colleagues:

This correspondence is a follow-up to my e-mail of April 2nd this year to which I never received a response or an acknowledgement (e-mail below). Since this e-mail there have been a number of developments, most notably our e-Pub in Chest entitled “Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study” has gone “viral”. The media people tell me that our study has had over 150 million (yes million) hits to date with over 500 000 links on Google. The response to our study has been almost universally very favorable; except from the “Sepsis Experts” who almost unanimously consider our study to be “Fake Science”, “Tooth Fairy Science”, “Witchcraft” and worse. Their comments have mostly been very unprofessional and personal. What they have failed to realize is that unlike EGDT, our protocol is based on a very impressive body of scientific research dating back to 1949; our protocol was not sucked out of thin air (like EGDT). Furthermore, we now have data on over 250 patients; the effects and benefits are reproducible time over time, over time again. Most importantly; this protocol is devoid of any known side effects. We have been monitoring oxalate levels in the at risk patients (chronic renal failure); these levels have been consistently in the safe range. An independent data analytics company which has access to the discharge data of hospitals in this country became aware of our study; they independently (and without our hospital requesting this data) have shown that the sepsis mortality for our entire hospital has fallen from 23% to 8% from January 2016 to January 2017; quite, remarkable considering that this protocol has only been used in our MICU. Similarly, the standardized mortality ratio in our MICU has fallen from 0.69 to 0.33. I suppose the “experts” will again consider this “fake data”. Our protocol is now being used by over 50 medical centers in the USA and across the world (I have lost count of the numbers). The reported results are reproducible time over time, over time again. Furthermore, a number of RCT’s are about to initiated worldwide. An essential component of our strategy to improve the outcome from sepsis is a conservative, physiologic based approach to fluid management (see Steps to the Cure, Below). Having done Webinars with multiple health systems across this country they believe that the Federal Government has a gun to their heads (namely SEP-1); they are torn between doing the right thing for their patients and what the Federal Government wants them to do. As clinicians our primary responsibly is and will always be to do what is right for the patient. SEP-1 must go, NOW.

I have become acutely aware of the enormous impact and power of the Internet and Social Media to influence behavior and dialogue. Furthermore, living in a country which values the freedom of speech and the freedom to tell the truth, this letter will be published in its entirety on the Internet.

Yours Sincerely,

Paul Marik, MD

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A Youtube Lecture Paul Linked to on EGDT

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From: Marik, Paul E.

Sent: Sunday, April 02, 2017 4:12 PM

Subject: CMS SEP-1 QUALITY MANDATE HARMFUL TO PATIENTS

Importance: High

Dear Dr Lemeneh and Colleagues:

This communication serves as a followup to my e-mail correspondence of March 2016. Following my initial correspondence there have been several important publications which require reconsideration of this issue and which must lead to the abandonment of the Federally mandated SEP-1 protocol, which as I indicated in my initial communication is potentially harmful to patients. In my opinion, as well as many other thought leaders in our country and abroad that the continued enforcement of the SEP-1 protocol is scientifically, morally and ethically unacceptable.[1,2] It is noteworthy that in response to the publication of the 2016 Surviving Sepsis Campaign Guidelines (SSC),[3,4] Dr’s Timothy Buchman and Elie Azoulay the Editors of Critical Care Medicine and Intensive Care Medicine respectively have stated that “As clinicians, we are bound to deviate from guidelines when such deviation is reasonably expected to improve an individual patient outcome. As clinical scientists, we are bound to evaluate the prevailing standard against emerging alternatives. These three imperatives are inseparable. We therefore caution against any quality metric or reimbursement policy that mandates slavish adherence to a particular recommendation.” [5] Furthermore in sworn testimony under oath (January 2017), Dr Mitchell Levy one of the architects of SEP-1, has stated that the SSC Guidelines do not represent the best distillation of scientific information, that they do not need to be rigidly followed and that a 20 ml/kg fluid bolus may be harmful! (see excerpts of his sworn testimony in Appendix 1).

The updated SSC Guidelines state” We recommend that, in the resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 h (strong recommendation, low quality of evidence)”. [3,4] Both the Federal Government and the authors of the SSC decree there are NO EXCEPTIONS to this rule; astonishingly, they mandate that patients with pneumonia or Acute Lung Injury be intubated so that they can receive the potentially harmful 30ml/kg fluid bolus [6]. .. this can only be described as reckless and medical malpractice (see Trial Verdicts below). It is critical to stress that the SSC recommendation and the SEP-1 mandate are devoid of any scientific evidence, indeed, a strong body of scientific evidence suggests that such an approach may be harmful.

In a recent study from Mayo Clinic, Kelm and colleagues demonstrated that the SSC approach to fluid resuscitation results in fluid overload in 67% of patients with fluid overload being an independent predictor of death with an odds ratio 1.92 (1.16-3.22).[7] A recent study from Professor Jean-Louis Vincent’s ICU (a founding member of the SSC) demonstrated that a large positive fluid balance starting on ICU day two was an independent predictor of death.[8] In the largest study to date, we evaluated day 1 fluid intake (from all sources) in a representative sample of 23 513 patients with severe sepsis and septic shock in the USA.[9] In this analysis we demonstrated that American clinicians administer far less fluid than recommended by the SSC, that over-resuscitation (> 5 liters) significantly increases the risk of death while under-resuscitation was associated with a small but statistically significant survival advantage. These findings debunk the SSC and SEP-1 mandate, and are in keeping with an expanding body of scientific knowledge, including that of the landmark “Feast” study, [10] that have demonstrated that large fluid boluses and a large cumulative fluid balance increase the risk of death in patients with sepsis and a variety of other syndromes.

A simple understanding of cardiovascular physiology and the pathological changes that occur with sepsis together with a review of the medical literature clearly highlights the dangers of the SEP-1 mandate forcing physicians to give qualifying patients a 30ml/kg bolus of crystalloid. It is important to emphasize that in general, sepsis is not a volume depleted state and that patients in septic shock are generally poorly responsive to fluids. This is not a new concept and was elegantly demonstrated in a series of studies performed at the NIH by Frederick Ognibene, Margaret Parker and colleagues in the late 80’s. These authors demonstrated that patients in septic shock were unable to increase left ventricular end-diastolic volume (LVEDV) and stroke volume in response to a fluid challenge.[11,12]

It is important to emphasize that some patients with sepsis are dehydrated (due to poor oral intake, etc) and may respond to SMALL boluses of fluid. However, the mandate to give a 30 ml/kg bolus of fluid may lead to “salt water drowning”,[13] and is unsupported by the scientific literature. It is remarkable that the Federal Government has mandated that physicians use a therapeutic intervention that is scientifically unproven; this is unprecedented in the history of medicine. It is noteworthy that in a lawsuit filed in the third District Court of Salt Lake County (Civil Case #140900123) by the Estate of Melvin Richins arising from the death of Mr Richins, a patient with severe sepsis who died of “salt-water drowning”, all the defendants in this case were found guilty of causing the patients’ death by fluid overload. The legal precedent has now been set. In a more recent case (March 2017) a Fulton County State Court Jury (Atlanta, GA) awarded the plaintiff $45.8 million in a case resulting from fluid overload. “In his opening statement, Attorney Stone used a bucket and a table full of water bottles to highlight his contention that [the Hospitals’] negligent care set in motion an ultimately catastrophic fluid overload. Walking jurors through [the patients’] treatment records, Stone poured water into a one-gallon bucket each time entries showed that [the patient] was given additional IV fluids, despite notes that she was not urinating enough. The water soon overflowed into a larger container Stone said represented [the patient’s] body, and, importantly, her lungs.” Similarly, the High Court of Ireland awarded damages of 3 million Euros in a case where “the plaintiff received excessive intravenous fluid, exposing him to a significant risk of fluid overload, and causing him to develop pulmonary edema and cardiac arrest”.

In our hospital we manage patients with a conservative physiologically guided fluid strategy, state-of-the-art supportive care together with a novel pharmacologic intervention.[14] Our patients with sepsis and septic shock simply do not develop progressive organ failure from sepsis and our mortality in these patients is less than 10%. This is despite the fact that we are 11% compliant with the SEP-1 mandate.

Furthermore, SEP-1 mandates measurement of a serum lactate within 3-hours of presentation in all patients (Dr Levy does not agree with this; see Appendix 1) with repeat measurement within 6 hours if the initial lactate level is elevated. This mandate is without a scientific basis. A recent analysis which included 16 studies found that 6-hour lactate measurement compliance was unrelated to mortality. Furthermore, it should be noted that in the development of the qSOFA score (SEPSIS-3) the “addition of lactate measurement did not meaningfully improve predictive the validity.” [15]

In summary, there is now overwhelming scientific evidence, supported by legal precedent that not only is the EGDT, SSC and SEP-1 protocols of no benefit to patients they are potentially harmful.[16-18] These protocols violate the American Medical Association (AMA) and American College of Physicians (ACP) code of ethics, [19,20] and the basic Hippocratic Principle of Medicine, “Primum Non Noncere”. We have entered the era of precision medicine [21] and the SEP-1 mandate must be abandoned immediately, before additional patients are harmed. In addition to the harm caused to patients, the SEP-1 mandate has created an administrative nightmare that has wasted hundreds of thousands of work hours and millions of dollars.[1]

Paul E Marik, MBBCh, MD, M.Med,(FCP(SA), DA(SA), Bsc Pharmacology (Hons), DTM&H, FRCP (C), FACP, FCCM, FCCP.



Appendix 1.

Excerpts of the sworn Testimony of Dr Mitchel Levy, dated January 9th 2017, in the State of South Carolina, County of Aiken, in the Court of Common Pleas, Second Judicial Circuit, Civil Action No. 15-CP-02-00794 (this information is in the public domain and available from the court).

Did the 2008 guidelines until 2012 represent the best consensus of knowledge of experts about the treatment of sepsis?

A (Dr Levy). The guidelines represent suggestions for clinicians at the bedside. I think the important thing to remember about guidelines that we always say is they're called guidelines

because they're meant to guide, not dictate care. So, even if someone says I think the Surviving Sepsis Campaign guidelines represent the appropriate standard of care, even if they say that, that doesn't mean they should do everything that the guidelines recommend. They still have to take into account the individual patient in front of them and apply the guidelines to be consistent with what they know this patient would benefit from

Is it true that related to the guidelines from the Surviving Sepsis Campaign that as with all guidelines they represent the best available synthesis of contemporary knowledge in reducing mortality in severe sepsis and therefore should have clinical applicability?

I can't agree with that statement.

And what happens if they're hypotensive?

If they become hypotensive CVP can be a good guiding adjunct for the direction of fluid therapy.

It's either low blood pressure or elevated serum lactate, right?

So, I would not agree with that. Again, I would say that based on the patient's clinical presentation it's reasonable for a physician even in following these guidelines to, in the presence of normotension without evidence of severe acidosis to not get a serum lactate.

The only way that you can follow this guideline is if you get both a blood pressure management and a lactate measurement because you have to have both data points at the first bullet point on the first set of chart, right?

Again, I'm just not going to agree with that.

So, how were you determining in your practice before how much fluid a patient would need?

Well, we would start with 20 CCs per kilogram, which is about two liters, one and-a-half to two liters of fluid. And they would get that fluid immediately upon arriving in the emergency department.

Okay. And for some people that proved adequate?

Right.

And some people it proved inadequate?

And for some people it proved to be too much. And so, for some patients with left ventricular dysfunction with an unrecognized cardiomyopathy, they did worse with that amount of fluid.

References

Klompass M, Rhee C. The CMS Sepsis Mandate: Right Disease, Wring Measure. Ann Intern Med 2016. Rhee C, Gohil S, Klompas M. Regulatory mandates for sepsis care- Reasons for caution. N Engl J Med 2014; 370:1673-76. Rhodes A, Evans L, Alhazzani W et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock:2016. Intensive Care Med 2017. Rhodes A, Evans L, Alhazzani W et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock:2016. Crit Care Med 2017. Buchman TG, Azoulay E. Practice guidelines as implementation science: the journal editors perspective. Intensive Care Med 2017. Dellinger RP, Schorr cA, Levy MM. A users guide to the 2016 Surviving Sepsis Guidelines. Intensive Care Med 2017. Kelm DJ, Perrin JT, Cartin-Cebra R et al. Fluid overload in patients with severe sepsis and septic shock treated with Early-Goal Directed Therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock 2015; 43:68-73. Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015; 19:251. Marik PE, Linde-Zwirble WT, Bittner EA et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes. An analysis of a large national database. Intensive Care Med 2016; ePub:DOI 10.1007/s00134-016-4675-y. Maitland K, Kiguli S, Opoka RO et al. Mortality after fluid bolus in african children with severe infection. N Engl J Med 2011; 364:2483-95. Ognibene FP, Parker MM, Natanson C et al. Depressed left ventricular performance: response to volume infusion in patients with sepsis and septic shock. Chest 1988; 93:903-10. Parker MM, Suffredini AF, Natanson C et al. Response of left ventricular function in survivors and nonsurvivors of septic shock. J Crit Care 1989; 4:19-25. Marik PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Ann Intensive Care 2014; 4:21. Marik PE, Khangoora V, Rivera R et al. Hydrocortisone, Vitamin C and Thiamine for the treatment of severe sepsis and septic shock: A retrospective before-after study. Chest 2017; ePub:http://dx.doi.org/10.1016/j.chest.2016.11.036. Singer M, Deutschman CS, Seymour CW et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801-10. Mouncey PR, Osborn TM, Power S et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372:1301-11. Angus DC, Barnato AE, Bell D et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe investigators. Intensive Care Med 2015; 41:1549-60. Marik PE. The demise of early goal-directed therapy for severe sepsis and septic shock. Acta Anaesthesiol Scand 2015; 59:561-67. Brotherton S, Kao A, Crigger BJ. Professing the values of medicine. The Modernized AMA Code of Medical Ethics. JAMA 2016; 316:1041-42. Snyder L. American College of Physicians Ethics Manual. Sixth Edition. Ann Intern Med 2012; 156:73-104. Marik PE, Varon J. Precision medicine and the Federal sepsis initiative! Crit Care Shock 2016; 19:1-3.