Coyle’s Conundrums: Sepsis Early Detection is the Best Direction

Posted on Thu, Jul 17, 2014

By Dr. John Coyle, EVP, EmCare Physician Services

Hippocrates claimed that sepsis was the process by which flesh rots, swamps generate foulsepsis airs, and wounds fester.1 In an early study of sepsis it was postulated that the systemic pathogen spread was the primary cause. Even with advancement of antibiotic therapy, that concept did not fully explain the pathophysiology behind the morbidity and mortality rates of the disease process.

The term “sepsis” was more formally defined in 1992 by an international consensus panel as a systemic inflammatory response to infection (systemic inflammatory response syndrome, or SIRS), noting also that septicemia (commonly thought of as the presence of “positive blood cultures”) was neither a necessary condition nor a useful term.2 Patients could be minimally ill with “positive blood cultures” or in the ICU in shock without “positive blood cultures”. Speaking of septic shock, this is defined as severe sepsis complicated by either hypotension that is refractory to resuscitation or hyperlactemia (lactate level > 4).3 Since signs of hypotension and tachycardia are seen in other presentations they should be considered a contributing sign rather than defining signs.

The number of cases of sepsis in the United States exceeds 750,000 per year with pneumonia being the most common cause, followed by intra-abdominal and urinary tract infections.4 The infectious process, if not treated, can lead to hypoperfusion followed by a cascade of responses by multiple organ systems. Hypoperfusion is manifested by oliguria, hypoxemia, altered mental status and elevated serum lactate levels. The final stages of sepsis include end organ damage followed by end organ failure and death.

Early manifestations of the body’s response to an infectious agent’s systemic spread can be nonspecific and include fever, lethargy, fatigue, chills, nausea and vomiting. These signs and symptoms may be subtle, especially in the very young and older population. Since these patients at the extremes of age (the young with immature immune response, and the elderly with diminished immune response due to age and disease) are more vulnerable to systemic manifestations, a higher index of suspicion for early sepsis is prudent in the differential diagnosis.

Fever, tachycardia, tachypnea, hypotension and leukocytosis with bandemia, are the criteria and hallmarks for SIRS. The physical exam must be thorough and include searching for any potential sources of infection. Those would include the 3 W's (wind, water and wound): pneumonia, urinary tract infection and wound infection. Additional physical signs such as a cardiac friction rub or murmur (endocarditis), abdominal findings consistent with acute abdomen or pelvic inflammatory disease, and unexplained pain (osteomyelitis and necrotizing fasciitis) should also be considered in the initial physical assessment.

According to the latest evidence and information on best practices, initial workup, at the discretion of the treating physician, may include CBC, chemistry including lactate and liver function tests, coagulation studies, and cultures of blood and any potential sources or sites of infection. Various studies have shown that less than 33% of patients with sepsis have “positive blood cultures.”5 Chest radiograph, EKG, appropriate CT scans, ultrasound, joint aspirations, and lumbar puncture may also be considered in the search for sources of infection.

Treatment modalities include support of ABC's with supplemental oxygen and fluid resuscitation, which may be vigorous, particularly in the presence of hypotension, which if persistent may lead to or worsen hypoperfusion of critical organ systems and at the cellular level.6 Fluid resuscitation is a cornerstone of therapy and should be aggressive with isotonic crystalloid. Additional adjunctive therapy should be considered if fluids alone cannot adequately and consistently maintain mean arterial pressure (MAP) between 65 and 70. Adjunctive pressor agents such as dopamine, dobutamine, or norepinephrine may be considered. Broad-spectrum antibiotics, based on suspected sources of infection, should be administered early in the emergency department after appropriate cultures are obtained, but not delayed for culture procurement if the patient is severely ill. If an internal infectious process amenable to surgical intervention is suspected, urgent surgical consultation should be sought. Debridement of external sources with appropriate sterile techniques should include removal of any foreign bodies.

In summary, as is the case with most diseases, early detection and treatment is the cornerstone to improving patient outcomes. A higher index of suspicion for early sepsis must be employed especially for those on either end of the age spectrum. There is no one specific sign of early sepsis; however, common findings of fever, tachycardia, tachypnea and hypotension, if not addressed, can lead to development and/or worsening of SIRS. If undiagnosed or inadequately treated, the inflammatory cascade will likely continue resulting in end organ damage and possibly organ failure and death. Aggressive fluid resuscitation, oxygenation and ventilation, the use of broad-spectrum antibiotics, and continuous monitoring (invasive if indicated in an ICU setting) will help mitigate further extension and help improve outcomes.


  1. Manjong. The Acient riddle of sigma eta psi iota (sepsis). J Infect Dis 1991;163:937-945
  2. Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM Consensus Conference on sepsis and organ failure. Chest 1992; 101: 1481-1483
  3. Derek C. Angus, M.D., M.P.H. and Tom Van der Poll, M.D., PhD. N Engl J Med 2013; 369: 840-851 2013 Aug 29
  4. Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalization, costs, and outcomes of severs sepsis in the United States 2003 to 2007. Crit Care Med 2012; 40: : 754-756{Erratum, Crit Care Med 2012;40:2932
  5. Andre Kalil, M.D., M.P.H.; Chief Editor:  Michael R. Pinsky M.D., CM, Dr hc, FCCP, MCCM , Medscape 2014 Mar 31
  6. Asfar P. Meziani F. Hamel JF, etal; SEPSISPAM investigators. High versus low blood - pressure target in patients with septic shock N Engl J Med. 2014; 370: 1583-1593 April 24, 2014


John CoyleDr. John Coyle is the Executive Vice President of EmCare Physician Services. Dr. Coyle is a member of the American Osteopathic Association, the American College of Osteopathic Emergency Physicians, the Florida Osteopathic Medical Association, the American College of Emergency Physicians and the American Heart Association. He is certified in Advanced Trauma Life Support and serves as an instructor for Advanced Cardiac Life Support. In addition to his commitment to patient care, Dr. Coyle has dedicated much of his career to mentoring and developing physician leaders and supporting medically underserved areas.

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