Sepsis is a whole-body inflammatory, overwhelming and life-threatening response to an infection that can lead to tissue damage, organ failure and death. Sepsis kills approximately 258,000 Americans each year, which ranks it as the third leading cause of death in the United States after heart disease and cancer.1
Severe cases of sepsis can lead to septic shock, where systemic inflammation causes tiny blood clots to form, blocking oxygen from vital organs. This leads to organ failure and causes a life-threatening drop in blood pressure.2
Severe sepsis affects more than a million Americans each year, and often occurs in people who are elderly or have weak immune systems.
It’s been estimated that 28–50% of severe sepsis patients die—far more than the number of U.S. deaths from prostate cancer, breast cancer and AIDS combined.3
The number of sepsis cases per year has been on the rise in the U.S.3 This is likely due to a combination of factors, including increased awareness and tracking of the condition, an aging population, the increased longevity of people with chronic diseases, the spread of antibiotic-resistant organisms, an upsurge in invasive procedures and broader use of immunosuppressive and chemotherapeutic agents.
There are more than 1.6 million cases of sepsis every year.4 Up to half of the people who survive face the long-term effects of “post-sepsis syndrome,” including worsened cognitive or mental and physical function.5,6 This commonly results in survivors requiring readmission to the hospital.
One study reports that over 62% of the patients who had a primary diagnosis of sepsis were readmitted to the hospital within 30 days of discharge, and nearly half of children diagnosed with severe sepsis end up being hospitalized again.7
When accounting for all acute care hospital costs, sepsis is the most expensive in-hospital condition in the U.S., costing more than $20 billion a year, or 5.2% of national healthcare costs.8
Sepsis hasn’t typically been a focus of prehospital care providers. But that’s now changing because the medical community has realized that prehospital personnel can accurately detect a patient suspected of being septic, and that by alerting hospital facilities, the receiving hospital can zero in on and attempt to correct the septic shock state before it becomes irreversible.
In 1992, the American College of Chest Physicians and the Society of Critical Care Medicine introduced definitions for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock and multiple organ dysfunction syndromes (MODS). SIRS, is defined as two or more of the following variables:
- Temperature > 38 degrees C (100.4 degrees F) or < 36 degrees C (96.8 degrees F);
- Heart rate > 90 beats per minute;
- Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg; or
- White blood cell count > 12,000/µL or
- < 4,000/µL or > 10% immature [band] forms.9
Stage one of the sepsis continuum, SIRS can be caused by ischemia, inflammation, trauma, infection or several insults combined. Thus, SIRS isn’t always related to infection, but an infection is suspected.
Not all patients with SIRS require hospitalization or have diseases that progress to serious illness. Indeed, patients with a seasonal head cold due to rhinovirus usually fulfill SIRS criteria. Respiratory rate is the most sensitive marker of the severity of illness.
Stage two, defined as “sepsis,”is when two or more SIRS criteria have been met but there’s also a confirmed infection. The patient will demonstrate positive blood and urine cultures as well as positive diagnostic imaging.
Stage three is “severe sepsis.” This is when the patient has a diagnosis of sepsis and also shows the beginnings of multiorgan failure or dysfunction, hypoperfusion or hypotension. Patients will demonstrate systemic symptoms such as hypoxia, oliguria (i.e., decreased urine output), lactic acidosis, altered mental status, skin and platelet dysfunction.
Stage four is “septic shock.” Septic shock is diagnosed if there’s refractory hypotension, and that IV fluid administration alone isn’t enough to maintain a patient’s blood pressure. Diagnosis of sepsis-induced hypotension is made when systolic blood pressure (SBP) is < 90 mmHg, mean arterial pressure (MAP) is < 70 mmHg, or SBP decreases ≥ 40 mmHg without other causes for hypotension.10
Watch: Author Paul Banerjee discusses septic shock assessment, treatment and protocol at EMS Today 2016.
Pathophysiology & Treatment
Shock is a fluid and dynamic state. During the initial phase of septic shock, the immune system’s large-scale inflammatory response results in hypoperfusion due to massive vasodilation, increased capillary permeability, decreased systemic vascular resistance and hypotension.
The lack of oxygen leads to hypoxia and impaired cellular respiration that leads to lower pH levels, and cells are forced to metabolize glucose anaerobically, which leads to lactate formation and lactic acidosis characterized by lactate levels > 4 mmol/L and serum pH < 7.35.
To compensate, the body employs physiological mechanisms in an attempt to reverse the early condition of shock. The body releases norepinephrine, which causes vasoconstriction with a mild increase in heart rate, as well as epinephrine, which causes an increase in heart rate with a small effect on the vascular tone.
The combined effect is an increase in blood pressure and a diversion of blood to the heart, lungs and brain.
If the infection isn’t successfully treated, the body’s compensatory mechanisms begin to fail and the shock proceeds to the progressive stage. The prolonged vasoconstriction and decreased perfusion of cells causes vital organs to be compromised due to reduced perfusion. Anaerobic metabolism continues and increases the body’s metabolic acidosis state.
The refractory stage of shock results when the vital organs have failed, leading to brain damage and cell death. This ultimately causes the patient’s death.
Early goal-directed therapy (EGDT) has been the primary treatment for severe sepsis and septic shock in the intensive care unit after a study showed that patients with severe sepsis and septic shock had lower mortality when EGDT is initiated within six hours of presentation.11 This approach involves adjustments of cardiac preload, afterload and contractility to balance oxygen delivery with oxygen demand.
As in other forms of shock, initial treatment involves IV fluid administration to combat the body’s loss of fluids. When fluid therapy isn’t successful in improving hypotension and reversing the shock state, vasopressors may be used. Recent guidelines suggest the use of dopamine or norepinephrine.10
Dopamine increases heart rate and stroke volume, leading to an increase in cardiac output and MAP. The vasoconstrictive characteristics of norepinephrine can increase MAP, effective circulating blood volume, and venous return and preload, with minimal increase of heart rate or stroke volume. Although observational studies have shown higher death rates with dopamine vs. norepinephrine in patients with shock, the few randomized trials to date have been too small to provide meaningful data.12
EGDT is deemed successful when there’s a normalization of hemodynamics. This is guided primarily by keeping the body’s urine output> 0.5 mL/kg/hr, maintaining a MAP > 65 mmHg, and normalizing lactate levels.10
The treatment of sepsis includes rapid blood culture sampling and IV delivery of antibiotic medication within the first hour of recognition of severe sepsis and septic shock.10
The Role of Shock Index
Many agencies use SIRS criteria to screen for sepsis. SIRS criteria does correlate to mortality rates, however, the SIRS criteria are nonspecific to infection and can be physiologically manipulated by psychosocial stresses. EtCO2 is also being used, however, EtCO2 doesn’t correlate directly with lactate levels, which is considered the gold standard for the diagnosis of sepsis and septic shock.
The cost of point-of-care lactate monitors can run about $10,000, not to mention the cost of calibration and test strips or cartridges. So how can a lactate equivalence be obtained without the cost of a lactate monitor?
Shock index (SI), the ratio of heart rate to SBP, has been shown to identify high-risk septic patients.15
SI is used as a marker for severe hypovolemia during trauma. There’s a growing body of evidence that SI is the most promising vital sign to detect acute hypovolemia and circulatory failure. In a retrospective analysis of 21,853 patients, 275 patients who presented to the ED for urgent medical care with an SI > 0.9 needed immediate treatment and admission. Although heart rate and SBP still presented within normal limits, these patients displayed reduced central venous oxygen saturation and lactate acidosis, all indicators for the presence of hypovolemic shock.16
Three recent studies attempted to correlate lactate levels with SI in the prehospital setting.
The first looked to see if SI and fever were a valuable prehospital protocol for the identification of suspected SIRS patients who would benefit from EGDT. Researchers studied 5,182 ED patients, of which 3,550 were brought in by EMS and 1,632 by private vehicle. They screened for patients with an SI > 0.9 and a body temperature > 100.4 degrees For < 96.5 degrees F. Patients in the EMS group had increased age, were more likely to be male and had a marked increased mortality and hospital length of stay (p < 0.01). The SI and SIRS criteria for temperature were highly sensitive for increased mortality (96%) and moderately specific (52%).17
The use of SI and temperature to rapidly identify septic patients by EMS providers could provide for more rapid fluid resuscitation and improved outcomes.
Another study—a retrospective analysis of a cohort of adult ED patients at an academic community trauma center—correlated serum lactate to the SI of 2,824 patients with a suspected infection and who were screened for sepsis. Patients with an SI > 0.7 were three times more likely to have elevated serum lactate. Patients with an SI ≥ 0.7 performed as well as SIRS in negative predictive value and it was the most sensitive screening test for hyperlactatemia and 28-day mortality. Interestingly, patients with an SI ≥ 1.0 were found to be the most specific predictor of both outcomes. Patients screened for sepsis with an SI performed as well as any initial screening tool for sepsis.15
The third study aimed to determine whether modified shock index (MSI)—the ratio of heart rate to MAP—is associated with mortality rate that’s superior to heart rate, blood pressure, or the SI in emergency patients. A retrospective database review performed in the ED looked at 22,161 patients who received IV fluids and found that MSI was a better predictor of ED patient mortality vs. heart rate and blood pressure alone. Patients with an MSI > 1.3 or < 0.7 were considered to be strong predictors of death.
Most notably, patients with these vital signs were also found to be important predictors for worsening patient’s outcomes: SBP < 90 mmHg; diastolic blood pressure (DBP) < 60 mmHg; and heart rate > 120 beats per minute. Mechanical obstruction of normal cardiac output and a subsequent lowering in systemic perfusion, most specifically, was found in patients with an MSI > 1.3, which was typically associated with hypovolemic shock, cardiogenic shock and obstructive shock. Signs of a hypodynamic circulation shock state occurred in these clinical states, with low stroke volume and ow systemic vascular resistance. Distributive shock patients were found to have an MSI < 0.7. These patients were found to be in a clinical hyperdynamic state with increased circulatory volume, decreased peripheral vascular resistance, systemic vasodilation with a decreased blood pressure. In addition, these patients exhibited increased intracranial pressure and arrhythmias.18
The reason MSI was so diagnostically helpful was based on the fact that the DBP of a critical patient will decrease before the SBP does. MAP is a predictor for patient mortality and clinically best represents organ tissue perfusion. Furthermore, it was a good indicator of hemodynamic instability and clinical severity of illness.
MSI was seen to be a valuable tool for raising suspicion in shock, sepsis and lactate. MSI can be positive predictor of shock, especially when heart rate and blood pressure are not, such as when a patient is in the compensatory shock phase.
Polk County Sepsis Protocol
Polk County Fire Rescue (PCFR), located in central Florida, covers 2,010 square miles and serves a population of 650,000. It’s the 39th largest fire department in the U.S and has a network of 44 fire and rescue stations, more than 150 vehicles and apparatus, and employs nearly 600 full-time personnel.
In 2014–2015, PCFR received 99,421 calls and transported 74,505 patients. PCFR incorporates three major ALS municipal city fire departments: Lakeland, Winter Haven and Lake Wales.
Polk County has five hospitals, with three percutaneous coronary intervention centers and an award-winning integrated 9-1-1 medical priority dispatch system. The system involves almost 1,000 prehospital providers, including volunteer and first response personnel.
The sepsis protocol was based on Centers for Disease Control and Prevention guidelines for vital signs. In addition, modified SIRS criteria is used to screen for sepsis. Because we can’t draw blood or obtain labs on patients, the white blood cell count criteria was removed and replaced with high-risk conditions for potentially septic patients. If at least two modified SIRS categories are deemed positive, then an SI or MSI is calculated to find a lactate equivalence. If either index is positive, a sepsis alert is activated and the receiving hospital is notified. (See Table 1 and Figure 1.)
The most shocking part of diving into the conundrum of sepsis is the lack of real hospital awareness of this emergent medical condition. Prior to the development of our protocol we found that the local hospitals only recorded the most basic of data in regard to sepsis. It was almost treated as a diagnosis of exclusion, and not treated with the same respect as would a STEMI, stroke or trauma alert.
International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign (SSC) and condensed into two care bundles. In 2010, the SSC published results from its improvement program showing that, although an absolute mortality reduction of 5.4% was seen over a two-year period in line with increasing compliance with the bundles, reliability wasn’t achieved and bundle compliance reached only 31%. Clearly, greater awareness and faster recognition of sepsis in order to quickly initiate basic care was required.19
On Oct. 1, 2015, the Centers for Medicare & Medicaid Services (CMS) issued new benchmarks for the care of severe sepsis and septic shock that all U.S. hospitals must meet for proper documentation and reimbursement.
First, lactate level > 2 mmoL is a criteria for defining severe sepsis. The EGDT inclusion criteria for severe sepsis or septic shock is a patient who meets two or more SIRS criteria, an SBP < 90 mmHg despite fluid challenge of 20–30 cc/kg,or a lactate level ≥ 4 mmoL.20
The SSC guidelines suggest the use of an initial crystalloid bolus of 30 cc/kg for resuscitation of severe sepsis and septic shock. They also recommend maintaining a MAP > 65 with vasopressors, as research suggests that a MAP < 65 is associated with an increase in mortality among septic shock patients.10
CMS guidelines state that you must have two blood culture sets drawn prior to antibiotic administration and don’t mention an exception for a significant delay in treatment. However, the advantages of drawing appropriate cultures prior to antibiotic administration must be weighed against the evidence showing that delaying appropriate antibiotic therapy causes an increase in mortality. One study shows that for every hour delay in antibiotic administration for a hypotensive septic shock patient, the mortality rate increases by 7.6%.21
All five Polk County hospitals are active participants in the sepsis protocol. The most impressive part of Polk County’s data, primarily accumulated from Lakeland Regional Health, is the amazingly low mortality rate of 17%, which is about twice lower than the national average of 33%. (See Tables 2 and 3.) This demonstrates the great work and diligence of our PCFR crews in the early recognition of this devastating disease. Furthermore, the crews are recognizing patients prior to the development of SIRS and finding them in a compensated shock state before progressive and irreversible shock.
By using MSI and SI, prehospital providers can recognize septic patients early in the compensatory shock phase. By correlating the respective values, we can get a correlative lactate value and provide an accurate sepsis screening tool that allows us to recognize sepsis earlier and provide treatment that will help lower mortality rates and the cost of care.
The sepsis protocol has enabled PCFR to collaborate more closely than ever before within our local hospital partners. The great outcomes have strengthened our partnership and have provided PCFR with a recognized, respected, appreciated and vital seat at the table in the role of patient care. This has helped improve patient care outcomes not just with sepsis but also stroke, pediatrics, cardiac arrest and trauma, and develop a patient-centered care approach.
1. Sepsis Alliance. (2016.) How large a problem is sepsis? Retrieved July 26, 2016, from www.sepsis.org/faq/problem.
2. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis.Virulence. 2014;5(1):4–11.
3. National Institute of General Medical Sciences. (August 2014.) Sepsis fact sheet. Retrieved July 26, 2016, from www.nigms.nih.gov/Education/Pages/factsheet_sepsis.aspx.
4. Elixhauser A, Friedman B, Stranges E. (October 2011.) Septicemia in U.S. hospitals, 2009: Statistical brief #122. Healthcare Cost and Utilization Project. Retrieved July 26, 2016, from www.hcup-us.ahrq.gov/reports/statbriefs/sb122.jsp.
5. Sepsis Alliance. (2016.) What is PSS? Retrieved July 26, 2016, from www.sepsis.org/sepsis/post_sepsis_syndrome/.
6. Iwashyna TJ, Ely E, Smith DM, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787–1794.
7. Sutton JP, Friedman B. (Sept. 2013.) Trends in septicemia hospitalizations and readmissions in selected HCUP states, 2005 and 2010: Statistical brief #161. Healthcare Cost and Utilization Project. Retrieved July 26, 2016, from www.hcup-us.ahrq.gov/reports/statbriefs/sb161.pdf.
8. Torio CM, Andrews RM. (August 2013.) National inpatient hospital costs: The most expensive conditions by payer, 2011: Statistical brief #160. Healthcare Cost and Utilization Project. Retrieved July 26, 2016, from www.hcup-us.ahrq.gov/reports/statbriefs/sb160.pdf
9. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–1655.
10. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.
11. 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;345:1368–1377.
12. Bohan JS. (Mar. 3, 2010.) Dopamine vs. norepinephrine in treatment of shock. NEJM Journal Watch. Retrieved July 26, 2016, from www.jwatch.org/em201003030000001/2010/03/03/dopamine-vs-norepinephrine-treatment-shock.
13. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.
14. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762–774.
15. Berger T, Green J, Horeczko T, et al. Shock index and early recognition of sepsis in the emergency department: Pilot study. West J Emerg Med. 2013;14(2):168–174.
16. Mutschler M, Nienaber U, Münzberg M, et al. The Shock Index revisited—A fast guide to transfusion requirement? A retrospective analysis on 21,853 patients derived from the TraumaRegister DGU. Crit Care. 2013;17(4):R172.
17. Milzman D, Moynihan M, Phillips C. 561: Early identification of sepsis patients using shock index and temperature in prehospital setting predicts increased hospitalization and survival. Crit Care Med. 2012;40(12 Suppl 1):1–328.
18. Liu Y, Liu J, Fang ZA, et al. Modified shock index and mortality rate of emergency patients. World J Emerg Med. 2012;3(2):114–117.
19. Daniels R. Surviving the first hours in sepsis: Getting the basics right (an intensivist’s perspective). J Antimicrob Chemother. 2011;66 Suppl 2:ii11–23.
20. Baciak K. (Dec. 12, 2015.) Sepsis care: What’s new? The CMS guidelines for severe sepsis and septic shock have arrived. emDocs. Retrieved July 26, 2016, from www.emdocs.net/sepsis-care-whats-new-the-cms-guidelines-for-severe-sepsis-and-septic-shock-have-arrived/.
21. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589–1596.
New Sepsis-3 Guidelines
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) evaluated the different categories of SIRS and sepsis in an attempt to simplify the diagnosis of sepsis.
The Sepsis-3 recommendations, published in February, defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%.13
Sepsis-3 recommended that septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a MAP of > 65 mmHg and serum lactate level > 2 mmol/L ( > 18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates > 40%.13
The conclusion of Sepsis-3 was that, in out-of-hospital, ED,or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least two of the following clinical criteria that together constitute a new bedside clinical score, termed quick SOFA (qSOFA): respiratory rate > 22, altered mentation, or SBP of < 100 mmHg.13
The downfall of the new criteria, however, was that it was based on only an ICU-related study. The recommendations were to develop a two-tiered category of sepsis and septic shock, with severe sepsis removed. Further review of the data showed that qSOFA was equivocal to SIRS for sepsis screening outside of the ICU patients with a 0.79 vs. 0.76, 95% CI.14
So the bottom line is that your agency shouldn’t change protocols for sepsis recognition, and should continue to use SIRS criteria until prospective validation of the new recommendations is achieved.