Sepsis detection and monitoring in EMS

For EMS providers to truly understand sepsis, they must also understand the systemic inflammatory response syndrome (SIRS) cascade.

SIRS, as a term to describe the complex physiological response to insult, first originated at a critical care medicine conference in 1991 [1]. By establishing a conceptual framework for this progressive injurious process, researchers laid the groundwork for the study of SIRS and its sequelae.

What is sepsis?

SIRS is an inflammatory response that affects the entire body rather than a localized area [1]. A variety of infectious and non-infectious factors can trigger this inflammatory response. For a diagnosis of SIRS, the patient must have at least two of these signs [1]:

1. Hyperthermia or hypothermia,

2. Tachycardia,

3. Tachypnea or hyperventilation, or

4. Leukocytosis (an increase in the number of white blood cells) or leukopenia (a decrease in white blood cells).

If SIRS is caused by a confirmed infectious process, the condition is known as sepsis [1]. An analysis of state hospital discharge records estimates 751,000 cases of sepsis in the U.S. each year with more than half of those patients requiring admission into an intensive care unit [2]. Although the rapid rise of overall sepsis mortality seen in previous decades has slowed, significant race, ethnic, and gender disparities in mortality continue to exist while population aging continues to drive increases in sepsis-associated mortality [3].

In both SIRS and sepsis, inflammatory mediators produce vasodilation. The clinical effect of this vasodilation is usually not apparent however, because of the body’s compensatory mechanisms. Increases in the patient’s heart rate will produce greater cardiac output which will maintain normal blood pressures.

However, as sepsis continues, compensatory mechanisms become weaker and eventually are not able to overcome the effects of systemic vasodilation. As a result, the patient begins to develop signs of inadequate tissue perfusion. If sepsis produces organ dysfunction, a hypoperfusion abnormality, or hypotension, the term severe sepsis applies [1].

If the hypotension persists despite adequate fluid resuscitation in patients with severe sepsis, the condition has progressed to septic shock [1]. Septic shock affects about 230,000 patients in the U.S. every year resulting in about 40,000 deaths [4].

As many as 30 percent of patients with septic shock will develop myocardial depression [5]. Although lactate measurement and monitoring is widely used, the specific threshold for diagnosis and the role of continued monitoring in septic shock is unknown [4].

Of the patients who develop SIRS, roughly one in five will develop sepsis, 18 percent will develop severe sepsis, and about 4 percent will progress to septic shock [6]. Finally, the patient reaches the multiple organ dysfunction stage when impairment in two or more organ systems develops and the patient can no longer maintain homeostasis without therapeutic intervention [7].

Sepsis alert by EMS improves patient outcomes

Early recognition and management of sepsis are critical components of reducing mortality from multiple organ dysfunction syndrome [8]. Survival to hospital discharge may be as high as 79 percent when patients receive antibiotic therapy within one hour of the onset of hypotension secondary to septic shock [9]. For every hour delay in administration of effective antibiotic therapy beyond the first hour, survival drops almost 8 percent [9].

Fortunately, patients with sepsis receive both intravenous fluids and antibiotics much sooner if they arrive in the emergency department (ED) by ambulance instead of a different mode of transportation [10]. When paramedics document a primary impression of sepsis, patients generally receive antibiotic treatment even sooner [11]. Patients are three times more likely to survive to hospital discharge when EMS personnel identify severe sepsis in the field and initiate a Sepsis Alert Protocol before arrival in the ED [12]. This type of alert protocol includes the administration of high-flow oxygen, a 20 mL/kg bolus of crystalloid fluids, close monitoring of the patient’s vital signs, breath sounds, and glucose levels, and early notification of hospital personnel.

Unfortunately, EMS providers fail to recognize the presence of severe sepsis about half of the time [12]. One significant reason for this failure is incomplete vital signs assessment, including temperature measurement. EMS personnel were 11 times more likely to recognize and document sepsis when they obtained the patient’s temperature [13].

Lactate monitoring as a tool

One test that may prove useful for the prehospital diagnosis of sepsis is lactate measurement. In a process called glycolysis, cells of the body convert glucose into a molecule called pyruvate, which releases small amounts of energy for the cells to stay alive. Pyruvate then undergoes further chemical reactions involving oxygen, which releases even greater amounts of energy. However, when the body is under stress, glycolysis can increase between 100 and 1000 times normal resulting in a build-up of pyruvate in the tissues [14]. The reaction that fully metabolizes the pyruvate is significantly slower than the reaction that creates the pyruvate in the first place. The excess pyruvate is converted to a different molecule called lactate.

The hypoperfusion present in sepsis reduces oxygen delivery to the tissues resulting in an increase in lactate levels [15]. Although many clinicians use a lactate level of 4.0 mmol/L as the diagnostic threshold for sepsis [16], patients with abnormal lactate levels below this threshold are still at an increased risk for death even when those patients are hemodynamically stable [17].

Handheld point-of-care (POC) lactate monitors can provide rapid and accurate measurement of the patient’s blood lactate levels [18,19]. These devices allow the health care team to obtain a measurement at the patient’s bedside rather than having to wait for laboratory results. Additionally, lactate levels continue to rise in the unprocessed sample, which could result in falsely elevated measurements if there is a delay in laboratory processing. Venous sample analysis with a handheld monitor can be delayed for up to 15 minutes at room temperature without a significant change in results [20].

Monitoring CO2 may work

Although handheld POC lactate monitors are relatively inexpensive, they are not widely available in the prehospital setting. As a result, researchers have attempted to find a more commonly available and reliable alternative for the field. End-tidal carbon dioxide (ETCO2) measurement may be that alternative.

In a prospective observational study conducted at Orlando Regional Medical Center, researchers investigated the relationship between capnography and serum lactate values and whether baseline capnography values could serve as a predictor for mortality in patients with suspected sepsis [21]. Inclusion criteria required at least two of the four criteria for SIRS and a suspicion of having an infection. The researchers ordered baseline capnography readings and lactate levels early in the treatment and the capnography readings were obtained before any mechanical ventilation. The study was adequately powered to detect a 6 mm Hg ETCO2 difference between survivors and non-survivors.

Upon analysis, the researchers found a significant inverse relationship between baseline ETCO2 readings and serum lactate levels across patients with sepsis, severe sepsis, and septic shock. After adjusting for other factors associated with mortality in sepsis, patients with an abnormal baseline ETCO2 value (defined as above 45 mm Hg or below 35 mm Hg) were six and a-half times more likely to die than patients with a normal reading.

In an undifferentiated patient population, ETCO2 values outperformed all other vital signs normally obtained by EMS agencies (pulse, blood pressure, respiratory rate, and oxygen saturation) in predicting in-hospital mortality [22]. The predictive qualities of ETCO2 may be directly related its relationship with perfusion [23,24], hypoventilation [25], bicarbonate levels [26-29], and lactate levels [21,30,31].

Although the Orlando Regional Medical study [21] demonstrated an association between baseline capnography values and mortality, researchers at the University of Florida Health Jacksonville found no correlation between changes in ETCO2 levels and changes in either central venous oxygen saturation or serum lactate levels over a six hour period in patients diagnosed with severe sepsis or septic shock [32]. There was a trend however, toward a significant relationship between ETCO2 and lactate at baseline. The authors conclude that even though ETCO2 had no utility as a clinical end point for resuscitation, it may have value as a screening tool for patients with suspected sepsis.

Summary

The pathway from SIRS to septic shock and multiple organ failure is a significant source of morbidity and mortality in the U.S. Early recognition and prompt administration of resuscitative fluids and antibiotics as part of a quantitative resuscitation protocol are critical for improving outcomes from septic shock [33].

Unfortunately, EMS providers often fail to recognize the early warning signs of sepsis, often as a result of an incomplete assessment. The addition of temperature and ETCO2 monitoring may provide field personnel with objective evidence with which to make a more accurate field diagnosis.

References

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