Sepsis: Clinical sciences

Sepsis is an exaggerated immune response to infection associated with organ dysfunction, shock, and death. The infection can be bacterial, viral, or fungal, and may originate from any tissue, initiating a complex interplay between infectious virulence factors and host defense mechanisms. The main goals of management are to identify and treat the infection while maintaining hemodynamic stability to prevent or minimize organ damage. Once you identify sepsis or septic shock, you should provide immediate supportive care and begin searching for the underlying source of infection.

When you encounter a patient presenting with signs and symptoms of sepsis, first perform an assessment with a validated metric, such as the systemic inflammatory response syndrome, or SIRS criteria. There are numerous causes of SIRS like sepsis, dehydration, and adrenal insufficiency; so sepsis will cause SIRS, but SIRS is not always due to sepsis.

To diagnose SIRS, at least two criteria must be met. These include WBCs either below 4,000, so leukopenia, or above 12,000, so leukocytosis; as well as a body temperature either below 36 degrees celsius, so hypothermia, or over 38 degrees celsius, so fever; heart rate above 90 beats per minute, so tachycardia; and respiratory rate over 20 breaths per minute, so tachypnea. Now, if the SIRS criteria are not met, you should consider an alternative diagnosis. On the other hand, the presence of known or suspected infection together with SIRS should raise suspicion for sepsis. In addition, if systolic blood pressure, or SBP, is below 90 mmHg or falls 40 mmHg below baseline, your patient has septic shock.

While the SIRS criteria help you identify patients with sepsis, other metrics, such as the Sequential Organ Failure Assessment or SOFA score, may help identify those at greatest risk of poor outcomes. SOFA evaluates parameters including mental status, mean arterial pressure, or MAP, respiratory function, creatinine, bilirubin levels, and platelet count. The higher the score, the worse your patient’s prognosis.

Now that sepsis or septic shock has been identified, there are several tasks, known as the 1-hour sepsis bundle, that you’ll need to complete. These measures are to ensure that the underlying infection and hemodynamic status are addressed quickly, as failure to do so can result in disastrous outcomes for your patient. First, measure blood lactate level STAT, which will be used soon to help guide hemodynamic management. Second, collect blood cultures, after which you will begin broad spectrum IV antibiotics. Finally, focus on the SBP and the lactate level results.

If the SBP is above 90 mmHg and the lactate level is normal, your patient has sepsis without shock. On the other hand, if your patient's presenting or subsequent SBP is below 90 mmHg or has fallen 40 mmHg below baseline, or if the lactate level is above reference range, your patient has septic shock. The presence of an elevated lactate level is an indirect indicator of organ dysfunction, as lactate is produced in the setting of hypoperfusion.

Alright, let’s take a look at sepsis without shock. These patients can be continued on maintenance IV fluids. The rate of IV fluid infusion should be adequate to maintain a urine output of 0.5 mL/kg/h or more and a capillary refill time (CRT) of less than 3 seconds, as these are reliable indicators of tissue perfusion that can be observed at the bedside in a stable patient.

On the flip side, there’s patients with septic shock. These patients are inherently unstable and will require hemodynamic resuscitation. Once septic shock is recognized, immediately begin an IV infusion of IV crystalloids dosed at 30 mL/kg. Consider admission to the ICU and placement of catheters for invasive hemodynamic monitoring, including an arterial line and a central venous catheter, or CVC. During the infusion, MAP should be monitored, with a target of 65 mmHg or above. MAP can be calculated from manual blood pressure readings, but these are much less accurate in the setting of hypotension than those measured by an arterial line.

If the MAP falls below 65 mmHg, IV vasopressors, such as norepinephrine or dopamine, should be added. Vasopressors are best administered through a CVC, but if one has not been placed, they can also be given through a peripheral IV. However, there is a small risk of peripheral tissue necrosis associated with peripheral infusion of vasopressors, especially if given for long periods of time. If the MAP remains below target, additional vasopressors, corticosteroids, and even RBC transfusion may be added to reach a MAP of 65 or more. Once a MAP of 65 mmHg is achieved, the rate of crystalloid infusion and doses of vasopressors should be continued and subsequently titrated to maintain this goal.

Now, whether your patient has sepsis with or without shock, establishing hemodynamic maintenance completes the 1-hour bundle, but you’re far from done! You’ll need to closely monitor indicators of perfusion and hemodynamic parameters, as even stable patients with sepsis or septic shock can decompensate quickly. Failure to maintain adequate perfusion will inevitably lead to hypoperfusion of vital organs and organ system failure.