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Continuing Education for Health Professionals

Sepsis: Immune Response Meltdown

Module 11


Sepsis is a potentially lethal syndrome. When the septic response is triggered by an infection, inflammation can be found throughout the entire vascular system of the body. Inflammatory molecules pour into the circulation and spread through the body, injuring the endothelium that lines the blood vessels. The damaged vascular endothelial cells reduce perfusion into adjacent tissues, and organs or portions of organs become hypoxic.

Capillaries with injured endothelia become leaky in sepsis and blood volume is lost. Under the onslaught of systemic inflammation and organ dysfunction, the normal systemic mechanisms can no longer replenish the depleted blood volume. The result is hypovolemia and a further reduction in the perfusion of tissues. Without treatment and supportive medical management, hypoxia causes key organs to fail, and, as more organs begin to fail, the patient becomes more likely to die.

In sepsis, volume loss is a critical problem. To resuscitate a septic patient requires administration of multiple liters of fluid. Sometimes, however, even copious fluid resuscitation cannot shore up the patient’s dropping blood pressure; at this point, septic shock has set in. Even with optimal treatment, mortality from severe sepsis or septic shock averages 40% and can exceed 50% in the sickest patients.

In its early stages, sepsis may resemble a variety of other disorders, so it can be difficult to diagnose. Rapid diagnosis is essential, however, because sepsis is a worsening disorder with a mortality rate that steadily increases the longer treatment is delayed.

The mortality and morbidity of severe sepsis can be improved by effective clinical interventions applied in a timely and systematic manner. Like heart attacks and strokes, sepsis treatment is time-dependent and must be initiated upon recognition of the disease.

Clinical studies have led to a protocol optimizing the diagnosis and treatment of sepsis. This protocol is called early goal directed therapy (EGDT). EGDT should be started when a patient presents to the ED, standard Med/Surg unit or ICU with signs and symptoms of sepsis.

Source control should be accomplished within the first 12 hours when the patient is able to tolerate it. Any infected or potentially infected sites should be drained, cleaned, or removed, because persisting pockets of microbes will continue to trigger the septic reaction. All indwelling devices are examined and, if infected, must be removed. Surgical advice or participation is often needed because abscesses and empyemas must be drained and infected tissues should be debrided or removed.

Protective and supportive measures for a critically ill patient should be set in place. These provisions include ensuring adequate nutrition, treating hyperglycemia, and instituting prophylaxis against deep venous thromboses and stress ulcers.

The guidelines also recommend that goals of care and prognosis be discussed with the patient and family and that they be incorporated into the treatment and end-of-life planning. Palliative care principles are used where appropriate. These goals need to be addressed as soon as feasible, but no later than 72 hours after ICU admission (Buckman, 2013).

Sepsis is common: it affects millions of people around the world and kills 1 in 4 (often more) and the incidence of sepsis is increasing. Sepsis is also expensive: the average medical cost is >$22,000 per case.

Sepsis is a major concern of the critical care health system. More than half of patients with severe sepsis need ICU care. And, although 2% to 3% of all hospitalized patients have severe sepsis, those patients account for 20% of hospital ICU admissions.

In spite of intensive research, sepsis remains potentially fatal. Severe sepsis and septic shock are the tenth leading cause of death in the United States, officially accounting for 9.3% of all deaths each year. Organ failure is more often listed as the cause of death than is the sepsis that caused it, and it has been estimated that sepsis actually causes or contributes to approximately 30% of all U.S. deaths.

Although time zero is defined differently in some hospitals, the Surviving Sepsis Campaign defines it as the time a septic patient is triaged in the ED. The 2012 guidelines recommend two bundles that should be completed within three hours and six hours of time zero.

The bundle to be completed within three hours of time zero is (Buckman, 2013):

  1. Draw lactate levels.
  2. Draw blood cultures before antibiotics are given, but do not delay administration of broad-spectrum antibiotics more than 45 minutes for blood culture draw
  3. Broad-spectrum anti-infective agents should then be administered that target likely pathogens (bacterial, fungal or viral)
    • Anti-infective therapy should be reassessed daily for possible de-escalation
  4. A 30 ml/kg bolus of crystalloid (eg normal saline) should be given for hypotension or a lactate of 4 mmol/l
    • Colloids may be given if large amounts of crystalloids are required
    • Avoid hetastarch

Once severe sepsis is recognized, a central venous catheter should be placed to measure central venous pressure and central venous oxygen saturation. During the first 6 hours, basic diagnostic data is collected and a brief search for the site of the infection needs to be made. Initial data includes blood work and blood cultures; all possible sites of infection are also cultured.

The underlying infection must be treated, because sepsis is difficult to stop unless the infection is controlled. When the microbe causing the infection is unknown, broad-spectrum antibiotics are started. Giving antibiotics should not be delayed by long searches for the infection. In one large study of septic shock, 80% of the patients survived if given an appropriate antibiotic within 1 hour, but each additional hour of delay reduced the survival rate by 8%.

The bundle to be completed within six hours of time zero is:

  1. Vasopressors should be given for hypotension that does not respond to initial fluid boluses to maintain mean arterial pressure (MAP) of 65 mm Hg.
    • Norepinephrine is recommended as the first-choice vasopressor.
    • Epinephrine is recommended when norepinephrine does not maintain adequate blood pressure.
    • Dopamine is recommended only in selected cases with low risk of tachyarrhythmias.
  2. For persistent hypotension despite fluid resuscitation or initial lactate ≥ 4 mmol/l:
    • Measure CVP: resuscitation target is 8–12 mm Hg.
    • Give fluid boluses of 500 ml every 30 minutes to achieve this goal.
    • Measure ScvO2 (central venous oxygen saturation): resuscitation target is ≥ 70 %.
      • Once CVP and MAP are at goal, the clinician’s attention should then turn to the central venous oxygen saturation, ScvO2. The clinician must decide between the additions of dobutamine versus transfusing blood if the ScvO2 is less than 70%. For a hematocrit less than 30%, blood is transfused. Re-measure lactate if initial lactate is elevated—goal is normalization of lactate. (Boodoosingh et al., 2013)
Answer: B

Test Your Knowledge:

Antibiotics should always be delayed until the source of the infection is located for best outcome.

  1. True
  2. False
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