An 81-year-old woman with diabetes mellitus presents with a three-day history of fever, chills, left-side flank pain, and dysuria. Her blood pressure upon presentation is 75/45 mm/Hg, her heart rate is 120 beats per minute, and she has a temperature of 103.1°`F and a respiratory rate of 22 breaths/minute. On physical examination, she is an ill-appearing elderly woman, with dry oral mucosa and left costo-vertebral angle tenderness. Lab work shows leukocytosis of 18,000 mg/dL with 88% polymorphonuclear leukocyte (PMN), the urine analysis is consistent with a urinary tract infection, and a chemistry panel reveals elevated BUN and creatinine levels of 52 mg/dL and 2.4 mg/dL, respectively. In the emergency department, she is given a bolus of 2 liters normal saline, but her blood pressure remains 78/49 mm/Hg. She is then started on broad-spectrum antibiotics and a norepinephrine drip, and is admitted to the ICU.
What role would steroids add to her management?
Sepsis is the clinical syndrome defined by the presence of systemic inflammatory response syndrome (SIRS) in the setting of an infection. SIRS is defined by the presence of at least two of the following: fever or hypothermia; leukocytosis, leukopenia, or bandemia; heart rate >90 bpm; or tachypnea or hypocapnia.
When acute organ dysfunction, such as acute renal failure, altered mental status, or acute lung injury (hypoxemia), is present, sepsis is classified as severe.
Septic shock is a state of sepsis associated with acute circulatory collapse characterized by persistent arterial hypotension (defined as a systolic blood pressure <90 mmHg, a mean arterial pressure <60 mmHg, or a reduction in systolic blood pressure of >40 mmHg from baseline) despite fluid resuscitation attempts.1
The incidence and mortality due to sepsis and septic shock is directly related to the age of the patient, many of whom require ICU hospitalization.2 Clinically, this portends a great challenge, as the incidence of sepsis is likely to increase as the U.S. population ages.
Initial management of a patient with sepsis/septic shock is goal-directed therapy, which consists of early administration of broad-spectrum antibiotics, crystalloid or colloid fluid resuscitation, and use of vasopressor support to improve hemodynamics and maintain a mean arterial
pressure ≥65 mmHg. Patients with acute lung injury may also require prompt ventilator support.
The role of steroids in sepsis is controversial.
Review of Steroids
Steroids have long been known for their anti-inflammatory properties. From the 1950s to the 1980s, high-dose steroids (methylprednisolone 30mg/kg and dexamethasone 3 mg/kg to 6 mg/kg in divided doses) were used in the management of sepsis. This was based on a study by Schumer that showed steroids reduced mortality to 10% from 38%.3
Later, Sprung and colleagues demonstrated reversal of shock and improved short-term survival with high-dose steroids in patients with sepsis, but subsequent prospective randomized trials did not support this beneficial effect of high-dose steroids.4-6 In fact, two meta-analyses in 1995 concluded that high-dose steroids are ineffective and potentially harmful, and associated with higher mortality, secondary infections, and renal and hepatic dysfunction.7,8 Thereafter, the use of high-dose steroids fell into disfavor.