Antibiotics Chemother., vol. 21, pp. 201-203 (Karger, Basel 1976)
Steroids in Septic Shock W.A. ALTEMEIER
The use of steroids in the treatment of gram-negative septic shock is controversial. There is confusion and difference of opinion as to their value and their disadvantages or dangers. When used there are also marked differences of opinion as to the dosage and duration of treatment. The concern of some investigators relates to the lack of evident clinical and experimental benefit, no evidence of decreased overall mortality, the possibility of increased gastrointestinal hemorrhage, and the likelihood of producing greater dissemination of the infection. On the other hand, the clinical and laboratory experiences of some investigators indicate that steroids may be of definite advantage in improving the vital signs in patients with septic shock, prolonging their life for three or more days until the antibacterial effects of the antibiotic therapy and the benefits of surgery can be obtained, and in blocking the toxic effects of circulating bacterial products on organs and cells. In patients with septic shock who remain hypotensive and oliguric after adequate fluid replacement with balanced salt solution and digitalization and who have a rising central venous pressure, the author uses steroid therapy. When immediately available, evidence of elevated pulmonary arterial pressure and increased wedge pressure is also noteworthy. The advantages of corticosteroid therapy are still largely empirical or theoretical. They consist of the following: (1) Establishment and maintenance of adequate blood pressure and blood flow.
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Departement of Surgery, Cincinnati General Hospital, University of Cincinnati Medical Center, Cincinnati, Ohio
ALTEMEIER
202
(2) Establishment of urinary flow, presumably as a result of decreased renal arterial spasm and increased renal perfusion. (3) Extension of life during this critical illness long enough to obtain the antimicrobial effect of the antibiotic therapy and the benefit of appropriate or necessary surgical operation. (4) Stabilization of lysosomal membranes. (5) Prevention of the release of proteolytic enzymes. (6) Decrease of peripheral resistance. Corticosteroids may act as 0\blocking agents, diminishing pre- and postcapillary vasoconstriction, and improving microcirculatory flow. (7) Improvement of cardiac output by an inotropic effect.
Selection of Corticosteroids
The corticosteroids recommended for administration in the treatment of acute septic shock include hydrocortisone, dexamethasone, and methylprednisolone. The author's preference is first to use hydrocortisone intravenously in doses of 100 mg/I,OOO ml of intravenous fluid and giving additional doses as necessary to titrate the need by the effect obtained. This has proven to be highly effective in our hands, the therapy being discontinued in 48 h in most instances. Dexamethasone can be administered intravenously in doses of 5 mg/kg as a bolus. In a similar manner, a bolus of methylprednisolone in a dose of 30 mg/kg may be given. In the latter two instances the dose is pharmacologic. The therapy is continued at reduced doses of 100 mg dexamethasone or of 1,000 mg methylprednisolone at 6-hour intervals for 24-48 h and then abruptly discontinued.
During the acute hypotensive and oliguric phase of septic shock, the intravenous route should be utilized to insure rapid distribution of an adequate antimicrobial effect. .After the initial treatment, intravenous corticosteroid therapy should be continued at reduced doses of 100 mg dexamethasone or 1,000 mg methylprednisolone at 6-hour intervals for 24-48 h and then abruptly discontinued.
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Route of Administration
Steroids in Septic Shock
203
Laboratory and Clinical Experimental Studies
Dr. W.A. ALTEMEIER, Department of Surgery, Surgical Research Bacteriology Laboratory, University of Cincinnati Medical Center, Cincinnati, OH 45219 (USA)
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Significant tissue p02 increases and pC0 2 changes are correlated with the cardiac output, peripheral and pulmonary resistance, lactate levels, and pulmonary artery and capillary wedge pressures. Arterial p02 was maintained approximately between 80 and 100 mm Hg. Arterial pC0 2 varied in response to the acid-base status of the patient. In our experience, patients in septic shock showed improvement within 3-6 h after the infusion of the corticosteroids, tissue p02 began to increase and within 16-24 h usually returned to normal levels. Tissue pC0 2 began to decline and returned to near normal levels at 18-24 h. Cardiac output increased along with an improved urinary output which began within I or 2 h after the start of the corticosteroids.
Steroids in Septic Shock W.A. ALTEMEIER
The use of steroids in the treatment of gram-negative septic shock is controversial. There is confusion and difference of opinion as to their value and their disadvantages or dangers. When used there are also marked differences of opinion as to the dosage and duration of treatment. The concern of some investigators relates to the lack of evident clinical and experimental benefit, no evidence of decreased overall mortality, the possibility of increased gastrointestinal hemorrhage, and the likelihood of producing greater dissemination of the infection. On the other hand, the clinical and laboratory experiences of some investigators indicate that steroids may be of definite advantage in improving the vital signs in patients with septic shock, prolonging their life for three or more days until the antibacterial effects of the antibiotic therapy and the benefits of surgery can be obtained, and in blocking the toxic effects of circulating bacterial products on organs and cells. In patients with septic shock who remain hypotensive and oliguric after adequate fluid replacement with balanced salt solution and digitalization and who have a rising central venous pressure, the author uses steroid therapy. When immediately available, evidence of elevated pulmonary arterial pressure and increased wedge pressure is also noteworthy. The advantages of corticosteroid therapy are still largely empirical or theoretical. They consist of the following: (1) Establishment and maintenance of adequate blood pressure and blood flow.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/6/2017 1:49:26 PM
Departement of Surgery, Cincinnati General Hospital, University of Cincinnati Medical Center, Cincinnati, Ohio
ALTEMEIER
202
(2) Establishment of urinary flow, presumably as a result of decreased renal arterial spasm and increased renal perfusion. (3) Extension of life during this critical illness long enough to obtain the antimicrobial effect of the antibiotic therapy and the benefit of appropriate or necessary surgical operation. (4) Stabilization of lysosomal membranes. (5) Prevention of the release of proteolytic enzymes. (6) Decrease of peripheral resistance. Corticosteroids may act as 0\blocking agents, diminishing pre- and postcapillary vasoconstriction, and improving microcirculatory flow. (7) Improvement of cardiac output by an inotropic effect.
Selection of Corticosteroids
The corticosteroids recommended for administration in the treatment of acute septic shock include hydrocortisone, dexamethasone, and methylprednisolone. The author's preference is first to use hydrocortisone intravenously in doses of 100 mg/I,OOO ml of intravenous fluid and giving additional doses as necessary to titrate the need by the effect obtained. This has proven to be highly effective in our hands, the therapy being discontinued in 48 h in most instances. Dexamethasone can be administered intravenously in doses of 5 mg/kg as a bolus. In a similar manner, a bolus of methylprednisolone in a dose of 30 mg/kg may be given. In the latter two instances the dose is pharmacologic. The therapy is continued at reduced doses of 100 mg dexamethasone or of 1,000 mg methylprednisolone at 6-hour intervals for 24-48 h and then abruptly discontinued.
During the acute hypotensive and oliguric phase of septic shock, the intravenous route should be utilized to insure rapid distribution of an adequate antimicrobial effect. .After the initial treatment, intravenous corticosteroid therapy should be continued at reduced doses of 100 mg dexamethasone or 1,000 mg methylprednisolone at 6-hour intervals for 24-48 h and then abruptly discontinued.
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/6/2017 1:49:26 PM
Route of Administration
Steroids in Septic Shock
203
Laboratory and Clinical Experimental Studies
Dr. W.A. ALTEMEIER, Department of Surgery, Surgical Research Bacteriology Laboratory, University of Cincinnati Medical Center, Cincinnati, OH 45219 (USA)
Downloaded by: National Univ. of Singapore 137.132.123.69 - 4/6/2017 1:49:26 PM
Significant tissue p02 increases and pC0 2 changes are correlated with the cardiac output, peripheral and pulmonary resistance, lactate levels, and pulmonary artery and capillary wedge pressures. Arterial p02 was maintained approximately between 80 and 100 mm Hg. Arterial pC0 2 varied in response to the acid-base status of the patient. In our experience, patients in septic shock showed improvement within 3-6 h after the infusion of the corticosteroids, tissue p02 began to increase and within 16-24 h usually returned to normal levels. Tissue pC0 2 began to decline and returned to near normal levels at 18-24 h. Cardiac output increased along with an improved urinary output which began within I or 2 h after the start of the corticosteroids.
