318
Haemodynamic improvement in refractory septic shock with cortisol replacement therapy Dear Sir, We agree with Dr. Schneider and Dr. Voerman that physiological doses of hydrocortisone improve haemodynamics in late septic shock [1]. However, we would like to extend the indication. We use cortisoi replacement therapy (hydrocortisone: 100mg loading dose, continuous infusion of 10 mg/h) in a clinical condition which is referred to as refractory septic shock [2]. In a series of 14 patients we found a haemodynamic improvement in all cases: after 48 h vasopressor therapy was discontinued in 6 patients (group I), 3 were infused with a dose of dopamine less than 5 Ixg/kg per rain (group II), and 5 needed doses between 5 and 15 gg/kg per min (group III) [3]. Furthermore and in contrast to Schneider and Voerman we found a decrease in the cardiac index in 12 of the 14 patients within 48 h (Fig. 1). [llmin.m']
The underlying mechanism of the haemodynamic improvement following hydrocortisone is unclear and speculative. Since cortisol production may be depressed during septic shock [4] and the hypothalamic-pituitary-adrenal axis may be dissociated [5] we also hypothesize that a relative deficit of cortisol contributes to septic chock. In animal models treatment with hydrocortisone enhanced vascular responsiveness to catecholamines [6] and prevented the cardiovascular response to endotoxin [7]. The decrease in cardiac index in our series may also indicate a reversal of the sepsis syndrome. Cortisol plays a major role in the immunoregulatory feedback system. The activity of phospholipase A 2 is mediated by lipocortins, a group of cortisol-induced phospholipase inhibitors [5]. In animal models infusion of phospholipase A 2 causes hypotension and releases vasoactive eicosanoids like 6-ketoprostaglandin Fj~ and thromboxane B~ [8]. In a current investigation on septic shock we found a rapid decrease in phospholipase A 2 activity following hydrocortisone infusion. In 3 cases tapering the effective dose of hydrocortisone resulted in a circulatory collapse combined with a marked increase of phospholipase A 2 activity. A second infusion of hydrocortisone resulted in shock reversal and a decrease in phospholipase activity to near normal values (Fig. 2). Yours faithfully, J. Briegel, H. Forst, W. Kellermann, M. Haller, and K. Peter
References 1
Group I
Group II
Group III
0 of 6
1 of 3
3 of 5
Mortality
Fig. 1. Cortisol replacement therapy in septic shock; trend of cardiac index within 48 h
jso
PLA [U/I]
Cor tisol [IJgldl] 160
Hydrocortisone
140
I
70
120
60
100
50
80
40
60
30
40
20
20
10
0
1. Schneider AJ, Voerman HJ (1991) Abrupt hemodynamic improvement in late septic shock with physiological doses of glucocorticoids. Intensive Care Med 17:436-437 2. Bone RC (1991) Sepsis, the sepsis syndrome, multi-organ failure: a plea for comparable definitions. Ann Intern Med 114:332-333 3. Briegel J, Forst H, Hellinger H, Haller M (1991) Contribution of cortisol deficiency to septic shock. Lancet 338:507-508 4. Catalano RD, Parameswaran V, Ramachandran J, Trunkey DD (1984) Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1I9:145-150 5. Vadas P, Pruzanski W, Stefanski E, Ruse J, Farewell V, McLaughlin J, Bombardier C (1988) Concordance of endogenous cortisol and phospholipase A 2 levels in gram-negative septic shock: a prospective study. J Lab Clin Med 111:584-590 6. Kalsner S 0969) Mechanism of hydrocortisone potentiation of responses to epinephrine and norepinephrine in rabbit aorta. Circ Res 24:383 - 395 7. Kadowitz P J, Yard AC (1970) Circulatory effects of hydrocortisone and protection against endotoxin shock in cats. Eur J Pharmacol 9:311-318 8. Vadas P, Pruzanski W, Stefanski E, Sternby B, Mustard R, Bohnen J, Fraser I, Farewell V, Bombardier C (19'88) Pathogenesis of hypotension in septic shock: Correlation of circulating phospholipase A 2 levels with circulatory collapse. Crit Care Med 16:1-7
0 0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 21
Days lFig. 2, Plasma cortisol and phospholipase A 2
Dr. J. Briegel, Intensive Care Unit, Institute of Anaesthesiology, Klinikum Grol3hadern, Universit~t Manchen, W-8000Mtinchen70, FRG
Haemodynamic improvement in refractory septic shock with cortisol replacement therapy Dear Sir, We agree with Dr. Schneider and Dr. Voerman that physiological doses of hydrocortisone improve haemodynamics in late septic shock [1]. However, we would like to extend the indication. We use cortisoi replacement therapy (hydrocortisone: 100mg loading dose, continuous infusion of 10 mg/h) in a clinical condition which is referred to as refractory septic shock [2]. In a series of 14 patients we found a haemodynamic improvement in all cases: after 48 h vasopressor therapy was discontinued in 6 patients (group I), 3 were infused with a dose of dopamine less than 5 Ixg/kg per rain (group II), and 5 needed doses between 5 and 15 gg/kg per min (group III) [3]. Furthermore and in contrast to Schneider and Voerman we found a decrease in the cardiac index in 12 of the 14 patients within 48 h (Fig. 1). [llmin.m']
The underlying mechanism of the haemodynamic improvement following hydrocortisone is unclear and speculative. Since cortisol production may be depressed during septic shock [4] and the hypothalamic-pituitary-adrenal axis may be dissociated [5] we also hypothesize that a relative deficit of cortisol contributes to septic chock. In animal models treatment with hydrocortisone enhanced vascular responsiveness to catecholamines [6] and prevented the cardiovascular response to endotoxin [7]. The decrease in cardiac index in our series may also indicate a reversal of the sepsis syndrome. Cortisol plays a major role in the immunoregulatory feedback system. The activity of phospholipase A 2 is mediated by lipocortins, a group of cortisol-induced phospholipase inhibitors [5]. In animal models infusion of phospholipase A 2 causes hypotension and releases vasoactive eicosanoids like 6-ketoprostaglandin Fj~ and thromboxane B~ [8]. In a current investigation on septic shock we found a rapid decrease in phospholipase A 2 activity following hydrocortisone infusion. In 3 cases tapering the effective dose of hydrocortisone resulted in a circulatory collapse combined with a marked increase of phospholipase A 2 activity. A second infusion of hydrocortisone resulted in shock reversal and a decrease in phospholipase activity to near normal values (Fig. 2). Yours faithfully, J. Briegel, H. Forst, W. Kellermann, M. Haller, and K. Peter
References 1
Group I
Group II
Group III
0 of 6
1 of 3
3 of 5
Mortality
Fig. 1. Cortisol replacement therapy in septic shock; trend of cardiac index within 48 h
jso
PLA [U/I]
Cor tisol [IJgldl] 160
Hydrocortisone
140
I
70
120
60
100
50
80
40
60
30
40
20
20
10
0
1. Schneider AJ, Voerman HJ (1991) Abrupt hemodynamic improvement in late septic shock with physiological doses of glucocorticoids. Intensive Care Med 17:436-437 2. Bone RC (1991) Sepsis, the sepsis syndrome, multi-organ failure: a plea for comparable definitions. Ann Intern Med 114:332-333 3. Briegel J, Forst H, Hellinger H, Haller M (1991) Contribution of cortisol deficiency to septic shock. Lancet 338:507-508 4. Catalano RD, Parameswaran V, Ramachandran J, Trunkey DD (1984) Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1I9:145-150 5. Vadas P, Pruzanski W, Stefanski E, Ruse J, Farewell V, McLaughlin J, Bombardier C (1988) Concordance of endogenous cortisol and phospholipase A 2 levels in gram-negative septic shock: a prospective study. J Lab Clin Med 111:584-590 6. Kalsner S 0969) Mechanism of hydrocortisone potentiation of responses to epinephrine and norepinephrine in rabbit aorta. Circ Res 24:383 - 395 7. Kadowitz P J, Yard AC (1970) Circulatory effects of hydrocortisone and protection against endotoxin shock in cats. Eur J Pharmacol 9:311-318 8. Vadas P, Pruzanski W, Stefanski E, Sternby B, Mustard R, Bohnen J, Fraser I, Farewell V, Bombardier C (19'88) Pathogenesis of hypotension in septic shock: Correlation of circulating phospholipase A 2 levels with circulatory collapse. Crit Care Med 16:1-7
0 0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 21
Days lFig. 2, Plasma cortisol and phospholipase A 2
Dr. J. Briegel, Intensive Care Unit, Institute of Anaesthesiology, Klinikum Grol3hadern, Universit~t Manchen, W-8000Mtinchen70, FRG
