Comparison of Corticosteroids and Prostaglandins in Treatment of Hemorrhagic Shock GEORGE W. MACHIEDO, M.D., BENJAMIN F. RUSH, JR., M.D., F.A.C.S.
The hemodynamic and microcirculatory effects of prostaglandin E1 and methylprednisolone sodium succinate were compared in a standard canine shock model. Prostaglandin significantly increased cardiac output and decreased total peripheral resistance when compared to control animals while steroids did not. There was no significant effect upon heart rate or arterial pressure by either drug. Methylprednisolone sodium succinate significantly increased arterial pH at the conclusion of the experiment and showed directional improvement in venous lactate and proteolytic activity. Prostaglandin significantly increased length of survival compared to both steroid and control infusion. It is concluded that prostaglandin and steroid have different hemodynamic effects in shock, that steroid protects microcirculatory flow more efficiently and that the prolongation of survival seen with prostaglandin infusion is not entirely due to its hemodynamic or lysosomal stabilizing
effects.
administered as part of the therapeutic regimen for shock of various etiologies. The rationale for this is that steroids are known to exert a stabilizing effect on the cell membrane, 1) that they cause an increase in cardiac output 2) and that they cause peripheral vasodilatation. Prostaglandin E1 exerts many of the same effects as steroids in regard to lysosomal stability,7 and cardiovascular activity.5 The purpose of this study was to compare the effect of these two agents in a standard shock model. CORTICOSTEROIDS ARE OFTEN
Materials and Methods Eighteen splenectomized conditioned beagles were anesthetized with 30 mg/kg sodium pentothal. Catheters were inserted into the right femoral artery for measurement of arterial pressure, into inferior vena cava through the right femoral vein for blood sampling, and into the left femoral artery for blood withdrawal and return. A cuffed endotracheal tube was inserted and attached to a Collins spirometer filled with 100%o oxygen. Reprint requests: George W. Machiedo, M.D., Department of Surgery, College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103. Supported by NIH grant HL 13193-09 and a CMDNJ Foundation grant.
Submitted for publication: March 8, 1979.
From the Department of Surgery,
College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey
Following a one hour stabilization period, measurements were made of mean arterial pressure and central venous pressure using a standard strain gauge and recorder. Oxygen consumption was measured over a one-half hour period using the Collins Spirometer, arterial and central venous oxygen contents measured directly on a Lex-O-Con 02 content meter (Lexington Instruments, Cambridge, Mass.) at the midpoint of the oxygen consumption and a cardiac output calculated by the Fick equation. Total peripheral resistance was calculated from standard formula. Heart rate was taken from the arterial pressure recording. Arterial pH was measured on a Beckman pH meter and arterial lactate levels measured by the technique of Rosenberg and Rush.8 Lysosomal enzyme activity was measured in venous blood by the technique of Anson,1 using Cathepsin D as the measured enzyme and expressing the results as proteolytic activity units. Each of these measurements was done twice at 30 minute intervals during the control period (C). Following the control period, all dogs were subjected to hemorrhagic shock by withdrawal of blood from the left femoral artery into a siliconized container elevated above the dog so as to maintain the mean arterial pressure at 30 mmHg. Three sets of measurements are reported for each dog during the shock (S) period. The first was obtained 30 minutes after the animal was placed into shock. Measurements were repeated at 30 minute intervals while the animal remained in shock. The second reported shock measurement was taken from the 30 minute interval nearest the midpoint of the shock period and the third as the last set of measurements before the animal spontaneously took back 25% of the maximal shed blood volume. At that point the shock period was terminated, the remainder of the shed blood reinfused and the dogs divided into three equal groups. Group I received prostaglandin El
0003-4932/79/1200/0735 $00.75 C J. B. Lippincott Company
735
736 P< O.05
higher than in the
cardiac outputs
1201
being statistically equal
but
PGE,
treatment,
nificantly (p
0
The hemodynamic and microcirculatory effects of prostaglandin E1 and methylprednisolone sodium succinate were compared in a standard canine shock model. Prostaglandin significantly increased cardiac output and decreased total peripheral resistance when compared to control animals while steroids did not. There was no significant effect upon heart rate or arterial pressure by either drug. Methylprednisolone sodium succinate significantly increased arterial pH at the conclusion of the experiment and showed directional improvement in venous lactate and proteolytic activity. Prostaglandin significantly increased length of survival compared to both steroid and control infusion. It is concluded that prostaglandin and steroid have different hemodynamic effects in shock, that steroid protects microcirculatory flow more efficiently and that the prolongation of survival seen with prostaglandin infusion is not entirely due to its hemodynamic or lysosomal stabilizing
effects.
administered as part of the therapeutic regimen for shock of various etiologies. The rationale for this is that steroids are known to exert a stabilizing effect on the cell membrane, 1) that they cause an increase in cardiac output 2) and that they cause peripheral vasodilatation. Prostaglandin E1 exerts many of the same effects as steroids in regard to lysosomal stability,7 and cardiovascular activity.5 The purpose of this study was to compare the effect of these two agents in a standard shock model. CORTICOSTEROIDS ARE OFTEN
Materials and Methods Eighteen splenectomized conditioned beagles were anesthetized with 30 mg/kg sodium pentothal. Catheters were inserted into the right femoral artery for measurement of arterial pressure, into inferior vena cava through the right femoral vein for blood sampling, and into the left femoral artery for blood withdrawal and return. A cuffed endotracheal tube was inserted and attached to a Collins spirometer filled with 100%o oxygen. Reprint requests: George W. Machiedo, M.D., Department of Surgery, College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103. Supported by NIH grant HL 13193-09 and a CMDNJ Foundation grant.
Submitted for publication: March 8, 1979.
From the Department of Surgery,
College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey
Following a one hour stabilization period, measurements were made of mean arterial pressure and central venous pressure using a standard strain gauge and recorder. Oxygen consumption was measured over a one-half hour period using the Collins Spirometer, arterial and central venous oxygen contents measured directly on a Lex-O-Con 02 content meter (Lexington Instruments, Cambridge, Mass.) at the midpoint of the oxygen consumption and a cardiac output calculated by the Fick equation. Total peripheral resistance was calculated from standard formula. Heart rate was taken from the arterial pressure recording. Arterial pH was measured on a Beckman pH meter and arterial lactate levels measured by the technique of Rosenberg and Rush.8 Lysosomal enzyme activity was measured in venous blood by the technique of Anson,1 using Cathepsin D as the measured enzyme and expressing the results as proteolytic activity units. Each of these measurements was done twice at 30 minute intervals during the control period (C). Following the control period, all dogs were subjected to hemorrhagic shock by withdrawal of blood from the left femoral artery into a siliconized container elevated above the dog so as to maintain the mean arterial pressure at 30 mmHg. Three sets of measurements are reported for each dog during the shock (S) period. The first was obtained 30 minutes after the animal was placed into shock. Measurements were repeated at 30 minute intervals while the animal remained in shock. The second reported shock measurement was taken from the 30 minute interval nearest the midpoint of the shock period and the third as the last set of measurements before the animal spontaneously took back 25% of the maximal shed blood volume. At that point the shock period was terminated, the remainder of the shed blood reinfused and the dogs divided into three equal groups. Group I received prostaglandin El
0003-4932/79/1200/0735 $00.75 C J. B. Lippincott Company
735
736 P< O.05
higher than in the
cardiac outputs
1201
being statistically equal
but
PGE,
treatment,
nificantly (p
0
