End Of Resuscitation Research Articles

Effect of hemorrhagic shock on endotoxin-inducing TNF production and intra-tissue lipopolysaccharide-binding protein mRNA expression and their relationship.

In order to further elucidate effect of hemorrhagic shock on endotoxin-inducing cytokine production, the present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) of lipopolysaccharide (LPS) and its cellular sources after hemorrhagic shock (HS) in rats. With combination of expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs, and kidneys, we further analyzed a possible mechanism for increasing sensitivity to LPS by shock. We found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than those in the HS group (p < .01) and 2.7-fold higher than those in the LPS group (p < .05). It was shown in vitro that the capacity of the peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (p < .01) and 57% (p < .05) compared with the pre-shock levels and sham group, respectively, at the end of resuscitation following shock, and still markedly inhibited 3 h after resuscitation, while the capacity of hepatic Kupffer's cells to produce TNF alpha was significantly increased by 110% compared with the sham group (p < .01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs, and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly strengthen endotoxin to induce TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and the tissue macrophage population may be the main source for cytokine production in shock.

COMPARATIVE EFFECTS OF 7% NaCI IN 6% DEXTRAN 70 AND 0.9% NaCI ON OXYGEN TRANSPORT IN ENDOTOXEMIC DOGS

We compared the effects of 7% NaCl in 6% dextran 70 (HSD) and 0.9% NaCl (IS) resuscitation of endotoxic dogs on hemodynamic and cardiorespiratory parameters and the oxygen consumption-delivery relationship. Escherichia coli endotoxin (3 mg.kg-1, intravenously) was infused over 5 min into 13 paralyzed, chloralose-anesthetized, splenectomized dogs. Six additional dogs received a sham endotoxin infusion (saline) and served as controls. After 30 min, the endotoxic animals were resuscitated to 150% of their baseline cardiac output (CO) and maintained at this CO for 30 min using 7% NaCl in 6% dextran 70 (HSD at 1 ml.kg-1.min-1; n = 7) or 0.9% NaCl (IS at 4 ml.kg-1.min-1; n = 6). Oxygen consumption (VO2), measured by indirect calorimetry, hemodynamic parameters, and oxygen delivery (DO2), improved in similar temporal patterns in both groups during resuscitation and VO2 reached steady-state values. Oxygen delivery, VO2, mean arterial pressure, and cardiac output did not significantly differ between groups at the end of resuscitation, but VO2 increased significantly from baseline values only in the HSD group. The total volume of HSD administered averaged 10.0 +/- 0.2 ml.kg-1 which was significantly less than the volume of IS, which averaged 67.2 +/- 9.3 ml.kg-1. Incremental hemorrhages (2-5 ml.kg-1) were then performed in all dogs to determine the oxygen consumption-delivery relationship and the critical level of oxygen delivery (DO2Crit). The average DO2Crit values of the HSD, IS, and control groups were 9.42, 9.15, and 6.82 ml.min-1.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed gut absorptive capacity early after trauma-hemorrhagic shock.

The authors investigated the effect of the calcium channel antagonist diltiazem on gut absorptive capacity after hemorrhage in rats. Carotid and femoral arterial catheters, portal and jugular venous catheters, and nasogastric tubes were placed in 12 anesthetized animals. After recovery from the anesthetic, eight animals (groups 2 and 3) were bled via the femoral catheter to a mean arterial pressure (MAP) of 40 mm Hg. This level of hypotension was maintained by continued bleeding to the maximal bleedout volume (approximately 60% of the animal's circulating blood volume), followed by infusion of lactated Ringer's solution until 40% of the maximal bleedout volume had been returned. The animals were then resuscitated with lactated Ringer's solution. Four rats (group 1) were not hemorrhaged and served as sham controls. During resuscitation the animals in group 2 received an additional 1 mL of saline, whereas those in group 3 were treated with diltiazem 400 μg/kg body weight in 1 mL of saline. MAP was measured throughout the experiment. Portal and central venous pressures were measured at the onset of hemorrhage, maximal bleedout, end of hemorrhage, end of resuscitation, and just before the D‐xylose absorption tests. Gut absorptive, capacity was determined using the 1‐hour D‐xylose absorption test at 2 hours and 4 hours after the end of hemorrhage. The D‐xylose was administered via the nasogastric tubes; portal blood was sampled 1 hour later and assayed for D‐xylose.The animals treated with diltiazem had a significantly lower MAP 2 hours after the end of hemorrhage, whereas at 4 hours, both hemorrhaged groups were significantly lower than controls. Central venous and portal pressures were significantly lower in the hemorrhaged groups at maximal bleedout and end of hemorrhage compared with the sham‐operated animals. However, these values returned to normal by 2 hours after the end of hemorrhage. There were no differences in the venous pressures between the animals receiving saline or diltiazem. The saline‐treated animals' gut absorptive capacity as measured by D‐xylose absorption was significantly reduced at 2 and 4 hours after the end of hemorrhage. Diltiazem administration restored gut absorptive capacity to normal at both time points after the end of hemorrhage.

Protective effects of preheparinization on the microvasculature during and after hemorrhagic shock.

Despite the fact that trauma patients are not heparinized at the time of injury, most models of hemorrhagic shock involve heparinization before the initiation of hemorrhage. To determine whether preheparinization has any effects on the microvasculature of organs during or after hemorrhage, rats (with and without preheparinization) were bled to a mean arterial blood pressure (BP) of 40 mm Hg. In two groups, this pressure was maintained by withdrawing additional blood until BP could no longer be maintained at 40 mm Hg (maximal bleedout, MB). In another two groups, the BP was maintained at 40 mm Hg until 40% of the MB volume was returned in the form of lactated Ringer's solution. The rats were then resuscitated with four times the volume of MB with lactated Ringer's. At MB or immediately after resuscitation, colloidal carbon black was rapidly infused and the liver, kidney, and spleen were excised, fixed, and sectioned. In additional animals, blood samples for platelet counts and total body fibrinogen estimates were taken before hemorrhage and at MB or at the end of resuscitation. The results indicate that at MB, microvascular patency in the kidney and liver was significantly depressed in the nonheparinized rats but not depressed in the preheparinized rats. This protective effect of heparin is not directly attributable to its anticoagulant properties, since there were no differences in the consumption of platelets or fibrinogen between the nonheparinized and preheparinized groups. Although the microvascular patency improved with resuscitation in the nonheparinized group, the glomeruli counts and perfusion of the spleen remained significantly lower than in the preheparinized group.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystalloid Vs. Colloid Resuscitation

The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.