Hypertonic saline as a resuscitation solution in hemorrhagic shock: effects on extravascular lung water and cardiopulmonary function

To determine the effect of resuscitation with hypertonic saline on extravascular lung water, seven adult sheep were endotracheally intubated; mean arterial pressure (MAP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) were monitored. A 5-French, thermistor-tipped catheter was used to measure extravascular lung water (EVLW). Colloid oncotic pressure (COP), serum electrolytes and osmolality, and arterial and mixed venous blood gas tensions were measured. The COP-PCWP gradient and the shunt fraction (Qsp/Qt) were calculated. After baseline measurements, the animals were bled to an MAP of 50 mm Hg (blood volume removed, 16.2 +/- 3.6 ml/kg), which was maintained for 30 min, measurements then being repeated. Three percent sodium chloride solution was infused at 500 ml/15 min until two of three parameters--cardiac output (CO), PCWP, or MAP--were restored to baseline values. Data were recorded again and then 60 min later. No shed blood was reinfused. The total volume of hypertonic saline infused was 39 +/- 19 ml/kg. Pulmonary artery pressure did not vary throughout the study. PCWP, MAP, and CO were significantly lower than baseline (P less than 0.05) 30 min after bleeding but all except MAP returned to baseline with resuscitation. Throughout the study, EVLW did not vary despite a COP-PCWP gradient less than 4 mm Hg. Serum sodium levels and serum osmolality were significantly above baseline values after resuscitation. In this animal model of hemorrhagic shock, infusion of hypertonic saline effected resuscitation without compromising cardiopulmonary function or increasing EVLW.     

Measurement of extravascular lung water in sheep during colloid and crystalloid resuscitation from smoke inhalation

The pathophysiology of pulmonary inhalation injury, a major cause of morbidity and mortality from fires, is poorly understood. To examine the effects of colloid and crystalloid resuscitation on extravascular lung water (EVLW) during a standard smoke inhalation injury, we subjected 12 sheep to 8 minutes of cool pine smoke inhalation. The animals were then resuscitated to a pulmonary capillary wedge pressure (PCWP) of 10 +/- 1.5 mm Hg with either lactated Ringer's solution or plasma protein derivative. EVLW, cardiac output, vascular resistance, colloid oncotic pressure (COP), arterial and pulmonary artery pressures, PCWP, and blood gases were monitored during 4 hours of resuscitation. In colloid-treated animals, EVLW increased from 8.3 +/- 1.2 to 11.1 +/- 0.9 ml/kg with injury; it increased only to 12.5 +/- 1.3 ml/kg during resuscitation. In crystalloid-treated animals, EVLW increased from 8.0 +/- 1.0 to 10.3 +/- 0.8 ml/kg with injury and further increased to 17.4 +/- 1.6 ml/kg during resuscitation, a level significantly higher than that in the colloid group (P less than 0.05). The increases in EVLW were associated with progressive hypoxia, which was worse in the crystalloid group. In the crystalloid group, COP decreased from 27.3 +/- 0.9 to 14.2 +/- 0.4 mm Hg and intravascular driving force (COP-PCWP) dropped from 17.6 to 3.26 +/- 1.5 mm Hg; COP and COP-PCWP were maintained in the colloid group. These data demonstrate that supporting serum COP minimizes the increase in EVLW with smoke inhalation injury and suggests that smoke inhalation does not lead to a dramatic increase in alveolar capillary membrane permeability to protein.     

A comparison of lactated ringer's solution to hydroxyethyl starch 6% in a model of severe hemorrhagic shock and continuous bleeding in dogs

In this randomized, controlled study in dogs, we examined the short-term effects of blood pressure targeted fluid resuscitation with colloids or crystalloids solutions on systemic oxygen delivery, and lactate blood concentration. Fluid resuscitation using hydroxyethyl starch (HES) 6% to a mean arterial blood pressure (MAP) of 60 mm Hg was compared with lactated Ringer's solution (LR) to a MAP of 60 or 80 mm Hg (LR60 and LR80, respectively). The model was one of withdrawal of blood to a MAP of 40 mm Hg through an arterial catheter that was then connected to a system allowing bleeding to occur throughout the study whenever MAP exceeded 40 mm Hg. Target MAP was maintained for 60 min with a continuous infusion of the designated fluid replacement. All 15 dogs (5 in each group) survived until the last measurement. Blood loss in the LR80 group (2980 +/- 503 mL) (all values mean +/- SD) was larger than in the LR60 and HES60 groups (1800 +/- 389 mL, and 1820 +/- 219 mL, respectively) (P < 0.001). Whereas 840 +/- 219 mL of HES60 was needed to maintain target MAP, 1880 +/- 425 mL of LR was needed in the LR60 group, and 4590 +/- 930 mL in the LR80 group (P < 0.001). Lactate blood concentrations were smaller and delivered O(2) higher in the HES60 group (35 +/- 17 mg/dL and 239 +/- 61 mL/min, respectively) in comparison to the LR60 group (89 +/- 18 mg/dL and 140 +/- 48 mL/min, respectively) and the LR80 group (75 +/- 23 mg/dL and 153 +/- 17 mL/min, respectively) (P = 0.02 and P = 0.026). In conclusion, fluid resuscitation during uncontrolled bleeding, to a target MAP of 60 mm Hg, using HES60 resulted in larger oxygen delivery and smaller systemic lactate A resuscitation to a target MAP of 60 or 80 mm Hg using LR. IMPLICATIONS: Fluid resuscitation to a target mean arterial blood pressure of 60 mm Hg during uncontrolled bleeding resulted in larger oxygen delivery and smaller systemic lactate concentrations when hydroxyethyl starch 6% was used, in comparison to lactated Ringer's solution resuscitation to a target mean arterial blood pressure of 60 or 80 mm Hg.     

Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study.

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.     

Control of afterload by intravenous nitroglycerin in patients undergoing myocardial revascularisation (author's transl)]

In 18 patients undergoing aortocoronary bypass grafting haemodynamic measurements were made before and after hypertensive episodes and intravenous administration of nitroglycerin (NTG). Patients of group I (n = 10) had good left heart function before operation. The mean arterial pressure (MAP) rose during the hypertensive episode from 82 +/- 12 mm Hg to 119 +/- 8 mm Hg (p less than 0.001), the pulmonary capillary wedge pressure (PCWP) increased from 11 +/- 3 mm Hg to 15 +/- 2 mm Hg (p less than 0.05). The cardiac index (CI) was not significantly altered. Infusion of NTG decreased the MAP to 84 +/- 3 mm Hg (p less than 0.001), the PCWP to 9 +/- 3 mm Hg (p less than 0.01). The CI remained unchanged. Patients of group II (n = 8) had poor left heart function before operation. During the hypertensive episode the MAP increased from 77 +/- 15 mm Hg to 115 +/- 6 mm Hg (p less than 0.001), the PCWP from 13 +/- 4 mm Hg to 25 +/- 5 mm Hg (p less than 0.001). The CI decreased from 2.2 +/- 0.3 1/min x m2 to 1.5 +/- 3.41/min x m2. Infusion of NTG decreased the MAP to 83 +/- 4 mm Hg (p less than 0.001), the PCWP to 11 +/- 3 mm Hg (p less than 0.001). The CI rose to 2.3 +/- 0.3 1/min x m2 (p less than 0.01). The authors conclude that NTG is an effective antihypertensive agent. No untoward side effects were noted.     

Does a hyperoncotic cardiopulmonary bypass prime affect extravascular lung water and cardiopulmonary function in patients undergoing coronary artery bypass surgery?

OBJECTIVE: Different types of colloidal priming for cardiopulmonary bypass (CPB) have been used to reduce fluid load and to avoid the fall of plasma colloid osmotic pressure (COP) that leads to edema formation and consequently can cause organ dysfunction. The discussion about the optimal priming composition, however, is still controversial. We investigated the effect of a hyperoncotic CPB-prime with hydroxyethyl starch (HES) 10% (200;0.5) on extravascular lung water (EVLW) and post-pump cardiac and pulmonary functions. METHODS: In 20 randomized patients undergoing elective coronary artery bypass graft surgery (CABG), a colloid prime (COP: 48 mmHg, HES-group, n = 10) and a crystalloid prime (Ringer's lactate, crystalloid group, n = 10) of equal volume were compared with respect to the effects on cardiopulmonary function. Cardiac index (CI), mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), pulmonary vascular resistance index (PVRI), alveolo-arterial oxygen difference (AaDO(2)), pulmonary shunt fraction (Q(s)/Q(T)), EVLW (double-indicator dilution technique with ice-cold indocyanine green), COP, fluid balance and body weight were evaluated peri-operatively. RESULTS: Pre-operative demographic and clinical data, CPB-time, cross-clamp time and the number of anastomoses were comparable for both groups. During CPB, COP was reduced by 20% in the HES-group (18.9 +/- 3.7 vs. 23.7 +/- 2.2 mmHg, P < 0.05) while it was reduced by more than 50% of the pre-CPB value (9.8 +/- 2.0 vs. 21.4 +/- 2.1 mmHg, P < 0.05) in the crystalloid group (P < 0.05 HES- vs. crystalloid group). Post-CPB EVLW was unchanged in the HES-group but it was elevated by 22% in the crystalloid group (P < 0.05 HES- vs. crystalloid group), CI was higher in the HES-group (3.4 +/- 0.3 vs. 2.7 +/- 0.5l/min, P < 0.05). Fluid balance was less in the HES-group (813 +/- 619 vs. 2143 +/- 538, P < 0.05). Post-operative weight gain could be prevented in the HES-group but not in the crystalloid group (1.5 +/- 1.2 vs. -0.3 +/- 1.5, P < 0.05). No significant differences were seen for MAP, PAP, PCWP, SVRI, PVRI, AaDO(2) and (Q(s)/Q(T)) between the two groups at any time. CONCLUSIONS: Hyperoncotic CPB-prime using HES 10% improves CI and prevents EVLW accumulation in the early post-pump period, while pulmonary function is unchanged. This effect can be of benefit especially in patients with congestive heart failure.     

Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury

BACKGROUND: Traumatic brain injury (TBI) remains an exclusionary criterion in nearly every clinical trial involving hemoglobin-based oxygen carriers (HBOCs) for traumatic hemorrhage. Furthermore, most HBOCs are vasoactive, and use of pressors in the setting of hemorrhagic shock is generally contraindicated. The purpose of this investigation was to test the hypothesis that low-volume resuscitation with a vasoactive HBOC (hemoglobin glutamer-200 [bovine], HBOC-301; Oxyglobin, BioPure, Inc., Cambridge, MA) would improve outcomes after severe TBI and hemorrhagic shock. METHODS: In Part 1, anesthetized swine received TBI and hemorrhage (30 +/- 2 mL/kg, n = 15). After 30 minutes, lactated Ringer's (LR) solution (n = 5), HBOC (n = 5), or 10 mL/kg of LR + HBOC (n = 5) was titrated to restore systolic blood pressure to > or = 100 mm Hg and heart rate (HR) to < or = 100 beats/min. After 60 minutes, fluid was given to maintain mean arterial pressure (MAP) at > or = 70 mm Hg and heterologous whole blood (red blood cells [RBCs], 10 mL/kg) was transfused for hemoglobin at < or = 5 g/dL. After 90 minutes, mannitol (MAN, 1 g/kg) was given for intracranial pressure > or = 20 mm Hg, LR solution was given to maintain cerebral perfusion pressure at > or = 70 mm Hg, and RBCs were given for hemoglobin of < or = 5 g/dL. In Part 2, after similar TBI and resuscitation with either LR + MAN + RBCs (n = 3) or HBOC alone (n = 3), animals underwent attempted weaning, extubation, and monitoring for 72 hours. RESULTS: In Part 1, relative to resuscitation with LR + MAN + RBCs, LR + HBOC attenuated intracranial pressure (12 +/- 1 mm Hg vs. 33 +/- 6 mm Hg), improved cerebral perfusion pressure in the initial 4 hours (89 +/- 6 mm Hg vs. 60 +/- 3 mm Hg), and improved brain tissue PO2 (34.2 +/- 3.6 mm Hg vs. 16.1 +/- 1.6 mm Hg; all p < 0.05). Cerebrovascular reactivity and intracranial compliance were improved with LR + HBOC (p < 0.05) and fluid requirements were reduced (30 +/- 12 vs. 280 +/- 40 mL/kg; p < 0.05). Lactate and base excess corrected faster with LR + HBOC despite a 40% reduction in cardiac index. With HBOC alone and LR + HBOC, MAP and HR rapidly corrected and remained normal during observation; however, with HBOC alone, lactate clearance was slower and systemic oxygen extraction was transiently increased. In Part 2, resuscitation with HBOC alone allowed all animals to wean and extubate, whereas none in the LR + MAN + RBCs group was able to wean and extubate. At 72 hours, no HBOC animal had detectable neurologic deficits and all had normal hemodynamics. CONCLUSION: The use of HBOC-301 supplemented by a crystalloid bolus was clearly superior to the standard of care (LR + MAN + RBCs) after TBI. This may represent a new indication for HBOCs. Use of HBOC eliminated the need for RBC transfusions and mannitol. The inherent vasopressor effect of HBOCs, especially when used alone, may misguide initial resuscitation, leading to transient poor global tissue perfusion despite restoration of MAP and HR. This suggests that MAP and HR are inadequate endpoints with HBOC resuscitation. HBOC use alone after TBI permitted early extubation and excellent 72-hour outcomes.     

Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of fluid resuscitation versus improved outcome after vasopressin

In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of vasopressin versus an equal volume of saline placebo versus fluid resuscitation on hemodynamic variables and short-term survival. Twenty-one anesthetized pigs were subjected to severe liver injury. When mean arterial blood pressure was <20 mm Hg and heart rate decreased, pigs randomly received either vasopressin IV (0.4 U/kg; n = 7), an equal volume of saline placebo (n = 7), or fluid resuscitation (1000 mL each of lactated Ringer's solution and hetastarch; n = 7). Thirty minutes after intervention, surviving pigs were fluid resuscitated while bleeding was surgically controlled. Mean (+/- SEM) arterial blood pressure 5 min after the intervention was significantly (P < 0.05) higher after vasopressin than with saline placebo or fluid resuscitation (58 +/- 9 versus 7 +/- 3 versus 32 +/- 6 mm Hg, respectively). Vasopressin improved abdominal organ blood flow but did not cause further blood loss (vasopressin versus saline placebo versus fluid resuscitation 10 min after intervention, 1343 +/- 60 versus 1350 +/- 22 versus 2536 +/- 93 mL, respectively; P < 0.01). Seven of 7 vasopressin pigs survived until bleeding was controlled and 60 min thereafter, whereas 7 of 7 saline placebo and 7 of 7 fluid resuscitation pigs died (P < 0.01). We conclude that vasopressin, but not saline placebo or fluid resuscitation, significantly improves short-term survival during uncontrolled hemorrhagic shock. IMPLICATIONS: Although IV fluid administration is the mainstay of nonsurgical management of trauma patients with uncontrolled hemorrhagic shock, the efficacy of this strategy has been discussed controversially. In this animal model of severe liver trauma with uncontrolled hemorrhagic shock, vasopressin, but not saline placebo or fluid resuscitation, improved short-term survival.     

Optimal fluid management after aortic reconstruction: a prospective study of two crystalloid solutions

To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload.     

Intracranial pressure during diltiazem-induced hypotension in anesthetized dogs

The effect of diltiazem-induced hypotension on intracranial pressure (ICP) was studied in dogs with normal and elevated ICP. Eight dogs were anesthetized with intravenous pentobarbital, intubated, and ventilated with N2O:O2. Mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and cardiac out-put (CO) were recorded. A ventriculostomy was performed for measurement of ICP. Baselines were established, and diltiazem was infused to reduce MAP 40 +/- 1% for 10 min. After recording the effects of diltiazem-induced hypotension during normal ICP, ICP was elevated by infusion through a ventriculostomy cannula of pH-adjusted Ringer's lactate, baselines were reestablished, and MAP was again reduced by 40 +/- 1% with diltiazem. When baseline ICP was normal, diltiazem-induced hypotension produced a statistically significant increase in ICP (4.8 +/- 0.6 mm Hg) and a decrease in cerebral perfusion pressure (CPP). When baseline ICP was elevated, a smaller increase in ICP occurred (1.3 +/- 0.5 mm Hg). Although these increases in ICP were not clinically significant, the dose of diltiazem required to lower MAP 40% caused significant alterations in HR, systemic vascular resistance, CO, and PCWP. Serious cardiac rhythm disturbances occurred in five of eight dogs when baseline ICP was normal and in six of eight dogs when baseline ICP was elevated. The relatively long duration of diltiazem's hemodynamic effect and the high incidence of cardiac rhythm disturbances make it an unsuitable drug for inducing deliberate hypotension.     

Effect of a hypertonic lactated Ringer's solution on intracranial pressure and cerebral water content in a model of traumatic brain injury

There has recently been an increased interest in the use of hypertonic solutions for fluid resuscitation of trauma victims. In this study, we examined the acute cerebral effects of a hypertonic lactated Ringer's solution (measured osmolality = 469 mOsm/kg) in an animal model of traumatic brain injury. Following the production of a cerebral cryogenic lesion, eight New Zealand white rabbits were randomized to undergo hemodilution with either lactated Ringer's (measured osmolality = 254 mOsm/kg) or hypertonic lactated Ringer's. Over the course of the experiment the lactated Ringer's group required significantly more fluid than the hypertonic group to maintain stable central venous and mean arterial pressure (245 +/- 5 ml vs. 132 +/- 20 ml; p less than 0.0001). Osmolality increased in the hypertonic group by 13.5 +/- 3.3 mOsm/kg whereas it decreased in the lactated Ringer's group by 5.5 +/- 2.6 mOsm/kg. Intracranial pressure increased in both groups over the course of the experiment but the increase in pressure was greater in the lactated Ringer's group than the hypertonic group (9.5 +/- 2.4 mm Hg vs. 1.7 +/- 1.5 mm Hg; p less than 0.001). Brain water content was significantly increased in the region of the lesion as assayed by both the wet/dry weight method and cortical specific gravity determinations, but there was no difference between the two treatment groups. Water content of the nonlesioned hemisphere was significantly less in the hypertonic group. This study suggests that hypertonic saline solutions may be useful for the resuscitation of hypovolemic patients with localized brain injury.     

After spontaneous hypothermia during hemorrhagic shock,continuing mild hypothermia (34 degrees C) improves early but not late survival in rats

BACKGROUND: Spontaneous hypothermia is common in victims of severe trauma. Laboratory studies have shown benefit of induced (therapeutic) mild hypothermia (34 degrees C) during hemorrhagic shock (HS). Clinical data, however, suggest that hypothermia, which often occurs spontaneously in trauma patients, is detrimental. Because critically ill trauma patients are usually cool, the clinical question, which has not been explored in the laboratory with long-term outcome, is whether maintaining hypothermia or actively rewarming the patient improves outcome. We hypothesized that after spontaneous cooling during HS, continuing mild therapeutic hypothermia during resuscitation is beneficial compared with active rewarming. METHODS: In study A, under light isoflurane anesthesia, 24 Sprague-Dawley rats were bled over 10 minutes to, and maintained at, mean arterial pressure (MAP) of 40 mm Hg until reuptake of 30% of maximal shed blood volume was needed. Rectal temperature (Tr) decreased spontaneously to, and was then maintained at, 35 degrees C during HS. Fluid resuscitation included the remaining shed blood and up to 400 mL/kg of lactated Ringer's solution with 5% dextrose over 4 hours. During resuscitation, three groups (n = 8 each) were studied: normothermia (rapid rewarming to Tr 37.5 degrees C at the beginning of resuscitation); hypothermia-2 h (cooling to Tr 34 degrees C to resuscitation time 2 hours); and hypothermia-12 h (cooling to Tr 34 degrees C to 12 hours). Rats were observed to 72 hours. In study B, more severe HS than in study A was studied. HS was induced with 3 mL/100 g blood withdrawal over 15 minutes followed by maintenance of MAP of 40 mm Hg until 50% of maximal shed blood volume was needed. Two groups (n = 8 each) were studied: normothermia and hypothermia-12 h. Data are presented as mean +/- SD or median (range). RESULTS: In study A, both hypothermia groups had higher MAP and lower heart rates during resuscitation than the normothermia group (p < 0.01). Survival to 72 hours was achieved in three of eight rats in the normothermia group and two of eight in each hypothermia group. Thirteen of 17 deaths occurred after 24 hours. In study B, for resuscitation, the hypothermia group needed less fluid (53 +/- 6 mL vs. 79 +/- 32 mL, p < 0.05), but had higher MAP (p < 0.01), lower heart rate (p < 0.01), and lower lactate level (p = 0.06). All rats died before 72 hours. The hypothermia group had longer survival time (24.5 [13-48.5] hours) than the normothermia group (7.5 [1.5-19] hours) (p = 0.003 by life table analysis). CONCLUSION: After spontaneous cooling during moderately severe HS, mild, controlled hypothermia during resuscitation does not seem to affect long-term survival. After more severe HS, hypothermia increases survival time. Hypothermia supports arterial pressure during resuscitation from severe HS.     

Thermal skin injury: effect of fluid therapy on the transcapillary colloid osmotic gradient

The effects of fluid therapy on interstitial colloid osmotic and hydrostatic pressures in thermally injured skin were investigated in anesthetized rats subjected to full-thickness scald burns to 40% of the body surface area and resuscitation for 3 hr by either lactated Ringer's or plasma. Interstitial fluid hydrostatic pressure (Pif) was reduced from -2 mm Hg to -20 to -40 mm Hg after injury, which will profoundly increase transcapillary filtration. Following the onset of fluid therapy, Pif increased to slightly positive values. In control, colloid osmotic pressure in plasma (COPp) was 20.6 +/- 0.4 mm Hg and in interstitial fluid (COPif) 13.7 +/- 0.3 mm Hg (means +/- SEM). The transcapillary oncotic pressure gradient (COPgrad = COPp-COPif) was 6.9 +/- 0.4 mm Hg. Following nonresuscitated thermal injury, COPp declined to 18-19 mm Hg (P less than 0.05) and COPif was reduced to 10.4 +/- 0.5 mm Hg (P less than 0.05). Fluid therapy by lactated Ringer's markedly reduced COPp (12.3 +/- 0.3 mm Hg; P less than 0.05), and COPgrad was almost abolished (2.6 +/- 0.7 mm Hg; P less than 0.05). In contrast, plasma infusion maintained COPp, whereas COPgrad increased significantly (11.1 +/- 1.2 mm Hg; P less than 0.05). Noncolloid saline solutions have been preferred for the initial fluid therapy for burns. The present study provides evidence that this will reduce both COPp and COPgrad, a situation in which edema formation will be favored.     

Haemodynamic assessment of hypovolaemia under general anaesthesia in pigs submitted to graded haemorrhage and retransfusion

We have compared the value of different variables used in the assessment of blood loss during progressive hypovolaemia and resuscitation under general anaesthesia in anaesthetized pigs. We measured mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), the negative component of the systolic arterial pressure variation (delta Down) and left ventricular end-diastolic area (LVEDa) using echocardiography. Blood was progressively withdrawn (up to 35 ml kg-1 in seven steps) and then reinfused after the same pattern. Regression coefficient (r) and normalized slope (nS) of the regression relationship between each variable and amount of blood loss were determined. The difference between the withdrawal and reinfusion curves was assessed by the area between the curves. We also estimated the minimal loss of blood volume which induced significant changes in each variable compared with that under control conditions during withdrawal of blood (minWBV) and maximal loss in blood volume which induced no significant changes in a variable compared with control conditions during retransfusion (maxRBV). During haemorrhage, MAP decreased (from mean 74 (SD 9) to 31 (5) mm Hg; P < 0.001), delta Down increased (from 1.2 (1.4) to 11.4 (4.2) mm Hg; P < 0.001), PCWP decreased (from 6.2 (2.1) to 0.3 (1.0) mm Hg; P < 0.001) and LVEDa decreased (from 13.8 (2.0) to 5.1 (2.0) cm2; P < 0.01). The highest r values were obtained with MAP and LVEDa, and the highest nS value with delta Down. The least difference between withdrawal and reinfusion was with LVEDa, the lowest values of minWBV were with PCWP and LVEDa, and the highest value of maxRBV was obtained with PCWP. During progressive haemorrhage under general anaesthesia, LVEDa was an accurate variable for assessment of blood volume loss, delta Down contributed no further information compared with MAP, and PCWP was the most reliable variable for assessing return to baseline blood volume.      

Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) leads to reversal of anaerobic metabolism.

BACKGROUND: Traditional resuscitation regimens have been recently challenged. This study evaluates hypotensive resuscitation with a hemoglobin-based oxygen-carrying (HBOC) solution after severe hemorrhage in a porcine model. We hypothesized that HBOC-201 restores tissue perfusion at a lower mean arterial pressure than standard resuscitation fluids. METHODS: Yorkshire swine (55-65 kg, n = 30), were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and randomized into groups. Group I was resuscitated with an HBOC solution to a MAP of 60 mm Hg. Groups II and III were resuscitated to a MAP of 80 mm Hg with lactated Ringer's solution (LR) alone or LR (40 mL/kg) followed by shed blood, respectively. Group IV was resuscitated with shed blood alone to a MAP of 60 mm Hg. Group V received an HBOC solution to a MAP of 50 mm Hg. Hemodynamic variables, Swan-Ganz parameters, blood gas samples, and lactate levels were followed for 5 hours. Data were analyzed by analysis of variance/Duncan multiple range test. RESULTS: There were no significant differences in mortality between any groups. Groups I, IV, and V had lower (p < 0.05) cardiac output, pulmonary artery wedge pressure, and MAP than either group II or group III. Svo2 was significantly lower in the HBOC groups. There were no significant differences in arterial pH or lactate between groups I, III, and IV. Lactate levels, base excess, and arterial pH were significantly worse in the LR-alone and HBOC-50 groups. CONCLUSION: Hypotensive resuscitation with HBOC-201 at a MAP of 60 mm Hg after a controlled hemorrhage in swine provides sufficient tissue perfusion and oxygen delivery to reverse anaerobic metabolism on the basis of global physiologic markers despite continued hypotension, hypovolemia, and low cardiac output.     

液体复苏对严重脓毒症及脓毒性休克患者的治疗作用研究

目的评价液体复苏手段对严重脓毒症或脓毒性休克的治疗作用。方法通过液体复苏使20例严重脓毒症或脓毒性休克患者达到如下治疗目标：中心静脉压8—12mmHg（机械通气者12—15mmHg）、平均动脉压65～90mmHg、混合静脉血氧饱和度〉70％。测定达标前后血流动力学、组织灌注、血管内皮细胞功能的变化。结果液体复苏达标后,肺动脉楔压明显升高（P〈0．01）,心指数及体循环阻力指数增加（P〈0．01）,肺循环阻力指数下降（P〈0．01）,左心室做功指数上升（P〈0．01）;组织灌注指标中动脉血乳酸（ABL）在复苏后下降（P〈0．01）,胃黏膜二氧化碳分压与动脉血二氧化碳分压差（Pg—aCO2）在复苏后明显下降（P〈0．01）,血管内皮细胞功能中内皮素及血管性假血友病因子在液体复苏后下降（P〈0．05）。结论液体复苏早期达标可改善严重脓毒症或脓毒性休克患者血流动力学和组织灌注并可减轻血管内皮细胞的损伤,是一种有效的治疗方式。     

Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%) resuscitation

Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury. Sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6) or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial pressure (ICP) were followed. At the end of resuscitation brain water content was determined in injured and uninjured hemispheres. No differences were detected in cardiovascular parameters; however, ICPs were lower in animals resuscitated with HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05). Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1; p less than 0.05). No differences were detected in the injured hemispheres. We conclude that hypertonic saline abolishes increases in ICP seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood-brain barrier is still intact. Hypertonic saline may prove useful in the early management of multiple trauma patients.     

Furosemide during sustained left atrial hypertension in functionally anephric dogs: intravascular and extravascular pulmonary fluid volumes. V

The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volume was examined using double-indicator techniques (thermal-green dye) in 11 open-chest anesthetized dogs during the production of sustained left atrial (LA) hypertension by a LA balloon over a period of 195 min. In 6 of these animals data were also acquired after the intravenous administration of furosemide (1 mg/kg). The renal effects of the diuretic were blocked by tying off the ureters and the vascular supply of both kidneys. Left atrial pressure (N = 11) was abruptly increased from 2.2 +/- 2.1 mm Hg to 30.2 +/- 4.0 mm Hg (P less than 0.01) and maintained at that level for 120 min. Data were obtained prior to pressure elevation, immediately upon pressure elevation, and then every 60 min for a total of 120 min. At that point EVLW had increased (8.1 +/- 0.8 cc/kg at control to 21.7 +/- 2.0 cc/kg at 120 min, P less than 0.001), as had PBV (6.2 +/- 2.1 cc/kg to 9.1 +/- 3.1 cc/kg P less than 0.01). After furosemide injection (N = 6), LA pressure declined (mean peak reduction of approximately 6 mm Hg at 60-75 min, P less than 0.01), aortic and pulmonary arterial pressure both declined (P less than 0.01). However, EVLW remained unchanged, though PBV decreased significantly (peak decrease at 75 min after furosemide administration of 2.0 +/- 0.4 cc/kg, P less than 0.01). In the untreated dogs, EVLW continued to climb (P less than 0.05 vs treated dogs at 75 min postfurosemide).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bolus versus continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury

BACKGROUND: Using a standardized model of uncontrolled hemorrhagic shock induced by massive splenic injury (MSI), we compared bolus infusion of Ringer's lactate (RL) and hypertonic saline (HTS), combined with splenectomy, to continuous infusion of these solutions and splenectomy in rats. METHODS: Animals were randomized into six groups: group 1 (n = 8) was sham-operated. In group 2 (n = 8), MSI was untreated, and splenectomy was performed after 45 minutes. In group 3 (n = 8), MSI was treated after 15 minutes by a bolus of 40 mL/kg Ringer's lactate (LVRL-b), and splenectomy after 45 minutes. In group 4 (n = 8), MSI was treated by a bolus of 5 mL/kg 7.5% NaCl (HTS-b) and splenectomy. In group 5 (n = 8), MSI was treated by continuous infusion of 40 mL/kg/h Ringer's lactate (LVRL-c) and splenectomy. In group 6 (n = 8), MSI was treated by a continuous infusion of 5.0 mL/kg/h 7.5% NaCl (HTS-c) and splenectomy. RESULTS: After MSI, mean arterial pressure decreased in untreated group 2 from 119.2 +/- 5.6 mm Hg to 39.9 +/- 9.7 mm Hg (p < 0.001) in 60 minutes. Total blood loss (TBL) was 20.9 +/- 4.4% of blood volume and mean survival time (MST) was 177.1 +/- 21.3 minutes. LVRL-b infusion was followed by an early increase in mean arterial pressure from 67.9 +/- 7.2 mm Hg to 91.5 +/- 9.5 mm Hg (p < 0.01) after 30 minutes and then rapidly dropped to 34.4 +/- 5.7 mm Hg (p < 0.01) after 60 minutes. TBL was 38.8 +/- 4.7% (p < 0.001) and MST was 197.5 +/- 21.9 minutes. HTS-b infusion was followed by TBL of 28.1 +/- 5.3% and MST of 212.5 +/- 19.5 minutes. LVRL-c infusion was followed by TBL of 27.3 +/- 4.1% and MST of 219.6 +/- 12.9 minutes (p < 0.05). HTS-c infusion was followed by TBL of 23.9 +/- 1.6% and MST of 227.5 +/- 9.4 minutes (p < 0.03). CONCLUSION: Continuous infusion of RL combined with splenectomy was followed by significantly less bleeding than bolus infusion of RL and improved survival time compared with untreated animals. Continuous HTS infusion and bolus infusion of HTS with splenectomy resulted in minimal blood loss and improved survival compared with untreated animals. No significant difference in blood loss or survival time was observed between bolus and continuous HTS infusion.     

Intracranial pressure during nifedipine-induced hypotension

The effect of nifedipine-induced hypotension on intracranial pressure (ICP) was investigated in cats with normal and artificially increased ICP. Eleven cats were anesthetized with intraperitoneal pentobarbital (25 mg/kg), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), and mean pulmonary artery pressure (PAP) were continuously recorded. A double 19-gauge needle was inserted into the cisterna magna; ICP was continuously monitored from one needle and the other was used to increase and maintain ICP at 27 +/- 4 mm Hg by infusion of pH-adjusted Ringer's lactate solution. After control measurements were taken, nifedipine was given intravenously in each cat when ICP was normal and increased. Infusion of 96 +/- 12 micrograms (SEM) nifedipine (approximately equal to 33 micrograms/kg) reduced MAP 35-45% for 2.5 +/- 0.8 min when ICP was normal, and for 2.0 +/- 0.6 min when ICP had been increased. When initial ICP was normal, nifedipine-induced hypotension produced a small (2.2 mm Hg) but statistically significant increase in ICP and decrease in cerebral perfusion pressure (P less than 0.01). When ICP was initially elevated, nifedipine-induced hypotension produced a larger increase in ICP (5 +/- 1 mm Hg) and a proportionately larger decrease in cerebral perfusion pressure (P less than 0.01).