Septic shock: a goal-directed therapy using volume loading, dobutamine and/or norepinephrine

In patients with septic shock and acute respiratory failure, norepinephrine (NE) alone or in combination with dobutamine was used. The aim of therapy was to obtain or maintain Cl greater than or equal to 4.5 l.min-1.m-2, SVR greater than or equal to 700-800 dyn.s.cm-5 and oxygen delivery (Do2) greater than or equal to 550 ml.min-1.m-2. Twenty-three patients (58 +/- 3 years) were studied. Initially patients were given intravenous fluid resuscitation to obtain optimal cardiac filling pressures. Eleven patients were considered to be in hyperdynamic septic shock (cardiac index (CI) greater than 4.5 l.min-1.m-2, SVR less than or equal to 600 dyn.s.cm-5 and oliguria) and were given NE as a single agent (0.9 +/- 0.2 micrograms kg-1.min-1). The other 12 patients had Cl less than 3.5 l.min-1.m-2 and were given a combination of dobutamine (12 +/- 0.09 micrograms.kg-1.min-1) and NE (1.1 +/- 0.2 micrograms.kg-1.min-1). The latter drug was added since systemic vascular resistance (SVR) was less than 600 and oliguria persisted while on dobutamine. In all patients, during NE infusion SVR was greater than 700 dyn.s.cm-5, Cl greater than or equal to 4.5 l.min-1.m-2 and Do2 greater than 550 ml.min-1.m-2. Urine flow was significantly increased during NE infusion, and only four patients remained oliguric. Anion gap and oxygen consumption were not modified. A complete resolution of septic shock was seen in 16 out of 23 patients (70%). Hospital mortality was 56%.     

Optimal adrenergic support in septic shock due to peritonitis

BACKGROUND: The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock. METHODS: Twenty-eight mature, female, anesthetized sheep (weight, 30.5 +/- 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringer's solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5-5 microg. kg(-1). min(-1)) was titrated to maintain mean arterial pressure between 75-85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 microg. kg(-1). min(-1) dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 microg. kg(-1). min(-1) to get a 15% increase in cardiac output. RESULTS: The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do(2)), and oxygen consumption ([OV0312]o(2)); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco(2)) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 +/- 4 h), dopamine- norepinephrine (24 +/- 6 h), and norepinephrine (20 +/- 1 h) groups than the control group (17 +/- 2 h; P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 +/- 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups. CONCLUSIONS: In this prolonged septic shock model, association of norepinephrine with either dopamine or dobutamine resulted in the longest survival and the least severe pulmonary lesions. The combination of dobutamine with norepinephrine was associated with a better myocardial performance, greater Do(2) and [OV0312]o(2), lower blood lactate concentration and Pco(2) gap, and less anatomic injury.     

Cerebrovascular effects of small volume resuscitation from hemorrhagic shock: comparison of hypertonic saline and concentrated hydroxyethyl starch in dogs

To determine if hypertonic and hyperoncotic resuscitation solutions exerted comparable effects on cerebral hemodynamics following hemorrhagic shock, we compared randomly assigned, equal volumes (6.0 ml/kg) of hypertonic (7.2%) saline (HS) and hyperoncotic (20%) hydroxyethyl starch (HES) for resuscitation from acute experimental hemorrhage in 12 anesthetized dogs. Regional cerebral blood flow (radiolabeled microspheres), intracranial pressure (cisternal catheter), and systemic hemodynamics were recorded. Rapid hemorrhage reduced the mean arterial pressure to 45 mm Hg for 30 min. Resuscitation fluids were infused over 5 min. Both fluids restored mean arterial pressure and cardiac output equally. However, at 60 min following resuscitation, cardiac output decreased in the HS group in comparison to the HES group (1.7 +/- 0.1 vs. 3.1 +/- 0.2 L/min, p <0.05). Cardiac output rapidly declined, however, in the HS group in comparison to the HES group (p <0.05 60 min following resuscitation). Intracranial pressure and cerebral perfusion pressure were similar at all intervals. Regional cerebral blood flow was similar following both fluids. Neither fluid restored cerebral oxygen transport to baseline values. Based on these data, the authors conclude that, following severe hemorrhagic shock of brief duration, systemic and cerebral hemodynamic values are restored equally well by highly concentrated colloid or by hypertonic saline, although hypertonic saline only transiently improves cardiac output.     

Optimal Adrenergic Support in Septic Shock Due to Peritonitis

Background: The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock.

Methods: Twenty-eight mature, female, anesthetized sheep (weight, 30.5 +/- 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringer's solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5-5 [mu]g [middle dot] kg-1 [middle dot] min-1) was titrated to maintain mean arterial pressure between 75-85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 [mu]g [middle dot] kg-1 [middle dot] min-1 dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 [mu]g [middle dot] kg-1 [middle dot] min-1 to get a 15% increase in cardiac output.

Results: The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do2), and oxygen consumption ([latin capital V with dot above]o2); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco2) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 +/- 4 h), dopamine- norepinephrine (24 +/- 6 h), and norepinephrine (20 +/- 1 h) groups than the control group (17 +/- 2 h;P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 +/- 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups.     

Hypertonic saline solution-hetastarch for fluid resuscitation in experimental septic shock

Hypertonic colloid solutions have been found efficacious in the resuscitation from hemorrhagic/traumatic shock. The present study investigated the hemodynamic, gasometric, and metabolic effects of hypertonic colloids in endotoxic shock in the dog. Thirty minutes after administration of 3 mg/kg normal body weight of Escherichia coli endotoxin, dogs were randomly assigned to receive 10 mL/kg hydroxyethylstarch (HES) either in 0.9% NaCl (HES, 10 dogs) or in 7.5% NaCl (HT-HES, 10 dogs) in 30 min. Thereafter, 0.9% NaCl solution was administered in volumes adequate to maintain pulmonary artery balloon-occluded pressure at baseline levels. Total fluid administered averaged 64 +/- 30 mL/kg (mean +/- SD) in the HES group and 73 +/- 34 mL/kg in the HT-HES group. As these differences were not statistically significant, total sodium load was higher in the HT-HES group. The persistent volume effect was associated with persistently lower hematocrit and protein levels in the HT-HES group. Initial fluid resuscitation with HT-HES resulted in arterial pressure, cardiac filling pressures, cardiac output, stroke volume, and rates of oxygen delivery and oxygen consumption that were greater than those with HES. Vascular resistances were similar. Analysis of left ventricular function curves also indicated an improvement in cardiac performance. However, these effects almost completely vanished during the remainder of the study. In the HT-HES group, serum sodium and osmolality levels increased to 167 +/- 4 mEq/L and 344 +/- 4 mOsm/kg H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial depression characterizes the fatal course of septic shock.

The relationship between cardiac and vascular abnormalities was studied in 68 patients with established septic shock. At time of hemodynamic evaluation, after initial resuscitation, there was no significant difference in arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac index between the 38 survivors of shock and the 30 patients who died of shock, but the left ventricular stroke work index and the right ventricular (RV) stroke work index were higher in survivors than in those who died (mean +/- SD: 25.0 +/- 9.1 vs 20.1 +/- 9.4 gm/m2 [p less than 0.05] and 6.6 +/- 3.6 vs 4.8 +/- 2.8 gm/m2 [p less than 0.05], respectively). Survivors had also higher thermodilution RV ejection fraction and lower RV end-diastolic volumes than had those who died (43.9% +/- 16.3% vs 31.1% +/- 13.7% [p less than 0.01] and 82 +/- 30 vs 99 +/- 31 ml/m2 [p less than 0.05], respectively). Calculated systemic vascular resistance was similar in the two groups, but vasopressors had been required in 22 (58%) of 38 survivors and 25 (83%) of 30 patients who died (p less than 0.01). Moreover, when the patients were separated into two groups according to their cardiac output, higher or lower than 3 L/min/m2, in both subgroups patients who died had lower blood pressure than had survivors. Blood lactate levels were significantly lower in survivors than in nonsurvivors (5.1 +/- 2.1 vs 8.1 +/- 4.7 mEq/L, p less than 0.01). Final data obtained before recovery of shock or death indicated that the survivors had higher arterial pressure, lower pulmonary artery pressure and right atrial pressure, higher stroke volume, and higher RV ejection fraction than had the patients who died. No survivors but all patients who died had been treated with vasopressors. These data therefore indicate that death as a result of septic shock is characterized by both myocardial depression and altered vascular tone and both are probably interrelated.     

Ethanol impairs cardiocirculatory function in treated canine hemorrhagic shock

This study examined the hypothesis that ethanol-induced alterations in cardiac function and regional blood flow impair recovery from shock after resuscitation. Blood ethanol levels 45 minutes after ethanol (3 gm/kg) was administered intrajejunally were 276 +/- 30 mg/100 ml (N = 14 dogs). Twelve dogs received saline solution and served as control animals. Elevated blood ethanol levels increased the rate of left ventricular pressure rise (+763 +/- 80 mm Hg X sec) and coronary blood flow (+0.77 +/- 0.18 ml X min X gm), decreased respiration, and caused a significant metabolic acidosis (arterial pH, 7.25 +/- 0.02; arterial lactate, 1.5 +/- 0.07 mmol/L). Two hours of hemorrhagic shock impaired cardiovascular function and regional blood flow to a similar extent in all dogs. Volume replacement (shed blood and lactated Ringer's solution, 50 ml/kg) transiently improved cardiac performance in the ethanol group. Two hours after volume replacement, a lower cardiac output, stroke volume, stroke work, myocardial oxygen efficiency, and persistent acidosis occurred in the intoxicated dogs (p less than 0.05) despite adequate coronary perfusion. Myocardial sensitivity to acidosis after shock may account for the reduced cardiac function in the ethanol group. However, it is possible that shock aggravated ethanol-induced pancreatic ischemia and contributed to impaired cardiocirculatory function in postinfusion shock.     

不同液体输注对犬失血性休克时的血流动力学、氧转运及血管外肺水的影响

目的:以犬为实验对象研究不同液体输注对失血性休克时的血流动力学、氧转运及血管外肺水的影响。方法:选择成年健康犬15只,静脉麻醉后通过动脉放血至平均动脉压4.67kPa制作失血性休克模型,继分别以乳酸钠林格氏液、全血及多聚明胶等三种液体输注复苏,以PAWP值恢复至2.0kPa为输血输液终点,观察血流动力学、氧转运和血管外肺水等各指标的变化。结果:乳酸钠林格氏液组的血流动力学各项指标虽然于复苏即刻恢复至对照水平,但复苏后30分钟CI、SVI即降至低于对照水平,而全血组和多聚明胶组于复苏即刻及复苏后30分钟均可明显恢复血流动力学各指标,并且多聚明胶组在CI、SVI、SVRI等各指标较其它两组为好。结论:在失血性休克输液治疗过程中,胶体液较晶体液更为有效,且对血管外肺水影响较小。多聚明胶能更有效地改善血流动力学状态,全血能明显增加氧转运。     

犬烧伤休克延迟复苏的实验研究

目的探讨应用林格液进行烧伤休克延迟复苏的效果.方法12只犬随机分为对照组(S组,6只)和治疗组(LR组,6只).LR组采用35%TBSAⅢ度烧伤模型,伤后6h以乳酸林格液进行复苏,并以尿量为1.0ml@kg-1@h-1及心输出量为伤前值的70%～80%来调整输液速度及输入量,观察其在伤后第一个24h复苏中的容量负荷、平均动脉压(MAP)、左心室收缩压(LVSP)、左室内压最大上升/下降速率(±dp/dtmax)、心脏排血指数(CI)、氧供给(DO2)及氧消耗(VO2)等的变化.结果乳酸林格液在烧伤休克延迟复苏后第一个24h的复苏中,每1%烧伤面积的输液量为(887±1.02)ml/kg,比采用Parkland公式复苏多1.2倍,其中在复苏后4h内的输液量为(3.63±0.99)ml/kg,为总入量的41%;MAP、LVSP、±dp/dtmax、CI、DO2及VO2等指标在复苏后2h即达到或接近对照组水平.结论乳酸林格液在烧伤休克延迟复苏中,比早期复苏需要更多的液体量才能满足需求,而血流动力学、心肌功能及氧动力学等在复苏后2h即有明显改善.     

Adrenergic support during anesthesia in experimental endotoxin shock: norepinephrine versus dobutamine

The effects of norepinephrine and dobutamine were compared during endotoxin shock in dogs anesthetized either with enflurane (E: 1.5%, N = 12) or with i.v. ketamine (K: 5 mg.kg-1 + 0.2 mg.kg-1.min-1, N = 12). An i.v. bolus of 1.5 mg.kg-1 E. coli endotoxin was followed by saline infusion to restore left-sided filling pressures at baseline. With E, heart rate, mean arterial pressure and stroke index decreased (P less than 0.01). The decrease in oxygen delivery (DO2) and in oxygen consumption (VO2) was associated with an increase in blood lactate. In contrast, K anesthesia was associated with remarkable hemodynamic stability. DO2 was well maintained, VO2 decreased (P less than 0.01) and blood lactate did not change. Under E anesthesia, mean arterial pressure increased more with norepinephrine and heart rate increased more with dobutamine. Under K anesthesia, cardiac index, stroke index and left ventricular stroke work index increased similarly with both agents. In both groups DO2 and VO2 increased markedly. The amount of fluid infused was higher with dobutamine than with norepinephrine. Thus, enflurane but not ketamine had depressant cardiovascular effects at the doses used in this model. With both anesthetics, norepinephrine and dobutamine could effectively improve cardiac function. Dobutamine could therefore represent a valuable alternative to norepinephrine for cardiovascular support during anesthesia in septic shock.     

Adjuvant effects of beta-adrenergic drugs on indomethacin treatment of newborn canine endotoxic shock.

Newborns are susceptible to gram-negative sepsis/septic shock, but there is no established method of its treatment. This study was performed to evaluate the adjuvant effects of dopamine and dobutamine in the indomethacin treatment of newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2 to 10 days old; 300 to 800 g) by Escherichia coli lipopolysaccharide (LPS; 1.5 mg/kg, intravenously [IV]). Indomethacin (1.5 mg/kg, IV) was injected 5 minutes after LPS injection. Dopamine (5 micrograms/kg/min) or dobutamine (5 micrograms/mg/min) infusion started 5 minutes after LPS injection immediately following indomethacin injection. Hemodynamic parameters were monitored serially for 120 minutes. LPS induced bradycardia and hypotension, decreased the cardiac output and cardiac performance, and increased the total vascular resistance. When dopamine, dobutamine, or indomethacin were used alone, they attenuated the hemodynamic deterioration by LPS. Dopamine infusion following indomethacin administration improved the hemodynamics further, although dobutamine infusion did not. Therefore, we conclude that the adjuvant therapy of dopamine in the indomethacin treatment of newborn endotoxic shock is beneficial.     

Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates

Neutrophil adherence or aggregation may be important in the development of organ injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both adherence and aggregation. Therefore we investigated MAb 60.3 treatment in prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca mulatta). We performed esophagogastroscopy and placed catheters to measure cardiac output, mean arterial pressure, arterial blood gases, and urine output. Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered intravenously. Monitoring and fluid resuscitation continued for 24 hours, with lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus additional lactated Ringer's solution to maintain CO at preshock levels. Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3-treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg), gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05; Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb 60.3 at the time of resuscitation reduces fluid requirements and gastric injury in monkeys after hemorrhagic shock.     

Use of norepinephrine in the treatment of septic shock

The effects of noradrenaline were studied in 16 patients, with either a hyperkinetic septic shock syndrome or a septic shock resistant to dobutamine treatment. The study aimed to restore normal tissue perfusion pressure, assessed by a return to normal of urine output or blood pressure. An optimal left ventricular filling pressure, estimated by the pulmonary capillary wedge pressure, was obtained for each patient using a Swan-Ganz catheter. The administration of 10.6 +/- 0.5 micrograms.kg-1.min-1 dobutamine (starting dose: 6 micrograms.kg-1.min-1) was started when the cardiac index (CI) was less than 3.3 l.min-1.m-2 after vascular filling with plasma expanders. Patients became eligible for noradrenaline treatment when they fulfilled the following conditions: arterial systolic pressure (Pasys) less than or equal to 90 mmHg; systemic vascular resistances less than or equal to 600 dyn.s.cm-5; CI greater than 3.5 l.min-1.m-2; persistent oliguria (less than 30 ml.h-1). This drug was given at a constant rate with a starting dose of 0.5 micrograms.kg-1.min-1, increased every 10 min by 0.3 to 0.6 micrograms.kg-1.min-1 according to the effects on Pasys and hourly urine output. Eight patients received noradrenaline alone; the efficient dose was 0.9 +/- 0.2 micrograms.kg-1.min-1, and it was used for a mean 5.1 +/- 1 days. CI increased in those patients who were given both noradrenaline and dobutamine. Thirteen out of the 16 patients had a dramatic increase in urine output; only three patients remained oliguric. There were no effects on serum creatinine concentration, anion gap, intrapulmonary shunt and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of dobutamine in hyperkinetic septic shock treated with norepinephrine

A prospective study of the haemodynamic effects of dobutamine was carried out in six men and four women suffering from hyperkinetic septic shock, already treated with noradrenaline and dopamine. All ten patients had septic shock, defined as a mean arterial blood pressure of less than 70 mmHg and an urine output under 15 ml.h-1, persisting despite fluid loading, associated with positive blood cultures, increased white blood cell counts, and a septic area. Initial treatment consisted in fluid loading, so as to increase cardiac output whilst keeping pulmonary wedge pressure (Ppw) between 8 and 10 mmHg. Dopamine was then added, up to a dose of 15-20 micrograms.kg-1.min-1, in an attempt to improve coronary and renal blood flows. In patients in whom this failed, the amounts of dopamine were then decreased, down to 3 micrograms.kg-1.min-1, and replaced by noradrenaline. When patients had as steady cardiac index (CI) greater than 3 l.min-1.m-2 and a systemic arterial resistance index (RsaI) of less than 1,800 dyn.s.cm-5.m-2 for more than 60 min, they were included in the protocol. Dopamine was then replaced by increasing doses of dobutamine (0, 5, 7.5, 10, 15 and again 0 micrograms.kg-1.min-1). The usual haemodynamic parameters were measured and calculated once a steady state had been obtained at each dose (within 20 to 30 min). Ppw was kept between 8 and 10 mmHg by fluid loading with a 4% albumin solution. At the beginning of the study, patients had a mean blood pressure of 78 +/- 6 mmHg, a CI of 4.8 +/- 1.5 l.min-1.m-2 and a RsaI of 1,285 +/- 341 dyn.s.cm-5.m-2 RsaI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a Dobutamine-induced Increase in Splanchnic Blood Flow on Hepatic Metabolic Activity in Patients with Septic Shock

Background: Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2 spl). The increased Qspl, however, may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2 spl), however, was challenged because most of the elevated VO2 spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2 spl leads to increased VO sub 2 spl associated with accelerated HGP in patients with septic shock.

Methods: Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure greater or equal to 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2 spl, and VO sub 2 spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radioactive-labeled glucose using a primed-constant infusion approach.

Results: Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34 l [center dot] min sup -1 [center dot] m2; P < 0.001) producing a parallel increase of DO2 spl (from 141 +/- 33 to 182 +/- 44 ml [center dot] min sup -1 [center dot] m2; P < 0.001), there was no effect on VO2 spl (73 +/- 16 and 82 +/- 21 ml [center dot] min sup -1 [center dot] m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg [center dot] kg sup -1 [center dot] min sup -1 (P < 0.001).     

Vasopressin,but not fluid resuscitation,enhances survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs

BACKGROUND: The authors compared the effects of vasopressin fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. METHODS: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n = 9), or fluid resuscitation (n = 7), or saline placebo (n = 7), respectively. A continuous infusion of 0.08 U x kg(-1) x min(-1) vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed. RESULTS: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean +/- SD, 72 +/- 26 vs 38 +/- 16 vs 11 +/- 7 mmHg, respectively; P< 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressin-treated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (approximately 15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 +/- 6 vs 42 +/- 4 vs 43 +/- 6 ml/kg, respectively; P< 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05). CONCLUSIONS: Vasopressin, but not fluid resuscitation or saline placebo, ensured survival with full recovery in this liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.     

Comparative effects of dopamine, naloxone, and prostacyclin in the resuscitation of fecal-Escherichia coli peritonitis-induced septic shock in neonatal swine

To explain the high neonatal mortality from peritonitis-induced septic shock despite current resuscitation practices, the efficacy of dopamine, naloxone, and prostacyclin was evaluated in an experimental neonatal model. Hemodynamics were monitored and survival was measured in anesthetized neonatal swine, which were subjected to fatal fecal-Escherichia coli peritonitis-induced septic shock. All the animals received fluid resuscitation, antibiotics, and bicarbonate to correct acidosis. Pharmacologic resuscitation began when cardiac output dropped below baseline in the experimental groups. Although significant differences were observed between groups in cardiac output, mean arterial and mean pulmonary arterial pressures, left ventricular stroke work, stroke volume, and pulmonary vascular resistance indices (P less than 0.02), and each animal exhibited favorable hemodynamic responses during the first several hours of dopamine and naloxone infusion, these drugs failed to prolong survival. Also, 5 of the 9 naloxone-treated pigs (56%), died with histologically proven intestinal ischemia (P less than 0.02). Thus, dopamine, naloxone, and prostacyclin (at doses commonly recommended for the treatment of septic shock) fail to positively influence the fatal course of this condition, and the use of naloxone in this model is associated with profound intestinal ischemia.     

Vasopressin, but Not Fluid Resuscitation, Enhances Survival in a Liver Trauma Model with Uncontrolled and Otherwise Lethal Hemorrhagic Shock in Pigs

Background: The authors compared the effects of vasopressin versus fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.

Methods: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n = 9), or fluid resuscitation (n = 7), or saline placebo (n = 7), respectively. A continuous infusion of 0.08 U [middle dot] kg-1 [middle dot] min-1 vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed.

Results: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean +/- SD, 72 +/- 26 vs. 38 +/- 16 vs. 11 +/- 7 mmHg, respectively;P < 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressin-treated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (~15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 +/- 6 vs. 42 +/- 4 vs. 43 +/- 6 ml/kg, respectively;P < 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05).     

Effect of moderate hypothermia in the treatment of canine hemorrhagic shock.

This study evaluated a possible protective and therapeutic effect of moderate hypothermia in the treatment of severe hemorrhagic shock. A modified Wiggers shock preparation was used. Normothermic dogs (Group I, N = 6) were maintained at normal body temperature throughout hemorrhagic shock and resuscitation. In Group II, hypothermia was initiated after 15 minutes of hemorrhagic shock (N = 12) and maintained for 60 minutes after fluid resuscitation. Animals were then rewarmed with Group IIA (N = 7) receiving sodium bicarbonate to correct acidosis, while Group IIB (N = 5) did not; all dogs were studied for an additional 120 minutes. During shock heart rate was lower in both hypothermic groups (IIA and IIB) compared to normothermic dogs (85.0 +/- 3.9, 77.7 +/- 4.6 vs. 136.7 +/- 4.2, respectively, p less than 0.05), while +dP/dt (mmHg/s) remained stable in all dogs. Furthermore, pH was lower in the hypothermic (Groups IIA and IIB) compared to normothermic animals at this time period (Group IIA: 7.19 +/- 0.02, Group IIB: 7.13 +/- 0.02 vs. Group I: 7.24 +/- 0.02). Arterial pCO2 was higher in the hypothermic hemorrhagic shock Groups IIA and IIB compared to normothermic group (34.5 +/- 2.2, 37.4 +/- 2.2 vs. 20.3 +/- 20,3 +/- 2.0, p less than 0.05) due to hypothermia-depressed respiration. A higher myocardial O2 consumption and a negative myocardial lactate balance occurred in the normothermic animals during hemorrhagic shock. After resuscitation and rewarming, stroke volume (mL/beat) and cardiac output (L/min) were lower in hypothermic animals with persistent acid-base derangements (12.6 +/- 2.5, 1.3 +/- 3.0, respectively) compared to hypothermic dogs with acid-base correction (20.1 +/- 3.3, 2.2 +/- 0.3) and normothermic dogs (24.6 +/- 3.0, 3.0 +/- 0.3, p less than 0.05), while myocardial O2 extraction and myocardial lactate production were higher. Results suggest hypothermia decreases the metabolic needs and maintains myocardial contractile function in hemorrhagic shock. Hypothermia may have a beneficial effect and, with normalization of acid-base balance, a therapeutic role in hemorrhagic shock.     

Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns.

Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringer's was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.