Uncontrolled Hemorrhagic Shock Research Articles

Regional and Local Brain Oxygenation During Hemorrhagic Shock: A Prospective Experimental Study on the Effects of Small-Volume Resuscitation With Norepinephrine

Patients with uncontrolled hemorrhage may benefit if resuscitation with large amounts of fluids is replaced by a small volume or vasopressor until surgery. Norepinephrine (NE) is commonly used as a vasopressor to control hypotension. The purpose of this study was to compare the effects of hypertonic-hyperoncotic saline starch solution (HHS) either alone or combined with NE on brain tissue oxygen pressure (PbtO2) and brain oxygen saturation (rSO2) in a model of uncontrolled hemorrhage. After approval of the animal investigation committee, 22 anesthetized pigs underwent simulated penetrating liver trauma. At hemodynamic decompensation, animals were randomly assigned to receive HHS (Hyperhaes; 4 mL/kg; n = 8) with normal saline placebo, low-dose NE (low NE; 500 microg, and 1 microg/kg/min; n = 7), or high-dose NE (high NE; 1,000 microg, and 1 microg/kg/min; n = 7). Bleeding was controlled manually 30 minutes after drug administration. Cerebral perfusion pressure (CePP), PbtO2, and rSO2 decreased with hemorrhage in all groups (baseline vs. decompensation, CePP-HHS, 83 +/- 5 mm Hg vs. 9 +/- 1 mm Hg; low NE, 67 +/- 6 mm Hg vs. 16 +/- 2 mm Hg; high NE, 77 +/- 7 mm Hg vs. 15 +/- 1 mm Hg. PbtO2-HHS, 100% vs. 29%; low NE, 100% vs. 33%; high NE, 100% vs. 27%. rSO2-HHS, 100% vs. 70%; low NE, 100% vs. 76%; high NE, 100% vs. 63%). Therapy with HHS, low NE, and high NE resulted in a comparable increase of CePP, PbtO2, and rSO2, respectively (5 minutes after therapy, CePP-HHS, 29 +/- 3 mm Hg; low NE, 27 +/- 3 mm Hg; high NE, 28 +/- 3 mm Hg. PbtO2-HHS, 207%; low NE, 129%; high NE, 170%. rSO2-HHS, 94%; low NE, 83%; high NE, 87%). Overall survival was six of eight, four of seven, and six of seven, respectively. After uncontrolled hemorrhagic shock, addition of different dosages of NE to HHS, compared with HHS alone, showed no beneficial effect on CePP, rSO2, or PbtO2.

QS397. Comparison of Inhaled and Intravenous Anesthetic Regimens on Hemodynamics and Inflammation in a Porcine Model of Goal-Directed Resuscitation of Hemorrhagic Shock

Introduction: Previous studies have suggested that a ketamine-based total intravenous anesthetic (TIVA) regimen is superior to an inhaled anesthetic by producing fewer adverse effects. While the use of TIVA has been documented in elective operations, there is limited data on its performance during traumatic shock. The purpose of this study was to evaluate the differential effects of an inhalational anesthetic with a TIVA regimen in the setting of uncontrolled hemorrhagic shock secondary to an induced Grade V liver injury.

Effect of limited volume resuscitation on hemodynamic changes in pregnant rabbit with hemorrhagic shock

To determine the effects of two fluid resuscitation strategies on the changes of hemodynamic variables, serum concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a clinically relevant model of uncontrolled hemorrhagic shock in pregnant rabbits. Hemorrhagic shock was induced by bleeding via carotied artery, followed by transection of a medium vessel in gestational sac. Experimental design consisted of three phases, shock phase (0-30 min), prehospital phase (30-90 min) and hospital phase (90-180 min). Twenty pregnant rabbits were randomly divided into two groups (n=10 /group), aggressive fluid resuscitation group (PNL group) and limited volume resuscitation group (PLH group). In the shock phase, animals were hemorrhaged by blood withdrawal to mean arterial pressure (MAP) of 40-45 mm Hg (1 mm Hg=0.133 kPa) via carotid artery. In the prehospital phase, a medium vessel in the gestational sac was transected, then the animals in the PNL group and PLH group were resuscitated with 0.9% normal saline (NS) and shed blood to MAP of 80, 60 mm Hg respectively. In the hospital phase, bleeding was controlled by surgical intervention and all the animals were reinfused with shed blood and NS to MAP 80 mm Hg. Hemodynamic variables and respiration rate were monitored and blood samples were collected for TNF-alpha and IL-6 measurement, and finally subsequent volume resuscitation and survival rate were recorded. (1) At 120 min, the respiration rate and heart rate in the animals assigned to PLH group was (66+/-16) bpm, (235+/-41) bpm respectively, which were significantly lower than those in PNL group (P<0.01), while MAP and central venous pressure in the PLH group was (80.4+/-7.2) mm Hg, (8.0+/-4.4) cm H2O, respectively, which were significantly higher than those in PNL group (P<0.01); (2) The serum concentration of TNF-alpha, IL-6 of all the animals were markedly increased after hemorrhagic shock, and peak at 24 min. The serum concentration of TNF-alpha, IL-6 in animals assigned to PLH group were (105+/-67) ng/L, (118+/-51) ng/L respectively, which were significantly lower than those in PNL group (P<0.01). The serum concentration of TNF-alpha, IL-6 in the animals assigned to PLH group were decreased to normal at 480 min; (3) The subsequent blood transfusion volume and NS resuscitation volume in PLH group in prehospital phase were (16.0+/-2.2) ml, (39.0+/-5.5) ml respectively, while those in hospital phase were (28.0+/-6.7) ml, (90.0+/-7.1) ml respectively, which were significantly lower than those in PNL group (P<0.05); (4) The 24 and 72 hours survival rate in the animals assigned to PLH group were 100%, 90% respectively; which were significantly higher than those in PNL group (P<0.01). Limited volume resuscitation improves thermodynamic changes of pregnant rabbit, attenuates the increase of serum concentration of TNF-alpha, IL-6, and results in higher survival rate. Limited volume resuscitation is an ideal means for hemorrhagic shock resuscitation in pregnant rabbit.

Use of recombinant activated factor VII in intractable bleeding during pediatric neurosurgical procedures

OBJECTIVE:: To report the use of recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical procedures and experiencing massive uncontrolled hemorrhagic shock. DESIGN:: Retrospective review of patients and analysis of clinical and biological effects of an intravenous administration of recombinant activated factor VII. SETTING:: Neurosurgical anesthesia and critical care unit of a pediatric university hospital. PATIENTS/SUBJECTS:: Four children, <12-kg body weight, experiencing life-threatening perioperative hemorrhage required conventional treatment (massive red blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic maneuvers) that failed to obtain definite hemostasis. INTERVENTIONS:: Intravenous administration of recombinant activated factor VII (100 mug/kg). RESULTS:: Intravenous administration resulted in a significant decrease in blood loss within minutes (preventing further need of transfusion), normalization of biological hemostasis markers, and improved surgical hemostasis. No side effects of recombinant activated factor VII were noted, and all patients, except one, had a good recovery. CONCLUSIONS:: These four patients support the use of recombinant activated factor VII as a useful adjunct to control massive life-threatening bleeding during pediatric neurosurgical procedures when other means failed. However, the data are still limited in children, and more extensive research is needed to define the indications of recombinant activated factor VII in massive surgical hemorrhage in low-weight children.

Experimental Study of Controlled Fluid Resuscitation in the Treatment of Severe and Uncontrolled Hemorrhagic Shock

Hemorrhagic shock is a common clinic emergency case. The fluid resuscitation method in the presurgical care of hypotensive trauma patients is open to debate. This study was conducted to evaluate the general and pathophysiologic effects of controlled fluid resuscitation in the treatment of severe and uncontrolled hemorrhagic shock. A model of rat with severe hemorrhagic shock and active bleeding was established in 32 Sprague-Dawley rats. The rats were randomly divided into the control group, no fluid resuscitation group (NF group), controlled fluid resuscitation group (NS40 group), and aggressive fluid resuscitation group (NS80 group). Each group contained eight rats. The changes of survival, blood loss, blood platelet, hemoglobin, hematocrit, and serum lactate level were dynamically monitored in the "prehospital phase". In addition, the apoptosis in the liver, kidney, lung, and small intestinal mucosa of survivors after hemorrhage and resuscitation was detected by light microscopy in hematoxylin-eosin stained tissue sections, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Via the above-mentioned indexes, the curative effects of three fluid resuscitation methods were compared. Compared with the survival in the NF group (3 of 8), the higher survival rate of the NS40 and NS80 groups (14 of 16) showed significant difference (p < 0.05). After fluid resuscitation, serum lactate levels in the NS40 and NS80 groups obviously decreased (p < 0.01 compared with control and NF groups). The shed blood loss from bleeding tail in the NS80 group was obviously increased (p < 0.01 for the NS80 group compared with the control, NF, and NS40 groups). Compared with that of the control, NF, and NS40 groups, the hemoglobin, hematocrit, and blood platelet of the NS80 group quickly descended in the prehospital phase and showed statistical differences. At the same time, there was some apoptosis in the liver, kidney, lung, and small intestinal mucosa of all survivors. Compared with that of the NF and NS40 groups, the apoptosis of liver, kidney, and small intestinal mucosa of the NS80 group was obviously increased, and showed statistical differences. In severe and uncontrolled hemorrhagic shock, some fluid must be given in proper time to improve tissue perfusion and avoid early death. Among three fluid resuscitation methods, controlled fluid resuscitation can effectively decrease additional blood loss, avoid excessive hemodilution and coagulopathy, improve the early survival rate, and reduce the apoptosis of visceral organs in rats with severe and uncontrolled hemorrhagic shock. This model supports the concept that when surgical care is not readily available, controlled fluid resuscitation should be considered in the treatment of uncontrolled hemorrhagic shock.

Improved Survival after Resuscitation with Norepinephrine in a Murine Model of Uncontrolled Hemorrhagic Shock

Recent studies have challenged current guidelines on fluid resuscitation. However, studies on resuscitation using norepinephrine in uncontrolled hemorrhagic shock are lacking. The authors examined the effects of norepinephrine in combination with saline infusion in uncontrolled hemorrhage in rats. Rats subjected to a 15-min controlled hemorrhage (withdrawal of 3 ml blood/100 g body mass) followed by a 60-min uncontrolled hemorrhage (75% tail amputation) were randomly assigned to one of several treatment groups (10 rats/group) receiving different doses of norepinephrine (0 [NE0], 5 [NE5], 50 [NE50], or 500 [NE500] microg.100 g(-1).h(-1)). In the four hypotensive resuscitation groups (n = 40), mean arterial pressure was not allowed to fall below 40 mmHg by titrated infusion of normal saline. In the four normotensive resuscitation groups (n = 40), it was not allowed to fall below 80 mmHg. The endpoint was survival at 210 min. There was a significant difference (P < 0.05) in survival rate among groups. Among the hypotensive rats, 6 (60%) survived in the NE0 and NE5 dose groups, 9 (90%) survived in the NE50 dose group, and none survived in the NE500 dose group. Among the normotensive rats, none survived in the NE0 group, 4 (40%) survived in the NE5 dose group, all 10 (100%) survived in the NE50 group, and none survived in the NE500 group. The early use of norepinephrine in uncontrolled hemorrhagic shock in rats significantly improved survival when infused at a rate of 50 microg.100 g(-1).h(-1) in normotensive and hypotensive resuscitation strategies.

Management of Uncontrolled Hemorrhagic Shock

Management of Uncontrolled Hemorrhagic Shock

This Month in Anesthesiology

In awake patients undergoing carotid endarterectomy, stump pressure monitoring, near-infrared spectroscopy, and transcranial Doppler sonography provide similar accuracy for the detection of cerebral ischemia.Vocal cord sequelae after fiberoptic intubation with a flexible silicon tube were similar to conventional tracheal intubation.Poor agreement between American College of Cardiology/American Heart Association guideline recommendations for perioperative care and daily clinical practice.See the accompanying Editorial View on page 526 The December 2001 Food and Drug Administration (FDA) black box warning about droperidol, commonly used as premedication for postoperative nausea and vomiting, was based on 10 case reports. To determine the true incidence of QTc prolongation and/or drug-induced torsade de pointes (TdP) associated with droperidol use, Nuttall et al. conducted a retrospective study using the electronic Anesthesia Quality Assurance database at their institution. They reviewed charts of surgical patients from three years prior to December 2001 and from three years after the FDA warning. Prior to the black box warning, 12% of patients received droperidol for antiemesis; none were administered droperidol after the warning. Of an estimated 16,791 patients exposed to droperidol, none experienced documented torsade de pointes. In light of these findings, the FDA warning may be excessive and unnecessary for low-dose droperidol therapy. See the accompanying Editorial View on page 524 Poloujadoff et al. subjected rats to uncontrolled hemorrhagic shock to test the efficacy of norepinephrine for resuscitation. Different doses of norepinephrine (from 0 to 500 μg · 100 g−1· h−1) were given in four hypotensive and four normotensive resuscitation groups, and animals were observed for 210 min posthemorrhage. Rats treated with high doses of norepinephrine died early. Survival significantly improved when norepinephrine was infused early at a rate of 50 μg · 100 g−1· h−1in both the normotensive and hypotensive resuscitation groups. More widely available than vasopressin, norepinephrine might be a useful strategy in resuscitation after hemorrhagic shock. See the accompanying Editorial View on page 529 In some children, midazolam does not relieve presurgery anxiety. Kain et al. administered a series of behavioral tests, including the modified Yale Preoperative Anxiety Scale (mYPAS), to children scheduled for surgery and their parents. Based on the mYPAS and other scores, 14.1% of the children were nonresponders to midazolam. Correlation analysis revealed that these children tended to be younger, more emotional, and more anxious at baseline. Alternative anxiety-reducing strategies, including behavioral techniques, may be in order for this subgroup of children before surgery.Patients over the age of 65 scheduled for coronary artery bypass surgery were randomized to receive moderate (hematocrit ≥ 27%) or profound (hematocrit 15–18%) hemodilution during cardiopulmonary bypass. Authors Mathew et al. measured the patients' cognitive function preoperatively and 6 weeks postoperatively, to determine the effects of hemodilution on cognition. The trial was terminated after randomization of only 108 patients due to significant pulmonary complications evidenced in the moderate hemodilution group. In the patients who did complete the study, greater neurocognitive impairment was observed in those older patients receiving extreme hemodilution.This article has been selected for the Anesthesiology CME Program.

Use of Nuclear Magnetic Resonance Spectroscopy to Assess Renal Dysfunction After Hypertonic-Hyperoncotic Resuscitation in Rats

The aim of this study was to evaluate the renal tolerance of a hypertonic-hyperoncotic solution (HHS) administration during uncontrolled hemorrhagic shock (UHS). UHS was produced in rats by a preliminary bleed followed by tail amputation. Hydroxyethylstarch (HHS) 200/0.5 6% in NaCl 7.2% was administered to the HHS groups (n = 20) and normal saline (NS) to the NS group (n = 20). Infusion rates were adjusted to prevent mean arterial pressure (MAP) from falling either below 40 mm Hg in the HHS40 (n = 10) and NS40 groups (n = 10), or below 80 mm Hg in the HHS80 (n = 10) and NS80 groups (n = 10). Data obtained were compared with a sham group and a no resuscitation (NR) group. Nephrotoxicity was evaluated by nuclear magnetic resonance analysis in urine samples. Survival was 60% in the NS40 group and 40% in the NS80 group, 70% in the HHS40 group, and 60% in the HHS80 group (p = not significant). Within and between target groups of 40 mm Hg MAP and 80 mm Hg MAP, there was no significant difference in survival. The mean values of renal metabolites to creatinine (ct) ratios were not significantly different among the six groups. Principal component analysis showed that the HHS80 group was characterized by an increase in allantoin/ct and urea/ct ratios demonstrating acute renal dysfunction and failure of nitrogen metabolism. In prolonged UHS, an infusion of HHS may not increase the rate of survival. HHS infusion in normotensive resuscitation appears to be associated with renal toxicity.

Lactated Ringer's is Superior to Normal Saline in the Resuscitation of Uncontrolled Hemorrhagic Shock

Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.

Vasopressin improves survival in a porcine model of abdominal vascular injury

IntroductionWe sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs.MethodsDuring general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.ResultsAfter 68 ± 19 min (mean ± standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).ConclusionVasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.

Continuous infusion of small-volume fluid resuscitation in the treatment of combined uncontrolled hemorrhagic shock and head injury.

To determine the effect of continuous limited fluid resuscitation on the hemodynamic response and survival in rats in a model of uncontrolled hemorrhage shock due to massive splenic injury (MSI) and head injury (HI). An experimental study. Dicle University Animal Research Laboratory, Turkey, between January and February 2005. Seventy Sprague-Dawley rats were used in this study. Group 1 rats (n=10) was sham-operated. In group 2 (n=10), only Massive Splenic Injury (MSI) was performed and untreated. In group 3 (n=10), only head injury (HI) was performed and untreated. In group 4 (n=10), HI and MSI were performed and were untreated. In group 5 (n=10), HI and MSI were performed and 15 minutes later treated with 7.5% NaCl. In group 6 (n=10), HI and MSI were performed, and rats were treated with Ringer's Lactate (RL) solution. In group 7 (n=10), HI and MSI were performed, rats were treated with 0.9 % NaCl. In groups 2,4,5,6 and 7 midline incision was reopened and splenectomy was performed at 45 minutes. In group 4 rats, Mean Arterial Pressure (MAP) was decreased from 104 +/- 6.1 mmHg to 75 +/- 19.5 mmHg at 15 minutes; heart rate decreased from 357 +/- 24.9 beats/min to 321 +/- 62.1 beats/min and hematocrit decreased from 46 +/- 1.3 % to 43 +/- 2.5 % (p<0.01). Similar early changes in MAP, heart rate and hematocrit were observed in groups 5, 6, and 7, at 15 minutes. At 45,60 and 120 minutes, in fluid resuscitated rats (group 5,6,7) MAP, heart rate and hematocrit values were measured higher than group 2 and 4 (p<0.01 for all). At 120 min. in group 6, hematocrit was higher than group 4, 5 and 7, in group 6, total blood loss after splenectomy was calculated at 20 +/- 2.4% of blood volume and was the best value compared to other fluid resuscitated group 5 and 7 (28% and 27% of blood volume) (p<0.01). Mortality was lower in all fluid resuscitated groups when compared to group 3 and 4 (p<0.05). The median survival time was again higher in fluid resuscitated groups. Continuous infusion of 7.5% NaCl, RL and 0.9 % NaCl following uncontrolled hemorrhagic shock with massive splenic injury and combined head injury resulted in better survival and RL did not increase abdominal bleeding before splenectomy was performed.

Effect of Induction Rate for Mild Hypothermia on Survival Time During Uncontrolled Hemorrhagic Shock in Rats

Rapid induction of hypothermia has been shown to improve survival in uncontrolled hemorrhagic shock (UHS) rat studies. We hypothesized that prolonged induction of hypothermia would be equally beneficial for survival during UHS. Light anesthesia was induced with halothane in 30 rats, and spontaneous breathing was maintained. Rectal temperature (Tr) was monitored and maintained at 38 degrees C. UHS was induced by blood withdrawal of 2.5 mL/100 g during a 15-minute period, followed by 75% tail amputation. Immediately after cutting the tail, rats were randomized into three groups of 10 rats each: Group 1, maintained at Tr 38 degrees C; group 2, passively cooled to 34 degrees C by exposure to room temperature (23 degrees C); and group 3, actively cooled to 34 degrees C by applying alcohol to the skin and under an electric fan. Next, rats were controlled at each target Tr and observed without fluid resuscitation until either death or a maximum of 240 minutes. Cooling rate was -0.09 +/- 0.01 degrees C/min in group 2 and -0.36 +/- 0.9 degrees C/min in group 3 (p < 0.01). Mean survival time was 72 +/- 21 minutes in group 1 (38 degrees C), and was nearly doubled by hypothermia to 132 +/- 62 minutes for group 2 (p < 0.01 vs. group 1) and 150 +/- 69 minutes for group 3 (p < 0.01 vs. group 1). No significant difference in survival was noted between groups 2 and 3. Additional blood loss from the tail stump did not differ significantly between groups. Therapeutic mild hypothermia, induced either slowly (approximately -0.1 degrees C/min) or rapidly (approximately -0.4 degrees C/min) prolongs survival during lethal UHS in rats.

Effects of ethanol on limited resuscitation in a model of traumatic brain injury and hemorrhagic shock

Limited resuscitation following uncontrolled hemorrhagic shock (HS) has been associated with improved outcomes in various animal models, although it has not been previously studied in the setting of traumatic brain injury (TBI) and ethanol intoxication. The aim of the present study was to determine the effects of ethanol intoxication in a model of experimental TBI and HS treated with limited resuscitation. After induction of anesthesia and the placement of instruments, swine were subjected to a fluid-percussion injury of 3 atm. Simultaneously, hemorrhage was induced from an arterial catheter via a computerized roller pump to a mean arterial blood pressure (MABP) of 50 mm Hg, at which time uncontrolled hemorrhage was induced by the creation of an aortic tear. When the MABP decreased to 30 mm Hg, limited resuscitation to a MABP of 60 mm Hg was begun. After 60 minutes, animals were aggressively resuscitated to baseline MABP levels. Two groups of animals were studied: those receiving tap water by gastrostomy tube and those receiving ethanol (4 g/kg) by gastrostomy tube. Animals were monitored for 180 minutes after TBI. Hemorrhage volumes were significantly greater in ethanol-infused animals (mean +/- standard deviation, 41 +/- 34 mm Hg) compared with tap water-infused animals (17 +/- 18 mm Hg; p = 0.048). Resuscitation requirements were significantly higher and metabolic parameters significantly worse in the ethanol group. Survival time was also significantly decreased in the animals infused with ethanol (81 +/- 60 minutes) compared with those infused with tap water (130 +/- 51 minutes; p = 0.035). Ethanol intoxication led to increased hemorrhage volume and worsened hemodynamic and metabolic profiles in this model of limited resuscitation after TBI and HS. Ethanol-exposed animals had increased resuscitation requirements and decreased survival times.

Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats

In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival. An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats were randomized to four groups (n=10 each) for hypotensive resuscitation from 20 to 90 min (mean arterial pressure [MAP] > or = 40 mmHg): HTS/starch group received 7.2% NaCl/10% hydroxyethyl starch; HTS/albumin group received 7.5% NaCl/20% albumin; HTS/PNA group received 7.5% NaCl/20% PNA; HTS/albumin+tempol group received 7.5% NaCl/20% albumin plus tempol. Resuscitation phase II (180 min) included hemostasis, return of shed blood and administration of fluids to restore MAP > or = 80 mmHg. Observation phase III was to 72 h. The total amount of fluid required to maintain hypotensive MAP during HS was low and did not differ between groups (range: 3.4+/-1.9 to 5.3+/-2.5 ml/kg). The rate of fluid administration required was higher in the HTS/albumin+tempol group compared to all other groups (p=0.006). Additional uncontrolled blood loss was highest in the HTS/PNA group (16.2+/-5.7 ml/kg [p=0.01] versus 10.4+/-7.9 ml/kg in the HTS/starch group, 7.7+/-5.2 ml/kg in the HTS/albumin group and 8.2+/-7.1 ml/kg in the HTS/albumin+tempol group). MAP after start of resuscitation in phase I was lower in the HTS/albumin+tempol group than the HTS/albumin or HTS/PNA groups (p<0.01). This group was also less tachycardic. Long-term survival was low in all groups (2 of 10 after HTS/starch and 1 of 10 after HTS/albumin, 3 of 10 after HTS/PNA, 1 of 10 after HTS/albumin+tempol). Median survival time was shortest in the HTS/albumin+tempol group (72 min [CI 34-190]) compared to all other groups (p=0.01). Despite its benefits in other model systems, free tempol is potentially hazardous when combined with hypertonic fluids. PNA abrogates these deleterious effects on acute mortality but may lead to increased blood loss in the setting of UHS.

An observational study of vasopressin infusion during uncontrolled haemorrhagic shock in a porcine trauma model: Effects on bowel function

The effects of vasopressin on the gut in a porcine uncontrolled haemorrhagic shock model are described. In eight anaesthetised pigs, a liver laceration was performed; when haemorrhagic shock was decompensated, all animals received 0.4 IU/kg vasopressin, followed by 0.08 IU/kg min over 30 min, which maintained a mean arterial blood pressure >40 mmHg. Subsequent surgical intervention, infusion of whole blood and fluids resulted in a stable cardiocirculatory status. Three hours after stabilisation, all pigs developed non-bloody diarrhoea which converted into normal bowel movements within 24 h. All histological samples retained 7 days after the experiment revealed no histopathological changes. In conclusion, in this small observational study of uncontrolled porcine haemorrhagic shock, a resuscitation strategy that included high dose vasopressin was associated with transient diarrhoea and good long term survival.

Vasoactivity of Bovine Polymerized Hemoglobin (HBOC-201) in Swine With Traumatic Hemorrhagic Shock With and Without Brain Injury

We previously reported that bovine polymerized hemoglobin (HBOC- 201) improved outcome in swine with hemorrhagic shock (HS) with and without traumatic brain injury (TBI). Herein, we add analyses of blood pressure (BP) responses, associated physiologic data, and HS fluid infusion guidelines. HBOC-201 versus standard fluid resuscitation was compared in four anesthetized invasively monitored swine models: moderate controlled HS, severe controlled HS, severe uncontrolled HS (liver injury), and severe uncontrolled HS/TBI (liver/parietal brain injuries). Pigs received fluid for hypotension and tachycardia, and were followed up to 6 (HS alone) or 72 hours (HS/TBI). The change in mean arterial pressure (DeltaMAP) response severity was stratified and analyzed based on infusion number and HS severity, using Student's t and Fisher's exact tests. HBOC-201 vasoactivity resulted in higher MAP in all studies. Among HBOC-201 pigs, DeltaMAP responses were significant for the first two infusions and inversely related to HS severity. Among controls, DeltaMAP responses remained significant through the fourth infusion in controlled HS models, and through the first in severe uncontrolled HS/TBI; none were significant in severe uncontrolled HS. DeltaMAP was higher with HBOC-201 through the first infusion in moderate controlled HS, the fifth in severe uncontrolled HS, and the second in severe uncontrolled HS/TBI; there were no group differences in severe controlled HS. No severe MAP responses occurred. Higher DeltaMAP severity did not impact outcome. Hypotension satisfied fluid reinfusion criteria less consistently than tachycardia. Overall, HBOC-201 improved physiologic parameters and survival without causing hypoperfusion; in severe HS, perfusion improved. In swine with HS +/- TBI, HBOC-201 had mild to moderate vasoactivity, resulting in significant DeltaMAP responses mainly after initial infusions, no severe/adverse responses, and improved outcome. Our data suggest that use of physiologic parameters (e.g., tachycardia), in addition to hypotension to guide fluid reinfusion during HS resuscitation with HBOC-201, will minimize hypoperfusion risk and maximize potential benefit.

Effects of hypotensive resuscitation on uncontrolled hemorrhagic shock in rats

目前国内外的动物实验和部分临床研究结果显示,低压复苏是治疗非控制性出血性休克较为合理的方案[1～4],但还没有人从增加血容量,减少应激反应引起的血管收缩、改善组织微循环氧供方面进行研究.本研究拟观察低压及低压扩容复苏对腹腔实质脏器损伤非控制性出血性休克的治疗效果。

Cerebral Metabolism Assessed with Microdialysis in Uncontrolled Hemorrhagic Shock After Penetrating Liver Trauma

In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of fluid resuscitation versus arginine vasopressin (AVP) combined with hypertonic-hyperoncotic hydroxyethyl starch solution (HHS) on cerebral perfusion pressure (CPP) and on cerebral metabolism using intracerebral microdialysis. Sixteen anesthetized pigs were subjected to uncontrolled liver bleeding until hemodynamic decompensation, followed by resuscitation using either fluid (n = 8) or AVP/HHS (n = 8). Thirty minutes after drug administration, bleeding was controlled by manual compression, and colloid and crystalloid solutions were administered in both groups. All surviving animals were observed for one hour. After hemodynamic decompensation, fluid resuscitation resulted in a smaller increase of CPP than did AVP/HHS (mean +/- sem; 24 +/- 5 vs 45 +/- 7 mm Hg; P < 0.01). Mean (+/- sem) cerebral venous partial pressure of oxygen was significantly decreased (P < 0.01) 5 min after fluid compared with 5 min after AVP/HHS administration (36 +/- 3 vs 64 +/- 4 torr). Cerebral metabolism was comparable in both groups. In conclusion, AVP/HHS proved to be superior to fluid in the initial phase of therapy with respect to CPP and cerebral oxygenation, but was comparable to fluid regarding cerebral metabolism and secondary cell damage in surviving animals.

Effects of different therapy strategies on brain metabolism in uncontrolled hemorrhagic shock: a microdialysis study

Department of Anesthesiology, National Cardiovascular Center, Osaka, Japan Abstracts published in the Journal of Neurosurgical Anesthesiology have been reviewed by the organizations or JNA Affiliate Societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Editorial Board of the Journal of Neurosurgical Anesthesiology. 34th Annual Meeting of the Society of Neurosurgical Anesthesia and Critical Care, Chicago, Illinois, October 13th, 2006