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Life-threatening hemorrhage and exsanguination from Crohn's disease. Report of four cases.

PURPOSE AND METHODS: From 1979 through 1991, four patients of 631 admissions (0.6 percent) for Crohn's disease in Erie, Pennsylvania, presented with life-threatening gastrointestinal hemorrhage. These and 34 similar cases from the medical literature were reviewed to provide a composite of those at risk and elucidate appropriate diagnostic and therapeutic maneuvers. RESULTS: The study revealed a preponderance of young men (2:1 ratio) with an average age of 35 (range, 14-89) years, the majority of whom had known Crohn's disease (60 percent) for an average of 4.6 (range, 0-18) years. The site of bleeding resembled the general distribution for Crohn's disease, with small bowel disease predominating (66 percent involved the ileum). The five cases of exsanguination (13 percent of the total) were all men with known Crohn's disease (average, 5.8 years) involving the ileum alone or in part. Mesenteric arteriography was positive in 17 patients, providing precise preoperative localization resulting in no mortality in this group. Excluding those who presented with exsanguination, surgery was necessary to cease hemorrhage in 91 percent (30/33) of patients. Ileocolectomy was the most frequently performed procedure (53 percent). In follow-up, only one patient required further surgical resection for recurrent bleeding (3.5 percent), and two other patients (7 percent) required further therapy for nonhemorrhagic recurrence. CONCLUSION: Crohn's disease may be responsible for life-threatening gastrointestinal hemorrhage and even exsanguination. Many of the characteristics of these patients resemble the general Crohn's disease population. Surgical resection provides excellent palliation. A long-term benign course can be expected in this subgroup of Crohn's disease patients.

Adolescent↗

The crepe bandage as an alternative to the Esmarch bandage for upper limb exsanguination: a volumetric comparison study.

A study was carried out to compare the effectiveness of upper limb exsanguination using the Esmarch bandage, a crepe bandage and the Rhys-Davies exsanguinator. Upper limb volume changes were measured in ten volunteers using a water displacement method. The crepe bandage produced a mean volume reduction of 59 ml (range, 39-94), which was very similar to the Esmarch bandage, which achieved 63 ml (range, 42-101). This difference is negligible in practical terms. Both bandages were more effective than the Rhys-Davies exsanguinator, which reduced the volume by a mean of 28 ml (range, 11-54). It is our opinion that the use of the Esmarch bandage in hand surgery is unnecessary and recommend the crepe bandage as a safer alternative.

Adult↗

Reliable variables in the exsanguinated patient which indicate damage control and predict outcome.

BACKGROUND: Exsanguination as a syndrome is ill defined. The objectives of this study were to investigate the relationship between survival and patient characteristics--vital signs, factors relating to injury and treatment; determine if threshold levels of pH, temperature, and highest estimated blood loss can predict survival; and identify predictive factors for survival and to initiate damage control. MATERIAL AND METHODS: A retrospective 6-year study was conducted, 1993 to 1998. In all, 548 patients met one or more criteria: (1) estimated blood loss > or =2,000 mL during trauma operation; (2) required > or =1,500 mL packed red blood cells (PRBC) during resuscitation; or (3) diagnosis of exsanguination. Analysis was made in two phases: (1) death versus survival in emergency department (ED); (2) death versus survival in operating room (OR). Statistical methods were Fisher's exact test, Student's t test, and logistic regression. RESULTS: For 548 patients, mean Revised Trauma Score 4.38, mean Injury Severity Score 32. Penetrating injuries 82% versus blunt injuries 18%. Vital statistics in emergency department: mean blood pressure 63 mm Hg, heart rate 78 beats per minute. Mean OR pH 7.15 and temperature 34.3 degrees C. Mortality was 379 of 548 (69%). Predictive factors for mortality (means): pH < or =7.2, temperature <34 degrees C, OR blood replacement >4,000 mL, total OR fluid replacement >10,000 mL, estimated blood loss >15 mL/minute (P <0.001). Analysis 1: death versus survival in ED, logistic regression. Independent risk factors for survival: penetrating trauma, spontaneous ventilation, and no ED thoracotomy (P <0.001; probability of survival 0.99613). Analysis 2: death versus survival in OR, logistic regression. Independent risk factors for survival: ISS < or =20, spontaneous ventilation in ED, OR PRBC replacement <4,000 mL, no ED or OR thoracotomy, absence of abdominal vascular injury (P <0.001, max R(2) 0.55, concordance 89%). CONCLUSIONS: Survival rates can be predicted in exsanguinating patients. "Damage control" should be performed using these criteria. Knowledge of these patterns can be valuable in treatment selection.

Adolescent↗

Tourniquet-induced exsanguination in patients requiring lower limb surgery. An ischemia-reperfusion model of oxidant and antioxidant metabolism.

BACKGROUND: Surgically induced ischemia and reperfusion is frequently accompanied by local and remote organ injury. It was hypothesized that this procedure may produce injurious oxidants such as hydrogen peroxide (H2O2), which, if unscavenged, will generate the highly toxic hydroxyl radical (.OH). Accordingly, it was proposed that tourniquet-induced exsanguination for limb surgery may be a useful ischemia-reperfusion model to investigate the presence of oxidants, particularly H2O2. METHODS: In ten patients undergoing knee surgery, catheters were placed in the femoral vein of the limb operated on for collection of local blood and in a vein of the arm for sampling of systemic blood. Tourniquet-induced limb exsanguination was induced for about 2 h. After tourniquet release (reperfusion), blood samples were collected during a 2-h period for measurement of H2O2, xanthine oxidase activity, xanthine, uric acid (UA), glutathione, and glutathione disulfide. RESULTS: At 30 s of reperfusion, H2O2 concentrations increased (approximately 90%) from 133 +/- 5 to 248 +/- 8 nmol.ml-1 (P < 0.05) in local blood samples, but no change was evident in systemic blood. However, in both local and systemic blood, xanthine oxidase activity increased approximately 90% (1.91 +/- 0.07 to 3.93 +/- 0.41 and 2.19 +/- 0.07 to 3.57 +/- 0.12 nmol UA.ml-1.min-1, respectively) as did glutathione concentrations (1.27 +/- 0.04 to 2.69 +/- 0.14 and 1.27 +/- 0.03 to 2.43 +/- 0.13 mumol.ml-1, respectively). At 5 min reperfusion, in local blood, H2O2 concentrations and xanthine oxidase activity peaked at 796 +/- 38 nmol.ml-1 (approximately 500%) and 11.69 +/- 1.46 nmol UA.ml-1.min-1 (approximately 520%), respectively. In local blood, xanthine and UA increased from 1.49 +/- 0.07 to 8.36 +/- 0.33 nmol.ml-1 and 2.69 +/- 0.16 to 3.90 +/- 0.18 mumol.ml-1, respectively, whereas glutathione and glutathione disulfide increased to 5.13 +/- 0.36 mumol.ml-1 and 0.514 +/- 0.092 nmol.ml-1, respectively. In systemic blood, xanthine oxidase activity peaked at 4.75 +/- 0.20 UA nmol.ml-1.min-1. At 10 min reperfusion, local blood glutathione and UA peaked at 7.08 +/- 0.46 mumol.ml-1 and 4.67 +/- 0.26 mumol.ml-1, respectively, while the other metabolites decreased significantly toward pretourniquet levels. From 20 to 120 min, most metabolites returned to pretourniquet levels; however, local and systemic blood xanthine oxidase activity remained increased 3.76 +/- 0.29 and 3.57 +/- 0.37 nmol UA.ml-1.min-1, respectively. Systemic blood H2O2 was never increased during the study. During the burst period (approximately 5-10 min), local blood H2O2 concentrations and xanthine oxidase activities were highly correlated (r = 0.999). CONCLUSIONS: These studies suggest that tourniquet-induced exsanguination for limb surgery is a significant source for toxic oxygen production in the form of H2O2 and that xanthine oxidase is probably the H2O2-generating enzyme that is formed during the ischemia-reperfusion event. In contrast to the reperfused leg, the absence of H2O2 in arm blood demonstrated a balanced oxidant scavenging in the systemic circulation, despite the persistent increase in systemic xanthine oxidase activity.

Adult↗

Bovine hemoglobin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine. Carolina Resuscitation Research Group.

In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringer's and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringer's in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.

Animals↗

Effect of cerebrospinal fluid drainage and/or partial exsanguination on tolerance to prolonged aortic cross-clamping.

Paraplegia as a consequence of spinal cord ischemia associated with procedures on the thoracic and thoracoabdominal aorta has been linked to the interaction of proximal hypertension with elevated cerebrospinal fluid pressure (CSFP) during aortic cross-clamping (AXC). CSFP reduction via cerebrospinal fluid (CSF) drainage is thought to significantly prolong the cord's tolerance to AXC. Likewise, partial exsanguination is reported to effectively reduce ischemic injury by controlling proximal hypertension. To evaluate the individual and collective efficacy of both techniques, 18 mongrel dogs (25 to 35 kg), divided into three equal groups, underwent a fourth interspace left thoracotomy AXC. Baseline proximal arterial blood pressure (PABP), distal arterial blood pressure (DABP), and CSFP were established and monitored at 5-minute intervals during 120 minutes of AXC, and for 30 minutes thereafter. Group I animals were partially exsanguinated prior to AXC to maintain PABP at a mean of 115 to 120 mmHg. Group II animals had sufficient (16 +/- 5 cc) CSF withdrawn to maintain a DABP-CSFP gradient, i.e., spinal cord perfusion pressure (SCPP) of 20 mmHg. Group III animals were treated with both CSF drainage and partial exsanguination in the same manner as groups I and II, respectively. Perioperative somatosensory evoked potential (SEP) monitoring evaluated cord function. Postoperative neurological outcome was assessed with Tarlov's criteria. SEPs degenerated approximately 22 minutes following AXC for groups II and III. In contrast, group I exhibited rapid (10 +/- 7 min) SEP loss. All five surviving group I animals displayed paralysis 48 hours postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguination cardiac arrest.

OBJECTIVES: Resuscitation attempts in trauma victims who suffer cardiac arrest (CA) from exsanguination almost always fail. The authors hypothesized that an aortic arch flush with cold normal saline solution (NSS) at the start of exsanguination CA can preserve cerebral viability during 20-minute no-flow. METHODS: Twelve dogs were exsanguinated over 5 minutes to CA of 20-minute no-flow, resuscitated by cardiopulmonary bypass, followed by post-CA mild hypothermia (34 degrees C) continued to 12 hours, controlled ventilation to 20 hours, and intensive care to 72 hours. At CA 2 minutes, the dogs received a 500-mL flush of NSS at either 24 degrees C (group 1, n = 6) or 4 degrees C (group 2, n = 6), using a balloon-tipped catheter inserted via the femoral artery into the descending thoracic aorta. RESULTS: The flush at 24 degrees C (group 1) decreased tympanic membrane temperature [mean (+/-SD)] from 37.5 degrees C (+/-0.1) to 35.7 degrees C (+/-0.2); the flush at 4 degrees C (group 2) to 34.0 degrees C (+/-1.1) (p = 0.005). In group 1, one dog achieved overall performance category (OPC) 2 (moderate disability), one OPC 3 (severe disability), and four OPC 4 (coma). In group 2, four dogs achieved OPC 1 (normal), one OPC 2, and one OPC 3 (p = 0.008). Neurologic deficit scores (0-10% normal, 100% brain death) [median (25th-75th percentile)] were 62% (40-66) in group 1 and 5% (0-19) in group 2 (p = 0.01). Total brain histologic damage scores were 130 (62-137) in group 1 and 24 (10-55) in group 2 (p = 0.008). CONCLUSIONS: Aortic arch flush of 4 degrees C at the start of CA of 20 minutes rapidly induces mild cerebral hypothermia and can lead to normal functional recovery with minimal histologic brain damage. The same model with aortic arch flush of 24 degrees C results in survival with brain damage in all dogs, which makes it suitable for testing other (e.g., pharmacologic) preservation potentials.

Animals↗

Emergent endovascular treatment with direct carotid puncture for exsanguinating Carotid Blowout Syndrome.

INTRODUCTION: Carotid Blowout Syndrome (CBS) carries an exceedingly high mortality rate. Various established endovascular techniques are successful in treating less acute CBS, but exsanguinating patients with hemodynamic compromise continue to pose a significant clinical challenge. METHODS: We report a 53-year-old male with squamous cell carcinoma of the anterior tongue presented with a sentinel hemoptysis followed by a massive oral hemorrhage. The patient suffered a cardiac arrest secondary to acute blood loss, from which he was successfully resuscitated. RESULTS: An occlusion technique is presented involving direct carotid puncture for successful treatment of hemodynamically unstable, exsanguinating patients. CONCLUSION: This technique accomplishes rapid arrest of exsanguination, minimal hemorrhage site manipulation, and successful carotid occlusion.

Balloon Occlusion↗

Limb exsanguination. I. The arm: effect of angle of elevation and arterial compression.

Limb exsanguination before tourniquet inflation is usually accomplished using mechanical devices although, where their use is contraindicated, exsanguination by elevation alone may be employed. Advice regarding duration of elevation within the literature is a little confusing with recommendations ranging from 20 s to 5 min. Volume changes, during elevation at 45 degrees and 90 degrees, were measured using strain gauge plethysmography in seven male volunteers. In addition, the superimposed effect of brachial arterial compression on elevation at 90 degrees was investigated. To achieve maximal exsanguination it is recommended that the arm should be elevated for 5 min at 90 degrees before tourniquet inflation. Supplementary brachial arterial compression is not recommended as this tends to attenuate changes in volume.

Adult↗

Limb exsanguination. II. The leg: effect of angle of elevation.

Although limb exsanguination prior to tourniquet inflation is usually accomplished using mechanical devices, elevation alone may still be employed under circumstances where mechanical means are contraindicated. The rather confusing advice within the literature as to duration of elevation, stimulated a study in the arm which revealed the optimal duration of elevation to be 5 min, a period somewhat longer than generally advised. Because the pattern of venous drainage within the leg is slightly different to that of the arm, we undertook a similar study to ascertain if our findings for the arm also held true for the leg. Volume changes in the calves of seven male volunteers during elevation at 45 degrees and 90 degrees were assessed using strain gauge plethysmography. To achieve maximal exsanguination it is recommended that the leg should be elevated at an angle of 45 degrees for 5 min. Higher angles of elevation produce slower and less complete exsanguination.

Adult↗

Resuscitation of subdiaphragmatic exsanguination.

Subdiaphragmatic exsanguination is a major cause of death in civilian trauma. In a 1-year review of 867 consecutive admissions to a Level I Trauma Center, a 4.3 per cent incidence (37 patients) of infradiaphragmatic exsanguination was found. Eleven per cent of all abdominal injuries and 35 per cent of pelvic fractures sustained massive hemorrhage. A treatment protocol incorporating immediate airway control, MAST device, super-large bore venous access, warming rapid infusors, immediate type O blood transfusion, emergency department thoracotomy, and emergent operation as required, produced an overall mortality of 54 per cent. Mortality was higher for pelvic fracture (59%) than abdominal injury (43%). No patient survived ED thoracotomy. Continued developments in resuscitation techniques, as well as prehospital, and operative care are required to reduce mortality from exsanguinating hemorrhage.

Abdominal Injuries↗

Cardiopulmonary arrest following penetrating trauma: guidelines for emergency hospital management of presumed exsanguination.

Exsanguination may be presumed in pale, mottled, unresponsive trauma victims with no palpable pulse nor spontaneous respirations with noncranial penetrating wounds. Under ideal circumstances, those victims initially witnessed to have some signs of life can be successfully revived in 5 to 25% of cases. The chance for a successful outcome influences the decision to initiate resuscitation and depends on the mode of injury, anatomic location of the wound, and elapsed time until presentation as well as the organization of the available facilities and personnel. The resuscitative algorithm for presumed exsanguination is markedly different from the ACLS guidelines for cardiogenic arrest and requires some degree of surgical expertise. After confirming the witnessed cardiopulmonary arrest from presumed exsanguination, the four phases of resuscitation are restoring central oxygenation, controlling internal hemorrhage, re-establishing spontaneous cardiac function, and definitively repairing the injury. Regardless of the type or location of the noncranial penetrating injury, these phases must be accomplished sequentially to minimize the risks of cerebral and cardiac anoxia.

Algorithms↗

A clinically applicable exsanguination shock model in swine.

In order to evaluate treatments of the rapid exsanguination seen in the majority of civilian trauma or combat fatalities, we designed a rapid exsanguination, conscious, unheparinized 100% fatal porcine hemorrhage model. Immature female swine were bled 60% of their estimated blood volume 5 days after placement of a bleeding catheter. The change in arterial base excess concentration (BE) and hematocrit (Hct) was followed after hemorrhage. Variables were bleeding time (120, 60, 30, and 15 min) and catheter placement (carotid, 7 cases; and distal aorta, 24 cases). The Hcts before hemorrhage were similar in both groups. The time for removal of 60% EBV for routine mortality was longer with the carotid (60 min) versus the distal aorta (15 min) catheter group. At autopsy the carotid catheters partially obstructed the orifice of the opposite carotid. In the aortic group, a rate of hemorrhage of 2.65 +/- 0.97 ml/kg/min was required to provide the ischemia necessary for 100% mortality. The BE after hemorrhage was significantly different in survivors versus nonsurvivors. A carotid artery catheter that extends into the porcine brachiocephalic artery appears to cause artifactual mortality by interfering with blood flow to the opposite carotid. A conscious, unheparinized, and reliably fatal exsanguination model has been standardized. The animal must sustain a 60% EBV loss from the distal aorta in 15 min.

Animals↗

Recovery and conversion of kinins in exsanguinated rat preparations.

A rat preparation in which the perfusion route bypassed the lungs, which were substituted by an artificial oxygenator, was exsanguinated and perfused with oxygenated 4% dextran (M.W. 70,000) in Tyrode's fluid; a peristaltic pump propelled the perfusing fluid at 20-25 ml/min through the aortic arch and the perfusion medium returned to the right ventricle. Known amounts of bradykinin (BK), kallidin (lysul-bradykinin, LBK) and methionyllysylbradykinin (MLBK) were administered as single injections and samples of the perfusion fluid removed between 1.5 to 6 min following injection. Average total kinin activity remaining in the circulating fluid was calculated from assays on the isolated guinea pig ileum against respective kinin injected and found to be after 3 and 6 min respectively: 20 and 5% for BK, 54 and 21% for LBK, 60 and 30% for MLBK. When the lungs were introduced in the perfusion circuit BK recoveries decreased to 0.4% at 4 min and 0% at 6 min. In 2 experiments 1 mg MLBK and, in another two, 1 mg of LBK were recirculated for 3 to 3.5 min in the rat preparation with lung bypass; enzymic reactions were interrupted in the perfusates after removal by lowering the pH to 4.7 and placing them in a boiling water bath for 5 min. Following proper dilution, kinin activity left in the perfusates was separated on carboxymethylcellulose columns; in 3 experiments about 50% of the activity was identified as BK from its elution position and resistance to trypsin digestion. The average BK-inactivating potency of the perfusate obtained from the rat with lung bypass was 0.3 mug BK/min x ml compared to 16 mug BK/min x ml of rat plasma. The arylamidase activity on arginylnaphthylamide of the perfusate was 2 n moles NA/min x ml and it was about 25-fold lower than that of rat plasma. Rat liver was exsanguinated and perfused in situ through the portal vein and inferior cava vein using the same conditions as for the whole animal. The perfusion rate was 12 ml/min. The recovery of injected BK in this preparation was 40% after 2 min of recirculation, declining progressively in the following minutes. When MLBK was perfused in this preparation for 3 min or glycylarginyllysylbradykinin (GALBK) for 3 and 5 min, significant amounts of BK were found in the perfusates. We conclude that LBK, MLBK and GALBK may be converted at a high rate into BK by tissue aminopeptidases found in the rat preparations used. BK inactivation in the whole rat is a fast reaction, even when the pulmonary tissue is not involved in the inactivation.

Aminopeptidases↗

[Distribution of blood in the kidney by death from exsanguination (author's transl)].

The distribution of blood in the human kidney in acute and protracted exsanguination has been examined by staining sections (30-50micro) with benzidine. After bleeding to death within a few minutes arteries, aterioles, glomeruli, and the capillary network in the renal cortex are empty. In protracted bleeding to death glomeruli are filled with blood, the vessels of renal cortex are empty except for some little arteries and some vasa afferentia. It may be possible to utilige the intrarenal blood distribution to reach an opinion as to the duration of the fatal hemorrhage and even to distinguish single or multiple episodes of hemorrhaging during the course of fatal exsanguination.

Acute Disease↗

Outcome of thoracoabdominal aortic operations using deep hypothermia and distal exsanguination.

BACKGROUND: Operation of the descending and thoracoabdominal aorta may be affected by a significant perioperative morbidity, mainly because of ischemic damage of the spinal cord and malperfusion of the abdominal organs. METHODS: A comparative analysis was performed on two consecutive series of patients operated between 1982 and 1998. Group 1 consisted of 90 patients operated with moderate hypothermic left heart bypass. Group 2 included 38 patients operated using deep hypothermic cardiopulmonary bypass and a period of circulatory arrest while performing the proximal anastomosis and distal exsanguination during confection of the distal anastomosis. RESULTS: Main demographic factors and causes of the aortic disease were similar in both groups. Early mortality was significantly higher in the group of patients with aortic cross-clamping (15 of 90, 16%) than in those operated with circulatory arrest (2 of 38, 5.2%), p < 0.001. Paraplegia occurred in 8 patients in the group operated with mild hypothermia (8.8%) but in only 1 patient (2.6%) when deep hypothermia had been used. CONCLUSIONS: In our experience, deep hypothermia combined with distal exsanguination significantly improved the early postoperative outcome after operation of the descending and thoracoabdominal aorta. This technique allowed easy confection of proximal and distal anastomoses, and the duration of the operation was not prolonged significantly through this approach.

Aorta↗

Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study.

We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4 degrees C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24 degrees C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20-28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received assisted circulation to 2 h, 34 degrees C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24 degrees C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n=14). In group 2 (n=9), thiopental (variable total doses of 15-120 mg/kg) was added to the flush and given with reperfusion. In group 3 (n=7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36 degrees C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 (p=0.5). Median NDS were 36% (IQR 22-62%) in group 1; 51% (IQR 22-56%) in group 2; and 55% (IQR 38-59%) in group 3 (p=0.7). Median total HDS were 67 (IQR 56-127) in group 1; 60 (IQR 52-138) in group 2; and 76 (IQR 48-132) in group 3 (p=1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can consistently provide 'clinically significant' cerebral preservation for 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.

Animals↗