Effects of naloxone on splanchnic perfusion in hemorrhagic shock

Endogenous opiate peptides are released in early hemorrhagic shock and may mediate hypotension during hypovolemia. We compared the effects of naloxone alone versus incomplete volume resuscitation on survival and splanchnic blood flow. Dogs were bled to a MAP of 35 mm Hg for 2 hours. In eight dogs, shed blood was returned; eight dogs received naloxone (2 mg/kg bolus and 2 mg/kg/hr in 0.5 ml/kg/hr normal saline) with no shed blood returned. Seven dogs received normal saline alone without shed blood or naloxone and served as untreated controls. Untreated dogs survived a mean of 18.6 minutes. All other dogs survived for 180 minutes. Naloxone and shed blood were equally effective in improving hepatic and renal blood flow; gastric, intestinal, pancreatic, and splenic blood flow remained unchanged from shock values in both groups. These data indicate that in the face of hypovolemia naloxone improves survival and blood flow (ml/min/gm) to splanchnic organs despite no return of shed blood.     

纳洛酮治疗失血性休克的临床效果观察

失血性休克时如何在短时间内有效地改善患者的血循环,是抗休克治疗的关键。本文就本院近3年收治的115例失血性休克病人,设对照组观察早期应用纳洛酮治疗的临床疗效和安全性。1临床资料1.1一般资料:115例均符合1982年全国急诊“三衰”会议制定的诊断试行标准。男89例,女26例;年龄18～55岁,平均35.5岁。其中轻度休克16例,中度休克78例,重度休克21例。1.2原发病因:消化性溃疡出血30例,脾破裂30例,下肢及骨盆粉碎性骨折25例,肝破裂10例,肾脏破裂5例,胸部开放性损伤25例,宫外孕破裂8例。用抛币法随机分成纳洛酮组(n=58)和对照组(n=57)。各组的年…     

Effects of naloxone on stress-induced analgesia after hemorrhagic shock

BACKGROUND AND OBJECTIVES: To investigate whether endogenous opioids might be involved in the mechanisms that underlie hemorrhagic shock-induced analgesia, formalin tests were performed after hemorrhage and reinfusion in naloxone pretreated and untreated rats. METHODS: Twenty-four adult male Sprague-Dawley rats were divided into control (n = 6), saline (n = 6), naloxone 10 mg/kg (n = 6), and naloxone 100 mg/kg (n = 6) groups. The mean blood pressure (mBP) was kept at 50 to 60 mm Hg for 30 minutes by draining arterial blood in the saline group and the naloxone groups. After 15 minutes of returning mBP to normal levels by reinfusion of the drained shed blood, 10% formalin (3.7% formaldehyde solution, 0.1 mL) was injected into the left rear paw. Nociceptive behaviors were observed for 1 hour after the formalin injection. RESULTS: Nociceptive behaviors of the posthemorrhagic shock groups were significantly lower than those of the control group. No significant difference was seen in nociceptive behaviors among the saline and naloxone groups. CONCLUSION: Naloxone did not reverse the hemorrhagic shock-induced analgesia, which suggests that endogenous opioids might not be a major factor that governs stress-induced analgesia (SIA) after hemorrhagic shock.     

The interaction of corticosteroids and naloxone in canine hemorrhagic shock

β-Endorphin is released concomitantly with adrenocorticotropin from the pituitary following stress and, during hemorrhagic shock, can alter cardiovascular hemodynamics. In 41 anesthetized dogs, we assessed the combined effects of pituitary suppression with dexamethasone (D) or methylprednisolone (M) and opiate receptor blockade with naloxone (N) during hemorrhagic shock. We found that N alone was the most effective treatment in improving arterial pressure, cardiac output, and left ventricular contractility and resulted in the best survival. D and M alone were little better than saline. When combined with N, D and M were better than saline but not as good as N alone. This attenuation of the N effect may be due to corticosteroid: suppression of β-endorphin and ACTH release from the pituitary; alterations in opiate metabolism; or changes in opiate receptor availability.     

Variations in transmucosal gastric potential difference during hemorrhagic shock in the rat

Transmucosal gastric potential difference (TGPD) was measured in the antrum and fundus of the stomach in two groups of rats submitted to hemorrhagic shock. In the first group the stomach contained 2 cm3 of 0.1 N HCl and in the second 2 cm3 of physiological saline. After the hemorrhage both antral and fundal TGPD diminished significantly in both groups. Antral TGPD dropped from -20 to -6 mV (p less than 0.001) in the first group and from -22 to -12 mV (p less than 0.01) in the second group; fundal TGPD dropped from -41 to -16 mV (p less than 0.001) in the first group and from -40 to -17 mV (p less than 0.05) in the second group. 20 min after reinfusion of blood extracted during the hemorrhage, both antral and fundal TGPD returned to normal values in the rats instilled with physiological saline, while in those treated with HCl TGPD values remained at levels significantly lower than the baseline values (in the antrum -10 mV, p less than 0.001; in the fundus -25 mV, p less than 0.02). Only those rats whose stomachs contained HCl developed ulcers, mainly located in the fundus of the stomach. These results suggest that the energy metabolism of the cells of the gastric mucosa undergoes constant alteration from the earliest stages of hemorrhagic shock. These alterations are greater in the fundus than in the antrum, a fact compatible with the greater incidence of ulcers in the fundus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothermia-induced coagulopathy during hemorrhagic shock

A porcine model of hemorrhagic shock was used to study the effect of hypothermia on hemodynamic, metabolic, and coagulation parameters. The model was designed to simulate the events of severe blunt injury with hemorrhage occurring initially, to a systolic blood pressure of 30 mm Hg, followed by simultaneous hemorrhage and crystalloid volume replacement, followed by cessation of hemorrhage and blood replacement. Half of the animals were rendered hypothermic by external application of ice, and half remained normothermic. There was seven pigs in each group. Two deaths occurred in each during the hemorrhage phase. The hypothermic pigs demonstrated larger reduction in cardiac output than normothermic pigs. Volume replacement in the normothermic group restored cardiac output to baseline values. In the hypothermic group, cardiac output remained depressed despite volume replacement. Prothrombin times and partial thromboplastin times showed significantly more prolongation in the hypothermic group. Furthermore, this was not corrected by replacement of shed blood in the hypothermic group, as was seen in the normothermic group. We conclude that when shock and hypothermia occur together, their deleterious effect on hemodynamic and coagulation parameters are additive. The effects of hypothermia persist despite the arrest of hemorrhage and volume replacement. Thus, it is necessary to aggressively address both shock and hypothermia when they occur simultaneously.     

Detection of organ ischemia during hemorrhagic shock

BACKGROUND: In a porcine hemorrhagic shock model we aimed to determine: (a) whether blood flow to the intestine and kidney was more reduced than cardiac output; (b) whether parameters of anaerobic metabolism correlated with regional blood flow; and (c) whether metabolic parameters in intestine, kidney and skeletal muscles detected a compromised metabolic state at an earlier stage than did systemic parameters. METHODS: In an animal research laboratory at a university hospital six domestic pigs were subjected to volume-controlled hemorrhage. Every 30 min samples of blood were withdrawn. Systemic and regional hemodynamic parameters and tissue levels of PCO2 were monitored. Whole body and organ-specific oxygen consumption (VO2) and veno-arterial (VA) differences of lactate, glucose, potassium (K+), PCO2, H+ and base excess (BE) were calculated every 30 min. RESULTS: With progressive hemorrhage, intestinal blood flow decreased to the same extent as cardiac output, whereas the reduction in renal blood flow was more pronounced. We found a concomitant reduction in VO2 (onset of supply dependent metabolism) in intestine, kidney and skeletal muscles. In muscular tissue PCO2 increased to levels three times higher than baseline, while renal and intestinal PCO2 increased eightfold. Supply dependency was associated with a concomitant increase in VA CO2 and VA H+. Also, VA lactate increased, mostly in intestine and least in skeletal muscle. Intestinal and renal VA K+ increased, while muscular VA K+ decreased. Arterial lactate and H+ increased considerably, whereas arterial BE decreased. CONCLUSION: With progressive hemorrhage, renal blood flow, but not intestinal and skeletal muscle blood flow, was reduced more than cardiac output. Supply dependent oxygen metabolism (VO2) and organ acidosis occurred simultaneously in the three organs, despite differences in blood flow reductions. Organ ischemia coincided with a pronounced change in arterial lactate and systemic acid base parameters.     

Muscle lactate concentration during experimental hemorrhagic shock

Purpose. Blood lactate concentration does not correspond well to oxygen transport variables during circulatory shock. Prolonged washout of lactate from tissues during shock has been reported. This study was designed to test the hypothesis that the discrepancy between serum lactate and oxygen metabolism is caused by the failure of lactate to wash out from the tissues and that tissue lactate may reflect the oxygen metabolism better. Methods. Using a canine model of hemorrhagic shock, lactate concentration measured in a muscle biopsy specimen and in arterial blood was compared with the cumulative deficit in oxygen consumption. Result. The cumulative deficit in oxygen consumption correlated with the concentration of lactate in muscle (r= 0.67,P<0.01) but not with that in blood. During shock, all muscle lactate levels were greater than those in serum, and a linear relationship was demonstrated between arterial(X) and muscle(Y) lactate levels (Y=2.45X-2.72,r=0.82,P<0.001). The muscle/serum lactate concentration ratio increased from 1 to 2.5 as the blood volume decreased. Conclusion. In the setting of experimental hemorrhagic shock, only tissue lactate levels reflected the true deficit in oxygen metabolism. The difference between lactate levels in muscle and serum represented the severity of the shock.     

An intrathoracic scapular prolapse with hemorrhagic shock after a thoracotomy

We herein present a case in which an emergency operation was performed for an intrathoracic hemorrhage resulting from a scapular prolapse after a thoracotomy, a rare complication of this procedure. A 59-year-old man had undergone a right upper lobectomy with an extended resection of the posterior chest wall including the second to fourth ribs due to a direct invasion by a lung cancer. On postoperative day 80, we performed an emergency operation as the patient had gone into shock due to an intrathoracic hemorrhage with a right scapular prolapse. The scapula protruded through the enlarged fourth intercostal space. The prolapsed scapula was reduced and the defect in the chest wall was covered with Marlex mesh.     

Renal tissue gas tensions during hemorrhagic shock

To evaluate the development of renal hypoxia during hemorrhagic shock, fourteen dogs were induced in this study. The animals were divided equally into a group in which mean arterial pressure (MAP) was kept at 50mmHg (group 1), and into another where MAP was kept at 40mmHg for 180mim (group 2). Renal tissue gas tensions were determined by a mass spectrometer. In the 50-mmHg group, renal tissue oxygen tension (Pr_{O 2}) dropped for 15min following hemorrhage, remained constant for 90min, then fell further for 150min before a plateau was established. In the 40-mmHg group, the Pr_{O 2} dropped for 90min before reaching a plateau. The second Pr_{O 2} decline occurred at the same level in both the 50-mmHg group and the 40-mmHg group. The point at which the same Pr_{O 2} level occurred for each group suggests the cessation of oxygen consumption and the conditions of renal hypoxia. It is assumed that renal hypoxia occurs in 120min at a MAP of 50-mmHg and in 60min at a MAP of 40mmHg.(Murakawa K, Izumi R, Kobayashi A: Renal tissue gas tentions during hemorrhagic shock. J Anesth 3: 10–15, 1989)     

Glucocorticoid effects on gluconeogenesis during hemorrhagic shock

This study was undertaken to determine if there was evidence of impaired gluconeogenesis during shock and to test the effectiveness of steroids on gluconeogenesis during such conditions. Hemorrhagic shock in previously adrenalectomized rats was produced by bleeding the animals to a mean arterial pressure of 40 mm Hg, which was maintained for 2 hr. Liver and kidney slices from control animals and from animals in shock were prepared and incubated under aerobic conditions for 3 hr at 37°C in Krebs-Henseliet bicarbonate buffer containing 10 mM alanine or glutamine in the presence or absence of steroids. Following incubation, glucose and urea production in the medium was measured. Hydrocortisone addition at 10^?7M increased the quality of glucose and urea appearing in the medium by 16% in the presence of control slices as well as in the presence of slices from animals in shock. The addition of 10^?4M hydrocortisone inhibited gluconeogenesis by 30%, whereas with 10^?2M hydrocortisone there was complete inhibition of gluconeogenesis with both groups of slices. Similar results were obtained using dexamethasone or hydrocortisone 21-sodium succinate. Thus, basal gluconeogenic capability was unaltered during shock in an adrenalectomized animal and steroids were as effective in stimulating or inhibiting gluconeogenesis during hemorrhagic shock as they were under control conditions.     

Occurrence of bacteremia during and after hemorrhagic shock

In recent research, hemorrhagic shock and septic shock have been studied as two separate entities. We have developed a treated model of hemorrhagic shock in which unrestrained and unanesthetized rats are bled to a mean arterial pressure of 30 torr until 80% of the maximum shed volume must be returned. Rats are maintained preshock and treated post shock with a 20% glucose-electrolyte solution. Survival of these animals is 62% at 24 hours post shock and all animals are dead at 72 hours post shock. Blood cultures obtained during shock become positive at 2 hours into the shock period and are significant compared to controls at 3 to 5 hours of shock (p less than 0.0001). Blood cultures obtained after the period of shock are significantly positive at 24 and 48 hours post shock (p less than 0.05) compared to controls. Intrashock cultures are monomicrobial; the majority of post-shock cultures are polymicrobial. All cultured organisms are normal rat enteric flora. Histologic changes of renal failure are also demonstrated post shock. We suggest that bacterial invasion, possibly from the gut, plays a role in the sepsis seen in patients following severe hemorrhagic shock. Sepsis may precede rather than follow the immune incompetence which accompanies shock.