Irreversible Hemorrhagic Shock Research Articles

The injury patterns, management and outcomes of retroperitoneal haemorrhage caused by lumbar arterial bleeding at a Level-1 Trauma Centre: A 10-year retrospective review

PurposeHaemorrhagic shock remains a leading preventable cause of death amongst trauma patients. Failure to identify retroperitoneal haemorrhage (RPH) can lead to irreversible haemorrhagic shock. The arteries of the middle retroperitoneal region (i.e., the 1st to 4th lumbar arteries) are complicit in haemorrhage into the retroperitoneal space. However, predictive injury patterns and subsequent management implications of haemorrhage secondary to bleeding of these arteries is lacking. Materials and methodsWe performed a retrospective cohort study of patients diagnosed with retroperitoneal haemorrhage who presented to our Level-1 Trauma Centre (2009–2019). We described the associated injuries, management and outcomes relating to haemorrhage of lumbar arteries (L1–4) from this cohort to assess risk and management priorities in non-cavitary haemorrhage compared to RPH due to other causes. ResultsHaemorrhage of the lumbar arteries (LA) is associated with a higher proportion of lumbar transverse process (TP) fractures. Bleeding from branches of these vessels is associated with lower systolic blood pressure, increased incidence of massive transfusion, higher shock index, and a higher Injury Severity Score (ISS). A higher proportion of patients in the LA group underwent angioembolisation when compared to other causes of RPH. ConclusionThis study highlights the injury patterns, particularly TP fractures, in the prediction, early detection and management of haemorrhage from the lumbar arteries (L1–4). Compared to other causes of RPH, bleeding of the LA responds to early, aggressive haemorrhage control through angioembolisation. These injuries are likely best treated in Level-1 or Level-2 trauma facilities that are equipped with angioembolisation facilities or hybrid theatres to facilitate early identification and management of thoracolumbar bleeds.

Selective Prehospital Advanced Resuscitative Care - Developing a Strategy to Prevent Prehospital Deaths From Noncompressible Torso Hemorrhage.

Hemorrhage, and particularly noncompressible torso hemorrhage remains a leading cause of potentially preventable prehospital death from trauma in the United States and globally. A subset of severely injured patients either die in the field or develop irreversible hemorrhagic shock before they can receive hospital definitive care, resulting in poor outcomes. The focus of this opinion paper is to delineate (a) the need for existing trauma systems to adapt so that potentially life-saving advanced resuscitation and truncal hemorrhage control interventions can be delivered closer to the point-of-injury in select patients, and (b) a possible mechanism through which some trauma systems can train and incorporate select prehospital advanced resuscitative care teams to deliver those interventions.

Energy of blood circulation during blood loss

The state of circulatory energy in blood loss has been studied in 44 patients with spleen injury. Kinetic (final diastolic and systolic volumes of the left ventricle, heart rate), dynamic (effective arterial and central venous pressure, total peripheral resistance), hemic (oxygen content in arterial and venous blood) parameters of blood circulation, as well as the level of lactate reflecting the degree of hypoxia were studied. The energy indicators of blood circulation were determined: the power consumed by tissues, the oxygen reserve (reflecting the correspondence of the oxygen consumed by tissues to their needs) and the integral energy indicator - circulatory reserve. It has been determined that with an increase in blood loss, the energy indicators of blood circulation decrease: the power consumed by tissues decrease to (48.0±6.1); (41.1±8.7) and (23.5±9.3) mW/m2, the oxygen reserve decrease to (0.43±0.04); (0.37±0.05) and(0.27+0.07), the circulatory reserve decrease to (229+93); (180±41) and (47±25) mW/m2 respectively at blood loss 20 %, 30 % and 40 % of blood volume. Apparently 20 % blood loss is the maximum amount of blood loss in relation to compensatory possibilities of autoregulation of blood circulation. 30 % blood loss causes more strain on the compensatory mechanisms, at 40 % blood loss the possibility of autoregulation is exhausted. All patients with blood loss up to 20 and up to 30 % of the blood volume survived in the future, with 40 % blood loss 30 % of patients could not be saved. In all deceased patients the circulatory reserve was below 50 mW/m2. It has been determined that a decrease in the circulatory reserve to 100 mW/m2 or lower is a serious threat to life and requires great intensive therapy for blood loss, the level of the circulatory reserve of 50 mW/m2 is not compatible with life, that is, it corresponds to irreversible hemorrhagic shock. Keywords: blood loss, hypovolemia, circulatory energy, blood flow power, oxygen reserve, circulatory reserve.

Emergency obstetric hysterectomy: A clinical study

Emergency obstetric hysterectomy is a life saving procedure. Its incidence is on the rise as is the increasing incidence of caesarean sections and placenta accrete spectrum.Methods: This descriptive prospective study was conducted for a period of two years on patients who underwent emergency obstetric hysterectomy to determine the frequency, demographic characters, indications and fetomaternal outcomes from July 17 to June 19 at tertiary care institute of Punjab in Department of Obstetrics and Gynaecology, GMC Patiala.Results: There were 40 cases of obstetric hysterectomy out of 10859 deliveries giving an incidence of 3.6 per 1000 births, Most of the patients were unbooked (87.5%). 65% were multiparas. Maximum number of women (50%) were in age group 26 to 30 years. 75% patients were cases of previous caesarean. 80% among these had placenta accrete spectrum and these ended up in caesarean hysterectomy. There were five maternal deaths attributed to late referral, irreversible haemorrhagic shock and acute respiratory distress syndrome. Maternal death to maternal near miss ratio during study period was 1:6.4.Conclusion: Emergency obstetric hysterectomy is definitely life saving procedure but we should reduce its iatrogenic incidence by reducing the incidence of scarred uterus.

Abdominal Travmada Mortaliteyi Etkileyen Risk Faktörlerinin Analizi

The present study aims to analyze blunt and penetrating abdominal traumas that were evaluated in our emergency department, the treatment approaches and risk factors of mortality. Six hundred and sixty-four patients were admitted to our emergency department for surgical evaluation for trauma between January 2009 and April 2019. After the exclusion of dead on arrival, patients with missing data and patients without abdominal trauma were excluded from this study. Hundred and thirteen patients with abdominal trauma admitted to our department were evaluated in this study. Demographic, clinical, prognostic and mortality related factors were retrospectively analyzed. The mean age of the patients was 36.08±16.1 years. There were 90 male patients. Eighty patients (70.8%) had blunt abdominal trauma (BAT). Twenty-eight patients (24.7%) had isolated liver and two patients (1.7%) had isolated spleen injury. Combined liver and spleen injury was found in two patients (1.7%). Twenty-two (19.4%) patients had mortality. Causes of mortality were an irreversible hemorrhagic shock (40.9%) and central nervous system (13.6%) injuries. BAT was the main mechanism of injury in patients with mortality (86.4% versus 67%; p<0.001). The frequency of retroperitoneal injury was significantly higher in patients with mortality (50% versus 16.5%, p<0.001). The frequency of extra-abdominal injury in patients with mortality was higher (68.1% versus 49.4%; p=0.047). Mean arterial pressure at admission was found to be significantly lower in patients with mortality (67±26.8 mmHg versus 84.3±17 mmHg; p=0.02). The number of packed erythrocytes transfused in patients with mortality was higher (8.8±8.6 versus 3.3±5.9 units; p=0.047). Mean international normalized ratio (INR) was significantly higher in patients with mortality (4.3±7.1 versus 2.7±4; p=0.016). Mean lactate dehydrogenase level was higher in patients with mortality (1685.7±333.8 versus 675.8±565.3 IU/mL; p<0.001). Mean alanine aminotransferase (ALT) was significantly higher in patients with mortality (430±619 versus 244±448 IU/mL; p<0.001). Mean alkaline phosphatase (ALP) level in patients with mortality was higher (76.9±72.8 versus 67.3±27.8 IU/mL; p=0.003). The presence of retroperitoneal injury and ALT >516 IU/mL were independent risk factors o mortality. We have found certain laboratory variables to increase in patients with mortality. These are related to the severity of trauma. Retroperitoneal injury and increased ALT levels being risk factors of mortality is the most important finding of this study. Our results can guide other centers in the evaluation of trauma patients, and high-risk groups can be identified.

Cardiovascular effects of H3 histamine receptor inverse agonist/ H4 histamine receptor agonist, clobenpropit, in hemorrhage-shocked rats.

Hemorrhagic shock has a potential to be life-threatening when it is not treated. The main causes of hemorrhagic shock involve: (1) forces causing injury; and (2) diseases that can cause hemorrhage., Therefore, due to the causes of hemorrhagic shock and the life-threatening potential, the search for new methods of shock treatment is extremely valuable to the modern medicine. The aim of this study was to investigate the influence of clobenpropit in the model of hemorrhagic shock. The experiments were conducted in 110 adult male Wistar rats weighing between 205 and 470g. 1, 2 and 5 μmol/kg of intravenous H3 receptors reverse agonists, clobentropit, and/or 1, 5 and 10 μmol/kg H3 receptor agonist, imetit, were used as general anesthetics. Irreversible hemorrhagic shock was induced by the paused bleeding until the mean arterial pressure (MAP) lowered to the level of 20–25 mmHg. It was proved that, in cases of critical hypotension, clobenpropit triggered a dose-dependent increase of: systolic blood pressure (SBP), diastolic blood pressure (DBP), MPA and heart rate (HR) of rats with critical hypotension. The most significant changes in hemodynamic parameters were achieved by administrating dosages of 2 mmol/kg. This resulted in the survival rate increase to up to 100%. However, imetit did not trigger any hemodynamic changes nor an increase in SBP, DBP, MAP or HR. Furthermore, it was found that the premedication with prazosin, yohimbine, 6-hydroxydopamine and the vasopressin V1a receptor antagonist blocked the effects of clobenpropit. Additionally, premedication with propranolol, captopril and ZD 7155 did not cause any significant changes in the measured hemodynamic parameters. In conclusion, after an intravenous injection clobenpropit, the inverse agonist of H3 histamine receptors/agonist of histamine receptors H4, causes a resuscitating effect on rats in hemorrhagic shock. Moreover, such effect is based on the effector mechanisms of sympathetic nervous system and vasopressin.

Abruptio Placentae 116 Cases: Role of PGE1 in Cervical Ripening and Induction of Labor, January 2006-August 2006

OBJECTIVES: In the very high risk obstetric cases of placental abruption, expediting delivery is of utmost urgency, since the complications are related to the abruption delivery interval. Before the introduction of prostaglandins for labor induction, it was a routine practice to do amniotomy and use oxytocin drip to accelerate labor when vaginal delivery was contemplated. We present 116 cases of placental abruption, including the severe cases, managed in the year 2006 during a period of 8 months, at Modern Government Maternity Hospital, which was the biggest maternity hospital in the combined state of Andhra Pradesh, and is the biggest in the state of Telangana, attached to Osmania Medical College. The role of prostaglandin E1 (PGE1), for cervical ripening and labor induction/augmentation has been analyzed in this observational study. A variety of variables including age, parity, gestational age, severity of abruption and maternal and fetal status, associated preeclampsia, Bishop score, availability of blood and blood products, associated complications, all factors influence the management adopted. MATERIAL METHODS: The response to PGE1 induction has been studied in terms of efficacy, the total number of doses of vaginal PGE1 in relation to parity, induction delivery interval, successful vaginal delivery rate, the indications for caesarean delivery, perinatal outcome and complications. A decision was made for either abdominal delivery or vaginal delivery on a case to case basis. A routine amniotomy was performed when the cervical os was open, both for confirmation of diagnosis and to release intra uterine pressure, and also it would help in the acceleration of labor. When the Bishop score was more than six, amniotomy was performed and an oxytocin intravenous drip was started. If the Bishop score was less than six, 25/50 mcg. Misoprostol (PGE1) was placed high in the vagina. OBSERVATIONS: Primies that had abruption were 27/116 = 23.27% and multies were 89/116 = 76.72%. In our study 68/116, (58.62%) had preeclamsia. In our series, gestational age at abruption was less than 36 weeks in 89/116, (76.72%) and >36 weeks in 27/116 (23.27%) at presentation. It is significant to note that 100/116 (86.2%) were unbooked and 16/116 (13.79%) were booked cases at our institute. Vaginal deliveries were 84 (74.2%) and caesarean deliveries were 30 (25.8%) in 116 placental abruptions. There were four maternal deaths 3.4%, two died undelivered. Perinatal mortality in our series was 92/116 (79.3%). PGE1 induced labours—49: When PGE1 was used for labor induction in 49 women, 40 (81.63%) had vaginal delivery and caesarean delivery was done in 9 (18.36%) cases for non progress of labor. Induction delivery interval was less than 12 hours in 45 (91.83%), more than 12 hours in 4 (8.1%). Preterm delivery in PGE1 induced cases was 40/49 = 81.63% versus preterm in 116 cases, 76.72%. This indicates that more numbers of preterm deliveries were allowed vaginal delivery. DISCUSSION: Maternal mortality: Better facilities of transfusion of blood products may have reduced maternal mortality in our series. Government maternity hospital is a public sector tertiary health facility providing free treatment. Early referral would make some difference. Acute defibrination leading to disseminated intravascular cougulation was the cause of three deaths, irreversible haemorrhagic shock in another. CONCLUSION: Induction of labor with PGE1 was useful and effective when cervix was unfavorable and Bishop score was less than six. With PGE1 induction (49) 91.83% delivered in less than 12 hours. There were no maternal deaths and PPH in 49 women induced with PGE1. Hence PGE1 was safe to use in these emergency high-risk obstetric patients. PGE1 usage to expedite delivery can reduce Caesarean section rate.

Enteral tranexamic acid attenuates vasopressor resistance and changes in α1-adrenergic receptor expression in hemorrhagic shock

Irreversible hemorrhagic shock is characterized by hyporesponsiveness to vasopressor and fluid therapy. Little is known, however, about the mechanisms that contribute to this phenomenon. Previous studies have shown that decreased intestinal perfusion in hemorrhagic shock leads to proteolytically mediated increases in gut permeability, with subsequent egress of vasoactive substances systemically. Maintenance of blood pressure is achieved in part by α1 receptor modulation, which may be affected by vasoactive factors; we thus hypothesized that decreases in hemodynamic stability and vasopressor response in shock can be prevented by enteral protease inhibition. Rats were exposed to experimental hemorrhagic shock (35 mm Hg mean arterial blood pressure for 2 hours, followed by reperfusion for 2 hours) and challenged with phenylephrine (2 μg/kg) at discrete intervals to measure vasopressor responsiveness. A second group of animals received enteral injections with the protease inhibitor tranexamic acid (TXA) (127 mM) along the small intestine and cecum 1 hour after induction of hemorrhagic shock. Blood pressure response (duration and amplitude) to phenylephrine after reperfusion was significantly attenuated in animals subjected to hemorrhagic shock compared with baseline and control nonshocked animals and was restored to near baseline by enteral TXA. Arteries from shocked animals also displayed decreased α1 receptor density with restoration to baseline after enteral TXA treatment. In vitro, rat shock plasma decreased α1 receptor density in smooth muscle cells, which was also abrogated by enteral TXA treatment. Results from this study demonstrate that experimental hemorrhagic shock leads to decreased response to the α1-selective agonist phenylephrine and decreased α1 receptor density via circulating shock factors. These changes are mitigated by enteral TXA with correspondingly improved hemodynamics. Proteolytic inhibition in the lumen of the small intestine improves hemodynamics in hemorrhagic shock, possibly by restoring α1 adrenergic functionality necessary to maintain systemic blood pressure and perfusion.

Postinjury fibrinolysis shutdown: Rationale for selective tranexamic acid.

Moore, Ernest E. MD; Moore, Hunter B. MD; Gonzalez, Eduardo MD; Chapman, Michael P. MD; Hansen, Kirk C. PhD; Sauaia, Angela MD, PhD; Silliman, Christopher C. MD, PhD; Banerjee, Anirban PhD Author Information

Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats

Centrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20–25mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured. Leptin given intracerebroventricularly (20μg) evoked long-lasting rises in MAP and heart rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood flows and a 100% survival at 2h. MAP and peripheral blood flow changes were inhibited by a pre-treatment with α1- and α2-adrenoceptor antagonists prazosin (0.5mg/kg) and yohimbine (1mg/kg), while β-adrenoceptor antagonist propranolol (1mg/kg) blocked leptin-induced HR changes, without influence on MAP, peripheral blood flows and survival. Twenty min after leptin treatment, there were higher plasma concentrations of noradrenaline, but not adrenaline, in comparison with the saline-treated control group. In conclusion, centrally acting leptin induces a long-lasting pressor effect with an improvement in the survival rate in haemorrhage-shocked rats. The effect may be associated with the activation of the sympathetic nervous system.

Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis-induced portal hypertension

A 75-year old man had been diagnosed at 42 years of age as having polycythemia vera and had been monitored at another hospital. Progression of anemia had been recognized at about age 70, and the patient was thus referred to our center in 2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy findings. Hematemesis due to rupture of esophageal varices occurred in January and February of 2011. The bleeding was stopped by endoscopic variceal ligation. Furthermore, in March of the same year, hematemesis recurred and the patient was transported to our center. He was in irreversible hemorrhagic shock and died. The autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers, an observation consistent with myelofibrosis. The liver weighed 1856 g the spleen 1572 g, indicating marked hepatosplenomegaly. The liver and spleen both showed extramedullary hemopoiesis. Myelofibrosis is often complicated by portal hypertension and is occasionally associated with gastrointestinal hemorrhage due to esophageal varices. A patient diagnosed as having myelofibrosis needs to be screened for esophageal/gastric varices. Myelofibrosis has a poor prognosis. Therefore, it is necessary to carefully decide the therapeutic strategy in consideration of the patient's concomitant conditions, treatment invasiveness and quality of life.

Vasopressin in paediatric practice

Arginine vasopressin (AVP) is a nine amino acid peptide hormone, which is synthesized in the hypothalamus as a precursor, transported down the portal system and stored in the posterior pituitary gland. It is also known as argipressin or antidiuretic hormone (ADH) and it is closely related in structure to oxytocin, which is also released from the posterior pituitary. Physiologically, it acts though the kidney with several other hormones to conserve solute-free water, but in hypovolemic states its potent arterial and venoconstrictor properties act to preserve blood pressure. Vasopressin has been used for many years in the treatment of diabetes insipidus and in control of bleeding esophageal varices (utilizing its potent vasoconstrictor effect on the slanchnic circulation), but its role as a pressor agent in the context of resuscitation, septic shock and pediatric cardiac surgery has only emerged in the last few years. Vasopressin is released physiologically in response to a rise in osmolarity, which is sensed within sensitive receptors in the hypothalamus. A fall in osmolarity below 280 mOsmAEkg will trigger its release (1). It acts via V2 receptors to open aquaporin (water channels) in the collecting tubules thereby increasing central water reabsorption. Reduction in afferent transmission from baroreceptors or cardiopulmonary volume receptors associated with hypovolemia or hypotension will also trigger vasopressin release which then acts via V1a receptors of smooth muscle to produce vasoconstriction of both veins and arteries (2). Similarly, increases in circulating ANG11 act via the hypothalamus to trigger release (3). The vasoconstictive effects are specific to different organ beds with the slanchnic bed being particularly sensitive to the circulating concentrations of vasopressin. In addition, increase in vasopressin activity is associated with increased release of corticotrophin releasing hormone via V1b (V3) receptors within the CNS, an increase in release of FV111, Von Willebrand Factor and enhanced platelet aggregation. The physiological effects on the heart are unclear. In the isolated healthy myocyte AVP produces improved contractility (4) probably by increasing intracellular calcium in myocardial cells through a GTP mechanism (5): The integrated position is less clear: pharmacological doses cause coronary vasoconstriction, while improved inotropic performance in pathological states may occur due both primary myocardial effect of secondary effects because of improved coronary perfusion. Pathologically, vasopressin is known to rise in heart failure and conditions of cardiovascular compromise. There are less data in children: in a study of neonates with congenital heart disease, AVP levels in infants with congestive heart and no outflow tract obstruction was significantly higher than normal controls but those with failure and left ventricular outflow tract obstruction had reduced levels (6). The available data suggest that while vasopressin levels are often raised appropriately in hypotensive states because of a variety of conditions this is not necessarily the case. Small studies have been published documenting vasopressin deficiency in catecholamine resistant hypotension (7,8). Vasopressin became of interest when it was observed that organ donors who had brain death and diabetes insipidus were cardiovascularly more stable with reduced inotrope requirements and better organ preservation. Additionally, it was observed that patients who survived cardiac arrest had higher levels of vasopressin compared to nonsurvivors (9). In contrast, there is a correlation of poorer outcome after cardiopulmonary resuscitation with higher levels of endogenous catecholamines (10). These observations led to initial adult studies which questioned whether the purer vasoPediatric Anesthesia 2008 18: 579–581 doi:10.1111/j.1460-9592.2008.02520.x

The Guanylyl Cyclase Inhibition by MB as Vasoplegic Circulatory Shock Therapeutical Target

There were strong evidences that NO has capital importance in the progressive vasodilatation that associates to the varied circulatory shock forms. The decreased systemic vascular resistance observed in irreversible hemorrhagic (hypovolemic) and septic shock may be due to the excess production of nitric oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS) and ischemia reperfusion injury (cardiogenic shock, organ transplants), may involve nitric oxide overproduction. In these situations, the nitric oxide-induced loss of vascular sensitivity to catecholamines and myocardial depression contributes to lethal hypotension. As NO vasodilatation is cyclic GMP-mediated, there were two therapeutical options: a) The unspecific NO synthesis inhibition by L-arginine analogs, iNOS-specific inhibition by corticoids and/or aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis inhibition is associated to tissue necrosis and adverse hemodynamic effects and its clinical use was associated with high mortality, the second option using MB is safer and more rational. The elaboration of this text was motivated to suggest the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.

The effect of experimental haemorrhagic shock on the bacterial content of thoracic duct lymph.

The effect of haemorrhagic shock on the simultaneous appearance of enteric micro-organisms in the central lymph and the portal blood was studied in 30 dogs. Irreversible haemorrhagic shock results in portal bacteraemia but the lymph remains sterile. Thoracic duct drainage is harmful and hastens the onset of irreversibility.

Modeling damage in irreversible hemorrhagic shock

Modeling damage in irreversible hemorrhagic shock

Use of Near-Infrared Spectroscopy in Early Determination of Irreversible Hemorrhagic Shock

In field situations, patient triage may require early determination of patients progressing to irreversible shock. We investigated the utility of near-infrared spectroscopy (NIRS) in early detection of irreversible hemorrhagic shock. Twenty instrumented pigs were treated with a protocol involving 35% blood volume hemorrhage, 90 minutes of shock, and stepwise resuscitation with lactated Ringer's. Hemodynamics and NIRS measurements of skeletal muscle (leg), stomach, and liver tissue oxyhemoglobin saturation (StO2) were measured at baseline, every 30 minutes during shock, and after each resuscitative step. Measurements were compared between animals that expired during resuscitation (unresuscitatable) and animals that survived all resuscitative steps (resuscitatable). Neither global oxygen delivery, oxygen consumption, nor lactate distinguished resuscitatable from unresuscitatable animals. Invasive measurements of SvO2 did distinguish resuscitatable from unresuscitatable animals. After the first fluid bolus, both stomach and leg StO2 differed significantly between resuscitatable and unresuscitatable animals. Regression analysis revealed skeletal muscle (leg) StO2 obtained after the first resuscitative step was a significant mortality predictor despite resuscitation (r2=0.45) (p = 0.005). Non-invasive NIRS monitoring of leg and stomach StO2 differentiates resuscitatable from unresuscitatable animals after the initial resuscitative bolus. Use of this non-invasive tool may guide appropriate use of resuscitative fluids and has possible point-of-care applications.

Desmopressin (DDAVP) and factor VIII

Desmopressin (DDAVP) and factor VIII

Utility of clinical parameters of tissue oxygenation in a quantitative model of irreversible hemorrhagic shock.

The aim of this study was to assess the value of parameters of tissue oxygenation in monitoring the progression to irreversibility in a quantitative model of hemorrhagic shock. Rats were bled to a mean arterial pressure of 40 mmHg and were maintained at this level by further blood withdrawal until the compensation endpoint; this point was defined as the time at which the rat was no longer able to maintain its blood pressure at this level and shed blood was required for transfusion. The shock period was maintained until 0%, 20%, 40%, or 50% of the maximum shed blood volume (MBV) had been returned (n = 10 in each group, total n = 40). The animals were then resuscitated with remaining shed blood plus twice MBV as lactated Ringer's solution to MAP > 80 mmHg. Blood gas and serum lactate samples were measured at baseline, compensation endpoint, and at the time of resuscitation, and 24 h survival was recorded. Increasing the severity of shock progressively worsened the acidosis, with increased base deficit and lacticacidemia, and deterioration in central venous oxygen saturation (CvO2). Tissue oxygenation parameters, particularly CvO2, predicted subsequent mortality. Lactate levels only predicted irreversibility in late, severe shock. This quantitative model of hemorrhagic shock showed that tissue oxygenation parameters can be used to monitor the progression from the decompensated phase of hemorrhagic shock to irreversibility. Furthermore, this experimental study suggests that venous indices may be a valuable tool in reflecting the severity of hemorrhagic insult in a setting when arterial blood samples may not be easily available.

Transfusiological potential of hemocorrector “lactoproteinum” in irreversible hemorrhagic shock (IHS) in dogs: Influence of acid-base balance (ABB) and survival time

Transfusiological potential of hemocorrector “lactoproteinum” in irreversible hemorrhagic shock (IHS) in dogs: Influence of acid-base balance (ABB) and survival time

Physiologic and molecular characterization of the role of nitric oxide in hemorrhagic shock: evidence that type II nitric oxide synthase does not regulate vascular decompensation.

To determine the role of nitric oxide (NO) in decompensated and irreversible hemorrhagic shock, rats were subjected to hemorrhagic shock (HS) for 3 or 5 h. Lung, liver, and plasma samples were studied for evidence of NO formation using Northern analysis and immunohistochemistry for Type II NOS, as well as measurement of plasma nitrite/nitrate, cyclic GMP, and nitrosylated hemoglobin levels. Comparisons were made with similarly instrumented time-matched sham rats. Type II NOS mRNA and protein were detectable in lung and liver only in the irreversible phase of HS (5 h). A large accumulation of nitrosylated hemoglobin and nitrite/nitrate appeared in the irreversible phase. Significant accumulation of cyclic GMP or nitrite/nitrate was not detectable in the decompensation phase. Despite the hemodynamic decompensation at 3 h of HS, Type II NOS mRNA and protein expression, as well as NO metabolites were not elevated. To assess whether NO plays a physiologically significant role in decompensation, rats in the decompensation phase and sham animals were subjected to nonspecific NOS inhibition. Both groups displayed a similar magnitude and duration of blood pressure elevation. Hemodynamic decompensation in HS is not mediated by Type II NOS induction. NO production increases only after prolonged HS; significant NO production is observed only in severe, irreversible HS.