End-tidal CO2 pressure in the monitoring of cardiac output during canine hemorrhagic shock

The value of end-Tidal CO₂ pressure (PETCO₂) in monitoring circulatory status has been recently established in cardiac arrest. In an effort to extend its usefulness to other low-flow states, we studied the changes of PETCO₂ during progressive hemorrhage in anesthetized, mechanically ventilated dogs. PETCO₂ correlated with cardiac index (CI) in a logarithmic way (r = .95, P < .001), not only in the whole group but in any individual experiment as well. Venoarterial and arterial-end-tidal CO₂ gradients also correlated with CI (r = .85, P < .001 and R = .63, P < .001, respectively). These results suggest that cardiac output reductions are followed by increments in respiratory dead space, so CO₂ accumulates in venous blood and its pulmonary excretion is decreased. In this way, sequential changes in PETCO₂ during mechanical ventilation could noninvasively contribute to hemodynamic evaluation in hemorrhagic shock.     

Roles of cyclooxygenase-2 in tissue injury during hemorrhagic shock

Prostaglandins (PGs), which play a pivotal role in the cytokine network, have been implicated in the pathophysiology of circulatory shock, but the precise role of cyclooxygenase-2 (COX-2) in circulatory shock is still not known. This study investigated whether or not COX-2 affects liver and bowel injury during hemorrhagic shock (HS). Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. Besides the time course of tissue injury and mRNA expression of COX-2 in the liver and bowel during HS, we investigated the effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS398), a specific inhibitor of COX-2, on injury to these organs. The liver injury, evaluated by plasma aminotransferase levels and histology, was evident at the end of the shock period (Shock-0h) and had significantly increased 1 h after the start of resuscitation (Shock-1h) (P < 0.01). The bowel injury, assessed by histological findings in the terminal ileum, was scarcely detectable at Shock-0h but became noticeable at Shock-1h (P < 0.01). COX-2 mRNA expression was up-regulated in the liver during HS whereas it did not change in the bowel. NS398 treatment significantly exacerbated both liver and bowel injury. These lines of evidence suggest that COX-2-derived PGs provide protection against HS-induced liver and bowel injury.     

Influence of negative expiratory pressure ventilation on hemodynamic variables during severe hemorrhagic shock

OBJECTIVE: Outcome after trauma with severe hemorrhagic shock is still dismal. Since the majority of blood is present in the venous vessels, it might be beneficial to perform venous recruiting via the airway during severe hemorrhagic shock. Therefore, the purpose of our study was to evaluate the effects of negative expiratory pressure ventilation on mean arterial blood pressure, cardiac output, and short-term survival during severe hemorrhagic shock. DESIGN: Prospective study in 21 laboratory animals. SETTING: University hospital research laboratory. SUBJECTS:: Tyrolean domestic pigs. INTERVENTIONS: After induction of controlled hemorrhagic shock (blood loss approximately 45 mL/kg), 21 pigs were randomly ventilated with either zero end-expiratory pressure (0 PEEP; n = 7), 5 cm H2O positive end-expiratory pressure (5 PEEP; n = 7), or negative expiratory pressure ventilation (up to -30 cm H2O at the endotracheal tube during expiration; n = 7). MEASUREMENTS AND MAIN RESULTS: Mean (+/-sd) arterial blood pressure was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (38 +/- 5 vs. 27 +/- 3 mm Hg; p = .001) and the 5 PEEP animals (38 +/- 5 vs. 20 +/- 6 mm Hg; p < .001) after 5 mins of the experiment. Cardiac output was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (3.1 +/- .4 vs. 1.9 +/- .9 L/min; p = .001) and 5 PEEP animals (3.1 +/- .4 vs. 1.2 +/- .8 L/min; p < .001) after 5 mins of the experiment. All seven negative expiratory pressure ventilation animals, but only three of seven 0 PEEP animals (p = .022), survived the 120-min study period, whereas all seven of seven 5 PEEP animals were dead within 35 mins (p < .001). Limitations include that blood loss was controlled and that the small sample size limits the evaluation of survival outcome. CONCLUSIONS: When compared with pigs ventilated with either 0 PEEP or 5 PEEP, negative expiratory pressure ventilation during severe hemorrhagic shock improved mean arterial blood pressure and cardiac output.     

End-tidal CO2 monitoring in critically ill infants and children

End-tidal carbon dioxide (ETCO2) monitoring is an effective tool to continuously assess the adequacy of ventilation in critically ill infants and children. Optimal clinical application of this noninvasive monitoring technique requires an understanding of the physiologic principles of ETCO2 monitoring and its unique technologic considerations.     

Oxyradical-mediated hepatocellular Ca2+ alterations during hemorrhagic shock and resuscitation

Both altered Ca2+ homeostasis and injury by oxygen-free radicals (OFR) are pivotal mechanisms of cellular dysfunction. The purpose of this study was to evaluate the role of OFR and xanthine oxidase in hepatocellular Ca2+ dysregulation following hemorrhagic shock and resuscitation. Anesthetized rats were bled to a mean arterial blood pressure of 40 mm Hg for 60 min and then resuscitated with 60% of shed blood and 3-fold the shed blood volume as lactated Ringer's for another 60 min. Total Ca2+ uptake (Ca2+(up)), rate of Ca2+ influx (Ca2+(in)), and membrane Ca2+(flux) (Ca2+(flux)) were determined in isolated hepatocytes using 45Ca2+ incubation techniques. Hepatocyte oxidant injury was fluorometrically determined by thiobarbituric acid-reactive substances, oxidized, and reduced glutathione. Hemorrhage/resuscitation significantly increased Ca2+(up), Ca2+(in), and Ca2+(flux) compared with sham-operated rats. Continuous administration of superoxide dismutase or catalase (60,000 IU/kg body weight) during resuscitation substantially decreased Ca2+(up), Ca2+(in), Ca2+(flux), and oxidant injury. Pretreatment with allopurinol (50 mg/kg/day for 2 days) significantly inhibited enhanced plasma xanthine oxidase activity and hepatocyte glutathione oxidation, however, it did not prevent hepatocellular Ca2+ dysregulation. These data suggested a significant role of oxyradicals in ischemia/reperfusion-induced Ca2+ overload, however, xanthine oxidase activation seemed not to be a main source of these radicals.     

End-tidal carbon dioxide as a noninvasive indicator of cardiac index during circulatory shock

OBJECTIVE: To document the relationships between cardiac index and end-tidal carbon dioxide tension (PetCO2 during diverse low-flow states of circulatory shock. DESIGN: Randomized, prospective, controlled studies on animal models of hemorrhagic, septic, and cardiogenic shock. SETTING: University-affiliated research laboratory. SUBJECTS: Sixteen anesthetized domestic pigs weighing 35-45 kg. INTERVENTIONS: Hemorrhagic shock was induced in five pigs by bleeding followed by reinfusion of shed blood. Septic shock was induced in five pigs by infusion of live Escherichia coli. Cardiogenic shock followed an interval of global myocardial ischemia after inducing and reversing ventricular fibrillation in six pigs. MEASUREMENTS AND MAIN RESULTS: PetCO2 was continuously measured. Cardiac index was measured intermittently by using conventional thermodilution techniques. Cardiac index was correlated with PetCO2 by polynomial regression and Bland-Altman analyses. PetCO2 was highly correlated with cardiac index during hemorrhagic shock (r2 = .69, p < .01), septic shock (r2 = .65, p < .01), and cardiogenic shock (r2 = .81, p < .01). PetCO2 predicted thermodilution cardiac index with bias of -11+/-27 (+/-2 SD) mL/min/kg during hemorrhagic shock, 1.3+/-20.4 (+/- 2 SD) mL/min/kg during septic shock, and -1+/-12 (+/-2 SD) mL/min/kg during cardiogenic shock. CONCLUSIONS: Cardiac output and PetCO2 were highly related in diverse experimental models of circulatory shock in which cardiac output was reduced by >40% of baseline values. Therefore, measurement of PetCO2 is a noninvasive alternative for continuous assessment of cardiac output during low-flow circulatory shock states of diverse causes.     

呼气末二氧化碳监测在机械通气早产儿中的临床应用

目的:探讨呼气末二氧化碳监测在早产极低出生体重儿中的应用。方法:对32例气管插管机械通气的早产极低出生体重儿进行持续主流呼气末二氧化碳监测,并同时配对检测75人次动脉血气分析,比较呼气末二氧化碳分压(PetCO2)与动脉二氧化碳分压(PaCO2)的关系。结果:75人次早产极低出生体重儿动脉血气分析,PaCO2平均为(39.1±6.4)mmHg,对应的PetCO2平均为(34.8±5.2)mmHg,两者有显著相关性,相关系数r为0.74;肺部病变较轻者比肺部病变较严重者PetCO2更能准确地反映PaCO2。结论:无创性主流呼气末二氧化碳监测适用于气管插管机械通气的早产极低出生体重儿,能较准确地反映PaCO2的水平。     

Exogenous nitric oxide induces protection during hemorrhagic shock

Introduction

This study analyzed the systemic and microvascular hemodynamic changes related to increased nitric oxide (NO) availability during the early phase of hemorrhagic shock. Hemodynamic responses to hemorrhagic shock were studied in the hamster window chamber.

Materials and Methods

Exogenous NO was administered in the form of nitrosothiols (nitrosylated glutathione, GSNO) and was given prior the onset of hemorrhage. Moderate hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume, and the hypovolemic shock was followed over 90 min.

Results

Animals pre-treated with GSNO maintained systemic and microvascular conditions during hypovolemic hemorrhagic shock, when compared to animal treated with glutathione (GSH) or the Sham group. Low concentrations of NO released during the early phase of hypovolemic shock from GSNO mitigated arteriolar vasoconstriction, increased capillary perfusion and venous return, and improved cardiac function (recovered of blood pressure and stabilized heart rate). GSNO's effect on resistance vessels influenced intravascular pressure redistribution and blood flow, preventing tissue ischemia.

Discussion

Increases in NO availability during the early phase of hypovolemic shock could preserve cardiac function and microvascular perfusion, sustaining organ function. Direct translation into a clinical scenario may be limited, although the pathophysiological importance of NO in the early phase of hypovolemia is clearly highlighted here.     

Complement activation during hemorrhagic shock and resuscitation in swine

Activation of the complement (C) cascade is known to play a key role in the adverse immune consequences of hemorrhagic trauma with subsequent shock and resuscitation. However, it is not clear whether hypovolemia per se, without trauma and resuscitation, can also lead to C activation. To address this question, we studied the presence, kinetics, and cause of C activation in a porcine model of hemorrhagic shock and resuscitation in the absence of trauma. Pigs were bled to and kept at 35 mmHg for 90 min, followed by hypotensive resuscitation with different fluids and, finally, with shed blood. The animals developed severe lactic acidosis between 30 and 90 min, which was accompanied by a trend for initial rise and subsequent 40% drop of CH50/mL, indicating massive C activation even before resuscitation, i.e., before reperfusion damage could have occurred. Resuscitation with plasma expanders caused 20% additional C consumption, whereas whole blood raised CH50/mL. Plasma C5a decreased initially and then significantly increased at 60 and 180 min, whereas thromboxane B2 showed a 3-fold increase at 30 and 60 min. Plasma LPS was also increased above baseline at 90 and 180 min. In in vitro studies with pig blood, spontaneous C5a formation, as well as zymosan-induced C consumption, was significantly enhanced under the conditions of lactic acidosis. Our data suggest that lactic acidosis, endotoxemia, and possibly other ischemia-related tissue alterations act in a vicious cycle in inducing C activation and, hence, aggravation of shock. The biphasic course of CH50/mL and C5a changes may reflect yet unrecognized physiological responses to hemorrhage-related C activation.     

Arterial vs venous blood gas differences during hemorrhagic shock

AIM: To characterize differences of arterial (ABG) and venous (VBG) blood gas analysis in a rabbit model of hemorrhagic shock.METHODS: Following baseline arterial and venous blood gas analysis, fifty anesthetized, ventilated New Zealand white rabbits were hemorrhaged to and maintained at a mean arterial pressure of 40 mmHg until a state of shock was obtained, as defined by arterial pH ≤ 7.2 and base deficit ≤ -15 mmol/L. Simultaneous ABG and VBG were obtained at 3 minute intervals. Comparisons of pH, base deficit, pCO₂, and arteriovenous (a-v) differences were then made between ABG and VBG at baseline and shock states. Statistical analysis was applied where appropriate with a significance of P < 0.05.RESULTS: All 50 animals were hemorrhaged to shock status and euthanized; no unexpected loss occurred. Significant differences were noted between baseline and shock states in blood gases for the following parameters: pH was significantly decreased in both arterial (7.39 ± 0.12 to 7.14 ± 0.18) and venous blood gases (7.35 ± 0.15 to 6.98 ± 0.26, P < 0.05), base deficit was significantly increased for arterial (-0.9 ± 3.9 mEq/L vs -17.8 ± 2.2 mEq/L) and venous blood gasses (-0.8 ± 3.8 mEq/L vs -15.3 ± 4.1 mEq/L, P < 0.05). pCO₂ trends (baseline to shock) demonstrated a decrease in arterial blood (40.0 ± 9.1 mmHg vs 28.9 ± 7.1 mmHg) but an increase in venous blood (46.0 ± 10.1 mmHg vs 62.8 ± 15.3 mmHg), although these trends were non-significant. For calculated arteriovenous differences between baseline and shock states, only the pCO₂ difference was shown to be significant during shock.CONCLUSION: In this rabbit model, significant differences exist in blood gas measurements for arterial and venous blood after hemorrhagic shock. A widened pCO₂ a-v difference during hemorrhage, reflective of poor tissue oxygenation, may be a better indicator of impending shock.     

低血容量性休克大鼠全身氧动力学的变化研究

目的：研究低血容量性休克时全身氧动力学的变化特点。方法：按４ｍｌ／ｋｇ,每隔０．５分次从静脉放血,观察大鼠休克过程中全身氧供给（ＤＯ２）,氧消耗（ＶＯ２）和氧摄取率（ＥｘｔＯ２）的变化。结果：失血后１．５小时血红蛋白浓度开始显著降低,心率明显加快,失血２．０小时平均动脉压明显下降,此时ＤＯ２亦开始进行性下降,由于ＥｘｔＯ２出现代偿升高,ＶＯ２维持相对不变;     

Redistribution of cardiac output during hemorrhagic shock in sheep

OBJECTIVE: Our goal was to evaluate the robustness of one of the assumptions used by esophageal Doppler monitors to compute systemic stroke volume and cardiac output; i.e., a constant flow proportion between supra-aortic vessels and descending aorta. For this purpose, we measured ascending and descending aortic blood flows during acute hemorrhage in anesthetized ewes. DESIGN: Prospective, experimental study. SETTING: Animal research facility. SUBJECTS: Adult ewes. INTERVENTIONS: Anesthetized animals were implemented with an aortic pressure transducer and two ultrasound transit time flowmeters placed around ascending and descending aorta, respectively. After baseline measurements, three incremental blood withdrawals were followed by progressive blood restitution in three similar steps. MEASUREMENTS AND MAIN RESULTS: Ascending and descending aortic blood flows were reduced in a proportional manner after hemorrhage (-48% and -46%, respectively; p < .05 vs. baseline). Following blood restitution, flows were not fully restored, but ascending aortic flow was reduced by 27% with respect to initial control values while descending aortic flow was only 15% below. The agreement between ascending aortic flow and cardiac output calculated as descending aortic flow divided by 0.7 was characterized by a bias of 0.07 L/min and limits of agreement of +1.24 L/min and -1.10 L/min. CONCLUSIONS: Minor blood flow redistribution between supra-aortic and descending aortic territories was seen only following blood restitution but not during hemorrhage in these anesthetized ewes. This observation supports the robustness of the assumption of constant flow proportion used by the esophageal Doppler monitor to calculate systemic stroke volume from descending aortic flow measurements.     

Exogenous nitric oxide prevents cardiovascular collapse during hemorrhagic shock

This study investigated the systemic and microvascular hemodynamic changes related to increased nitric oxide (NO) availability following significant hemorrhage, made available by administration of NO releasing nanoparticles (NO-nps). Hemodynamic responses to hemorrhagic shock were studied in the hamster window chamber. Acute hemorrhage was induced by arterial controlled bleeding of 50% of blood volume, and the resulting hemodynamic parameters were followed over 90 min. Exogenous NO was administered in the form of NO-nps (5 mg/kg suspended in 50 μl saline) 10 min following induced hemorrhage. Control groups received equal dose of NO free nanoparticles (Control-nps) and Vehicle solution. Animals treated with NO-nps partially maintained systemic and microvascular function during hypovolemic shock compared to animals treated with Control-nps or the Vehicle (50 μl saline). The continuous NO released by the NO-nps reverted arteriolar vasoconstriction, partially recovered both functional capillary density and microvascular blood flows. Additionally, NO supplementation post hemorrhage prevented cardiac decompensation, and thereby maintained and stabilized the heart rate. Paradoxically, the peripheral vasodilation induced by the NO-nps did not decrease blood pressure, and combined with NO's effects on vascular resistance, NO-nps promoted intravascular pressure redistribution and blood flow, avoiding tissue ischemia. Therefore, by increasing NO availability with NO-nps during hypovolemic shock, it is possible that cardiac stability and microvascular perfusion can be preserved, ultimately increasing survivability and local tissue viability, and reducing hemorrhagic shock sequelae. The relevance, stability, and efficacy of exogenous NO therapy in the form of NO-nps will potentially facilitate the intended use in battlefield and trauma situations.     

TSC for hemorrhagic shock: effects on cytokines and blood pressure

Previous studies have shown that administering trans-sodium crocetinate (TSC) as a treatment of hemorrhagic shock leads to increased whole-body oxygen consumption and survival as well as protection of the liver and kidney. It has been suggested that TSC increases oxygen delivery by increasing the diffusivity of oxygen through plasma. However, as with any novel mechanism of action, there are always questions about whether the results could also be ascribed to other, previously described mechanisms of action. This study was designed to look at some aspects of that by examining the effect of different TSC dosing regimens on the blood pressure and the production of cytokines after hemorrhage because both responses have been reported with compounds that act via other mechanisms. In a constant-pressure rat model of hemorrhagic shock, it was seen that a singe bolus injection of TSC results in an immediate but transient increase in the arterial blood pressure. This is similar to the effect reported previously for using 100% oxygen. It was also found that if the TSC injections were repeated periodically over an hour, a sustained increase in the blood pressure would occur. Because inflammatory cytokines have been implicated in mortality and tissue damage, it has been suggested that TSC may affect the production of cytokines. Thus, the effect of TSC on the production of TNF-alpha and IL-10 was also examined. The data show that treatment with TSC results in lower concentrations of TNF-alpha in the liver and spleen as well as lower concentrations of IL-10 in the spleen. Again, similar effects on other cytokines have been seen with 100% oxygen. These results support the hypothesis that the effects of TSC on hemorrhagic shock are mediated via an effect on oxygen.