Effects of hemorrhage on gastrointestinal oxygenation

OBJECTIVES: (1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO(2)). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. DESIGN: Prospective, interventional study. SETTING: Research laboratory at a university center. SUBJECTS: Fourteen anesthetized, mechanically ventilated dogs. INTERVENTIONS: Twenty milliliters per kilogram bleeding. MEASUREMENTS AND MAIN RESULTS: We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO(2). We calculated systemic and intestinal oxygen transport (DO(2)) and consumption (VO(2)), pHi and arterial minus intramucosal PCO(2) (DeltaPCO(2)). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO(2) fell (26.0+/-7.3 versus 8.9+/-2.6 and 71.9+/-17.3 versus 24.6+/-9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO(2) remained unchanged (5.5+/-1.3 versus 5.4+/-1.3 and 15.7+/-5.0 versus 14.9+/-5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13+/-0.11 versus 6.96+/-0.17, 7.18+/-0.06 versus 6.97+/-0.15, 7.12+/-0.11 versus 6.94+/-0.14, p<0.05) and DeltaPCO(2) (21+/-13 versus 35+/-23, 15+/-5 versus 33+/-16, 23+/-17 versus 38+/-20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7+/-0.9 versus 3.7+/-1.4 and 1.8+/-0.8 versus 4.3+/-1.5 mmol/l, 0.1+/-0.6 versus 0.6+/-0.7 mmol/l, p<0.05). CONCLUSIONS: During hemorrhage, systemic and intestinal VO(2) remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.     

Effects of levosimendan in normodynamic endotoxaemia: a controlled experimental study

OBJECTIVES: Levosimendan is an inotropic and vasodilator drug that has proved to be useful in cardiogenic shock. Pretreatment with levosimendan in experimental hypodynamic septic shock in pigs has shown valuable effects in oxygen transport. Our goal was to assess the effects of levosimendan in a normodynamic model of endotoxaemia. METHODS: Twelve sheep were anaesthetized and mechanically ventilated. After taking basal haemodynamic and oxygen transport measurements, sheep were assigned to two groups during 120 min: (1) endotoxin (5 microg/kg endotoxin); (2) levosimendan (5 microg/kg endotoxin plus levosimendan 200 microg/kg followed by 200 microg/kg/h). Both groups received hydration of 20 ml/kg/h of saline solution. RESULTS: In the endotoxin group, cardiac output, intestinal blood flow and systemic and intestinal oxygen transports and consumptions (DO(2) and VO(2)) remained unchanged. In the levosimendan group, systemic and intestinal DO(2) were significantly higher than in the endotoxin group. Because stroke volume did not change (basal versus 120': 0.9+/-0.1 ml/kg versus 0.9+/-0.2 ml/kg, p=0.3749), the elevation in cardiac output by levosimendan (145+/-17 ml/min/kg versus 198+/-16 ml/min/kg, p=0.0096) was related to an increased heart rate (159+/-32 beats l/min versus 216+/-19 beats l/min, p=0.0037). Levosimendan precluded the development of gut intramucosal acidosis at 120' (endotoxin versus levosimendan, ileal intramucosal-arterial PCO(2) difference: 19+/-4 Torr versus 10+/-4 Torr, p=0.0025). However, levosimendan decreased mean arterial blood pressure (99+/-20 Torr versus 63+/-13 Torr, p=0.0235) and increased blood lactate levels (2.4+/-0.9 mmol/l versus 4.8+/-1.5 mmol/l, p=0.0479). All p-values are differences in specific points (paired or unpaired t-test with Bonferroni correction) after two-way repeated measures ANOVA. A p-value<0.05 was considered significant. CONCLUSIONS: Levosimendan improved oxygen transport and prevented the development of intramucosal acidosis in this experimental model of endotoxaemia. However, systemic hypotension and lactic acidosis occurred. Additional studies are needed to show if different doses and timing of levosimendan administration in septic shock might improve gut perfusion without adverse effects.     

Cell metabolism in patients undergoing major valvular heart surgery: relationship with intra and postoperative hemodynamics, oxygen transport, and oxygen utilization patterns

The relationships between cell metabolism and both hemodynamics and oxygen transport/utilization (VO2/DO2) pattern were evaluated intra and postoperatively in eight patients undergoing major valvular heart surgery with the aid of moderately hypothermic cardiopulmonary bypass (CPB). Quadriceps femoris specimens were obtained by the needle biopsy technique for muscle ATP, ADP, AMP, phosphocreatine (PCr), creatine and lactate determination at anesthesia induction, after CPB, as well as in the ICU 18 h after surgery. Moreover, hemodynamic variables, oxygen transport and utilization indices, and plasma lactate were measured at the same intervals and throughout the CPB period. After CPB, muscle ATP and PCr contents were reduced (p less than .05) as compared to those of both pre-CPB patients and healthy control subjects; muscle and plasma lactate levels were increased (p less than .05). Mean VO2 and DO2 values measured during CPB significantly decreased (p less than .05), but VO2 reduction was proportionally greater than that of DO2 (-62% vs. -41%). No correlation was found between VO2 and DO2 at that time, but a significant relationship (p less than .05) was found at the end of CPB. A further decrease in muscle ATP and PCr levels was measured in the ICU, as muscle and plasma lactate levels were still elevated. At that time, VO2 and DO2 were not significantly different from pre-CPB values, but were significantly (p less than .05) correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

The oxygen debt during routine cardiac surgery: illusion or reality?

BACKGROUND: Patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB) are often thought to have tissue hypoxia and intraoperative oxygen debt accumulation despite the lack of sufficient data to support this assumption. METHODS AND RESULTS: Oxygen uptake and related parameters, including the plasma lactate and pyruvate concentrations, were studied during the perioperative period in a group of 15 consecutive patients who underwent coronary artery bypass graft surgery. The actual oxygen uptake (VO2) and delivery (DO2) were compared with the individual expected (computed) oxygen transport values. The mean values of DO2 and VO2 were in the range of the expected values. Our results demonstrate a leading role for body temperature in perioperative changes of oxygen consumption rate (r2=0.65, p<0.001). Plasma lactate and pyruvate did not exceed the physiological range in any patient. However, with initiation of CPB, the lactate to pyruvate (LA/PVA) ratio increased (from 9.87 +/- 2.43 at T1 to 12.08 +/- 1.51 at T2, p<0.05). The mean value of the LA/ PVA ratio was elevated during surgery. Later, upon lowering of the plasma lactate concentration in the postoperative period, the LA/PVA ratio decreased to normal values. Without any other evidence of hypoxia, this increase in the LA/PVA ratio could be explained by washout of lactate from previously hypoperfused tissues and intraoperative decrease of lactate clearance. CONCLUSION: Systemic oxygenation was not impaired during CPB, or during 18 h after surgery in the studied group of patients.     

Metformin overdose,but not lactic acidosis <Emphasis Type="Italic">per se</Emphasis>, inhibits oxygen consumption in pigs

ABSTRACT: INTRODUCTION: Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30-60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues. METHODS: Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4-8g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for 9h. Oxygen extraction was computed as VO2/DO2. Activities of main components of mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study. RESULTS: Pigs infused with metformin (6+/-2 g; final serum drug level 77+/-45 mg/L) progressively developed lactic acidosis (final arterial pH 6.93+/-0.24 and lactate 18+/-7 mmol/L, P<0.001 for both). Their VO2 declined over time (from 115+/-34 to 71+/-30 ml/min, P<0.001) despite grossly preserved DO2 (from 269+/-68 to 239+/-51 ml/min, p=0.58). Oxygen extraction accordingly fell from 43+/-10 to 30+/-10 % (P=0.008). None of these changes occurred in either sham controls or pigs infused with lactic acid (final arterial pH 6.86+/-0.16 and lactate 22+/-3 mmol/L). Metformin intoxication was associated with inhibition of complex I in liver (P<0.001), heart (P<0.001), kidney (P=0.003), skeletal muscle (P=0.012) and platelets (P=0.053). The activity of complex II and III diminished in liver (P<0.001), heart (P<0.001) and kidney (P<0.005) while that of complex IV declined in heart (P<0.001). CONCLUSIONS: Metformin intoxication induces lactic acidosis, inhibits global oxygen consumption and causes mitochondrial dysfunction in liver and other tissues. Lactic acidosis per se does not decrease whole-body respiration.     

Prevention of systemic hyperlactatemia during splanchnic ischemia

Arterial blood lactate increases as a result of poor tissue perfusion. In splanchnic hypoperfusion, increased hepatic lactate uptake may delay increases in arterial blood lactate. We hypothesized that during isolated reduction of mesenteric blood flow, maintaining systemic blood volume and flow by fluid resuscitation may prevent systemic hyperlactatemia and therefore mask splanchnic ischemia. In a randomized study, 7 pigs were subjected to 4 h of splanchnic hypoperfusion by reducing the superior mesenteric artery blood flow to 4 +/- 0.8 mL/kg min [mean +/- standard deviation (SD)]. Seven pigs served as controls. Fluid was administered in order to keep the pulmonary artery occlusion pressure at 5 to 8 mm Hg. Cardiac output, portal vein, superior mesenteric, and hepatic arterial blood flow were measured every 30 min. Arterial, mixed venous, hepatic, portal, and mesenteric venous blood lactate, and jejunal mucosal pCO2 were measured at baseline and thereafter at 30-min intervals. The initial decrease in portal venous blood flow in the ischemic animals was subsequently counterbalanced by increasing hepatic arterial blood flow from 2 +/- 1 mL x kg(-1) x min(-1) at baseline to 11 +/- 4 mL x kg(-1) x min(-1) [after 4 h of ischemia; mean +/- standard deviation (SD), P = 0.02]. Jejunal mucosal- and mesenteric vein-arterial pCO2 gradients increased in the ischemic group from 11 +/- 8 mm Hg to 73 +/- 5 mm Hg (P = 0.02), and from 10 +/- 4 mm Hg to 44 +/- 8 mm Hg, respectively (P = 0.02). Mesenteric and portal venous lactate increased in the ischemic animals from 1.1 +/- 0.3 mmol/L to 4.2 +/- 1.0 mmol/L (P = 0.02), and from 1.0 +/- 0.2 mmol/L to 1.6 +/- 0.3 mmol/L, respectively (P = 0,03). While mesenteric lactate production and hepatic lactate uptake increased in parallel in the ischemic animals from 5 +/- 6 micromol x kg(-1) x min(-1) to 14 +/- 5 micromol x kg(-1) x min(-1) (P = 0.04), and from 14 +/- 7 micromol x kg(-1) x min(-1) to 24 +/- 6 micromol x kg(-1) x min(-1), respectively (P = 0.02), hepatic venous and arterial lactate, and apparent splanchnic lactate uptake and extraction did not change. We conclude that the hepatic lactate uptake increases in response to hepatic lactate influx. Systemic hyperlactatemia and increased hepatic venous lactate concentrations are late consequences of mesenteric hypoperfusion if hypovolemia is prevented. The net exchange of lactate across the splanchnic region does not reflect hepato-portal lactate kinetics in this animal model of intestinal hypoperfusion.     

Hepatic and splanchnic oxygen consumption during acute hypoxemic hypoxia in anesthetized pigs

OBJECTIVE: To compare the hepatosplanchnic oxygen consumption (VO2) with the hepatic and splanchnic VO2 and to calculate the critical oxygen delivery (DO2crit) below which VO2 decreases in the hepatic, splanchnic, and hepatosplanchnic regions in a model of hypoxemic hypoxia. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated pigs (n = 7). INTERVENTIONS: The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, two flow probes were positioned around the portal vein and the hepatic artery to measure portal vein blood flow and hepatic artery blood flow. Oxygen and lactate contents in the carotid artery, the portal vein, and the hepatic vein were measured in blood samples obtained from the appropriate catheters. MEASUREMENTS AND MAIN RESULTS: After a 2-hr stabilization period, hemodynamic and biological variables were recorded during acute hypoxemic hypoxia (FIO2 = 0.5, 0.4, 0.3, 0.21, 0.15, 0.10, and 0.07). VO2, DO2, and DO2crit were determined in the hepatic, splanchnic, and hepatosplanchnic regions. The hepatosplanchnic VO2 was 48 +/- 5 mL/min at high FIO2 (40% for the liver and 60% for the splanchnic organs) and decreased below FIO2 of 0.15. Lactate uptake in the whole hepatosplanchnic region remained steady at FIO2 values of 0.5 to 0.15 and then switched to a lactate release at low FIO2. However, the splanchnic region released lactate, whereas lactate was taken up by the liver. DO2crit in the hepatic, splanchnic, and hepatosplanchnic regions was 24 +/- 3, 38 +/- 2, and 49 +/- 4 mL/min, but the systemic DO2crit, below which regional VO2 became oxygen supply dependent, did not differ in the liver, splanchnic, and hepatosplanchnic regions. CONCLUSIONS: The variables of oxygenation and lactate flux measured in the hepatosplanchnic region summarize the metabolic changes of various organs that may vary in different ways during hypoxemic hypoxia.     

Systemic and regional oxygen uptake and delivery and lactate flux in endotoxic dogs infused with dopexamine

OBJECTIVE: To test whether dopexamine, a dopaminergic and beta 2-adrenergic receptor agonist, would: a) direct a greater share of cardiac output to gut than to muscle when used to increase systemic oxygen delivery (DO2) in endotoxic dogs; and b) enhance the ability of peripheral tissues to extract oxygen. DESIGN: Two groups of eight dogs infused for 1 hr with 2 mg/kg Escherichia coli endotoxin. One group was continually infused with dopexamine (12 micrograms/min.kg) and the other group was not (control group). After 2 hrs, oxygen extracting ability was challenged by changing inspired gas to 12% oxygen for 30 mins. SUBJECTS: Anesthetized, paralyzed, pump-ventilated mongrel dogs. INTERVENTIONS: Donor RBCs and dextran used during endotoxin infusion to maintain cardiac output while preserving hematocrit near 40%. MEASUREMENTS AND MAIN RESULTS: In the dopexamine-treated group, cardiac output, systemic DO2, and oxygen consumption (VO2) were higher than in the control group during the first 90 mins, but were not thereafter. Gut and muscle blood flow did not differ between groups, but the fraction of cardiac output going to each region tended to be less in the dopexamine-treated dogs. Arterial lactate values increased to about 6 mmol/L in all dogs. In both groups, limb muscle first produced lactate but then took up lactate after the first hour. The gut in controls converted from lactate uptake in the first hour to producing about 20 mumol/min.100 g, whereas the gut never produced lactate in the dopexamine-treated group. During hypoxia, systemic DO2 and VO2 decreased only in the dopexamine-treated group, even though oxygen extraction was only slightly above 40%. Oxygen extraction was not demonstrably improved by dopexamine treatment. CONCLUSIONS: Dopexamine temporarily increased systemic DO2 and VO2 in volume-expanded endotoxic dogs during normoxia and may have caused gut mucosa to be preferentially perfused and thus to be kept better oxygenated.     

The effect of cardiopulmonary bypass resuscitation on cardiac arrest induced lactic acidosis in dogs

The adequacy of end organ blood flow following a cardiac arrest varies depending on the artificial reperfusion technique utilized and may critically affect patient outcome. Both oxygen consumption (VO2) and arterial lactate values have previously been used to assess tissue perfusion. Cardiopulmonary bypass resuscitation (CPB) is a reperfusion technique capable of providing near normal end organ blood flow. The purpose of this investigation was to study the effect of femoro-femoral veno-arterial CPB resuscitation compared to standard CPR on VO2 and arterial lactic acid values after a prolonged cardiac arrest. Ten mongrel dogs were electrically fibrillated and left in cardiopulmonary arrest without therapy for 12 min. Resuscitation was attempted according to a standardized protocol utilizing either CPB (n = 5) or standard external CPR (n = 5). Oxygen consumption values and arterial lactic acid samples were obtained at baseline, at timed intervals throughout resuscitation and after return of spontaneous circulation in successfully resuscitated dogs. Baseline hemodynamic and biochemical measurements were similar in both treatment groups (P greater than 0.05). Oxygen consumption (440 +/- 50 ml/min/M2) and mean arterial lactic acid values (7.44 +/- 2.25 mmol/l) were significantly higher at 1 min of resuscitation in CPB-treated dogs compared to dogs treated with CPR (60 +/- 10 ml/min/M2) (3.16 +/- 0.69 mmol/l) respectively (P less than 0.05). Mean arterial lactic acid values rose significantly at each sampling interval during CPR (P less than 0.05) but began to decrease after 5 min of resuscitation in the CPB animals and were not significantly different than baseline after 60 min of bypass (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodilution improves organ function during normothermic cardiopulmonary bypass: investigations in isolated perfused pig kidneys

We investigated the effects of haemodilution on kidney function during normothermic cardiopulmonary bypass (CPB) by performing in vitro haemoperfusion of pig kidneys for 90 min after cold preservation. We compared two groups (n = 14 each) with respect to rheologic and haemodynamic parameters and glomerular and tubular function. Group 1 was perfused at a haematocrit of 0.33 +/- 0.01, group 2 at 0.21 +/- 0.01. Blood flow was adjusted according to blood pressure. Blood viscosity and vascular resistance were reduced in group 2. Comparison of group 1 versus group 2 revealed a metabolic rate of oxygen 3.4 +/- 1.7 versus 4.3 +/- 1.8 ml/min/100 g, sodium transport 1.2 +/- 1.2 versus 1.8 +/- 1.2 mmol/min/100 g, and creatinine clearance 9.9 +/- 9.1 versus 15.6 +/- 11.9 ml/min/100 g, p < 0.05. We conclude that haemodilution leads to an overproportional decrease in blood viscosity and improves the properties of flow and kidney function. In the ongoing discussion about the optimal extent of haemodilution in CPB, the importance of viscosity and blood flow should be further emphasized.     

Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen tension in pigs

OBJECTIVE: To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, mucosal tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS: Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.     

Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats

We studied the effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis in peritonitis and shock in rats. Sepsis was induced by cecal ligation and perforation. After tracheostomy, rats were randomized to spontaneous breathing (S) or mechanical ventilation with paralysis (V). Five animals were studied in each group. The V animals were paralyzed with pancuronium bromide to eliminate respiratory effort. Mechanical ventilation consisted of controlled ventilation using a rodent respirator with periodic adjustment of minute ventilation to maintain PaCO2 and pH within normal range. Arterial and central venous blood gases and thermodilution cardiac output were measured at baseline before abdominal surgery, and sequentially at 0.5, 3.5, and 6 h after surgery. At 6 h, cardiac output was 193 +/- 30 ml/kg.min in S animals and 199 +/- 32 ml/kg.min in V animals (NS). The central venous oxygen saturation was 27.4 +/- 4.7% in S animals and 30.0 +/- 6.4% in V animals (NS). Systemic oxygen extraction was 70 +/- 5% in S animals and 67 +/- 6% in V animals (NS). Arterial lactate was 2.4 +/- 0.4 mmol/L in S animals and 2.2 +/- 0.5 mmol/L in V animals (NS). The S animals developed lethal hypotension at 6.6 +/- 0.4 h compared to 6.8 +/- 0.4 h in V animals (NS). These data suggest that mechanical ventilation does not decrease systemic oxygen extraction or ameliorate the development of lactic acidosis during septic shock.     

体外循环中空气法胃粘膜pH值与氧供 氧耗的变化

目的观察体外循环（CPB）中空气法胃粘膜pH值与氧供、氧耗的变化了解体外循环期间胃粘膜的血流灌注。方法选择择期行体外循环心脏手术30例，麻醉后置入TONO胃管通过空气法胃粘膜张力模块自动持续监测胃粘膜二氧化碳分压（PgCO2），在监护仪中输入麻醉诱导后30min、体外循环30min、60min、停体外循环后30min和60min时间点的动脉和混合静脉血气分析结果，计算获得各时点的胃粘膜pH值（pHi）、氧供（DO2）和氧耗（VO2）等数据。结果PgCO2在CPB期间明显低于术前（P〈0．01），停CPB后恢复到术前水平；pHi的变化体外环循期间显著升高（P〈0．01），停CPB后恢复术前水平；DO2和VO2变化：CPB期间明显低于术前（P〈0．01），停CPB后明显高于CPB期间（P〈0．01），停CPB 60min后明显高于术前（P〈0．01）。结论本研究中的病例在低温体外循环期间未存在胃肠粘膜血流灌注不足。     

Whole body oxygen consumption and critical oxygen delivery in response to prolonged and severe carbon monoxide poisoning

BACKGROUND: Carbon monoxide (CO) poisoning remains the leading cause of death by poisoning in the world. One of the major proposed mechanisms for CO toxicity is the binding of CO to cytochrome oxidase and interference with cellular oxygen utilization but evidence for this is inconclusive. AIM OF STUDY: This study examined the effects of prolonged CO exposure on the dynamics of whole body oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe if CO exposure results in a defect of oxygen utilization defect as determined by a reduction in VO(2) during the course of poisoning prior to reaching the point where VO(2) is directly dependent on DO(2). This critical level of DO(2) (DO(2)crit) produced by CO poisoning was compared to historical values produced by other insults, which decrease global body DO(2). METHODS: Five small dogs were ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death. Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb) levels increased linearly over 2.5 h to values above 80% until death. VO(2) remained constant and not significantly different from baseline below a COHb of 80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate levels were not significantly elevated from baseline until VO(2) dropped. DO(2) decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/-5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg, which is not significantly different from values ranging from 7 to 13 ml/min/kg reported in the literature due to other insults, which reduce DO(2). CONCLUSION: In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or increase in systemic lactate prior to reaching DO(2)crit was noted. In addition, CO exposure does not appear to change the DO(2)crit. The combination of these findings does not support the theory that CO produces a whole body intracellular defect in oxygen utilization.     

Oxygen delivery and consumption in patients with hyperdynamic septic shock

We analyzed the relationship of increases in oxygen delivery to changes in oxygen consumption in ten patients with hyperdynamic septic shock. Increases in oxygen delivery from 413 +/- 14 (SEM) to 535 +/- 19 ml/min X m2 (p less than .01) were associated with increases in oxygen consumption from 136 +/- 10 to 161 +/- 5 ml/min X m2 (p less than .05). Arterial lactate decreased from 4.6 +/- 1.6 to 2.1 +/- 0.3 mmol/L (p less than .05). These observations suggest that oxygen utilization is perfusion-limited in hyperdynamic septic shock.     

Increases in oxygen extraction during rapidly fatal septic shock in rats

Oxygen utilization was studied in a lethal model of rat peritonitis. Cecal ligation and perforation induced rapidly fatal septic shock in five animals. Five animals served as sham-operated controls. Arterial pressure, cardiac output, arterial blood lactate concentration, and arterial and central venous blood gases were sequentially measured over a period of 3 hours. In septic animals, systemic oxygen extraction increased from 33% +/- 5% to 70% +/- 5% (P less than 0.01) to maintain total body oxygen consumption. However, arterial lactate level increased from 0.5 +/- 0.1 mmol/L to 4.9 +/- 0.5 mmol/L (P less than 0.01) over the same study interval. Cardiac output was correlated with central venous oxygen desaturation (r = 0.66, P less than 0.001). Central venous oxygen saturation was inversely correlated with lactate concentration (r = -0.87, P less than 0.001). These data suggest that cellular oxygen utilization is largely maintained during rapidly fatal septic shock.     

Blood transfusion and oxygen consumption in surgical sepsis

OBJECTIVE: To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption (VO2) in response to increasing oxygen delivery (DO2) after blood transfusion in surgical sepsis. DESIGN: Prospective study. SETTING: Tertiary care, trauma center. PATIENTS: Twenty-one patients, postsurgical or posttrauma, judged septic by defined criteria. INTERVENTIONS: Serum lactic acid concentrations, DO2, and VO2 were measured before and after transfusion therapy. MEASUREMENTS AND MAIN RESULTS: Overall, the DO2 increased from 532 +/- 146 to 634 +/- 225 (SD) mL/min.m2 (p less than .001), and the VO2 increased from 145 +/- 39 to 160 +/- 56 mL/min.m2 (p = .02). These changes occurred with an Hgb increase from 9.3 +/- 1.1 to 10.7 +/- 1.5 g/dL (p less than .001). The patients were grouped by their pretransfusion serum lactic acid values. In those patients with normal (less than 1.6 mmol/dL) serum lactic acid (n = 10), DO2 increased from 560 +/- 113 to 676 +/- 178 mL/min.m2 (p less than .02), and VO2 increased from 150 +/- 25 to 183 +/- 46 mL/min.m2 (p less than .02). However, in the increased serum lactic acid group (n = 17), VO2 was not significantly changed after transfusion (143 +/- 46 to 146 +/- 58 mL/min.m2) despite increased DO2 (515 +/- 163 to 609 +/- 251 mL/min.m2, p less than .01). CONCLUSIONS: Blood transfusion can be used to augment DO2 and VO2 in septic surgical patients. Increased serum lactic acid values do not predict patients who will respond. The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent VO2. Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in VO2 with increasing DO2.     

Local lactate and histamine changes in small bowel circulation measured by microdialysis in pig hemorrhagic shock

Hemorrhagic shock results in inadequate tissue oxygenation. Plasma lactate (L) can characterize the degree of systemic oxygen debt (OD), but gives no information on local changes. The aim of this study was to characterize different degrees of hemorrhagic shock by microdialysis measurement of L and histamine (H) in small bowel circulation. Thirty-eight pigs were randomized to five groups of increasing OD (< 50 --> 120 ml/kg). The OD was accrued by hemorrhage over 60 min and was followed by retransfusion and observation for 3 days. In parallel to plasma probes, subserosa(ss)-, submucosa(sm)-, and intraluminal(il)-L- and H-probes were obtained by small bowel microdialysis every 30 min for 210 min. Ss- and sm-L increased during hemorrhage from 1.2 +/- 0.06 and 1.18 +/- 0.06 to 2.57 +/- 0.15 and 2.96 +/- 0.27 mmol/L. Highest mean L > 3.5mmol/L resulted 90 and 120 min after induction of hemorrhage. Although ss- and sm- levels hardly differed, il-L was significantly decreased with 0.27 +/- 0.02 mmol/L at 0 min and highest mean il-L at 120 min: 2.45 +/- 0.51 mmol/L. Sm-L was significantly increased after 60, 90, 120, and 150 min of highest hemorrhage severity (OD > 100 mL/kg). In parallel, systemic L increased significantly during hemorrhage and correlated well with the severity of shock. Although systemic H increased significantly during hemorrhage (from 1.3 +/- 0.31 to 15.2 +/- 0.67 ng/mL), H-dialysates showed no effect either over time nor with the degree of hemorrhage. In conclusion, microdialysis allows evaluation of local L changes in small bowel circulation in pig hemorrhagic shock. Sm-L levels appear to correlate with the degree of shock. Local H changes were not observed during hemorrhagic shock in this study.     

Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. DESIGN: Prospective, nonrandomized study. SETTING: Operating room in a university hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. METHODS: Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.     

Pulmonary oxygen consumption: a hypothesis to explain the increase in oxygen consumption of low birth weight infants with lung disease

OBJECTIVE: We determined pulmonary oxygen consumption (VO2lung) in low-birthweight infants with acute lung disease to help explain the greater whole-body oxygen consumption (VO2wb) in these infants with than in those without lung disease. METHODS AND MATERIALS: Eleven infants (birth weight 1,076+/-364 g; gestational age 28+/-3 weeks) undergoing mechanical ventilation for respiratory distress syndrome were studied in their first week of life. We measured VO2wb by indirect calorimetry and simultaneously determined systemic oxygen uptake (VO2Fick) as the product of cardiac output (echocardiography) and the arterial-mixed venous oxygen content difference (cooximetry) assuming that VO2wb-VO2Fick accounts for VO2lung. Right atrial blood samples were used to determine mixed venous oxygenation, and infants were excluded if samples returned saturations greater than 89%. RESULTS: VO2lung was 1.92+/-1.74 ml x kg(-1) x min(-1), representing 25% of their VO2wb (7.58+/-1.48 ml x kg(-1) x min(-1)). VO2lung was not correlated with clinical measures of acute disease severity. However, infants with the most severe changes on follow-up radiography (Edwards score 5 as assessed by radiologist blinded for VO2 data) all had a VO2lung level greater than 2.0 ml x kg(-1) x min(-1). CONCLUSION: VO2lung can account for the elevated metabolic rate in low-birthweight infants with lung injury. We speculate that this reflects in part inflammatory pulmonary processes and may herald chronic lung disease.