Arterial Blood Lactate Levels Research Articles

Decreased fluid volume to reduce organ damage: A new approach to burn shock resuscitation? A preliminary study

To evaluate the impact of decreased fluid resuscitation on multiple-organ dysfunction after severe burns. This approach was referred to as "permissive hypovolaemia". Two cohorts of patients with burns>20% BSA without associated injuries and admitted to ICU within 6 h from the thermal injury were compared. Patients were matched for both age and burn severity. The multiple-organ dysfunction score (MODS) by Marshall was calculated for 10 days after ICU admission. Permissive hypovolaemia was administered by a haemodynamic-oriented approach throughout the first 24-h period. Haemodynamic variables, arterial blood lactates and net fluid balance were obtained throughout the first 48 h. Twenty-four patients were enrolled: twelve of them received the Parkland Formula while twelve were resuscitated according to the permissive hypovolaemic approach. Permissive hypovolaemia allowed for less volume infusion (3.2+/-0.7 ml/kg/% burn versus 4.6+/-0.3 ml/kg/% burn; P<0.001), a reduced positive fluid balance (+7.5+/-5.4 l/day versus +12+/-4.7 l/day; P<0.05) and significantly lesser MODS Score values (P=0.003) than the Parkland Formula. Both haemodynamic variables and arterial blood lactate levels were comparable between the patient cohorts throughout the resuscitation period. Permissive hypovolaemia seems safe and well tolerated by burn patients. Moreover, it seems effective in reducing multiple-organ dysfunction as induced by oedema fluid accumulation and inadequate O2 tissue utilization.

The therapeutic effects of fluid resuscitation in severe sepsis and septic shock

To evaluate the therapeutic effect of fluid resuscitation on severe sepsis and septic shock. Twenty patients with severe sepsis and septic shock were given fluid resuscitation and got the following parameters in the ranges as follow: central venous pressure (CVP) 8 - 12 mm Hg (for ventilation patient: 12 - 15 mm Hg), mean artery pressure (MAP) 65 - 90 mm Hg, mixed venous oxygen saturation (SmvO(2)) > 70%. Hemodynamics, tissue perfusion and vascular endothelial cell function were measured and compared before and after fluid resuscitation. Pulmonary arterial wedge pressure (PAWP), cardiac index (CI), left ventricular stroke work index (LVSWI) and systemic vascular resistance index (SVRI) increased significantly after reached the goal of fluid resuscitation (P < 0.01) whereas pulmonary vascular resistance index (PVRI), lactate level in arterial blood and gastric-to-arterial carbon dioxide partial pressure gap (Pg-aCO(2)) decreased significantly (P < 0.01), and the serum levels of endothelin (ET) and von Willebrand factor (vWF) were also decreased significantly after fluid resuscitation (P < 0.05). Early goal-directed fluid resuscitation can improve hemodynamics, tissue perfusion and alleviate vascular endothelial cell injury in patients with severe sepsis and septic shock, it is an effective therapy for these patients.

Terlipressin or norepinephrine in hyperdynamic septic shock: A prospective, randomized study*

To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function. Prospective, randomized, open-label study. Intensive care unit of a university, tertiary, and referral center. Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation. Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured. Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 +/- 17 to 104 +/- 11 beats.min(-1), p < .01) and cardiac index (from 5.1 +/- 1.7 to 4.2 +/- 1.6 L.min(-1).m(-2)) was observed, with no change in stroke volume. Oxygen delivery index (from 784 +/- 131 to 701 +/- 92 mL.min(-1).m(-2)) and consumption index (from 244 +/- 69 to 210 +/- 54 mL.min(-1).m(-2)) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs. In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.

Stable Myocardial Function and Endocrine Dysfunction During Experimental Brain Death

The origin of cardiac impairment during brain death (BD) is controversial. Using a pig experimental model we sought to assess hormonal changes during the first stage of brain death and how these changes contribute to hemodynamic alteration and myocardial dysfunction. Twenty-two pigs were randomized into 2 groups: a control (C) group and a BD group. BD was induced by sub-dural inflation of a balloon catheter. Micromanometers and ultrasonic flow probes were placed on the myocardium to measure cardiovascular parameters. Blood samples and hemodynamic parameters were analyzed before and after induction of BD. A biphasic release of catecholamines was observed, with an initial peak occurring 1 minute after BD induction, followed by a second peak at 60 minutes. Similarly, a biphasic evolution of dP/dt(max) and systolic blood pressure (SBP) was observed at BD, in parallel with catecholamine evolution. In the BD group, both cortisol and aldosterone decreased progressively over time. Circulating triiodothyronine (T3), levothyroxine (T4), prolactin and melatonin concentrations were similar to those of the control group. The difference in arteriovenous (AV) lactate level in arterial and coronary sinus blood was not significantly different between the 2 groups, suggesting an absence of myocardial ischemia. Furthermore, myocardial contractility was not altered during the 3 hours of BD. During the initial period after induction of brain death, cerebral and thyroid hormones remained stable while cortico- and medullo-surrenal hormones varied significantly. We suggest that suprarenal gland impairment is among the first events occurring during brain death. Paradoxically, hemodynamic parameters and myocardial function were not found to be altered.

Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis*

We sought to assess the effects of four different CO2 tensions on systemic oxygenation, oxygen consumption, and arterial blood lactate levels early after bidirectional superior cavopulmonary anastomosis. Prospective study. Quaternary pediatric cardiac critical care unit. Nine children aged 2-23 months (median, 7 months). All patients were sedated, muscle relaxed, and mechanically ventilated. Baseline Paco2 was adjusted to 35 mm Hg by changing tidal volume. CO2 was added via the inlet port of the ventilator to maintain the Paco2 at 45 and 55 mm Hg. Measurements were repeated after discontinuing additional CO2 gas at a Paco2 of 40 mm Hg. Arterial blood gases and lactate were measured at each level of Paco2. We measured oxygen consumption continuously by respiratory mass spectrometry. Mean (95% confidence interval) Paco2 increased from 35 (34-36) to 45 (44-46) to 55 (54-56) mm Hg (4.7 [4.5-4.9] to 6 [5.7-6.3] to 7.3 [7.2-7.4] kPa), arterial pH decreased from 7.43 (7.39-7.47) to 7.35 (7.31-7.39) to 7.28 (7.24-7.32). Pao2 increased from 36 (32-40) to 44 (40-48) to 50 (45-55) mm Hg (4.8 [4.3-5.3] to 5.9 [5.4-6.4] to 6.7 [6.2-7.2] kPa), and oxygen saturation increased from 72% (67-79%) to 77% (73-81%) to 80% (76-84%). Oxygen consumption decreased significantly, with each increase in Paco2, from 146 (125-167) to 132 (112-152) to 126 (107-145) mL.min.m (p = .0001), and lactate decreased from 1.5 (1-2.0) to 1.2 (0.8-1.6) to 0.8 (0.5-1.1) mmol/L (p < .01). These changes returned toward baseline at a Paco2 of 40 mm Hg. Moderate hypercapnia with respiratory acidosis improved arterial oxygenation and reduced oxygen consumption and arterial lactate levels, thus improving overall oxygen transport in children after bidirectional superior cavopulmonary anastomosis.

Contractile Fatigue, Muscle Morphometry, and Blood Lactate in Chronic Obstructive Pulmonary Disease

We hypothesized that patients with chronic obstructive pulmonary disease developing contractile fatigue of the quadriceps during cycle exercise may have characteristic metabolic and muscle features that could increase their susceptibility to fatigue, thus differentiating them from those who do not develop fatigue. We examined, in 32 patients, the fiber-type proportion, enzymatic activities, and capillary density in the vastus lateralis and the arterial blood lactate level during constant work-rate cycling exercise. Contractile fatigue was defined as a postexercise fall in quadriceps twitch force greater than 15% of resting values. Twenty-two patients developed contractile fatigue after exercise. No significant differences were found between fatiguers and non-fatiguers for the endurance time, fiber-type proportion, and oxidative enzyme activities. The lactate dehydrogenase activity was significantly higher (p < 0.05) and muscle capillarization significantly reduced in fatiguers (p < 0.05). Compared with non-fatiguers, the arterial lactate level during exercise was significantly higher in fatiguers (p < 0.001). A significant relationship was found between the fall in quadriceps twitch force and lactate dehydrogenase activity, capillary/fiber ratio, and blood lactate level. We conclude that changes in muscle enzymatic profile and capillarization with a greater reliance on glycolytic metabolism during exercise are associated with contractile fatigue in patients with chronic obstructive pulmonary disease.

Blood Lactate But Not Serum Phosphate Levels Can Predict Patient Outcome in Fulminant Hepatic Failure

Early identification of those patients with fulminant hepatic liver failure (FHF) who need a transplant greatly helps in their management. A number of prognostic criteria have recently been proposed, including arterial blood lactate and serum phosphate concentrations. To validate their use, we retrospectively studied 83 consecutive patients with FHF admitted to our intensive treatment unit between August 2000 and March 2003. A total of 48 patients (58%) survived with medical management only (group I) and 35 patients (42%) failed to survive spontaneously (group II). This group included 19 patients (23%) who underwent orthotopic liver transplantation (LT), and 16 patients (19%) who died without undergoing LT (group IIa). A total of 5 patients (6%) who underwent liver transplantation died. Within paracetamol overdose (POD) and non-POD subgroups, phosphate concentrations were not significantly higher in group II patients (P = 0.08 and P = 0.27, respectively), when compared to group I patients. In multivariate analysis, post admission 12-hour lactate level was the only predictor of survival for the POD subgroup, whereas in non-POD patients, 12-hour lactate and admission bilirubin levels were significant in predicting patients' outcome. In conclusion, we found that while serum phosphate concentrations have limited clinical utility as prognostic markers, persistently elevated arterial blood lactate levels despite adequate fluid resuscitation are indicators of a poor prognosis in FHF.

172 Early Hemodynamic Effect of Patent Ductus Arteriosus in Preterm Infants with Intra-Uterine Growth Restriction of Placental Origin

Background: Significance of patent ductus arteriosus (PDA) is low during the first hours of life because of high pulmonary vascular resistance (PVR). However, clinical symptoms of significant PDA such as systemic hypotension, oliguria, hyperpulsatile pulses… are described early after birth in preterm infants with intra-uterine growth restriction (IUGR) of placental origin. We therefore hypothesized that significant ductal shunting can occur early after birth in IUGR. We compared the hemodynamic effects of PDA between 6 and 10 hours of life in IUGR versus eutrophic preterm infants. Methods: Infants from 24 to 32 weeks of gestational age (GA) admitted to our unit were prospectively studied. Exclusion criteria were: DA closure between 6 and 10 hours of life, premature rupture of membranes > 1 week, malformations, severe respiratory disease (FiO2 30 % and/or need for high frequency oscillatory ventilation), no antenatal corticosteroids, materno-fetal infection, need for vasoactive drugs, non-placental IUGR. The following parameters were assessed using bidimensional and Doppler echocardiography: left atrial aortic root ratio (LA:Ao), mean (mLPA) and telediastolic (tLPA) velocities in the left pulmonary artery, left ventricle shortening fraction (SF), DA diameter, mesenteric resistance index (MRI). Mean arterial blood pressure (MABP) and blood lactate level were also recorded. Results: 30 eutrophic and 19 IUGR infants were included (GA: 28.9±0.4 vs 28.9±0.5 weeks, NS; BW: 1300±60 vs 800±40 g, p<0.05, respectively). MABP, mLPA and SF were similar in both groups. The other parameters were significantly increased in IUGR infants: DA diameter (2.7±0.1 vs 2.1±0.1 mm, p<0.05), LA:Ao (1.5±0.08 vs 1.2±0.06, p<0.05), tLPA (0.23±0.02 vs 0.16±0.01 m/s, p<0.05), MRI (0.86±0.04 vs 0.7±0.02, p<0.05), lactate level (4.7±0.6 vs 3.1±0.3 mmol/l, p<0.05). Conclusion: Our results indicate that significant PDA may occur during the first 10 hrs of life in preterm infants with IUGR of placental origin. The hemodynamic consequences of PDA are higher in IUGR than in eutrophic preterm infants. The data suggest also that poor tolerance of PDA in IUGR infants is not due to an altered ventricular contractility but to a higher shunt flow through the DA. The significance of PDA should be assessed early after birth in IUGR.

Circulatory, respiratory and metabolic changes after thigh tourniquet release in combined epidural-propofol anaesthesia with preservation of spontaneous respiration.

Twelve elderly patients undergoing total knee arthroplasty received lumbar epidural anaesthesia and propofol infusion at 5 mg.kg(-1).h(-1) following a 1.5-2.0 mg.kg(-1) bolus dose with preservation of spontaneous respiration via a laryngeal mask airway. Circulatory, respiratory and metabolic variables were measured before and 1, 3, 5, 15 and 30 min after release of a pneumatic thigh tourniquet. The blood pressure was decreased at all time-points and the respiratory rate increased at 1 min. The P(a)CO(2) was increased only at 1 min. Arterial blood pH and base excess were decreased at 1 and 3 min and 1, 3 and 5 min, respectively. Arterial blood lactate levels were increased at all times. These characteristics were considered to be identical to those under regional anaesthesia with conscious spontaneous respiration, showing that spontaneous respiration under this anaesthetic regimen has a similar respiratory capacity to that of conscious spontaneous respiration.

Effect of the cardioselective ATP-sensitive potassium channel inhibitor HMR 1883 in a porcine model of cardiopulmonary resuscitation

Objective: HMR 1883 (the free acid form of HMR 1098) selectively inactivates myocardial ATP sensitive potassium channels, which may be a potential important therapeutic approach to prevent life-threatening arrhythmias. This study was designed to assess the effects of HMR 1883 combined with adrenaline on haemodynamic variables, blood gases, and cardiac arrhythmias in a porcine cardiac arrest model. Methods: After 8 min of untreated cardiac arrest, followed by 1 min of cardiopulmonary resuscitation (CPR), 12 pigs weighing 30–40 kg were assigned randomly to receive either 45 μg/kg adrenaline alone ( n=6), or 45 μg/kg adrenaline combined with 3 mg/kg HMR 1883 ( n=6), followed by up to three defibrillation attempts 2 min later. Five minutes after return of spontaneous circulation, cardiac arrest was induced for 1 min, with the CPR protocol following as described above. All animals subsequently underwent four cardiac arrest intervals of 1, 2, 3, and 4 min duration which were separated by four episodes of 5 min of return of spontaneous circulation. Results: Haemodynamic variables, cardiac arrhythmias in the acute resuscitation phase between termination of chest compressions and return of spontaneous circulation, and after return of spontaneous circulation in both groups were comparable throughout the experiment. Survival rates throughout the experiment were comparable between groups. Arterial blood gases, electrolyte, glucose, and lactate levels in both groups during the experiment indicated comparable severe metabolic acidosis, with increasing levels after each episode of simulated refibrillation, and subsequent return of spontaneous circulation. Conclusion: Combining HMR 1883 with adrenaline during CPR resulted in comparable haemodynamic variables, return of spontaneous circulation rates, cardiac arrhythmias, lactate and glucose levels compared with adrenaline alone. This indicates that injection of HMR 1883 was safe under these conditions.

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy

Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Oxygen consumption after cardiopulmonary bypass surgery in children: Determinants and implications

Objective: We sought to assess oxygen consumption and its determinants in children shortly after undergoing cardiopulmonary bypass operations. Methods: Twenty children, aged 2 months to 15 years (median, 3.75 years), undergoing hypothermic cardiopulmonary bypass operations were studied during the first 4 hours after arrival in the intensive care unit. Central and peripheral temperatures were monitored. Oxygen consumption was continuously measured by using respiratory mass spectrometry. Oxygen delivery was calculated from oxygen consumption and arterial and mixed venous oxygen contents, which were sampled every 30 minutes. Oxygen extraction was derived by the ratio of oxygen consumption and oxygen delivery. Arterial blood lactate levels were measured every 30 minutes. Results: There was a correlation between oxygen consumption and age in patients older than 3 months (r = –0.76). Mean oxygen consumption increased by 14.7% during the study. The increase in oxygen consumption was correlated with the increase in central temperature (r = 0.73). Nine patients had an arterial lactate level above 2 mmol/L on arrival. There were no significant differences in oxygen consumption, oxygen delivery, and oxygen extraction between the group with lactate levels between 2 and 3 mmol/L and the groups with normal lactate levels both on arrival and at 2 hours. One patient with a peak lactate level of 6.8 mmol/L had initially low oxygen delivery (241.3 mL · min–1 · m–2). Conclusions: During the early hours after a pediatric cardiac operation, the increase in oxygen consumption is mainly attributed to the increase in central temperature. Oxygen consumption is negatively related to age. Mild lactatemia is common and does not appear to reflect oxygen delivery or oxygen consumption or a more complicated recovery. (J Thorac Cardiovasc Surg 2000;119:525-33)

Arterial Blood Lactate Level and pH as a Predictor of Outcome in Very Low Birth Weight Babies

Arterial Blood Lactate Level and pH as a Predictor of Outcome in Very Low Birth Weight Babies

Lactate in scalp and cord blood from fetuses with ominous fetal heart rate patterns

Objective: We investigated lactate concentrations in fetal scalp and cord blood to determine the sources of fetal lactacidosis in fetuses with ominous heart rate patterns. Methods: Cord blood was collected from newly delivered infants who had been monitored by fetal scalp blood sampling during labor. In 250 cases umbilical arterial and venous cord blood lactate levels were measured. We assessed the umbilical arterial lactate concentrations in relation to the venous lactate levels, the arterial pH level, base excess, and arteriovenous lactate differences in cord blood. In 103 cases the levels of lactate in fetal scalp blood, sampled within 60 minutes of delivery, were compared with those in the umbilical artery and vein and the pH level and base excess immediately after birth. Results: Lactate level in the umbilical artery showed a significant correlation to that in umbilical venous blood ( r = .84, P < .001), to arteriovenous lactate differences ( r = .52, P < .001), as well as to pH ( r = −.55, P < .001) and base excess ( r = −.63, P < .001) in arterial cord blood. Lactate concentrations in fetal scalp blood shortly before delivery showed a significant correlation to lactate levels in the umbilical arterial ( r = .65, P < .001) and venous blood ( r = .62, P < .001). Conclusion: The study indicates a close correlation between lactate levels in arterial and venous cord blood, as well as between the lactate levels and pH and base excess in cord arterial blood in patients with ominous fetal heart rate patterns. We also found an increased fetal contribution with increasing lactacidemia. Lactate concentrations in fetal scalp blood correlated well with those in cord arterial and venous blood.

Lactate in Scalp and Cord Blood From Fetuses With Ominous Fetal Heart Rate Patterns

In Brief Objective We investigated lactate concentrations in fetal scalp and cord blood to determine the sources of fetal lactacidosis in fetuses with ominous heart rate patterns. Methods Cord blood was collected from newly delivered infants who had been monitored by fetal scalp blood sampling during labor. In 250 cases umbilical arterial and venous cord blood lactate levels were measured. We assessed the umbilical arterial lactate concentrations in relation to the venous lactate levels, the arterial pH level, base excess, and arteriovenous lactate differences in cord blood. In 103 cases the levels of lactate in fetal scalp blood, sampled within 60 minutes of delivery, were compared with those in the umbilical artery and vein and the pH level and base excess immediately after birth. Results Lactate level in the umbilical artery showed a significant correlation to that in umbilical venous blood (r = .84, P < .001), to arteriovenous lactate differences (r = .52, P < .001), as well as to pH (r = −.55, P < .001) and base excess (r = −.63, P < .001) in arterial cord blood. Lactate concentrations in fetal scalp blood shortly before delivery showed a significant correlation to lactate levels in the umbilical arterial (r = .65, P < .001) and venous blood (r = .62, P < .001). Conclusion The study indicates a close correlation between lactate levels in arterial and venous cord blood, as well as between the lactate levels and pH and base excess in cord arterial blood in patients with ominous fetal heart rate patterns. We also found an increased fetal contribution with increasing lactacidemia. Lactate concentrations in fetal scalp blood correlated well with those in cord arterial and venous blood. During labor with fetal distress, lactate levels in scalp blood obtained shortly before delivery are correlated with those in cord blood.

Evaluation of a New Portable System for Cord Lactate Determination

To evaluate a new reflectance photometer (Accusport^®) for blood lactate determination, a prospective non-interventional study was performed on blood obtained from the umbilical cord artery immediately after delivery of the baby in 109 consecutive women. For each sample, the results of cord arterial blood lactate values measured with the reflectance photometer were compared with those obtained using a reference method in the laboratory. The values obtained using Accusport were comparable in accuracy with those obtained using a laboratory reference method (Ektachem 9501RC). The instrument provides a simple and reliable method for determining cord arterial blood lactate levels in a small blood sample.

Effects of altered F iO 2 on maximum V̇ O 2 in the horse

Although the horse is considered an elite athlete with a specific V̇ O 2max some 2–4 times higher than man, maximal O 2 transport is compromised both by moderately severe arterial desaturation and by failure to extract all O 2 from blood perfusing exercising muscle. This prompted the present study to ascertain whether correction of arterial desaturation would proportionally augment V̇ O 2max and, if so, would O 2 extraction behave in a manner predicted by diffusional transport limitation. Six two year old throughbreds were exercised to V̇ O 2max on a treadmill each on three separate occasions breathing gases of F i O 2 = 0.15, 0.21 and 0.35, each used once in balanced order. V̇ O 2 , ventilation, arterial and pulmonary arterial blood gases, pressures and lactate levels were measured both submaximally and maximally at each F i O 2 and cardiac output was computed by mass balance for O 2. At F i O 2 = 0.21, V̇ O 2max = 143.9 ± 4.8 ml kg −1 min −1, arterial saturation (Sa O 2 ) was 81.6 ± 3.3% while venous P O 2 (P v O 2 ) was 15.3 ± 1.4 Torr. At F i O 2 = 0.35, V̇ O 2max was 172.6 ± 8.2 ml kg −1 min −1, Sa O 2 reached 97.4 ± 0.4% and P v O 2 was 23.4 ± 0.7 Torr. V̇ O 2max at F i O 2 = 0.15 was 109.8 ± 4.1 ml kg −1 min −1, Sa O 2 fell to 68.1 ± 2.5% and P v O 2 was 10.6 ± 1.0 Torr, all changes being significant, p < 0.01. As F i O 2 was varied, V̇ O 2max changed proportionally to calculated mean capillary P O 2 as well as to total O 2 delivery. These data confirm substantial O 2 supply dependence of V̇ O 2max in the horse, and in such a manner as to be consistent with the hypothesis of combined diffusive and convective transport limitation within muscle.

Transvisceral Lactate Fluxes During Early Endotoxemia

The pathogenesis of hyperlacticemia during sepsis is poorly understood. We investigated the role of lung, kidney, gut, liver, and muscle in endogenous lactate uptake and release during early endotoxemia in an intact, pentobarbital-anesthetized dog model (n = 14). Ultrasonic flow probes were placed around the portal vein and hepatic, renal, and femoral arteries. After splenectomy, catheters were inserted into the pulmonary artery, aorta, and hepatic, left renal, and femoral veins. Whole blood lactate and blood gases from all catheters, organ flows, and cardiac output were measured before and 30 to 45 min after a bolus infusion of Eacherichia coli endotoxin (1 mg/kg). After endotoxin infusion, mean arterial blood lactate level increased from 0.92 +/- 0.11 to 1.60 +/- 0.15 mmol/L (p < 0.0001). Lung lactate flux changed from uptake to release of lactate adding a mean of 9.97 +/- 16.23 mmol/h (p < 0.05) to the systemic circulation. Liver and muscle lactate fluxes remained neutral at all times, while kidney and gut took up lactate from the circulation both before and after endotoxin infusion (mean renal uptake, 2.73 +/- 3.85 mmol/L; p < 0.001; mean gut uptake, 2.46 +/- 2.31 mmol/h; p < 0.002). Except for the kidney, where a decrease in blood flow correlated with diminished uptake, there was no correlation between changes in transvisceral lactate fluxes and organ or systemic oxygen delivery during endotoxemia. A positive correlation between lactate uptake and oxygen consumption during endotoxemia was seen for both gut (p < 0.0001) and kidney (p < 0.002). We conclude that, in the dog, the pathogenesis of endotoxin-induced hyperlacticemia is complex. The lung may be responsible for significant lactate release, and other viscera that normally take up lactate are unable to adequately clear this increased lactate.

Correlation of serial blood lactate levels to organ failure and mortality after trauma

To define the value of serial measurements of blood lactate levels after trauma, the present study investigated the correlation between blood lactate, mortality, and organ failure in 129 trauma patients, including 100 intensive care unit (ICU) survivors and 29 ICU fatalities. On admission, injury severity score (ISS) was higher and Glasgow coma score (GCS), revised trauma score (RTS), and trauma revised ISS (TRISS) were lower in the nonsurvivors than in the survivors. Serial arterial blood lactate levels were measured on admission and at least three times a day until normalization. Both initial lactate and highest lactate levels were higher in the nonsurvivors than in the survivors. Organ failure developed in 84 (65%) of the 129 patients. Patients with organ failure had significantly lower RTS and TRISS. Initial lactate and highest lactate levels were significantly higher in patients with organ failure than without organ failure (3.4 [0.7 to 12.7] versus 2.4 [0.4 to 7.6] mEq/L and 4.1 [0.7 to 12.7] versus 2.8 [0.4 to 8.9] mEq/L, respectively, both P < .01). The duration of hyperlactatemia averaged 2.2 days in the former but 1.0 day in the latter patients ( P < .01). The data therefore indicate that not only the initial or the highest lactate value but also the duration of hyperlactatemia can be correlated with the development of organ failure. These observations stress the importance of the initial resuscitation in the prevention of organ failure. Serial blood lactate measurements are reliable indicators of morbidity and mortality after trauma.

Effects of platelet-activating factor antagonist on preservation/reperfusion injury of the graft in porcine orthotopic liver transplantation.

To investigate the role of platelet-activating factor (PAF) in the preservation/reperfusion injury of the liver graft, the effect of treatment with a potent PAF antagonist (E5880) was evaluated in a pig orthotopic liver transplantation model. The graft liver was flushed out and preserved for 8 hr at 4 degrees C using a simplified University of Wisconsin solution. The PAF antagonist was administered into the University of Wisconsin solution (1 mg/L), into the rinsing solution (1 mg/L), and to a recipient pig (0.3 mg/kg d.i.v.) in group 1. The PAF antagonist was not given in the control group (group 2). Postoperative survival of more than 12 hr was 100% (9/9) in group 1 and 56% (5/9) in group 2 (P < 0.05). At 12 hr after reperfusion of the graft (RPF), the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate) increased to 1.54 +/- 0.15 (mean +/- SEM) in group 1, compared with 0.95 +/- 0.09 (P < 0.05) in group 2. In group 2, blood leukocyte count decreased to 8.3 +/- 0.9 (x 10(3)/microliters) at 2 hr after RPF, in contrast to a slight increase in group 1 (14.3 +/- 1.8 x 10(3)/microliter, P < 0.01). At 4 hr after RPF, glutamic oxaloacetic transaminase (461 +/- 59 vs. 712 +/- 97 U/L, P < 0.05), glutamic pyruvic transaminase (65 +/- 4 vs. 82 +/- 5 U/L, P < 0.05), and the lactate level (6.2 +/- 1.1 vs. 9.4 +/- 1.0 mmol/L, P < 0.05) in arterial blood were significantly lower in group 1 than in group 2. Light and electron microscopic study at 1 hr after RPF showed neutrophil sludging in the sinusoids and sinusoidal endothelial cell damage in group 2, while these findings were attenuated in group 1. It is suggested that PAF plays a key role in microcirculatory disturbance of the liver graft manifested on reperfusion, and that the treatment with E5880 has a protective effect against preservation/reperfusion injury of the graft in liver transplantation.