Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia

OBJECTIVE: Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a university laboratory. SUBJECTS: Eight adult Landrace/Yorkshire pigs. INTERVENTIONS: The microdialysis probe was inserted in the brain along with a multiparameter sensor and intracranial pressure (ICP) probe. The animals were ventilated in a pressure-controlled mode according to the open lung concept with an inspired oxygen fraction of 0.4/1.0. Starting at normoventilation (PaCO(2) +/-40 mmHg) two steps of both hypercapnia (PCO(2) +/- 70 and 100 mmHg) and hypocapnia (PaCO(2) +/- 20 and 30 mmHg) were performed. Under these conditions, brain glucose and lactate levels as well as brain oxygen (PbrO(2)), brain carbon dioxide (PbrCO(2)), brain pH (brpH), brain temperature and ICP were measured. RESULTS: At hypercapnia (PaCO(2) = 102.7 mmHg) there were no significant changes in brain glucose and lactate but there was a significant increase in PbrCO(2), PbrO(2) and ICP. In contrast, at hypocapnia (PCO(2) = 19.8 mmHg) there was a significant increase in brain lactate and a significant decrease in both brain glucose and PbrCO(2). CONCLUSIONS: Hypocapnia decreases brain glucose and increases brain lactate concentration, indicating anaerobic metabolism, whereas hypercapnia has no influence on levels of brain glucose and brain lactate.     

Diagnostic efficiency of four lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction

We compared the diagnostic efficacy of the ratios LD-1/LD-2, LD-1/LD-3, LD-1/LD-4, and LD-1/LD-5 in 69 documented cases of myocardial infarction. We used 149 patients with congestive heart failure and 67 patients with nonmyocardial infarct as controls. We used a computer program to produce receiver-operating characteristic curves, decision threshold plots, and likelihood ratios for these LD ratios at 6-h intervals up to 108 h after the onset of chest pain or hospital admission. All ratios in the myocardial infarction cases peaked around 36 h after the onset of chest pain, while those for the nonmyocardial and congestive cardiac failure cases did not change over the 108-h period. In all patients with infarctions, LD-1/LD-4 and LD-1/LD-5 increased by 1.7 times (when LD-1 was less than 40%) and 3.4 times (when LD-1 was greater than 40%), respectively, over control values. Optimum decision threshold values were obtained at 13-24 h (LD-1/LD-5), 31-36 h (LD-1/LD-4 and LD-1/LD-3), and 55-60 h (LD-1/LD-2) after onset of symptoms. The highest likelihood ratio was obtained with the LD-1/LD-4 ratio; therefore, we suggest that this is a better diagnostic test for myocardial infarction than LD-1/LD-2.     

Time-related changes in the diagnostic utility of total lactate dehydrogenase, lactate dehydrogenase isoenzyme-1, and two lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction

Using receiver-operating characteristic (ROC) curve and likelihood ratio analysis, we examined the diagnostic utility of total lactate dehydrogenase (LD; EC 1.1.1.27) activity (I). LD isoenzyme-1 activity (II), and the LD-1 percentage of total LD activity (III), LD-1 LD-2 (IV), and LD-1/LD-4 (V) in 347 persons admitted to the Cardiac Care Unit (of whom 173 were subsequently proven to have had myocardial infarction). Blood was sampled from these subjects at about 6-h intervals for up to 96 h from the onset of chest pain. Defining an "effective" test as one having an area under the ROC curve of greater than or equal to 0.9, we determined the ranked utility (greatest to least) of these tests as V = IV greater than III greater than II greater than I. Tests III, IV, and V had by this criterion, diagnostic effectiveness equivalent to measurements of creatine kinase-2 in serum but in samples obtained at later time intervals. The decision thresholds for both high (constant) test sensitivity and specificity varied with time, to differing extents, over the entire 96-h period, a finding with important diagnostic implications. We document positive and negative likelihood ratio values for each of these tests throughout the entire period of study.     

Cooling and Comfort: The COMFORTNeo-scale during therapeutic hypothermia after perinatal asphyxia

The therapeutic effect of moderate hypothermia in infants with HIE after perinatal asphyxia can be counteracted by stress which should therefore be minimized.Objectiveof study was to gain insight in the COMFORTNeo-scale to measure stress during therapeutic hypothermia. Stress was measured prospectively by means of the COMFORTNeo-scale (CNS), twice a day, during hypothermia-, rewarming- and stabilization phase in a cohort of 133 neonates with perinatal asphyxia who participated in the PharmaCool study.A total of 994 CNS scores were collected; median score CNS 9 (IQR 7–11). Despite analgesic, sedative and anticonvulsant drugs 10% of the scores indicated moderate to severe stress during treatment. The use of these drugs as well as mechanical ventilation interfered with CNS score (respectively odds ratio 0.74 and 0.61) Interference of aEEG, hypothermia phase and gender were not confirmed.The COMFORTNeo-scale can, with the necessary caution, be used for the assessment of stress during therapeutic hypothermia treatment. Other options should be explored.     

Serum lactate dehydrogenase activity ratios with different substrates.

1. The lactate dehydrogenase activity of 89 sera from patients suffering myocardial infarction and of 55 sera from patients with hepatocellular damage was assayed under optimal conditions using pyruvate, alpha-oxobutyrate, hydroxypyruvate and glyoxylate as substrates. Activity was also measured with lactate as substrate at different pH values. 2. The ratios of activities under these different assay conditions were calculated for both series of patients. Correct differentiations for single ratios ranged from virtually nil for hydroxypyruvate/alpha-oxobutyrate to is greater than 93 per cent for glyoxylate/hydroxypyruvate and glyoxylate/alpha-oxobutyrate. This was little improved by the use of multiple ratios involving up to seven separate assays. 3. The activity ratio of hydroxypyruvate to pyruvate which is consistently greater than unity was found to be inverted in a case of morphine poisoning.     

LD1 and several ratios of lactate dehydrogenase isoenzymes in acute myocardial infarction

The sensitivity and specificity of three parameters--ECG, creatine kinase MB isoenzyme and LD isoenzymes--were compared in 385 consecutive patients hospitalized for clinically suspected acute myocardial infarction (MI). In 147 patients acute MI was diagnosed on the basis of three parameters. In the remaining 238 patients acute MI was ruled out. Decision values for LD1, LD1/total LD, LD1/(LD2 + LD3 + LD4 + LD5), and the sum of LD1/LD2 + LD1/total LD + LD1/LD2 + LD3 + LD4 + LD5) were selected as 70 U/L, 0.33, 0.5, and 1.79, respectively for the test positivity of LD isoenzymes for acute MI. These new criteria, with the decision values, are proposed as test positivity of CK-MB and LD isoenzymes for acute myocardial infarction.     

Brain lactate during partial global ischemia and reperfusion: effect of pretreatment with dichloroacetate in a rat model

Elevated cerebral lactate levels following cerebral ischemia have been associated with brain cell damage and death. We previously found that pre- or postischemia treatment with dichloroacetate (DCA), presumably by its activation of brain pyruvate dehydrogenase, effectively lowers cerebral lactate levels in rats subjected to 30 minutes of partial global ischemia (PGI) followed by 30 minutes of recirculation. The goal of the present study was to determine the effects of preischemia DCA treatment on cortical lactate levels during the ischemia period or during early recirculation. Rats (four in each group) received preischemia treatment with DCA and were then subjected to 0, 10, or 30 minutes of PGI or 30 minutes of PGI followed by 15 minutes of recirculation. Cortical lactate levels in pretreated animals were not significantly different from lactate levels of untreated rats at any time during PGI, but were significantly lower than levels in untreated rats at 15 minutes of recirculation (P less than .05, ANOVA). These results suggest that preischemia treatment with DCA does not limit the accumulation of cortical lactate during PGI but may promote its clearance during recirculation following PGI. If reperfusion events influence the degree of brain cell injury, DCA may enhance cell recovery by lower cortical lactate levels in the reperfusion period.     

Splanchnic and peripheral glucose and lactate metabolism during and after prolonged arm exercise.

Splanchnic and peripheral exchange of glucose and gluconeogenic substrates was examined in 12 healthy subjects during 2 h of arm or leg exercise on a bicycle ergometer and during a 40-min postexercise recovery period. The work intensity corresponded to 30% of the maximal pulmonary oxygen uptake. The regional exchange of substrates was evaluated using catheter technique and indicator dilution methods for blood flow measurements. Our findings indicate that prolonged arm exercise as compared with exercise with the legs results in a greater increase in heart rate (25-40%) and a more marked reduction in splanchnic blood flow (10-30%) as well as higher arterial concentrations of lactate, free fatty acids, and catecholamines. The respiratory exchange ratio was consistently higher with arm exercise. In addition, arm exercise results in a greater fractional extraction and utilization of glucose by exercising muscle as well as a greater hepatic gluconeogenesis from lactate and glycerol. During recovery from prolonged arm exercise, leg muscle becomes an important site of lactate release to the splanchnic bed, despite a lack of net glucose uptake by the leg. Simultaneously, arm muscle shows an increase in glucose uptake in the absence of a net release of lactate. These coincident but discordant processes in the leg and arm during recovery suggest the occurrence of a redistribution of muscle glycogen from previously resting (leg) muscle to previously exercising (arm) muscle.     

8例颈椎前路术后康复期患者进食中窒息的原因分析及对策

报告了8例颈椎前路术后康复期患者进食期间发生窒息的原因与护理对策。认为主要原因为疾病因素、手术因素、心理因素、食物因素、机体及环境因素、知识缺乏等。提出了相应的护理对策:①术前必须进行气管、食管推移训练。②必须重视进食指导,包括术前进行卧位进食训练,根据术后不同阶段选择合适的食物和方法。③完善健康教育的内容,采用口头指导与图片相结合的方式进行防止进食窒息的教育。④加强对护理人员进行窒息急救的技能培训。     

Esophageal capnometry during hemorrhagic shock and after resuscitation in rats

Background  

Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO ₂) and arterial partial carbon dioxide tension (PaCO ₂) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor.     

腺苷对窒息大鼠复苏及心肌微循环的影响

目的观察腺苷在窒息大鼠心肺复苏中对复苏成功率和心肌微循环的影响。方法采用窒息法制作大鼠窒息模型,将实验动物随机分为对照组(A组)、肾上腺素组(B组)和肾上腺素合并腺苷组(C组)。持续窒息3 min后,行胸外心脏按压,呼吸机辅助呼吸,4 min后静脉给药。A组(n=15)不用复苏药物;B组(n=14)静脉注射肾上腺素90μg·kg~(-1);C组(n=14)静脉注射肾上腺素90μg·kg~(-1)并持续静滴腺苷70μg·kg~(-1)·min~(-1)至复苏结束。观察自主循环恢复率、复苏成功率和心肌微循环。结果C组自主循环恢复率(92．9%)和复苏成功率(64．3%)＞B组(78．6%,50%)＞A组(60%,20%);C组心肌毛细血管数目和面积好于A组和B组。结论心肺复苏时肾上腺素合并腺苷可能会减轻肾上腺素部分负作用,改善大鼠心肌微循环,提高复苏成功率。     

Clinical value of triage lactate in risk stratifying trauma patients using interval likelihood ratios

Emergency physicians face the challenge of rapidly identifying high-risk trauma patients. Lactate (LAC) is widely used as a surrogate of tissue hypoperfusion. However, clinically important values for LAC as a predictor of mortality are not well defined. Objectives: 1. To assess the value of triage LAC in predicting mortality after trauma. 2. To compute interval likelihood ratios (LR) for LAC.

Brain metabolism in uremic and adenosine-infused rats

Analyses of nucleotides and glycolytic intermediates were performed on perchlorate extracts of blood and quick-frozen brain from rats nephrectomized 48 hr previously, and from rats infused for 6 hr with adenosine or AMP. Blood nucleotides of acutely uremic rats were normal. Uremic brain showed an increase of creatine phosphate (CP), ATP, and glucose with a corresponding decrease in creatine, ADP, AMP, and lactate. Other nucleotide triphosphates were increased, but total adenine nucleotide in brain was unchanged. Uremic brain failed to use ATP or produce ADP, AMP, and lactate at normal rates when subjected to the stress of ischemic anoxia. Although levels of cation responsive ATPase in extracts of uremic brain were normal, the inhibition of glycolysis in the intact brain appeared to be due to a failure of ATP hydrolysis (a diminished ATPase activity). Adenosine infusion produced mild azotemia, marked hyperglycemia, an increase in blood ATP, and an increase in total blood adenine nucleotide. Brain from rats infused with adenosine or AMP also had high levels of ATP, creatine phosphate, and glucose, whereas levels of ADP, AMP, and lactate were low. However these brains responded with normal use of ATP and normal production of lactate when stimulated by ischemic anoxia.     

Association between brain tissue pH and brain injury during asphyxia in piglets

BACKGROUND: Acidosis may contribute to brain injury from asphyxia, but its role is unclear. In order to evaluate the association between brain acidosis and cerebral injury, we subjected piglets to hypoxia and hypotension (HYP-HOTN) or hypoxia alone (HYP) to inflict varying amounts of brain damage. We hypothesized that piglets with a more severe brain injury would have a lower brain pH. METHODS: Piglets had a pH microprobe inserted into the cerebral cortex. HYP animals breathed 5-8% O(2)/7% CO(2) for 30 min with mean arterial pressure (MAP) maintained at >40 mmHg. HYP-HOTN animals breathed the same gas for 30 min, but during the last 15 min, MAP was reduced to 25-30 mmHg by withdrawing blood. After 4 h of recovery, the animals were perfusion-fixed and pathology assessed. Somatosensory-evoked potentials (SEP) were also monitored. RESULTS: HYP-HOTN piglets had more neuropathology than HYP animals. During the last 15 min of injury, brain pH in the HYP-HOTN group was significantly higher than that in HYP. However, recovery of brain pH was prolonged in the HYP-HOTN animals. The amount of time for brain pH to recover to > or =7.00 correlated very well with both the degree of neuropathology and SEP recovery. The reduction in brain pH, either absolute or relative to baseline, was not associated with the severity of damage. CONCLUSIONS: The time needed for brain pH to recover after asphyxia, but not its severity, was associated with the amount of brain injury. Further study is warranted to determine whether immediate restoration of brain pH will reduce brain damage.     

Effects of albumin and Ringer's lactate on production of lung cytokines and hydrogen peroxide after resuscitated hemorrhage and endotoxemia in rats

RATIONALE AND HYPOTHESIS: Acute lung injury is a frequent complication of severe sepsis or blood loss and is often associated with an excessive inflammatory response requiring mechanical ventilation. We tested the hypothesis that the types of fluids used during early resuscitation have an important effect on the evolution of lung injury. METHODS: Rats were subjected to either hemorrhage or endotoxemia for 1 hr, followed by resuscitation to a controlled mean blood pressure with Ringer's lactate, 5% albumin, or 25% albumin for 1 hr. After resuscitation, blood cytokine levels were measured. The lung was then excised and ventilated with a tidal volume of 30 mL/kg for 2 hrs. RESULTS: The volume of fluids required was significantly smaller in the albumin-treated groups than in the Ringer's lactate groups. In the hemorrhagic shock model, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2 were significantly lower and interleukin-10 was significantly higher in the albumin-treated groups compared with the Ringer's lactate-treated group. The levels of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were lower and interleukin-10 was higher in the albumin-treated groups than in the Ringer's lactate group. The decreased cytokine production was associated with a reduction of hydrogen peroxide formation with albumin resuscitation. The lung wet/dry ratio was lower in the 5% albumin (0.54 +/- 0.01) and 25% albumin (0.55 +/- 0.02) groups than in the Ringer's lactate group (0.62 +/- 0.02; both p <.05). These effects of albumin seen in the hemorrhagic shock model were not observed in the endotoxic shock model. CONCLUSIONS: We conclude that resuscitation with albumin may have utility in reducing ventilator-induced lung injury after hemorrhagic shock, but not after endotoxic shock. These findings suggest that the mechanisms leading to ventilator-induced lung injury after hemorrhage differ from those after endotoxemia.     

纯氧与空气复苏对窒息新生大鼠心肌细胞凋亡及BCL-2,BAX蛋白表达的影响

目的：在建立新生大鼠窒息的动物模型基础上。比较纯氧与空气复苏对窒息新生大鼠心肌细胞凋亡及Bcl-2、Bax蛋白表达的影响。方法：采用SD新生大鼠建立窒息模型2．5h，并分组进行纯氧与空气复苏。实验分为正常对照组、纯氧复苏组（PO组）和空气复苏组（RA组），均在复苏后24h和72h取心肌组织，制成石蜡切片，HE染色光镜观察心肌组织病理变化，TUNEL法测定心肌细胞凋亡指数，免疫组织化学S-P法检测心肌组织Bcl-2、Bax蛋白的表达情况。结果：HE染色光镜观察，与正常对照组相比，PO组可见大部分心肌纤维肿胀，有少许断裂，心肌间质及小静脉明显淤血，RA组心肌纤维则表现明显的片状或灶性坏死。RA组心肌细胞凋亡指数明显高于PO组，且以24h升高最显著。PO组凋亡抑制基因Bcl-2表达高于RA组，RA组促凋亡基因Bax明显高于PO组。结论：空气复苏较纯氧复苏后心肌细胞凋亡更严重，且以复苏后24h最明显，空气复苏促进Bax基因的表达上调，纯氧复苏可使凋亡抑制基因Bcl-2表达上调，提示高浓度氧对窒息复苏后心肌有一定的保护作用     

Evolution of lactate/pyruvate and arterial ketone body ratios in the early course of catecholamine-treated septic shock

OBJECTIVES: To measure arterial lactate/pyruvate (L/P) and arterial ketone body ratios as reflection of cytoplasmic and mitochondrial redox state at different stages of catecholamine-treated septic shock and compare them with normal and pathologic values obtained in patients in shock who have decreased oxygen transport (cardiogenic shock), and to assess the relationship between the time course of lactate, L/P ratio, and mortality in septic shock. DESIGN: Prospective, observational human study. SETTING: A university intensive care unit. PATIENTS: Sixty consecutive adult patients who developed septic shock and lactic acidosis requiring the administration of vasopressors. Twenty patients in the intensive care unit without shock, sepsis, and hypoxia and with normal lactate values and 10 patients with cardiogenic shock were also studied. MEASUREMENTS: Hemodynamic measurements, arterial and mixed venous blood gases, arterial lactate and pyruvate concentrations, and arterial ketone body ratio were measured within 4 hrs after the introduction of catecholamine and 24 hrs later. MAIN RESULTS: Fifteen patients (25%) died within the first 24 hrs of septic shock, and these early fatalities had a higher blood lactate (12.2+/-3 versus 4.6+/-1.3 mmol/L; p<.01) concentration and a higher L/P ratio (37+/-4 versus 20+/-1; p<.01) than those who died later. No difference was found for arterial ketone body ratio (0.41+/-0.1 versus 0.50+/-0.06). Forty-five patients survived >24 hrs including 25 survivors and 20 nonsurvivors. Although there was no difference between survivors and nonsurvivors in initial lactate concentration (4.1+/-0.4 and 4.6+/-0.3, respectively), L/P ratio (19+/-1 and 20+/-1, respectively), and arterial ketone body ratio (0.5+/-0.06 and 0.52+/-0.07, respectively), blood lactate and L/P ratio significantly decreased during the first 24 hrs in the survivors (2.8+/-0.4 and 14+/-1, respectively; p<.05). and were stable in the nonsurvivors (4+/-0.3 and 22+/-1, respectively) Although returning to normal values after 24 hrs in survivors and nonsurvivors, arterial ketone body ratio was higher in survivors (1.72+/-0.17 versus 1.09+/-0.15; p<.05). Lactate and L/P ratio were closely correlated (r2 = .8, p<.0001). In the cardiogenic shock group, lactate concentration was 4+/-1 mmol/L, L/P ratio was 40+/-6, and arterial ketone body ratio was 0.2+/-0.05. The mortality rate was 60%. CONCLUSIONS: The main result of the present study is that hemodynamically unstable patients with sepsis needing catecholamine therapy had a lactic acidosis with an elevated L/P ratio and a decreased arterial ketone body ratio, suggesting a decrease in cytoplasmic and mitochondrial redox state. The duration of lactic acidosis is associated with the development of multiple organ failure and death.