[Hyperchloremic metabolic acidosis during plasma volume replacement].
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Acidosis↗
Biomedical subjects
C Ichai
Publications and source records attributed to C Ichai.
Glucose 6-phosphate hydrolysis is activated by glucagon in a low temperature-sensitive manner.
Glucagon affects liver glucose metabolism mainly by activating glycogen breakdown and by inhibiting pyruvate kinase, whereas a possible effect on glucose-6-phosphatase has also been suggested. Although such a target is of physiological importance for liver glucose production it was never proven. By using a model of liver cells, perifused with dihydroxyacetone, we show here that the acute stimulation of gluconeogenesis by glucagon (10(-7) m) was not related to the significant inhibition of pyruvate kinase but to a dramatic activation of the hydrolysis of glucose 6-phosphate. We failed to find an acute change in glucose-6-phosphatase activity by glucagon, but the increase in glucose 6-phosphate hydrolysis was abolished at 21 degrees C; conversely the effect on pyruvate kinase was not affected by temperature. The activation of glucose 6-phosphate hydrolysis by glucagon was confirmed in vivo, in postabsorptive rats receiving a constant infusion of glucagon, by the combination of a 2-fold increase in hepatic glucose production and a 60% decrease in liver glucose 6-phosphate concentration. Besides the description of a novel effect of glucagon on glucose 6-phosphate hydrolysis by a temperature-sensitive mechanism, this finding could represent an important breakthrough in the understanding of type II diabetes, because glucose 6-phosphate is proposed to be a key molecule in the transcriptional effect of glucose.
Allosteric Site↗
Exogenous Mg-ATP induces a large inhibition of pyruvate kinase in intact rat hepatocytes.
Mg-ATP infusion in vivo has been reported to be beneficial both to organ function and survival rate in various models of shock. Moreover, a large variety of metabolic effects has been shown to occur in several tissues due to purinergic receptor activation. In the present work we studied the effects of exogenous Mg-ATP in rat liver cells perifused with dihydroxyacetone to investigate simultaneously gluconeogenetic and glycolytic pathways. We found a significant effect on oxidative phosphorylation as characterized by a decrease in oxygen consumption rate and in the cellular ATP-to-ADP ratio associated with an increase in lactate-to-pyruvate ratio. In addition, exogenous Mg-ATP induced rapid and reversible inhibition of both gluconeogenesis and glycolysis. The main effect on gluconeogenesis was located at the level of the fructose cycle, whereas the decrease in glycolysis was due to a strong inhibition of pyruvate kinase. Although pyruvate kinase inhibition induced by exogenous Mg-ATP was allosteric when assessed in vitro after enzyme extraction, we found a large decrease in the apparent maximal velocity when kinetics were assessed in vivo in intact perifused hepatocytes. This newly described short-term regulation of pyruvate kinase occurs only in the intact cell and may open new potentials for the pharmacological regulation of pyruvate kinase in vivo.
Adenosine Diphosphate↗
The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations.
OBJECTIVE: To evaluate the origin of H+ ions participating in the generation of CO2 coming from sodium bicarbonate infusion during metabolic acidosis. We hypothesized that these H+ ions come from a back-titration of the main non-bicarbonate buffers present in the blood, i. e. the hemoglobin and the albumin, and thus postulated that the rate of CO2 release from a bicarbonate load is dependent on the concentration of these buffers. DESIGN: Prospective clinical and experimental study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS AND MATERIAL: (1) Sixteen stable sedated and artificially ventilated critically ill patients with a mild base deficit. (2) Acidotic human blood (bicarbonate 5 mM, pH 7.0) of hematocrit 5, 10, 20 and 40% regenerated from a mixture of frozen fresh plasma and packed red blood cells. INTERVENTIONS PATIENTS: infusion of 1.5 mmol/kg sodium bicarbonate over 5 min. Regenerated blood: 25 mM sodium bicarbonate load. MEASUREMENTS AND RESULTS PATIENTS: continuous measurement of CO2 production (VCO2) on the expired gas using a metabolic monitor and arterial blood gas analysis before (T0), at the end (T5) and at 10, 30 and 60 min after the beginning of the bicarbonate infusion. The increase in VCO2 was 18 +/- 7% leading to a rise in PaCO2 from 39.6 +/- 2.3 at T0 to 46.2 +/- 2.7 mmHg at T5. The increases in VCO2 and in PaCO2 were significantly correlated to the albumin (r = 0.73, p < 0.005 and r = 0.70, p < 0.005, respectively) and to the hemoglobin (r = 0.51, p < 0.05 and r = 0.65, p < 0.01, respectively) concentrations. Regenerated blood: gas analysis 1 min after the bicarbonate load. The increase in PCO2 was closely related to the hematocrit (Ht) of the blood as it was 15.9 +/- 7.5 mmHg for Ht 5%, 29.0 +/- 9.6 for Ht 10%, 44.2 +/- 5.9 for Ht 20% and 71.0 +/- 3.5 for Ht 40% (n = 5 for each, p < 0.001). CONCLUSIONS: The importance of the release of CO2 from a bicarbonate load is dependent on the concentration of the blood non-bicarbonate buffers. It is therefore likely that the adverse effects of bicarbonate therapy linked to the CO2 generation are more important in patients with high blood albumin and hemoglobin concentrations.
Acidosis↗
Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: a single-blind randomized study.
OBJECTIVE: The renal effects of dopamine in critically ill patients remain controversial. Low-dose dobutamine has been reported to improve renal function. We compared the effects of various doses of dopamine and dobutamine on renal function in critically ill patients. DESIGN: Prospective, single-blind, randomized study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Twelve hemodynamically stable patients with mild nonoliguric renal impairment. INTERVENTIONS: Each patient randomly received four different doses of dopamine and dobutamine (placebo, 3, 7, and 12 microg/kg/min). Each infusion lasted for 4 hrs. Cardiac output and systemic hemodynamic variables were measured using a pulmonary arterial catheter at the beginning (HO) and the end (H4) of each infusion. The bladder was emptied at HO and H4 to determine urine volume and to collect samples. MEASUREMENTS AND MAIN RESULTS: The cardiac index increased significantly with both dopamine and dobutamine (p < .001). Mean arterial pressure (MAP) increased, with the maximum effect of 20% seen with 12-microg/kg/min dopamine infusion (p < .01). No change in MAP was seen with dobutamine. Dobutamine infusions did not change any renal variables. Conversely, all dopamine infusions significantly increased diuresis, creatinine clearance, and the fractional excretion of sodium (p < .01). Creatinine clearance increased from 61+/-16.9 (SD) mL/min to a maximum of 85.7+/-30 mL/min at the 7-microg/kg/min dose; fractional excretion of sodium increased from 0.26%+/-0.28% to a maximum of 0.62%+/-0.51% at the 12-microg/kg/min dose (p < .01). During dopamine infusions, there was a significant relationship between MAP and creatinine clearance (p = .018). CONCLUSIONS: At all doses studied, 4-hr infusions of dopamine significantly increased creatinine clearance, diuresis, and the fractional excretion of sodium in stable critically ill patients. Conversely, dobutamine did not modify these variables. Although the level of MAP might partially contribute to the improvement in renal variables, it is more likely that the activation of renal dopamine receptors played a prominent role.
Adrenergic beta-Agonists↗
Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: a single-blind, prospective, controlled study.
OBJECTIVE: To evaluate the length of the effects of long-term (48 hrs), low-dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients. DESIGN: Prospective, single-blind, controlled clinical study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Eight hemodynamically stable, critically ill patients with a mild nonoliguric renal impairment (creatinine clearance between 30 and 80 mL/min). INTERVENTIONS: Each patient consecutively received 4 hrs of placebo, followed by a 3 microg/kg/min dopamine infusion during 48 hrs, then a new 4-hr placebo period. We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter. The bladder was emptied to determine urine volume and to collect urine samples. Measurements were performed at six times: after the initial control of 4 hrs of placebo (C1); after 4 hrs (H4), 8 hrs (H8), 24 hrs (H24), and 48 hrs (H48) of dopamine infusion; and after the second control of 4 hrs of placebo (C2). MEASUREMENTS AND MAIN RESULTS: We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion. Diuresis, creatinine clearance, and the fractional excretion of sodium (FENa) at C1 and C2 were not different. Urine flow, creatinine clearance, and FENa increased significantly 4 hrs after starting dopamine (for all these changes, p < .01 vs. C1 and C2). The maximum changes were obtained at H8, with an increase of 50% for diuresis, 37% for creatinine clearance, and 85% for FENa (for all these changes, p < .01 vs. C1 and C2). But these effects waned progressively from H24, and both creatinine clearance and FENa at H48 did not differ from control values. CONCLUSIONS: In stable critically ill patients, preventive low-dose dopamine increased creatinine clearance, diuresis, and the fractional excretion of sodium without concomitant hemodynamic change. These effects reached a maximum during 8 hrs of dopamine infusion. But despite a slight persistent increase in diuresis, improvement in creatinine clearance and FENa disappeared after 48 hrs. According to these data, it is likely that tolerance develops to dopamine-receptor agonists in critically ill patients at risk of developing acute renal failure.
APACHE↗
Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury.
OBJECTIVE: To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN: Open-label, prospective study. SETTING: University hospital, department of anesthesiology and intensive care unit. PATIENTS: Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS: At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS: Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.
Adult↗
Reliability of anion gap as an indicator of blood lactate in critically ill patients.
OBJECTIVE: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. DESIGN: Prospective study. SETTING: General intensive care unit of a university hospital. PATIENTS: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. MEASUREMENTS AND RESULTS: The anion gap was calculated as [Na+]-[Cl-]-[TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 +/- 3.2 mmol/l and the mean serum anion gap was 14.3 +/- 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44% [95% confidence interval (CI) 38 to 50], whereas specificity was 91% (CI 87 to 94 and the positive predictive value was 86% (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67% (CI 58 to 75) and specificity = 83% (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r2 = 0.41, p < 0.001) and the slope of this relationship (0.48 +/- 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 +/- 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 +/- 7.1 mmol/l). CONCLUSIONS: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap.
Acid-Base Equilibrium↗
[The internal environment and intracranial hypertension].
Intracranial pressure depends on cerebral tissue volume, cerebrospinal fluid volume (CSFV) and cerebral blood volume (CBV). Physiologically, their sum is constant (Monro-Kelly equation) and ICP remains stable. When the blood brain barrier (BBB) is intact, the volume of cerebral tissue depends on the osmotic pressure gradient. When it is injured, water movements across the BBB depend on the hydrostatic pressure gradient. CBV depends essentially on cerebral blood flow (CBF), which is strongly regulated by cerebral vascular resistances. In experimental studies, a decrease in oncotic pressure does not increase cerebral oedema and intracranial hypertension (ICHT). On the other hand, plasma hypoosmolarity increases cerebral water content and therefore ICP, if the BBB is intact. If it is injured, neither hypoosmolarity nor hypooncotic pressure modify cerebral oedema. Therefore, all hypotonic solutes may aggravate cerebral oedema and are contra-indicated in case of ICHT. On the other hand, hypooncotic solutes do not modify ICP. The osmotic therapy is one of the most important therapeutic tools for acute ICHT. Mannitol remains the treatment of choice. It acts very quickly. An i.v. perfusion of 0.25 g.kg-1 is administered over 20 minutes when ICP increases. Hypertonic saline solutes act in the same way, however they are not more efficient than mannitol. CO2 is the strongest modulating factor of CBF. Hypocapnia, by inducing cerebral vasoconstriction, decreases CBF and CBV. Hyperventilation is an efficient and rapid means for decreasing ICP. However, it cannot be used systematically without an adapted monitoring, as hypocapnia may aggravate cerebral ischaemia. Hyperthermia is an aggravating factor for ICHT, whereas moderate hypothermia seems to be beneficial both for ICP and cerebral metabolism. Hyperglycaemia has no direct effect on cerebral volume, but it may aggravate ICHT by inducing cerebral lactic acidosis and cytotoxic oedemia. Therefore, infusion of glucose solutes is contra-indicated in the first 24 hours following head trauma and blood glucose concentration must be closely monitored and controlled during ICHT episodes.
Acidosis, Lactic↗
[Fatal acute liver failure: a rare complication of exertion-induced heat stroke].
Liver injury is a well-known complication of exertional heat stroke. However severe acute irreversible liver dysfunction is rarely associated. Persistent centrolobular hepatocellular necrosis without any regeneration remains very uncommon. We report a case of fatal acute liver failure occurring after exertional heat stroke. Despite the conventional symptomatic treatment, especially active cooling, the patient experienced multiple organ failure with brain death 6 days after his admission. In this case, a chronic treatment with neuroleptic and anticholinergic agents may be considered as a predisposing factor.
Adult↗
Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients.
OBJECTIVE: To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients. DESIGN: Prospective, clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Ten critically ill patients with acute renal failure and stable blood lactate concentrations. INTERVENTIONS: Two-stage investigation: a) measurement of lactate concentrations in samples of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter; b) evaluation of total plasma lactate clearance by infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins. MEASUREMENTS AND MAIN RESULTS: Arterial lactate concentration was determined before, during, and after the infusion. Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates (by software). At the end of the infusion, median blood lactate concentration increased from 1.4 mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6 mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance accounted for < 3% of total lactate clearance. CONCLUSIONS: Continuous venovenous hemofiltration with dialysis cannot mask lactate overproduction, and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique.
Acidosis, Lactic↗
Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant.
OBJECTIVE: To evaluate the effects of nicardipine on hepatic blood flow in patients with recent liver transplants. Secondly, to evaluate the liver extraction of nicardipine in order to determine the influence of liver transplantation on its disposition. DESIGN: Prospective self-controlled clinical study. SETTING: University hospital intensive care unit. PATIENTS: Eight patients in the early postoperative period of orthotopic liver transplantation. MEASUREMENTS AND RESULTS: Patients were given 5 mg of i.v. nicardipine. Systemic and splanchnic haemodynamic and metabolic parameters were measured before nicardipine administration (T0) and at 5 min (T1), 30 min (T2), and 120 min (T3) after administration. A catheter was inserted into a hepatic vein to determine the total hepatic blood flow (HBF) and the hepatic extraction coefficient of nicardipine. Nicardipine caused no significant changes in HBF, oxygen delivery, oxygen uptake, hepatic venous oxygen saturation, or the hepatic venous partial pressure of oxygen. Likewise, neither blood lactate concentrations nor arterial and hepatic venous lactate-pyruvate ratios were modified by nicardipine. The hepatic extraction coefficient of nicardipine was approximately 0.70 in the first 3 min after complete infusion, then decreased and remained stable at approximately 0.50, showing a non-linear first-pass metabolism pattern. CONCLUSIONS: Nicardipine administration after liver transplantation appears to have no deleterious effects on HBF. Nicardipine can be classified as a drug of intermediate hepatic extraction coefficient, whose elimination partly depends on hepatic enzyme activity.
Adult↗
Intravascular absorption of glycine irrigating solution during shoulder arthroscopy: a case report and follow-up study.
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Absorption↗
Removal of methotrexate by continuous venovenous hemodiafiltration.
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Child↗
Thromboelastography and monitoring of coagulation in patients undergoing continuous venovenous hemofiltration.
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Blood Coagulation Disorders↗
[Severe antiphospholipid syndrome].
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Antiphospholipid Syndrome↗
[Osmolality and brain].
A modification of serum osmolarity induces always movements of water across cell membranes and therefore variations of cell volume of all tissues, including brain. To avoid a severe cell dehydration or hyperhydration, the organism has several regulation means called osmoregulation. Cerebral osmoregulation is essential as the brain is contained in a unexpandable box. In comparison with other organs, this phenomenon is complex and particular as: 1) cerebral volume consists of 3 sub spaces (intracellular, extracellular and cerebrospinal fluid [CSF]); 2) exists a blood-brain barrier (BBB) which behaves functionally as a semi-permeable membrane, essentially sensitive to osmolar disturbances. This brain volume regulation mechanism is working whatever the nature of the solutes initiating the osmotic deviation (sodium, glucose, mannitol...). Cerebral osmoregulation results from intracerebral osmolar modifications. Thus, every variation of plasma osmolarity elicits a similar variation of intracerebral osmolarity. This phenomenon results from modifications of the brain cell "protective" osmoles content. When the osmolar disturbance occurs quickly (in a few hours), cerebral osmoregulation is not complete. It results essentially from modifications of brain cell inorganic solutes content, i.e. electrolytes (Na, K, Cl) which originate from plasma, CSF and extracellular brain spaces uptake. When the osmolar disturbance is more progressive, cerebral osmoregulation is complete. The brain volume returns then to its initial value, by increasing its brain cell electrolytes, but above all organic "idiogenic" osmoles content. These idiogenic osmoles are identified as amino acids, polyols and trimethylamines. During treatment, the delayed normalization of brain osmolarity compared with plasma osmolarity prescribes a slow correction of the osmolar disturbance, as much as it is a chronic one.
Blood-Brain Barrier↗
Influence of region-specific alterations of neuropeptidase content on the catabolic fates of neuropeptides in Alzheimer's disease.
We established the cartography of 11 exo- and endopeptidases in the frontal and parietal cortices and in the cerebellum of brains of patients diagnosed with a senile dementia of the Alzheimer's type (SDAT). Comparison with those of four subjects who had died without known neurologic or psychiatric illness indicated that there existed a region-specific alteration of the peptidase contents in the disease. In the frontal area of SDAT brains, postproline dipeptidyl aminopeptidase and aminopeptidase M activities were significantly reduced. In the parietal cortex of SDAT brain, activities of three additional endopeptidases--angiotensin-converting enzyme, proline endopeptidase, and endopeptidase 24.15--were also drastically reduced. In contrast, the cerebellum displayed a set of proteolytic activities that remained unaffected in SDAT brain. The putative influence of the disease on the catabolic fates of neurotensin, neuropeptide Y, and somatostatin(1-14) was investigated. Neurotensin was catabolized at identical rates in the frontal and parietal cortices in nondemented and SDAT brains. In contrast, neuropeptide Y metabolism was slowed down in SDAT brains in the frontal but not in the parietal cortex. Finally, the degradation velocities of somatostatin(1-14) were lowered in both cortical areas of SDAT brains. It is interesting that, by means of specific peptidase inhibitors, we demonstrated that endopeptidase 24.15 participated in somatostatin(1-14) inactivation in the parietal but not in the frontal cortex. It is suggested that the lowering of the rate of somatostatin(1-14) inactivation in the parietal cortex of SDAT brains likely results from the depletion of endopeptidase 24.15 in this brain region.
Aged↗