sodium-bicarbonate and Hypercapnia

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

Topics: Acidosis; Clinical Trials as Topic; Disease Progression; Glomerular Filtration Rate; Humans; Hypercapnia; Hypocalcemia; Hypokalemia; Renal Dialysis; Renal Insufficiency, Chronic; Sodium Bicarbonate

Sodium bicarbonate has been standard therapy for the treatment of acidosis. In lactic acidosis and hypercapnic acidosis, however, there is no clinical data supporting its effectiveness. We reviewed the literature of the efficacy of sodium bicarbonate on lactic acidosis and hypercapnic acidosis. On both conditions, we have no solid evidence supporting its beneficial effect. Conversely, acidosis or hypercapnia might be protective in acute lung and systemic organ injury. Therefore, the unprepared use of bicarbonate might be harmful in terms of fluid and sodium overload and excess lactate concentrations. According to current literature, we cannot recommend sodium bicarbonate administration for patients with lactic acidosis and hypercapnic acidosis.

Topics: Acid-Base Imbalance; Acidosis; Evidence-Based Medicine; Humans; Hypercapnia; Sodium Bicarbonate

"Permissive hypercapnia" is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO(2), in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO(2) is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of hypercapnia. At present, protective ventilatory strategies that involve hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of hypercapnia in ARDS.

Topics: Acidosis, Respiratory; Humans; Hypercapnia; Respiration, Artificial; Respiratory Distress Syndrome; Sodium Bicarbonate; Survival Rate

Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined.. We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability.. In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W.. Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.

Topics: Acidosis; Animals; Enzyme Inhibitors; Hypercapnia; Hypoxia; Imines; Lung; Male; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroarginine; Pulmonary Circulation; Rabbits; Sodium Bicarbonate; Vasoconstriction

Prolonged hypercapnia is commonly encountered during the treatment of acute respiratory distress syndrome and acute respiratory failure attributable to other causes with protective ventilation strategies. In these circumstances, compensatory renal buffering returns pH to normal establishing a condition of buffered hypercapnia. It is also common intensive care practice to correct the pH more rapidly using bicarbonate infusions. Although it is well-established that hypercapnic acidosis has potent anti-inflammatory and protective effects, the effect of buffered hypercapnia on acute lung injury and acute respiratory distress syndrome is unknown. We therefore wished to determine the effects of buffered hypercapnia on acute lung injury induced by endotoxin or Escherichia coli infection in vivo.. Prospective, randomized animal study.. University research laboratory.. Adult male Sprague-Dawley rats.. We established buffered hypercapnia by exposing rats to a hypercapnic environment for 3 days before the induction of lung injury. Buffered hypercapnia rats (initial pH >7.35, FiCO2 = 0.05) and normocapnic controls (initial pH >7.35, FiCO2 = 0.00) were then anesthetized, mechanically ventilated, and lung injury induced by intra-tracheal inoculation of endotoxin (series I) or Escherichia coli (series II).. Buffered hypercapnia significantly increased both endotoxin and Escherichia coli-induced lung injury when compared to normocapnic controls, as assessed by arterial oxygenation, lung compliance, pro-inflammatory pulmonary cytokine concentrations, and measurements of structural lung damage. In additional in vitro experiments buffered hypercapnia did not alter neutrophil phagocytosis ability but did impaired epithelial wound healing.. Our results demonstrate that infection-induced injury in vivo is worsened after renal buffering of hypercapnic acidosis independently of any changes in tidal volume. These findings have important implications for our understanding of the pathogenesis of infection-induced lung injury during the use protective ventilation strategies that permits buffered hypercapnia and during infective exacerbations of chronic lung diseases associated with sustained hypercapnia.

Topics: Acidosis, Respiratory; Acute Lung Injury; Animals; Buffers; Endotoxins; Escherichia coli Infections; Hydrogen-Ion Concentration; Hypercapnia; In Vitro Techniques; Male; Neutrophils; Phagocytosis; Prospective Studies; Random Allocation; Rats; Rats, Sprague-Dawley; Sodium Bicarbonate; Wound Healing

Arterial partial pressure of carbon dioxide (paCO(2)) is commonly evaluated by an invasive test, the arterial blood gas analysis (ABG). The sodium [(13)C]bicarbonate breath test (SBT) can potentially estimate arterial paCO(2). We studied 55 subjects with respiratory disorders and performed the ABG and the SBT to determine if the SBT can predict hypercapnia. The percentage of (13)CO(2) recovered in exhaled breath at 30 minutes (PDR(30)) alone was able to discriminate clinically significant hypercapnia (>53 mmHg) with a sensitivity of 82 % and specificity of 93 % (p<0.001). To evaluate the clinical utility of the SBT as a non-invasive substitute to repeated ABG, we monitored the progress of seven chronic obstructive pulmonary disease (COPD) patients on therapy with both the ABG and the SBT. The PDR(30) values from the SBT were able to correctly predict improvement or worsening of paCO(2) with 100 % accuracy. In conclusion, the SBT is a simple test that can be used in clinical practice to detect clinically significant hypercapnia and monitor COPD patients before and after therapy.

Topics: Aged; Blood Pressure; Breath Tests; Carbon Dioxide; Carbon Isotopes; Female; Humans; Hypercapnia; Male; Middle Aged; Partial Pressure; Sensitivity and Specificity; Sodium Bicarbonate

Topics: Adult; Asthma; Carbon Dioxide; Female; Humans; Hypercapnia; Respiration, Artificial; Sodium Bicarbonate

This study was performed to investigate a role of the neonatal area postrema (AP) in the chemoreceptor response to hypercapnia which is defective in sudden infant death syndrome (SIDS). AP responses to CO2 inhalation were monitored in 1 to 5 week old piglets by mapping neurons that were induced to express the c-fos gene product, Fos--a marker of functional activation. Interpretive confounds were minimized by controlling for hypoxia, the effects of surgical procedures and ambient environmental stressors on neuronal activity (c-fos expression). The AP demonstrated a powerful and reproducible response in neonatal swine breathing 10% CO2 for 1 h. Intensely immunolabeled nuclei were detected throughout the longitudinal extent of the circumventricular organ, and were especially heavily concentrated at rostral levels proximal to obex. Quantitative analysis verified statistically significant increases in numbers of cells that were induced to express Fos-like immunoreactivity (FLI) in the AP of CO2- stimulated piglets as compared to control groups. No detectable age-related differences were observed in AP response patterns. Conclusions. The AP responds to hypercapnic stress in the newborn piglet. A mature circumventricular organ response in the neonate may be crucial in defending against common environmental stressors, such as nicotine exposure--an emetic agent acting via the AP and a major risk factor in SIDS. Hence, a defect of the AP or its network may underlie a loss of state-dependent controls over cardiopulmonary reflex function in SIDS.

Topics: Animals; Animals, Newborn; Brain Mapping; Cerebral Ventricles; Chemoreceptor Cells; Gene Expression Regulation; Genes, fos; Humans; Hypercapnia; Immunohistochemistry; Infant; Infant, Newborn; Sodium Bicarbonate; Sudden Infant Death; Swine

To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia.. Prospective, controlled study.. Research laboratory.. Female Marino ewes.. Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation).. Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr).. Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Topics: Acute Disease; Animals; Blood Gas Analysis; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Hemodynamics; Hydrogen-Ion Concentration; Hypercapnia; Positive-Pressure Respiration; Prospective Studies; Random Allocation; Respiratory Distress Syndrome; Sheep; Sodium Bicarbonate; Time Factors

Despite the absence of outcome evaluation, the use of sodium bicarbonate in cardiac arrest has declined based on advanced cardiac life-support guidelines. The effects of bicarbonate therapy on outcome in a canine model of ventricular fibrillation cardiac arrest of brief (5-min) and prolonged (15-min) duration were examined.. Prospective, randomized, controlled trial.. Experimental animal laboratory in a university medical center.. Thirty-two adult dogs, weighing 10 to 17 kg.. The animals were prepared with ketamine, nitrous oxide/oxygen, halothane, and pancuronium. Ventricular fibrillation was then electrically induced and maintained in arrest for 5 mins (n = 12) or 15 mins (n = 20). Canine advanced cardiac life-support protocols were instituted, including defibrillation, cardiopulmonary resuscitation (CPR), and the administration of epinephrine (0.1 mg/kg), atropine, and lidocaine. The bicarbonate group received 1 mmol/kg of sodium bicarbonate initially, and base deficit was corrected to -5 mmol/L with additional bicarbonate, whereas acidemia was untreated in the control group. Cardiopulmonary values were recorded at intervals between 5 mins and 24 hrs, and the neurologic deficit score was determined at 24 hrs after CPR.. The treatment group received an additional 2 to 3 mmol/kg of bicarbonate in the early postresuscitation phase. Compared with controls, the bicarbonate group demonstrated equivalent (with brief arrest) or improved (with prolonged arrest) return of spontaneous circulation and survival to 24 hrs, with lessened neurologic deficit. The acidosis of arrest was decreased in the prolonged arrest group without hypercarbia. Improved coronary and systemic perfusion pressures were noted in the bicarbonate group with prolonged arrest, and the epinephrine requirement for return of spontaneous circulation was decreased.. The empirical administration of bicarbonate improves the survival rate and neurologic outcome in a canine model of cardiac arrest.

Topics: Acidosis; Animals; Atropine; Blood Circulation; Dogs; Epinephrine; Heart Arrest; Hemodynamics; Hydrogen-Ion Concentration; Hypercapnia; Lidocaine; Prospective Studies; Resuscitation; Sodium Bicarbonate; Time Factors; Ventricular Fibrillation

Although it has been hypothesized that exogenously administered bicarbonate can exacerbate intramyocardial acidosis and compromise contractile function, this phenomenon has not been demonstrated in an intact model in which intramyocardial pH (pH(int)), regional venous pCO2, and regional contractile function have been simultaneously monitored. In 20 anesthetized dogs, we studied the effects of intracoronary infusions of sodium bicarbonate NaHCO3 30 mEg over 15 min, on regional pH(int), (glass electrode) and regional stroke work (SW, sonomicrometry) before and after creating systemic hypercarbic acidosis by hypoventilation. During NaHCO3 administration, regional coronary venous pCO2 increased rapidly during the first minute (eucapnea; 34 +/- 7 to 55 +/- 18 mm Hg; hypercapnea: 70 +/- 15 to 98 +/- 23 mm Hg, P < 0.05 for both increases). Regional venous pH rose from 7.36 +/- .04 to 7.55 +/- .06 (P < 0.05) after the first minute of NaHCO3 infusion during eucapnea and from 7.09 +/- .09 to 7.22 +/- .09 (P < 0.05) during hypercapnea. During the first minute of NaHCO3 infusion, pH(int) declined minimally. However, during the remaining 14 min of each infusion, pH(int) increased significantly (eucapnea: 7.19 +/- 0.10 to 7.43 +/- 0.12; hypercapnea: 6.86 +/- 0.14 to 7.02 +/- 0.15, P < 0.05 for both changes). Regional SW decreased significantly during the first minute of infusion, both during eucapnea (23,400 +/- 7,400 to 18,000 +/- 6,300 ergs/cm2, P < 0.05) and hypercapnea (27,000 +/- 9,100 to 25,000 +/- 10,000 ergs/cm2, P < 0.05). The first minute of contractile dysfunction was followed by recovery and ultimately supranormal contractile function during the remainder of each bicarbonate infusion. To test the hypothesis that transient intracellular acidosis during bicarbonate infusions was underestimated by measurements of pH(int), measurements of intracellular pH using the pH-sensitive dye, BCECF, were performed in isolated guinea pig papillary muscles incubated in vitro. These measurements confirmed the presence of transient intracellular acidosis during bicarbonate infusion. In conclusion, (1) the intracoronary administration of sodium bicarbonate causes a transient depression in myocardial contractile function that is related to transient intracellular acidosis; and (2) despite exacerbating hypercarbia, sodium bicarbonate ultimately neutralizes intracellular acid and augments myocardial contractile function.

Topics: Acidosis; Animals; Carbon Dioxide; Cardiomyopathies; Coronary Circulation; Dogs; Extracellular Space; Guinea Pigs; Heart; Hemodynamics; Hydrogen-Ion Concentration; Hypercapnia; Injections; Lactates; Lactic Acid; Myocardium; Oxygen Consumption; Papillary Muscles; Sodium Bicarbonate; Veins

The objective of this study was to compare the in vivo effects of sodium bicarbonate (NaHCO3) and Carbicarb infusion on regional contractile performance and acid-base status in the setting of hypercarbic acidosis. Animals (N = 9) were anesthetized and paralyzed using sodium pentothal, halothane, and pancuronium bromide, and mechanically ventilated with an air-O2 mixture so that arterial PO2 was > or = 300 mm Hg. Following beta-adrenergic blockade, alveolar ventilation was gradually reduced over a 50-minute period to increase arterial PCO2 to 60 to 80 mm Hg. Each of the following solutions was then infused in consecutive order directly into the left anterior descending artery coronary artery for 15 minutes: (1) 8.4% NaHCO3 at 2 mL/min; (2) 5% sodium chloride at 2 mL/min, equivalent to NaHCO3 in osmolality; (3) 6.3% Carbicarb at 0.5 mL/min, equivalent to NaHCO3 in buffer capacity; and (4) 6.3% Carbicarb at 2 mL/min, equivalent to NaHCO3 in volume. Regional stroke work analog (ultrasonic dimension transducers), interstitial myocardial pH (Khuri electrode), coronary blood flow (doppler flow probe), and hemodynamic/metabolic variables (heart rate, blood pressure, arterial and coronary venous blood gases) were measured at 1, 5, 10, and 15 minutes during each infusion and 10 minutes after the infusion was discontinued, ie, at 25 minutes. Animals were allowed to recover for 45 minutes between interventions. Values at each time point were compared with baseline for statistical significance. Small reductions in interstitial myocardial pH (P < .05) and stroke work (P > .05) were observed within 1 minute of NaHCO3 administration. Both parameters increased significantly from baseline levels thereafter, ie, interstitial myocardial pH at 5 minutes and stroke work at 15 minutes. Infusion of Carbicarb invariably was associated with an increase (P < .05) in interstitial myocardial pH. Stroke work increased (P < .05) during low-dose Carbicarb administration, but infusion of the higher dose was accompanied by a biphasic response, ie, an increase (P < .05) from 0 to 5 minutes, followed by a gradual decrease that achieved statistical significance 10 minutes after termination of the infusion. End-diastolic length was inversely proportional to changes in stroke work, and coronary blood flow varied directly with changes in coronary venous Pco2. Myocardial O2 consumption decreased (P < .05) during Carbicarb infusion, but changes during NaHCO3 did not reach statistical significance

Topics: Acidosis; Animals; Bicarbonates; Carbonates; Coronary Circulation; Dogs; Drug Combinations; Heart; Hydrogen-Ion Concentration; Hypercapnia; Myocardium; Oxygen Consumption; Sodium Bicarbonate; Sodium Chloride; Stroke Volume

The effects of acidosis and alkalosis on pulmonary gas exchange were studied in 32 pentobarbital sodium-anesthetized intact dogs after induction of oleic acid (0.06 ml/kg) pulmonary edema. Gas exchange was assessed at constant ventilation and constant cardiac output, by venous admixture calculations and by intrapulmonary shunt measurements using the sulfur hexafluoride (SF6) method. Metabolic acidosis (pH 7.20) and alkalosis (pH 7.60) were induced with HCl and Carbicarb (isosmolar Na2CO3 and NaHCO3), respectively. Hypercapnia was induced by adding inspiratory CO2, whereas pH was allowed to change (respiratory acidosis, pH 7.20) or maintained constant (isolated hypercapnia). Mean intrapulmonary shunt and pulmonary arterial minus wedge pressure difference, respectively, changed from 44 to 33% (P less than 0.05) and from 9 to 10 mmHg (P greater than 0.05) in metabolic acidosis, from 44 to 62% (P less than 0.001) and from 12 to 8 mmHg (P less than 0.01) in metabolic alkalosis, from 40 to 42% (P greater than 0.05) and from 13 to 16 mmHg (P less than 0.05) in respiratory acidosis, from 42 to 52% (P less than 0.05) and from 8 to 12 mmHg (P less than 0.01) in isolated hypercapnia. These results indicate that acidosis, alkalosis, and hypercapnia markedly influence pulmonary gas exchange and/or pulmonary hemodynamics in dogs with oleic acid pulmonary edema.

Topics: Acidosis; Alkalosis; Animals; Bicarbonates; Carbonates; Cardiac Output; Dogs; Drug Combinations; Hemodynamics; Hydrochloric Acid; Hypercapnia; Lung; Oleic Acid; Oleic Acids; Pulmonary Edema; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Sodium Bicarbonate

Rats subjected to ammonium chloride-induced metabolic acidosis or respiratory acidosis caused by hypercapnia were given alkalinization therapy with either sodium bicarbonate or Carbicarb. Ammonium chloride induced dose-dependent systemic acidosis but did not affect intracellular brain pH. Hypercapnia caused dose-dependent systemic acidosis as well as decreases in intracellular brain pH. Sodium bicarbonate treatment resulted in systemic alkalinization and increases in arterial PCO2 in both acidosis models, but it caused intracellular brain acidification in rats with ammonium chloride acidosis. Carbicarb therapy resulted in systemic alkalinization without major changes in arterial PCO2 and intracellular brain alkalinization in both acidosis models. These data demonstrate that bicarbonate therapy of systemic acidosis may be associated with "paradoxical" intracellular brain acidosis, whereas Carbicarb causes both systemic and intracellular alkalinization under conditions of fixed ventilation.

Topics: Acidosis; Acidosis, Respiratory; Ammonium Chloride; Animals; Arteries; Bicarbonates; Blood Pressure; Brain; Carbon Dioxide; Carbonates; Drug Combinations; Hydrogen; Hydrogen-Ion Concentration; Hypercapnia; Partial Pressure; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate

Administration of sodium bicarbonate during cardiopulmonary resuscitation (CPR) is controversial, and our aim was to elucidate whether or not its administration is beneficial by analyzing the acid-base status and the level of carbon dioxide in central venous blood during CPR, and their changes following administration of sodium bicarbonate. Six patients were studied. They had all been admitted to the intensive care unit (ICU), had already had pulmonary arterial or central venous catheters inserted, and had acute episodes of circulatory collapse during their stay in the ICU. The following phenomena were observed: 1) hypercapnia and acidosis of central venous blood were prominent during both cardiogenic shock and CPR, although arterial hypocapnia was maintained by hyperventilation; 2) administration of sodium bicarbonate during cardiogenic shock and CPR induced exacerbation of hypercapnia and acidosis of central venous blood; 3) when arterial hypercapnia was present due to disturbed ventilation, administration of sodium bicarbonate exacerbated hypercapnia and acidosis of both arterial and central venous blood; 4) administration of sodium bicarbonate did not induce hypercapnia of central venous blood in a septic shock patient in whom the septic hyperdynamic state was prevalent in spite of low systemic perfusion pressure. It was concluded that hypercapnia and acidosis of the central venous blood and tissues were exacerbated by administration of sodium bicarbonate during CPR, and that such an effect might be dependent on the severity of the decrease in tissue perfusion.

Topics: Acid-Base Equilibrium; Acidosis; Aged; Bicarbonates; Carbon Dioxide; Catheterization, Central Venous; Female; Humans; Hydrogen-Ion Concentration; Hypercapnia; Male; Middle Aged; Resuscitation; Shock, Cardiogenic; Sodium; Sodium Bicarbonate; Vena Cava, Inferior

The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.

Topics: Acidosis, Respiratory; Acute Disease; Animals; Bicarbonates; Cyclic AMP; Diet; Extracellular Space; Glomerular Filtration Rate; Hydrogen-Ion Concentration; Hypercapnia; Parathyroid Hormone; Phosphates; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate; Stimulation, Chemical

This study was designed to establish the relationship between urinary pCO2 and systemic blood pCO2 during acute hypercapnia and to investigate the significance of this relationship to collecting duct hydrogen ion (H+) secretion when the urine is acid and when it is highly alkaline. In rats excreting a highly alkaline urine, an acute increase in blood pCO2 (from 42 +/- 0.8 to 87 +/- 0.8 mmHg) resulted in a significant fall in urine minus blood (U-B) pCO2 (from 31 +/- 2.0 to 16 +/- 4.2 mmHg, P less than 0.005), a finding which could be interpreted to indicate inhibition of collecting duct H+ secretion by hypercapnia. The urinary pCO2 of rats with hypercapnia, unlike that of normocapnic controls, was significantly lower than that of blood when the urine was acid (58 +/- 6.3 and 86 +/- 1.7 mmHg, P less than 0.001) and when it was alkalinized in the face of accelerated carbonic acid dehydration by infusion of carbonic anhydrase (78 +/- 2.7 and 87 +/- 1.8 mmHg, P less than 0.02). The finding of a urinary pCO2 lower than systemic blood pCO2 during hypercapnia suggested that the urine pCO2 prevailing before bicarbonate loading should be known and the blood pCO2 kept constant to evaluate collecting duct H+ secretion using the urinary pCO2 technique. In experiments performed under these conditions, sodium bicarbonate infusion resulted in an increment in urinary pCO2 (i.e., a delta pCO2) which was comparable in hypercapnic and normocapnic rats (40 +/- 7.2 and 42 +/- 4.6 mmHg, respectively) that were alkalemic (blood pH 7.53 +/- 0.02 and 7.69 +/- 0.01, respectively). The U-B pCO2, however, was again lower in hypercapnic than in normocapnic rats (15 +/- 4.0 and 39 +/- 2.5 mmHg, respectively, P less than 0.001). In hypercapnic rats in which blood pH during bicarbonate infusion was not allowed to become alkalemic (7.38 +/- 0.01), the delta pCO2 was higher than that of normocapnic rats which were alkalemic (70 +/- 5.6 and 42 +/- 4.6 mmHg, respectively, P less than 0.005) while the U-B pCO2 was about the same (39 +/- 3.7 and 39 +/- 2.5 mmHg). We further examined urine pCO2 generation by measuring the difference between the urine pCO2 of a highly alkaline urine not containing carbonic anhydrase and that of an equally alkaline urine containing this enzyme. Carbonic anhydrase infusion to hypercapnic rats that were not alkalemic resulted in a fall in urine pCO(2) (from 122+/-5.7 to 77+/-2.2 mmHg) which was greater (P <0.02) than that seen in alkalemic normocapnic controls (fr

Topics: Acidosis, Respiratory; Acute Disease; Animals; Bicarbonates; Carbon Dioxide; Carbonic Anhydrases; Hydrogen-Ion Concentration; Hypercapnia; Kidney Tubules; Kidney Tubules, Collecting; Partial Pressure; Protons; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate; Time Factors

The rise in urinary pCO2 above blood pCO2 which occurs in response to bicarbonate loading (i.e. the urine to blood (U-B) pCO2 gradient), is used with increasing frequency as an index of collecting duct hydrogen ion secretion. We recently proposed, however, that the U-B pCO2 gradient is not an appropriate index of collecting duct hydrogen ion secretion when blood pCO2 is altered acutely. This issue was further investigated by examining the effect of chronic hypercapnia on urinary pCO2 generation. In rats exposed to chronic hypercapnia induced by breathing 10% CO2 for 3 days in an environmental chamber, acute sodium bicarbonate infusion resulted in a U-B pCO2 lower than that of normocapnic control rats (11 +/- 4.6 and 30 +/- 1.8 mm Hg, p less than 0.001). This finding could be interpreted to indicate that collecting duct hydrogen ion secretion is depressed in rats with chronic hypercapnia. The urinary pCO2 of rats with chronic hypercapnia was lower than that of the blood (54 +/- 6.0 and 86 +/- 1.2 mm Hg, p less than 0.005, respectively). In these rats, NaHCO3 infusion, while blood pCO2 was kept constant, elicited a marked rise in urine pCO2 (from 54 +/- 6.0 to 104 +/- 6.0 mm Hg, p less than 0.005) which was not significantly different from that observed in normocapnic control rats. The infusion of carbonic anhydrase resulted in a comparable fall in urine pCO2 in hypercapnic and normocapnic rats (-27 +/- 5 and -30 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiloride; Animals; Bicarbonates; Carbon Dioxide; Glomerular Filtration Rate; Hydrogen-Ion Concentration; Hypercapnia; Male; Oxygen; Partial Pressure; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate

The effects of hyperlactatemia on cerebral glucose metabolism of normoglycemic 20-day-old rats were studied in animals breathing air or 20% CO2:21% O2:59% N2. Sodium lactate or sodium bicarbonate were given intraperitoneally, together with a mixture of [3H]deoxyglucose and [2-14C]glucose. Animals were sacrificed in a freeze-blowing apparatus at intervals of 2-15 min after injection. Blood lactate levels in the lactate-injected rats were 4-6 mM. Hyperlactatemia caused a gradual decline in the brain rate of glucose utilization in air-breathing animals to 50-70% of control rates. Results with both tracers were similar. Concentrations of Krebs cycle intermediates and glutamate did not decrease. These findings indicate that lactate can partially replace glucose as an oxidative fuel for developing rat brain. Hypercapnia depressed the rate of glucose utilization by developing brain and rates were 30-40% lower still in lactate-injected hypercapnic rats. Decreases in levels of Krebs cycle intermediates and glutamate were similar in both groups. Thus, lactate and CO2 are additive in their depressant effects on brain glucose utilization. The observation that lactate did not prevent the decreases in Krebs cycle intermediates and glutamate caused by hypercapnic acidosis suggests an inhibition of flux through pyruvate dehydrogenase during hypercapnia. The data from this study, coupled with data on lactate transport across the blood-brain barrier, indicate that the direction of movement of lactate and its rate of utilization by developing brain are functions of its concentration on blood relative to brain. Physiological and pathological conditions which elevate blood lactate levels above those in brain will, then, have a sparing effect upon brain glucose utilization.

Topics: Alkalosis; Animals; Bicarbonates; Blood Glucose; Brain; Glucose; Hypercapnia; Lactates; Lactic Acid; Rats; Rats, Inbred Strains; Sodium Bicarbonate

The present studies evaluate the effect of acute hypercapnia on distal nephron H+ secretion (DNH+S) in vivo by means of the urine-blood PCO2 difference (U-B PCO2) in alkaline urine. Bicarbonaturia was induced by either a sodium bicarbonate infusion or L-lysine administration. Our results demonstrate that the U-B PCO2, as a function of the urinary bicarbonate concentration, was significantly lower during acute respiratory acidosis; this effect was not dependent on changes in glomerular filtration rate and/or fractional excretion of sodium, potassium, and chloride. Infusion of the sodium salts of sulfate, a nonreabsorbable anion, did not correct the diminished U-B PCO2. Amiloride caused the U-B PCO2 to fall in normocapnic dogs but not in hypercapnic dogs. When hypercapnia was superimposed in dogs with extracellular fluid volume contraction, there were no changes in the U-B PCO2. This study indicates that acute hypercapnia in the intact dog decreases DNH+S and is compatible with an effect of hypercapnia on the voltage-dependent component of urine acidification. The mechanism appears to be direct rather than secondary to factors that influence the rate of sodium delivery to the distal nephron.

Topics: Acidosis, Respiratory; Amiloride; Animals; Bicarbonates; Carbon Dioxide; Diuresis; Dogs; Extracellular Space; Female; Hydrogen-Ion Concentration; Hypercapnia; Lysine; Male; Nephrons; Potassium; Sodium; Sodium Bicarbonate

We investigated the relative contribution of peripheral and central chemosensory mechanisms to ventilatory responses to metabolic alkalosis in anesthetized cats by simultaneously measuring steady-state carotid body chemosensory activity and ventilation. The effects of graded steady-state levels of metabolic alkalosis at constant levels of arterial O2 and CO2 partial pressure (PaO2 and PaCO2, respectively) were studied first. Then the responses to isocapnic hypoxia and hyperoxic hypercapnia before and after the induction of a given level of metabolic alkalosis were studied. From the relationship between the carotid chemosensory activity and ventilation, the contribution of the two chemosensory mechanisms was estimated. The depression of ventilation that could not be accounted for by a decrease in the carotid chemosensory activity is attributed to the central effect. We found that metabolic alkalosis decreased both carotid chemosensory activity and ventilation at all levels of PaO2 or PaCO2. The ventilatory effect of alkalosis increased during hypoxia due to suppression of both peripheral chemosensory input and its interaction with the central CO2-H+ drive. During hyperoxia the central effect of alkalosis was predominant, although the peripheral effect increased with hypercapnia. We conclude that acute metabolic alkalosis suppresses both peripheral and central chemosensory drives, and its ventilatory effect grows larger with decreasing PaO2.

Topics: Action Potentials; Alkalosis; Animals; Bicarbonates; Carbon Dioxide; Carotid Sinus; Cats; Chemoreceptor Cells; Female; Hypercapnia; Hypoxia; Oxygen; Partial Pressure; Sodium Bicarbonate