Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor alpha, and other biologic mediators by endotoxin-stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure. Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identified and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.

Cardiopulmonary Bypass↗

PubMed1994

Thoracic impedance and pulmonary atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in humans.

Head up and down tilts were used for manipulating the central blood volume in eight volunteers. During head-up tilt thoracic electrical impedance (TI) increased from 36.7 (33.9-52.1) ohm (mean and range) to 41.9 (36.9-59.2) ohm, heart rate from 60 (49-72) to 80 (65-90) beats min-1 (P < 0.05) and decreased again to 57 (48-67) beats min-1 accompanying a fall in mean arterial pressure from 86 (76-97) to 54 (41-79) mmHg and in cardiac output from 9.2 (5.9-12.1) to 6.9 (3.4-8.8) 1 min-1 (n = 7, P < 0.07). Central venous pressure did not change significantly. Pulmonary arterial mean, 6 (3-12) mmHg, and wedge pressures, 4 (1-9) mmHg, decreased to 4 (1-11) and 1 (0-7) mmHg, respectively, and mixed, 78 (77-79%), and central venous oxygen saturations, 72 (71-73)%, fell to 62 (46-75) and 54 (44-58)%, respectively (P < 0.05). Atrial natriuretic peptide (ANP) was determined from blood of the superior vena cava and pulmonary and brachial arteries. Pulmonary artery ANP, 18.4 (7.5-30.7) pmol l-1, was higher than in vena cava, 13.3 (5.2-20.9) pmol l-1 (P < 0.05). At the time of presyncope, pulmonary artery ANP decreased from 20.8 (37.4-10.1) to 13.7 (19.7-5.7) pmol l-1, in vena cava from 13.8 (23.1-7.1) to 10.2 (17.9-6.7) pmol l-1 and in the brachial artery from 16.9 (34.1-5.2) to 11.3 (18.5-5.1) pmol l-1 (P < 0.05). Head-down tilt did not affect the recorded variables significantly. Thoracic electrical impedance, pulmonary artery pressure and venous oxygen saturations were sensitive indices of the central blood volume as reflected in the release of atrial natriuretic peptide from the right side of the heart.

Adult↗

PubMed1994

Bicarbonate does not increase left ventricular contractility during L-lactic acidemia in pigs.

Explore the source record for details and available documents.

Acidosis, Lactic↗

PubMed1994

Hypoxic lactic acidosis.

Explore the source record for details and available documents.

Acidosis, Lactic↗

PubMed1994

Safety and efficacy of intravenous Carbicarb in patients undergoing surgery: comparison with sodium bicarbonate in the treatment of mild metabolic acidosis. SPI Research Group. Study of Perioperative Ischemia.

OBJECTIVES: To compare the safety and efficacy of intravenous Carbicarb with intravenous sodium bicarbonate in well-oxygenated patients who developed metabolic acidosis while undergoing major surgery. Carbicarb is an equimolar solution of sodium bicarbonate and sodium carbonate (Na2CO3). It does not undergo significant breakdown to CO2 and H2O, nor does it increase CO2 concentrations to the same extent as does pure sodium bicarbonate. Because of these characteristics, Carbicarb may be a more suitable agent than bicarbonate in the treatment of metabolic acidosis. DESIGN: Prospective, double-blind, randomized, multicenter trial. SETTING: Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco), and the University of Massachusetts Medical Center, Worcester, MA. PATIENTS: We prospectively studied 36 patients who underwent either cardiac surgery or major noncardiac surgery and developed intraoperative metabolic acidosis (pH < 7.35 and whose serum bicarbonate concentration decreased by > 3 mmol). INTERVENTIONS: Patients were randomly assigned to receive either sodium bicarbonate (1 mEq sodium/mL, n = 18) or 1 mol Carbicarb (1 mEq sodium/mL, n = 18) administered by intravenous bolus over a 30-sec period. MEASUREMENTS AND MAIN RESULTS: For Carbicarb-treated patients, the mean arterial pH increased from 7.31 +/- 0.008 (baseline) to 7.36 +/- 0.009 10 mins after treatment; for the sodium bicarbonate-treated patients, the mean pH increased from 7.31 +/- 0.006 to 7.37 +/- 0.01. The increases in pH were statistically significant for both groups (p = .0001). There was no statistically significant difference between treatment groups in the number of repetitions of initial dose that was required to correct acidosis. Hemodynamic variables remained unchanged in both treatment groups during the study period, with the exception of the mean cardiac output which increased from 6.1 +/- 0.4 (baseline) to 6.9 +/- 1.4 L/min (60 mins after treatment) in a subset of Carbicarb-treated patients and decreased from 6.7 +/- 1.3 to 6.0 +/- 1.2 L/min in a subset of sodium bicarbonate-treated patients, p = .048 (between groups); and the mean pulmonary artery occlusion pressure decreased from 19 +/- 2 mm Hg (baseline) to 8 +/- 3 mm Hg (45 mins after treatment) in the Carbicarb-treated patients, and decreased from 18 +/- 2 to 13 +/- 4 mm Hg in the sodium bicarbonate-treated patients, p = .012 (between groups). Systemic utilization of lactate increased from 0.3 +/- 1.0 mmol/min (baseline) to 5.6 +/- 4.3 mmol/min (45 mins after treatment) in Carbicarb-treated patients, and increased from 1.0 +/- 0.6 mmol/min (baseline) to 1.5 +/- 1.3 mmol/min in the sodium bicarbonate-treated patients, p = .033 (between groups). The administration of Carbicarb was safe. No patients were discontinued from the study because of adverse events. CONCLUSIONS: Carbicarb corrects metabolic acidosis as well as sodium bicarbonate. However, the potential therapeutic advantage of Carbicarb remains to be determined, especially in patients with more severe metabolic acidosis.

Acidosis↗

PubMed1994

The relationship between base deficit and lactate concentration in resuscitation.

Explore the source record for details and available documents.

Animals↗

PubMed1994

Correction of intramyocardial hypercarbic acidosis with sodium bicarbonate.

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.

Acidosis↗

PubMed1993

Sodium bicarbonate versus Carbicarb in canine myocardial hypercarbic acidosis.

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. Our findings lend support to the hypothesis that intramyocardial pH determines myocardial function independent of CO2 production by buffer therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Acidosis↗