sodium-bicarbonate and Myocardial-Ischemia

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.. Prospective, double-blind, randomized, multicenter trial.. Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco), and the University of Massachusetts Medical Center, Worcester, MA.. 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).. 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.. 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.. 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.

Topics: Acidosis; Adult; Aged; Blood Gas Analysis; Carbonates; Critical Care; Double-Blind Method; Drug Combinations; Hemodynamics; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Intraoperative Complications; Middle Aged; Multicenter Studies as Topic; Myocardial Ischemia; Prospective Studies; Safety; Sodium Bicarbonate

Recent recommendations suggest that sodium bicarbonate may not be useful for the treatment of metabolic acidosis. However, these recommendations are based primarily on both clinical studies and animal models of metabolic acidosis with arterial hypoxemia (PaO2 of < 80 torr [< 10.7 kPa]). This study was designed to determine the safety and physiologic effects of low-dose sodium bicarbonate in humans who developed intraoperative metabolic acidosis in the absence of hypoxemia.. Prospective, double-blind, randomized trial.. Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco).. We prospectively studied 40 patients with coronary artery disease who underwent major surgery and developed mild intraoperative metabolic acidosis (decrease of plasma bicarbonate by > 3 mM).. Patients were randomly assigned to receive either sodium bicarbonate (n = 20) or sodium chloride (n = 20) by intravenous bolus, up to a maximum dose of 88 mmol of sodium.. Bicarbonate treatment significantly increased the mean arterial pH from 7.36 to 7.39; the mean serum bicarbonate concentration from 21 to 25 mmol/L; and PCO2 from 41 to 44 torr (5.5 to 5.9 kPa). Total body oxygen consumption and lactate production did not change. Similarly, no adverse changes occurred in systemic or pulmonary arterial pressures or in cardiac ejection fraction. After bicarbonate administration, both the cardiac output and systemic oxygen consumption decreased by 8% to 11%, while both variables increased by 13% after sodium chloride administration; but, none of the changes was significant. One patient in the bicarbonate group developed myocardial ischemia, compared with three patients in the saline group.. Administration of sodium bicarbonate to well-oxygenated patients with mild metabolic acidosis resulted in a correction of the acidosis, without significant changes in cardiac output, total body oxygen use, or PaO2 (oxygen tension). These effects remain to be validated in patients with hypoxemia, more severe acidosis, or less stable circulation.

Topics: Acidosis, Lactic; Aged; Bicarbonates; Blood Gas Analysis; Blood Glucose; Calcium; Cardiac Output; Coronary Disease; Double-Blind Method; Drug Monitoring; Electrolytes; Humans; Injections, Intravenous; Intraoperative Complications; Lactates; Lactic Acid; Male; Middle Aged; Monitoring, Intraoperative; Myocardial Ischemia; Oxygen Consumption; Prospective Studies; Sodium; Sodium Bicarbonate; Stroke Volume

Metformin-associated lactic acidosis (MALA) is one of the most important drug toxicities with a high morbidity and mortality rate. We report herein a case of suicide attempt with metformin presenting as MALA and acute renal failure on admission to emergency department and acute myocardial injury later on hospitalisation. An obvious improvement of metabolic parameters was seen in our patient provided by anti-ischaemic treatment together with bicarbonate infusion and haemodialysis. Although myocardial injury due to MALA is not a common disorder, we must be aware that metformin overdose with lack of tissue oxygenation, hypoperfusion, and arrhythmias may cause myocardial ischaemia.

Topics: Acidosis, Lactic; Acute Kidney Injury; Emergency Medical Services; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Myocardial Ischemia; Renal Dialysis; Sodium Bicarbonate; Suicide, Attempted; Treatment Outcome

To examine the impact of administration of NaHCO3 on contractility and energy metabolism of the myocardium during hypoxemia.. Regional myocardial hypoxia was induced in the left anterior descending (LAD) artery myocardium in anesthetized, open-chest dogs, using a perfusion circuit between the right atrium and the LAD artery, and a membrane oxygenator. The rate of flow in LAD artery was maintained constant with the use of a roller pump. During hypoxia, eight dogs were administered isotonic NaHCO3 in the circuit and six other dogs received equimolar NaCl. Myocardial contractile function was assessed using sonomicrometry for measurement of percentage of systolic shortening and preload recruitable stroke work. Oxygen consumption and the rate of appearance of lactate were measured. Clamp-frozen tissue samples were obtained at the end of the experiment from the hypoxic LAD myocardium and the nonhypoxic circumflex myocardium for measurement of tissue lactate level.. During hypoxia, there was a significant decrease in oxygen consumption by the LAD myocardium (35 +/- 7 micromol/min in the NaCl group and 40 +/- 7 micromol/min in the NaHCO3 group during hypoxia vs. 131 +/- 11 micromol/min during aerobic perfusion). There was also a significant decrease in myocardial contractility as measured by percentage of systolic shortening (14 +/- 3% to -8 +/- 3%); NaHCO3 infusion during hypoxia did not improve myocardial contractility (-7 +/- 2%). Similar results were obtained with measurements of preload recruitable stroke work. The rate of production of lactate during hypoxia was substantially lower than expected, based on the calculated oxygen deficit, and was not significantly increased by the administration of NaHCO3 (33 +/- 9 micromol/min in the NaCl group and 51 +/- 5 micromol/min in the NaHCO3 group). Tissue lactate was not statistically different in the hypoxic myocardium supplied by the LAD artery and the nonhypoxic myocardium supplied by the circumflex artery in either group.. The response of the myocardium to hypoxia is to decrease its mechanical work and metabolic demand. The infusion of NaHCO3 did not enhance myocardial contractile function or flux in glycolysis during hypoxia. We speculate that this diminished mechanical work and metabolic demand may represent an adaptive response to preserve cellular integrity until oxygen delivery is restored.

Topics: Acidosis, Lactic; Analysis of Variance; Animals; Blood Gas Analysis; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Energy Metabolism; Female; Hemodynamics; Hydrogen-Ion Concentration; Hypoxia; Lactic Acid; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Stunning; Oxygen Consumption; Sodium Bicarbonate; Stroke Volume

Methemoglobinemia may occur after the administration of various drugs, including some local anesthetics. We report a patient with chronic renal failure and ischemic heart disease who developed clinically significant methemoglobinemia after an axillary block with bupivacaine and additional injection of lidocaine in the operative field. Although the two local anesthetics usually do not cause methemoglobinemia, we suspect that the displacement of lidocaine from protein binding by bupivacaine, in combination with metabolic acidosis and treatment with other oxidants, was the reason for the development of methemoglobinemia.

Topics: Acidosis; Alkalies; Anesthetics, Local; Antidotes; Axilla; Bupivacaine; Drug Interactions; Female; Humans; Intraoperative Care; Kidney Failure, Chronic; Lidocaine; Methemoglobinemia; Methylene Blue; Middle Aged; Myocardial Ischemia; Nerve Block; Oxidants; Protein Binding; Sodium Bicarbonate

We examined the impact of alkali therapy on myocardial contractility in a model of myocardial ischemia in dogs using direct measurements of myocardial contractile function. Myocardial ischemia in the left anterior descending (LAD) artery territory was induced using a perfusion circuit from the internal carotid artery to the LAD artery. Myocardial contractile function was assessed using sonomicrometry for measurement of percent systolic shortening (%SS), preload recruitable stroke work (PRSW) slope, and end-systolic pressure-length relationship (ESPLR) area. Because the blood flow in LAD artery was diminished by approximately 70%, there was a significant decrease in O2 delivery and uptake by the ischemic myocardium. Ischemia led to a significant fall in LAD regional contractile function with %SS decreasing from 15 +/- 2 to 7 +/- 2%, PRSW slope from 82 +/- 10 to 37 +/- 5 mmHg, and ESPLR area from 121 +/- 2 to 48 +/- 14 mmHg.mm (P < 0.05). In six dogs, the intracoronary administration of NaHCO(3) resulted in a significant increase in pH in LAD arterial and venous blood. There was, however, no significant increase in %SS (6 +/- 2), PRSW slope (43 +/- 10 mmHg), or ESPLR area (60 +/- 13 mmHg.mm). Since administration of NaHCO(3) resulted in a significant increase in PCO2 in LAD arterial and venous blood, similar experiments were carried out in five dogs, but with the intracoronary infusion of the amine buffer THAM [tris(hydroxymethyl)aminomethane (Tris) buffer; 2-amino-2-hydroxyl-1,3-propandiol] instead of NaHCO3. Although administration of THAM resulted in a significant increase in pH and a significant decrease in PCO2, in both LAD arterial and venous blood, there was no significant improvement in any of the parameters used to assess myocardial contractile function. In conclusion, administration of alkali (NaHCO3 or THAM) does not enhance the contractile function of the ischemic myocardium.

Topics: Alkalies; Animals; Coronary Circulation; Coronary Vessels; Dogs; Hemodynamics; Hydrogen-Ion Concentration; Myocardial Contraction; Myocardial Ischemia; Oxygen Consumption; Sodium Bicarbonate; Tromethamine

To review the data on pharmacology, pathophysiology and treatment of cocaine toxicity, with particular relevance to the heart and cardiovascular system.. Published epidemiology, laboratory and clinical studies on the pharmacology, electrophysiology and pathophysiology of cocaine toxicity and its treatment.. Cocaine toxicity-related morbidity and mortality are frequent due to the potent pharmacological effects of the drug as an indirect-acting sympathomimetic agent and its class I antiarrhythmic property paradoxically inducing pro-arrhythmia. The cardiac and cardiovascular toxic effects of cocaine include various degrees of myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular effects and a hypercoagulable state. Treatment of cocaine toxicity must be based on the multiple factors leading to the toxicity. Sodium bicarbonate appears to have an important role in the acute setting with conduction abnormalities, seizures or acidosis. Unopposed alpha-stimulation provided by beta-blockade should be avoided. Central nervous system hyperexcitability should be treated with diazepam. The use of calcium antagonists appears logical.. Cocaine is an alkaloid with widespread illicit use. The rationale for treating acute cocaine intoxication has become clearer and more logical with increased knowledge of its mechanisms of action.

Topics: Arrhythmias, Cardiac; Cerebrovascular Disorders; Cocaine; Heart; Humans; Hypertension; Myocardial Ischemia; Sodium Bicarbonate