CARDIOPULMONARY RESUSCITATION Improved hemodynamic function during hypoxia with carbicarb,* a new agent for the management of acidosis

Carbicarb is a mixture of Na2CO3/NaHCO3 that buffers similarly to NaHCO3, but without net generation of CO2. We studied the effects of carbicarb in an animal preparation of hypoxic lactic acidosis (HLA). HLA was induced by ventilating dogs with an hypoxic gas mixture (8% 02/92% N2). Dogs with HLA (n = 28) were then treated with 2.5 meq/kg of either NaHCO3 or carbicarb over 1 hr. Measurements were made, after 1 hr of hypoxia and 1 hr of therapy, of: cardiac hemodynamics, blood gases, liver intracellular pH (pHi), oxygen consumption, and regional lactate production. After therapy, the arterial pH rose with carbicarb (7.22 to 7.27, p<.01), and fell with NaHCO3 (7.18 to 7.13, p<.01). Mixed venous Pco2 did not change with carbicarb but increased with NaHCO3 (p<.05). Arterial lactates stabilized with carbicarb but rose with NaHCO3 (by 3.1 mmol/liter, p<.005). Lactate use by muscle, gut, and liver all improved with carbicarb and decreased with NaHCO3. The liver pHi (normal = 6.99, hypoxia = 6.80) improved with carbicarb (to 6.92), but decreased further with NaHCO3 (to 6.40). Muscle 02 consumption rose with carbicarb, whereas it decreased with NaHCO3. Arterial pressure fell less with carbicarb ( 12 vs -46 mm Hg, p<.006) and the cardiac output was stable with carbicarb but decreased with NaHCO3 (from 143 to 98 ml/kg/min, p<.004). Stroke volume also improved with carbicarb but there was no change in pulmonary capillary wedge pressure, suggesting that carbicarb had a beneficial effect on myocardial contractility. These data demonstrate that administration of carbicarb to dogs with HLA results in improvements in the arterial blood gases, tissue pHi, lactate production, and cardiac hemodynamics. These findings are in contrast to the effects of NaHCO3 and may be related to less systemic CO2 generation by carbicarb. Carbicarb thus appears to be superior to NaHCO3 for the treatment of hypoxic states in the presence of lactic acidosis. Circulation 77, No. 1, 227-233, 1988. THEMOSTCOMMON causes of metabolic acidosis are cardiopulmonary arrest and other states characterized by impaired cardiac performance and reduced tissue perfusion.1 In these states, hypoxia and circulatory insufficiency combine to reduce tissue oxygen availability, causing anaerobic metabolism and lactic acidosis. The lactic acidosis in turn appears to have direct negative effects on myocardial function.38 Indeed, From the Cardiology and Geriatrics Division, Department of Medicine, Veterans Administration Medical Center and the University of California School of Medicine, San Francisco. Supported by grants from the National Heart, Lung, and Blood Institute, No. HL01791, the Research Service of the Veterans Administration and International Medication Systems, Limited. Address for correspondence: Robert M. Bersin, M.D., Cardiology Division (Box 0124), UCSF Moffitt Hospital, 505 Parnassus Ave, San Francisco, CA 94143. Received Aug. 19, 1987; accepted Sept. 24, 1987. Dr. Bersin is a recipient of the Physician-Scientist Award, National Institutes of Health. Presented in part at the 59th Scientific Session, American Heart Association, November, 1986, Dallas, and the Annual Meeting, American Society for Clinical Investigation, May 1987, San Diego. Carbicarb is a registered trademark. Vol. 77, No. 1, January 1988 this effect appears to be most pronounced when the acidosis is due to hypoxia, since myocardial contractile function is depressed more by the combination ofhypoxia and lactic acidosis than by either process alone.9' 1O Since tissue oxygen delivery is critically dependent on cardiac output in hypoxic states and cardiopulmonary arrest, the negative inotropic effect of lactic acidosis assumes a critically important role in determining clinical outcome in these situations. Because of this, the goal of cardiopulmonary resuscitation has been to correct both the hypoxia and the lactic acidosis simultaneously in order to restore myocardial function as rapidly as possible.11 The correction of lactic acidosis in hypoxic states has traditionally been accomplished with the administration of sodium bicarbonate (NaHCO3). However, investigations from our laboratory and others12-16 suggest that the administration of NaHCO3 in this setting may be counterproductive. Using an animal preparation of hypoxic lactic acidosis (HLA) in dogs, we 227 by gest on A ril 0, 2017 http://ciajournals.org/ D ow nladed from