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a) To determine the relationship of acid-base balance (pH, PCO2) of blood samples from the intraosseous and the mixed venous route during prolonged cardiopulmonary resuscitation; b) to compare the effect of separate infusions of epinephrine, fluid boluses, or sodium bicarbonate through the intraosseous sites on the acid-base status of intraosseous and mixed venous blood during cardiopulmonary resuscitation; and c) to compare pH and PCO2 of intraosseous and mixed venous blood samples after sequential infusions of fluid, epinephrine, and sodium bicarbonate through a single intraosseous site.Prospective, randomized study.Animal laboratory at a university center.Thirty-two mixed-breed piglets (mean weight, 30 kg).Piglets were anesthetized and prepared for blood sampling and cardiopulmonary resuscitation. After anoxic cardiac arrest, ventilation was resumed and chest compression was resumed. Blood gas samples from the pulmonary artery and both intraosseous sites were obtained simultaneously at baseline, at cardiac arrest, and at 5, 10, 15, 20, and 30 mins of cardiopulmonary resuscitation for group 1 (control group) and after drug (epinephrine and sodium bicarbonate) and saline infusions via one of the intraosseous cannulas in groups 2 through 5.We found no differences between intraosseous and mixed venous pH and PCO2 during periods of <15 mins of cardiopulmonary resuscitation. However, this relationship was not maintained during prolonged cardiopulmonary resuscitation and after bicarbonate infusion. After large volume saline infusion, the pH and PCO2 of mixed venous and intraosseous blood were similar. During epinephrine infusion, the relationship between intraosseous and mixed venous pH and PCO2 was similar to that found in the control group.The intraosseous blood sample could be used to assess central acid-base balance in the early stage of arrest and cardiopulmonary resuscitation of <15 mins. However, during cardiopulmonary resuscitation of longer duration, drug infusions may render the intraosseous site inappropriate for judging central acidosis.