JOURNAL OF SURGICAL RESEARCH 51,425-433 (1991) Low Oxygen Delivery Produced by Anemia, Hypoxia, and Low Cardiac Output ROBERT E. CILLEY, M.D.,’ ANDREW M. SCHARENBERG, M.D., PHILLIP F. BONGIORNO, M.D., KENNETH E. GUIRE, M.S., AND ROBERT H. BARTLETT, M.D. Section of General Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0331 Submitted for publication September 20, 1990 few studies have the variables DO, and VO, been mea- In pentobarbital-anesthetized dogs, oxygen delivery sured entirely independently [6, 7,8]. (DO,) was measured by thermodilution cardiac output In an earlier study, we controlled DO, and measured and cooximeter determined oxygen content, while oxy- VO, independently in anesthetized dogs [7]. In the gen consumption (VO,) was measured independently by current study, using a canine model, the components of spirometry. Oxygen delivery was decreased by isovole- oxygen delivery were manipulated independently to de- mic dilutional anemia, breathing hypoxic gas mixtures, termine if DO,,, is dependent upon the component that or cardiac tamponade to reduce cardiac output. Base- is altered. In addition total body oxygen consumption line VO, (cc/hg/min) for the three groups was 5.9 f 0.7 was measured independently of oxygen delivery. Volu- (anemia), 5.4 + 0.4 (hypoxia), and 5.6 f 0.1 (low C.O.) metric spirometry was used to measure oxygen con- (NS). A critical level of oxygen delivery (DO,& was sumption while oxygen delivery was calculated from found at 9-10 cc/kg/min (anemia), lo-11 cc/kg/min thermodilution cardiac output and arterial oxygen con- (hypoxia), and 9-10 cc/hg/min (low C.O.) (NS.). Below tent. In order to analyze the data in a statistically valid this level, VO, fell (became supply dependent) and lac- fashion, a method of interpolation was applied to the tic acidosis occurred, regardless of the mechanism of data set. impaired oxygen delivery. 0 1991 Academic Press, Inc. The hypothesis of this experiment is that DOZctit is independent of the method by which DO, is reduced. INTRODUCTION METHODS Mammalian studies have identified critically low lev- els of oxygen delivery (DO,) below which total body oxy- Experimental Design. gen consumption (VO,) is dependent upon oxygen deliv- (See Fig. 1) Mongrel dogs (15-20 kg) were fasted over ery and above which oxygen consumption is indepen- night, anesthetized with pentobarbital (15 mg/kg), and dent of oxygen delivery [l-5]. This critical level of ventilated with a volume ventilator to a pCOZ of 30-45 oxygen delivery (DO,,,,) is much lower than the normal mm Hg. FiO, was 0.3-0.5 except in the induced hypoxia DO, for any species and is associated with lactatemia, group. Supplemental pentobarbital was given through- acidosis, and hypotension. out the experiment to ablate the inner canthal reflex. In previous studies, the three components of oxygen Temperature was maintained at 37.5”C by external delivery (hemoglobin, arterial oxygen content, and car- warming. A right groin dissection was performed for in- diac output) have not been manipulated independently. troduction of an 8 French arterial catheter for arterial Also, in most studies, the same measured variable was blood sampling and systemic arterial blood pressure used to calculate both oxygen delivery and oxygen con- monitoring. An injectate catheter for cardiac output de- sumption. Either cardiac output and blood oxygen con- termination was positioned in the right atrium via the tent were measured and used to calculate oxygen con- right femoral vein. A balloon-tipped pulmonary artery sumption by the Fick relationship or oxygen consump- catheter with a thermistor was inserted through the tion was measured and used similarly to calculate right external jugular vein for measuring cardiac out- cardiac output in order to determine oxygen delivery. In puts. Position was confirmed by identifying the pulmo- nary artery pressure tracing that changed to a pulmo- 1 To whom reprint requests should be addressed at Pediatric Sur- nary capillary wedge pressure tracing with 1 ml air in- gery, L2110 University of Michigan Medical Center, 1500 E Medical jected into the balloon. Additionally, the catheter was Center Drive, Ann Arbor, MI 48109-0245. palpated in the pulmonary artery at autopsy. 425 0022-4804/91 $1.50 Copyright 0 1991 by Academic Press, Inc. All rights of reproduction in any form reserved. 426 JOURNAL OF SURGICAL RESEARCH: VOL. 51, NO. 5, NOVEMBER 1991 co* IR Scrubber Juh II - One Way One Way] 1 Inhalation _-._- .“..., I ----- u 11 Blower M $-- Slave Endctracheal Bellows Tube I I Pericardial Catheter Harvard lor Tamponade Ventilator FIG. 1. Experimental diagram. Ventilator-respirometer measures VO,; cardiac instrumentation. A right subcostal incision was then performed and the into the pericardial catheter to maintain cardiac output spleen was removed. Splenectomy was performed to pre- at baseline levels. Oxygen consumption was measured at vent splenic autotransfusion. A small area of pericar- progressively lower levels of oxygen delivery as the dogs dium was exposed through an incision in the right hemi- became more anemic. When very low levels of oxygen diaphragm and an 8 French catheter was secured inside delivery were reached, below the critical level of oxygen the pericardium by a purse string suture for the portion delivery, oxygen consumption fell and hemodynamic in- of the experiment requiring tamponade. stability occurred. To acquire more data points above The animal was then attached to the ventilator respi- and below the DO,,, , some dogs were resuscitated with rometer (see below, measurement of VO,) and sequen- whole blood to raise their oxygen delivery and return tial oxygen consumption measurements were performed their oxygen consumption to baseline. These animals over a 3-8 hr period during which oxygen delivery was were then bled further and data collection continued. As manipulated as described below. Dogs were assigned to cardiac output fell at very low levels of DO,, tamponade one of three experimental groups. In Group I seven dogs was released in an effort to keep the cardiac output at were made anemic with oxygenation and cardiac output baseline levels. All animals eventually died of heart fail- constant. In group II five dogs were made hypoxic at ure secondary to anemia and low DO,. constant hemoglobin and cardiac output. In Group III Hypoxia. Animals were made hypoxic by adding ni- four dogs underwent cardiac tamponade by injection of trogen to the ventilator-respirometer to decrease the isotonic saline into the pericardium to reduce cardiac FiO, in the apparatus. FiO, was changed in 2% incre- output at constant oxygenation and hemoglobin. ments until very low levels of DOz were reached. Ani- mals were returned to the original FiO, to confirm that Manipulation of Oxygen Delivery baseline VO, had not changed when DO, was above DOzctit. The lowest levels of oxygen delivery were inves- Anemia. Whole blood was removed from Group I tigated immediately prior to death from hypoxia. Car- animals in 200-ml aliquots followed by crystalloid re- diac tamponade was used to prevent the compensatory placement to return pulmonary capillary wedge pressure increase in cardiac output that occurs with hypoxia. As to the baseline level. As the dogs became anemic and DO, was lowered by hypoxia, marked respiratory muscu- began to develop tachycardia and increased cardiac out- lar activity was noted at very low DO, (<DO,,&. When put, cardiac tamponade was used to restrict this compen- this phenomenon occurs the animal promptly dies, (un- satory response. Small aliquots of saline were injected published observation) presumably as a result of in- CILLEY ET AL.: CRITICAL DO,: ANEMIA, HYPOXIA AND LOW C.O. 427 creased VO, from muscular activity and the fixed low firmed at the end of the experiment by ventilating the level of oxygen delivery. In an effort to examine the low- animal after death and noting that no change in volume est DO, induced by hypoxia, pancuronium bromide (3 in the circuit occurred. Oxygen consumption, measured mg) was given intravenously to the hypoxic animals at atmospheric temperature and pressure, saturated was prior to final reduction of DO, before death. converted to standard temperature and pressure, dry, Low cardiac output. The pericardial catheter was using standard tables based on the ideal behavior of at- used to create cardiac tamponade by progressive volume mospheric gases. Oxygen consumption was expressed as infusion. Animals were tamponaded until a desired car- cc0, (STPD)/kg/min. diac output was obtained. Tamponade was then adjusted Atmospheric pressure was measured during each ex- to maintain this cardiac output. The amount of tampon- periment using a mercury barometer. ade was varied to acquire data points above and below the DOzctiit until the lowest levels of DO, caused instabil- Lactate Determination ity and death. Venous blood samples (3 ml) were drawn during data Measurement of Oxygen Delivery collection and immediately centrifuged. The serum was decanted and frozen. Lactate determinations were made Cardiac output was measured using the thermodilu- using the ACA lactic acid method (DuPont Automatic tion system described earlier. This system employed two Clinical Analyzer, Wilmington, DE). This method is a catheters, one for injecting iced saline in the right atrium modification of the Marbach and Weil method and em- and one for measuring the temperature change in the ploys the enzymatic oxidation of lactate to pyruvate. pulmonary artery. This ensured that the injectate was The absorption of NADH produced in this reaction is mixed over the same anatomic distance in all animals measured using a 2 filter endpoint technique and is di- regardless of the animal size. A Sorensen research car- rectly proportional to the lactate concentration. diac output computer (Model 03950-00, Salt Lake City, UT) was used to calculate the cardiac output using a Data Collection Stewart-Hamilton calibration factor of 0.442.