Cardiac Output, Stroke Volume, Total Peripheral Resistance, and Intrathoracic Blood Volume
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HEMODYNAMIC CHANGES DURING THIOPENTAL ANESTHESIA IN HUMANS: CARDIAC OUTPUT, STROKE VOLUME, TOTAL PERIPHERAL RESISTANCE, AND INTRATHORACIC BLOOD VOLUME Benjamin Etsten, T. H. Li J Clin Invest. 1955;34(3):500-510. https://doi.org/10.1172/JCI103099. Research Article Find the latest version: https://jci.me/103099/pdf HEMODYNAMIC CHANGES DURING THIOPENTAL ANESTHESIA IN HUMANS: CARDIAC OUTPUT, STROKE VOLUME, TOTAL PERIPHERAL RESISTANCE, AND INTRATHORACIC BLOOD VOLUME 1, 2 By BENJAMIN ETSTEN AND T. H. LI 8 (From the Department of Anesthesia, Tufts College Medical School and New England Center Hospital, Boston, Mass.) (Submitted for publication August 13, 1954; accepted November 24, 1954) Thiopental, monosodium 5-ethyl-5- (1-methyl- the patient was brought to a quiet anesthesia preparation butyl) -thiobarbiturate, is extensively used in room for study and was placed in the supine position clinical anesthesia either as a primary with one arm resting on a pillow above the angle of anesthetic Louis. A 15-gauge needle was placed in the median agent for short surgical procedures or as a sup- basilic vein of the elevated arm and was connected with plementary drug in conjunction with other anes- a three-way stopcock for the administration of T-1824 thetics. Fatalities have been attributed to its use (Evans Blue) and thiopental. A thin-walled 18-gauge (1, 2) and cardiac arrest has occurred following needle with stylet was inserted into the brachial artery of its administration to patients under spinal anes- the other arm for the collection of blood samples. Elec- trocardiograph electrodes were appropriately placed and thesia (3). electroencephalograph electrodes were positioned accord- Most of the information concerning the cardio- ing to the method of Kiersey, Bickford, and Faulconer circulatory effects of thiopental has been derived (8). from animal experimentation (4, 5). Although Control observations were made after a steady rest- there have been numerous clinical reports de- ing state was maintained for at least 30 minutes. It was considered that a basal resting state was obtained only scribing changes in blood pressure, pulse rate when the pulse rate was below 84 per minute. An in- and respiration during its administration, quanti- travenous drip of 0.2 per cent thiopental was adminis- tative investigations on the effect of this agent on tered slowly. The rate of flow was adjusted to produce the cardiocirculatory dynamics in man are meagre specific levels of anesthesia as defined by Kiersey, Bick- (6, 7). In view of its extensive use and the com- ford, and Faulconer (8) and monitored by continuous EEG tracings. The observations were correlated ac- plications ascribed to its administration, a critical cording to the specific levels of narcosis as shown in the analysis of the hemodynamic changes which occur following classification: at various levels of thiopental narcosis in patients prior to surgery will form the basis of this com- E.E.G. Pattern Level of Anesthesia 0 Control munication. I Hypnosis METHOD II Light III and IV Deep Cardiac output and related hemodynamic determina- tions were obtained on 14 patients prior to surgery. The average duration of each study was two hours and These subjects were in good physical condition and had the total dosage of thiopental ranged from 0.6 to 1.0 gm.; no discernible cardiovascular or pulmonary disease (aver- 100 per cent oxygen was administered throughout the age age-41 years; range 14 to 60 years). The pre- procedure. anesthetic dosage of morphine and scopolamine varied After specific levels of thiopental anesthesia were according to the age, weight, and physical status. Ninety maintained for 15 minutes, the following observations minutes after a subcutaneous administration of morphine were made: cardiac output, mean arterial pressure, total (5.4 to 8.0 mgm.) and scopolamine (0.26 to 0.43 mgm.), peripheral resistance, stroke volume, mean circulation time, intrathoracic blood volume, arterial oxygen con- 'Aided by a research grant from the National Insti- tent and capacity, carbon dioxide content and pH, and tutes of Health, U. S. Public Health Service, No. H-1711 electrocardiographic recording. (C2). The cardiac output was determined by the dye dilution 2A preliminary report was presented at the meeting of technique (9). The injection of T-1824 in a 0.5 per the Federation of American Societies for Experimental cent solution and collection of samples from the brachial Biology, Atlantic City, New Jersey, April 16, 1954. artery were carried out according to the modified 8 Charlton Fellow-Tufts College Medical School. method of Etsten, Li, and Fisher (10, 11). The stand- 500 HEMODYNAMICS DURING THIOPENTAL ANESTHESIA 501 ard deviation of the difference between the Fick and dye curve until recirculation appears. The last term methods was 12.7 per cent, and the standard deviation CK+1 (TK+1 + rL) equals the sum of the products for the difference of duplicate values of cardiac indexes by the modified dye technique was 2.4 per cent (10, 11). of all extrapolated terms multiplied by time. Brachial arterial pressure was measured by means of a The mean circulation time was determined by plotting Statham strain gauge (model P-23A) and continuously on semi-logarithmic graph paper the concentration of recorded on a multi-channel, direct-writing oscillograph the dye in each sample against the time of collection of with a frequency response of 60 C.P.S. The mean ar- the sample. The mean circulation time is in close agree- terial pressure was determined by planimetry of the pulse ment to a vertical line that divides the area subtended by wave. Samples of arterial blood were drawn immediately the primary dye curve into two equal parts. after the cardiac output determination for analysis of 3. Intrathoracic blood volume (15, 16): The volume oxygen content and capacity, carbon dioxide content, and calculated from the mean circulation time X repre- pH (Cambridge Electron Ray pH Meter-Research C6O. Model). Values of the pH were accepted when the du- sents the volume of circulating blood from the point of plicates checked within a 0.02 unit. The carbon dioxide injection of the dye in the peripheral arm veins, right tension was calculated from the carbon dioxide serum heart, pulmonary vasculature, the left heart and the ar- content and pH values using the nomogram of Peters teries to the point of sampling. and Van Slyke (12). The hematocrit was determined Intrathoracic blood volume (liters) = C XO.X M.C.T., by centrifuging the heparinized blood in Wintrobe tubes. 60 The following values were calculated from the formulae: where C.O. = cardiac output in L. per min. and M.C.T. = 1. Cardiac output: The cardiac output was calculated mean circulation time in seconds. Changes of the intra- from the dye dilution curve according to the modified thoracic blood volume were not considered as significant method of Hamilton, Moore, Kinsman, and Spurling when they were less than 15 per cent of the control val- ues (7, 17). 60X 10 (10, 13): F = s X 00 -H~ : F represents the car- 4. Total peripheral resistance: diac output in liters per minute, I the amount of in- T.P.R( dYnes- sec.) jected dye in mgm., H the hematocrit (not corrected for trapped plasma) and S the sum of all the dye concen- Mean arterial blood pres. (mm. Hg) X 1,332 trations in the primary circulation taken at 1-second C.O. (cc./sec.) intervals. The gradient was represented by the arterial pressure A semi-log plot is made from the experimental data only, since it has been found that the right auricular and the value of S is obtained in the following manner pressure is unchanged during thiopental anesthesia (18). (10, 11, 14): S = A + B. A equals the sum of CQ + C2 + 5. Left ventricular work: ... CK, i.e., all dye concentrations in mgm. per liter ex- L.V.W (Kg.-meters per min.) = 0.0135 X C.O. (L. per cept the last term on the descending limb of the primary min.) X mean arterial blood pressure (mm. Hg) curve before recirculation starts. This last term is 6. Statistical analysis: The per cent change refers to designated CK+1, and CK is the one just prior to this the mean per cent change of each group. Each patient last term. A straight line is extrapolated from CG, and served as his own control. Only the control values for B equals the sum of the concentrations obtained from the those patients studied under a specific level of anesthesia extrapolated portion of the descending limb of the curve. were used to calculate the per cent change found during The last three or more points of the primary circula- that specific level. The mean of the control values for tion fall on a straight line corresponding to an exponen- the whole group was not used to calculate the per cent tial fall in dye concentration. From these few points a change found during any specific level of anesthesia since straight line is extrapolated to complete the graph of some patients were not studied throughout all of the the primary circulation. The sum of the dye concentra- levels. tions in this extrapolated portion of the graph is com- The probability or "P" value was obtained by the method of the Fisher's T-test. puted by the formula for geometric series. B = IC+1 and is added to the sum of A; r is the ratio of any term RESULTS of the series to the preceding term. 2. Mean circulation time: The mean circulation time The pertinent data are summarized in Table I; is the time taken by the dye particle of average speed to the mean, the standard deviation, and the stand- pass through the veins from the point of injection, the right heart, the lungs, the left heart, and the arteries to ard error of the mean of the absolute values are the point of sampling.