March, 1967 T h e J o u r n a l o[ P E D I A T R I C S
407
Evaluation of sedation during cardiac catheterization of children Analysis o] PaO~, PaCO~, pH, and base excess determinations during hemodynamic investigation
The effect o[ sedation by an ataractic mixture was evaluated in 58 children undergoing cardiac catheterization. Oxygen tension, carbon dioxide tension, and hydrogen ion concentration in arterial blood were measured by polarographic and potentiometric methods in these patients, who had minimal or no heart deject s. Ninety per cent had PaOx and PaC02 values within the adult normal range, indicating that the sedation had little effect on ventilation and oxygenation regardless o[ age. Significantly lower p H and calculated base excess values were [ound in children under I2 years o[ age. This tendency to acidosis in the younger child,ten, all of whom were made to last, may be on a metabolic ba;is since a comparison o/pre- and postfasting determinations revealed lower fasting values.
Raquel Israel, M.D.,** Arno R. Hohn, M.D., Iain F. S. Black, M.D.,** and Edward C. Lambert, M.D.* B U F F A L O , N. Y.
SEDATION is usually e m for children undergoing cardiac catheterization, its effect on blood gases has not been adequately evaluated. Whereas deep sedation may depress respiration, anxiety may lead to hyperventilation. Either alteration can result in disturbed cardiopulmonary function ALTHOUGH ployed
Supported in part by grants from the National Institutes o[ Health, United States Public Health Service (Grant T I HD-39 and N I H General Research Support Grant I-S10-FR-05493-03). ~Address, Children's Hospital, 219 Bryant St., Buffalo N. Y. 14222 "~eDrs. Israel and Bsack were Postdoctoral Research Fellows, National Heart Institute, United States Public Health Service.
or acid-base balance. As a result, exact assessment of a patient's status may be difficult. With the development of polarographic and potentiometric techniques f o r blood gas analysis, simple, fast, and accurate methods for the measurement of arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2), and hydrogen ion concentration (pH) have become available. With these determinations the state of oxygenation, ventilation, and acid-base balance can be evaluated. Consideration of these factors is important for proper interpretation of hemodynamic data. In order to assess the effect of sedation on children undergoing cardiac Vol. 70, No. 3, part 1, pp. 407-412
408
Israel et al.
The Journal of Pediatrics March 1967
catheterization, PaO~, PaCO~., and pH determinations were made on children with minimal heart disease during this procedure. PATIENTS
AND
METHODS
Children who were found during diagnostic cardiac catheterization and selective cineangiocardiography to have minimal disturbance of their hemodynamics, with either small left-to-right shunts or mild ventricular obstructions, were selected for this study. Fifty-eight patients, aged 3 to 19 years, met these criteria and were evaluated during the procedure. In 8 of them, no cardiac anomaly was demonstrated at the time of the study. Because of the selection of patients with minimal or no heart defects, it was assumed that cardiac disease did not affect the ventiiatory state or the oxygenation of arterial blood samples analyzed. The patients fasted from 12 to 15 hours prior to the time of blood sampling. All received the widely used sedative mixture ~ of 50 mg. (1 c.c.) meperidine, 12.5 mg. (0.5 c.c.) chlorpromazine, and 12.5 mg. (0.5 c.c.) promethazine. This mixture was given intramuscularly in a dosage of 1 c.c. per 10 kilograms of body weight with a maximum dose of 2 c.c. The children were studied in the supine position. The body temperature was monitored by means of a rectal thermistor and the respiratory rate was recorded. In 9 patients the PaO2, PaCO.,, and pH were also determined on the afternoon before cardiac catheterization, and the values obtained were compared to those taken after sedation. During cardiac catheterization arterial blood samples were obtained from the left atrium, the left ventricle, or the aorta within 2 hours of administration of the sedative. In the case of patients studied prior to sedation, the blood sample was obtained from the radial artery by means of a special needle. 2 Sampling was done under anaerobic conditions with the use of syringes wet with heparin. PaO2, PaCOs, and pH determinations were made within 3 minutes after sampling. All measurements were carried out at 37.5 ~ C. with the use of the Instrumenta-
tion Laboratory pH/gas analyzer Model 113. ~ The calibration of the PO2 electrode, a modified Clark electrode, was checked at monthly intervals using 6 known gases of varying oxygen concentrations: O.)-free, 7 per cent, 15 per cent, 78.2 per cent, 90.85 per cent, and 99.7 per cent 02. The PO2 electrode response to the known gases was found to be linear within 2 mm. Hg in the Iow tension range and within 6 mm. Hg in the high range. The same linearity was found with tonometered blood if the readings were corrected by a membrane factor (see below). Each day the electrode was calibrated with oxygen-free gas and with 15 per cent oxygen, and recalibration with 15 per cent oxygen was also performed before each determination. Duplicate samples checked within 2 him. Hg. Blood from each study-patient was tonometered in an Instrumentation Laboratory tonometer for 10 minutes with a gas of known oxygen content to obtain a membrane factor which was used to correct the difference between the response of the electrode to gas and blood by multlplying the PaO2 readings by the membrane factor. These membrane factors varied between 1.03 and 1.13 with an average of 1.08. When indicated, the resulting PO2 was corrected for pH and temperature factors with the use of the Severinghaus nomogram. 3 The PaCO., was determined with a Severinghaus electrode. Duplicate determinations checked within 1 mm. The pH was measured with a glass electrode with checks within 0.01 pH unit. Both electrodes were calibrated before each determination. The base excess was calculated with the use of the Severinghaus blood gas calculator.t RESULTS
Table I shows mean, range, and standard deviation of the PaO2, PaCO2, pH, and base excess determinations for the 58 patients studied. An analysis of this information according to the presence or absence of heart ~Made by the Instrumentation Laboratory, Watertown, Mass. ~Obtalned from Radlometer, Copenhagen, Denmark.
Volume 70 Number 3, part 1
Sedation during cardiac catheterization
disease, as well as the type of heart defect, revealed a lack of significant variation of these values among the 8 patients with no cardiac defect, the 18 with mild outflow obstruction, and the 32 with small shunts. Thus the data indicated that the presence of mild heart disease had no influence on the results obtained. In Figs. 1, 2, 3, and 4 the values for PaO2, PaCO2, pH, and base excess, respectively, are plotted against age. The dotted horizontal lines indicate the limits of normal of PaO2 and PaCOo for adults suggested by Severinghaus, 4 the pH by Pitts 5 and Davenport, 6 and base excess by Siggaard-Andersen5 As demonstrated in Figs. 1 and 2, no correlation was found between age and PaO2 or PaCO2. With a single exception, the low PaO2 values were not the result of hypoventilation, since in all but one the corresponding PaCO2 values were below 45 mm. Hg. In the one exception the PaCO2 was 49 at the same time that the PaO2 was 66 ram. Hg. Three patients had evidence of hypoventilation as manifested by slight elevation of the PaCO2 (Fig. 2). On the same basis, 6 patients had evidence of hyperventilation with slightly low PaCO2's. Ninety per cent
Table I. Analysis of results
I No. PaO~ PaCO~ pH BE~
58 57 55 55
I Range
I Mean I S.D.
66-116 93.0 30-49 39.2 7.30-7.46 7.37 -9.70-+4.0 -2.5
-+10.8 +- 4.06 -+ 0.034 + 2.1
409
of the patients studied had neither hypoventilation nor depression of arterial oxygen tension by these standards. Figs. 3 and 4 appear to show that the pH and base excess are influenced by age. The younger patients had lower pH and base excess than the older ones, and after the age of 12 years no pH values were below 7.35. The children below 12 years of age had a mean pH of 7.35 and a mean base excess of -3.9 mEq. per liter. In the older patients the mean pH and base excess were 7.40 and -0.42 mEq. per liter, respectively. The difference between the two groups was significant, with p = .001 for both pH and base excess. In Table I I are the data obtained from 9 patients on whom the studies were done before and after sedation. There was no significant depression in PaO2 before and after sedation. In 4 instances minimal changes in the PaCO2 were present. However, with the exception of the last patient, the pH and base excess were found to be lower after fasting and sedation. This is significant, with a p value between 0.05 and 0.02. DISCUSSION
1V~eai~ values of PaO~ ranging from 70 to 100 mm. Hg have been reported in the past 5 years with tests performed in normal and preoperative adults by polarographic techniques. 8-11 Although Severinghaur has proposed a lower limit of normal of 80 mm. Fig, no recent values obtained by these methods are available for normal children. In this
Table II. Comparison of values obtained before and after fasting and sedation
Age (years) 5 589 10 10 13 14 1489 15 15r~ ~'Base excess.
] I
PaOe 88 93 91 9,6 96 97 86 104 93
Presedation [ PaCOe t pH 37 33 38 31 37 46 38 39 43
7.43 7.40 7.43 7.42 7.40 7.44 7.42 7.40 7.42
. I
BE~ +1,0 -4,0 +1.5 -3.0 +6,0 +0.8 0 +2.2
Post [asting and sedation PaOe I PaC02 I pH [ 95 95 90 103 95 108 97 103 87
33 37 39 40 43 38 39 40 35
7.33 7.35 7.40 7.37 7.35 7.40 7.37 7.37 7.46
BE~ -7.5 -4.5 -0.2 -1.8 -0.9 -2.1 -1.8 +1.1
4 10
Israel et al.
The Journal of Pediatrics March 1967
n20 T 50--
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Fig. 1. Arterial oxygen tension (PaO2) obtained during cardiac catheterization in sedated children with minimal or no heart disease. Horizontal line indicates the lower limit of normal for unsedated adults. 4 There is no significant variation with age. 7.46 --
Fig. 9. Arterial carbon dioxide tension (PaCe2) obtained during cardiac catheterization in sedated children with minimal or no heart disease. The two horizontal lines indicate the upper and lower limits of normal for unsedated adults. 4 There is no significant variation with age.
9
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8
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Fig. 3. Arterial pH obtained during cardiac catheterization in sedated children with minimal or no heart disease. The two horizontal lines indicate the upper and lower limits of normal for adults.5, 6 significantly lower pH values were found in younger patients.
Fig. 4. Arterial base excess (mill 9 per liter) obtained during cardiac catheterization in sedated children with minimaI or no heart disease. The two horizontal lines indicate the usual limits for adults. ? A significant change appears to occur at 12 years of age, lower values being obtained in the younger patients.
study 90 p e r c e n t of the sedated c h i l d r e n h a d values a b o v e this level (Fig. 1), i n d i c a t ing t h a t in these p a t i e n t s t h e s e d a t i o n did n o t significantly i n t e r f e r e w i t h oxygenation. T h e lowest v a l u e of 66 m m . H g was e q u i v a l e n t to 92 p e r c e n t o x y g e n saturation. T h e
lack of significant effect on PaO2 by t h e s e d a t i o n was c o n f i r m e d in 9 patients by t h e finding of a n insignificant c h a n g e in the PaO~ b e f o r e a n d after s e d a t i o n ( T a b l e I I ) . T h e r e were, h o w e v e r , c e r t a i n c h i l d r e n in this study w h o s e b l o o d 0 2 tensions w e r e n o t
Volume 70 Number 3, part 1
within the anticipated range. Three of the 5 patients who had PaO2 values of 110 ram. Hg or more had corresponding PaCO~ values which were below 35 ram. Hg indicating hyperventilation as a cause for the high oxygen tensions. In the others no explanation could be found. Hypoventilation accounted for only one of the six instances in which the PaO2 was found to be below 80 ram. Hg (Fig. 1). An explanation for low PaO2 values in the presence of a normal PaCO2 has been advanced by Bendixen, Hedley-Whyte, and Lauer. 12 They found that tidal breathing in anesthetized patients was associated with progressive atelectasis. This may be prevented or relieved in the normal, awake individual by periodic deep respirations. Arteriovenous shunts, which develop as a result of the atelectasis, cause the low PaO2 values. Data obtained in a case not included in this study seem to verify this hypothesis. This individual had a resting PaO2 of 69 which rose to 87 ram. Hg following the onset of crying. A corresponding change in PaCO2 from 38 to 35 mm. Hg was also noted. Sedation was also found to have little effect on ventilation as measured by the PaCO2, which Avery *a has termed the "best single measure of alveolar ventilation." Accepting the normal range of 35 to 45 mm. Hg proposed by Severinghaus, ~ 3 of the 57 study patients were hypoventilating to a slight degree, the highest value being 49 mm. Hg. Only i of these 3 patients had hypoxemia; she was the 5-year-old girl with shallow respirations whose PaO2 was 66 mm. Hg and PaCO, was 49 ram. Hg. The older 2 patients with PaCO2 of 46 and 47 mm. Hg had PaO2's of 88 mm. Hg and 1 t I ram. Hg, respectively. Six children were hyperventilating, as indicated by PaCO2 measurements between 30 and 33 ram. Hg. The hyperventilation in these few instances was probably due to the excitement produced by the cardiac catheterization. Similarly, in the 9 patients for whom determinations were made before and after sedation, the slight decreases in PaCO2 found in 2 before and 2 after study were probably also the result of anxiety. The blood gas data presented confirm and
Sedation during cardiac catheterization
4 11
amplify the work of Lundborg and associates, 14 who measured the PaO2 and PaCO2 in 20 children during diagnostic cardiac catheterization. The majority of their children, who had been sedated with the same ataractic mixture used in the current study, had values for PaO2 and PaCO2 within the adult normal range. Consequently, it is felt that whereas premedicating doses of narcotics may evoke measurable ventilatory changes, 15 the sedation used in this study with few exceptions did not significantly alter the PaO2 or PaCO2. In regard to pH and base excess, the group of patients under 12 years of age had significantly lower pH values (Fig. 3) than those over 12. A mild metabolic acidosis as a result of fasting may have caused these lower values. The low base excess values found (Fig. 4) appear to confirm a metabolic cause for the acidosis. Table II indicates that blood samples from sedated fasting patients have lower pH and base excess values than samples taken the previous afternoon. One younger child had pH and 2 had base excess values below adult normal levels during the catheterization (i.e., after sedation and fasting), whereas these values were within the normal adult range prior to the test. These findings correlate well with the work of Cassels and Morse, 16 who found lower pH and CO2 contents in younger children during their study of acid-base balance. Since their patients' blood samples were drawn before breakfast, it was suggested that the overnight fast decreased bicarbonate concentration as a result of increased keto acids in the blood. While the observed pH and base excess changes can be explained by the data presented, other possibilities exist. Further studies may show that younger children usually have lower pH and calculated base excess values. SUMMARY
AND CONCLUSIONS
The effect of sedation during cardiac catheterization was evaluated by polarographic and potentiometric methods in 58 sedated, fasting children with mild or no heart disease. The sedation consisted of the
4 12
Israel et al.
widely used a t a r a c t i c mixture of meperidine, chlorpromazine, a n d promethazine. Arterial blood was analyzed for oxygen tension ( P a O 2 ) , carbon dioxide tension ( P a C O 2 ) , a n d pH. Ninety per cent of the patients were found to have normaI oxygenation a n d ventilation as manifested by n o r m a l PaO2 and PaCO2 values. O n l y 3 patients h a d m i n i m a l elevation of PaCO2 values, indicating slight hypoventilation. N o correlation between age a n d PaO2 or PaCO2 was found. However, the p H a n d calculated base excess were found to be significantly lower in those less than 12 years of age. C o m p a r i s o n of prea n d postfasting p H and base excess determination revealed t h a t the fasting values were lower. T h u s this tendency to metabolic acidosis in the younger children m a y have been due to the fasting state. I t is concluded that these measurements are of special value in d e t e r m i n i n g the clinical state of children undergoing cardiac catheterization. T h e ataractic sedative mixture h a d m i n i m a l effect on the ventilatory state a n d level of oxygenation in the great m a j o r i t y of the study children, all of w h o m h a d essentially normal hemodynamics.
The Journal o[ Pediatrics March 1967
5. 6. 7. 8.
9.
10.
11.
12.
13.
REFERENCES
1. Smith, C., Rowe, R. D., and Vlad, P.: Sedation of children for cardiac catheterization with an ataractic mixture, Canad. Anaesthetists' Soc. J. 5: 35, 1958. 2. Bucci, G., Scalamandre, A., Savignoni, P. G., Orzalesi, M., and Mendicini, M.: Crib-side sampling of blood from the radial artery, Pediatrics 37: 497, 1966. 3. Severinghaus, J. W.: Oxyhemoglobin dissociation curve corrections for temperature and pH variation in human blood, J. Appl. Physiol. 12: 485, 1958. 4. Severinghaus, J. W.: Blood gas concentra-
14.
15.
16.
tions, in Fenn, W. O., and Rahn, H., editors: Handbook of physiology, Sect. 3, respiration, Washington, D. C., 1965, American Physiological Society, vol. 2, p. 1475. Pitts, R. F.: Physiology of the kidney and body fluids, Chicago, 1963, Year Book Medical Publishers, Inc., p. 146. Davenport, H. W.: The ABC of acid-base chemistry, ed. 4, Chicago, 1965, University of Chicago Press, p. 84. Siggaard-Andersen, O.: The acid-base status of the blood, ed. 2, Baltimore, 1964, The Williams & Wilkins Company. Cosby, R. S., Stowell, E. C., Jr., Morrison, D. M., Mayo, M., Ruymann, F. B., and Bernard, B.: Continuous measurement of alveolo-arterial gradients at ambient and anoxic levels, J. Appl. Physiol. 17: 1, 1962. Conway, C. M., Payne, J. P., and Tomlin, P. J.: Arterial oxygen tensions of patients awaiting surgery, Brit. J. Anaesthetists 37: 405, 1965. Stephen, C. R., and Talton, I.: Immediate postoperative care, with particular reference to blood-gas studies, Canad. Anaesthetists' Soc. J. 11: 586, 1964. Ayres, S. M., Criscitello, A., and Grabovsky, E.: Components of alveolar-arterial O.~, difference in normal man, J. Appl. Physiol. 19: 43, 1964. Bendixen, H. H., and Hedley-Whyte, J., and Lauer, M. D.: Impaired oxygenation in surgical patients during general anesthesia with controlled ventilation. A concept of atelectasis, New England J. Med. 269: 991, 1963. Avery, M. E.: The lung and its disorders in the newborn infant, Philadelphia, 1964, W. B. Saunders Company, p. 40. Lundborg, R. O., Sessler, A.D., and Moffitt, E. A.: Anesthesia in a clinical cardiovascuIar laboratory, S. Clin. North America 45: 863, 1965. Severinghaus, J. W., and Larson, C. P., Jr.: Respiration in anesthesia, in Fenn, W. O., and Rahn, H.: editors: Handbook of physiology, Sect. 3, respiration, Washington, D. C., 1965, American Physiological Society, vol. 2, p. 1237. Cassels, D. E., and Morse, M.: Arterial blood gases and acid-base balance in normal children, J. Clin. Invest. 32: 824, 1953.