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ATROPINE REVERSAL OF HYPERCARBIA DURING ENFLURANE ANAESTHESIA
Br.J. Anaesth. (1979), 51, 221
ATROPINE REVERSAL OF HYPERCARBIA DURING ENFLURANE ANAESTHESIA W. M . WAHBA AND J. SADKOVA SUMMARY
During a study of the pattern of breathing during enflurane anaesthesia, we found that there was a relationship between the forced expiratory volume in one second (FEV^o) and Pa C02 . The increase in FaCOa during anaesthesia compared with the value before anaesthesia correlated with the ratio FEV1.0/ vital capacity* while the values during anaesthesia correlated with the ratio FEV1.0/height.f We suggested that airway resistance (-RAW) m a v influence the increase in Pacc,2 occurring under general anaesthesia with spontaneous ventilation. If this is so, a reduction in i? A W should improve pulmonary ventilation. The present study was designed to test this hypothesis by measuring expired minute volumes (VE) and arterial blood-gas tensions before and after the i.v. administration of atropine in 35 healthy adult patients undergoing minor peripheral surgery. Atropine was chosen because its effects on flow resistance have been measured by Don and Robson (1965). METHODS
Thirty-five healthy adults undergoing elective operations on the periphery of the body gave consent for the study, which was approved by the Hospital o, (kPa) = 10.08-0.08 (r = 0.6 P< 0.01). t Paco, (kPa) = 9.17-1.2 FEV^o/height (m) (r = 0.65 P< 0.001). W. M. WAHBA, M.B., B.CH., M.SC. (MCGILL), F.R.C.P.(C).;
J. SADKOVA, M.D., F.R.C.P.(C).; Department of Anaesthesia,
Queen Elizabeth Hospital of Montreal, and McGill University. Correspondence to W. M. Wahba, Department of Anaesthesia, Queen Elizabeth Hospital of Montreal, 2100 Marlowe Avenue, Montreal, Quebec H4A 3L6, Canada. 0007-0912/79/030221-06 S01.00
Research and Ethics Committee. Measurements were made in all patients (group I) 5 min after the injection of atropine and in 20 (group II) the measurements were repeated 20 min after injection. The 15 patients in group I who were studied only at 5 min were not distinctly different from the other patients. The biometric data are summarized in table I. Premedication consisted of anileridine (U.S.P.) 12.5-37.5 mg and promethazine 12.5-25 mg, according to body weight, given i.m. 1 h before operation. After induction of anaesthesia with thiopentone 2-3 mg kg" 1 i.v. and orotracheal intubation facilitated by suxamethonium 1 mg kg" 1 , all the subjects received enflurane in nitrous oxide 3 litre min" 1 and oxygen 2 litre min" 1 from a semi-closed circle system with carbon dioxide absorption. Ventilation was assisted manually until the patient resumed adequate spontaneous breathing. The vaporizer (Cyprane) setting of 2-3% was adjusted on the basis of arterial pressure, heart rate, lack of lacrimation and the absence of response to surgical stimulation. No change in the vaporizer setting was made during the period of study. Twenty to 30 min after the surgical incision was made, when tidal volume and frequency were steady for 5 min, VE was measured using a Wright respirometer connected to a low resistance, uni-directional valve. Tidal volume ( F T ) was derived from the measured values of VE and breathing frequency (/). The measured values were not corrected to BTPS. Arterial blood was obtained from a radial artery anaerobically into heparinized syringes, which were packed in ice. Blood-gas tensions and pH were determined within 10 min using standard electrodes calibrated with 0,5 and 10% carbon dioxide (Corning 165 blood-gas analyser). The results were not corrected for time, introducing a © Macmillan Journals Ltd 1979
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Atropine was given i.v. to 35 spontaneously breathing healthy adults anaesthetized with enflurane to determine if it would reduce Paco, by improving gas exchange. Five minutes after administration of atropine, P^co, decreased from mean 7.18 to 6.65 kPa ( —7%), while mean 9?. increased from 4.8 to 6.1 litre min" 1 ( + 27%). These changes were maintained 15 min later in the 20 patients studied at that time. Older and more obese patients showed a more significant change. Respiratory frequency and Pao, did not alter.
222
BRITISH JOURNAL OF ANAESTHESIA TABLE I. Details of patients studied {mean ± SEM) Weight (kg)
Height (cm)
Weight Height
Surface area*
(yr)
Measurements at 5 min only (» = 35)
40.1 2.9
70.2 3.2
167.5 2.3
0.42 0.01
1.79 0.03
Measurements at 5 and 20 min (n = 20)
41.3 4.1
71.6 5.8
169.9 2.2
0.43 0.01
1.80 0.05
Age
Group I II
Basis of classification
(m 2 )
* Dubois and Dubois (1916).
RESULTS
There were no significant differences between the two groups with respect to age and body build (table I) or in the blood-gas and ventilation values before the administration of atropine (table II). Ventilation before atropine in the 15 patients studied at 5 min was slightly greater than that in the other 20 patients (P<0.1) but there was no significant difference in •^aco2-
Five minutes after the injection of atropine, mean VE increased by 27% from 4.8 ±0.18 to 6.1 + 0.24 litre min""1 in group I (P<0.001). In group II, mean VE also increased by 27% from 4.49 + 0.21 to 5.69 + 0.28 litre min (P< 0.001). Arterial Pacc,2 in group I decreased by 7% from 7.18±0.16 to 6.65±0.19kPa (P< 0.001). In group II, mean Pa C02 before atropine was 6.91 + 0.17 kPa and mean Pacc,2 5 min after atropine was 6.17 + 0.20 (P< 0.001). The measurements at 5 min in group II were maintained at 20 min (table II) without any significant difference between the values at these time intervals. For analysis of these data, two-way analysis of variance and Student's t test were used. Respiratory frequency, Pa 02 , pH and standard bicarbonate did not change significantly at any time in either group. The values of VE were standardized to allow for differences in size between individuals by the use of
TABLE II. Measurements of ventilation and arterial blood-gases before and after atropine (mean±SEM) Group II (n = 20)
Group I (n = 35) Before
5 min after
19.16 0.8 22.6 (mmol litre" 1 ) 0.4 7.25 (unit) 0.01 7.18 (kPa) 0.16 (b.p.m.) 16.0 0.8 (ml) 316.9 15.2 4.8 (litre min" 1 ) 0.18 2.66 (litre min" 1 m" 2 ) 0.10
19.06 0.67 20.7 0.4 7.26 0.01 6.65 0.19 16.9 0.8 374.2 17.4 6.1 0.24 3.39 0.13
Measurement Pa 0 , HCO 3 P
H
•Paco, / VT VE
VEISA
(kPa)
P
Before
5 min after
n.s.
19.61 1.09 22.2 0.5 7.24 0.02 6.91 0.17 15.9 0.8 295.0 18.2 4.49 0.21 2.46 0.10
19.57 1.08 22.0 0.6 7.24 0.08 6.17 0.20 16.9 0.7 339.0 25.0 5.69 0.28 3.13 0.15
n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
P
n.s. n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
20 min after 18.96 1.04 21.4 0.6 7.26 0.02 6.33 0.21 16.8 0.7 350.0 20.0 5.81 0.35 3.21 0.16
P
n.s. n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
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possible error of 0.07-0.01 kPa for Pacc,2 (Kelman and Nunn, 1966). Atropine 0.01 mg kg" 1 was injected i.v. and the measurements repeated 5 min later in all patients, and 20 min after the injection in 20 patients. Statistical analysis of the data was performed using Student's t test, two-way analysis of variance and by regression analysis using the least squares method.
ATROPINE AND Pco 2 DURING ENFLURANE ANAESTHESIA the ratio FE/surface area (SA). Mean F E / S A for all subjects increased from 2.66 + 0.1 to 3.39 + 0.13 litre m i n ^ m - 2 5 min after atropine (P< 0.001). In group II patients, F E / S A increased from 2.46 ±0.10 to 3.13+ 0.15 litre min- 1 m- 2 (P<0.001), at 5 min, a value not significantly different from that noted at 20 min (3.21 + 0.16 litre min- 1 m~2). Figure 1 shows the observed mean values of Pa C02 and F E / S A in the two groups at the stated time intervals.
223
-7
O-
Group I j s min after
1 Before
r •• s min after
1 20 min after
I,
i
1.5
e.o
2.5
4.5
5.5
1/E/SA (litre m' 2 )
r 4.0
<
-5
,1
A
I
FIG. 1. Changes in mean Paco, a n d P E / S A before and after administration of atropine.
The relationship between F E / S A and PaC0]! for all the data is shown in figure 2. This relationship is expressed by the following equation: PaC0!! = 8.5-0.61 FE/SA
(r = 0.51, P<0.001)
DISCUSSION
The anaesthetic technique used in this study may be criticized because alveolar concentrations of the anaesthetic agents were not identical. However, we believe that it is preferable to use the standard technique appropriate for the surgery. The purpose of the present study was to determine if the i.v. injection of atropine during enflurane anaesthesia would have beneficial effects on gas exchange. Although there were individual differences in the degree of change in Pa C02 in our patients, mean PaCOa decreased and mean ventilation increased markedly following the injection of atropine. These
FIG. 2. Relationship between KE/SA and Paco, for all measurements. There is a trend with reference to time of sampling. O = before atropine; • = 5 min after atropine; • = 20 min after atropine.
changes may result from a reduction in airway resistance or central stimulation of ventilation. Central stimulation would cause an increase in respiratory rate or tidal volume, or both. We found no change in respiratory frequency, but the effect may have been masked by narcotic premedication. An increase in central respiratory drive can be measured by comparing the tracheal pressures generated during airway occlusion (Po) at functional residual capacity (FRC) before and after atropine. These measurements would differentiate between changes in central inspiratory drive and peripheral effects (Milic-Emili and Grunstein, 1976). We performed these measurements in four other subjects (G. B. Drummond and W. M. Wahba, unpublished observations) premedicated with diazepam and anaesthetized with enflurane in a mixture of nitrous oxide in oxygen and found no changes in occlusion pressure or in the ratio of inspiration to expiration. Frequency was unchanged also. These preliminary results suggest that the main site of action of i.v. atropine is peripheral rather than central. Mean flow rates must have increased following the injection of atropine, probably as a result of reduced airway resistance. There are conflicting reports on the effects of atropine on RAW during
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f Before
Group E
BRITISH JOURNAL OF ANAESTHESIA
224
The lack of a relationship between F E / S A and Pa c02 with time of measurement (fig. 2) is a reflection of individual variability in the change in •PaC02 and in deadspace, and of the non-steady state. Analysis of individual data at 5 min revealed that the extent of change in Pacc,2 could be related to the age and body build of the patient. By arbitrarily choosing a change in Pa C02 greater or less than 0.67 kPa, we subdivided our subjects into two groups (table III). The patients with greater reductions in Pa C02 (mean change of -0.97kPa) were older and more obese (P<0.05). These patients showed a greater increase in F E / S A (P<0.01) and a greater decrease in Pa C02 (P< 0.001) after atropine. It is known that the reduction in FRC following the induction of anaesthesia is greater in older subjects (Hewlett et al., 1974) and also in patients with high weight : height ratios (Don et al., 1970). An inverse relationship exists between lung volume and airway resistance. Greater improvements following atropine may be expected in patients with smaller FRC values where airways resistance has a more marked influence on ventilation. However, obese patients received a larger dose of atropine, since dosage was based on body weight. If this increase in dose was inappropriate, the changes may be a reflection of a dose-response relationship. Changes in VE precede those in -PaC02 because of the size of the body stores of carbon dioxide. Consequently, the disproportionate increase in F E (+ 27%) compared with the decrease in Pa C02 (—7%) may indicate that a steady state was not present 5 min after injection of atropine. Fifteen minutes later a more clearly defined difference in the distribution of the data relative to the time of measurement could be noted (fig. 3). However, the reduction in Pa C02 may have been limited by the increasing deadspace and the deepening of anaesthesia. By inference, a steady state was probably absent at 20 min.
TABLE III. Data grouped for patients who exhibited a change in Paco, greater or less than 0.67 kPa following i.v. atropine KE/SA
(ml m" 2 ) Age (yr)
Wt./ht. (kgcrn- 1 )
Before
After
(kPa) Before
After
Change <0.67kPa
35.7 3.4
0.40 0.01
2.76 0.24
3.33 0.28
7.2 0.21
6.84 0.21
Change >0.67kPa
48.5 5.1
0.44 0.02
2.61 0.10
3.39 0.14
7.22 0.27
6.21 0.33
P
<0.05
n.s.
< 0.001
<0.05
n.s.
<0.01
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anaesthesia. Don and Robson (1965) reported that total flow resistance in patients anaesthetized with nitrous oxide was decreased by 33% following atropine in the same dosage as was used in our study. On the other hand, Brakensiek and Bergman (1970) reported that atropine 0.8 mg i.v. during halothane anaesthesia reduced RAW only in subjects with pre-existing high airways resistance. In awake subjects, i? A W is reduced markedly by atropine (Vincent et al., 1970). These authors found that total pulmonary resistance during both inflation and deflation was reduced, with a greater effect during inflation. They confirmed also that lung volume history influences resistance. Daly, Ross and Behnke (1963) reported a small reduction in RAW following atropine in awake man. Groto, Whitman and Arakawa (1978) have reported recently that i.v. atropine 0.008 mg kg" 1 significantly increased expiratory flow functions (FEV 1 . 0 %, maximum mid-expiratory flow and maximum expiratory flow at 50% total lung capacity) with a small, transient and insignificant decrease in -RAW. The authors interpreted these observations in six awake volunteers as a decrease in small airways resistance. The improvement in expiratory flow functions was detectable lOmin after injection and lasted longer than 1 h. Thus the bulk of evidence supports the thesis that our results may be explained on the basis of a reduction in -RAW. The increase in tidal volume noted here is greater and of longer duration than that following the insertion and the subsequent removal of resistances (threshold and tubular) in the breathing circuit reported by Nunn and Ezi-Ashi (1961). Vagally mediated respiratory reflexes were probably operative in Nunn's study despite the use of anticholinergic drugs, and this may explain the differences in the results between the two studies.
ATROPINE AND Pco2 DURING ENFLURANE ANAESTHESIA
225
9
Don, H. F., Wahba, W. M., Cuadrado, L., and Kellar, K. (1970). The effects of anesthesia and 100 percent oxygen on the functional residual capacity of the lungs. Anes-
-8
Dubois, E., and Dubois, D. (1916). Clinical calorimetry. A formula to estimate the approximate surface area if height and weight be known. Arch. Intern. Med., 17,863. Groto, H., Whitman, R. A., and Arakawa, K. (1978). Pulmonary mechanics in man after administration of atropine and neostigmine. Anesthesiology, 49, 91. Hewlett, A. M., Hulands, G. H., Nunn, J. F., and Heath, J. R. (1974). Functional residual capacity during anaesthesia. II: Spontaneous ventilation. Br.J. Anaesth., 46, 486. Kelman, G. R., and Nunn, J. F. (1966). Nomograms for correction of blood, Po 2 , Pco 2 , pH and base excess for time and temperature. J. Appl. Physiol., 21, 1484. Milic-Emili, J., and Grunstein, M. M. (1976). Drive and timing components of ventilation. Chest (Suppl. 1), 70, 131. Nunn, J. F., and Ezi-Ashi, T. I. (1961). The respiratory effects of resistance to breathing in anesthetized man.
r
thesiology, 32, 521.
6
fc/SA (litre m" ) FIG. 3. Relationship between F E / S A and Paco, before and 20 min after atropine (group II). There is a distinct trend with reference to time of sampling. O = before; • = 20 min after.
Hypercarbia causes bronchodilatation (Aviado, 1975) and it is surprising that atropine can still exert such an effect under these circumstances. The clinical implications of this study are that hypercarbia during enflurane anaesthesia can be limited but not reversed by the use of atropine, particularly in older and more obese patients. ACKNOWLEDGEMENTS
The authors thank Professor J. Milic-Emili and Dr I. D. S. Gillies for their very valuable advice. Ohio Chemical Products, Canada, donated a supply of Ethrane and financial support for the purchase of a desk-top calculator for the statistical analysis.
Vincent, N. J., Knudson, R., Leith, D. E., Macklem, P. T., and Mead, J. (1970). Factors influencing pulmonary resistance. J. Appl. Physiol., 29, 236. INVERSION DE L'HYPERCARBIE PAR L'ATROPINE PENDANT UNE ANESTHESIE A L'ENFLURANE RESUME
On a administre de l'atropine par voie intraveineuse a 35 adultes en bonne sant£, respirant spontanement, anesthesias a l'aide d'enflurane, pour voir si Ton pourrait reduire la Paco, e n ameliorant l'echange de gaz. Cinq minutes apres l'administration d'atropine, la Paco, a diminue d'une moyenne de 7,18 a 6,65 kPa ( — 7%), alors que le VE moyen.a augmente de 4,8 a 6,1 litre min- 1 ( + 27%). Ces variations existaient toujours 15 min plus tard sur les 20 patients qui faisaient a ce moment-la l'objet de P6tude. Les patients plus ages et plus obeses ont accuse des variations plus prononcees. La frequence respiratoire et la Pao, n'ont pas ete modifiees. DURCH ATROPIN BEWIRKTE AUFHEBUNG VON HYPERKARBIE WAHREND ENFLURAN-NARKOSE
REFERENCES
Aviado, D. M. (1975). Regulation of bronchomotor tone during anaesthesia. Anesthesiology, 42, 68. Brakensiek, A. L., and Bergman, N. A. (1970). The effects of halothane and atropine on total respiratory resistance in anesthetized man. Anesthesiology, 33, 341. Daly, W. J., Ross, R. C , and Behnke, R. H. (1963). The effect of changes in the pulmonary vascular bed produced by atropine, pulmonary engorgement and positive pressure breathing on diffusing and mechanical properties of the lung. J. Clin. Invest., 42, 1083. Don, H. F., and Robson, J. G. (1965). The mechanics of the respiratory system during anesthesia. The effects of atropine and carbon dioxide. Anesthesiology, 26, 168.
ZUSAMMENFASSUNG
Atropin wurde intravenos an 35 spontan atmende, gesunde Erwachsene verabreicht, die mit Enfluran narkotisiert waren; es sollte festgestellt werden, ob dies durch verbesserten Gasaustausch zu einer Verringerung von Paco fuhren wiirde. Funf Minuten nach Verabreichung der Droge sank Paco, v ° n einem Mittelwert von 7,18 auf 6,65 kPa ( — 7%), wahrend der Mittelwert von VE von 4,8 auf 6,1 Liter min- 1 (+ 27%) anstieg. Diese Veranderungen blieben erhalten bei den 20 Patienten, die 15 Min spater untersucht wurden. Altere und fettleibigere Patienten zeigten starkere Veranderungen. Respirationsrate und Pao, veranderten sich nicht.
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Anesthesiology, 22, 174. 2
226
BRITISH JOURNAL OF ANAESTHESIA INVERSION POR ATROPINA DE HIPERCAPNIA DURANTE ANESTESIA DE ENFLURANO SUMARIO
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Se administro atropina intravenosamente a 35 adultos saludables anestesiados con enflurano que respiraban espontaneamente, a fin de determinar si se reduciria el Pago, mediante el mejoramiento del intercambio de gas. Cinco minutos despues de la administration de atropina, el Paco, disminuyo de un promedio de 7,18 a 6,65 kPa ( — 7%), mientras que el VE aumento de 4,8 a 6,1 litros min"1 ( + 27%). Estos cambios continuaban 15 min mas tarde en los 20 pacientes estudiados en esa oportunidad. Los pacientes de mas edad y mas obesos acusaron un cambio mas significativo. La frecuencia el Pao, no variaron.
ATROPINE REVERSAL OF HYPERCARBIA DURING ENFLURANE ANAESTHESIA W. M . WAHBA AND J. SADKOVA SUMMARY
During a study of the pattern of breathing during enflurane anaesthesia, we found that there was a relationship between the forced expiratory volume in one second (FEV^o) and Pa C02 . The increase in FaCOa during anaesthesia compared with the value before anaesthesia correlated with the ratio FEV1.0/ vital capacity* while the values during anaesthesia correlated with the ratio FEV1.0/height.f We suggested that airway resistance (-RAW) m a v influence the increase in Pacc,2 occurring under general anaesthesia with spontaneous ventilation. If this is so, a reduction in i? A W should improve pulmonary ventilation. The present study was designed to test this hypothesis by measuring expired minute volumes (VE) and arterial blood-gas tensions before and after the i.v. administration of atropine in 35 healthy adult patients undergoing minor peripheral surgery. Atropine was chosen because its effects on flow resistance have been measured by Don and Robson (1965). METHODS
Thirty-five healthy adults undergoing elective operations on the periphery of the body gave consent for the study, which was approved by the Hospital o, (kPa) = 10.08-0.08 (r = 0.6 P< 0.01). t Paco, (kPa) = 9.17-1.2 FEV^o/height (m) (r = 0.65 P< 0.001). W. M. WAHBA, M.B., B.CH., M.SC. (MCGILL), F.R.C.P.(C).;
J. SADKOVA, M.D., F.R.C.P.(C).; Department of Anaesthesia,
Queen Elizabeth Hospital of Montreal, and McGill University. Correspondence to W. M. Wahba, Department of Anaesthesia, Queen Elizabeth Hospital of Montreal, 2100 Marlowe Avenue, Montreal, Quebec H4A 3L6, Canada. 0007-0912/79/030221-06 S01.00
Research and Ethics Committee. Measurements were made in all patients (group I) 5 min after the injection of atropine and in 20 (group II) the measurements were repeated 20 min after injection. The 15 patients in group I who were studied only at 5 min were not distinctly different from the other patients. The biometric data are summarized in table I. Premedication consisted of anileridine (U.S.P.) 12.5-37.5 mg and promethazine 12.5-25 mg, according to body weight, given i.m. 1 h before operation. After induction of anaesthesia with thiopentone 2-3 mg kg" 1 i.v. and orotracheal intubation facilitated by suxamethonium 1 mg kg" 1 , all the subjects received enflurane in nitrous oxide 3 litre min" 1 and oxygen 2 litre min" 1 from a semi-closed circle system with carbon dioxide absorption. Ventilation was assisted manually until the patient resumed adequate spontaneous breathing. The vaporizer (Cyprane) setting of 2-3% was adjusted on the basis of arterial pressure, heart rate, lack of lacrimation and the absence of response to surgical stimulation. No change in the vaporizer setting was made during the period of study. Twenty to 30 min after the surgical incision was made, when tidal volume and frequency were steady for 5 min, VE was measured using a Wright respirometer connected to a low resistance, uni-directional valve. Tidal volume ( F T ) was derived from the measured values of VE and breathing frequency (/). The measured values were not corrected to BTPS. Arterial blood was obtained from a radial artery anaerobically into heparinized syringes, which were packed in ice. Blood-gas tensions and pH were determined within 10 min using standard electrodes calibrated with 0,5 and 10% carbon dioxide (Corning 165 blood-gas analyser). The results were not corrected for time, introducing a © Macmillan Journals Ltd 1979
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Atropine was given i.v. to 35 spontaneously breathing healthy adults anaesthetized with enflurane to determine if it would reduce Paco, by improving gas exchange. Five minutes after administration of atropine, P^co, decreased from mean 7.18 to 6.65 kPa ( —7%), while mean 9?. increased from 4.8 to 6.1 litre min" 1 ( + 27%). These changes were maintained 15 min later in the 20 patients studied at that time. Older and more obese patients showed a more significant change. Respiratory frequency and Pao, did not alter.
222
BRITISH JOURNAL OF ANAESTHESIA TABLE I. Details of patients studied {mean ± SEM) Weight (kg)
Height (cm)
Weight Height
Surface area*
(yr)
Measurements at 5 min only (» = 35)
40.1 2.9
70.2 3.2
167.5 2.3
0.42 0.01
1.79 0.03
Measurements at 5 and 20 min (n = 20)
41.3 4.1
71.6 5.8
169.9 2.2
0.43 0.01
1.80 0.05
Age
Group I II
Basis of classification
(m 2 )
* Dubois and Dubois (1916).
RESULTS
There were no significant differences between the two groups with respect to age and body build (table I) or in the blood-gas and ventilation values before the administration of atropine (table II). Ventilation before atropine in the 15 patients studied at 5 min was slightly greater than that in the other 20 patients (P<0.1) but there was no significant difference in •^aco2-
Five minutes after the injection of atropine, mean VE increased by 27% from 4.8 ±0.18 to 6.1 + 0.24 litre min""1 in group I (P<0.001). In group II, mean VE also increased by 27% from 4.49 + 0.21 to 5.69 + 0.28 litre min (P< 0.001). Arterial Pacc,2 in group I decreased by 7% from 7.18±0.16 to 6.65±0.19kPa (P< 0.001). In group II, mean Pa C02 before atropine was 6.91 + 0.17 kPa and mean Pacc,2 5 min after atropine was 6.17 + 0.20 (P< 0.001). The measurements at 5 min in group II were maintained at 20 min (table II) without any significant difference between the values at these time intervals. For analysis of these data, two-way analysis of variance and Student's t test were used. Respiratory frequency, Pa 02 , pH and standard bicarbonate did not change significantly at any time in either group. The values of VE were standardized to allow for differences in size between individuals by the use of
TABLE II. Measurements of ventilation and arterial blood-gases before and after atropine (mean±SEM) Group II (n = 20)
Group I (n = 35) Before
5 min after
19.16 0.8 22.6 (mmol litre" 1 ) 0.4 7.25 (unit) 0.01 7.18 (kPa) 0.16 (b.p.m.) 16.0 0.8 (ml) 316.9 15.2 4.8 (litre min" 1 ) 0.18 2.66 (litre min" 1 m" 2 ) 0.10
19.06 0.67 20.7 0.4 7.26 0.01 6.65 0.19 16.9 0.8 374.2 17.4 6.1 0.24 3.39 0.13
Measurement Pa 0 , HCO 3 P
H
•Paco, / VT VE
VEISA
(kPa)
P
Before
5 min after
n.s.
19.61 1.09 22.2 0.5 7.24 0.02 6.91 0.17 15.9 0.8 295.0 18.2 4.49 0.21 2.46 0.10
19.57 1.08 22.0 0.6 7.24 0.08 6.17 0.20 16.9 0.7 339.0 25.0 5.69 0.28 3.13 0.15
n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
P
n.s. n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
20 min after 18.96 1.04 21.4 0.6 7.26 0.02 6.33 0.21 16.8 0.7 350.0 20.0 5.81 0.35 3.21 0.16
P
n.s. n.s. n.s. < 0.001 n.s. < 0.001 < 0.001 < 0.001
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possible error of 0.07-0.01 kPa for Pacc,2 (Kelman and Nunn, 1966). Atropine 0.01 mg kg" 1 was injected i.v. and the measurements repeated 5 min later in all patients, and 20 min after the injection in 20 patients. Statistical analysis of the data was performed using Student's t test, two-way analysis of variance and by regression analysis using the least squares method.
ATROPINE AND Pco 2 DURING ENFLURANE ANAESTHESIA the ratio FE/surface area (SA). Mean F E / S A for all subjects increased from 2.66 + 0.1 to 3.39 + 0.13 litre m i n ^ m - 2 5 min after atropine (P< 0.001). In group II patients, F E / S A increased from 2.46 ±0.10 to 3.13+ 0.15 litre min- 1 m- 2 (P<0.001), at 5 min, a value not significantly different from that noted at 20 min (3.21 + 0.16 litre min- 1 m~2). Figure 1 shows the observed mean values of Pa C02 and F E / S A in the two groups at the stated time intervals.
223
-7
O-
Group I j s min after
1 Before
r •• s min after
1 20 min after
I,
i
1.5
e.o
2.5
4.5
5.5
1/E/SA (litre m' 2 )
r 4.0
<
-5
,1
A
I
FIG. 1. Changes in mean Paco, a n d P E / S A before and after administration of atropine.
The relationship between F E / S A and PaC0]! for all the data is shown in figure 2. This relationship is expressed by the following equation: PaC0!! = 8.5-0.61 FE/SA
(r = 0.51, P<0.001)
DISCUSSION
The anaesthetic technique used in this study may be criticized because alveolar concentrations of the anaesthetic agents were not identical. However, we believe that it is preferable to use the standard technique appropriate for the surgery. The purpose of the present study was to determine if the i.v. injection of atropine during enflurane anaesthesia would have beneficial effects on gas exchange. Although there were individual differences in the degree of change in Pa C02 in our patients, mean PaCOa decreased and mean ventilation increased markedly following the injection of atropine. These
FIG. 2. Relationship between KE/SA and Paco, for all measurements. There is a trend with reference to time of sampling. O = before atropine; • = 5 min after atropine; • = 20 min after atropine.
changes may result from a reduction in airway resistance or central stimulation of ventilation. Central stimulation would cause an increase in respiratory rate or tidal volume, or both. We found no change in respiratory frequency, but the effect may have been masked by narcotic premedication. An increase in central respiratory drive can be measured by comparing the tracheal pressures generated during airway occlusion (Po) at functional residual capacity (FRC) before and after atropine. These measurements would differentiate between changes in central inspiratory drive and peripheral effects (Milic-Emili and Grunstein, 1976). We performed these measurements in four other subjects (G. B. Drummond and W. M. Wahba, unpublished observations) premedicated with diazepam and anaesthetized with enflurane in a mixture of nitrous oxide in oxygen and found no changes in occlusion pressure or in the ratio of inspiration to expiration. Frequency was unchanged also. These preliminary results suggest that the main site of action of i.v. atropine is peripheral rather than central. Mean flow rates must have increased following the injection of atropine, probably as a result of reduced airway resistance. There are conflicting reports on the effects of atropine on RAW during
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f Before
Group E
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The lack of a relationship between F E / S A and Pa c02 with time of measurement (fig. 2) is a reflection of individual variability in the change in •PaC02 and in deadspace, and of the non-steady state. Analysis of individual data at 5 min revealed that the extent of change in Pacc,2 could be related to the age and body build of the patient. By arbitrarily choosing a change in Pa C02 greater or less than 0.67 kPa, we subdivided our subjects into two groups (table III). The patients with greater reductions in Pa C02 (mean change of -0.97kPa) were older and more obese (P<0.05). These patients showed a greater increase in F E / S A (P<0.01) and a greater decrease in Pa C02 (P< 0.001) after atropine. It is known that the reduction in FRC following the induction of anaesthesia is greater in older subjects (Hewlett et al., 1974) and also in patients with high weight : height ratios (Don et al., 1970). An inverse relationship exists between lung volume and airway resistance. Greater improvements following atropine may be expected in patients with smaller FRC values where airways resistance has a more marked influence on ventilation. However, obese patients received a larger dose of atropine, since dosage was based on body weight. If this increase in dose was inappropriate, the changes may be a reflection of a dose-response relationship. Changes in VE precede those in -PaC02 because of the size of the body stores of carbon dioxide. Consequently, the disproportionate increase in F E (+ 27%) compared with the decrease in Pa C02 (—7%) may indicate that a steady state was not present 5 min after injection of atropine. Fifteen minutes later a more clearly defined difference in the distribution of the data relative to the time of measurement could be noted (fig. 3). However, the reduction in Pa C02 may have been limited by the increasing deadspace and the deepening of anaesthesia. By inference, a steady state was probably absent at 20 min.
TABLE III. Data grouped for patients who exhibited a change in Paco, greater or less than 0.67 kPa following i.v. atropine KE/SA
(ml m" 2 ) Age (yr)
Wt./ht. (kgcrn- 1 )
Before
After
(kPa) Before
After
Change <0.67kPa
35.7 3.4
0.40 0.01
2.76 0.24
3.33 0.28
7.2 0.21
6.84 0.21
Change >0.67kPa
48.5 5.1
0.44 0.02
2.61 0.10
3.39 0.14
7.22 0.27
6.21 0.33
P
<0.05
n.s.
< 0.001
<0.05
n.s.
<0.01
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anaesthesia. Don and Robson (1965) reported that total flow resistance in patients anaesthetized with nitrous oxide was decreased by 33% following atropine in the same dosage as was used in our study. On the other hand, Brakensiek and Bergman (1970) reported that atropine 0.8 mg i.v. during halothane anaesthesia reduced RAW only in subjects with pre-existing high airways resistance. In awake subjects, i? A W is reduced markedly by atropine (Vincent et al., 1970). These authors found that total pulmonary resistance during both inflation and deflation was reduced, with a greater effect during inflation. They confirmed also that lung volume history influences resistance. Daly, Ross and Behnke (1963) reported a small reduction in RAW following atropine in awake man. Groto, Whitman and Arakawa (1978) have reported recently that i.v. atropine 0.008 mg kg" 1 significantly increased expiratory flow functions (FEV 1 . 0 %, maximum mid-expiratory flow and maximum expiratory flow at 50% total lung capacity) with a small, transient and insignificant decrease in -RAW. The authors interpreted these observations in six awake volunteers as a decrease in small airways resistance. The improvement in expiratory flow functions was detectable lOmin after injection and lasted longer than 1 h. Thus the bulk of evidence supports the thesis that our results may be explained on the basis of a reduction in -RAW. The increase in tidal volume noted here is greater and of longer duration than that following the insertion and the subsequent removal of resistances (threshold and tubular) in the breathing circuit reported by Nunn and Ezi-Ashi (1961). Vagally mediated respiratory reflexes were probably operative in Nunn's study despite the use of anticholinergic drugs, and this may explain the differences in the results between the two studies.
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Don, H. F., Wahba, W. M., Cuadrado, L., and Kellar, K. (1970). The effects of anesthesia and 100 percent oxygen on the functional residual capacity of the lungs. Anes-
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Dubois, E., and Dubois, D. (1916). Clinical calorimetry. A formula to estimate the approximate surface area if height and weight be known. Arch. Intern. Med., 17,863. Groto, H., Whitman, R. A., and Arakawa, K. (1978). Pulmonary mechanics in man after administration of atropine and neostigmine. Anesthesiology, 49, 91. Hewlett, A. M., Hulands, G. H., Nunn, J. F., and Heath, J. R. (1974). Functional residual capacity during anaesthesia. II: Spontaneous ventilation. Br.J. Anaesth., 46, 486. Kelman, G. R., and Nunn, J. F. (1966). Nomograms for correction of blood, Po 2 , Pco 2 , pH and base excess for time and temperature. J. Appl. Physiol., 21, 1484. Milic-Emili, J., and Grunstein, M. M. (1976). Drive and timing components of ventilation. Chest (Suppl. 1), 70, 131. Nunn, J. F., and Ezi-Ashi, T. I. (1961). The respiratory effects of resistance to breathing in anesthetized man.
r
thesiology, 32, 521.
6
fc/SA (litre m" ) FIG. 3. Relationship between F E / S A and Paco, before and 20 min after atropine (group II). There is a distinct trend with reference to time of sampling. O = before; • = 20 min after.
Hypercarbia causes bronchodilatation (Aviado, 1975) and it is surprising that atropine can still exert such an effect under these circumstances. The clinical implications of this study are that hypercarbia during enflurane anaesthesia can be limited but not reversed by the use of atropine, particularly in older and more obese patients. ACKNOWLEDGEMENTS
The authors thank Professor J. Milic-Emili and Dr I. D. S. Gillies for their very valuable advice. Ohio Chemical Products, Canada, donated a supply of Ethrane and financial support for the purchase of a desk-top calculator for the statistical analysis.
Vincent, N. J., Knudson, R., Leith, D. E., Macklem, P. T., and Mead, J. (1970). Factors influencing pulmonary resistance. J. Appl. Physiol., 29, 236. INVERSION DE L'HYPERCARBIE PAR L'ATROPINE PENDANT UNE ANESTHESIE A L'ENFLURANE RESUME
On a administre de l'atropine par voie intraveineuse a 35 adultes en bonne sant£, respirant spontanement, anesthesias a l'aide d'enflurane, pour voir si Ton pourrait reduire la Paco, e n ameliorant l'echange de gaz. Cinq minutes apres l'administration d'atropine, la Paco, a diminue d'une moyenne de 7,18 a 6,65 kPa ( — 7%), alors que le VE moyen.a augmente de 4,8 a 6,1 litre min- 1 ( + 27%). Ces variations existaient toujours 15 min plus tard sur les 20 patients qui faisaient a ce moment-la l'objet de P6tude. Les patients plus ages et plus obeses ont accuse des variations plus prononcees. La frequence respiratoire et la Pao, n'ont pas ete modifiees. DURCH ATROPIN BEWIRKTE AUFHEBUNG VON HYPERKARBIE WAHREND ENFLURAN-NARKOSE
REFERENCES
Aviado, D. M. (1975). Regulation of bronchomotor tone during anaesthesia. Anesthesiology, 42, 68. Brakensiek, A. L., and Bergman, N. A. (1970). The effects of halothane and atropine on total respiratory resistance in anesthetized man. Anesthesiology, 33, 341. Daly, W. J., Ross, R. C , and Behnke, R. H. (1963). The effect of changes in the pulmonary vascular bed produced by atropine, pulmonary engorgement and positive pressure breathing on diffusing and mechanical properties of the lung. J. Clin. Invest., 42, 1083. Don, H. F., and Robson, J. G. (1965). The mechanics of the respiratory system during anesthesia. The effects of atropine and carbon dioxide. Anesthesiology, 26, 168.
ZUSAMMENFASSUNG
Atropin wurde intravenos an 35 spontan atmende, gesunde Erwachsene verabreicht, die mit Enfluran narkotisiert waren; es sollte festgestellt werden, ob dies durch verbesserten Gasaustausch zu einer Verringerung von Paco fuhren wiirde. Funf Minuten nach Verabreichung der Droge sank Paco, v ° n einem Mittelwert von 7,18 auf 6,65 kPa ( — 7%), wahrend der Mittelwert von VE von 4,8 auf 6,1 Liter min- 1 (+ 27%) anstieg. Diese Veranderungen blieben erhalten bei den 20 Patienten, die 15 Min spater untersucht wurden. Altere und fettleibigere Patienten zeigten starkere Veranderungen. Respirationsrate und Pao, veranderten sich nicht.
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Anesthesiology, 22, 174. 2
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BRITISH JOURNAL OF ANAESTHESIA INVERSION POR ATROPINA DE HIPERCAPNIA DURANTE ANESTESIA DE ENFLURANO SUMARIO
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Se administro atropina intravenosamente a 35 adultos saludables anestesiados con enflurano que respiraban espontaneamente, a fin de determinar si se reduciria el Pago, mediante el mejoramiento del intercambio de gas. Cinco minutos despues de la administration de atropina, el Paco, disminuyo de un promedio de 7,18 a 6,65 kPa ( — 7%), mientras que el VE aumento de 4,8 a 6,1 litros min"1 ( + 27%). Estos cambios continuaban 15 min mas tarde en los 20 pacientes estudiados en esa oportunidad. Los pacientes de mas edad y mas obesos acusaron un cambio mas significativo. La frecuencia el Pao, no variaron.