Br.J. Anaesth. (1979), 51, 503
PATTERN OF RESPIRATION AND RESPONSES TO CARBON DIOXIDE DURING TRICHLOROETHYLENE ANAESTHESIA IN THE CAT S. GREGORETTI, G. B. DRUMMOND AND J. MILIC-EMILI SUMMARY
The characteristic pattern of breathing during anaesthesia with trichloroethylene (TCE) is a reduction in tidal volume ( F T ) and an increase in respiratory frequency (/). Although this pattern has been known for many years (Hewer and Hadfield, 1941; Dundee, 1953), information about the effect of TCE on the pattern of respiration and the ventilatory response to carbon dioxide is sparse and often conflicting. Whitteridge and Biilbring (1944) suggested that TCE caused a persistent sensitization of the inflation and deflation receptors in the cat lung and this could account for the reduction in tidal volume and tachypnoea seen during TCE anaesthesia. However, section of the vagi did not prevent the onset of tachypnoea after inhalation of TCE in decerebrate cats (Ngai, Katz and Farhie, 1965), suggesting that TCE causes this effect by a central action. Talcott, Larson and Buechel (1965) reported that TCE did not influence the ventilatory response to carbon dioxide in man, but the response was severely depressed in cats (Ngai, Katz and Farhie, 1965). We have studied the effects of TCE anaesthesia on S. GREGORETTI,* M.D.; G. B. TJRUMMOND,-)-, F.F.A.R.C.S.,
Department of Anaesthesia; J. MILIC-EMILI, M.D., Department of Physiology, McGill University, Montreal, Quebec, Canada. Present addresses: * Ente Ospedaliera Regionale, Ospedale Maggiore, Piazza Ospedale, 34100 Trieste, Italy. t Department of Anaesthetics, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW. Correspondence to G. B. D. 0007-0912/79/060503-09 $01.00
the pattern of breathing in adult cats. In addition to measurements of minute ventilation (FE), / and F T , we measured the volume inspired in the first 0.1 s of inspiration (F 0-1 ), and the duration of inspiration, expiration and the total respiratory cycle ( r l 5 T E and Ttot respectively). We calculated the mean inspiratory flow rate ( F T / T Z ) and the ratio of inspiratory to total cycle duration (7yr t ( ? t ). We occluded the airway at the onset of inspiration and measured the pressure change in the first 0.1 s of an inspiratory effort (P 0 .i) (Whitelaw, Derenne and Milic-Emili, 1975). This pressure change indicated the tension generated by the inspiratory muscles. The occlusion was performed with t i e lung filled to functional residual capacity, and no flow of gas or change of volume occurred during the measurement (apart from the negligible decompression of gas in the lungs). Consequently, the dimensions of the respiratory system were nearly constant, and the magnitude of the tension developed in the respiratory muscles during isometric contraction had a consistent proportion to the degree of neural activation ofthese muscles. In this way, Pol was used as an index of the rate of increase of activity of inspiratory motoneurones, or central inspiratory activity (Bradley et al., 1975; Eldridge, 1975). V01 and F T / ^ also indicate the rate of increase of inspiratory activity but they may be affected by changes in flow resistance or elastance (impedance) of the respiratory system (Whitelaw, Derenne and Milic-Emili, 1975). The relationship between Pol and Vol indicates changes in the © Macmillan Journals Ltd 1979
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 29, 2015
Tidal volume (KT), minute ventilation (KE), the duration of inspiration and expiration, and Paco, were measured via a tracheostomy in adult cats anaesthetized with 0.7%, 1% and 1.5% (inspired) trichloroethylene (TCE). The tracheal cannula was occluded at intervals at the start of inspiration and the tracheal pressure was measured to assess the force of contraction of the respiratory muscles. Anaesthesia with TCE 0.7% was associated with an increase in VE, a reduction in VT, and a marked increase in respiratory frequency and mean inspiratory flow rate, but Pacot values did not differ significantly from those in conscious animals. Ventilation was also greater than in conscious animals during anaesthesia with TCE 1%. TCE 1.5% caused a significantly greater Paco, than in conscious animals. All concentrations of TCE caused a reduction in the ventilatory response to carbon dioxide, measured by the steady-state method. Cervical vagal section did not abolish the tachypnoea caused by TCE.
504
BRITISH JOURNAL OF ANAESTHESIA
not modify the respiratory pattern of cats anaesthetized with either halothane or pentobarbitone. Anaesthesia was induced with TCE 2% in 50% oxygen in nitrogen using a mask connected to a T-piece system with a gas flow rate of 8 litre min" 1 . TCE was vaporized using a recently calibrated Tritec Mark 3 vaporizer (Cyprane Ltd). After 15-20 min a tracheal cannula was ligated firmly in the caudal part of the trachea and a femoral artery was cannulated. In five cats both vagi were dissected free in the neck and placed in loose ligatures to facilitate subsequent section. The cat lay supine in a volume displacement body 7yr t o t (1) plethysmograph (Emerson) which had a linear resThe advantage of expressing ventilation in this way ponse at frequencies less than 7 Hz. Tracheal pressure is that the first component ( F T / T J ) is related only to (from a sidearm in the tracheal cannula) and systemic the increasing activity of the inspiratory muscles and arterial pressure were measured with Hewlettthe second only to the proportional timing of the Packard 267B and Statham P23AC transducers events in the respiratory cycle. This is not so for the respectively and recorded with the volume signal on a Honeywell oscillograph. TCE was given by a Tconventional relationship: piece connected to the tracheal cannula and the gas F E = F T X 1/7V
1000
FIG. 3. Relationship of ventilation with arterial .PcOj in individual cats anaesthetized with TCE 0.7% and 1%. Each cat is indicated by a reference number. The broken line represents the mean response of awake cats (Gamier, 1976).
was measured again. An aqueous solution of sodium chloride 0.9% was infused into the artery at a rate of 5 ml h" 1 for the duration of the experiment (4-6 h) and sampled blood was replaced with twice the volume of the saline solution. Statistical analysis was made with Student's t test for paired and unpaired data as appropriate.
1"
RESULTS
200
E Q. XI 150
3 100
cr
I50 Paco2 (kPa)
FIG. 4. Relationship of tidal volume, respiratory frequency, VT/TI and 7i/7"tot with Ps^ot in individual cats anaesthetized with TCE 0.7%. The broken lines represent the mean response of awake cats (Gautier, 1976).
The mean values of the measured and derived variables for cats breathing TCE 0,7% and 1% in 50% oxygen are shown in table I, with similar data for conscious adult cats breathing air, studied by H. Gautier (personal communication). The weights of the groups were comparable. When compared with cats breathing air, the cats breathing TCE 0.7% had a greater FE, a smaller F T and a markedly greater frequency. The mean rate of inspiration ( F T / T J ) was greater in proportion to the greater ventilation and ^i/^tot w a s slightly but statistically significantly greater. P&cOi was less but this was not statistically significant. The cats breathing TCE 1% had F T similar to those breathing 0.7%, but Tx and Ttot were greater. Consequently F E and VT/TX were less, T T not il iotwas significantly different, and PaCOa was greater than in cats breathing TCE 0.7%. These differences are shown in figure 2, in which spirograms have been drawn using the mean values from table I. In the two cats studied during anaesthesia with TCE 1.5%, ventilation was less than in the 1% group but F T was about the same. Mean VE was 1546 ml
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 29, 2015
(kPa)
RESPIRATORY EFFECTS OF TRICHLOROETHYLENE
trated in figure 5 for the TCE 0.7% group. ^ decreased in all animals, except one breathing TCE 0.7%. The ventilatory response to carbon dioxide was characterized by an increase in F T as />aCOa was increased. However, VE increased in only three animals when PaCOa was increased (two breathing TCE 0.7%, and one breathing TCE 1%) and was associated with an increase in VT/TJ. The changes in timing of respiration that occurred with increasing PaCOa did not show a consistent pattern. Vagal section did not influence mean arterial pressure which remained greater than 100 mm Hg throughout the experiment. DISCUSSION
Choice of species. We studied cats because there is a large amount of previous experimental work on their
increase in F T / T J and F T in all the animals, but /
decreased in seven of the nine animals as PaCOa increased, and TJTtot decreased in five. In the cats breathing TCE 1% the changes were less consistent and no clear pattern was evident to account for the small increase in VE that occurred with increased carbon dioxide in three of the five animals. Before carbon dioxide was given, both F o x and Pol were less in the 1% than in the 0.7% group. The difference was greater for F o 15 but the ratio -Po.i/^o.i was not significantly greater than in the TCE 1% group. No change in the ratio of . P 0 1 / F 0 1 occurred with the increase in />aCOa at any of the inhaled TCE concentrations. Vagotomy. Bilateral section of the vagi in the neck in three animals breathing TCE 0.7% (table II) and in two animals breathing TCE 1% did not cause a significant change in F E , but r x and F T increased and frequency was reduced. However, only the change in F T in the TCE 0.7% group was significant using the paired t test (P
PATTERN OF RESPIRATION AND RESPONSES TO CARBON DIOXIDE DURING TRICHLOROETHYLENE ANAESTHESIA IN THE CAT S. GREGORETTI, G. B. DRUMMOND AND J. MILIC-EMILI SUMMARY
The characteristic pattern of breathing during anaesthesia with trichloroethylene (TCE) is a reduction in tidal volume ( F T ) and an increase in respiratory frequency (/). Although this pattern has been known for many years (Hewer and Hadfield, 1941; Dundee, 1953), information about the effect of TCE on the pattern of respiration and the ventilatory response to carbon dioxide is sparse and often conflicting. Whitteridge and Biilbring (1944) suggested that TCE caused a persistent sensitization of the inflation and deflation receptors in the cat lung and this could account for the reduction in tidal volume and tachypnoea seen during TCE anaesthesia. However, section of the vagi did not prevent the onset of tachypnoea after inhalation of TCE in decerebrate cats (Ngai, Katz and Farhie, 1965), suggesting that TCE causes this effect by a central action. Talcott, Larson and Buechel (1965) reported that TCE did not influence the ventilatory response to carbon dioxide in man, but the response was severely depressed in cats (Ngai, Katz and Farhie, 1965). We have studied the effects of TCE anaesthesia on S. GREGORETTI,* M.D.; G. B. TJRUMMOND,-)-, F.F.A.R.C.S.,
Department of Anaesthesia; J. MILIC-EMILI, M.D., Department of Physiology, McGill University, Montreal, Quebec, Canada. Present addresses: * Ente Ospedaliera Regionale, Ospedale Maggiore, Piazza Ospedale, 34100 Trieste, Italy. t Department of Anaesthetics, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW. Correspondence to G. B. D. 0007-0912/79/060503-09 $01.00
the pattern of breathing in adult cats. In addition to measurements of minute ventilation (FE), / and F T , we measured the volume inspired in the first 0.1 s of inspiration (F 0-1 ), and the duration of inspiration, expiration and the total respiratory cycle ( r l 5 T E and Ttot respectively). We calculated the mean inspiratory flow rate ( F T / T Z ) and the ratio of inspiratory to total cycle duration (7yr t ( ? t ). We occluded the airway at the onset of inspiration and measured the pressure change in the first 0.1 s of an inspiratory effort (P 0 .i) (Whitelaw, Derenne and Milic-Emili, 1975). This pressure change indicated the tension generated by the inspiratory muscles. The occlusion was performed with t i e lung filled to functional residual capacity, and no flow of gas or change of volume occurred during the measurement (apart from the negligible decompression of gas in the lungs). Consequently, the dimensions of the respiratory system were nearly constant, and the magnitude of the tension developed in the respiratory muscles during isometric contraction had a consistent proportion to the degree of neural activation ofthese muscles. In this way, Pol was used as an index of the rate of increase of activity of inspiratory motoneurones, or central inspiratory activity (Bradley et al., 1975; Eldridge, 1975). V01 and F T / ^ also indicate the rate of increase of inspiratory activity but they may be affected by changes in flow resistance or elastance (impedance) of the respiratory system (Whitelaw, Derenne and Milic-Emili, 1975). The relationship between Pol and Vol indicates changes in the © Macmillan Journals Ltd 1979
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 29, 2015
Tidal volume (KT), minute ventilation (KE), the duration of inspiration and expiration, and Paco, were measured via a tracheostomy in adult cats anaesthetized with 0.7%, 1% and 1.5% (inspired) trichloroethylene (TCE). The tracheal cannula was occluded at intervals at the start of inspiration and the tracheal pressure was measured to assess the force of contraction of the respiratory muscles. Anaesthesia with TCE 0.7% was associated with an increase in VE, a reduction in VT, and a marked increase in respiratory frequency and mean inspiratory flow rate, but Pacot values did not differ significantly from those in conscious animals. Ventilation was also greater than in conscious animals during anaesthesia with TCE 1%. TCE 1.5% caused a significantly greater Paco, than in conscious animals. All concentrations of TCE caused a reduction in the ventilatory response to carbon dioxide, measured by the steady-state method. Cervical vagal section did not abolish the tachypnoea caused by TCE.
504
BRITISH JOURNAL OF ANAESTHESIA
not modify the respiratory pattern of cats anaesthetized with either halothane or pentobarbitone. Anaesthesia was induced with TCE 2% in 50% oxygen in nitrogen using a mask connected to a T-piece system with a gas flow rate of 8 litre min" 1 . TCE was vaporized using a recently calibrated Tritec Mark 3 vaporizer (Cyprane Ltd). After 15-20 min a tracheal cannula was ligated firmly in the caudal part of the trachea and a femoral artery was cannulated. In five cats both vagi were dissected free in the neck and placed in loose ligatures to facilitate subsequent section. The cat lay supine in a volume displacement body 7yr t o t (1) plethysmograph (Emerson) which had a linear resThe advantage of expressing ventilation in this way ponse at frequencies less than 7 Hz. Tracheal pressure is that the first component ( F T / T J ) is related only to (from a sidearm in the tracheal cannula) and systemic the increasing activity of the inspiratory muscles and arterial pressure were measured with Hewlettthe second only to the proportional timing of the Packard 267B and Statham P23AC transducers events in the respiratory cycle. This is not so for the respectively and recorded with the volume signal on a Honeywell oscillograph. TCE was given by a Tconventional relationship: piece connected to the tracheal cannula and the gas F E = F T X 1/7V
1000
FIG. 3. Relationship of ventilation with arterial .PcOj in individual cats anaesthetized with TCE 0.7% and 1%. Each cat is indicated by a reference number. The broken line represents the mean response of awake cats (Gamier, 1976).
was measured again. An aqueous solution of sodium chloride 0.9% was infused into the artery at a rate of 5 ml h" 1 for the duration of the experiment (4-6 h) and sampled blood was replaced with twice the volume of the saline solution. Statistical analysis was made with Student's t test for paired and unpaired data as appropriate.
1"
RESULTS
200
E Q. XI 150
3 100
cr
I50 Paco2 (kPa)
FIG. 4. Relationship of tidal volume, respiratory frequency, VT/TI and 7i/7"tot with Ps^ot in individual cats anaesthetized with TCE 0.7%. The broken lines represent the mean response of awake cats (Gautier, 1976).
The mean values of the measured and derived variables for cats breathing TCE 0,7% and 1% in 50% oxygen are shown in table I, with similar data for conscious adult cats breathing air, studied by H. Gautier (personal communication). The weights of the groups were comparable. When compared with cats breathing air, the cats breathing TCE 0.7% had a greater FE, a smaller F T and a markedly greater frequency. The mean rate of inspiration ( F T / T J ) was greater in proportion to the greater ventilation and ^i/^tot w a s slightly but statistically significantly greater. P&cOi was less but this was not statistically significant. The cats breathing TCE 1% had F T similar to those breathing 0.7%, but Tx and Ttot were greater. Consequently F E and VT/TX were less, T T not il iotwas significantly different, and PaCOa was greater than in cats breathing TCE 0.7%. These differences are shown in figure 2, in which spirograms have been drawn using the mean values from table I. In the two cats studied during anaesthesia with TCE 1.5%, ventilation was less than in the 1% group but F T was about the same. Mean VE was 1546 ml
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 29, 2015
(kPa)
RESPIRATORY EFFECTS OF TRICHLOROETHYLENE
trated in figure 5 for the TCE 0.7% group. ^ decreased in all animals, except one breathing TCE 0.7%. The ventilatory response to carbon dioxide was characterized by an increase in F T as />aCOa was increased. However, VE increased in only three animals when PaCOa was increased (two breathing TCE 0.7%, and one breathing TCE 1%) and was associated with an increase in VT/TJ. The changes in timing of respiration that occurred with increasing PaCOa did not show a consistent pattern. Vagal section did not influence mean arterial pressure which remained greater than 100 mm Hg throughout the experiment. DISCUSSION
Choice of species. We studied cats because there is a large amount of previous experimental work on their
increase in F T / T J and F T in all the animals, but /
decreased in seven of the nine animals as PaCOa increased, and TJTtot decreased in five. In the cats breathing TCE 1% the changes were less consistent and no clear pattern was evident to account for the small increase in VE that occurred with increased carbon dioxide in three of the five animals. Before carbon dioxide was given, both F o x and Pol were less in the 1% than in the 0.7% group. The difference was greater for F o 15 but the ratio -Po.i/^o.i was not significantly greater than in the TCE 1% group. No change in the ratio of . P 0 1 / F 0 1 occurred with the increase in />aCOa at any of the inhaled TCE concentrations. Vagotomy. Bilateral section of the vagi in the neck in three animals breathing TCE 0.7% (table II) and in two animals breathing TCE 1% did not cause a significant change in F E , but r x and F T increased and frequency was reduced. However, only the change in F T in the TCE 0.7% group was significant using the paired t test (P
