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Pressures are recorded as mm Hg (torr). The Thai formula was used because the experi- mental design did not include measurement of the respiratory quotient ...
A COMPARISON O F THE EFFECTS OF CONTINUOUS KETAMINE INFUSION A N D HALOTHANE ON OXYGENATION DURING ONE-LUNG ANAESTHESIA IN DOGS

PHILIP D. LUMB, GEORGE SILVAY. AVRON |. WEINREICH AND HOWARD SHIANG

ON['- LUNG VENTILATION with high inspired oxygen fi'action and a volatile anaesthetic agentmuscle relaxant sequence is a commonly used technique for endobronchial anaesthesia for pulmonary resection and has been associated with significant arterial hypoxaemia in 15 to 25 per" cent of cases.t The major determinant of the hypoxaemia is continued perfusion in the nonventilated lung. 2 Contributory causes are: (1) abolition of the hypoxic vasoconstrictive reflex by inhalational agents; 3 (2) direct myocardial depression consequent on the use of halothane, which causes a decrease in total cardiac output without parallel changes in shunt; ~3) atelectatic areas in the dependent ventilated and perfused lung;: (4) possible increase in absorption atelectasis due to high inspired oxygen concentration; 4 (5) increase in shunt fi'action due to positive pressure ventilation. 5'6 This experiment was designed to study the effects of a continuous infusion of ketamine on Pao2. cardiac output and shunt fraction during one lung anaesthesia compared with the effects of halothane under similar experimental conditions.

the Gordon-Greene endobronchial tube is a long, right-sided single lumen device, it was chosen because it enabled ventilation of both lungs with ease, and, at appropriate times, the extra length was employed when the tube was advanced into the lung to be inflated, so ensuring total isolation of the unventilated lung.) The femoral artery was cannulated and the chest was opened by a median sternotomy. The right atrium and pulmonary artery were cannulated directly and left atrial pressures were obtained by puncture of the left atrium with a 21-gauge needle. All cannulae were attached to Statham P 23 ID transducers and continuously flushed using a Sorenson MK-3-40 monitoring set. Pressures, waveforms and lead I[ of the electrocardiogram were continuously displayed on an Electronics for Medicine Physiological monitoring and recorder system. The dogs were ventilated with oxygenenriched air mixtures using a Bennett MA-I ventilator at 12 breaths per minute with a tidal volume of 10-12 ml/kg. Inspired oxygen fi'action was continuously monitored with an InMrumcntation Laboratories 1. L, 404 oxygen analyzer and halothane was added at appropriate times using a METHOD Fluotec Mark II vaporiser incorporated into the inspiratory limb of the breathing circuit. Six mongrel dogs weighing 21-28 kg were in each dog, control values were oblained with anaesthetized with an intravenous injection of pentobarbital-curare-oxygen anaesthesia alone sodium pentobarbitone 4 m g . k g -~, intubaled and these values were then compared with the with a cuffed Gordon-Greene endobronchial tube effects due first to ketamine and second to halothane in all dogs. (Table l indicates the exand paralyzed with d-tubocurarine at an initial dose of 0.2 rag" kg -t. Supplemental doses of 0. l perimental flow pattern.) The dogs were allowed m g . k g -~ were given as necessary but never to stabilize with each anaesthetic agent at 50 per within 15 minutes of a measurement. (Although cent and 100 per cent inspired oxygen and also during one and two hmg anaesthesia. No attempt Philip D. Lumb, M.B.B.S,. Clinical Instructor in was made to selectively collapse the right o1" left Anesthesiology; George Silvay. M.D., Ph.D., As- lung initially; but subsequently the same lung was sociate Professor of Clinical Anesthesia, Associate collapsed throughout the individual experiments. Attending Anesthesiologist; Avron I. Weinreich. M. D., Blood was withdrawn from the femoral and pulAssociate Professor of Clinical Anesthesia, Associate Attending Anesthesiologist; Howard Shiang, D.V.M.. monary arteries at specified times during the experiment and determinations of pH, Po2, Pr Assistant in Surgery. Division of Cardiothoracic Surgery. From the Deparlments of Anesthesiology and base excess, standard base excess, and haemathe Division of Cardiothoracic Surgery of the Depart- tocrit were made, Saturation was measured diment of Surgery, The Mount Sinai School of Medicine of the City University of New York. and The Mount rectly with an Instrumentation Laboratories 182 Sinai Hospital and Medical Center, One Gustave Levy co-oximeter. Cardiac output was measured as determined by protocol using an indocyanine Place. New York, New York. 10029. 394 Canad. Anaesth. Soc. J,, vo[. 26. no. 5, September 1979

LUM B, et

aL:

C O N T I N U O U S K E T A M I N E INFUSION

395

TABLE I EXPERIMENTAL PATTERN AND SCHEMA OF SAMPLING ORDER

Sampling order Pentobarbitone - curare CI 21~ oxygen C2 50~ oxygen C3 1007o oxygen C4 1007. oxygen C5 507o oxygen

both lungs both lungs both lungs one lung one lung

Ketamine - curare KI K2 K3

50~ oxygen 1007.. oxygen 1007o oxygen

one lung one lung both lungs

50~o o x y g e n

both lungs

K4

cardiac output 1 cardiac output 2 cardiac output 3

cardiac output 4 cardiac output 5 cardiacoutput 6

Halothane - curare HI 507. oxygen both lungs cardiac output 7 H2 100~ oxygen both lungs H3 1007, oxygen one lung cardiac output 8 H4 50~ oxygen one lung End experiment - 30 minutes after cessation of halothane 50~ oxygen both lungs cardiac output 9 B l o o d w a s w i t h d r a w n as stated at e a c h i n s p i r e d oxygen c o n c e n t r a t i o n .

green dye dilution technique utilizing a Columbus cardiac output computer coupled to a Harvard constant infusion/withdrawal pump and to a direct writing X-Y plotter. Measurements were made in duplicate and only when the second output differed by more than two p e r c e n t of the first was a third measurement necessary. This occurred on only three occasions, attesting to the stability o f the preparation. At the time of each sampling, systemic and pulmonary pressures were recorded and a permanent copy of the wave forms was made, These data were subsequently used to calculate the full range of frequently used cardiovascular parameters, Ketamine was given at an induction dose of 2 rag. k g - ' by bolus intravenous injection and accurately maintained at I rag-kg-~/hr using an IVAC 530 infusion pump for the duration of the relevant experimental period. A 30-minute period free of stimulation or challenge followed the cessation of ketamine infusion, Halothane was then introduced incrementally until a slight decrease in left atrial pressure occurred or to a maximum concentration of 1.5 per cent, I f a drop in filling pressure was noted, the concentration was reduced by 0.2 per cent. Halothane percentage was adjusted by keeping left atrial pressure constant in an attempt to minimize decrease in cardiac output while at the same time maximizing the abolition of the hypoxic vasoconstrictor reflex. Calculation o f the shunt fraction will be altered by any significant change in cardiac output. 7 Once

this percentage level of halothane was established, it was used for the duration of'thls portion of the study. Po2. Pco2, pH, base excess and standard base excess were measured and calculated using an ABL-I machine. Shunt fi'action was calculated using the original shunt equation: Qs/Qt = (Coo= - Caot) ( C c o 2 - C0o2) utilizing Severinghaus correction factors. Po2 values greater than 150 tor," (19.95 kPa) were corrected for linearity using the formula: Actual Po2 = indicated Po2 ((Pp.. indicated -

150)

x 0, I)

The oxygen content of pulmonary capillary blood, CCo~ was calculated by assuming that this would be the oxygen content that arterial blood would have if fully equilibrated with alveolar air. This is a standard assumption and necessary because of the inaccessibility of pulmonary capillary blood for direct measurement. The formulae used resulting from this assumption are as follows: C c o 2 = [Sao2(Hb x 1.39) + Pap2 x 0.0031] mffl00 ml blood PAo~ = PB - P a c o z - PHzO -- Pan z PANs "~ partial pressure of nitrogen in the alveolus determined by subtracting Fie2 fi'om I and multiplying the resulting (PB - P n z o - Pace2)

(.'AI~ADIAN ANAESTHETISTS' SOCIETY JOURNAl..

396

T A B L E ]I MEAN VALUESOF RESULTS WITH STANDARD DEVIATIONS

Systemic Blood Pressure

CI C2 C3 C4 C5 KI K2 I(3 K4 HI H2 H3 H4

Pulse

Systolic

Diastolic

Mean

PA

148+__19 150 + 17 152 _+ 23 145 __+ 15 147 -I- 12 137 _ 18 137 __. 16 138 _ 13 133 + 14 120 + 9 115_+!5 116_.+19 123_+21

1414_18 140 -4- )0 147 + 13 142__+ 16 146 + 20 140 _ 20 ) 4 0 _ 25 137 + 20 140 ___ 21 122 -+ 12 114_+5 115_+15 114_+ 17

904_16 90 _+ 12 86 5: 9 85 __ t3 91 _ 14 88 5: 21 88 4- 18 89 + 11 92 + 14 77 + 6 724-15 705:12 68+13

108+14 104 _4._10 107 _+ 10 106_____14 106 ___ 14 99 _+ 19 104 4_ 20 105 + 12 105 _ 15 89 4- 7 87-1-10 825:9 83+14

20+9 20 + 8 19 + 6 20__ 8 19 + 7 20 _ 9 21 _+ 9 16 __. 4 17 + 6 15 _+ 6 154-5 17_+7 184- 8

PAOP

CVP

134-9 9+3 11 _ 3 9 _ 2 12 _ 3 9 + 2 12 4- 6 9 4- 3 12 _ 6 8 + 2 14 _+ 8 9 _+ 5 13 4_ 6 11 + 4 I1 + 2 9 4_ 2 12 __. 5 9 5: 2 II -I- 5 8 4- 2 10+3 84-2 115:6 105:6 12+ 7 10_+6

Q

Qi

4.14-0,9 4.1 _ 0.9 4 . 2 _+ 1.1 3 . 7 4- 1.3 3 . 7 + 1.3 3 . 7 + 1.1 3 . 5 +_ 0 . 8 3.4 + 7 3.4 _ 0.7 2 . 9 4_ 0 . 8 2.9_+0.8 2.85:0.5 2.8+0.5

5.2+_1.7 5 . 2 + 1.7 5 . 2 _+ 1.8 4 . 3 __ ! . 1 4 . 3 _ 1.1 4.4 + 0,9 4 . 2 4- 0 , 6 4.2 + !.2 4 . 2 _+ 1.2 3 . 6 4- 1 . 4 3.64-1.4 3.5+0.8 3.54-0.8

P A -- p u l m o n a r y artery pressure. P A O P = p u l m o n a r y artery occluded pressure. C V P = central venous pressure. Q = cardiac output. Qi = cardiac output indexed for b o d y surface area. Pressures are recorded as m m H g (torr). The Thai formula was used because the experimental design did not include measurement of the r e s p i r a t o r y q u o t i e n t , w h i c h is n e c e s s a r y if t h e m o r e c o r r e c t a l v e o l a r a i r e q u a t i o n is u s e d . Alv e o l a r o x y g e n s a t u r a t i o n o n 50 p e r c e n t a n d 100 p e r c e n t o x y g e n is a s s u m e d t o b e 100 p e r c e n t , same as D (A-a)or s Throughout the experiment normothe,'mia. normovolaemia and haemalocrit were maintained.

RESULTS T h e m e a n v a l u e s a n d s t a n d a r d eta'ors f o r e a c h m e a s u r e d p a r a m e t e r a r e s h o w n in T a b l e s 11 a n d 111.

A. S h u n t A v e r a g e s h u n t f r a c t i o n w a s h i g h e r b y 6 . 5 0 _+ 2.51 u n d e r h a l o t h a n e t h a n u n d e r k e t a m i n e a n a e s t h e s i a - T a b l e IV. T h e d i f f e r e n c e w a s s t a t i s t i c a l l y s i g n i f i c a n t a t the five p e r c e n t level b y S t u d e n t ' s t - t e s t w i t h five d e g r e e s o f f r e e d o m . Y e t more clearly significant contrasts were found for o x y g e n ( 1 0 0 p e r c e n t v e r s u s 5 0 p e r c e n t ) 5.25 __+ 0.75 a n d f o r o n e l u n g v e r s u s t w o l u n g s 16.84 • 2.34. T h e b a s i s o f t h e s e t e s t s w a s t h e c o n s i s t e n c y f o r t h e g i v e n f a c t o r a m o n g t h e six d o g s . A s s h o w n in t h e t a b l e , t h e a v e r a g e s h u n t f r a c t i o n in t h e f o u r periods under one condition was subtracted from that for the four periods under the opposite cond i t i o n , s e p a r a t e l y f o r e a c h d o g . T h e six r e s u l t i n g contrasts were averaged and their variance calculated to obtain the t-test. A more detailed form

of statistical analysis, the analysis of variance. a l s o s h o w n in T a b l e IV, g a v e c o n s i s t e n t b u t m o r e e x t e n s i v e r e s u l t s . D i f f e r e n c e s in a v e r a g e s h u n t fi-action a m o n g d o g s w e r e s t a t i s t i c a l l y s i g n i f i c a n t (p < 0.01). T h e t h r e e m a i n f a c t o r s w e r e a l s o s i g n i f i c a n t b y this a n a l y s i s w h e r e in t h e c a s e o f t h e h a l o t h a n e v e r s u s k e t a m i n e c o n t r a s t the s i g n i f i c a n c e level w a s p < 0 . 0 1 . E v i d e n c e th~ll a n y o f t h e t h r e e m a i n f a c t o r s a f f e c t e d t h e r e s p o n s e to either of the other was tested for and found abs e n t . N o n e o f the i n t e r a c t i o n t e r m s w a s c l o s e to significance. Finally, the shunt fi'action wtriance w a s S z = 3 5 . 8 7 , r e f l e c t i n g a level o f u n a c c o u n t a ble v a r i a t i o n p e r p e r i o d in a n y d o g o f •

B. A g r e e m e n t be t w e e n calculated shunt fi'actinn and D (A -alp ~. i n this s m a l l s a m p l e , a s t a t i s t i c a l l y s i g n i f i c a n t but weak association between calculated shunt fraction and alveolar arterial oxygen concentration d i f f e r e n c e w a s s h o w n . T a b l e V s h o w s s h u n t f r a c t i o n a d j u s t e d f o r D(A-a)o2 f o r i n d i v i d u a l d o g s d u r i n g t h e e i g h t s a m p l i n g p e r i o d s K) t h r o u g h H4. (The adjustment, calculated by regression of s h u n t f r a c t i o n o n D(A-a)o~ w i t h i n d o g s . p o o l e d o v e r t h e six d o g s , w a s o b t a i n e d b y s u b t r a c t i n g from shunt fraction the quantity 4.6 per cent of t h e d e v i a t i o n o f t h e p a r t i c u l a r D(A-a)u~ v a l u e f r o m 3 3 1 . 0 , t h e a v e r a g e D(A-a)o=.) It is e v i d e n t t h a t d i f f e r e n c e s o f s h u n t f r a c t i o n a t t r i b u t a b l e to t r e a t m e n t w e r e c o n s i d e r a b l y l e s s , a s w a s t h e residual error term, among adjusted values. The o v e r a l l r e d u c t i o n in v a r i a n c e w a s , in f a c t , 4 0 p e r cent. Nevertheless, highly significant differences

67____. 9 1364- 26 327 • 57 137_+ 88 74• 16 I14_+ 46 190 +- 125 258 4- 96 181+148 178-+ 79 275_+ 84 95-+ 51 76+__ 23

29__+6 30+6 32 -+ 6 34_+6 34+6 33__+8 32 -+ 6 31____.6 32+6 32+7 34_+6 38-+7 37-+7

Pac% 42__+ 5 5[__+ $ 62 _+ i0 52_+12 45-+ 6 49-+ 4 52 -+ 8 54 4- 7 48_+ 3 51+ 5 56_+ 7 47__ 8 45-+ $

Pvo~ 7,41____.0,01 7,4 -+0.07 7,38 __+0,07 7.36_+0.07 7.36__+0.07 7,37__+0,09 '/.39-+ 0,07 7.41-+0,07 7,39__+0,08 7.41+0.07 7.36__+0,05 7.33_+0,07 7,32-+0.07

pHa 35_+ 6 25-+ 8 30 + 9 41__+ 4 41 4- 5 36__I0 38 _+ I0 26__+ 9 21_+11 234-15 31__+11 50_+ 8 44+ 8

Qs/Qt 53_+ 14 189__+ 30 254 • 60 543_+ 87 248• 19 237__+125 509 __+147 352_+143 177_+ 53 171_+ 94 378+-109 579+132 245 4- 154

D(A-a)o2

Blood gas tensionsare recorded as mm Hg (tort).

LVSWi = left ventricularstroke work index, RVSWi = right ventricularstroke work index,

C! C2 C3 C4 C5 K1 K2 K3 K4 HI H2 H3 H4

Pao~ 3.3 _____09 3.1 _+08 2.98 _+ 0.7 3.4 ____.I.3 3.4 _+1.4 3,2 __+0.9 3.4 _+ 0,6 3.2 +0.6 3.6 _+1,1 3.1 _+0.4 3,2 +_0.7 3.0 +0.5 3,I +-0,7

C(a-~)o~

MEAN VALU~ OF RESULTSWITH STANDARDDEVIATIONS

TABLE III

52,1+18 49 +14 48 __+15 44 • 43 _+14 40 +- II 42 4-__i0 43 _+II 40 -+14 40 + 17 37 +14 35 _+ 15 36 -+ 15

LVSWi

3.7____.3.3 5.4+__48 2.9 ____. 2.7 3,6_+I,8 2,9• 3.4__+2.4 3.8 • 2.7 2,9__2.3 2.6_+2.0 2.4+ i,6 2.2+1.9 2.6+I.0 2,9• I.I

Rvswi

41,8+__6 40 _+6 42 _+ 6 41 -+6 40 +6 42 • 41 __ 3 41 _+3 42 _+4 40 -+3 40 -+5 39 __6 39 4-5

Hot

CANADIAN ANAESTHETISTS' SOCIETY JOURNAL

398

T A B L E IV SHUNT FRACTION M a n F a c t o r s Averages D o g No.

Average

KI

K2

K3

K4

HI

Ha

Ha

H4 Average

28.2 43.5 35.4 42.3 27.5 41.8

39.5 46.6 34.0 46.0 29.5 34.6

18.0 41.8 23.6 22.5 29.2 20.6

16.7 36.1 12.7 17.9 23.9 17.3

21.1 50.5 18.0 11.8 20.6 15.7

33.7 51,0 25,0 27.8 26.2 23.4

45.7 62,0 48.6 38.0 51.4 51.5

47.9 55.2 34.6 34,1 48.0 43.3

31.35 48.34 28.99 30.05 32.04 31.02

3 6 . 4 5 3 8 . 3 7 2 5 . 9 5 2 0 . 7 7 22.95 3 1 . 1 8 4 9 . 5 3 4 3 . 8 5

33.63

Anaes. 11.50 12,68 5.12 -4.25 9.02 4.90 6.50 2.584 0.05

t =

Lungs

5.75 4.02 7.62 7.05 4.08 3.00

17.95 6.98 18,32 20,10 14.12 23.55

5.25

SE = • p =

Oxyg,

16.84





6,96