Journal of Neurology, Neurosurgery, and Psychiatry, 1976, 39, 221-230

Changes in CO2 responsiveness and in autoregulation of the cerebral circulation during and after halothane-induced hypotension Y. OKUDA, D. G. McDOWALL, M. M. ALI, AND J. R. LANE From the Department of Anaesthesia, the University of Leeds, Leeds SYNOPSIS C02 responsiveness of the cerebral circulation has been measured in baboons before, during, and after halothane-induced hypotension. At a systolic blood pressure (BP) of 60 mmHg, CO2 responsiveness was abolished, but was maintained at higher levels of BP. After hypotension, CO2 responsiveness returned to control values. Autoregulation to BP increases induced by intravenous noradrenaline was impaired when cerebral perfusion pressure during the hypotensive period had been below 30-40 mmHg. It is concluded that at levels of halothane-induced hypotension commonly employed clinically, CO2 responsiveness of the cerebral circulation may be absent. The return of CO2 responsiveness in the post-hypotensive phase argues in favour of controlled hyperventilation after neurosurgery which has involved induced hypotension.

maintained with halothane, N20, and 02. After intramuscular injection of suxamethonium (50 mg), the animals were intubated and ventilated by intermittent positive pressure (Starling ventilator). Muscle relaxation was obtained by injecting pancuronium (1 mg) intramuscularly at 30 min intervals. Oesophageal temperature was held at 37°C by automatically controlled heating lamps. Catheters were inserted into one femoral artery and into the sagittal sinus. These catheters were connected to Statham strain gauges and a multi-channel heated stylus recorder (Devices) for continuous monitoring of arterial pressure and cerebral venous pressure throughout the experiment. Arterial P02. PCO2, and pH were measured with Radiometer blood gas equipment, and the halothane concentration in cerebral venous blood was measured by gas chromatography (Pye-Unicam). One femoral vein was catheterized for the continuous infusion of replacement fluid (30 ml/h Hartmann's solution) and for the infusion of noradrenaline during autoregulation testing. Cerebral blood flow (CBF) was measured by two METHODS methods: (1) by the Xenon clearance technique; and (2) by electromagnetic flowmeter (Statham) on one Five baboons weighing between 7.2 and 13.8 kg were carotid artery. The common carotid artery and its premedicated with phencyclidine (0.8-1.0 mg/kg) branches were exposed in the neck, a catheter for intramuscularly and anaesthesia was induced and 133Xenon injection was inserted into a branch of the external carotid artery and directed centrally to(Accepted 22 October 1975.)

Harper and Glass (1965) reported loss of cerebrovascular responsiveness to Paco2 changes during haemorrhagic hypotension, while Haggendal and Johansson (1965) reported that some degree of response was retained in these circumstances. Recent evidence (Fitch et al., 1973) shows that the cerebral circulation responds differently during drug-induced hypotension compared with hypotension produced by haemorrhage. It seemed important, therefore, to establish whether changes in cerebrovascular responsiveness to PaC02 occurred during drug-induced hypotension, since the combination of hypotension and hyperventilation could, by a combined action on cerebral perfusion, be clinically undesirable. Consequently, we decided to investigate cerebrovascular responses to changes in PaCO2 during hypotension induced with halothane at a level of systolic blood pressure commonly employed clinically.

221

222

Y. Okuda, D. G. McDowall, M. M. Ali, and J. R. Lane

wards the carotid bifurcation, and all other branches of the external carotid artery were tied off. An electromagnetic flow probe, placed around the common carotid artery, measured internal carotid blood flow (CarBF) continuously, since the external carotid circulation had been ligated. The scalp and temporalis muscle were reflected and a collimated gamma radiation detector was placed over the lateral aspect of the parietal bone mounted in a coronal plane. Xenon 0.5 ml, dissolved in saline, was injected within 2 s and a clearance curve recorded on a chart recorder and stored on magnetic tape in digital form. The bi-exponential equation of the clearance curve was calculated from the digital data by a small computer (WANG 720) using a programme of the best fitting line,, based on the least squares method. Mean cerebral blood flow (CBF) was estimated by the infinite integration of this equation. When the surgical preparation was complete, control measurements of CBF were made during light halothane anaesthesia and arterial Pco2 was altered both by varying the ventilation volume and by adding CO2 to the inspired gases. Blood pressure was then reduced by increasing the inspired halothane concentration and CO2 responsiveness again tested. Finally, all measurements were repeated after discontinuance of halothane and recovery of blood pressure.

Autoregulation in the cerebral circulation to a rise of blood pressure (BP) was tested by infusing noradrenaline (NA) intravenously before and after halothane-induced hypotension. Mean blood pressure was calculated as diastolic+ one-third pulse pressure and mean cerebral venous pressure as diastolic+ one-half pulse pressure measured during the expiratory pause. Mean cerebral perfusion pressure was calculated as the difference between these two values.

Expt.134

20OL&N

Expt.35

20pLf

Exp1.136

"

X 20

80 60-

Expt.138

20OLLLL l

Expt.l40 20 25

jL 50

75

100

125

150

Mean Arterial Blood Pressure ImmHlg)

1 Histogram of mean arterial bloodpressure for each experiment individually during both normotensive and hypotensive phases. The frequency scale is in units of 2 min of observation. FIG.

similar presentation of cerebral perfusion pressure, but during the hypotension stage only. The numerical data on systolic blood pressure, mean arterial BP, and cerebral perfusion pressure, together with the results of blood gas RESULTS analysis and of cerebral venous halothane conFREQUENCY HISTOGRAMS OF MEAN ARTERIAL centration during the stages of normotension, BLOOD PRESSURE AND CEREBRAL PERFUSION hypotension, and post-hypotension, are prePRESSURE During each experiment, the values sented in Table la. Table lb is a similar presentafor mean arterial blood pressure and cerebral tion of the numerical data on Expt 140, in which perfusion pressure were stored in a computer moderate hypotension was studied. (Wang 720) at two minute intervals and frequency histograms were printed out. In Fig. 1, RESPONSIVENESS OF CEREBRAL CIRCULATION TO the histogram of each experiment is shown. As Paco, CHANGE C02 responsiveness of the cerecan be seen, the histograms of Expts 134, bral circulation was observed during light 135, 136, and 138 have two peaks clearly N20/02/halothane anaesthesia before the inducseparated, but the peaks of Expt 140 were not tion of hypotension. Each CBF result was distinct because of the lesser degree of hypo- expressed as a percentage of the CBF at Paco2 of tension studied in this experiment. Figure 2 is a 40 mmHg, as estimated from individual tests.

Changes in CO2 responsiveness during and after halothane-induced hypotension frequency Expt. 134

TABLE la

meant.SAn

27

20-

223

BLOOD PRESSURE AND CEREBRAL PERFUSION PRESSURE (MEANS ± SDS) WITH RESULTS OF BLOOD GAS ANALYSIS AND OF CEREBRAL VENOUS HALOTHANE CONCENTRATION, AT

6 mmHg

EACH STAGE OF EXPERIMENTS

Expt.135

Expt.136

Normotension

335 tmmHg

20 30

After hy-potension

30I S29 10 20-

Hypotension

5mmHg

SBP (mmHg) mBP (mmHg) CPP (mmHg)

PaO2 (mmHg) Paco2 (mmHg) pHa Cerebral

113±14

59+12 44±9 33 ± 7 194±45

89 ± 12 77 ± 10

176+23 25.-70 7.27 7.53

24- 74 7.17 7.57

6.5 ± 2.3

24.1 ± 6.7

-

124±17 101±10 81±15 193±54 28-i51 7.21

-

-

7.40

venous

halothane concentration (mg/dl)

1020 6¶ 11.

7.7 ± 3.2

......

Experiment 140 is excluded from the columns of hypotension and after hypotension.

Expt.138

30r EXptLU

5 ~~'mmHg1

51

20-

t

TABLE lb BLOOD PRESSURE AND CEREBRAL PERFUSION PRESSURE (MEANS + SDS), WITH RESULTS OF BLOOD GAS ANALYSIS AND

10

20

t0

30

Cerebrtl perfusion

50

pressure

60

70

1 mnNg )

CEREBRAL VENOUS HALOTHANE CONCENTRATION DURING HYPOTENSION AND AFTER HYPOTENSION IN EXPT 140

FIG. 2 Frequency histograms of cerebral perfusion pressure for each experiment individually during the

hypotensive phase only. The frequency scale is in units of 2 min.

Moderate

hypotension SBP (mmHg) mBP (mmHg) CPP (mmHg)

Pao2 (mmHg) Paco2 (mmHg)

The percentage values equation shown below: °F

%F2

were

calculated by the

F1 100 =

After

moderate

hypotension 81+ 5 59 ± 4 51± 5 161

30.53

129± 6 95 ± 5 86± 2 -

pHa

7.35 -7.56

Cerebral venous halothane concentration (mg/dl)

31 52 7.33 7.52

10.0 + 2.0

2.9 ± 0.3

-

This experiment was deliberately performed at a higher level of blood pressure than the others.

F2 X 100

-F,) -(PaC02)1] .+(F2(PaCO2)2 - (PaCO2)1 [40

measurement by Xe clearance was not performed after hypotension. F1: CBF at (PacO2)1. Percentage changes of mean CBF by Xe clearance and Paco2 from all the experiments F2: CBF at (PacO2)2. the normotensive stage have been plotted during F5t: standard CBF at PaCO2 = 40 mmHg. in Fig. 3a. The plots for each animal are shown Table 2a lists the individual values of PaCO2, with different symbols. There was no statistically mean BP, cerebral perfusion pressure, CBF by significant difference in CO2 responsiveness beXe clearance, CarBF by electromagnetic flow- tween the individual animals, since the F-value of meter, and cerebral venous halothane concentra- one-way analysis of variance was less than 500 of tion during the normotensive stage. Tables 2b the critical values [F-value = 3.95 < 6.59 = F(0.95) and 2c give the same values for the hypotensive d.f.(3.4)]. The linear regression equation of these and post-hypotensive stages respectively. CBF plots was y = 3.9x -53.6 and the correlation Fs

x

Y. Okuda, D. G. McDowall, M. M. Ali, and J. R. Lane

224

TABLE 2a CO2 RESPONSIVENESS BEFORE HYPOTENSION Xe clearance (ml/i1O

Experiment no.

Paco2 (mmHg)

135

34 45 33 43 25

mBP (mmHg) 84 89 77 85 81

136

30 53 27

67

81 123 82

107

77 104

138

35 70 32

52

97

30

88

134

140

42

93

89

50

90

33

80 82

52 31

44

80 88

FI

FG

73 71 70 66 72

-

-

-

-

-

-

82

58

88

128

34

72

76 104 68 91 61 89 81 81 79

52 111

72 139

18 20

38

36 145

185

53

27 139

45 185

10 24 22 31

11153

74 151

43

28 95

54

28

71 104 51 81

24 44

(mmHg)

75

38 57

FM

/

CarBF

(ml/min)

CarBF4o

-

-

-

-

-

-

-

-

-

89 109 71 113

88

25

52

75 103 72 136

53 65 44 70 45

17

34

18 28

72 27 103 30 103 42 99 35

80 41

82 32 53

52 199 74 255 65 153 61 139 73 146 69 114

67 48 83

blood

/

FM40

123

44 90

74 73 74 82

FW

Halothane in CV

glmin)

CPP

(mg/dl) } }

6.8 48

709 f 104 76 131

}

8.0

56 192

40 138 35 112 40 74 40 69

1. 10.2 7679 f 243

47 81 46 49

7939 136 96 4.2 j 102

75 138

}

51 7347 132

}

%/,FM40 = percentage relationship of meanCBF to the calculated mean CBF at Paco2 = 40 mmHg. Similarly, Y/CarBF40 = percentage relationship of carBF to the calculated carBF at Paco2 = 40 mmHg. The details of the calculations are given in the text. Fl = flow based on initial slope of clearance curve. FG = flow grey matter. FW = flow white matter. FM = mean flow.

TABLE 2b C02 RESPONSIVENESS DURING HYPOTENSION Experinment no.

134

135

Paco2

(mmHg) 31 48 30 49 24 45 28

mBP

CPP

(mmHg)

(mmHg)

37 39 34 35 49 42

26 26 24 24

34 34

44 31 62

39 35

136

31 43 32 74

41 51 51 55

138

28 53

49 56 54

27 45

140

34 52 30 53

58

54 58 63 61

FI

Xe clearance (ml/100 glmin) FM FW FG

--

-

-

22 15 17 19

23

30

40

-

41 35

-

-

-

31 31 35 32

23 19 25 19

25 31 43 43

23 31 32 33 39 45

43

51 51 40 57 61

44

45

%FM40 and Y/CarBF4o have the same meanings

53 43 95 33 83 as

in Table 2a.

34 ~~-

-

45 47 46 56 47

(ml/min)

23 16 28 23 28 29 30 20 21 22 24

44 37 42 51 50 50 51 36 74 33 63

CarBF4, 87

103 99 100 100 93 102 97 111 101 99 99 101 78 160

40 30 30 29 28 19 20 34 26 48 53 39 37 31 54

112 113 96 100 100 101 98 96 101 105 80 95 105 104 99 80 140

71

37

82

44

22 24 24

Halothane in CV blood

%

(mg/dl)

40 100 ~~ ~~~ 40 100 ~~~-

-

-=

56

FM4o ~~

-

67 74 58 83 69 69 67 53 118 49 98

CarBF

~~

-

-

°/0

136

47

56

124

20.0 }

9.

}

22.4 2. 39.2 3

j j f } }

20.8

8. 189 209 2

9.0 9 .

12.3 13

Changes in CO2 responsiveness during and after halothane-induced hypotension

225

TABLE 2c CO2 RESPONSIVENESS AFTER HYPOTENSION

Experiment no.

134

136 138

Paco2 (mmHg) 28 40 31 46 38 50

mBP (mmHg)

CPP (mmHg)

101 82 103 97 114

84 66

40 51 38 47

100 112 104 88 91 97 92 101

32 43 31 52

140

% CarBF40

60 70 59 84 38 79 91 99 71 88 35

86 100 92

(ml/min)

85 49 98 86 85 94 92 71 84 88

110

CarBF

54

85

41 82

85

131 85 176 100 109 95 118 72 111l 70 140

Halothane in CV blood

(mg/dl)

f

11.2 5

S

}

111

f

9.3

4.3

3.1 pf

2.7 .

Y/CarBF40 has the same meaning as in Table 2a.

(a) Normotension CBF (

'1.

Xe133 clearance ) 0

* Expt. 135 O Expt. 136 zx Expt. 138 o3 Expt. 140

y: 3-9x- 53-6 r= 0.9698 n= 16 --I

20

I

I

°°

Paco2 ( mmHg )

( b) Hypotension '1. Change of mean CBF ( Xe133 clearance)

1501_ I

20

I

Ch

AI

"311Y

40

50L

W

I

-

50 '*

I

1

60-

I

AI

70

80 PaCo2 ( mmHg)

FIG. 3

Plots of percentage change in mean cerebral blood flow, plotted against arterial Pco2 (in the upper panel in normotension, and in the lower during hypotension).

Y. Okuda, D. G. McDowall, M. M. Ali, and J. R. Lane

226

/.chunge of carotid blood flow ( E.M.F.) 250 r

(a) llormotention

0

A Expt. 13L

* O s @

Expt. 135 Expt. 136 Expt. 135 Expt. 140

200

F /

rgn:20

I0,r

.--l

3P A

-Qen

33.1

-

r a 0.956 3

I

20

3-4x

y

150

I

I

I

50

I

.

I

I

70

60

Poco2

80 mmHg

0

Changes in CO2 responsiveness and in autoregulation of the cerebral circulation during and after halothane-induced hypotension.

Journal of Neurology, Neurosurgery, and Psychiatry, 1976, 39, 221-230 Changes in CO2 responsiveness and in autoregulation of the cerebral circulation...
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