Acta anaesth. scand. 1978, 22, 130-144

Cardiovascular Effects of Local Adrenaline Infiltration During Halothane Anaesthesia and Adrenergic Beta-Receptor Blockade in Man P. J. PONTINEN Department of Anaesthesia, Kainuu Central Hospital, Kajaani, Finland

Adrenergic beta-receptor blocking agents, alprenolol, propranolol and practolol were given as a prophylactic measure to patients undergoing middle-ear microsurgery where adrenaline was deliberately infiltrated during halothane-Nz0/02 anaesthesia. These three beta blockers did not differ in their action on heart rate, arterial blood pressure, right ventricular pressure, CVP or peripheral pulse wave in equipotent doses, which were 0.04 mg/kg for alprenolol and propranolol and 0.4 mg/kg for practolol in this study. Atropine caused a highly significant increase in heart rate in the spontaneously ventilating group and maintained blood pressure at higher levels, although the latter difference was not significant. Alprenolol and propranolol offered partial protection for over 40 min against adrenaline-induced arrhythmias. Occasionally occurring tachyarrhythmias were easily terminated with a further dose of a beta blocker. The effective half-life of practolol was less than 15 min and doses up to 0.4 mg/kg were unable to prevent arrhythmias during adrenaline challenge.

Received 24 March, accepted for publication 21 June 1977

Halothane is known to sensitize the myocarAlthough KATZet al. (1962) reported that dium to catecholamines (RAVENTOS 1956). adrenaline can be used safely during haloThis is the reason for ventricular arrhythmias thane anaesthesia - provided certain preand even cardiac arrest when catecholamines cautions concerning the dose, concentration are released into circulation or applied and time of the administration are takenexogenously during halothane anaesthesia. local adrenaline infiltration has been genThis experimental finding has been confirmed erally regarded as contraindicated (KATZ in many clinical reports (BRINDLEet al. 1957, & EPSTEIN 1968). MILLARet al. 1958, JOHNSTONE & NISBET IKEZONO et al. (1969) have shown that all 1961, CATENACCI et al. 1963, DE LANGE 1963, patients receiving more than 6 pg/kg body ROSEN& ROE 1963, VAREJES 1963, FORBESweight adrenaline, either topically or sub1966). cutaneously during halothane anaesthesia, The increased sensitivity of the myo- developed ventricular arrhythmias. These cardium to tachyarrhythmias may be due to were also common in patients receiving a the direct stimulating effect of halothane on single dose of adrenaline of between 0.5 and adrenergic beta receptors (KLIDE 1966, 3.7 pg/kg. I n all these patients the end-tidal PRICE1970). On the other hand, respiratory carbon dioxide tension was within the normal acidosis and arterial hypotension did not range. The arrhythmogenic dose of adrenaline increase sympathetic tone during halothane anaesthesia (PRICE during relatively light levels of halothane et al. 1959, 1960).

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

131

anaesthesia has been the same in other reports differ in their action depending on their concerning experiments on dogs (JOAS & specificity as beta blockers and on their other STEVENS 1971, TUCKER et al. 1974, MUNSON properties. Propranolol can be regarded as a & TUCKER 1975, REISNER& LIPPMAN1975, prototype adrenergic beta-receptor blocking TUCKER & MUNSON 1975, ZINKet al. 1975). agent and its actions are well known (NICKERAdrenergic beta-receptor blockade has SON 1970). It has no intrinsic sympathomigained wide acceptance in the treatment of metic activity and the inhibition of cardiac hypertension (GILLAM& PRICHARD 1964, tachyarrhythmias, especially those caused by LYDTIN et al. 1972), angina pectoris digitalis is partially due to its local (MACALPIN et al. 1965, BJORNTORP1967), anaesthetic property and membrane-stabitachyarrhythmias (HARRIS 1966, SCHAM- lizing, quinidine-like effect. Alprenolol has a ROTH 1966), hypertrophic obstructive cardioslight intrinsic sympathomimetic activity and myopathy (CHERIAN et al. 1966), thyrotoxic also membrane-stabilizing properties (ABLAD tachycardia (TURNER et al. 1965, DA ROSA et al. 1967). Propranolol and alprenolol block et al. 1973) and phaeochromocytoma (DE both beta,- and beta2-receptors. Practolol is a BLASI 1966, PRICHARD & Ross 1966) where specific beta,-receptor blocker with some increased sympathetic activity is important. intrinsic sympathomimetic activity, and is It is also widely used during anaesthesia in almost free of membrane-stabilizing properthe control of cardiac arrhythmias due to ties (MACDONALD & MCNEILL1968). The sympathetic overactivity (PAYNE & SENFIELDimportance of these specific properties during 1964, PONTINEN& EKHOLM1964, HELLE- halothane anaesthesia is not clear. It has been WELL & POTTS1965, PONTINEN et al. 1965, reported that cardiac output is reduced PONTINEN & REINIKAINEN 1966, JOHNSTONE to the same degree by all these agents (STE1966, 1968, 1969, FUKUSHIMA et al. 1968, PHEN et al. 1971). Many studies ol'the haemoMCCLISHet al. 1968, BUKY 1970, JENKINS dynamic effects of adrenergic beta-receptor 1970,MATHIAS & PAYNE 1970, FESSL-ALEMANY blockade during anaesthesia have been per& WECEHAUPT 1973). More specific fields of formed in spontaneously breathing patients application are the diminution of the peri- or animals who may have been hypercapnic pheral blood flow in order to reduce bleeding ( FREY& KAERGAARD-NIELSEN 1966, JOHNduring surgery (JOHNSTONE 1966, 1969, STONE 1 9 6 6 , s 1~9 ~ 6 7~ , ~ S ~~ ~ pal.~ 1971, ~~et et al. 1971, 1972). JOHNSTONE & HORSFALL 1966), and to combat STRONG tachycardias during deliberate hypotension I n a series of studies on the cardiovascular (HELLEWELL & POTTS1966, HEWITTet a]. effects of pretreatment with adrenergic betareceptor blockers during halothane anaes1967). and his co-workers The tachyarrhythmias occurring during thesia, PRYS-ROBERTS surgery for phaeochromocytoma and thyro- have shown that this combination is safe and toxicosis have also been successfully treated that the changes are predictable, provided with adrenergic beta-receptor blocking certain precautions on ventilation and acidagents (ROBERTSON 1965, DE BLASI 1966, base balance are taken (PRYS-ROBERTS et al. COOPERMAN et al. 1967, BIRD et al. 1969, 1971, FoEx & PRYS-ROBERTS 1974, ROBERTS BLACKet al. 1969, DAS& KRIEGER1969, DA et al. 1976a, b, c). The aim of this study was to evaluate the ROSAet al. 1973). Adrenergic beta-receptor blockade has also cardiovascular effects of adrenaline infiltrabeen tried in the prevention of tachyarrhy- tion during halothane anaesthesia and betathmias due to exogenous catecholamines receptor blockade, with special reference to (IWATSUKI et al. 1966, JOHNSTONE 1966, the importance of the specific properties of SHARMA 1967, 1969, IKEZONO et al. 1969, three different beta-receptor blocking agents in the prevention of adrenaline-induced KATZ1969). Adrenergic beta-receptor blocking agents cardiac arrhythmias.

132

P. J. PONTINEN

MATERIAL AND METHODS The series comprised 60 patients (29 men and 31 women between the ages of 7 and 61 years), none of whom showed signs or symptoms of respiratory or cardiovascular diseases. The subjects were fully informed of the nature of the experiments and agreed to participate. All patients were to undergo middle-ear microsurgery, where the surgical trauma is minimal but where the operation field is infiltrated with adrenaline to reduce bleeding. Cardiovascular parameters were studied prior to surgery during a steady state of halothane anaesthesia. Adrenergic beta-receptor blocking agents (alprenolol, propranolol or practolol) were given as a single intravenous injection during the steady state of halothane anaesthesia approx. 15 min after intubation. T h e present study was divided into two parts. The first part deals with cardiovascular changes due to

beta-receptor blockade during halothane anaesthesia. Patients were divided into 10 groups according to the type of ventilation, beta-receptor blocking agent and atropinization (Table 1). The second part deals with cardiovascular changes due to adrenaline infiltration. Patient groups and the doses of infiltrated adrenaline are presented in Table

2. Anaesthetic technique All patients were prernedicated with 10 mg ofdiazepam orally the night before and on the morning of the operation day. Atropine 0.01 mg/kg body weight was given intravenously at the induction of anaesthesia. Anaesthesia was induced with a sleep dose of thiopentone ( 100-400 mg). Intubation was facilitated by suxamethonium (50-75 mg). In groups A and B, anaesthesia was maintained with 1.5-2.0% halothane in nitrous oxideloxygen (2 I/

Table 1 Patients grouped according to the type of ventilation, adrenergic betareceptor blocking agent and atropinization (mg/kg). -__-No. of Group patients Ventilation Atropine Beta blocker Dose A 13

4 9 5 5 16 7 4

c D E F C H I

spontaneous spontaneous controlled controlled controlled controlled controlled con trolled controlled controlled

2 4 4

J

0.01

-

0.01

0.01 0.01

-

0.01

alprenolol alprenolol alprenolol alprenolol alprenolol propranolol propranolol practolol practolol practolol

-

0.04 0.04 0.04 0.05 0.04 0.04 0.06 0.2 0.3 0.4

Table 2 Doses of infiltrated adrenaline (pg/kg) and time from beta blockade adrenaline challenge (min). NO.

Group

C D E F G H

I

Time from beta blockade to adrenaline challenge

3 3 15

20-30 20-30 20-30 20-30 20-30 20-30

7 4 1 I 2

2

J

or

patients

4

3 20-30 3 15

to

Dose of adrenaline (meanf s.d.) 4.83f2.09 6-63? 1.41 4.70+ 1.76 3.42 + 0.65 3.45 0.7U 2.50 5.40 4.15f 0.14 6.85 f2.54 2.85f 0.51

+-

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

min each) from a circle system fed by a Fluotec Mark 3 vaporizer situated outside the circuit. Ventilation was spontaneous. In groups C to J, patients were relaxed with alcuronium. Their ventilation was controlled by a Bird 4/8 anaesthesia ventilator. Anaesthesia was maintained with 0.5-1 .O% halothane in nitrous oxide/oxygen, as above. Vasoconstriction was achieved locally by infiltrating the skin of the posterior meatal wall with Rosen’s solution (2% mepivacaine 3 m1+0.1% adrenaline 0.6 ml). The site of the incision, either endaural or retroauricular, as well as the site of the fascia1 graft, were infiltrated with 0.25% bupivacaine containing 1 :200.000 adrenaline.

133

heart rate and radial artery pressure during beta blockade with alprenolol are presented in Table 3. Atropine caused a highly significant increase in heart rate (PcO.01) only in patients breathing spontaneously. Neither atropine nor the type of ventilation changed the effect of the beta blockade on arterial pressure. Alprenolol, propranolol and practolol had similar effects on heart rate, arterial pressure, right ventricular pressure and CVP (Table 4). The changes in heart rate and arterial pressure were dose related, although they did not reach the level of significance. Monitoring technique Adrenaline infiltration induced an immedBlood pressure was monitored via a percutaneously placed polypropylene cannula from a radial artery iate pressure rise when alprenolol or propran(Intranule, Vygon) (PONTINEN & WIHEKVAARA 1970). 0101 had been given before the adrenaline This cannula was connected to a Hewlett-Packard challenge. Peripheral vasoconstriction took 1280B pressure transducer and was also used for place at the same time (Fig. 1). During the arterial blood sampling. beta-receptor blockade with practolol, this The right ventricle or pulmonary artery was catheterized via cephalic or jugular veins (Intracath, Bard) pressure effect was two-phasic. After a n for pressure monitoring through a Hewlett-Packard initial slight pressure rise, a fall in blood 1280C pressure transducer. pressure was recorded. Then the definite The upper vena cava was catheterized for central venous pressure (CVP) monitoring (Intracath), using pressure rise took place. These changes correlated well with changes in peripheral a simple water manometer (Fenwal). Peripheral circulation was monitored from a n ear pulse wave from an ear lobe (Fig. 2). Similar lobe or nasal wall with a photo cell (Hewlett-Packard changes had previously been recorded 780-16). during neurolept analgesia when adrenaline Chest electrodes not corresponding to any standard leads were used for continuous ECG monitoring was infiltrated without beta-receptor blockade (PONTINEN 1978). (Hewlett-Packard 780-7). Arterial and venous pressures, peripheral pulse wave Adrenaline-induced changes in monitored and ECG were continuously displayed on a cathode ray parameters disappeared within 15 min. The oscilloscope (Hewlett-Packard 764 or 7803), and mean values for heart rate, radial artery simultaneously recorded on paper (Sanborn 322T or pressure, right ventricle pressure and CVP 15 7702). Arterial blood samples were taken during the steady min after the adrenaline challenge are state of anaesthesia, 15 min after the injection of the presented in Table 5. beta-blocking agent and 15 min after adrenaline Acid-base balance, blood gases and electroinfiltration for acid-base balance, blood gases and lytes are presented during the steady state of serum sodium, and potassium measurements. These were performed immediately with a n I L 113 Blood halothane anaesthesia, be ta-receptor blockGas Analyzer and an I L 127 Flame Photometer, using ade and 15 rnin after the adrenaline challenge an IL 144 Automatic Dilutor (Instrumentation in Table 6 . Laboratories). I n the present series, seven patients All parameters were recorded continuously during received more than 6 pg/kg adrenaline in a beta blockade and for 20 min after the adrenaline infiltration. Occasionally occurring persistent tachy- single infiltrated dose (Table 7). Ventricular arrhythmias occurred in two of these patients. arrhythmias were treated with an additional dose of a beta-receptor blocking drug. Altogether, 11 patients developed transient ventricular arrhythmias during adrenaline RESULTS challenge. The doses of infiltrated adrenaline, The effects of atropine and ventilation on beta-receptor blocker and arrhythmias are

=

5

Alprenolol 0.04+atropine 0.01 C.V.n = 10

AlprenololO.04 C.V. n

Alprenolol 0.04+ atropine 0.01 S.V. n = 9

Alprenolol 0.04 S.V. n = 4

*

12.7k1.6 7.9 0.9

13.3k1.0 8.9 0.9

12.5k1.5 7.6k 1.3

13.52 1.2 8.2 k 0.7

systolic B. Radial artery pressure diastolic W a )

12.3k1.5 7.85 1.1

13.151.0 8.7+ 1.0

12.5k1.5 7.6+ 1.3

13.45 1.2 8.2 0.6

98.7k9.2

Alprenolol 0.04+ atropine 0.01 C.V. n = 16 103.9+11.0

12.1k1.4 7.6k 1.0

12.71-0.9 8.4+ 1.2

12.7k1.4 7.9k 1.1

13.22 1.2 7.9 1- 0.7

97.3k8.7

97.8k5.1 97.054.5

84.Ok5.7 101.6k5.0

1

86.3k3.1

0

91.3t4.3

-5

92.3j14.8 Alprenolol 0.04 S.V. n = 4 Alprenolol 0.04+atropine 0.01 S.V. n = 9 85.9k5.2 103.0k5.3 Alprenolol0.04 C.V. n = 5

Time (min)

A. Heart rate (beatslmin)

12.251.5 7.7k 1.1

12.4k0.9 8.1+ 1.1

12.5k1.3 7.8+ 1.1

13.0k 1.2 7.6k0.8

95.3k10.4

12.1k1.6 7.8 5 1.O

12.3k0.9 8.0 1- 1.2

12.251.1 7.6k 1.1

13.0+ 1.4 7.6 f0.8

93.8k9.7

96.0k5.4 91.4t4.8

82.651.0

83.55 1.1 97.0k5.9 92.824.8

3

2

11.9k1.4 7.31-0.8

*

12.2k1.0 7.9 1.3

12.1k1.2 7.4* 1.2

12.92 1.5 7.7k0.8

93.8k10.0

95.0k5.5 89.2k4.8

80.85 1.5

5

11.6k1.4 7.1 k0.7

11.851.1 7.7* 1.2

11.8k0.9 7.1k0.9

12.7k 1.5 7.6k0.7

93.5k9.3

93.8k5.1 88.0k5.5

78.8k2.2

10

11.7k1.4 7.1 k0.6

12.1k1.3 7.9 f 1.4

11.7k0.8 7.120.8

12.3k0.9 7.3k 0.6

92.1+10.2

92.2k5.9 88.0k5.5

77.8k2.3

15

-

4

Effect of atropine (mg/kg) and the type of ventilation (s.v. = spontaneous ventilation, C.V. = controlled ventilation) on heart rate and radial artery pressure during beta-receptor blockade with alprenolol (mg/kg) under halothane anaesthesia (means fs.d., n = number of patients).

8'2

T i

v

Table 3

7.7* 1.1 0.6+0.2

7.6 f 1.O

0.6 & 0.3 6.0 + 4.4

7.8+ 1.1

0.6T0.3

6.0 f4.4

7.9 f0.9

0.6k0.4

6.0 & 4.4

RVP

CVP

7.6 2 1.2

0.8 k 0.3 7.3 t2.9

7.52 1.2

0.8 k 0.3

7.3 f2.9

7.5+ 1.2

0.8 k 0.3

7.3k2.6

RVP

CVP

12.2k1.9

12.2k2.0

12.3 k 2.0

diast.

102.3k 11.4

100.7+ 16.7

102.7k16.5

HR

R R syst.

B. Propranolol 0.04 mg/kg+atropine 0.01 mg/kg (n = 7)

7.4k3.0

7.8

+ 1.2 0.8 + 0.3

12.3+ 1.6

94.9k7.3

6.0 f4.4

7.6 +_ 3.2

0.8 k 0.3

7.8 k 1.2

12.3+_1.5

92.6k6.3

7.4k3.3

0.8 & 0.2

7.6+ 1.1

12.1 f 1.4

91.1k6.5

6.0 k 4.4

0.6 & 0.3

0.6 & 0.3 6.0 & 4.4

7.3 f 0.8

11.9k1.4

93.81-10.0

5

7.8+ 1.0

12.1k1.6

diast.

95.3k9.7

12.2+ 1.5

12.1k 1.4

12.3f 1.5

12.7+ 1.6

3

97.3510.4

98.7k8.7

102.7f9.2

103.9k11.0

HR

R R syst.

2

1

0

Time

-5

A. AlprenololO.04 mg/kgfatropine 0.01 mg/kg (n = 16)

7.7f 3.4

0.8 f0.3

7.5 f 1.5

11.8k1.9

89.3f8.1

6.0 f4.4

0.7 _+ 0.3

7.1 k0.7

11.6k 1.4

93.5k9.3

10

15

8.1 f3.4

0.8k0.3

7.3f 1.8

11.7k2.2

89.4k8.1

6.2k4.4

0.6 f0.3

7.1 f0.6

11.7+ 1.4

92.1k10.2

~

cmH20

kPa

kPa

/min

cmHzO

kPa

kPa

/min

min

Heart rate (HR), radial artery pressure (RR), right ventricle pressure (RVP) and central venous pressure (CVP) during adrenergic beta-receptor blockade under halothane anaesthesia (means k s.d.).

Table 4

136

P. J. PONTINEN

*

-

N

-

-

oicj,.om' +I +I +I +I +I L?c???.-K!

w . m q y m

~ +I

o

+I

o

o

+I +I +I

r - - C o o r -

co-

c

? ? V l c q Q , - - o m

l 6 ? c 9 L ? Q ?

+I +I

+I

0 0 - w o r .

rcW9- a o? ?w? .o- cr 9-

tl +I +I 9c9??.-9

O D -

-

0

o

+I +I

o m +I +I

z- m0, c 0q - -0? =mc q +I +I +I +I +I 9 1 9 c 9 T

0 - w o r Q , -

% ? ? . - ? ?

- 0 o o m +I

+I

-

+I +I

c ? c 9 - ? 9

m - - c ; o r i.?

w "= "- -o - m +I

+I

+I +I +I

m w m r - m m m ' c 6 o w

2 -

q - r q - -

r - & - O m ' +I +I +I +I +I

V??ZZ 0

+I

m

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

137

k Pa

0

i

OL

Fig. 1. The effect of adrenaline infiltration (3.8 pg/kg) on radial artery pressure (above) and peripheral pulse wave (below) during beta-receptor blockade with alprenolol (0.04 mg/kg+atropine 0.01 mg/kg) under halothane anaesthesia.

%GT

Fig. 2. The effect of adrenaline infiltration (2.8 pg/kg) on radial artery pressure (above) and peripheral pulse wave (below) during beta-receptor blockade with practolol (0.4 mg/kg+atropine 0.01 mg/kg) under halothane anaesthesia.

c-------l 10 sec

Heart rate (HR), radial artery pressure (RR), mean right ventricle pressure (RVP) and central venous pressure (CVP) 15 min after adrenaline infiltration during beta-receptor blockade under halothane anaesthesia. (Alp 4 = alprenololO.04 mg/kg, Alp 5 = AlprenololO.05 mg/kg, Alp 4a = alprenololO.04 mg/kg+atropine 0.01 mg/kg, Pro 4 = propranololO.04 mg/kg+atropine 0.01 mg/kg, Pro 6 = propranolo1 0.06 mg/kg+atropine 0.01 mg/kg, Pra = practolol 0.4 mg/kg+atropine 0.01 mg/kg.) Alp 4 ~

Alp 5 ~

Pro 4

Alp 4a ~~

~~~~~

~~

Pro G

Pra

~~

89.3k2.5

87.3k9.2

87.059.8

88.1k9.9

8.5.8kA.7

84.0+ 13.7/min

syst.

12.2k0.7

12.4k0.2

12.OkO.8

12.4.k 1.9

13.0k2.8

11.Ok0.9 kPa

diast.

8.1k0.8

8.0+0.5

7.3+0.7

7.9k1.6

8.4k2.0

6.320.9

RVP

0.8k0.3

0.8k0.2

0.7k0.5

1.0+0.2

0.9k0.3

0.9k0.5 kPa

CVP

5.3k3.1

8.7k5.1

6.8k4.5

8.9k3.1

7.0k4.2

8.6k3.9 cmHlO

HR

RK

presented in Table 8. A typical response to 8.6 pg/kg adrenaline during beta blockade with alprenolol in a 14-year-old boy is presented in Figure 3.

DISCUSSION The role of atropine in the maintenance of stable circulation during beta-receptor blockade under halothane anaesthesia was not clearly decided by this study. Although the heart rate and arterial blood pressure

remained at somewhat higher levels when atropine was given concomitantly with betareceptor blockers, this difference was not statistically significant. The spontaneously ventilating group formed the only exception, for in that group atropine caused a highly significant increase in heart rate. The vagolytic action of alcuronium was considered to be the reason for the initially higher heart rates during controlled ventilation. It has been previously shown that atropine is mandatory if beta-receptor blockade in-

138

P. J. P ~ N T I N E N

Table 6 Acid-base balance, blood gases (kPa) and electrolytes (mM) during halothane anaesthesia, beta-receptor blockade and adrenaline challenge (rneans+s.d., n = number of patients, S.V. = spontaneous ventilation, C.V. = controlled ventilation). -

Alprenolol 0.04 mg/kg,

PH

Pace,

Pao, BE K Na

S.V.

n =4

Halothane

Beta blockade

Adrenaline

7.348+0.020 6.5k0.5 21.7 5 5.1 -1.04 1.2 3.6kO.O 135.04 1.9

7.340+0.010 6.3 f0.6 22.8k 0.6 -0.5k2.7 3.7 f0.2 135.8+ 1.3

-

-

-

-

Alprenolol 0.04 mg/kg+atropine 0.01 mg/kg, S.V. n = 8 PH

Pace, Pao, BE K Na

7.397 4 0.074 5.74 1.3 24.7 +_ 3.0 -0.3 f 1.4 3.7k0.2 134.142.4

Alprenolol 0.04 mg/kg, PH

Pace,

Pao, BE K Na

C.V.

-

7.433k0.039 4.8 0.7 20.4f 3.0 -l.O* 1.0 3.8k0.1 135.0+ 2.0

-

7.410+0.051 4.9 0.6 22.5k4.7 -1.Ok 1.0 3.7 kO.1 130.0k 1.0

-

-

-

n =5

7.431 f 0.040 4.8 4 0.7 21.04 4.7 -1.0+1.0 3.850.1 134.04 1.0

Alprenolol 0.05 mg/kg, PH P%O, Pa,, BE K Na

C.V.

7.393 k0.071 5.6 k 1.3 26.1 k 3.6 -l.O+ 1.2 3.7 f0.3 134.4+ 1.2

-

-

n =5

7.4085 0.057 5.040.4 21.45 3.9 -1.Ok2.0 3.7 40.1 130.0k 1.0

-

-

Alprenolol 0.04 mg/kg+atropine 0.01 mg/kg, C.V. n = 14 PH Paco, Pa,, BE K

Na

7.4194 0.046 4.7k 0.7 20.95 2.8 - 1.o+ 2.0 3.9402 133.05 2.1

7.42 1f 0.049 4.6 0.7 20.7f 3.1 - 1.6& 2.4 3.9* 0.2 132.0k2.4

7.4304 0.100 4.5k0.7 22.5k2.9 - 1.1 k2.2 3.9 f0.2 132.9k1.9

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

Table 6 cont. Propranolol 0.04 mg/kg+atropine 0.01 mg/kg, C.V. n = 7 7.358 2 0.067 5 . 5 + 1.0 2 I .4+_4.6 -2.Ok 0.0 4.0 k 0.2 137.0k 6.0

PH Paco, Pao2 BE K Na

7.359 2 0.060 5.3 k 0.9 20.5 5.1 -2.02 1.0 4.0 k 0.2 137.0k5.0

7.3842 0.070 5.0f 1.1 20.3 f 3.8 -2.6k2.3 4.1 k 0.0 136.8f5.5

Propranolol 0.06 mg/kg+atropine 0.01 mg/kg, C.V. n = 4 7.412 2 0.070 4.8k 1.1 15.6k 3.3 -1.3k 1.2 3.8 2 1 .O 134.0+ 1.0

PH Paco, Paoz BE K Na

-

-

-

-

-

-

-

-

___Practolol 0.4 mg/kg+atropine 0.01 mg/kg, C.V. n = 4

7.343 k 0.022 5.6 2 0.2 21.7k5.7 - T O _ + 1.0 4.2k0.1 139.0k 1.0

PH Paco, pa,, BE K Na

7.363 k 0.010 5.3 5 0.2 18.6+ 7.9 -2.O+ 1.0 4.1 kO.1 138.0+0.9

7.398f 0.083 4.8 k 1.O 22.9f5.8 -2.3k0.8 3.7 f0.3 134.8k5.6

Table 7 Patients receiving more than 6 pg/kg adrenaline during halothane anaesthesia.

Sex

Age (Yr)

Beta blocker mglkg

Atropine mglkg

Adrenaline Iclkg

1.

Female

39

-

9.4

2.

Female

60

0.01

8.6

3.

Male

14

-

8.6

4.

Male

42

0.01

7.7

5.

Female

33

__

7.3

ventricular tachycardia

6.

Female

28

0.01

7.0

-

7.

Male

34

practolol 0.3 alprenolol 0.04 alprenolol 0.05 alprenolol 0.04 alprenolol 0.04 alprenolol 0.04 alprenolol 0.04

0.01

6.3

Case

Arrhythmia scattered ventricular extrasystoles -

139

140

P. J. PONTJNEN

Table 8 Arrhythmias during halothane anaesthesia and adrenergic beta-receptor blockade due to adrenaline infiltration. Beta blocker mg/kg

Sex Female

33

alprenolol

Atropine m g h

Adrenaline .%/kg

Arrhythmia

_.___

-

7.3

ventr. tachycardia

0.01

3.8

ventr. bigeminy

0.01

4.6

ventr. bigeminy

0.01

2.9

ventr. bigeminy

0.01

4.7

ventr. bigeminy

0.01

3.6

multifocal ventr. extrasystoles ventr. bigeminy

0.04 Male

24

Male

13

alprenolol 0.04 alprenolol

0.04 Female

20

propranolol

0.04 Female

60

Female

44

propranolol 0.04 propranolol

0.06 Female

33

A4ale

55

Fcmalc

39

2.5

practolol 0.2 practolol 0.2 practolol

5.4

4.0

scattered ventr. extrasystoles scattered ventr. ex trasystolcs ventr. bigeminy

2.8

ventr. tachycardia

9.4

0.3 Male

17

practolol

0.3 Male

30

practolol 0.4

0.01

duces circulatory failure during general 0.04 mg/kg for alprenolol and propranolol anaesthesia (JORFELDT et al. 1970, RADWAN and 0.4 mg/kg for practolol, all with atropine 1972). Atropine itself did not induce arrhyth- (0.01 mg/kg). The present study confirmed mias during beta-receptor blockade in the the compatibility of beta-receptor blockade with halothane, although the cardiovascular present series. The importance of a normal acid-base changes were more pronounced than during 1978). balance and carbon dioxide tension during neurolept-analgesia (PONTINEN Beta-receptor blockade was not able to give beta blockade has been emphasized (FoEx & PRYS-ROBERTS 1974, EIKARD& SKOVSTEDcomplete protection against adrenaline1975). I n the present study, the spontan- induced arrhythmias in the form presented. eously ventilating groups with p H down to The most reliable results were achieved with 7.340+0.010 and PacO, up to 6.3f0.6 kPa alprenolol and propranolol, both of which did not differ from others in any of the also have membrane-stabilizing properties. parameters monitored. In accordance with Practolol has a short effective half-life and it the study of STEPHENet a]. (1971), no induced at least the same degree of circulatory statistically significant differences were depression as the other beta-receptor blockers. recorded between the cardiovascular effects The duration of effective beta-receptor of alprenolol, propranolol and practolol. The blockade after a single intravenous dose lowest levels of arterial blood pressure were extends over 40 min with alprenolol and recorded in the practolol group. The doses propranolol, whereas it is less than 15 min of these three beta-receptor blockers which with practolol (Table 9). The short duration were equipotent in circulatory effects were of the effective antiarrhythmic potency of

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

141

practolol explains the poor results gained with the agent. Practolol's weaker antiarrhythmic effect against adrenaline-induced arrhythmias than against those induced by other catecholamines is also important (ABLAD1972, TORSTI 1973). All arrhythmias escaping the beta-receptor blockade were easily terminated with a further dose of a beta-blocking agent. The cardioselectivity of practolol was seen in the pressure response to adrenaline challenge. I t correlated well with peripheral vasodilatation followed by vasoconstriction, as seen in the pulse wave (Fig. 2). When adrenaline was infiltrated during betareceptor blockade induced by alprenolol or propranolol, the blood pressure rise was continuous and coincided with peripheral vasoconstriction (Fig. 1). The exaggerated individual pressure responses made comparison of the peak pressure effects between these three beta blockers difficult.

16 1L

12 10 8

6 L

2

0 120 110 10 0

90 80

I

I

I

I

I

I

-5

0

5

10

15

20

min

Fig. 3. The effect of 8.6 pg/kg adrenaline on (from top to bottom) radial artery pressure (kPa), pulmonary artery pressure (kPa), heart rate (beatslmin) and CVP (mmH20) in a 14-year-old boy during beta-receptor blockade with alprenolol(O.05 mg/kg) under halothane anaesthesia.

Table 9 Effective duration of adrenergic beta-receptor blockade after a single intravenous dose. Beta blocker

Time in min

References

~

Alprenolol

40 45

l'ropranolol

40-90 40-90 4045 60 150 150

Practolol

5 30 40-50 66 360 480-720

JOHNSTONE

(1968) (1967)

ABLADet al.

BLACKet al. (1965) IWATSUKI et al. (1966) PONTINEN & EKHOLM (1964) JOHNSTONE ( 1966) PATERSON et al. (1970) SHAND et al. (1970)

AELLIGet al. (1970) ( 1969) CARRUTHERS et al. (1973) MERIN(1972) SCALES & COSGROVE (1970) FITZCERALD & SCALES (1968)

JOHNSTONE

142

P. J. PONTINEN

OAKLEY, C. M. & GOODWIN, J. F. (1966) Betaadrenergic blockade in hypertrophic obstructive The compatibility of alprenolol, propranolol cardiomyopathy. Brit. med. 3. 1, 895. and practolol with halothane anaesthesia was COOPERMAN, L. H., ENGELMAN, K. & MANN,P. E. G. (1967) Anesthetic management of pheochromocytoconfirmed. Alprenolol and propranolol proma employing halothane and beta adrenergic vided partial protection against adrenalineblockade. A report of fourteen cases. Anesthesiology28, induced cardiac arrhythmias for over 40 575. min during halothane anaesthesia. Practo- DA ROSA,J. C., PIOVESAN, J. B. & CORADAZZI, M. S. 101’s short duration of effective half-life and (1973) Emprego de um bloqueador dos receptores beta-adrenbrgicos (bloqueador beta) no preparo weaker action against adrenaline-induced prk-operat6rio do hipertiroidismo. Rev. Bras. din. arrhythmias rendered it less suitable for Terap. 2, 115. prophylactic use. The occasionally occurring DAS,G. & KRIEGER,M. (1969) Treatment of thyroid tachyarrhythmias due to adrenaline were crisis with intravenous administration of propranolol. easily terminated with a repeated dose of Ann. intern. Med. 70,985. DE BLASI,D. (1966) The management of the patient these beta blockers. with a phaeochromocytoma. Brit. 3. Anaesth. 38,740. DE LANGE, J. J. (1963) Cardiac arrest with halothane REFERENCES and adrenaline. Anaesthesia 18, 537. ABLAD,B. (1972) Beta-reseptorien salpaajien farma- EIKARD,B. & SKOVSTED, P. (1975) Effects of respiratory kologia. Symposium on Hypertension, Hassle, Gothenburg, acidosis on the arrhythmia threshold during fluroxene and halothane anaesthesia. Ada anaesth. August 1972. ABLAD,B., JOHNSSON, NORRRY, A. & SOLVELL, L. scand. 19, 120. (1967) Potency and time-effect relationship in FESSL-ALEMANY, E. & WEGEHAUPT, R. (1973) Der man of propranolol and H 56/28 - comparative paradoxe oculokardiale Reflex und seine Behandlung mit Pindolol (Viskenm). Albrecht v. Graefes Arch. klin. studies after oral administration. Acta pharmacol. toxicol. 25, Suppl. 2, 85. exp. Ophthal. 188,23. AELLIG,W. H., PRICHARD, B. N. C. & SCALES, B. FITZGERALD, J. D. F. & SCALES, B. (1968) Effect of a (1970) Blood levels of practolol following intravenous new adrenergic beta-blocking agent (I.C.I. 50.172) on heart rate in relation to its blood levels. Znt. J . administration. Brit. 3. Pharmacol. 40, 573. T. H. &JONES, d i n . Pharmacol. 1, 467. BIRD,C. G., HAYWARD, I., HOWELLS, G. D. (1969) Cardiac arrhythmias during thyroid FoEx, P. & PRYS-ROBERTS, C. (1974) Interactions of surgery. Anaesthesia 24, 180. beta-receptor blockade and Pco2levels in the anaesBJORNTORP, P. (1967) The treatment of angina thetized dog. Brit. 3. Anaesth. 46, 397. pectoris with a new beta-receptor blocking agent FORBES,A. M. (1966) Halotbane, adrenaline and (H56/28). Acta med. scand. 182, 285. cardiac arrest. Anaesthesia 21, 22. BLACK,G. W., DUNCAN, W. A. N. & SHANKS, R. G. FREY,H. H. & KAERGAARD-NIELSEN, C. (1966) Study of (1965) Comparison of some properties of pronethalol the effect of a beta-adrenolytic agent upon thiobarbiturate-arrhythmias in the dog. Arch. int. and propranolol. Brit. 3. Pharmacol. 25, 577. J. T. F. & SMITH,B. T. Pharmacodyn. Ther. 162, 93. BLACK,G. W., GLASGOW, (1969) Management of a phaeochromocytoma in a FUKUSHIMA, K., FUJITA, T., FUJIWARA, T., OOSHIMA, H. child. Brit. 3. Anaesth. 41, 184. & SATO,T. (1968) Effect of propranolol on the BRINDLE, G. F., GILBERT, R. G . B. & MILLAR, R. A. ventricular arrhythmias induced by hypercarbia (1957) The use of fluothane in anaesthesia for during halothane anaesthesia in man. B r i f . 3. neurosurgery: a preliminary report. Canad. Aizaesth. Anaesth. 40, 53. GILLAM, P. M. S. & PRICHARD, Soc. 3. 4,265. B. N. C. (1964) Use of BUKY, B. (1970) Propranolol zur Behandlung der in propranolol (Inderal) in the treatment of hypertension. Brit. med. 3. 2, 725. Narkose auftretenden paroxysmalen Tachykardie im Sauglings- und Kindersalter. Anaesthesist 19, 125. HARRIS, A. (1966) Long-term treatment of paroxysmal cardiac arrhythmias with propranolol. Amer. 3. S. G., KELLY,J. G., MCDEVITT, D. G., CARRUTHERS, SHANKS, R. G. & WALSH,M. J. (1973) Duration of Cardiol. 18, 431. action of beta-blocking drugs. Brit. med. 3. 2, 177. HELLEWELL, J. & POTTS,M. W. (1965) Propranolol and ventricular arrhythmias with halothane. Anaesthesia A. J., DIPALMA, J. R., ANDLRSON, J. D. & CATENACCI, KING, W. E. (1963) Serious arrhythmias with 20, 269. vasopressors during halothane anesthesia in man. HELLEWELL, J. & POTTS,M. W. (1966) Propranolol 3. Amer. med. Ass. 183, 662 Brit. 3. Anaesth. during controlled hypotension. .. 38, 749. CHERIAN,G., BROCKINGTON, I. M., SHAH, P. M.,

CONCLUSIONS

BETA BLOCKADE AND ADRENALINE DURING HALOTHANE ANAESTHESIA

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77. KATZ,R . L. & EPSTEIN, R . A. (1968) The interaction of anesthetic agents and adrenergic drugs to produce cardiac arrhythmias. Anesthesiology 29, 763. KATZ,R . L., MATTEO,R. S. & PAPPER,E. M . (1962) The injection of epinephrine during general anesthesia with halogenated hydrocarbons and cyclopropane in man. 2. Halothane. Anesthesiology 23, 597. KLIDE,A. M . (1966) Mechanism for the reduction in airway resistance induced by halothane. Fed. Proc. 25, 229. LYDTIN,H., Kusws, T., DANIEL,W., SCHIERL,W., ACKENHEIL, M., KEMPTER,H., LOHMULLER, G., NIKLAS, M. & WALTER, I. (1972) Propranolol therapy in essential hypertension. Amer. Heart 3.83, 589. MACALPIN,R. M., KATTUS, A. A. & WINFIELD, M. E.

143

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1M

P. J.

PONTINEN

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Cardiovascular effects of local adrenaline infiltration during halothane anaesthesia and adrenergic beta-receptor blockade in man.

Acta anaesth. scand. 1978, 22, 130-144 Cardiovascular Effects of Local Adrenaline Infiltration During Halothane Anaesthesia and Adrenergic Beta-Recep...
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