Brain Research, 103 (1976) 157-160 ,JQ Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
157
Changes of skin nerve sympathetic activity during induction of general anaesthesia with thiopentone in man
B. GUNNAR WALLIN AND ULF KONIG Departments of Clinical Neurophysiology and Anaesthesiology, University Hospital, Uppsala (Sweden)
(Accepted October 21st, 1975)
Sympathetic recordings in intact animals are usually made during general anaesthesia and it is common knowledge that sympathetic function usually is influenced by the depth of anaesthesia. Due to technical difficulties, however, sympathetic activity has not previously been recorded during the induction of general anaesthesia and consequently the effects of the initial phases of anaesthesia on the spontaneous outflow of sympathetic impulses remain unknown. With the development of a technique for recording sympathetic activity in man such experiments have now become feasiblel,Z,4, ,5 and the present report will show that profound changes of human skin nerve sympathetic activity (SSA) occur during the induction of general anaesthesia with thiopentone. In connection with elective abdominal surgery, recordings of SSA were made on 3 subjects, 2 males and 1 female, aged 31-4l years. The patients volunteered for the experiments after detailed explanation of the experimental design. The operations to be performed were cholecystectomy (for cholelithiasis), colectomy (for ulcerative colitis) and transposition of the jejunum (for a postgastrectomy syndrome). No premedication was given and anaesthesia was initiated by intravenous injection of 300500 mg thiopentone (Pentothal). The depth of anaesthesia was monitored by 2-channel surface EEG with electrodes in position O1-P3 and O2-P4. Heart rate was monitored by two ECG electrodes placed on the chest, and respiratory movements by a strain gauge applied with a rubber band around the chest. The neural recordings were made with tungsten microelectrodes inserted manually into a skin nerve fascicle in the right peroneal nerve at the fibular head. All signals were stored on an 8-channel tape recorder (PI-6200). Details of the neural recording technique and the methods for analyzing and displaying the neural signals have been described previously 1,~. The skin nerve fascicles were identified by the afferent impulses that could be elicited by cutaneous stimuli within the innervation zone of the fascicle on the foot or the lower leg. Having identified the fascicle, minute electrode adjustments were made until a recording position was found where spontaneously occurring sympathetic impulses could be recorded. Such recording sites were easy to recognize since the sympathetic impulses in skin
158 nerves are discharged in irregular bursts occurring in a characteristic temporal pattern. Furthermore, stimuli such as a deep breath, a loud sound or a skin pinch anywhere on the body give rise to a distinct burst of sympathetic impulses which can be recorded after a reflex delay of 0.5-1.0 sec. A description of the characteristics of SSA and of the methods of establishing the sympathetic nature of the activity has been given previously ~.'~. Having found a recording position with good signal-to-noise ratio for sympathetic impulses, the spontaneous SSA was recorded for 5 10 rain before 300-500 mg thiopentone was injected intravenously. During this period the resting sympathetic discharge was quite prominent. The effects of the thiopentone injection were similar in all three patients and are illustrated in Fig. 1, in which the multiunit sympathetic activity is displayed as an integrated neurogram (time constant 0.1 sec). Regardless of whether the injection was given rapidly ( < 15 sec) or slowly (;> 2 rain) there was little change in the neurogram until the patient lost consciousness and developed the initial apnoea. When this occurred, however, there was a dramatic depression of the sympathetic activity: the spontaneous bursts were rapidly reduced in number and strength, until within approximately I min virtually no spontaneous activity remained. During this phase it was possible to elicit sympathetic reflexes in response to skin stimuli or respiratory events. In Fig. 1, middle part, the large burst in the integrated neurogram represents such reflex activity occurring in response to a sudden inspiratory gasp during the apnoea period. However, as the depth of anaesthesia increased, reflex bursts became progressively more difficult or impossible to elicit. This is illustrated m the right part of Fig. I where the delta-waves in the EEG and the high heart rate are evidence of the depth of anaesthesia. During this time repeated skin stimuli (marked by
Pentothol 500mg
2 rain Respiratory movements
Skin nerve
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S
4 min
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A
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....•.................................................................... 120 Heart rate
.
,.. . " . ...
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.................. '
..
................. ..,...'"'"'........ ........... ...."%.
- 100
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- 80
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lsec
Fig. 1. The effect of a slow injection of 500 mg Pentothal on integrated skin nerve sympathetic activitY recorded in the right peroneal nerve. The patient was consciousin the left and unconsciousin the middle and right part of the figure. The open arrows in the right part of the figure indicate attempts to elicit sympathetic reflex responses by skin pinches, the last two stimuli giving no detectable response. The breaks between the three parts of the figure comprise about 1 rain each. Note separate time scale for the EEG records.
159 arrows) failed to elicit reflex bursts. When a single dose of thiopentone had been given the depression of the sympathetic activity was shortlasting and both reflexly induced and 'spontaneous' bursts reappeared as the depth of anaesthesia lessened. A second injection of thiopentone in 2 subjects reproduced the same sequence of events. In one subject after 2 injections of thiopentone (total 750 mg), recording was continued during inhalational anaesthesia with 1 ~o halothane and 70 3~ nitrous oxide in oxygen. In this way it became possible to vary the depth of anaesthesia in a slower and more controlled way, and again the strength of the SSA proved to be closely related to the depth of the anaesthesia. This is illustrated in Fig. 2 which shows the reflex effects of repeated skin and sound stimuli during the course of recovery from deep halothane-nitrous oxide anaesthesia (upper part) and renewed halothane-nitrous oxide inhalation (lower part). The first records in the upper part show that skin pinches elicited no reflex response until after about 6 m in of breathing 100 ~o oxygen. After 7.5 min the reflex responses to skin pinches had recovered to a constant level, but sound stimuli were still ineffective, and not until 11.5 min after the cessation of the anaesthesia could reflex responses to such stimuli be recorded. At about the same time small spontaneous bursts were seen and withdrawal reflexes were noted in response to skin stimulation. When the halothane-nitrous oxide anaesthesia was reinstated (in the lower part of the figure) the patient had been curarized (8 mg pancuronium bromide) pinches
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157
Changes of skin nerve sympathetic activity during induction of general anaesthesia with thiopentone in man
B. GUNNAR WALLIN AND ULF KONIG Departments of Clinical Neurophysiology and Anaesthesiology, University Hospital, Uppsala (Sweden)
(Accepted October 21st, 1975)
Sympathetic recordings in intact animals are usually made during general anaesthesia and it is common knowledge that sympathetic function usually is influenced by the depth of anaesthesia. Due to technical difficulties, however, sympathetic activity has not previously been recorded during the induction of general anaesthesia and consequently the effects of the initial phases of anaesthesia on the spontaneous outflow of sympathetic impulses remain unknown. With the development of a technique for recording sympathetic activity in man such experiments have now become feasiblel,Z,4, ,5 and the present report will show that profound changes of human skin nerve sympathetic activity (SSA) occur during the induction of general anaesthesia with thiopentone. In connection with elective abdominal surgery, recordings of SSA were made on 3 subjects, 2 males and 1 female, aged 31-4l years. The patients volunteered for the experiments after detailed explanation of the experimental design. The operations to be performed were cholecystectomy (for cholelithiasis), colectomy (for ulcerative colitis) and transposition of the jejunum (for a postgastrectomy syndrome). No premedication was given and anaesthesia was initiated by intravenous injection of 300500 mg thiopentone (Pentothal). The depth of anaesthesia was monitored by 2-channel surface EEG with electrodes in position O1-P3 and O2-P4. Heart rate was monitored by two ECG electrodes placed on the chest, and respiratory movements by a strain gauge applied with a rubber band around the chest. The neural recordings were made with tungsten microelectrodes inserted manually into a skin nerve fascicle in the right peroneal nerve at the fibular head. All signals were stored on an 8-channel tape recorder (PI-6200). Details of the neural recording technique and the methods for analyzing and displaying the neural signals have been described previously 1,~. The skin nerve fascicles were identified by the afferent impulses that could be elicited by cutaneous stimuli within the innervation zone of the fascicle on the foot or the lower leg. Having identified the fascicle, minute electrode adjustments were made until a recording position was found where spontaneously occurring sympathetic impulses could be recorded. Such recording sites were easy to recognize since the sympathetic impulses in skin
158 nerves are discharged in irregular bursts occurring in a characteristic temporal pattern. Furthermore, stimuli such as a deep breath, a loud sound or a skin pinch anywhere on the body give rise to a distinct burst of sympathetic impulses which can be recorded after a reflex delay of 0.5-1.0 sec. A description of the characteristics of SSA and of the methods of establishing the sympathetic nature of the activity has been given previously ~.'~. Having found a recording position with good signal-to-noise ratio for sympathetic impulses, the spontaneous SSA was recorded for 5 10 rain before 300-500 mg thiopentone was injected intravenously. During this period the resting sympathetic discharge was quite prominent. The effects of the thiopentone injection were similar in all three patients and are illustrated in Fig. 1, in which the multiunit sympathetic activity is displayed as an integrated neurogram (time constant 0.1 sec). Regardless of whether the injection was given rapidly ( < 15 sec) or slowly (;> 2 rain) there was little change in the neurogram until the patient lost consciousness and developed the initial apnoea. When this occurred, however, there was a dramatic depression of the sympathetic activity: the spontaneous bursts were rapidly reduced in number and strength, until within approximately I min virtually no spontaneous activity remained. During this phase it was possible to elicit sympathetic reflexes in response to skin stimuli or respiratory events. In Fig. 1, middle part, the large burst in the integrated neurogram represents such reflex activity occurring in response to a sudden inspiratory gasp during the apnoea period. However, as the depth of anaesthesia increased, reflex bursts became progressively more difficult or impossible to elicit. This is illustrated m the right part of Fig. I where the delta-waves in the EEG and the high heart rate are evidence of the depth of anaesthesia. During this time repeated skin stimuli (marked by
Pentothol 500mg
2 rain Respiratory movements
Skin nerve
"~,"v~
S
4 min
~ ~ , ~ , . . , ~ / ~
A
~
~
Beats/rnin
....•.................................................................... 120 Heart rate
.
,.. . " . ...
. ......
.................. '
..
................. ..,...'"'"'........ ........... ...."%.
- 100
""" '"
/ /
/ •
- 80
"-,,
5 ,e~'--~
\ ",,.\
/" /
",
,./
\
\
\
\ \
",,,,,
EEG
lsec
Fig. 1. The effect of a slow injection of 500 mg Pentothal on integrated skin nerve sympathetic activitY recorded in the right peroneal nerve. The patient was consciousin the left and unconsciousin the middle and right part of the figure. The open arrows in the right part of the figure indicate attempts to elicit sympathetic reflex responses by skin pinches, the last two stimuli giving no detectable response. The breaks between the three parts of the figure comprise about 1 rain each. Note separate time scale for the EEG records.
159 arrows) failed to elicit reflex bursts. When a single dose of thiopentone had been given the depression of the sympathetic activity was shortlasting and both reflexly induced and 'spontaneous' bursts reappeared as the depth of anaesthesia lessened. A second injection of thiopentone in 2 subjects reproduced the same sequence of events. In one subject after 2 injections of thiopentone (total 750 mg), recording was continued during inhalational anaesthesia with 1 ~o halothane and 70 3~ nitrous oxide in oxygen. In this way it became possible to vary the depth of anaesthesia in a slower and more controlled way, and again the strength of the SSA proved to be closely related to the depth of the anaesthesia. This is illustrated in Fig. 2 which shows the reflex effects of repeated skin and sound stimuli during the course of recovery from deep halothane-nitrous oxide anaesthesia (upper part) and renewed halothane-nitrous oxide inhalation (lower part). The first records in the upper part show that skin pinches elicited no reflex response until after about 6 m in of breathing 100 ~o oxygen. After 7.5 min the reflex responses to skin pinches had recovered to a constant level, but sound stimuli were still ineffective, and not until 11.5 min after the cessation of the anaesthesia could reflex responses to such stimuli be recorded. At about the same time small spontaneous bursts were seen and withdrawal reflexes were noted in response to skin stimulation. When the halothane-nitrous oxide anaesthesia was reinstated (in the lower part of the figure) the patient had been curarized (8 mg pancuronium bromide) pinches
Skin
Respiratory
I
1
l
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/'VX/V%
....... " ' " "
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- 120
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- 100 - 80
~5sec'""'"-60
]
0
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1% H o l o t h o n e
I
2
4
I 6
....
