0
1991 The British
Association of Oral and Maxillofmal
Surgeons
The biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions in patients having third molar surgery under general anaesthesia J. G. Meechan,
C. W. Thomson,
G. S. Blair, M , L). Kawlins
Department of Oral Surgery. The Dental School, University of Newcastle upon Tyne, Department of Anaesthesia, Freeman Hospital, .Newcastle upon Tyne, and Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne
SUMMARY. The etTects of adrenaline-containing and adrenaline-free lignocaine local anaesthetic solutions injected in doses consistent with clinical practice on plasma potassium concentration, blood glucose levels and haemodynamic responses were investigated in 20 patients having third molar surgery under general anaesthesia. All patients received a standard general anaesthetic regime. Ten patients were given 4.0 ml of 2% lignocaine as an inferior dental and long buccal block during their general anaesthetic and the other 10 received 4.0 ml of 2% lignocaine containing 1:80000 adrenaline in the same manner. There were no significant differences between treatments in blood pressure or heart rate. However, there were significant differences between treatments in plasma potassium concentration and blood glucose levels.
AND METHODS
INTRODUCTION
MATERIALS
The administration of locai anaesthetics during general anaesthesia is performed in patients having surgery to help in postoperative pain control, and the use of a vasoconstrictor-containing solution also aids haemostasis (McQuay et al., 1988; Tuffin et al., 1989). In addition the injection of adrenaline-free local anaesthetics during general anaesthesia for oral surgery has been shown to reduce the incidence of cardiac arrhythmias due to surgical stimulation (Plowman et al., 1974; Rashad & El-Attar, 1990). The systemic effects attributable to the injection of dental local anaesthetic solutions have been the subject of discussion for many years (Carr, 1948; Holroyd et al., 1960; Hayward, 1961; Glover, 1968; Cawson et al., 1983; Jastak & Yagiela, 1983). Most of the debate has been concerned with the haemodynamic effects of the vasoconstrictor component in both healthy and medically compromised patients. Recent evidence suggests that the quantities of adrenaline injected routinely during oral surgery procedures can produce biochemical changes in healthy volunteers (Meechan & Rawlins, 1987a, 1987b) and in patients having third molar surgery under local anaesthesia (Meechan & Rawlins, 1988). It was the purpose of the present study to investigate biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions when used in clinical doses in patients having third molar surgery under general anaesthesia. It was considered that this would be a useful model to demonstrate the effects of exogenous adrenaline in individuals who were undergoing a controlled stressful procedure.
Ethical approval for this investigation was received from the Joint Ethics Committee of Newcastle Health Authority and Newcastle University. The study sample consisted of 20 fit, otherwise healthy patients admitted for the removal of third molar teeth under general anaesthesia. The fact that all subjects were free of any medical complication meant that a uniform general anaesthetic technique could be employed for all the patients. Premeditation consisted of 10 mg diazcpam orally and 0.3 mg atropine intramuscularly 1 h preoperatively. Venous access for induction was established with a 22 gauge plastic cannula in a suitable vein in the dorsum of the left hand. The sequence of drugs used during the induction was as follows: 0.5 mg pancuronium 1 min prior to induction; 0.5 mg droperidol with 50 pg fcntanyl followed by 80-100 mg methohcxitone and 70 mg suxamethonium chloride. The patients received 50% nitrous oxide and oxygen with 2% enflurane prior to nasal intubation. When the suxamethonium wore off the patients were allowed to breathe spontaneously until the conclusion of the operation, being maintained with nitrous oxide, oxygen and enflurane. The same consultant anaesthetist administered the general anaesthetics for all the patients. Eleven minutes following the injection of the suxamethonium and before surgery commenced the subject received 4.0 ml of a local anaesthetic solution over a 1 min period. This was administered using an aspirating technique as an inferior dental block and long buccal block on one side of the mouth. Ten patients received 2% lignocaine and 10 were given 2% lignocaine with 1:80000 adrenaline 263
264
British Journal of Oral
and Maxillofacial
Sureerv
(that is a total of 50 ug adrenaline). The local anaesthetic allocation was random. All injections and surgery were performed by the same surgeon who was aware of the identity of the local anaesthetic used. However, the anaesthetist who made the haemodynamic recordings and removed the blood samples was blind in this respect. The following recordings and blood samplings were made for each subject. Prior to induction 5 ml of blood was removed via the indwelling venous catheter for measurement of plasma potassium and blood glucose concentrations. Plasma potassium was measured using an ion specific electrode (Beckman Instruments Incorporated, Brea, California) and blood glucose by the oxygen rate method using an oxygen electrode (Beckman Instruments Incorporated, Brea, California). Ten minutes after the administration of the suxamethonium (that is 1 min before local anaesthetic injection) blood pressure and heart rate were recorded using a Datascope automatic recorder (Datascope Corporation, Paramus, New Jersey), end tidal carbon dioxide level was measured (Datex Instrumentarium, Helsinki, Finland) and 5 ml of blood was removed for potassium and glucose assay. These recordings and samplings were repeated immediately following, and at i0 and 20 min after the local anaesthetic administration. Surgery b.egan following the immediate post-injection recordings and was still in progress for all patients when the 20 min recordings were taken. This meant that the 10 and 20 min readings were taken at times when the patient was subjected to surgical stress. The patients’ electrocardiograms were monitored throughout the general anaesthetic. The changes from the pre-local anaesthetic (baseline) values with each treatment were compared by analysis of variance and Student’s t test. The changes within each treatment were compared with the paired t test.
There were no significant differences in the changes in blood pressure, heart rate or end tidal carbon dioxide level between treatments at any of the times recorded. There was no significant change in the plasma potassium concentration between the immediate prc-induction concentration and that recorded immediately before the injection of the local anaesthetic.
SYSTOLIC
80 BP
(mmlig)
0
nm (ml@
296Lignocaine 2”/.Lignocaine
+ i:80 000 Adrenaline
T
PRELA
--a---
--c-
10
Fig. 1 - The pooled values (means and standard deviations)
for
both treatments showing blood pressure versus time. Pre-LA represents the recording taken immediately before local anaesthetic injection.
RESULTS The ages of the patients in this investigation wcrc 25.5k6.7 years for those in whom the adrenalinecontaining local anacsthetic was used and 23.6k5.3 years for those who received the vasoconstrictor-free solution. The body weights of both groups were similar being 70.W14.5 kg and 68.5k15.2 kg respectively. The surgical stress experienced by both groups of patients (as measured by operating time) did not differ significantly. The time for completion of surgery for those who received lignocaine with adrenaline was 27.4f5.1 min and for those who wcrc given the plain lignocaine solution operating time was 31.6k9.8 min. The results of the study arc shown in Figs 1-5 and statistical data are presented in Tables 1 and 2. In the analysis of the results the readings performed 1 min before the administration of the local anaesthetic were taken as baseline values and the changes at zero, IO and 20 min from this baseline were analysed.
80 HR
@pm) .I.
1
____o.--
2% Lignocaine
-
2% Lignocaine
+I :80 000 Adrenaline
PRELA
0
10
20
Time (mm) Fig. 2 - The pooled values (means and standard deviations) both treatments showing heart rate versus time. Prc-LA represents the recording taken immediately before local anacsthetic injection.
for
Effects of adrenaline
in lignocainc local anacsthetic
solutions
265
6.5 -
e I I o)-
6.0 5
x fz n
% Lignocaine
32 30
____o---
2% Lignocaine
-
2% Lignocaine
+1:80 000 Adrenaline
LA
1 20
I
I 1 PRE 0
10
4.4
4.3
4.2
4.1
4s
]
0
10
3.I
---0--
Z%Lignocaine
_
2% Ugnocaine
mmol/l wilh 1~60 000 Adrenaline
3.6
,
“pCO.02 ‘pd.05
3.7
Time
(mtn)
Fig. 5 - The pooled values (means and standard deviations) for both treatments showing blood glucose concentration versus time. Pre-GA is the reading made immediately bcforc induction of general anaesthesia and pre-LA represents the recording prior to local anaesthetic injection.
There were significant changes in plasma potassium concentrations between treatments immediately following and 20 min after the local anaesthetic injection (Table 1). Immediately following the injection of the adrenaline-containing solution there was a significant rise in plasma potassium from the baseline concentration. The increase in plasma potassium concentration from baseline with the injection of plain lignocaine was significant at 10 min. There was a significant rise in blood glucose during the early stage of the general anaesthetic. The mean (k standard deviation) increase from the pre-induction concentration to that recorded immediately before the injection of the local anaesthetic for all 20 patients being 0.57kO.37 mmol/l (t=6.89, 19 degrees of freedom, p
1991 The British
Association of Oral and Maxillofmal
Surgeons
The biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions in patients having third molar surgery under general anaesthesia J. G. Meechan,
C. W. Thomson,
G. S. Blair, M , L). Kawlins
Department of Oral Surgery. The Dental School, University of Newcastle upon Tyne, Department of Anaesthesia, Freeman Hospital, .Newcastle upon Tyne, and Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne
SUMMARY. The etTects of adrenaline-containing and adrenaline-free lignocaine local anaesthetic solutions injected in doses consistent with clinical practice on plasma potassium concentration, blood glucose levels and haemodynamic responses were investigated in 20 patients having third molar surgery under general anaesthesia. All patients received a standard general anaesthetic regime. Ten patients were given 4.0 ml of 2% lignocaine as an inferior dental and long buccal block during their general anaesthetic and the other 10 received 4.0 ml of 2% lignocaine containing 1:80000 adrenaline in the same manner. There were no significant differences between treatments in blood pressure or heart rate. However, there were significant differences between treatments in plasma potassium concentration and blood glucose levels.
AND METHODS
INTRODUCTION
MATERIALS
The administration of locai anaesthetics during general anaesthesia is performed in patients having surgery to help in postoperative pain control, and the use of a vasoconstrictor-containing solution also aids haemostasis (McQuay et al., 1988; Tuffin et al., 1989). In addition the injection of adrenaline-free local anaesthetics during general anaesthesia for oral surgery has been shown to reduce the incidence of cardiac arrhythmias due to surgical stimulation (Plowman et al., 1974; Rashad & El-Attar, 1990). The systemic effects attributable to the injection of dental local anaesthetic solutions have been the subject of discussion for many years (Carr, 1948; Holroyd et al., 1960; Hayward, 1961; Glover, 1968; Cawson et al., 1983; Jastak & Yagiela, 1983). Most of the debate has been concerned with the haemodynamic effects of the vasoconstrictor component in both healthy and medically compromised patients. Recent evidence suggests that the quantities of adrenaline injected routinely during oral surgery procedures can produce biochemical changes in healthy volunteers (Meechan & Rawlins, 1987a, 1987b) and in patients having third molar surgery under local anaesthesia (Meechan & Rawlins, 1988). It was the purpose of the present study to investigate biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions when used in clinical doses in patients having third molar surgery under general anaesthesia. It was considered that this would be a useful model to demonstrate the effects of exogenous adrenaline in individuals who were undergoing a controlled stressful procedure.
Ethical approval for this investigation was received from the Joint Ethics Committee of Newcastle Health Authority and Newcastle University. The study sample consisted of 20 fit, otherwise healthy patients admitted for the removal of third molar teeth under general anaesthesia. The fact that all subjects were free of any medical complication meant that a uniform general anaesthetic technique could be employed for all the patients. Premeditation consisted of 10 mg diazcpam orally and 0.3 mg atropine intramuscularly 1 h preoperatively. Venous access for induction was established with a 22 gauge plastic cannula in a suitable vein in the dorsum of the left hand. The sequence of drugs used during the induction was as follows: 0.5 mg pancuronium 1 min prior to induction; 0.5 mg droperidol with 50 pg fcntanyl followed by 80-100 mg methohcxitone and 70 mg suxamethonium chloride. The patients received 50% nitrous oxide and oxygen with 2% enflurane prior to nasal intubation. When the suxamethonium wore off the patients were allowed to breathe spontaneously until the conclusion of the operation, being maintained with nitrous oxide, oxygen and enflurane. The same consultant anaesthetist administered the general anaesthetics for all the patients. Eleven minutes following the injection of the suxamethonium and before surgery commenced the subject received 4.0 ml of a local anaesthetic solution over a 1 min period. This was administered using an aspirating technique as an inferior dental block and long buccal block on one side of the mouth. Ten patients received 2% lignocaine and 10 were given 2% lignocaine with 1:80000 adrenaline 263
264
British Journal of Oral
and Maxillofacial
Sureerv
(that is a total of 50 ug adrenaline). The local anaesthetic allocation was random. All injections and surgery were performed by the same surgeon who was aware of the identity of the local anaesthetic used. However, the anaesthetist who made the haemodynamic recordings and removed the blood samples was blind in this respect. The following recordings and blood samplings were made for each subject. Prior to induction 5 ml of blood was removed via the indwelling venous catheter for measurement of plasma potassium and blood glucose concentrations. Plasma potassium was measured using an ion specific electrode (Beckman Instruments Incorporated, Brea, California) and blood glucose by the oxygen rate method using an oxygen electrode (Beckman Instruments Incorporated, Brea, California). Ten minutes after the administration of the suxamethonium (that is 1 min before local anaesthetic injection) blood pressure and heart rate were recorded using a Datascope automatic recorder (Datascope Corporation, Paramus, New Jersey), end tidal carbon dioxide level was measured (Datex Instrumentarium, Helsinki, Finland) and 5 ml of blood was removed for potassium and glucose assay. These recordings and samplings were repeated immediately following, and at i0 and 20 min after the local anaesthetic administration. Surgery b.egan following the immediate post-injection recordings and was still in progress for all patients when the 20 min recordings were taken. This meant that the 10 and 20 min readings were taken at times when the patient was subjected to surgical stress. The patients’ electrocardiograms were monitored throughout the general anaesthetic. The changes from the pre-local anaesthetic (baseline) values with each treatment were compared by analysis of variance and Student’s t test. The changes within each treatment were compared with the paired t test.
There were no significant differences in the changes in blood pressure, heart rate or end tidal carbon dioxide level between treatments at any of the times recorded. There was no significant change in the plasma potassium concentration between the immediate prc-induction concentration and that recorded immediately before the injection of the local anaesthetic.
SYSTOLIC
80 BP
(mmlig)
0
nm (ml@
296Lignocaine 2”/.Lignocaine
+ i:80 000 Adrenaline
T
PRELA
--a---
--c-
10
Fig. 1 - The pooled values (means and standard deviations)
for
both treatments showing blood pressure versus time. Pre-LA represents the recording taken immediately before local anaesthetic injection.
RESULTS The ages of the patients in this investigation wcrc 25.5k6.7 years for those in whom the adrenalinecontaining local anacsthetic was used and 23.6k5.3 years for those who received the vasoconstrictor-free solution. The body weights of both groups were similar being 70.W14.5 kg and 68.5k15.2 kg respectively. The surgical stress experienced by both groups of patients (as measured by operating time) did not differ significantly. The time for completion of surgery for those who received lignocaine with adrenaline was 27.4f5.1 min and for those who wcrc given the plain lignocaine solution operating time was 31.6k9.8 min. The results of the study arc shown in Figs 1-5 and statistical data are presented in Tables 1 and 2. In the analysis of the results the readings performed 1 min before the administration of the local anaesthetic were taken as baseline values and the changes at zero, IO and 20 min from this baseline were analysed.
80 HR
@pm) .I.
1
____o.--
2% Lignocaine
-
2% Lignocaine
+I :80 000 Adrenaline
PRELA
0
10
20
Time (mm) Fig. 2 - The pooled values (means and standard deviations) both treatments showing heart rate versus time. Prc-LA represents the recording taken immediately before local anacsthetic injection.
for
Effects of adrenaline
in lignocainc local anacsthetic
solutions
265
6.5 -
e I I o)-
6.0 5
x fz n
% Lignocaine
32 30
____o---
2% Lignocaine
-
2% Lignocaine
+1:80 000 Adrenaline
LA
1 20
I
I 1 PRE 0
10
4.4
4.3
4.2
4.1
4s
]
0
10
3.I
---0--
Z%Lignocaine
_
2% Ugnocaine
mmol/l wilh 1~60 000 Adrenaline
3.6
,
“pCO.02 ‘pd.05
3.7
Time
(mtn)
Fig. 5 - The pooled values (means and standard deviations) for both treatments showing blood glucose concentration versus time. Pre-GA is the reading made immediately bcforc induction of general anaesthesia and pre-LA represents the recording prior to local anaesthetic injection.
There were significant changes in plasma potassium concentrations between treatments immediately following and 20 min after the local anaesthetic injection (Table 1). Immediately following the injection of the adrenaline-containing solution there was a significant rise in plasma potassium from the baseline concentration. The increase in plasma potassium concentration from baseline with the injection of plain lignocaine was significant at 10 min. There was a significant rise in blood glucose during the early stage of the general anaesthetic. The mean (k standard deviation) increase from the pre-induction concentration to that recorded immediately before the injection of the local anaesthetic for all 20 patients being 0.57kO.37 mmol/l (t=6.89, 19 degrees of freedom, p
