Glycemic effect of administration

of epinephrine-containing local
anaesthesia in patients undergoing
dental extraction, a comparison
between healthy and diabetic patients
Fatima Ebrahim Tily and Sam Thomas
Ajman, United Arab Emirates

Objectives: To compare the effect of administration of epinephrine (in the dental local
anesthetic solution) on blood glucose concentration in healthy and diabetic dental patients
after extraction. To determine if there is any correlation between blood glucose level
changes and the number of carpules injected, number of teeth extracted and the gender
of the patient. Materials and method: An open study of 60 patients (30 healthy and 30
diabetics) visiting the Oral Surgery clinic of Ajman University of Science and Technology.
A drop of blood was taken from the tip of the patient's finger and placed on a glucometer
strip to determine the pre-operative blood glucose level. Dental local anaesthesia (1.8ml
carpule each) containing 1:80,000 epinephrine was injected either through infiltration or
block. Extraction was carried out atraumatically and 10 minutes post-extractionthe glucose
measurement was taken. Results: The difference in the blood glucose levels pre- and
post operatively were not significantly different (p>0.05) when a comparison was made
between the healthy and diabetic groups. Comparison of glucose changes in diabetics who
had taken their hypoglycaemic medication and those who had not, showed a significant
difference ( ~ ~ 0 . 0 5Statistical
). analysis showed no correlation between the blood glucose
level changes and the number of carpules used, number of teeth extracted and gender.
Conclusion: Dental local anaesthetic solution containing epinephrine is safe to use in
all healthy and diabetic patients (irrespective of their gender), excepting those diabetics
who have not taken their pre-operative hypoglycaemic medication. There is no relation
between the post-extraction glucose changes and the number of carpules used, number
of teeth extracted or gender.

Key words: Diabetic patients, local anaesthesia, hypoglycaemia, tooth extraction

It has been known for many years that the inclusion of
vasoconstrictors in dental local anaesthetic solutions of-
fers indisputable advantages. Vasoconstrictors promote
longer lasting anaesthesia, diminish the toxic effects by
delaying absorption, and reduce blood loss in surgcal
procedures'.
Plasma levels of glucose have been reported to be
affected following dental local anaesthetic injections of
adrenaline-containing solutions','. Whether this effect
is observed as a fall or a rise in blood glucose levels
is a subject of controversy, especially when it comes
to diabetic patients since they have an altered glucose
homeostatic mechanism. Thus, although numerous
studies have been conducted previously with regard
to this issue, no conclusive evidence has, as yet, been
found to put the issue to rest and researches in the field
continue to date3,4.

0 2007 FDlNVorld Dental Press

0020-6539/07/02077-07
78

Materials and method were started on oral hypoglycaemic medication but

eventually insulin injections had to be prescribed by
A n open study was conducted in the Oral Surgery clinic,
their physicians.
Faculty of Dentistry, Ajman University o f Science and
The procedure was well explained and written con-
Technology. T h e sample consisted of 60 patients (30
sent was taken from all volunteers or their guardlans.
healthy; 30 dlabetics). The research volunteers consisted
Sex, nationality and social background were not criteria
o f two groups: healthy patients (ie. patients with no
for patient selection. Through random patient selection,
history o f systemic disease, including diabetes, and not
the mean age o f the healthy patients was 42 years; 16
on any medication); and diabetic patients (ie. patients
males, 14 females. In the diabetic group, the mean age
with a history of diabetes, with or without other sys-
was 50 years; 22 males and 8 females. Twenty-five of the
temic diseases).
30 diabetic patients were on hypoglycaemic medication
T h e diabetic patients in this study belonged to one
and only five were on diet control. Out of these 25, eight
o f the following categories:
0 Uncontrolled diabetics of them did not take their medication pre-operatively
0 Controlled diabetics : on the day of extraction.
- Diet control
The following cases were excluded from the study:
- On insulin
Pregnant women
- On oral hypoglycaemic medication.
Paediatric extractions (age 1 2 or under)
Though our study was open, all our patients were Surgcal extractions
long standing type 2 diabetics (6 months or more) and Cases where local anaesthesia without epinephrine
none of them was instructed to deliberately take or miss was used
their hypoglycaemic medication. Some o f the patients Pre-operative blood glucose > 350 mg/dl.

Table 1 Demographic details of healthy patients

S.No. Sex No. of Teeth No. of L.A. Carpules Pre-op Glucose Post-op Glucose Difference
Extracted (1.8 ml each) (mg/dl) (mg/dl) (Post-Pre)
~

1 44 M 2 1 98 95 -3
2 38 M 4 5 109 97 -1 2
3 32 M 1 0.5 90 105 15
4 42 M 1 3 90 105 15
5 14 F 1 1.5 90 96 6
6 35 F 1 1 93 82 -11
7 40 F 1 0.75 87 92 5
8 31 F 2 1 94 90 -4
9 46 M 1 1 115 118 3
10 13 F 1 1 97 92 -5
11 54 M 1 1 124 103 -2 1
12 22 M 1 1 84 83 -1
13 34 F 1 1 97 124 27
14 48 F 1 1 77 85 8
15 39 F 2 1 135 114 -2 1
16 50 M 5 2.5 91 99 8
17 59 M 7 3 82 88 6
18 48 M 1 1 137 125 -1 2
19 40 F 2 1 85 94 9
20 35 F 1 2 95 92 -3
21 46 M 2 2 107 120 13
22 45 F 1 1 120 130 10
23 34 M 3 2 95 105 10
24 39 M 3 1 92 99 7
25 46 F 1 2 87 99 12
26 54 M 1 3 102 104 2
27 59 F 2 4 96 130 34
28 58 F 2 1 123 130 7
29 49 M 1 1 109 107 -2
30 49 M 1 1 78 86 8

International Dental Journal (2007) Vol. 57/No.2

 79

Armamentarium
Glucometer (Accu-Chek Active@,Roche)
Lidocaine hydrochloride with 1:80,000 adrenaline
(Lignospan special, Septodont@)
Timer
Sterile gauze
Alcohol gauze.
Method of experimentation
Patients were asked about their medical history, and
according to the presence or absence of diabetes, were
categorised as either healthy or diabetic. I f diabetic,
patients were asked about any medications taken and
their doses. Other essentials, like age, sex, etc. were also
noted. After getting the patient's consent, the finger
(from which the blood was to be drawn) was cleaned
with alcohol gauze. T h e area was then dried with sterile
gauze and a drop o f blood obtained which was placed
on the strip o f the meter, using Accu-Chek Active@,and
a record made o f the pre-operative glucose readmg in
the patient's record form.
Anaesthetic solution (1.8ml cartridge) with epine-
phrine 1:80,000, was injected either as an infiltration
or as a block. Sometimes two or more injections were
g v e n and this was recorded. Extraction was performed
and the teeth were removed atraumatically. T h e aver-
age extraction time and the maximum number o f teeth
extracted in each patient were recorded. T h e second
recording was done 10 minutes after the complete ex-
traction procedure was over. This was recorded as the
post-operative blood glucose readmg. The time taken for
the whole procedure was recorded using a timer.
The results were statistically analysed with paired
t-tests and Pearson correlation.

Table 2 Demographic details of diabetic patients

S.No Sex Medications No. of Teeth No. of L.A. Carpules Pre-op Glucose Post-op Glucose Difference
Extracted (1.8 ml each) (mg/dl) (mg/dl) (Post-Pre)
~ ~

1 45 F Insulin 1 1.5 353 284 -69

2 50 M Hypoglycemic 3 3 180 162 -1 8
3 58 M Diet Control 2 2 160 140 -20
4 52 F Hypoglycemic 3 2 211 201 -1 0
5 64 F Mixtard 1 1.5 142 147 5
6 56 M Diet Control 2 2 138 120 -1 8
7 51 M Diet Control 1 2 137 132 -5
8 40 M Daonil 1 1 209 21 3 4
9 50 F Diamacron* 1 2 252 331 79
10 52 F Hypoglycemic 7 3 170 159 -1 1
11 58 M Daonil* 1 0.75 196 250 54
12 52 M Glizide* 1 6 139 239 100
13 50 F Insulin 1 1 143 137 -6
14 35 M Daonil* 2 1.5 141 168 27
15 50 M Diet Control 2 2 290 264 -26
16 45 M Hypoglycemic* 1 1 102 251 149
17 50 F Insulin 1 1 243 222 -2 1
18 50 M Daonil 1 1 282 264 -1 8
19 48 M Hypoglycemic 1 2 164 147 -1 7
20 51 M Daonil 1 3 228 225 -3
21 51 M Daonil 1 1 29 1 281 -1 0
22 48 M Hypoglycemic 1 2 200 190 -1 0
23 48 M Hypoglycemic 1 2 257 209 -48
24 50 M Hypoglycemic* 1 1 180 220 40
25 54 M Hypoglycemic* 1 2 180 270 90
26 52 M Hypoglycemic 1 1 198 170 -28
27 33 M Daonil 1 2 21 0 193 -1 7
28 54 M Hypoglycemic* 2 2 150 164 14
29 47 M Diet Control 1 2 178 154 -24
30 51 F Hypoglycemic 1 2 189 167 -22

- * This is the patient's usual medication but was not taken on the day of extraction (uncontrolled diabetics)
- "Hypoglycemic" was written when patient did not know name of medication.
Tily and Thomas: Glycaemic effect of dental treatment in healthy and diabetic patients
80

Results Analysis o f glucose level changes in those diabetics

T h e results showed that injection o f epinephrine-con-
taining local anaesthesia showed no significant differ-
ence in glucose levels when healthy and dlabetic patients
were compared (p > 0.05, using the paired t-test) (Tabb
3A and B).
In the healthy patients, post-extraction baseline
increase in blood glucose levels was seen in 56.67%
o f cases, in 26.67% of the patients glucose levels fell,
whereas, in 16.67%, no significant change was seen. In
the case of diabetics, 66.7% showed a fall in glucose
levels and only 26.7% showed a rise. Therefore, 20 out
of the 30 diabetic patients acbally showed a glucose
level fall, while eight showed a rise and two showed no
difference.
who had not taken their pre-operative hypoglycaemic
medication showed that baseline glucose changes in this
group were very significant (p < 0.05) (Tabb 3A, and
Figzre 7). There was marked increase in blood glucose
levels in 100% of cases where the medication had not
been taken, whereas in those who took the medication,
a comparative fall in the glucose level was observed.
The correlation between the number o f anaesthetic
carpules injected and the blood glucose level change
post was found to be not significant a
limit of six carpules (p > 0.05) in both the healthy and
diabetic groups 'Orrelation was used).
groupswere tested The between the
number o f teeth extracted and the change in glucose

Table 3a P-Values (compatison of blood glucose level changes in healthy and diabetic patients)
Type Of Patient Healthy Diabetics Diabetics
(without medication)
Mean S.D. Mean S.D. Mean S.D.

Pre-op Glucose 99.3 15.86 197.1 57.09 167.5 45.32

Post-op Glucose 102.97 14.7 202.47 54.45 236.63 54.34
Difference 3.67 12.15 5.37 46.84 69.13 44.33
P-values (paired t-test) P > 0.05 P > 0.05 P < 0.05
Interpretation Not Significant Not Significant Very Significant

Table 3b Confidence Intervals (compatison of blood glucose level changes in healthy and diabetic patients)
Type Of Patient Healthy Diabetics Diabetics
(without medication)
Confidence interval (95%) Upper Lower Upper Lower Upper Lower
Pre-op Glucose 105.22 93.38 218.41 175.79 205.39 129.61
Post-op Glucose 108.45 97.48 222.8 182.14 282.06 191.19
Difference 8.20 -0.87 22.86 -12.12 106.19 32.057

HEALTHY DIABETICS DIABETICSWITHOUT

MEDICATION
Pre-op glucose
Patient type
Post-op glucose
Figure 7. Comparison of pre and post operative blood glucose means
International Dental Journal (2007) Vol. 57/No.2

levels was tested in both groups and was also found to
be "not significant'' (p > 0.05), i.e. the two variables are
independent of each other (Pearson correlation).
A final aspect that was compared was the change in
glucose levels in females and males (usingpaired t-tests).
Separate tests were conducted for both healthy and
diabetic patients and in both cases, the results showed
that there was no significant difference (p > 0.05) in the
blood glucose level change between the two genders
(Table 4).
Discussion
This study was done to discover the glycaemic effect
o f the administration o f epinephrine in dental local an-
aesthetic solution in both healthy and diabetic patients.
Little and Fallace' estimated that a dental practice serv-
ing an adult population of 2,000 people could expect to
encounter about 40-70 people with diabetes, about half
o f whom will be unaware of their condition.
In the present study, there were four such cases of
probable undiagnosed diabetes (the word 'probable' is
used because a confirmatory diagnosis can only made if
the hyperglycaemia is persistent; detected on more than
two occasions). However, in people without diabetes,
post meal sugars rarely go over 140mg/dL6. But occa-
sionally, after a large meal, a 1-2 hour post-meal glucose
level can reach 180mg/dL or higher. Thus, the patients
were made aware of a possible diagnosis of diabetes and
were asked to contact their physician immediately.
In diabetics, theoretically, an injection of adrenaline
should cause a significant increase in the blood glucose
level^^,^. But clinically, this did not happen, as in 66.7%
o f cases the blood sugar level actually decreased. The
following possibilities could be the reason for the hy-
p oglyc aemia:
These diabetic patients are 'stressed out' and so the
body muscles require an increasing source of energy
to compensate. Thus, during the extraction proce-
dure, when increasing stress makes the body utilise
the glucose present in the blood, the recovery from
this condition is delayed.
Another reason could be related to the half-life
o f the hypoglycaemic medications that were tak-
e n by the patient pre-operatively. For example,
Table 4 P-Values (compatison of blood glucose level changes in males & females (healthy and diabetic patients))
Type Of Patient Healthy
Males
Mean S.D.
Pre-op Glucose 100.19 15.96
Post-op Glucose 102.44 11.74
Difference 2.25 10.35
P-values (paired t-test) P > 0.05
Interpretation Not Significant
81
Daonil@(Hoechst AG, Germany) was a common
hypoglycaemic taken by many diabetics and has a
duration of action o f 12-16 hours9. Mixtard (Novo
Nordisk, A-S Denmark) insulin is an intermediate-
acting insulin and its effect lasts from 10-20 hours.
Even the effects of the short-acting insulin last from
4-9 hours9.
We separated the set o f diabetics who had not
taken their medication and analysed their data. T h e
result was a surprising revelation. All diabetic patients
who had not taken their medication showed a marked
increase in glucose levels post-operatively, the change
being significantly different (p<0.05). This made for an
interesting finding and it led us to believe that in cases
where the patients had taken the hypoglycaemic agents,
these drugs had been the factor which prevented the
glucose levels from rising. This means that even if the
glucose levels had increased due to the epinephrine, the
hypoglycaemic agents ensured that the glucose levels
came down again.
However, in cases where the patients had not taken
their hypoglycaemic medication, the blood glucose lev-
els increased significantly (p < 0.05) since there was no
hypoglycaemic agent to drown its effect. This shows that
the hypoglycaemic medication taken by the patients was
maslung the actual effect of the epinephrine in the local
anaesthetic solution on the blood glucose levels. This
transient rise in blood glucose levels is a cause of great
concern for us because of its clinical significance. Acute
changes in blood glucose concentration have major ef-
fects on gastrointestinal motor function in both normal
subjects and patients with diabetes mellituslO.Marked
hyperglycaemia affects motility in the oesophagus'',
s t o m a ~ h ' ~gallbladder14,
~'~, small intestine'', colon'', and
an~rectum'~.
Studies have shown that the amounts of epinephrine
contained in one to three cartridges of local anaesthetic
(0.018 to 0.054mg) may be enough to significantly in-
crease the risk of a complications like ketoacidosis
in patients with unstable diabetes, and so should be
avoided until their condition is brought under glycaemic
control". Well-controlled diabetics better tolerate vaso-
constrictors and have fewer episodes of hyperglycaemia
than poorly controlled diabetics.
Diabetic
Females Males Females
Mean S.D. Mean S.D. Mean S.D.
98.29 16.29 191.36 52.28 212.88 70.09
103.57 17.95 201 . I 8 49.70 206 69.65
5.29 14.16 9.818 48.87 -6.88 41.11
P > 0.05 P > 0.05 P > 0.05
Not Significant Not Significant Not Significant
Tily and Thomas: Glycaemic effect of dental treatment in healthy and diabetic patients
82
According to a recent research, acute short-term
hyperglycaemia affects all major components of innate
immunity and impairs the ability of the host to combat
infection, even though certain distinctive proinflam-
matory alterations of the immune response can be
observed under these condition^'^. Furthermore, a
reduction o f endothelial nitric oxide formation takes
place, thus decreasing microvascular reactivity to dilat-
ing agents such as bradyhnin, and complement function
is impaired, despite elevations o f certain complement
factor^'^^'^. Acute hyperglycaemia pricks up hyperin-
sulinemia (which increases the circulating cytokine
concentrations) and these effects are more pronounced
in sepsis with impaired glucose tolerance. This sug-
gests a potential modulation o f immunoinflammatory
responses in human sepsis by hyperglycaemia’’.
On the other hand, in the healthy patients, literature
again suggests that there will be a rise in blood glucose
levels, but this increase in glucose is slight compared to
the increase in d i a b e t i ~ s ~ ~ ~Clinically
~ ” ~ ’ ~ . too, this effect
was mostly seen (in 56.67% o f cases), although not in
all patients. In some, it caused a slight decrease in blood
glucose levels (26.67 Yo) and in others (16.67%), there
was no significant difference between the pre- and post-
operative readings.
T h e question here would be whether the rise in
glucose levels is being caused by the exogenous ad-
ministration of epinephrine in the local anaesthetic
that is injected or is it because of a rise in the body’s
endogenous secretion o f adrenaline due to stress, and
whether the amount of epinephrine in the dental local
anaesthetic solution is enough to cause a systemic rise
in blood glucose levels.
A study done by Meechan et a1’ in 1991 on the
effects o f adrenaline-containing and adrenaline-free
dental local anaesthetic solutions on blood glucose
concentration in a group which was not undergoing any
stress compared with a group which was undergoing
third molar surgery (supposedly stressed) showed that
the results observed in both were similar: a significant
increase in blood glucose levels. Thus, although endog-
enous adrenaline would inevitably be released due to
stress (and may be playing a role in increasing the blood
glucose levels), the effect of the exogenous epinephrine
is undoubtedly, very Significant’.
Using improved methods for measuring catecho-
lamines, a number of investigators have shown that
epinephrine injected during dental local anaesthesia mark-
edly elevates the resting plasma concentration of the hor-
m~ne’~,’~. This in turn causes a rise in blood glucose levels.
A meta-analysis of several studies using similar designs
revealed that the mean resting venous plasma concentra-
tion of epinephrine is approximately doubled by the in-
traoral injection of a single cartridge of 2% lidocaine with
1:100,000 epinephrine, i.e. 18pg epinephrine26,27. Use of
radlolabelled epinephrine demonstrated that the injected
drug is the source of the increased epinephrine”.
International Dental Journal (2007) Vol. 57/No.2
The amount o f adrenaline injected during dental
local anaesthesia (exogenous administration) has been
known to directly raise circulating glucose levels and
reduce plasma potassium concentration. Blood glucose
concentration increases significantly following buccal
infiltrations of clinical doses o f adrenaline-containing
dental local anesthetics’.
The glucometer was the means of measurement o f
the blood glucose levels in this study. When accurately
performed, bedside glucose monitoring (BGM) is a
prompt, reliable, and cost-effective method o f man-
agmg patients who require a high degree of glucose
control. In one study on the use of glucometers it was
found that despite multiple technical errors when us-
ing self-monitoring o f blood glucose (SMBG), most
patients obtained clinically useful values. The results
showed that most of the values were clinically accept-
able3’. Many other studies validate the accuracy of the
gl~cometer~’-~~.
Conc Ius ion
It could be concluded that dental local anaesthetic
solution containing adrenaline may safely be used in
diabetic patients who have taken their hypoglycaemic
medications pre-operatively. On the other hand, it is
unsafe to use the anaesthetic solution in those patients
who have, for some reason or another, not taken their
medication.
Acknowledgement
The authors would like to record particular thanks to the
two referees o f this paper who provided such helpful
assistance in its preparation. Prof. Ahmed S. El-Aloosy,
Biostatistician, Ajman, UAE and Dr. Mahir Jallo, Asst.
Professor of Internal Medlcine-Diabetes & Endocrinol-
ogy, Gulf Medical College Hospital & Research Center,
Ajman, UAE.
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Correspondence to: Dr. Sam Thomas, Assistant Professor, Depart-
ment of Surgical Sciences, Faculty of Dentistry, Ajman University
of Science & Technology, P.0.Box: 50335, Dubai, U.A.E. Email:
drsamthomas@rediffmail.com