Keywords blood pressure - catecholamine - epinephrine - hemostasis - pituitary - vasoconstriction
Introduction
Endoscopic transsphenoidal pituitary surgery (ETSS) is the standardized and commonly
performed surgical technique for the treatment of pituitary tumors.[1 ] The nasal mucosa, especially of the inferior turbinates, being extremely vascular
is prone to oozing, which can considerably impair the view of the surgical field leading
to prolonged operative times, incomplete surgical interventions, difficulty in identifying
landmarks, and injury of important anatomical structures.[2 ]
[3 ] Various strategies to reduce bleeding during ETSS include head elevation, hypotensive
anesthesia, total intravenous (IV) anesthetics, injecting or topical usage of vasoconstrictive
drugs such as cocaine, oxymetazoline, and adrenaline.[4 ] Adrenaline functions as a capillary vasoconstrictor, and being inexpensive and easily
available it is commonly used intranasally (either as submucosal injection or topical
mucosal application) during ETSS.[5 ] Systemic absorption of adrenaline can cause hypertension and tachycardia secondary
to raised cardiac output (CO). The elevated CO can be counterproductive as it can
increase surgical site bleeding thereby obscuring the field. There is lack of consensus
on the exact dosage of adrenaline that should be used in ETSS and diverse concentrations
ranging from 1:200,000 to 1:1000 topically and 1:200,000 to 1:50,000 for infiltration
have been used.[6 ] Various techniques have been developed to determine the CO using the arterial wave
form. Among them, the FloTrac system (Edwards VigileoTM system; Edwards Lifesciences,
Irvine, California, United States) uses the FloTracTM sensor connected to arterial
pressure tubing, does not require calibration, and provides continuous CO measurements
from the arterial pressure wave[7 ] ([Fig. 1 ]). Additionally, cardiac index (CI), stroke volume (SV), stroke volume variation
(SVV), and stroke volume index (SVI) are some of the other values that can also be
derived by the analysis of arterial wave forms.
Fig. 1 FloTrac device.
In our institute, traditionally 1:100,000 dilution of adrenaline was used topically
for vasoconstriction in ETSS. We hypothesized that lowering the concentration of adrenaline
to 1:200,000 will provide lesser increase of CO and better preservation of hemodynamic
parameters measured sensitively using a FloTrac device without compromising hemostasis
and quality of the surgical field.
We, therefore, designed and undertook this randomized prospective comparative study
to compare two different concentrations—1 mg/mL saline (1:100,000) and 0.5 mg/mL in
100 mL saline (1:200,000) of nasal adrenaline instillation on the hemodynamic profiles
and CIs obtained from FloTrac device during ETSS for pituitary adenomas under general
anesthesia as the primary objective. Secondary objectives were to compare the quality
of surgical field, blood loss, and adverse effects encountered.
Materials and Methods
Following approval from the Institute Ethics Committee (2020-14-MD-114 dated 17 February
2020) and subsequent to registering the trial with the Clinical Trial Registry of
India (CTRI/2020/03/024374 [Registered on: 31/03/2020]), and obtaining written and
informed consent from eligible patients, 62 eligible patients who were undergoing
ETSS for pituitary adenoma under general anesthesia were enrolled in this prospective
randomized patients and data analysis blinded, parallel group study using consecutive
sampling ([Fig. 2 ]). The study was conducted between 20/07/2020 and 14/07/2021 in the neurosurgery
operation theaters of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow,
India. Enrolled patients were given the option to withdraw themselves from the study
at any moment without stating any reason. Patients (18–65 years) of either gender
belonging to American Society of Anesthesiologists physical status I or II and who
were undergoing transsphenoidal surgery for pituitary adenomas were eligible for inclusion.
Patients who were unable (legally incompetent) or unwilling to give consent, patients
with decreased level of consciousness, raised intracranial tension, recurrent pituitary
tumor, and pituitary apoplexy; patients with any cardiac pathology, severe hypertension,
or previous nasal surgery; patients with history of allergy to any of the study drugs;
and patients of body weight less than 40 kg were excluded from the study.
Fig. 2 Consolidated Standards of Reporting Trials (CONSORT) statement.
Sample size was calculated based on a pilot study conducted on five patients in each
group where COs were compared. CO in group 1 (0.5 mg) and group 2 (1 mg) obtained
were 4.05 ± 0.15 and 4.16 ± 0.13, respectively (effect size between means = 0.784).
At minimum two-sided 95% confidence interval and 80% power of the study, minimum required
sample size in group 1 and group 2 came out to be 27. Finally in this study, we included
30 patients in each group to account for study errors or attrition. Sample size was
estimated using software G Power version—3.1.9.2 (Düsseldorf University, Germany).
Based on a computer-generated sequence of randomization (obtained from http://www.randomization.com ), a 1:1 group allocation was done and was kept concealed in opaque sealed envelopes.
All the eligible participants were briefed about the study protocol, its potential
harm, and benefits. Only the willing patients were recruited after obtaining written
and informed consent in English or Hindi 1 day prior to surgery stating their willingness
to be included in the study. They were informed categorically that they can withdraw
themselves from the study at any time without stating any reason. The research participants
were treated with highest ethical standards as per the Declaration of Helsinki.
On the night before surgery, during their preanesthetic check-up, the eligible patients
were apprised of their inclusion in the trial and explained in detail the manner of
conducting the study. Their detailed history, examination, and routine preoperative
investigations were again reviewed.
All patients were premedicated with tablet alprazolam 0.04 mg/kg and tablet ranitidine
150 mg the night before and 2 hours before surgery. On the day of surgery, upon arrival
to the operation theater, IV access was achieved with 16 or 18 G IV cannula under
local anesthesia with 2% lignocaine. Five-lead-electrocardiogram, noninvasive blood
pressure (NIBP), and pulse oximetry were attached. Under local anesthetic infiltration,
a 22G arterial cannula was placed in the radial artery of the nondominant hand and
the FloTrac Vigileo monitor system (Edwards Lifesciences, Irvine, California, United
States) was connected to the cannula and baseline data (age, weight, and height) were
entered to calibrate the machine. Baseline values of CO, CI, SVV, SV and IBP were
recorded.
Following preoxygenation with 100% oxygen for 3 to 5 minutes, induction of anesthesia
was performed with titrated doses of midazolam (0.05–0.15 mg/kg IV), fentanyl (1–2 μg/kg
IV), and 2% propofol (20 mg/mL) (1–2.5 mg/kg IV). Following administration of IV vecuronium
(0.08–0.1 mg/kg IV), the patients' trachea was intubated with appropriate-sized polyvinyl
chloride cuffed endotracheal tube. Additional monitoring comprising of capnography
(ETCO2), nasopharyngeal temperature, bispectral index (BIS), train of four (TOF),
and Foley's catheter for urine output were attached. Anesthesia was maintained using
oxygen, air (50% each), and sevoflurane 0.6 to 2.4% (inspired) started immediately
after induction. Muscle relaxation was maintained by vecuronium infusion at 0.0008
to 0.001 mg/kg. Posterior pharyngeal packing was done with moist cotton gauze to avoid
entry of the surgical bleeding to trickle into the esophagus.
Based on random number tables generated through computer program, sequentially numbered
sealed envelopes containing the randomization codes were prepared beforehand for allotment
of patients in two different groups. These sealed envelopes were now opened by the
scrub nurse (not involved in the outcome assessment) before laying the surgical trolley
and based on the codes either of the two different concentrations of adrenaline solution
for instillation in the two groups were prepared and laid on the trolley for nasal
instillation using cotton strips.
Group 1: adrenaline (0.5 mg/mL) diluted in 100 mL normal saline (1:200,000)
Group 2: adrenaline (1 mg/mL) diluted in 100 mL normal saline (1:100,000)
The concentrations were not divulged to the anesthesiologist and the surgeon. Cotton
strips were now dipped in the solution to absorb it fully and then the excess solution
was carefully squeezed until the cotton strip was saturated but not dripping even
upon compression. Removal of the excess solution was done over the solution to avoid
waste. After sterile painting and draping, cotton strips were then inserted in the
nasal fossae (one each side), using nasal speculum and this procedure of nasal mucosal
preparation continued for 10 to 15 minutes. Thereby, patients in group 1 received
1:200,000 adrenaline solution, whereas those in group 2 received 1:100,000 adrenaline
solution in the nasal cavity by the operating surgeon. Patients were now placed in
supine with slight head raised and tilted position. After approximately 10 to 15 minutes
of repeated packing and removal of cotton strips soaked in adrenaline solution, which
allowed for the drug to be absorbed, surgery commenced. Hemodynamic parameters and
CIs were continuously recorded every 5 minutes for the first 1 hour and thereafter
at every 10 minutes interval till the end of surgery by the single anesthesiologist
who conducted all the cases and was blinded to the group allocation. All the patients
were monitored using BIS that was targeted to be maintained between 40 and 60 throughout
the operative procedure. TOF was kept less than 2 throughout the surgery. Normocapnia
was maintained (35–40 mm Hg) by adjustment of ventilatory parameters and normothermia
(35.5–36.5°C) was maintained with warming blankets, covering the exposed parts of
the body and warm saline infusions. Intraoperative fluid administration was guided
by the hourly maintenance requirements and losses and was done with 0.9% normal saline.
The hemodynamic parameters were targeted to be maintained within 20% of the baseline
values and the intraoperative management was done at the discretion of the attending
anesthesiologist. In case of persistent mean arterial pressure (MAP) more than 25%
of the preinduction baseline values and/or heart rate more than 90 bpm suggestive
of inadequate analgesia, initially 0.5 μg/kg of fentanyl was administered. This was
followed by injection metoprolol in intermittent dose of 1 mg/dose. If blood pressure
could not be controlled with metoprolol injection, injection labetalol 5 to 10 mg
bolus every 5 minute (maximum 200 mg) was administered. Lastly esmolol was considered
with a loading dose of 500 µg/kg over 1 minute and maintenance dose of 50 to 100 µg/kg/minute
over 4 minutes was used for controlling the blood pressure. In case of hypotension
(MAP < 25%) of baseline, correction was first attempted with fluid bolus (100 mL)
and if unresponsive, then with injection mephentermine 6 mg bolus. Treatment of bradycardia
(heart rate <40/min) with atropine (0.6 mg IV) and of arrythmias as per Advanced Cardiac
Life Support (ACLS) protocol was also planned. Usage of rescue drugs was also recorded
At the completion of surgery, the blood content in the suction canister and the blood
soaked in the gauze strips were measured. The volume of blood in the suction canister
was calculated by subtracting the irrigation saline used during the procedure and
the volume of blood soaked in cotton strips was calculated by counting the strips
that were partially or completely soaked with blood.
The single operating surgeon, who was blinded to the patient group allocation, evaluated
the surgical field quality using the Boezaart scale[8 ] and graded it. It included five grades with grade 0 being no bleeding, grade 1 stated
slight bleeding where no suction was required, grade 2 included slight bleeding and
occasional suction was required, grade 3 also included slight bleeding but frequent
suctioning was required, grade 4 defined moderate bleeding where frequent suctioning
was needed, and surgical field was threatened and grade 5 includes severe bleeding
that required constant suctioning and surgical field was threatened to such an extent
where surgery could not be possible due to flooding of surgical field view.
At the end of surgery, sevoflurane was discontinued and muscle relaxation was reversed
on obtaining a TOF count of 3. Oral throat pack was removed. All the patients were
extubated inside the operation theater when the extubation criteria were met. The
patients were then transferred to the post-anesthesia care unit for further care and
monitoring from where they were shifted out once the transfer criteria were fulfilled
(Aldrete score ≥9).
Results
In this study, a total of 62 patients were enrolled, of which 60 patients were analyzed.
Analysis of baseline characteristics (age, weight, height, body mass index, duration
of anesthesia and surgery, and blood loss) revealed no significant difference between
the study groups for the patients (p < 0.05; [Table 1 ]). Comparison of the CIs revealed that there was no difference in COs and CI of the
patients between two study groups during baseline to 55 minutes and at 80 minutes
and onward whereas difference was statistically significant at the time points of
60 minutes and 70 minutes (p < 0.05; [Fig. 3A ] and [B ]). Among other indices, SV and SVVs also did not vary among the groups throughout
the study period. Hemodynamic parameters (heart rate, systolic blood pressure, diastolic
blood pressure, MAPs, and ETCO2 readings) were similar among the two groups ([Table 2 ]). However, the values of ETCO2 varied at 60 and 70 minutes (p < 0.05; [Table 2 ]; [Fig. 4 ]). The quality of the field of surgery and assessment of blood loss was performed
using a standardized validated scale. Both the groups were comparable in terms of
the quality of the surgical fields (p = 0.549). Usage of rescue drugs for treating hemodynamic perturbations was also compared
and it was found to be similar in both the groups ([Table 3 ]).
Table 1
Baseline characteristics, duration, and blood loss in study patients (n = 60)
Variables
Concentration (mg/mL)
p -Value
Group 1
(0.5 mg/mL [n = 30])
Group 2
(1 mg/mL (n = 30)]
Mean
SD
Median
Mean
SD
Median
Age (years)
39.83
15.35
37.5
39.2
12.43
38
0.861
Weight (kg)
68.33
12.42
68
69.11
14.48
66.9
0.929
Height (cm)
161.24
8.19
162
161.03
8.45
163
0.767
BMI (kg/m2 )
26.26
4.31
25.59
26.68
5.31
26.86
0.626
Duration of anesthesia (minutes)
252.6
80.09
240
231.6
58.6
232.5
0.369
Duration of surgery (minutes)
178.17
62.58
170
168.03
53.14
157.5
0.806
Total blood loss (mL)
448.17
258.97
465
416.63
301.14
350
0.077
Abbreviations: BMI, body mass index; SD, standard deviation.
Independent samples t -test / Mann–Whitney U test used. p < 0.05 significant.
Fig. 3 (A ) Distribution of cardiac output (CO) of the study groups. (B ) Distribution of cardiac index (CI) of the study groups.
Table 2
Hemodynamic parameters during the perioperative course between the two groups
Sl.no.
SBP (mm Hg)
DBP (mm Hg)
MAP (mm Hg)
ETCO2 (mm Hg)
Group 1
Group 2
p
Group 1
Group 2
p
Group 1
Group 2
p
Group 1
Group 2
p -Value
BL
119.03 ± 19.68
116.83 ± 15.15
0.906
67.97
± 11.71
67.77
± 11.62
0.988
83.73
± 12.33
84.53
± 13.51
0.773
33.1
± 3.2
32.95 ± 2.51
0.871
0
119.43 ± 19.48
122.67 ± 24.49
0.877
67.53 ± 11.18
71.87 ± 17.83
0.520
84.9 ± 13.33
88.6 ± 19.47
0.673
32.87 ± 2.5
32.23 ± 3.04
0.33
5
120.87
± 18.74
123.73
± 22.29
0.574
68.87 ± 12.70
73.47 ± 16.33
0.290
86.03 ± 13.61
90.07 ± 17.82
0.482
32.97 ± 2.43
32.7 ± 2.53
0.725
10
131.67
± 64.16
120.2
± 20.35
0.796
69.97 ± 13.26
69.77 ± 14
0.734
86.3 ± 16.35
85.5 ± 22.33
0.982
32.83 ± 2.39
32.6 ± 2.19
0.638
15
118.67
± 25.83
114.8
± 20.84
0.668
67.9 ± 15.73
66.03 ± 15.45
0.544
84.9 ± 19.75
83.03 ± 18.09
0.636
32.5 ± 2.13
32.33 ± 2.12
0.782
20
115.77 ± 17.44
115.83 ± 19
0.923
67.3 ± 12.86
68.03 ± 14.98
0.773
84.13 ± 13.14
83.4 ± 16.19
0.75
32.23 ± 2.11
32.4 ± 2.13
0.952
25
112.47 ± 15.51
112.43 ± 19.27
0.819
64.57 ± 11.21
65.17 ± 12.36
0.807
80.67 ± 12.27
80.27v14.55
0.668
32.37 ± 2.14
32.33 ± 2.14
0.905
30
109.23 ± 17.21
110.97 ± 15.16
0.446
61.47 ± 10.97
64.37 ± 10.46
0.248
77.17 ± 12.38
79.93 ± 11.55
0.219
32.03 ± 2.17
32.27 ± 2.38
0.599
35
110.5 ± 18.33
110.93 ± 17.82
0.75
63.33 ± 10.96
64.8 ± 12.48
0.871
79.4 ± 13.14
77.07 ± 18.26
0.584
32.07 ± 1.89
32.37 ± 2.2
0.627
40
106.93 ± 13.96
108.03 ± 15.43
0.615
60.97 ± 8.9
63.87 ± 11.34
0.287
76.2 ± 10.03
78.17 ± 12.83
0.7
32 ± 2.13
32.3 ± 2.35
0.457
45
107.5 ± 14.58
106.33 ± 14.54
0.871
61.4 ± 7.95
63.03 ± 10.18
0.750
77 ± 10.13
77.27 ± 11.53
0.882
31.9 ± 2.19
32.2 ± 2.46
0.417
50
109.73 ± 21.89
105.47 ± 13.18
0.888
62.63 ± 11.17
61.73 ± 9.85
0.796
78.4 ± 14.33
76.6 ± 10.29
0.888
32.1 ± 2.09
32 ± 2.6
0.94
55
107 ± 13.46
105.17 ± 13.7
0.574
61.9 ± 9.96
62.77 ± 12.11
0.982
77.27 ± 10.55
77.47 ± 13
0.813
32.07 ± 2.26
32.17 ± 2.82
0.794
60
104.77 ± 11.36
103.53 ± 13.68
0.491
60.6 ± 8.64
60.67 ± 9.25
0.976
75.67 ± 8.26
75.03 ± 10.6
0.62
32.53 ± 1.67
33.66 ± 1.39
0.006[a ]
70
104. 9 ± 13.49
102.33 ± 13.57
0.433
60.6 ± 8.57
60.67 ± 9.8
0.929
72.49 ± 15.66
74.3 ± 10.27
0.801
32.84 ± 1.88
33.95 ± 1.04
0.011[a ]
80
105.27 ± 25.53
100.55 ± 14.54
0.143
62.6 ± 11.07
57.93 ± 11.19
0.2
78 ± 12.93
72.34 ± 10.82
0.111
32.33 ± 2.45
32 ± 2.54
0.697
90
102.3 ± 14.09
102.62 ± 14.3
0.611
58.8 ± 8.47
60.93 ± 11.04
0.58
73.43 ± 9.57
73.45 ± 9.68
0.909
32.27 ± 2.59
32.24 ± 2.65
0.897
100
102.5 ± 13.07
100.25 ± 21.59
0.981
59.9 ± 11.76
60.71 ± 9.47
0.396
72.77 ± 10.36
74.79 ± 10.01
0.548
32.3 ± 2.72
32.21 ± 2.41
0.863
110
99.52 ± 10.69
103 ± 12.02
0.379
57.9 ± 9.05
61.11 ± 11.84
0.388
72.03 ± 9.23
74.64 ± 10.73
0.314
32.14 ± 2.55
32.14 ± 2.34
0.891
120
105.69 ± 12.6
102.89 ± 17.76
0.302
59.19 ± 10.47
59.59 ± 11.96
0.957
74.5 ± 10.66
74.48 ± 14.13
0.922
32.62 ± 2.84
32.41 ± 2
0.577
130
101.04 ± 21.31
101.88 ± 28.34
0.114
58.28 ± 4.87
59.46 ± 15.69
0.298
72.16 ± 5.9
73.75 ± 20.38
0.164
32.56 ± 2.57
32.37 ± 2.22
0.664
140
103.63 ± 14
102.65 ± 13.99
0.835
60.68 ± 8.2
60.35 ± 12.98
0.588
75.6 ± 8.36
73.35 ± 11.24
0.265
32.05 ± 2.59
32.57 ± 2.36
0.584
150
109.61 ± 16.81
101.41 ± 11.78
0.245
60.83 ± 8.65
62.24 ± 14.07
0.732
74.22 ± 7.56
72.88 ± 9.22
0.443
32.44 ± 2.91
31.88 ± 1.76
0.395
160
103.21 ± 17.52
103.33 ± 12.2
0.880
62.67 ± 12.36
61.87 ± 12.7
0.967
74.2 ± 15.34
72.8 ± 8.76
0.902
32.4 ± 3.04
32.4 ± 1.92
0.95
170
103.77 ± 12.77
113 ± 16.11
0.110
59.69 ± 7.85
67.5 ± 12.06
0.11
74.15 ± 8.31
79.17 ± 13.13
0.376
30.36 ± 8.64
33.17 ± 1.47
0.362
180
96.73 ± 15.55
112.2 ± 17.41
0.061
58.09 ± 9.89
64.6 ± 13.16
0.349
72 ± 11.16
80.6 ± 14.1
0.223
31.82 ± 3.28
32.5 ± 1.18
0.773
190
97.64 ± 9.17
108 ± 10.77
0.069
58.3 ± 6.46
61.86 ± 8.13
0.23
71.4 ± 6.11
79 ± 7.66
0.043
32.1 ± 3
33.29 ± 1.6
0.489
Abbreviations: BL, baseline; DBP, diastolic blood pressure; ETCO2, end-tidal carbon
dioxide; MAP, mean arterial pressure; SBP, systolic blood pressure.
a Denotes statistical significance.
Fig. 4 Graphical presentation of hemodynamic parameters in both the groups. DBP, diastolic
blood pressure; ETCO2, end-tidal carbon dioxide; MAP, mean arterial pressure; SBP,
systolic blood pressure.
Table 3
Distribution of use of rescue drugs in the study group
Rescue drugs
Group 1 (n = 30)
Group 2 (n = 30)
p -Value
Metoprolol
10 (33.33%)
16 (53.33%)
0.121
Labetalol
15 (50%)
9 (30%)
0.117
Propofol
11 (36.67%)
10 (33.33%)
0.788
Mephentermine
8 (26.67%)
9 (30%)
0.777
Esmolol
1 (3.33%)
4 (13.33%)
0.165
None
7 (23.33%)
6 (20%)
0.756
Note: Chi-squared test/Fisher's exact test used. p < 0.05 significant.
Discussion
Pituitary tumors are relatively common tumors with their frequencies depending on
age (40–60 years) and sex (female preponderance).[9 ] Options for the treatment of pituitary adenomas include transsphenoidal surgical
resection, irradiation, and medical therapy[10 ] Surgery is usually considered as the first-line treatment for large nonfunctioning
adenomas with compression of the optic apparatus and majority of functioning tumors.[11 ] The transsphenoidal approach to the pituitary gland is frequently used because it
is less invasive, provides direct access, and is faster.[12 ] Hemostasis is essential for the endoscopic visualization of anatomic structures
and the avoidance of catastrophic injuries. Bleeding here is primarily capillary in
origin and responds to local vasoconstrictors.[8 ]
In our study, adrenaline was topically administered in the nasal cavity for decongestion
and invasive monitoring was performed to obtain accurate and precise hemodynamic data
by measuring the maximum absolute change from baseline using a FloTrac device and
Vigileo monitor. When CIs were compared in both the study groups, we found that baseline
readings of the CO were higher in the group 2 patients (1:100,000) concentration in
comparison to group 1 (1:200,000) patients. At the time of start of nasal packing
with the cotton wicks soaked with different adrenaline concentrations, it was found
that there was increase in mean values of CO in group 1 patients compared with group
2 but again 5 minutes after the endonasal packing, values of CO were found to be increased
in group 2 (1:100,000) patients and remained consistently high throughout the dissection
phase of the procedure. The values were found to be significant at 60 and 70 minutes
of the surgery ([Fig. 2A ]). The CO trends dropped in group 2 patients (1:100,000) after the tumor was removed
but again rose at the end of the surgery in comparison to group 1 patients (1:200,000).
Similarly, Panda et al compared the COs using FloTrac monitor in functional endoscopic
sinus surgery in 30 patients using two different concentrations of adrenaline (1 mg
of adrenaline diluted in 20 mL normal saline in group 1 and 4 mg adrenaline diluted
in 20 mL normal saline in group 2).[13 ] The numerical values of mean CO were found to be higher in group 2 patients compared
with group 1 patients. They concluded that there was no significant difference in
values of CO obtained (4.06 ± 0.161 vs. 4.145 ± 0.131).
CI was compared and no difference was observed in the patients between two study groups
during baseline to 55 minutes and at 80 minutes and onward (each p > 0.05), whereas difference was statistically significant at the time points of 60 minutes
and 70 minutes of the surgery in 1:100,000 concentration group (each p < 0.05) reflecting the similar trends of COs ([Fig. 2B ]).
In our study, we considered a systolic blood pressure greater than 20% of the baseline
as a hypertensive response. Upon analyzing this parameter in isolation, we found a
smaller proportion of patients in group 1 than in group 2 who exhibited an increase
in systolic blood pressure of more than 20% from baseline (hypertensive response)
following nasal mucosal instillation of adrenaline. This number could not reach statistical
significance probably due to the small sample size. This suggests that the dose needed
to reduce hypertensive responses could be considerably lower than either dose used
by us in our study. Similar study conducted by Panda et al in 2012 observed consistently
higher blood pressure in patients receiving high concentrations of adrenaline and
also there was significant increase in the requirement of rescue drug used to treat
hypertension in 4 mg adrenaline concentration group.[13 ] Bhatia et al found rise in blood group more than 20% of baseline in patients group
receiving infiltration of 1:200,000 adrenaline with 2% lignocaine as compared with
1:400,000 concentration group.[14 ]
ETCO2 also showed a significant difference during the peak time of dissection phase
at 60 and 70 minutes suggesting the proportional relationship between ETCO2 and CO
([Fig. 4 ]). Additionally, adrenaline due to its effect on glycogen, fatty acid storage, activation
of the adenylate cyclase (or cyclic adenosine monophosphate) cascade, results in glycogen
and triacyl glyceride mobilization as well as a general increase in metabolic rate
which causes an increase in carbon dioxide generation and consequently rise in ETCO2.[15 ] Likewise, Bhatia et al in their study had also reported a significant rise of ETCO2
from baseline values post-infiltration in both their groups.[14 ]
In our study, it was observed that the Boezaart grading of the quality of the surgical
field and volume of blood loss estimated in the groups were similar (448.17 vs. 416.63 mL;
[Table 1 ]). Panda et al observed 168 mL of blood loss in higher concentrations of adrenaline
group in comparison to 426 mL in group receiving lower dose of adrenaline topically.[13 ] Lee et al in their study reported a mean blood loss of 333.9 mL in patients receiving
1:100,000 of epinephrine.[16 ] Cohen-Kerem et al assessed a mean blood loss of 203.5 mL when adrenaline (1:1000000)
was infiltrated along with 1% lignocaine.[17 ]
Regarding the rescue drugs used to treat hemodynamic events that occurred during the
procedure, they were found to be similar ([Table 3 ]). In contrast, Panda et al[13 ] in their study had observed a significance increase in the requirement of rescue
drugs to treat hypertension in patients receiving higher concentration of adrenaline.
The mean infusion rate of nitroglycerine in group 2 (4 mg) was higher in comparison
with that in group 1 (1 mg). There were few patients in the higher concentration of
adrenaline who also required additional boluses of injection metoprolol.
Our study had certain limitations that deserved to be mentioned. First, we did not
assess the catecholamine plasma concentrations, particularly of adrenaline and noradrenaline
that would have provided us with a better estimate. Second, we had used a validated
grading scale provided by Boezaart et al to assess intraoperative surgical field quality
which the operating surgeon was comfortable with. This method has been criticized
for compressing grading scores and failing to distinguish modest bleeding variances.
The strengths of the study, on the other hand, were that it was an adequately powered
study with sizeable number of participants. Second, a single surgeon performed all
the surgeries to avoid any subjective bias. Third, invasive monitoring was used rather
than noninvasive hemodynamic monitoring to provide precise information.
Conclusion
The use of topical adrenaline in ETSS appears to be a safe and successful way to achieve
hemostasis, hence increasing the surgical visibility, and minimizing blood loss. The
key to obtain cardio-stable hemodynamic parameters is to use a lowered concentration
(1:200,000 solution) compared with the institutional standard concentration (1:100,000)
that provides an optimal balance between the hemodynamic variables and a clear surgical
field.
