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12, produces segmental block to the an estimation of anesthetic effect and could
sympathetic supply of the upper abdominal indicate adequate depth of anesthesia during
dermatomes without affecting lower surgery(10). The purpose of this study was to
abdomen or lower limbs sympathetic compare the effects of low thoracic epidural
supply(6). anesthesia (T10-12) with either bupivacaine
Combined Epidural-General Anesthesia 0.125% or 0.25% on hemodynamic variables,
(CEGA) technique has widely been used in sevoflurane requirements, and stress hormone
major abdominal surgery for decades(4). responses (epinephrine, cortisol) during
Clinical experience has shown that there pancreatic surgery under combined epidural-
are less general anesthetic requirements general anesthesia (CEGA). Sevoflurane
when the two techniques are provided anesthesia was monitored with bispectral
simultaneously. Epidural anaesthesia blocks index score (BIS) to keep the score between
the nociceptive input originating from the 40-60.
surgical site to some degree. Postoperative
pain state results from afferent C-fiber input MATERIALS AND METHODS
generated by the tissue injury, and the
central facilitation from the continuing Forty patients of both sexes scheduled
stimulus(6). Neuraxial anesthesia can alter for pancreatic surgery were included after
both processes by reducing the preterminal the study protocol was approved by the
release of neurotransmitters and local Ethical Review Board committee. All
hyperpolarizing the postterminal second- patients gave written informed consent.
order neurons(7). In addition, neuraxial Patients were selected to justify ASA
anesthesia has a supraspinal general physical status I, II, or III. Patients who had
anesthesia effect that suppresses the level a history of major back problems,
of consciousness(8). It is possible to perform coagulation abnormality, neurological
upper abdominal procedures under thoracic disease and advanced cardiopulmonary
epidural anesthesia alone, but the height of disabilities were excluded. Patients were
block required, with the position of the assigned to one of the two treatment groups
surgical retractors and manipulation near by using a table of random numbers.
the diaphragm, make it difficult to avoid Premedication consisted of 2.0 mg
significant patient discomfort and risk(6). lorazepam orally in the evening before
Epidural anesthesia should be combined surgery and 2 h before the induction of
with general anesthesia for intrathoracic anesthesia. Upon arrival to the holding
surgery and upper abdominal procedures area, standard monitors were connected to
near the diaphragm (7). Inhalational agents the patients (ECG, NIBP, SO2), and a 16-
provide amnesia and allow endotracheal gauge IV cannula was placed and the left
intubation in patients undergoing the radial artery were catheterized with a 20-
combined anesthetic technique. Minimal gauge catheter under local anesthesia.
expired concentrations of the volatile Patients were placed in the sitting position,
anesthetics (0.25-0.5 % isoflurane) are and an epidural catheter was inserted in the
required(8). Epidural analgesia allows earlier T10-11 or T11-12 interspace using the loss
mobilization, reduces the risk of deep of resistance technique. Instead of the
venous thrombosis, and allows better conventional method of a test dose with
cooperation with chest physiotherapy, lidocaine and adrenaline to confirm the
preventing chest infections and reduces catheter placement, we used a catheter
over-all postoperative morbidity(9). advancement technique (CAT)(11). With this
The ratio of the two techniques technique, after eliciting lack of resistance,
(epidural/general anesthesia) has been the ability to advance 20 cm of a soft
arbitrarily determined: varying concentrations epidural catheter without a stylet and with
of local anesthetic are used, and general minimal resistance was taken as a
anesthesia is administered empirically or successful indicator for catheter placement.
based on cardiovascular responses during The catheter was then withdrawn to the 15-
surgery without knowing the depth of cm mark, and gravity drainage of
anesthesia and the impact of epidural. The cerebrospinal fluid or blood was tested.
bispectral index score (BIS) was introduced as
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After the epidural catheter was fixed to the estimated at the end of the procedure. At
back, the patients were placed supine and the end of surgery, residual neuromuscular
received 10 ml bupivacaine of either block was reversed with neostigmine 50
0.125% (group I) or 0.25% (group II), g/kg and atropine 20 g/kg, and the
combined with fentanyl 2.0 g/ml and 2.0 patients were extubated if the procedure
mg morphine in a double-blinded manner. was of less than 6 hr, otherwise patient was
The bolus bupivacaine was given in kept ventilated overnight and then
increments of 3 mls/3 min aiming to block extubated. Upon arrival to the SICU an
the somatosensory level T5- T9. A 6.0 ml/hr epidural infusion of bupivacaine 0.0625% in
infusion of either 0.125% or 0.25% a dose of 6.0-8.0 ml/h was immediately
bupivacaine with fentanyl 2.0 g/ml was started and titrated according to the Visual
started and continued throughout the Analog Scale (VAS) measurements.
surgical procedure. Somatosensory Patients were told about VAS for pain
blockade was evaluated by touching the assessment during the preoperative visit.
skin with ice and performing the pinprick We used a vertical 100-mm VAS with ends
test. Induction of general anesthesia was marked as 0 (no pain) and 100 (worst
started after 30 min, during this period all imaginable pain), and patients were
the parameters of epidural anesthesia were assessed at 0, 2, 6, 12 and 24 hr after
recorded. operation and asked about their
Monitoring included invasive arterial blood justifications regarding pain control
pressure (BP), heart rate (HR), pulse oximetry, Systolic BP (SBP), HR, and BIS were
bispectral index (BIS), end-expired carbon recorded by an anesthesia registrar who
dioxide, and inspired (FISEVO) and end-expired was blinded to the study group: before
(E'SEVO) sevoflurane concentrations. General epidural anesthesia, before surgery, every
anesthesia was induced with fentanyl (2.0 5 min for the first 2 h during surgery, and
g/kg) and propofol. Dose of propofol was after the completion of surgery until
titrated according loss of lash reflex and the endotracheal extubation. So were FISEVO
amount of propofol and induction time was and E'SEVO except for the time point before
observed. Cisatracurium (0.15 mg/kg) was induction. Times from start of induction to
used to facilitate tracheal intubation. Ventilation loss of eyelash reflex (T1), times from end
was controlled with a tidal volume of 7.0 ml/kg of surgery to return of gag reflex (T2) and
(oxygen/air mixture: 50%/50%), obtaining an respond to verbal command (T3) were also
end-expiratory pressure (PEEP) of 5.0 cm measured. Plasma samples were taken
H02, and PaCO2 was approximated to 35 mm immediately before, and 1 and 2 h after the
Hg by adjusting the respiratory rate and the start of surgery for measurements of
minute volume. Anesthesia was maintained by epinephrine and cortisol. Epinephrine was
a continuous infusion of cisatracurium analyzed by high performance liquid
(0.12/kg/hr) and Sevoflurane adjusted to keep chromatography assay on an isocratic liquid
BIS score between 40-60 throughout the chromatograph interfaced with an
surgical procedure. A 14.0 F triluminal catheter electrochemical detector. Cortisol was
was inserted into the right jugular vein for fluid determined by radioimmunoassay assay.
resuscitation and CVP measurements. Epinephrine and cortisol were not
Another 14 G peripheral cannula was secured. measured postoperatively to avoid
Analgesia was intensified by increments of 1.0 misinterpretation of their values due to
g/kg fentanyl given IV in response to increase unpredictable stress factors during the
in BIS to a value greater than 60. The total weaning period.
requirement of intraoperative fentanyl IV was Patients were followed up at 0, 2, 6, 12,
noted. and 24 h after surgery for pain with VAS
Intraoperative fluid administration was during deep inspiration by the SICU
10 ml/kg/hr crystalloids and managed to registrar who was unaware of the drug
keep CVP between 8 to12 mmHg. Blood given. When VAS on deep inspiration was
loss during surgery has been replaced with more than 4, they received fentanyl 50 g in
packed RBCs and FFP to keep HB level 10 ml of normal saline through the epidural
around 10 gm/dl.Volume expander ,packed catheter. Patients were also questioned
RBCS and FFP as well as blood loss were about side effects, such as hallucinations,
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pruritus, and nausea and vomiting, in the test and 2-test, as appropriate. Mean and
first 24 h after surgery. Respiratory rate and change in SBP, HR, FISEVO, E'SEVO, and BIS
the patients response were used to were analyzed using Students t-test, and
diagnose respiratory depression. If the the MannWhitney test was used to
respiratory rate was <10 breaths/min and determine differences in the maximum level
the patient was not verbally responsive, of sensory blocks between groups. Plasma
respiratory depression was diagnosed. If the concentrations of epinephrine and cortisol
patient was not responding and the were analyzed using repeated-measures
respiratory rate was > 10 breaths/min, analysis of variance. P<0.05 was
excessive sedation was diagnosed. considered statistically significant.
Complications related to TEA were
recorded like: Failed block and dural RESULTS
puncture. All patients were asked to answer Patient characteristics, surgical
a questionnaire about their pain sensation procedures, blood loss and resuscitation
and general comfort 24 h after surgery. fluid were recorded in the two study groups
Statistics: Results are expressed as mean (table I). Patients of group I showed
(SD) unless otherwise stated. SBP, HR, significant increase in blood loss and
FISEVO, E'SEVO, and BIS values recorded requirements for packed RBCs, FFP,
every 5 min for the first 2 h during surgery Hydroxyethyl starch and lactated Ringer
were averaged to provide overall means as solution compared to group II. I.V. fluid and
summary statistics. Changes in SBP, HR, blood loss represent the values recorded
FISEVO, E'SEVO, and BIS were calculated from during the whole surgical procedures. Urine
the absolute values of the changes in output was significantly increased in group
corresponding values every 5 min. Patient II compared to patients of group I.
characteristics and anesthetic data in both
groups were compared using Students t-
Table I: Patient characteristics, surgical procedures, blood loss, fluid replacement and
urine output
Group I Group II
(Bupivacaine 0.125%) (Bupivacaine 0.25%)
(n = 20) (n =20)
Sex ratio (m/f) 14/6 15/5
Age (years) 5411 5316
Body weight (kg) 6913 6811
Height, cm 1689 1707
ASA classification:
ASA I 0 1
ASA II 17 16
ASA III 3 3
Operation time (min) 392125 371114
Anesthesia time (min) 468152 459167
Surgical procedures:
Whippels procedure 15 16
Pseudo pancreatic cyst 2 2
Roux en-y 3 2
Blood loss (ml) 1185589* 1030483
Urine output (ml) 984395 1246474*
Packed RBCs (ml) 1150650* 1000500
FFP (ml) 850480* 640390
Hydroxyethyl starch (ml) 1500500* 1000500
Lactated Ringer (ml) 5,2531,910* 4,5602,660
(number, mean SD)
*P is significant if <0.05. **P is significant if<0.001
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TEA was performed successfully in all During surgery, both groups were
patients without any observed similar for both mean and change per 5 min
complications. The mean upper sensory in BIS, SBP and HR. The mean and change
blockade level extended to T 4-5 (+/- 1.0 per 5 min in FISEVO and E'SEVO were
segments), and the lower blockade significantly higher in group I than in group II
extended to T10-11 (+/- 3.5 segments). The (P<0.05). But, ephedrine requirements were
upper levels of sensory block to cold and significantly high in group II compared to
pinprick 15 min after the bolus injection group I (P<0.001) (Table IV).
were similar in the two groups, whereas Plasma levels of both epinephrine and
bupivacaine 0.25% (group II) produced a cortisol showed significant increase in post-
significantly higher level of loss of touch induction values (after 1 hr and 2hr) in
sensation. Base-line SBP, HR, CVP, and group I compared to groupII. However,
BIS before epidural anesthesia was similar values of both groups showed significant
in both groups and showed insignificant increase when compared to base-line
change (table II). values (Table V, Fig 1)
The timings of special events of VAS ((Visual Analogue Scale) showed
anesthesia (T1, T2, T3) showed insignificant change between the two
insignificant decrease in group II compared groups and the time for the first
to group I. However, the total amount of postoperative bolus dose and number of
propofol used for induction of general doses were comparable in both groups
anesthesia and the total fentanyl used (table VI). Side effects were infrequent in
during anesthesia were significantly low in both groups and Patient satisfaction was
0.25% bupivacaine group (table III). almost the same in both groups (table VII).
Group I Group II
(bupivacaine 0.125%) (bupivacaine 0.25%)
(n= 20) (n= 20)
Epidural site:
T 10-11 7 6
T 11-12 13 14
Loss of sensation to cold T 5 (T4-T10) T4 (T3-T9)
Loss of sensation to pinprick T5 (T4-T11) T4 (T4-T10)
Loss of sensation to touch T 8 (T6-T12) T 6 (T4-T12)*
Base-line CVP (mmHg) 93 9 4
Base-line HR (beat/min) 7614 7716
Base-line mean BP (mm Hg) 7916 7615
Base-line BIS 96.80.7 97.20.8
Data are presented as mean (SD), absolute number or median (10th, 90th percentiles).
*P<0.05 between two groups
Table III: Anesthetic induction and recovery and total requirements of propofol and
fentanyl.
Group I Group II
(bupivacaine 0.125%) (bupivacaine 0.25%)
(n= 20) (n= 20)
T1: Loss of lash reflex (s) 66 16 6411
T2: Return of gag reflex (s) 498112 501120
T3: Verbal command (s) 528134 534137
Total IV propofol (mg) 14252 11324*
Total IV fentanyl (g) 412310 24640**
Data are presented as mean (SD). *P<0.05 , **P<0.001
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Table IV: BIS, FISEVO and E'SEVO, SBP, HR and dose of ephedrine during surgery
Group I Group II
(bupivac. 0.125%) (bupivac, 0.25%)
(n= 20) (n= 20)
Mean BIS 47.12.3 44.72.2
Change in BIS (/5 min) 3.42.4 3.73.1
Mean FISEVO (%) 1.410.36* 1.130.34
Change in FISEVO (% /5 min) 0.190.31* 0.120.23
Mean E'SEVO (%) 1.220.33* 0.890.19
Change in E'SEVO (% /5 min) 0.130.07* 0.070.04
Mean SBP (mm Hg) 98.815.7 95.913.6
Change in SBP (mm Hg /5 min) 7.95.7 6.65.1
Mean HR (beats min1) 70.314.5 68.110.4
Change in HR (beats/5min) 5.24.6 6.15.8
Dose of ephedrine (mg) 8.87.9 21.311.3**
Data are presented as mean (SD).
Mean BIS, FISEVO, E'SEVO, SBP, and HR reflect the average of corresponding values recorded
every 5 min for the first 2 h during surgery. Changes in BIS, FISEVO, E'SEVO and SBP were
calculated from the absolute values of the changes in respective values every 5 min.
*P<0.05 between groups, **P<0.001
70 90
60 80
50 70
60
40
group I 50
30 group I
group II 40
group II
20 30
20
10
10
0 0
0 hr 1 hr 2 hr 0 hr 1 hr 2 hr
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Table VI: VAS (Visual Analogue Scale) in the two groups after surgery
Group I Group II
(bupivac. 0.125%) (bupivac. 0.25%)
(n= 20) (n= 20)
VAS 0 2.9 1.1 2.8 1.0
VAS 2 2.9 1.8 2.8 1.6
VAS 6 3.2 2.1 3.3 2.4
VAS 12 2.9 1.9 2.7 1.8
VAS 24 2. 41.1 2.31.2
Patients satisfaction 100% 100%
Time of first bolus [(h)SD] 11.43.7 11.13.4
Total number of bolus doses 2.30.6 2.40.4
Table VII: Side effects, time of first bolus dose, number of bolus dose and patient
satisfaction score in the two groups
Group I Group II
(bupivac. 0.125%) (bupivac. 0.25%)
(n= 20) (n= 20)
Nausea/Vomiting [n (%)] 4 (20) 3 (15)
Pruritus [n (%)] 1 (5%) 0 (0)
Respiratory depression [n (%)] 0 (0) 0 (0)
Patient satisfaction score (range) 9.2 (8-10) 9.3 (8-10)
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In this study, the inspired anesthetic and perfusion of operative region, decrease
concentration was changed only on the of single doses of opioids analgesics, local
basis of BIS values to keep it between` 40- and general anesthetics followed by the
60. Less sevoflurane concentration was decrease of their side effects, better
recorded with 0.25% concentration of intensity and longer duration of analgesia
bupivacaine (Group II). In clinical practice, and improved total functional capability of
anesthetists do not change the inspired patients. Final subjective effect of
anesthetic concentration only on the basis analgesia, according to verbal descriptive
of BIS values(5,17). However, in view to the scale (VDS) of pain was satisfying with 75%
changes in SBP and HR during surgery of patients of the CSEGA group (compared
between the two groups, it is likely that the to 15% of patients of the general anesthesia
depth of general anesthesia is more group) which is very close to our results. In
variable and fluctuated with the use of lower the present study, 0.25% bupivacaine group
concentration of bupivacaine (0.125%). experienced an advantage which is
Zoric et al.(18) used thoracic epidural- reported before, where the urine output was
general anesthesia for all patients significantly increase compared to the
undergoing major abdominal surgery, since 0.125% group (although UOP in this group
1997 as a routine. For intraoperative was reasonable), and this observation
analgesia they used 0.25% plain might be attributed to the renal vasodilating
bupivacaine. The most important detail in effects of thoracic epidural.
their technique is the analgesic solution Christopher et al.(20) examined the
(AS) which contains bupivacaine 0.25% (25 degree of success at maintaining patients
mg), fentanyl (50 g) and morphine randomized to epidural or general
hydrochloride (2.0 mg), in total volume of 15 anesthesia for peripheral vascular surgery
ml. They maintained intraoperative within predetermined blood pressure (BP)
analgesia with bupivacaine 3 to 5 ml in and heart rate (HR) limits and investigated
intermittent bolus doses. For very light GA the associations between such
only artificial ventilation with 66% N2O in hemodynamic control and intraoperative
O2 and muscle relaxation with pancuronium myocardial ischemia and postoperative
is needed. Co analgesia with intravenous major cardiac morbidity in 100 patients. A
fentanyl was exceptionally seldom needed, greater percentage of patients randomized
except for induction. Intraoperative drugs to general anesthesia had intraoperative
consumption was very small and with BPs more above their limit (95% vs. 72%)
adequate liquid compensation (10 ml/kg/hr), and more rapid changes in HR (75% vs.
this technique achieves exceptionally 48%) or BP(100% vs 73%) than those
intraoperative homodynamic stability in randomized to epidural anesthesia. Patients
patients, despite long and big operations. experiencing intraoperative ischemia,
These results are consistent with our results regardless of anesthetic type, more
of the 0.25% bupivacaine group but not frequently had BPs greater than 10% above
0.125% group. However, we should their upper limit and more rapid HR
mention that our results with 0.25% changes compared with patients without
bupivacaine (Group II) were on expenses of ischemia. They concluded that, prevention
significant use of ephedrine to maintain of elevated intraoperative BP and rapid
hemodynamic changes in BP or HR may be more
According to the verbal Analogue scale successful with epidural than with general
(VAS < 4), 100% patients were satisfied anesthesia. In the present study, 0.125%
with this analgesia, which gave possibilities bupivacaine group I, showed better control
to mobilization and rehabilitation even in the of hemodynamic without need for inotropic
first postoperative day. Malenkovic et al.(19) support (ephedrine). However, the 0.25%
analyzed the advantages of combined bupivacaine group II patients showed
spinal, epidural and general anesthesia significantly less blood loss and accordingly
(CSEGA) versus general anesthesia (GA) they need less packed RBCs, FFP,
in abdominal surgery. Advantages of crystalloids, and colloid solution and
CSEGA versus GA in abdominal surgery significantly more urine output. These
were manifold: better hemodynamic stability effects of the 0.25% bupivacaine may be
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attributed to the extent and depth of the its use as a fixed element of anesthesia for
block and appeared to give these patients liver patient without fear of developing epidural
good surgical outcome and maintain body hematoma or the occurrence of sever
homeostasis(21). On the other hand, part of hemodynamic changes. Also, epidural
the hemodynamic changes that have been anesthesia significantly decreases the
observed during Whipples operation may intraoperative requirements of opioids and
be attributed to the presence of abdominal muscle relaxants in patients who are usually
mesenteric traction (MT) syndrome that very sick with multiple organ dysfunctions(25).
occur during major abdominal operations
and result in sudden hypotension and Conclusion: Our results support the
arterial hypoxemia due to a marked release routine use of low thoracic epidural
of prostacyclin. This hemodynamic analgesia as part of the anesthesia protocol
response following MT, result in a for patient undergoing pancreatic surgery.
deterioration of splanchnic perfusion, can The use of 0.25% bupivacaine with 1.0
occasionally is prolonged and severe(22). g/kg fentanyl plus 2.0 mg morphine gave
Alexander et al(23) observed an MT excellent anesthetic condition during
response with significant decrease in MAP surgery and was superior to 0.125%
in 72% of the patients undergoing pancreas preparation from all clinical aspect except
surgery. the need for more ephedrine which could be
In the present study, the side effects were precluded by reducing the bolus dose and
rare in both groups which highly support the maintenance rate of the 0.25% solution.
optimistic of this technique for upper
abdominal surgery. The work carried by REFERENCES
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