Effects of Epidural Anesthesia and Analgesia on
Coagulation and Outcome After Major Vascular Surgery
Kenneth J. Tuman, MD, Robert J. McCarthy, PharmD, Robert J. March, MD,
Giacomo A. DeLaria, MD, Rajesh V. Patel, MD, and Anthony D. Ivankovich,
Departments of Anesthesiology and Cardiovascular Surgery, Rush-Presbyterian-St. Lukes Medical Center,
Chicago, Illinois
To examine the interaction of epidural anesthesia,
coagulation status, and outcome after lower extrem-
ity revascularization, 80 patients with atherosclerotic
vascular disease were prospectively randomized to
receive general anesthesia combined with postopera-
tive epidural analgesia (GEN-EPI) or general anesthe-
sia with on-demand narcotic analgesia (GEN). Demo-
graphics did not differ between groups except that
the GEN-EPI group had a higher incidence of diabe-
tes mellitus and of previous myocardial infarction.
Coagulation status was monitored using throm-
boelastography. An additional 40 randomly selected
patients without atherosclerotic vascular disease un-
dergoing noncardiovascular procedures served as
controls for coagulation status. Vascular surgical pa-
tients were hypercoagulable compared with control
patients before operation and on the first postopera-
tive day. Postoperatively, this hypercoagulability was
attenuated in the GEN-EPI group and was associated
with a lower incidence of thrombotic events (periph-
P atients w i t h atherosclerosis who u n d e r g o major
peripheral vascular surgery a r e at increased
risk for postoperative cardiovascular complica-
tions (1-3). In a previous study by Yeager e t al. (4),
high-risk p a t i e n t s receiving c o m b i n e d e p i d u r a l -
general anesthesia for a variety of surgical procedures
exhibited a significantly lower postoperative cardio-
vascular complication rate c o m p a r e d w i t h general
anesthesia alone. Currently, clinical application of
t h e s e findings t o high-risk vascular surgical patients
h a s been limited by t h e small n u m b e r of s u c h patients
in t h e Yeager e t al. s t u d y and by t h e lack of confir-
matory s t u d i e s i n this s u b s e t of patients. Verification
of these rather striking findings i n a larger s a m p l e of
vascular surgical patients is necessary because of t h e
Accepted for publication July 1, 1991.
Address correspondence to Dr. Tuman, Department of Anes-
thesiology, Rush-Presbyterian-St. Lukes Medical Center, 1653
West Congress Parkway, Chicago, IL 60612.
696 Anesth Analg 1991;73:69&704
MD
eral arterial graft, coronary artery or deep vein throm-
boses). The rates of cardiovascular, infectious, and
overall postoperative complications, as well as dura-
tion of intensive care unit stay, were significantly
reduced in the GEN-EPI group. Stepwise logistic
regression demonstrated that the only significant
predictors of postoperative cardiovascular complica-
tions were preoperative congestive heart failure and
general anesthesia without epidural analgesia. We
conclude that in patients with atherosclerotic vascular
disease undergoing arterial reconstructive surgery (a)
thromboelastographic evidence of increased platelet-
fibrinogen interaction is associated with early postop-
erative thrombotic events, and (b) epidural anesthe-
sia and analgesia is associated with beneficial effects
on coagulation status and postoperative outcome
compared with intermittent on-demand opioid anal-
gesia.
(Anesth Analg 1991;73:69&704)
potential impact on patient management (5). In addi-
tion, s t u d y of a m o r e homogeneous surgical popula-
tion allows examination of t h e interaction of anes-
thetic choice w i t h o t h e r factors k n o w n t o affect
postoperative outcome.
Factors that m a y influence perioperative morbidity
in t h e s e patients a r e a d v a n c e d age, significant coro-
nary artery disease, hypertension, congestive heart
failure, a n d t h e stresses of peripheral vascular s u r -
gery itself. In addition, the hemostatic system is a n
i m p o r t a n t factor i n atherosclerosis and its complica-
tions. Hypercoagulability manifested by increased
fibrinogen and platelet activity has been implicated in
t h e genesis of unstable angina, intracoronary throm-
bosis, a n d myocardial infarction (6,7).Patients u n d e r -
going peripheral vascular surgery h a v e postoperative
increases in platelet reactivity and i n factor VIII-
related antigen a n d h a v e decreases in antithrombin
111 levels indicative of a hypercoagulable state t h a t c a n
be associated w i t h early arterial graft failure (8,9).
01991 by the International Anesthesla Research Society
0003-2999/91/$3.50
AhESTH ANALG
1991:73:696704 EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY
These disease-related changes in coagulation may be
exacerbated by surgical and postoperative stress (10).
As most cardiovascular morbidity occurs in the
hours and days after completion of vascular surgery,
postoperative stress-induced hypercoagulability
could play a causal role. Epidural anesthesia and
analgesia continuing into the postoperative period
can attenuate the postoperative stress response in
specific patient populations (4,ll-13). Epidural anes-
thesia and analgesia is also associated with direct and
indirect effects on the hemostatic system and may
result in diminished postoperative hypercoagulability
(14-16). If postoperative anesthetic management,
such as the use of continuous epidural analgesia,
positively influences outcome in high-risk patients in
the hours and days after major peripheral vascular
surgery, it may do so by altering the coagulation
system.
With these considerations in mind, this study was
designed to reevaluate the association of epidural-
general anesthesia and postoperative epidural anal-
gesia with improved cardiovascular and overall out-
come after major vascular surgery. We also sought to
study the previously untested hypothesis of an asso-
ciation between coagulation state, postoperative com-
plications, and choice of anesthetic in high-risk vas-
cular patients. An additional goal of this study was to
determine the relative importance of anesthetic man-
agement compared with preoperative risk factors for
adverse cardiovascular outcome in patients undergo-
ing major peripheral vascular surgery.
Methods
Perioperative Management
With institutional review board approval, 80 consent-
ing adults undergoing major vascular surgery of the
abdominal aorta and lower extremities were ran-
domly assigned to receive general anesthesia com-
bined with epidural anesthesia and analgesia (GEN-
EPI), or general anesthesia with postoperative
parenteral and/or oral narcotic administration (GEN).
Patients with preoperative coagulopathies or liver
disease, receiving anticoagulant or antiplatelet medi-
cations, or with any contraindication to the use of an
epidural catheter, or any of the standard anesthetic/
analgesic agents employed, were excluded from en-
try into this study.
Intraoperatively, patients in the GEN group re-
ceived an anesthetic consisting of inhaled nitrous
oxide, oxygen, isoflurane (51.5% inspired), and
515 pglkg of intravenous fentanyl. Postoperatively,
GEN patients received parenteral and/or oral narcotic
analgesics as requested for pain relief. Patients in the
GEN-EPI group had high lumbar or low thoracic
CARDIOVASCULAR ANESTHESIA TUMAh ET AL 697
(L-3-T-10) epidural catheters inserted using a stan-
dard loss of resistance technique before induction of
general anesthesia. Epidural catheters were evalu-
ated for accidental intravascular or intrathecal place-
ment and for evidence of dermatomal spread (tl
spinal segment) of analgesia using a 3-mL test dose of
lidocaine (1.5%)with epinephrine (1:200,000). Intra-
operatively, the anesthesia for the GEN-EPI patients
was maintained with inhaled nitrous oxide, low con-
centrations of isoflurane (10.5% inspired), 5 5 pg/kg
of intravenous fentanyl, and incremental injections of
1.5% lidocaine administered through the epidural
catheter to achieve surgical anesthesia. After initial
dosing with local anesthetic, the epidural catheter
was redosed at the discretion of the anesthesiologist
using approximately one-half of the original dose of
local anesthetic if hemodynamic changes and the
requirement for general anesthetic drugs suggested
that the level of analgesia provided by the local
anesthetic had decreased. The total volume of local
anesthetic used intraoperatively (12-20 mL) was de-
termined by analgesic and anesthetic requirements of
the individual patient. Nondepolarizing muscle relax-
ants were used in both groups to facilitate control of
ventilation, primarily during surgery of the abdomi-
nal aorta.
In the GEN-EPI group, a continuous epidural
infusion of fentanyl (0.001%) and bupivacaine (0.1%)
at 5-8 mL/h was initiated at least 30 min before
anticipated completion of the surgical procedure.
When necessary, parenteral narcotics were used to
supplement pain relief, and the duration of postop-
erative epidural analgesia was a clinical decision not
dictated by study protocol. Patients receiving epidu-
ral analgesia were evaluated at least daily by a mem-
ber of the Department of Anesthesiology acute post-
operative pain service, and care was given according
to established pain service protocols.
The trachea was intubated, and ventilation was
controlled, for at least the duration of the operation,
in both anesthetic groups. In both groups, choice of
premedication and specific doses of anesthetic and
nonanesthetic agents were at the discretion of the
anesthesiologist and depended on the patients con-
dition and the requirements for providing amnesia,
muscle relaxation, and hemodynamic stability.
Chronically administered cardiac medications were
given on the morning of operation. All patients had
inonitoring of electrocardiographic leads I1 and V,
and of intraarterial catheters for arterial blood pres-
sure measurements and for analysis of blood gas
tensions and hematocrit. All patients undergoing
procedures involving the abdominal aorta had central
venous catheters inserted in the operating room.
During the perioperative period, hemodynamic aber-
698 CARDIOVASCULAR ANESTHESIA TUMAN ET AL.
EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY
rations exceeding 20% of baseline, serious dysrhyth-
mias, and ischemia were treated.
Intraoperatively, all patients undergoing vascular
clamping received 50-75 mg of heparin, reversed
with protamine. No blood products except packed
red blood cells were administered. Postoperatively,
no patients received anticoagulants except for one
patient in the GEN group who received a heparin
infusion in the immediate postoperative period be-
cause of an acute vascular graft thrombosis.
Coagulation monitoring was performed using a
commercially available thromboelastograph (BICLOT
ELVI 816 Thromboelastograph, Logos Scientific,
Henderson, Nev.) (17,18). Forty patients without
clinical evidence of atherosclerotic vascular disease
undergoing noncardiovascular procedures involving
the abdomen or lower extremities were randomly
selected to serve as controls for coagulation status.
One-half of these control patients received general
anesthesia, and one-half received general-epidural
anesthesia and analgesia as described. Thromboelas-
tography was performed on whole blood after induc-
tion of anesthesia and on the first postoperative day
for the control patients and for the 80 vascular surgi-
cal patients.
Postoperatively, all patients were transferred to an
intensive care unit (ICU) and received postoperative
intensive care following standardized protocols. Post-
operative hemodynamic variables, arterial blood gas
tensions, electrolytes, hemoglobin, and urine output
were monitored closely under the direction of a staff
surgeon and an anesthesiologist who were not one of
the authors and who were unaware of the goals of the
study. Discharge of patients from the ICU was deter-
mined by the surgical staff and was dependent on the
assessment of overall patient course and cardiopul-
monary stability. Patients were transferred to a reg-
ular hospital bed only when they did not require
vasoactive infusions, invasive monitoring, fluid ad-
ministration above maintenance levels, or aggressive
pulmonary therapy for at least 24 h.
Data Collection
The physicians and nurses involved in the care of the
patients were unaware of the outcome variables that
were being monitored. Data were collected by a
full-time data manager. Preoperative patient demo-
graphics that might be associated with greater mor-
tality and morbidity after vascular surgery (1-3) were
selected for examination. Evidence of congestive
heart failure (defined as classic chest radiographic
changes in conjunction with either rales on lung
auscultation or an S 3 gallop on cardiac auscultation),
history of angina, prior myocardial infarction, pre-
operative arrhythmias requiring treatment, and
ANESTH ANALG
1991;73:696-704
chronic hypertensive therapy were noted. Left ven-
tricular dysfunction was defined by an ejection frac-
tion of less than 0.4. Renal dysfunction (defined as a
preoperative creatinine level greater than 1.4 mg/dL),
diabetes mellitus, age, preoperative antianginal ther-
apy (padrenergic or calcium channel blocking drugs
and topical or oral nitrates), duration of operation,
and estimated blood loss were also noted. Intraoper-
ative hypertension was considered present if the
systolic pressure exceeded 120% of the mean pre-
operative systolic blood pressure for more than 5 min;
hypotension, if the systolic pressure was less than
80% of the mean preoperative systolic pressure for
more than 5 min; and tachycardia, if the heart rate
exceeded 120% of the mean preoperative rate or 100
beats/min for more than 5 min.
Postoperative observations of clinical outcome
were made using prospectively defined definitions of
morbidity (Table 1). Electrocardiographic ischemia
was defined as 20.1 mV positive or negative horizon-
tal ST segment shift, which extended at least 80 ms
beyond the J point of the QRS complex in any lead.
Hard copies of lead I1 or CS, were obtained every 4 h
in the ICU and more frequently if changes suggestive
of ischemia (ST segment or T wave abnormalities) or
of arrhythmias appeared on continuous oscillo-
graphic displays. In addition, standard 12-lead elec-
trocardiograms were recorded twice daily in the ICU.
All hard-copy electrocardiographic recordings were
calibrated using a 1-mV standard.
Postoperative vascular graft patency was deter-
mined by clinical examination and by Doppler mea-
surements. Early vascular graft failure was defined as
a return of preoperative clinical status, lack of signif-
icant improvement in Doppler measurements, or
need of reoperation for thrombectomy or unplanned
amputation of any portion of the affected limb. All
patients in whom graft failure developed had intra-
operative arteriograms performed at the completion
of the initial procedure. These completion arterio-
grams were independently reviewed by two cardio-
vascular surgeons not involved in the primary oper-
ation; none of the patients with graft failure had any
evidence of technical error such as intimal flap or
anastomotic problems, and all had adequate outflow
on completion of the operation. Deep venous throm-
bosis of the lower extremities was diagnosed by
clinical examination and was documented with
venography .
Data Analysis
Patient demographics, perioperative risk factors, and
the incidence of postoperative morbidity were com-
pared between the GEN and GEN-EPI group. Patient
age, duration of operation, estimated blood loss,
ANESTH ANALG CARDIOVASCULAR ANESTHESIA TUMAN ET AL. 699
1991;73:696-704 EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY

Table 1. Definitions of Postoperative Morbidity Table 2. Patient Characteristics

~ ~~~

Complication Definition GEN GEN-EPI P

Major cardiovascular No. of patients 40 40
New myocardial infarction Creatine phosphokinase or lactate Age (yr) 65.5 5 9.9 69.6 ? 8.4 0.052
dehydrogenase isoenzyme and Sex (F) (%) 62.5 57.5 0.648
electrocardiographic changes Previous vascular surgery (%) 30.0 32.5 0.809
Congestive heart failure Classic radiographic changes with History of transient ischemic 15.0 17.5 0.762
either rales, S3 gallop, or attack or stroke (%)
pulmonary artery occlusion History of chronic obstructive 20.0 20.0 1.00
pressure 218 mm Hg, if pulmonary disease (%)
measured History of angina (%) 35.0 50.0 0.175
Serious arrhythmias Ventricular tachycardia, Ejection fraction <0.4 (%) 15.0 22.5 0.390
supraven tricular Congestive heart failure (%) 2.5 10.0 0.166
tachyarrhythmias or heart block Previous myocardial infarction (%) 25.0 47.5 0.036
requiring treatment History of hypertension (%) 72.5 62.5 0.339
Angina Chest discomfort and Renal dysfunction (%) 17.5 30.0 0.189
electrocardiographic changes Diabetes mellitus (%) 17.5 37.5 0.045
prompting pharmacologic therapy Antiarrhythmic medications (%) 27.5 32.5 0.626
Hypertensive crisis Marked arterial blood pressure PAdrenergic blocker (5%) 12.5 12.5 1.00
elevation with encephalopathy, Calcium channel blocker (%) 35.0 30.0 0.633
myocardial ischemia, or Nitrates (%) 20.0 22.5 0.785
congestive heart failure Infrainguinal revascularization (%) 50.0 62.5 0.260
Pulmonary Tracheal intubation >24 h or Duration of operation (h) 3.8 -C 1.3 3.5 5 1.1 0.455
tracheal reintubation and Estimated blood loss (mL) 404 ? 242 462 ? 468 0.621
mechanical ventilation after initial
GEN, general anesthesia; GEN-EPI, combined general-epidural
extubation anesthesia.
Renal Increase in serum creatinine Values are mean 2 SD.
2 2 mg%
Neurologic Sensory, motor, or reflex
abnormalities anytime after
surgery; global abnormalities
previously). The variables in the predictor set were
within 2 days of operation found by a forward selection process such that the
Gastrointestinal Gastrointestinal hemorrhage with a P value associated with the introduction of additional
decline in hemoglobin of 2 g%; variables was greater than 0.05. The estimate of the
acute surgical abdomen coefficient in the regression equation and the estimate
Infectious Pneumonia (radiographic infiltrate of the odds ratio calculated from this coefficient were
and two of three criteria: fever, maximum likelihood estimates. The odds ratio is the
leukocytosis, or positive sputum
culture); localized infection with
relative odds of the occurrence of a major cardiovas-
culture positive for a pathogen, cular complication associated with a change in the
requiring antibiotics and predictor variable.
accompanied by either fever or
leukocytosis
Results
The comparison of group characteristics that might
duration of ICU and total postoperative hospital stay, influence outcome after major peripheral vascular
and the total number of complications were com- operation is presented in Table 2. The study groups
pared between anesthesia groups using the Mann- are similar in terms of preoperative characteristics,
Whitney U test. Thromboelastographic variables (R, chronic drug therapy, and surgical variables, except
K, a, and MA) were compared using analysis of for a greater incidence of diabetes mellitus and prior
variance with repeated measures. When appropriate, myocardial infarction in the GEN-EPI group. Intraop-
secondary tests were performed using the Tukey-a eratively, the incidence of hypertension (30.0% vs
method. The conventional Pearson 2 statisticwas used 25.0%)and tachycardia (12.5%vs 7.5%)did not differ
to compare all other data between groups (19). The significantly between the GEN and GEN-EPI groups,
null hypothesis was rejected when P was less than respectively.
0.05. There were no baseline differences in coagulation
Patient characteristics from Table 2 were subjected state between the vascular surgery patients in the
to multivariate analysis using stepwise logistic regres- GEN or GEN-EPI groups (Table 3). After induction of
sion to determine the best set of variables predictive anesthesia (baseline), patients with atherosclerotic
of major cardiovascular complications (as defined vascular disease had accelerated coagulability (repre-
700 CARDIOVASCULAR ANESTHESIA TUMAN ET AL. ANESTH ANALG
EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY 1991;73:69&704

Table 3. Effect of Anesthesia on ThromboelastographicCoagulation Variables

Baseline Postoperative
Variables Vascular Nonvascular Vascular Nonvascular
General anesthesia ( n ) 40 20 40 20
R (min) 11.2 f 2.3 12.6 f 2.2 11.1 t 2.1 12.6 2 1.5
K (min) 4.8 5 0.9 5.5 5 1.3 4.5 f 0.9 5.1 t 0.8
0 (deg) 56.8 2 4.3"" 48.7 2 7.8" 59.0 f 6.4" ' ' 49.6 t 8.2',''
MA (mm) 61.8 f 4.5'' 50.2 5 6.W 63.9 f 5 3' 'I ' 51.8 f 6.9''
Combined general-epidural anesthesia (n) 40 20 40 20
R (min) 11.4 f 1.7 12.2 2 2.3 11.5 2 1 5 12.6 f 1.5
K (min) 4.8 f 0.7 5.2 f 1.2 4 9 2 0.8 5.4 f 0.7
a (deg) 56.2 2 6.0"' 48.0 2 5.1"'' 48.1 5 5.1' ''I 45.8 f 3.4"' 'I
MA (mm) 62.0 f 4.2"4' 51.7 2 4.61"7 53.8 I 5 . 2 " " ' 47.8 t 4.1','7,'

Values are mean -t SD

'"Designate significantlv different pairs, P = 0 05

Table 4. Postoperative Morbidity and Mortality

sented by larger a and MA values) compared with
control patients without clinical evidence of athero- GEN-
sclerotic vascular disease (Table 3 ) . These throm- GEN EPI
( n = 40) (ti = 40) P
boelastographic markers of fibrinogen-platelet activ-
ity increased on the first postoperative day in Mortality 0 0
vascular surgery patients receiving general anesthe- Morbidity
sia. Conversely, use of GEN-EPI anesthesia in pa- Cardiovascular" 11 4 0.045
Myocardial infarction 3 0 0.077
tients undergoing vascular surgery was associated
Congestive heart failure 4 2 0.409
with a significant decline in postoperative a and MA Ventricular tachyarrhythmia 4 0 0.040
values (Table 3). A decline of smaller magnitude in Supraventricular tachyarrhythmia 7 3 0.176
postoperative a and MA values from baseline was Hypertensive crisis 1 0 0.314
seen in control patients receiving GEN-EPI anesthesia Angina 1 1 1.00
for nonvascular surgery. Postoperatively, vascular Heart block 2 0 0.152
surgery patients in the GEN-EPI group had values of Respiratory" 5 1 0.089
Prolonged endotracheal intubation 5 1 0.089
a and MA that approached but still exceeded those of
Reintubation 1 0 0.314
nonvascular surgery patients who received similar Renal insufficiency 3 1 0.305
anesthetic management. Neurologic complications 3 0 0.078
The average duration of epidural catheter use for Gastrointestinal 1 2 0.556
analgesia was 2.40 ? 0.98 postoperative days. The Infectious" 8 2 0.043
average pain scores in the GEN-EPI group on the first Pulmonary 4 0 0.040
Urinary tract 4 2 0.409
three postoperative days were 2.3 2 2.6, 1.1 ? 1.4,
Vascular occlusions" 9 1 0.007
and 0.8 -C 1.0, respectively, as measured on a visual Vascular graft failure 8 1 0.013
analogue scale from 0 to 10 in which a score of 0 Deep venous thrombosis 1 0 0.314
represents no pain and a score of 10 represents Total complications 52 13 0.011
intense pain. Number of patients with
The duration of hospital stay after surgical proce- 2 1 Complications 18 8 0.017
dures performed under GEN-EPI anesthesia was 10.7 >2 Complications 11 3 0.019
t- 6.8 days compared with 13.2 f 11.7 days in those G E N , general anesthesia, GEN-EPI, combined general-epidural
receiving general anesthesia alone (P = 0.565). The anesthesia
"Number of pahents with one or more complications withln category.
duration of ICU stay was longer in the GEN group
compared with the GEN-EPI group (3.3 2 6.9 vs 1.5
t 1.4 days; P = 0.031). This longer ICU stay after
operation was associated with a larger number of (11140 vs 3/40). There was no in-hospital mortality in
serious complications in patients receiving general either group. An analysis of complication types
anesthesia alone (Table 4). In the GEN group, one or showed a larger incidence of cardiovascular and
more postoperative complications developed in 18 of infectious complications and a larger incidence of
40 patients compared with 8 of 40 in the GEN-EPI peripheral vascular occlusions (arterial graft failure or
group. The number of patients experiencing two or deep venous thrombosis) in the GEN group (Table 4).
more complications was also larger in the GEN group The larger incidence of vascular graft failure in the
ANESTH ANALG
1991;73:696-704
Table 5. Thromboelastographic Coagulation Data for Patients With Vascular Graft, Coronary Artery, or Deep
Vein Thromboses
Thrombosis
Variables (n = 12)
R (min) 10.9 f 2.6
K (min) 4.5 2 0.9
a (deg) 57.2 t 6.0
MA (mm) 61.2 t 4.6
Values are mean 5 SD.
04Designate significantly different pairs, D =
GEN group was also associated with a larger inci-
dence of reoperation on the affected limb (7/40 vs
1/40, P = 0.025). The incidence of postoperative
electrocardiographic evidence of ischemia did not
differ between the GEN and GEN-EPI groups (15/40
vs 13/40, respectively; P = 0.639). In addition to the
larger overall incidence of postoperative infections,
there was a larger incidence of pulmonary infections
in the GEN group (4/40 vs 0/40). Five of the 40
patients in the GEN group required tracheal intuba-
tion and mechanical ventilation for longer than 24 h
postoperatively, and one of these patients required
tracheal reintubation and mechanical ventilation.
None of the patients in the GEN-EPI group required
tracheal reintubation, and only one of 40 patients in
the GEN-EPI group required mechanical ventilation
for more than 24 h.
Postoperatively, three patients in the GEN group
experienced neurologic complications: one patient
suffered a hemispheric cerebral infarct, another had
severe exacerbation of multiinfarct dementia requir-
ing prolonged rehabilitation, and one had mental
obtundation and symptoms consistent with a tran-
sient ischemic event that resolved without sequelae.
None of the patients receiving GEN-EPI anesthesia
experienced postoperative neurologic complications.
Significant gastrointestinal complications developed
in three patients after operation: one patient required
reoperation for removal of a portion of ischemic small
bowel and gangrenous cholecystitis; ischemic colitis
with lower gastrointestinal bleeding developed in
one, requiring a diverting colostomy; and one expe-
rienced a severe form of Olgilvie's syndrome postop-
eratively. There was no difference in the occurrence
of these events between anesthesia groups, nor were
there differences in any outcome variable between
type of surgical procedure.
To determine if the occurrence of thrombotic
events in the postoperative period was associated
with hypercoagulability as measured by thromboelas-
tography, coagulation data for patients with clinical
evidence of coronary artery, deep vein, or vascular
CARDIOVASCULARANESTHESIA TUMAN ET AL. 701
EPIDURAL ANESTHESlA AND ANALGESlA FOR VASCULAR SURGERY
~~ ~
Baseline Postoperative
No thrombosis Thrombosis No thrombosis
(n = 68) ( n = 12) (ti = 68)
11.3 2 1.9 10.7 f 2.7 11.4 f 1.6
4.8 i- 0.8 4.5 t 1.1 4.7 ? 0.8
56.4 2 5.W 59.1 f 9.5b 52.6 5 7.3","
61.9 2 4.3' 63.7 2 7.9d 58.0 2 6.8c."
0.05
graft thrombosis (12 patients experiencing 13 events)
were compared with that for patients without these
complications (Table 5). There were no baseline dif-
ferences in coagulation state detectable by throm-
boelastography between patients with or without
postoperative thrombotic complications. However,
accelerated coagulation was observed postoperatively
in those patients experiencing thrombotic events
compared with those without thrombotic events ( n =
68). Of those patients in whom postoperative throm-
bosis of a coronary artery, deep vein, or vascular graft
developed, 11 received general anesthesia alone and
one received GEN-EPI anesthesia (P = 0.002). Multi-
variate analysis using stepwise logistic regression
considered all of the perioperative factors listed in
Table 2 as well as the type of anesthesia. The pres-
ence of preoperative congestive heart failure (P coef-
ficient = 3.02, P = 0.009) and the use of general
anesthesia without epidural analgesia ( p coefficient =
1.85, P = 0.022) were significant predictors of post-
operative cardiovascular complications with odds ra-
tios of 20.51 and 6.36, respectively (Table 6). None of
the other perioperative variables had predictive
value.
Discussion
The choice of anesthesia for patients undergoing
major peripheral vascular surgery remains controver-
sial. Yeager et al. (4) included patients undergoing
major peripheral vascular surgery as a subset of
high-risk surgical patients exhibiting a significantly
larger cardiovascular complication rate after general
anesthesia compared with combined regional-general
anesthesia. Another randomized trial (20) and a ret-
rospective review (5) were not able to demonstrate
differences in mortality or cardiac morbidity in pa-
tients receiving central neuraxial anesthesia com-
pared with general anesthesia for peripheral vascular
surgery. These conflicting results may be attributed
to differences in population characteristics, intraop-
erative management, and, perhaps most importantly,
702 CARDIOVASCULAR ANESTHESIA TUMAN ET AL. ANESTH ANALG
EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY 1991;73:h9&704

Table 6. Multivariate Predictors of Cardiovascular ated protein breakdown, increased hepatic synthesis
Complications of selected proteins (acute-phase reactants including
~ ~~~ ~

Odds fibrinogen) (26), and decreased synthesis of other

P p ratio
Variables in the equation
Congestive heart failure 0.009 3.02 20.51
General anesthesia without epidural 0.022 1.85 6.36
analgesia
Variables not in the equation
Diabetes 0.188
History of angina 0.255
History of chronic obstruchve 0.269
pulmonary disease
Age 270 yr 0.377
Previous myocardial infarction 0.400
Renal dysfunction 0.496
Estimated blood loss 0.630
Previous vascular surgery 0.680
Ejection fraction <0.4 0.689
Duration of surgery 0.719
History of hypertension 0.943
Inhainguinal revascularization 0.966
postoperative care (4,5,20). Specifically, postopera-
tive complications that occur many hours or days
after operation may be highly influenced by postop-
erative care, including the provision of better analge-
sia. The manner and extent of this influence on
postoperative morbidity that occurs temporarily sep-
arated from intraoperative events remains specula-
tive but may involve stress-modulated or direct anes-
thetic effects on the coagulation system.
In our study, patients about to undergo peripheral
vascular surgical procedures were hypercoagulable
before operation compared with control patients
without atherosclerotic vascular disease; the use of
epidural anesthesia and analgesia attenuated this
hypercoagulability postoperatively. Although we did
not measure biochemical markers of the stress re-
sponse, decreases in cortisol, renin, aldosterone, and
catecholamine levels have been associated with epi-
dural anesthesia and analgesia, especially when used
for procedures involving the abdomen and lower
extremities (4,ll-13,16,21-23). Stress-mediated in-
creases in angiotensin (secondary to higher renin
activity) and in catecholamines can increase platelet
aggregation (24,25). Reduction of the stress response
with epidural anesthesia and analgesia may indirectly
affect platelet function (16) and may be particularly
important in patients with atherosclerotic disease
who have a primary tendency to have accelerated
platelet activity. Epidural anesthesia and analgesia
may affect the coagulation state postoperatively by
attenuating the usual catabolism of proteins seen in
patients undergoing vascular reconstruction (8). The
metabolic response to stress is manifested by acceler-
proteins (such as antithrombin 111) (8). Improved
fibrinolytic activity with a larger concentration of
postoperative plasminogen activator occurs after ex-
tradural anesthesia and analgesia, compared with
general anesthesia with parenteral analgesics for
postoperative pain (14). The association of epidural
anesthesia and analgesia with reduced postoperative
stress responses (27-29) may translate to higher anti-
thrombin 111 and lower fibrinogen levels with atten-
uated platelet activity postoperatively, consistent
with the thromboelastographic findings in this study.
The effects of epidural anesthesia and analgesia on
coagulation are complex, and elucidation of the exact
mechanisms by which epidural anesthesia and anal-
gesia attenuate accelerated postoperative coagulabil-
ity in patients undergoing vascular reconstruction
will require further study.
The influence of epidural anesthesia and analgesia
on coagulation may have important clinical conse-
quences. Our data support the hypothesis that accel-
erated coagulability may be associated with throm-
botic events in coronary arteries and in peripheral
vascular grafts. Although the utility of thromboelas-
tography as a coagulation test remains controversial,
primarily because of its relatively nonspecific charac-
terization of the hemostatic process, this study sup-
ports the use of thromboelastography as a useful
biologic marker for accelerated coagulability in this
high-risk population. As used in this study, throm-
boelastography does not allow differentiation of the
exact coagulation mechanisms that are altered after
major vascular surgery. The data do suggest that
monitoring the coagulation state, especially platelet
activity, may identify patients who would benefit
from postoperative therapy such as antiplatelet drugs
or other forms of anticoagulation.
Effects on coagulation probably reflect only one
possible mechanism by which epidural anesthesia
and analgesia may modulate outcome in high-risk
patients undergoing vascular surgery. Blood flow in
the legs of patients with occlusive atherosclerotic
disease is increased after epidural anesthesia (30).
This effect may be enhanced when postoperative
epidural analgesia includes a dilute solution of local
anesthetic to maintain some degree of sympathetic
block after arterial reconstruction and may have con-
tributed to improved short-term graft patency in
those patients receiving epidural analgesia in this
study.
In addition to the effects on coagulation and vas-
cular graft patency, a lower total number of com-
plications, shorter duration of ICU stay, fewer
infections, and a trend toward fewer respiratory
ANESTH ANALG
1991;73:69&704 EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY
complications (manifested as a lower incidence of
prolonged tracheal intubation and respiratory infec-
tions) were observed in the patients who received
epidural anesthesia and analgesia. Previous findings
of shorter duration of ventilatory support and ICU
stay in patients receiving postoperative epidural an-
algesia have been questioned because of the inclusion
of high-dose opioid anesthesia in the nonepidural
group (4).A strength of the current study is the
confirmation of these findings in the absence of this
potentially confounding factor. Despite the use of
general anesthesia techniques with differing effects
on the neuroendocrine response to surgical stress,
these data and those of Yeager et al. (4) both demon-
strate that epidural anesthesia and analgesia is asso-
ciated with a beneficial effect on postoperative mor-
bidity. These findings suggest that any potential
benefits of epidural anesthesia and analgesia may be
related more to postoperative rather than intraoper-
ative influences. Several mechanisms may explain the
latter effects of epidural anesthesia and analgesia:
better analgesia, decreased duration of endotracheal
intubation and mechanical ventilation which dimin-
ish pulmonary defense mechanisms against infec-
tion, longer duration of postoperative ICU stay which
is associated with a higher risk of nosocomial infec-
tions, and better maintenance of postoperative im-
munocompetence (31). Our study design does not
allow us to confirm or refute these hypotheses but
does reconfirm the beneficial effects of a combination
of general with epidural anesthesia and analgesia
compared with general anesthesia with routine post-
operative pain management on several aspects of
outcome (4).
The major goal of this study was to compare the
use of combined general-epidural anesthesia and
continuous epidural analgesia with a specific general
anesthetic technique followed by the on-demand,
intermittent administration of opioids for postopera-
tive analgesia. No attempt was made to provide equal
degrees of postoperative analgesia in the study
groups, but rather, these modalities were compared
as to how they would commonly be used in clinical
practice. As a consequence, to avoid confounding
influences on the administration of and response to
intermittent, on-demand analgesia as it is usually
administered, these patients were not visited by a
member of the acute pain service. In contrast, an
essential standard of postoperative epidural analgesia
is the involvement of an acute analgesia service that
frequently evaluates patients to assess the efficacy of
analgesia, to ensure the use of supplemental analge-
sic medications, and to evaluate and treat side effects
such as pruritus and nausea. The excellent pain
scores in the epidural analgesia group attest to the
efficacy of the epidural analgesia service in these
CARDIOVASCULAR ANESTHESIA TUMAN ET AL. 703
high-risk patients. Although pain scores were inten-
tionally not obtained in the GEN group to avoid
altering the intrinsic nature of intermittent, on-
demand pain control and other aspects of these
patients care, it is very likely that the analgesia was
less than that observed in the epidural group. The
current study design does not allow confirmation or
rebuttal of the hypothesis that improved outcome in
the setting described may have been related primarily
to different degrees of postoperative analgesia.
Rather, it confirms earlier findings that epidural an-
esthesia and analgesia, used in the manner de-
scribed, is associated with better outcomes compared
with on-demand, intermittent opioid analgesia. Al-
though plausible, it seems unlikely that visitation by
acute pain service personnel of those patients not
receiving epidural analgesia after major vascular sur-
gery could result in similar improvements in out-
come, as analgesia would still remain intermittent.
Further studies will be required to clarify whether
other forms of analgesic therapy, such as patient-
controlled analgesia with or without continuous opi-
oid infusions, will also be associated with similar
outcome differences. Defining the relative contribu-
tion of effective analgesia per se, neuraxial sym-
patholysis, improvements in lower extremity blood
flow, and reduction in hypercoagulability to clinical
outcomes will also require further studies to deter-
mine the precise mechanism(s) by which epidural
anesthesia and analgesia may be related to these
findings. Because our study was designed as an
observational critique of the clinical outcome of two
methods of perioperative anesthetic management,
interpretation of the findings is limited in that specific
mechanisms were not sought to explain the inter-
group differences.
Although previous data have suggested an effect
of epidural anesthesia and analgesia on postoperative
mortality in high-risk patients (4),we are not able to
confirm or refute these findings as no in-hospital
mortality was observed in this study. Differences in
surgical populations, sample sizes, and patient man-
agement may be responsible for differences in the
incidence of mortality in different studies. Our data
do, however, confirm that preoperative congestive
heart failure is a significant predictor of adverse
cardiovascular outcome in high-risk patients under-
going noncardiac surgery ( 3 ) .
Despite the levels of significance of our major
findings, an important limitation of this investigation
is the small number of patients assigned to each
anesthetic group. Although univariate and multivari-
ate statistical analysis failed to detect any significant
bias against those patients assigned to the GEN
group, there may have been unquantifiable differ-
ences between the randomized anesthesia groups. In
704 CARDIOVASCULAR ANESTHESIA TUMAN ET AL.
EPIDURAL ANESTHESIA AND ANALGESIA FOR VASCULAR SURGERY
addition, a very select patient population was exam-
ined, so that the results of this study may not be
generalizable to patient subsets undergoing different
surgical procedures.
In summary, we have demonstrated that patients
with atherosclerotic occlusive vascular disease are
hypercoagulable to patients*and that
the use of epidural anesthesia and analgesia attenu-
ates this hypercoagulability after lower extremity
revascularization. The use of general anesthesia
bined with epidural analgesia using dilute solutions
of local anesthetic and narcotic is associated with
improved outcome compared with general anesthesia
and routine, on-demand narcotic analgesia for major
peripheral vascular surgery.
The authors thank Elizabeth R. Corey, RN, and Sharon Grande,
for their assistance in data collection.
References
1. Hertzer NR. Fatal myocardial infarction following abdominal
aortic aneurysm resection: 343 patients followed 6-11 years
postoperatively. Ann Surg 1980;192:667-73.
2. Hertzer NR. Fatal myocardial infarction following lower ex-
tremity revascularization: 273 patients followed 6-1 1 postop-
erative years. Ann Surg 1981;193:492-8.
3. Goldman L, Caldera DI., Nussbaum SR, et al. Multifactorial
index of cardiac risk in noncardiac surgcal procedures. N Engl
J Med 1977;29784550.
4. Yeager MP, Glass DD, Neff RK, Brinck-Johnsen T. Epidural
anesthesia and analgesia in high-risk surgical patients. Anes-
thesiology 1987;66:729-36.
5. Manolio TA, Beattie C, Christopherson R, Pearson TA. Re-
gional versus general anesthesia in high-risk surgical patients:
the need for a clinical trial. J Clin Anesth 1989;1:414-21.
6. Meade TW, Mellows S, Brozovic M, et al. Haemostatic func-
tion and ischemic heart disease: principal results of the North-
wick Park Heart Study. Lancet 1986;ii:53>7.
7. Trip MD, Cats VM, vancapelle FJL, Vreeken J. Platelet hyper-
eactivity and prognosis in survivors of myocardial infarction.
N Engl J Med 1990;322:1549-54.
8. Flinn WR, McDaniel MD, Yao JST, Fahey VA, Green D.
Antithrombin 111 deficiency as a reflection of dynamic protein
metabolism in patients undergoing vascular resconstruction.
J Vasc Surg 1984;1:88%95.
9. McDaniel MD, Pearce WH, Yao JST, et al. Sequential changes
in coagulation and platelet function following femorotibial
bypass. J Vasc Surg 1984;1:261-8.
10. Naesh 0, Friis JT, Hindberg I, Winther K. Platelet function in
surgcal stress. Thromb Haemostasis 1985;54:849-52.
11. Rutberg H, Hakanson E, Anderberg B, Jorfeldt L, Martensson
J, Schildt 8 . Effects of the extradural administration of rnor-
phine, or bupivacaine, on the endocrine response to upper
abdominal surgery. Br J Anaesth 1984;56:2334.
12. Christensen P, Brandt M, Rem J, Kehlet H. Influence of
ANESTH ANALG
1991;73.69&704
extradural morphine on the adrenocortical and hyperglycae-
mic response to surgery. Br J Anaesth 1982;43:23-7.
13. Kehlet H, Brandt MR, Prange-Hansen A, Alberti KFMM.
Effects of epidural analgesia on metabolic profiles during and
after surge&. Br J Surg-1979;66:5434.
14. Modig J, Borg T. Bagge L, Saldeen T. Role of extradural and of
general anesthesia in fibrinolysis and coagulation after total
hip replacement. Br 1 Anaesth 1983;55:625-8.
15. Borg T, Modig J. Potential antithrombotic effects of local
anaesthetics due to their inhibition of platelet aggregation.
Acta Anaesthesiol Scand 1985;29:73942.
16. Nielsen TH, Nielsen HK, Husted SE, Hansen SL, Olsen KH,
Fjeldborg N. Stress response and platelet function in minor
surgery during epidural buyivacaine and general anesthesia:
effect of epidural morphine addition. Eur J Anaesthesiol 1989;
6:409-17.
17. Spiess BD, Tuman KJ, McCarthy RJ, DeLaria GA, Schillo R,
Ivankovich AD. Thromboelastography as an indicator of post-
cardiopulmonary bypass coagulopathy. ] Clin Monit 1987;3:25
30.
18. Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD. Effects of
RN,
progressive blood loss on coagulation as measured by throm-
belastography. Anesth Analg 1987;66:85&63.
19. Haviland MG. Yate's correction for continuity and the analysis
of 2 x 2 contingency tables. Stat Med 1990;9:363-83.
20. Cook IT,Davies MJ, Cronin KD, Moran P. A prospective
randomized trial comparing spinal anesthesia using hyperbaric
cinchocaine with general anesthesia for lower limb vascular
surgery. Anaesth Intensive Care 1986;14:37340.
21. Brandt MR, Olguard K, Kehlet H. Epidural analgesia inhibits
renin and aldosterone response to surgery. Acta Anaesthesiol
Scand 1979;23:267-72.
22. Engquist A, Brandt MR, Fernandes A, Kehlet H. The blocking
effects of epidural analgesia on the adrenocortisol and hyper-
glycemic responses to surgery. Acta Anaesthesiol Scand 1977;
21 :330-5.
23. Engquist A, Fog-Moller F, Christiansen C, Thode J, Anderson
T, Nistrop-Madsen S. Influence of epidural analgesia on the
catecholamine and cyclic AMP response to surgery. Acta
Anaesthesiol Scand 1980;24:17-21.
24. Ardlie NG, Cameron HA, Garrett J . Platelet activation by
circulating levels of hormones: a possible link in coronary heart
disease. Thromb Res 1984;36:315-22.
25. Uza G, Crisnic I. Effects of angiotensin I1 upon platelet adhe-
siveness and the thrombelastogram in patients with essential
arterial hypertension. Pathol Eur 1975;10:327-32.
26. Weissman C. The metabolic response to stress: an overview
and update. Anesthesiology 1990;73:30&27.
27. Simpson PJ, Radford SG, Lockyer ]A. The influence of anaes-
thesia on the acute phase protein response to surgery. Anaes-
thesia 1987;42:69M.
28. Brandt MR, Fernandes A, Mordhorst R, Kehlet H. Epidural
analgesia improves postoperative nitrogen balance. Br Med J
1978;l :I 106-8.
29. Christensen T, Waaben J, Lindeburg T, Vesterberg K, Vinnars
E, Kehlet H. Effect of epidural analgesia on muscle amino acid
pattern after surgery. Acta Chir Scand 1986;152:407-11.
30. Haljamae H, Frid I, Holm J, Akerstrom G. Epidural versus
general anesthesia and leg blood flow in patients with occlu-
sive atherosclerotic disease. Eur I Vasc Surg 1988;2:395.400.
31. Hole A, Unsgaard G. The effect of epidural and general
anaesthesia on lymphocyte functions during and after major
orthopaedic surgery. Acta Anaesthesiol Scand 1983;27:13541.