Escolar Documentos
Profissional Documentos
Cultura Documentos
Priorities in Therapeutics
HENRI BISMUTH M.D., HENRI KUNTZIGER M.D.,* MARVIN B. CORLETTE M.D.t
881
tFormerly
at
J. Hepp).
882
~E
co
XE
.,
Ann.
E c
Surg..
00
IT
E0
.
E.o
c_
<~~~~~~~~~~~~~
4)
%O~~~~~~~~~~~~~~~
L4
.10
C4
'unur
t~~~1
00z
(bluOOT/&u)I
ulu.IUf3/Nflf
00
r4
00
W) (O
00
roen
~0
0D
It
et)
0)4
0t
0j
4)li
C.)3
0:
I..
0II
to
(sAvp) aJnJIed
Igual aioug
UO!puJp sisdaS
(Z
_-
oslnwedsoqd
au!)f
0s
t
1-4
'Itt
_.4
00
'-
*
*
C#)
ri4
WI
~~~~~~~00
xH
(1lUO01/w)
uiqruqig
.a +
V.
C-)
=+
ApleXawowdOH
"
06
r-
en
I"
sl:
en
'IT
C14
C)
es4
(a)
0oo
en
~~~~oR
+
+
++
'lOOMs
a.injInD
OG
c,
wunoD
IIaD aIR
Cu
0t
@X
Z0,
,8
rq
:alnsqo
"E 0 0
0,
4V()
00
I"
00
oo
0,
4-a 4.0
N-
Cu
4)
jo ainlWN
00
00
00
0--
4) cu
r--
-.J
ed
0,
.E
oo
0,
0
~~~~~~~~~~IL
c0%
Oc
N-
VD
el
4n
1en
0,
0
N-
n
all
t-
00
ZC
June 1975
~~~~~~~~~~~4)4)4)
2)
, co
0l0
01
u)
U<
U! <
_~
N-
0%
-~
I"
00
cn
.E
r.0
4t k
0,
<U
10
%
O-
%x
Nl
0
I
" 0I "
+.0.)-e
0
$t M 0"M0 2!"
; " ".,
I r. 0 , r.
.
gt k
883
Sepsis
1-
00
I"
00
'.
"I,
00
V,~
*.a
0
eq
*'1t
0
00
00
mI
e4
0%
0L
,
*
0.,
0
00
O0
0% ,
t
0
0o
I,.
0
_c
0
4)-i
t,.
I"
c
4)
0,o
._
._C
E
0
*0._
0
0
00 e=
C)
X8
8
00
c
Wi
8 0 0 ~~~'
8 8
a4
oe .&
ig'
02~~~~~~~~~~~~0
00
Q0
o.
o
N
Biliary Obstruction
The obstruction of the common duct was of two principal etiologies: lithiasis (13 patients), and tumor of the
ampulla of Vater (4 patients). Other tumors about the
vo^~~~~~~I
o
oo
o
884
TOTAL
SERUM
Ann.
Surg.- June
1975
BILIRUBIN
LO- CONCENTRATION
210
mg.100 ir-1
1800
150-
y=1Ox+82-6
=20* r =0 31 NS
120-
*
0 *
0
0
0
90-
available)
60-
301
I1
30-
20-
were not
10
20
sessed
10-
Renal Insufficiency
Twenty patients gave no previous history of renal disease. In one patient there was previous mild chronic
impairment of renal function which was aggravated by
the cholangitis, with renal function diminishing by more
than half, then returning to the previous baseline.
Anuria or oliguria was recorded in 12 patients (urine
output less than 500 ml per 24 hours). Nine patients had
high output renal failure, characterized by a urine urea to
plasma urea ratio (U/P) of less than 8, associated with a
high urinary sodium. The renal problem appeared
promptly (within 48 hours) after the onset of pain and
fever in eleven patients; in the remainder it was
documented later, generally during the second week of
illness. The onset of renal failure coincided with chills or
elevation of temperature above 39.in all patients except
one, and coincided with shock in 9. No patient had
undergone operation before the onset of renal failure.
The severity and duration of the renal disorder was
quite variable. Patients have been arbitrarily classified
into 3 groups of mild, moderate, and severe renal failure,
defined according to the following criteria: 1) oliguria or
anuria (urine volume less than 500 ml per 24 hours); 2)
necessity for dialysis; 3) BUN of 100 mg/100 ml or greater; 4) plasma potassium of 5.0 mEq/litre or over; 5)
plasma bicarbonate of 20 mEq/litre or less. Patients
exhibiting one or none of these 5 features were classified
as having mild renal failure; with more than one but less
than four, moderate; and with 4 or 5 of the criteria, as
severe. Only 17 patients could be classified because data
was not complete for 4 patients seen early in the series.
Thus defined, 6 patients had mild renal failure, 2 severe,
and the remainder moderate.
Six patients underwent preoperative dialysis; 3
peritoneally and 3 by hemodialysis. Four of these patients required dialysis both pre- and postoperatively.
Two patients were dialyzed in the postoperative period
only. In survivors the renal function eventually returned
to pre-illness levels.
series
MILD
MODERATE
(N-6)
(Nu 9)
were not
available.
SEVERE
(No 2)
Results of Treatment
Two patients died in shock within a few hours of their
arrival. One patient refused operation. This left 18 patients for evaluation of therapy. All patients were given
vigorous fluid replacement, including blood and plasma
as needed, and furosemide if urine output was low. All
patients were given antibiotics. All of the 18 patients
underwent surgical exploration. The outcomes of therapy
are presented in Table 2.
The first 3 patients, treated early in our experience,
were managed following the then-current doctrine of
emergency operation. In one of these patients, the course
after rehydration and antibiotics was followed for several
hours; as soon as temperature and urinary output returned to normal, operation was performed. All 3 of these
patients died.
The 15 subsequent patients were observed longer
under the influence of fluid and antibiotic therapy. Four
outcomes were seen. In two patients the infection persisted (cases 7 and 8). Both underwent emergency
hemodialysis, then were operated on and both survived.
The second course was seen in two patients (cases 9
Vol. 181-No. 6
Therapeutic Attitude
Emergency Operation:
(cases 4-6)
No. of Patients
Survivors
Deaths
3
Delayed Operation:
1. Sepsis Continues:
2. Improvement,
Then Relapse:
Urgent Operation
(cases 9-10)
3. Improvement:
Operation After
Renal Recovery
(cases 11-17)
4. Improvement,
But Other Major
Organ Failure
(cases 18-21)
Emergency Dialysis
Then Operation
(cases 7-8)
antibiotics but in whom other major organ failure supervened (i.e. cardiac, neurologic).
In one of these 4 (case 18) gastrointestinal hemorrhage
developed requiring emergency operation after dialysis;
this patient survived. Another (case 21) was operated for
recrudescent sepsis in coma after several cardiac arrests
and eventually died of cardiac causes. The remaining two
died postoperatively, one from cardiac failure, and one,
in whom choledochoduodenostomy was performed, from
diffuse hemorrhage associated with a blood clot blocking
the anastomosis. The occurrence of other major organ
failure in these patients, even though they were improving in terms of their sepsis, created a disparate group in
whom the choice and timing of operative biliary drainage
was
885
difficult.
Discussion
The selection of patients for this study may seem unnecessarily restrictive. Patients with sepsis and jaundice
in whom a biliary obstacle was not proven have been
eliminated because the absence of demonstrable biliary
obstruction raises a question as to the validity of the
diagnosis. Other lesions, e.g., the jaundice of septicemia
or leptospirosis, can cause a confusingly similar picture.
This requirement almost surely excluded patients with
true cholangitis but in whom the obstacle, e.g., a stone,
had passed spontaneously. Only when it is certain that
one is dealing with a single clinical entity can appropriate
conclusions be drawn regarding its evolution and treatment. Likewise, the presence of any factor that might,
alone, be related to renal insufficiency, such as acute
pancreatitis or sepsis outside the biliary tract, caused
elimination of the patient because the relationship of
biliary retention to the renal failure is then obscured.
Since the postoperative state introduces a variety of factors which can influence renal function, only patients
with preoperative renal failure were included.
The presence of cirrhosis, even the secondary biliary
type, similarly would not allow evaluation of the pure
syndrome.
The etiology of cholangitis with renal failure is primarily lithiasis, followed by ampulloma, as noted by Caroli.4
These causes of biliary obstruction, frequently partial or
intermittent, are most often complicated by sepsis, in
contradistinction to tumors of the pancreas and bile duct
which rarely become infected, as noted by Sherlock and
others.5'20 In this series, ampullomas occurred in younger
males, without previous biliary disease, in contrast to the
typical picture of lithiasis, occurring predominantly in
elderly females with months, sometimes years, of prior
biliary troubles.
Renal failure is occasionally associated with many diseases that produce jaundice. Although the term
"hepato-renal syndrome" was originally coined by
Merklen in 191517 in considering a case of cholangitis with
886
In our patients the onset of renal insufficiency coincided in every case with an infectious state including
shaking chills, and the clinical and laboratory findings
were the same as those described in the tubulopathy
occurring in septic settings without hepato-biliary disease.'4 "8 There was no significant correlation between
degree of bilirubinemia and the gravity of the renal failure, and in several cases the renal lesion improved spontaneously with clearing of infection but without change in
the bilirubin level.
The responsibility of biliary retention, particularly of
conjugated bilirubin, in the production of renal failure has
been suggested."2'9'22 It appears likely that excess conjugated bilirubin renders the kidney more susceptible to
ischemic insult.9 However, in the absence of infection,
such acute renal failure does not occur, even in extreme
degrees of biliary retention, e.g., neoplastic obstruction.3
Renal failure in these juandiced patients with suppurative
cholangitis remains a rare event and this study does not
confirm or deny that icteric patients are any more likely
to develop a renal lesion than others with sepsis. It appears that renal function can improve independent of the
serum bilirubin level.
The renal lesion occurring in obstructive cholangitis
should not be included under the term "hepato-renal
failure," nor should it be considered a special or mystical
form of kidney injury by an ailing liver. It is best considered and treated as an acute interstitial nephropathy
caused by infection-altered renal hemodynamics.
In the treatment of the three components of the syndrome of acute obstructive cholangitis with renal failure,
the infectious element is predominant. In contrast to the
experience of Glenn and Moody, Reynolds and Dargan,
and others,'2"9'20 our experience shows that the sepsis is
not routinely refractory to antibiotic therapy.
Either signs of sepsis regress, or infection persists or
worsens. In the latter case emergency operation is indicated. When sepsis continues, the renal and metabolic
status is evaluated, and if renal failure is moderate or
severe, hemodialysis should be undertaken before operation. We have selected as indications for dialysis a serum
potassium of 5.5 mEq/l or greater, BUN over 100 mg/100
ml or acidosis with a serum bicarbonate less than 15
mEq/l. Some patients exhibit an extremely rapid rate of
change in these metabolic measurements and this should
be taken into account, sometimes dialyzing for a less
severe but rapidly changing disturbance. Following such
a program, no patients have been lost due to complications of the renal failure.
In those patients who initially improve, three courses
were observed: 1) a recrudescence of the signs of sepsis.
At the first sign of returning sepsis, these patients are
managed as are patients with persistent sepsis, i.e.,
dialysis if necessary; urgent operation. 2) Continued improvement of sepsis with existence of other major organ
failure (pulmonary, cardiac, hemorrhage). The indication
for operation remains but the risk is greatly increased.
Judgment of the moment to operate is delicate, weighing
the probable evolution of the other problems against the
likelihood of recurrent sepsis. No guidelines concerning
these patients can be proposed. 3) Continued improvement of sepsis. The number of patients who maintained
improvement is striking. This may be related to spontaneous improvement in the degree of biliary obstruction
in some patients, but this does not seem to be a prerequisite. That germs are not eliminated from the bile duct by
antibiotics is demonstrated by the high number of positive bile duct cultures; one patient, after extensive antibiotherapy and regression of jaundice, still harbored 4
different organisms in his biliary tract. What deserves
emphasis is the fact that sepsis can often be controlled
allowing time for 1) the renal disorder to resolve spontaneously, and 2) the operation, always indicated, to take
place electively under ideal conditions with resultant improvement in mortality (7 survivors of 7). It thus seems to
be most desirable to abstain from operation for as long as
necessary to allow renal status to return to normal.
Operating immediately, or when temperature,
hemodynamic status, and diuresis first become normal,
has not provided encouraging results.
An additional reason for awaiting the maximum patient
improvement depends on the fact that in patients with
choledocholithiasis, cholangitis, and acute renal failure
the obstruction is most often complete, the stones frequently multiple. The stones, if multiple, may involve
the intrahepatic ducts, or a clay-like mold of the bile duct
may form (observed in two of our patients). In such
patients, the simple placement of a T-tube is evidently
insufficient. The extensive procedure of complete opening of the ducts, preferably with cholangiographic control, and frequently with bilioenteric anastomosis, is most
often required, and for this the patient must be in optimal
condition.
Stated otherwise, the moment of surgical intervention
887