Patterns of Septic Shock in Man-A Detailed Study

of 56 Patients
LLOYD D. MACLEAN, M.D., F.R.C.S.(C), WILLIAM G. MULIGAN, M.D.,
A. P. H. MCLEAN, M.D., F.R.C.S.(C), JoH H. DUFF, M.D., F.R.C.S.(C)
From the Departments of Surgery, Royal Victoria Hospital and McGill University,
Montreal, Canada

IT HAS BEEN our practice for several years

to establish a hemodynamic diagnosis for
all patients in shock. One of three possibilities is usually apparent after measuring
cardiac output, central venous pressure,
arterial blood pressure and urine output.
Two abnormalities are frequently seen: 1)
cardiogenic shock, in which state the cardiac output fails to meet the needs of the
body despite an adequate filling pressure;
and 2) hypovolemic shock, which is characterized by a low cardiac output and low
filling pressure. The third possibility is peripheral pooling, which is also characterized by a low filling pressure and a low
cardiac output but, in contrast to hypovolemia, there is a failure of sustained response of the central venous pressure and
cardiac output to volume replacement.9
As a guide to therapy and to ascertain
the severity of the shock, we have found it
useful to measure, in addition, arterial
blood lactate, P02, pCO2, pH and hematocrit.
It is the purpose of the present investigation to document from clinical observations, supported by these hemodynamic
and metabolic studies, the natural history
Presented at the Annual Meeting of the American Surgical Association, May 11-13, 1967, Colorado Springs, Colorado.
Supported by grant No. GM10438-04 from
United States Public Health Service, grant No.
DA-MD-49-193-66-G9205 United States Army,
and grant No. MT-2324 Medical Research Council of Canada.

543

of septic shock in man, to describe a syndrome seen in the early phases of septic
shock and to make suggestions for therapy
based on these experiences.
Material and Methods
Of the last 120 patients studied by a
shock team, 56 had sepsis as the clinical
cause. The patients were referred from all
departments of the hospital and were transferred to an intensive care unit for investigation and treatment. Most patients were
studied within 2 hours of the onset of
shock, but the time required to monitor
cardiac output precluded obtaining tiis
measurement before initiating treatment in
some patients with severe shock.
Clinical Procedure. Immediately after
admission to the intensive care unit, heart
rate was monitored using a MS-21 Electrodyne cardiac monitor and a #16 gauge
polyethylene needle 1.5 inches long (Buffalo needle) was inserted into the radial
artery at the wrist. The artery was not
ligated and return of the radial pulse after
removal of the needle was routine. Arterial
pressure was recorded continuously or intermittently using a No. 267-B Sanbom
transducer and a 2-channel Sanborn No.
296 portable recorder.
Central venous pressure was measured
on a simple saline manometer connected
to a 16-inch polyvinyl catheter (Sterilon)
threaded into the superior vena cava via
a 13-gauge Buffalo plastic cannula in an

Annals of Surgery
MACLEAN, MULLIGAN, McLEAN AND DUFF
544
October 1967
TABLE
1.
Syndrome of Early Septic Shock in
antecubital or cervical vein. The zero refNormovolemic Man
erence point for all pressures was 5 cm.
dorsal to the sternal angle with the patient
Hyperventilation
Respiratory alkalosis
flat in the supine position.
High central venous pressure
The cardiac output was measured by the
High cardiac index
indicator-dilution technic using indocyaLow peripheral resistance
Hypotension
nine green in a concentration of 5 mg./ml.
Oliguria
The technic used was as previously deLacticacidemia
scribed9 with the exception that a Waters
Warm, dry extremities
300X photoelectric densitometer rather
than a Gilford densitometer was used.
Calculations of total peripheral resistance albumin and of red cell volume with Cr5'
and cardiac index were made from the tagged red blood cells were done using
cardiac output, knowing mean arterial multiple samples during the equilibration
blood pressure, central venous pressure period. Changes in plasma volume were
and body surface area. Recently, patients thereafter followed by serial measurements
with low cardiac indices (below 3 L./min./ of hematocrit if no evidence of blood loss
M.2) have had cardiac output measured existed.
also by the Fick technic after advancing
Results
the central venous pressure catheter into
The 56 patients fell conveniently into
the right ventricle to obtain the mixed venous samples. This is done to avoid the two broad groups according to whether
significant errors of the dye dilution tech- central venous pressure was above or benic when measuring low cardiac outputs.10 low normal prior to treatment. They were
The pH, P02, and pCO2 were measured further subdivided according to arterial
using an IL micro pH and gas analyzing blood pH into those who were alkalotic or
system (Instrumentation Laboratory Inc., normal and those who were frankly acidotic.
Model 113-S2).
Group I-High CVP-Alkalotic or
Arterial blood lactate was measured by
Normal pH-28 patients. These patients
both the method of Barker and Summerhad a wide variety of clinical problems
son2 and the enzyme technic.
Arteriovenous oxygen differences were associated with or predisposing to septicalculated by withdrawing blood simul- cemia including septic abortion in seven,
taneously over a 5-minute period from the multiple injuries in two, pyelonephritis in
right ventricle and the radial artery in three, cirrhosis or hepatitis in three, malignant disease in three, peritonitis with
some patients. Oxygen uptake was measured during the same period in these pa- abscess in six and renal homograft rejectients. All patients had indwelling urethral tion crisis requiring large doses of cortisone
catheters and urine flow was measured at and other immunosuppressive agents in
one patient. Microorganisms recovered
hourly intervals.
Plasma volume was determined before from the blood stream or source of infectreatment was initiated and compared with tion were Gram-negative in 18, Gram-posithe estimated normal using 1131 tagged hu- tive in eight and a fungus in two patients.
All patients in whom the measurements
man serum albumin. A single sample was
taken 10 minutes after the injection and were made had a normal or elevated blood
the electronic device, the "volemetron" was volume at the onset of bacteremia. The
used. More recently, separate measure- clinical syndrome (Table 1) exhibited by
ments of plasma volume with I115 tagged these patients was easily identifiable, but

Volume 166
Number 4

545

PATTERNS OF SEPTIC SHOCK IN MAN

the truc diagnosis was frequently overlooked. Ilyperventilation was especially

valuable as an early sign of septic shock.
While frequently misinterpreted as an indication of postoperative atelectasis, pneumonia, pulmonary embolism or even myocardial infarction, this sign has prompted
earlier diagnosis recently.
Twenty-four of the 28 patients in this
group survived the shock period. Hospital
mortality was 11 of 28 due to malignancy,
extensive trauma or pneumonia. All seven
young patients with septic abortion treated
by hemodynamic support, antibiotics and
early evacuation of the uterus survived.
The average central venous pressure before treatment was 12.8 cm. of water.
Plasma volume estimation made on 20
showed an average increase above expected normal of 29%. All but two had a
pH greater than 7.46 with a group average
of 7.52.
Thirteen of the patients had positive
blood cultures at the time of investigation.
The remaining patients had strong clinical
evidence of septic shock and had a positive
culture from a likely focus. Most of the
latter were on massive antibiotic therapy
at the time of onset of the shock.
In none of the patients did the fall in
blood pressure accompany the highest peak
on the temperature chart. There was little
peripheral evidence of adrenergic activity
except at the height of the temperature response. The skin was usually warm, dry
and pale when the blood pressure was
lowest.
The initial cardiac index was above normal in all patients (mean 4.1 L./min./M.2 )

but despite this there was accumulation of

lactic acid, oliguria and hypotension. Treatment was designed to increase cardiac output even further and thereby increase tissue blood flow. A summary of treatment
used and response of central venous pressure, cardiac index, urine flow, arterial
blood lactate, peripheral resistance appears
in Figure 1. Attempts to increase cardiac

HIGH C.V.P

or

NORMAL (28)

ISOPROTERENOL
BLOOD
SALINE
ANTIBIOTICS
SURGERY

BEFORE R,
pH 752
PCO2 28

P02

ALKALOTIC

AFTER 8k
pH 746
PCO2 32
P02 73

61

*STATISTICALLY

14

DIFFERENT

10

6
2

CVP CI TPR Loc. Urine

c,HD L dynes mg% rn/
2

mn

hr.

,SHOCK

/M2

MORTALITY *

DEATHS

TOA

TOTAL

4
'26

',28

FIG. 1. The central venous pressure (C.V.P.),

cardiac index (C.I.), total peripheral resistance
(T.P.R.), arterial blood lactate (Lac.), urine flow
and blood pressure before and after treatment of
28 patients with septic shock. Treatment designed
to increase C.I. even higher than its pretreatment
elevated level by use of isoproterenol, fluids and
blood significantly raised C.I., lowered arterial
lactate concentration, elevated urine output and
blood pressure.

output by infusing whole blood or saline to

further elevate cardiac filling pressure was
usually followed by a marked increase in
central venous pressure without a significant rise in blood pressure or cardiac output. Small doses of isoproterenol (2 jug./
min.) combined with blood and saline produced a prompt response in cardiac output
and blood pressure with a decline in central venous pressure and in arterial blood
lactate. This effect was frequently achieved
without changing the pulse rate and was
probably due mainly to the positive inotropic effect of this drug (e.g., Case 1).
The hyperdynamic state seen in these 28
patients was not necessarily associated with
fever, and only three of the 28 patients had
cirrhosis of the liver.
Case 1. Mrs. P. S., aged 35, (Fig. 2, 3, 4), developed severe shock associated with septic abortion and E. coli bacteremia. There was multiple
organ dysfunction probably due to disseminated
intravascular coagulation as described by Hardaway and McKay.8 At onset of illness the patient
was febrile (105 F.) and bad markedly diminished circulating platelets (10,000/cm.) and low-

Annals of Surgery
October 1967

MACLEAN, MULLIGAN, McLEAN AND DUFF

546

support despite serious multiple organ involvement of the pancreas, liver, lung, kidney, brain, skeletal muscle and gastrointestinal tract. She demonstrates the adverse
progression from alkalosis to acidosis before starting hemodynamic support.
Case 2. Patient R. E., (Fig. 5), a 26-year-old

woman, 12 weeks pregnant, was admitted to hos-

pital with shaking chills of 24 hours' duration.

Blood pressure was 110/70 mm. Hg. She passed
the products of conception believed to be a complete abortion. An infusion of Penbritin was

..-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. .. .............X:

FIG. 2. Patient P. S. developed disseminated

intravascular coagulation with low platelets and
fibrinogen and evidence of multiple organ involvement including pulmonary edema, pancreatitis
myositis, renal cortical necrosis, grand mal seizures, gastrointestinal hemorrhage and severe liver
failure.

started after blood cultures were obtained.

Two hours later her temperature was 106 F.,
blood pressure 85/45 and urine output scanty.
Blood pressure further declined to 60/30 as the
temperature fell to 1010 F. The patient was
breathless and apprehensive with warm, pale extremities. Measurements made by the shock team
were as follows: blood gases: pO2 78; pH 7.58;
pCO2 16; arterial blood lactate 34 mg./100 ml.;
blood pressure 70/40; central venous pressure 6
SEPTIC ABORTION.

(E. coli)
MRS

P S.
SEPT

TIME

8 p-

Comment. This patient with disseminated intravascular coagulation survived

after adequate drainage and hemodynamic

SEPT 21"
2 20

SEPT

1 3 30 1 4 00 5 001700 112 30 1

23A

4 30 | 5 40 1 11 00

FN.

20

20

GASES

7I2
20 r

'74%

42- ___*__
__

Pj9RIN0GEN i,i
BLn0D

pressure.

The patient stabilized with near normal lactate

and hemodynamics without support after 3 days.
Further treatment (Fig. 4) was necessary for hepatic and renal failure and consisted of exchange
transfusions and hemodialysis. The patient survived with permanently impaired renal function.

2010

1I 3004

-.
100

ered fibrinogen. As manifestations of multiple organ involvement the patient experienced grand
mal seizures, abdominal pain (pancreatitis) with
serum amylase elevation and decreased concentration of serum calcium, intestinal hemorrhage, acute
renal cortical necrosis (proven on biopsy) with
associated anuria, severe jaundice, diffuse tenderness of skeletal muscles and pulmonary edema.
The patient was treated with fibrinogen and blood
as preparation for dilatation and curettage. After
onset of shock it became necessary to use isoproterenol in addition to fluid replacement to maintain cardiac output. Even after 2 days of this support temporary withdrawal of isoproterenal resulted in a markedly lowered flow and blood

age 35

TREATMENT

__

_\_

ISOPROTERENOL

tAINE
S

8L000
SORTER

FIG. 3. Mrs. P. S. Early support of this patient

with E. coli septicemia consisted of fibrinogen and
blood and drainage of the abscess (dilatation and
curettage). The C.I. was kept above normal with
isoproterenol for 3 days. When this was stopped
transiently the cardiac index and blood pressure
fell precipitously. The patient passed from respiratory alkalosis to metabolic acidosis before hemodynamic support was started and this after drainage of the abscess.

Volume 166
Number 4

PATTERNS OF SEPTIC SHOCK IN MAN

of water; cardiac index 3.75 L./min./M.2;

volume 3,225 ml.; withl estimated normal
2,550. Hematocrit was 33, sertum sodium 133
mEq. and potassium 2.8 mEq.
The patient received a saline infusion and antibiotics and within 2 hours the blood pressure rose
to 95/50 mm. Hg; the cardiac index rose to 4.1
L./min./M.2; repeat blood gas analysis showed a
PO2 of 100 mm. Hg; pH 7.49; pCO2 of 24 mm.
Hg. Temperature remained at 1010 F. and urine
output was slightly improved at 30 ml./hr.
Whole blood was infused in order to increase
the cardiac filling pressure, but contrary to the
expected response, as the central venous pressure
rose to 12 cm. of water, the blood pressure declined to 80/40 mm. Hg and cardiac index to 6.0
L./min./M.2. Isoproterenol added to the infusion
resulted in a prompt rise in blood pressure to
100/50 mm. Hg; cardiac index to 10.5 L./min./
M.2; urine volume 120 ml./hr. Two hours later
the lactate had dropped to 15.2 mg./100 ml.
The following morning blood pressure and
cm.

plasma

MRS. P S.
SEPTEMBER
24

22

20

28

26

30

OCTOBER
2
4

CR BUN
20

200
150

15

*/.~.
10-

-ICo

5-

-50

/A~

VOLLUE

"

1000

._

500

~~~~~~~~~~~~0
_'4IOSITlS
PYREXIA
tABORTION
e ANURIA
HYPOTENSION
4PAsMON EDEMA

CLINICAL

tD

LPYREXIA'

PANCREATITIS

HYPOCALCEMIA
-

MELENA

IGRAND MAL

4H

tPERITONEAL
DIALYSIS

*9LOOD e FIBRINOGEN
-_SUPREL

4H

HEMODIALYSIS

EXCHANGE

rYSTERECTOMY

TRANSFUSION

LDH
36002800

20o0-

12 DO

/--

T.B
IC

SGOT
\

60
120

s3o-

4) 4040
PLATELETS FIBRINOGEN
300000 60C
200000

AMYLASE

/N

-800
-600
400
-200

F400

1200

SEPTIC ABORTION.
(EE coli)
MRS',

1 L

1MS
EMP

uye 29
MAR(J5

U,

1I4bI)

MARCH

n1 8 cm
--3pmI4s6on
l| .U6
o9I

--,

0,p

MU-L

101-

MT

6 pm

8,

1966

8 pn 10 pm MIDNIGHT

98

BLOOD PRESSURE

e:2

PUJLSE

RATE

CP

4
.>
9

r-I I,2.

CI

PCO,

|B

kH

pH

40
30
20
10

GASES

,.

P-- 2

4'

,;

LACTATE

il'':

H" . S ;<!NE

BLOOD

bSOPROTEIRENOa

ISOPROT
CPERA T,ON

FIc. 5. Mrs. R. E. demonstrates a high output

form of shock associated with Gram-negative bacteremia. The C.I., blood pressure and urine output
dropped and the lactate rose on the second day of
treatment, indicating inadequate drainage. The patient was supported with isoproterenol and complete drainage performed following which the patient recovered uneventfully.

L\ RiNE

0-

TREATMENI

547

-----------

*0

FIG. 4. Mrs. P. S. Long-term support for the

complications of septicemia included: hemodialysis

(H), peritoneal dialysis, exchange transfusion for

liver failure, and late hysterectomy. The patient
survived with permanently unp aired renal function. Note marked elevation of L.D.H. and total
bilirubin (T.B.).

urine volume

were

maintained without the

sup-

port of isoproterenol. However, by the same evening, blood pressure again declined to 60/35 and
urine volume to 20 ml./hr. Extremities were cool

and slightly cyanosed. Repeat blood gas analysis

showed pO2 of 80 mm. Hg; pH of 7.41; pC02 of
31 mm. Hg. Lactate had again risen to 27.5 mg./
100 ml. Growth from a blood culture made 24
hours earlier was E. coli only moderately sensitive to Penbritin. Isoproterenol was restarted and
promptly restored blood pressure to 110/50, cardiac output to 10.8 L./min. She was taken immediately to the operating room for evacuation of
the uterus and subsequently recovered.

Comment. This patient with septic shock

due to E. coli bacteremia from an incomplete abortion showed the syndrome of
high cardiac output, alkalosis, hypotension,
lactic acidosis, and increased blood volume.
The recurrence of shock after successful
hemodynamic support indicated that surgical drainage was incomplete. The patient
responded promptly to complete drainage
of the septic process.
Group II-High Central Venous Pressure-Acidosis-11 Patients. The 11 pa-

ACIDOSIS (11)
ISOPROTERENOL
BLOOD
SAL INEr
SODIUM
BNEARS.
RESPIRATOR

edly elevated arterial blood lactate (92

ml.) indicated/po
m-g./100
poor or ineffective
C,
..
.
tissue perfusion
or impaired
oxygen uti-

HIGH cMvP -

DIGITALIS

BEFORE 13L
pH 721
PC02 31

P02

AFTER

HYDROCORTISONE
ANTIBIOTICS

F,

pH 7.29
PCO2 39
94

BEXCHANGETRANS11 PD2
DIBENZYUNE
_ 14
DIF eRENT

63

16

*STATISTICALLY

13

12
.92

79/44

61
4.3 _

HIVE

jmmLCVP Cl TPR Loc Urine BP

L
,y,es mg ,,m

cmRH20

'B2

MORTALITY

93/S
|
*

CVP CI TPR Loc. Brine P

TA
DEATH TOTAL
DA

FiG. 6. The response eto treatment in 11 Patients who presented Mvith high central venous
pressure and acidosis. De spite a high output which

could not be raised, the patients continued to accumulate lactic acid and 10 of 11 died in shock.

tients in this

group Nwere much less fortuOnly one of 1 1 survived the shock

period. The onset of shock was insidious.
Hyperventilation, res,tlessness, tachycardia
and a diminished urinary volume were the
signs which frequently drew attention to
the septic process. Hypotension was a late
feature. Initial blood gas analysis showed
hypoxemia, acidosis and a marked lacticacidemia. Average central venous pressure was 13 cm. of water. Although tentative clinical diagnosis was frequently pulmonary embolism, radiological examination often revealed pulmonary edema.
Blood cultures were obtained late, in some
not until death was imminent or had occurred. Ten of the 11 patients had a positive blood culture. In nine the organism
was Gram-negative and highly resistant, in
one Staphylococcus aureus and in one
Candida albicans.
Early hemodynamic studies did not predict the fulminating course of the septic
process. Cardiac index was often markedly
elevated, the average for the group being
4.2 L./min./M.2. Peripheral resistance was
usually strikingly reduced. However, despite the existence of a high flow state, and
warm, pale extremities, oliguria and mark-

nate.

Annals of Surgery
October 196 7

MAcLEAN, MULLIGAN, McLEAN AND DUFF

548

lization.

All patients in this group were vulner-

able

to sepsis and1.in most the focus was

not amenable to surgical drainage. Clinical diagnoses included severe burns, cirrhosis, renal homograft, mesenteric occlusion and pneumonia. While these patients
were seen early by usual standards, there
iS much clinical evidence to suggest that
they may have passed through the alkalotic phase. Hyperventilation and restlessness were observed by the nursing staff
for a considerable time prior to investigation and diagnosis.
All attempts to further enhance cardiac
output failed. The existing high flow state
did not meet metabolic requirements and
lactate continued to accumulate. A summary of therapy instituted and response
appears in Figure 6.
Case 3. Patient R. B. (Fig. 7), a 33-year-old
man was under treatment for burns involving 25%
of the body surface. During the early hours of the
fourth day,

sudden drop in hemoglobin to 11.3

JUNE

71ME

900am

(L/M2/m,nj

1, 1966

12 O0noon

OOpm

600 pm

9 00 pm

96

8 94

74

17

22

22

16

rn
BP(m

00.

'60

9448

92,
50

76X44

6434

PR

36

140

40

28

126

45

30

CVP (CmH20)

JRANE (c
BUFFER BASE
HEMATOCRIT

P02
PCO2
pH

C0

-18

40
28 5

22

L6
45

53 c

28
7 36

29 2

C N

129 3

5 6
7 04

IC3 29

5 65

ANT C4,0- -S
VA % % 1-

54 8

i7
7
IIC 2

LACTATE
PYRUVATE
TREATMENT 6

CARDIAC
ARREST

5 57

6H
I 3EN0-AVHTIN

:52 43
6 IC

VOHCC,

NoHCO,

FiG. 7. Mr. R. B., age 33-severe bum with

Gram-negative septicemia. Despite the very high
cardiac index, the patient continued to accumulate
lactate and was refractory to all treatment. It was
possible to maintain adequate oxygen tension in
arterial blood and a high flow rate.

Volume 166
Number 4

Gm. occurred followed shortly by an increase in

from 1010 F. to 1050 F. Tachypnea
was noted, but otherwise physical examination
was negative. Blood cultures were obtained and
Penbritin later added to the antibiotic regimen.
Four hours later, a chest x-ray revealed diffuse
opacification compatible with massive edema or
pneumonia. Blood pressure was 100/60, respiration 45/min., pulse 160 and urine output had declined to zero. The skin was warm, pale and dry.
Hemodynamic studies showed a central venous pressure of 22 cm. of water, and the cardiac
index 9.2 L./min./M. Blood gas analysis retemperature

TIsa

lactic acid was 110 mg./100 ml. Total blood volume was estimated to be 7,100 ml. with a normal
of 5,600 ml.
Because of pulmonary edema and high cardiac
rate, digitalis was administered and phlebotomy
performed, until the central venous pressure declined to 15 cm. of water. In addition, the patient
was given respiratory support with 100% oxygen
and attempts were made to correct the acidosis
with large quantities of sodium bicarbonate. In
spite of these efforts cardiac index declined to 7.4
L./min./M.2 and blood pressure to 76/44 mm. Hg.
Repeat blood gas analysis showed pO2 139 mm.
Hg; pH 7.04; pCO2 41.6 mm. Hg. Other measures,
including steroids in pharmacologic doses and
Gentamycin failed to halt rapid deterioration. At
the time of death, 8 hours after the onset of shock,
the arterial blood lactic acid was 155 mg./100 ml.
Autopsy revealed massive pulmonary congestion and edema with pyelonephritis and septicemia
due to a resistant strain of Aerobacter aerogenes.

Comment. This patient with septicemia

caused by a highly resistant organism probably of renal origin, died of pulmonary
edema. Response to the infection was a
marked increase in cardiac output and hyperventilation which failed to maintain
normal pH in the face of metabolic acidosis. It is likely that a direct effect of the
bacteria on pulmonary capillaries causes
the pulmonary edema seen in this type of
shock. Increased plasma volume is probably due to loss of indicator from the vascular space due to capillary damage.
Case 4. Patienit G. M. (Fig. 8), a 38-year-old
alcoholic, with cirrhosis, deep coma and
gastrointestinal bleeding, was referred to
the shock unit for management. Blood pressure

&

40p

ota5 swa
7

n-cornC

CENRL VEOUS FASM

as BLOOD FRASP f

RATE

CIL

vealed severe hypoxia and metabolic acidosis: PO2

40 mm. Hg; pH 7.12; pC02 33 mm. Hg. Blood

man,
upper

549

PATTERNS OF SEPTIC SHOCK IN MAN

40

SUFFER BANSE

10
t0

N20

0
i4

APin.

Poi

:5Ft
'sot
imm

lu.

10

--4

-..i
X1

bm
It
..
P
__t

FIG. 8. Mr. G. M.-a 38-year-old cirrhotic

with high output failure and acidosis. Please see
text.

had remained stable although urine volume was

markedly diminished. Two units of blood and
12.5 Gm. of mannitol had been administered.
On admission to the intensive care unit, blood
pressure was 120/78 mm. Hg, pulse 120 and respiration 44 per minute. The skin was warm, dry
and pale.
Metabolic studies revealed profound acidosis
with the following values: pH 7.17; pC02 14.5
mm. Hg; base deficit -23 mEq./L. Arterial blood
lactate was 192.9 mg./100 ml. Hemodynamic studies showed a central venous pressure of 12 cm. of
water and a cardiac index of 6.6 L./min./M.2.
After large quantities of sodium bicarbonate had
been administered the pH was 7.29 and base deficit -15 mEq. millimols/L. The serum sodium was
now 157 mEq./L.; potassium 4.6 mEq./L.; blood
sugar 72 mg./100 ml.
Gastric cooling resulted in a decline in body
was no further evidence of bleeding. Administration of tris buffer
resulted in further correction of pH to 7.38 and
base deficit to -6 millimols/L. Cardiac index was
now 7.3 L./min./M.2 but blood pressure had declined to 60/30. The pO2 remained at 71 mm. Hg,
btit repeat blood lactic acid remained elevated at
197.3 mg./100 ml.
The subsequent course was one of steadily increasing deterioration despite respiratory support,

temperature to 940 F. There

MAcLEAN, MULLIGAN, McLEAN AND DUFF

550

tonitis. The low central venous pressure reflected a loss of circulating volume prior to
the onset of bacteremia. Hematocrit was

LOW C.VP - ALKALOTIC or NORMAL (10)

BLOOD
SALI NE
ISOPROTERENOL
BEFOREFtz
k
BEFORE

SURGERYAFE
ANTIBIOTICS

AFTER
pH 7.41
PCO2 31
PO2 120

pH 7.41
PCO2 28
P02 73

* STATISTICALLY
DIFFERENT

1377

14

*:11

12
10
B
6
4
2

59

950

*
3

Ff

41

CVP CI TPR Loc Urine B P

cmH20

CVP C TPR Loc. Urine BP

LA5 dynes mg% ml/

/M2

MORTALITY

SHOCK

TOA

DEATH

TOTAL

10

Annals of Surgery
October 1967

5/

FIG. 9. Summary of 10 patients who presented

with a low central venous pressure and alkalotic
or normal pH. Volume replacement with added
cardiac support significantly elevated central venous pressure (C.V.P.), cardiac index (C.I.),
urine output and blood pressure, and significantly
lowered the arterial blood lactate and total peripheral resistance. One of 10 patients died of
shock.

isoproterenol and pharmacologic doses of steroids.

Death occurred 16 hours after admission. Postmortem blood cultures showed a heavy growth of
Aerobacter aerogenes.
Autopsy studies confirmed the diagnosis of cirrhosis with esophageal varices and there was massive pulmonary congestion with edema.

Comment. Patients with cirrhosis are

vulnerable to infection. The precipitation
of bleeding from varices may be linked to
infection because of the great increase in
cardiac output. This patient in all likelihood passed through a phase of alkalosis
but the blood pressure remained within
the normal range long after the patient
had passed into a refractory state of acidosis. Patients with a hyperdynamic circulation who have become acidotic respond
very poorly to circulatory support. Pulmonary edema is a prominent feature, and at
this time not susceptible to treatment. A
focus to drain was not apparent in this
patient.
Group III-Low Central Venous Pressure-Alkalotic or Normal-10 patients.
Seven of the 10 patients in this group had
bowel obstruction with infarction and peri-

high in those presenting early in keeping

with the rapid isotonic fluid loss invariably
associated with bowel obstruction.
Hemodynamic features were influenced
by the change in blood viscosity. Total peripheral resistance was raised, the average
being 1,377 dynes/sec./cm.-5. Cyanosis was
frequently noted and there was usually
evidence of adrenergic activity. Those seen
very early showed a slight alkalosis, but
more often the metabolic state was one of
fully compensated metabolic acidosis. The
average blood lactate was 41 mg./100 ml.,
with a range of 21 to 66.
Initial cardiac index was low, averaging
2.2 L./min./M.9, and improvement occurred when central venous pressure was
brought up from 3 to 8.6 by volume replacement. However, in spite of the increase of cardiac filling pressure, the blood
pressure and urine volume were not restored until an enhanced cardiac index approaching twice normal had occurred. This
was accomplished by the use of isoproterenol. A high index was maintained in
some patients following a successful surgical procedure, but in many the continued
use of isoproterenol was required for several hours following surgery.
The eight patients in whom surgical
drainage or excision was possible survived.
If hematocrit was under 40, circulating
volume was replaced with whole blood; if
over 40, saline was used. If, after restoring
cardiac filling pressure (CVP of about 10
cm. of water), the cardiac index was not
adequate to restore blood pressure and
urine flow to normal, isoproterenol was
added. In those treated successfully, arterial blood lactate, which initially was
only moderately elevated, steadily decreased to normal. A summary of treatment
and response appears in Figure 9.
Case 5. Patient E. M. (Fig. 10), a 52-year-old
woman was transferred from the gynecologic serv-

551

PATTERNS OF SEPTIC SHOCK IN MAN

Volume 166
Number 4

ice where she had received a course of radiotherapy for cancer of the cervix. The abdomen was

LOW C.V.P

distended, rigid and had recently become silent.

Blood pressure was 80/40 mm. Hg, pulse 140 and
the central venous pressure zero. Urine output had
declined to zero. Extremities were cool, moist and
slightly cyanosed.
Arterial blood gas studies showed

a PO2

TIIIE

1POj

*W

pl

1p0m

AFTER

pH

7.23

PCO2

44

P02

70

* STATISTICALLY

DIFFERENT
12

cmH20 L/ dy/M2

mg%

l/,
SHOCK
MORTAUTY

TOTAL

DEATH

/7

77

FIG. 11. Summary of response of patients who

presented with hypovolemia and acidosis due to
sepsis. First efforts were directed at increasing
circulating blood volume. This was followed by
cardiac and respiratory support and surgery. While
the cardiac filling pressure was promptly restored,
indicating that peripheral pooling was not the
cause, the cardiac output remained low as did the
blood pressure and urine flow. The arterial blood
lactate climbed.

Hg and the central venous pressure 6.5 cm. of

H20, yet cardiac index had again declined to 2.7
L./min./M.2. Repeat hematocrit was 51%, indicating a marked hemoconcentration. With correction of this disorder the cardiac index promptly
rose to 5.4 L./min./M.2, anid there was a marked
improvement in urine volume. Twelve hours later
blood lactic acid had declined from an initial
value of 61.4 mg./100 inl. to 15.5 mg./100 ml.
and the subsequent course was totally uneventful.

RS. EI t q5Z

22, INS

BEFORE v
pH 712
PCO2 40
P02 57

of 86

Hg; pH of 7.42; pC02 25 mm. Hg; base

deficit of -6.5 mEq./L. Hemoglobin was 10.0
Gm./100 ml., hematocrit 34% and the white blood
count 16,000/cm.
Prior to resuscitation, hemodynamic measurements revealed a cardiac index of 2.8 L./min./M.'
with central venous pressure zero. While preparation for surgery was made, blood, saline, mannitol
and sodium bicarbonate were given bringing the
central venous pressure to 6 cm. of water, cardiac
index to 3.2 L./min./M.2.
At operation, massive small bowel infarction
due to volvulus was found and extensive resection
carried out. During the operation central venous
pressure was maintained between 7 and 14.5 cm.
of water by administering blood, and the patient
remained normotensive.
Postoperatively blood pressure was 130/80 mm.
mm.

JUN

ACIDOSIS (7)

BLOOD
SALINE
ISOPROTERENOL
DIGITALIS
RESPIRATOR
SURGERY
ANTIBIOTICS
HYDROCORTISONE

2si _

l lpm

IN EX
2
CUBAC

20[ CENTRL VENOWJ PRESSLNtE

CmHjp

10

40

M"gs
*OD

asa
75

of
130
DI
7430

P L.ESSURE

FIG. 10. Mrs. E. M., aged 52, presented with

hypovolemic septic shock and fully compensated
metabolic acidosis. Volume replacement and appropriate surgery were beneficial but postoperative correction of hematocrit was necessary. The
cardiac index rose from 2.7 to 5.4 L./min./M.2
with correction of hematocrit and the arterial
blood lactate dropped from 61 mg.% to 15 mg.%o.
Both are excellent prognostic signs.

Comment. Preoperative correction of hypovolemia with early removal of the septic

process is ideal treatment for septic shock.
There is a tendency to treat hypotension
occurring during surgery for this type of
patient with blood. The high hematocrit
which can result will lower cardiac output
and decrease renal blood flow and urine
output. Saline or Ringer's lactate should be
used to keep the hematocrit between 35
and 40.
Group IV-Low Central Venous Pressure-Acidosis-7 Patients. Of the seven
patients in this group, five had peritonitis
due to bowel infarction. Most were seen
several hours after clinical signs of peri-

MAcLEAN, MULLIGAN, McLEAN AND DUFF

552
MR R M oge 68

APRIL 5, 1966

,~

TIME

CRDIAC

CA4

C..HO0

0 _

66

2:9009

9C vP

INDEX

CENTRAL VENOUS PRESSURE

@@

o
nHg

125 - BLOOD PRESSURE

*
75

.5
0

PULSE

20

RATE
*

CARDIAC

.-

ARREST

.
A*

HEMATOCRIT

"

_.

01

BUFFER BASE

-50
-20

200

BLOOD

GASES

50

LACTATE and PYRUVATE

60

4~~~~~~
TREATMENT

4'SOPROTERENOL

15P46

RE-()PFRATION
65 OGpm

T REr.

LEVOPF1ED

Fic. 12. Mr. R. M., aged 68, presented with

strangulating intestinal obstruction and bacteremia. The patient was hypovolemic and acidotic,
and despite modest restoration of cardiac output,
the blood pressuire remained low and the arterial
blood lactate remained high. There was no urine
output.

tonitis were first noted. All were marginally

responsive. Extremities were cool and cyanotic. The metabolic state was one of aci-

Annals of Surgery
October 1967

vomiting and increasing abdominal pain. Physical

examination revealed a distended, rigid, silent abdomen with generalized tenderness. There was
radiologic evidence of small bowel obstruction.
The patient's blood pressure was unobtainable, the
pulse rapid, and central venous pressure was zero.
Bladder catheterization produced no urine. After
the administration of 1,500 cc. of saline blood
pressure rose to 70/40 at which time the venous
hematocrit was still 56.
At operation a portion of the small intestine
was found herniated through a rent in the mesentery and there were 2,000 cc. of blood-tinged
fluid in the peritoneal cavity. Following reduction
of the hernia, intestinal intubation was performed
and the abdomen closed.
Postoperatively the patient remained in shock
despite hemodynamic support and over the subsequent 12 hours showed signs of increasing deterioration. At reoperation necrotic intestine was
found and massive small bowel resection performed. Following this procedure the patient remained in shock with a low fixed cardiac output
refractory to isoproterenol, norepinephrine and
massive doses of steroids.

Comment. This patient was seen late in

the course of septic shock. In retrospect,
inadequate surgery was initially performed.
A low, fixed cardiac output with progression of lactic acid accumulation occurred
with early death.
Discussion
The syndrome seen in early septic shock
herein described has been referred to, at
least in part, by several investigators. Hyperventilation and respiratory alkalosis in
the absence of fever was noted by Simmons
et al. in 11 patients with Gram-negative

dosis with a marked base deficit. Initial arterial blood lactates were high and continued to rise.
Cardiac index was low initially (average
1.90 L./min./M. ) and although an increase toward normal occurred with the
use of isoproterenol, in only one was blood
pressure and flow completely restored.
Other agents currently in use for hemodynamic support were tried but were of no
demonstrable value. Cardiac index remained low and fixed.
These patients represent a late stage in
septic shock that has developed in association with plasma loss. Therapeutic measures included the correction of acidosis,
restoration of blood volume, surgical drainage and respiratory and hemodynamic support. A summary of response to treatment
appears in Figure 11.

shock who had cardiac indices over 3.7 L./

min./M.2 and a total peripheral resistance
less than 1,000 dynes sec. cm.-5. Gilbert
et al.,7 in 1955 noted reduced peripheral
resistance with normal cardiac indices in
four patients in shock associated with in-

Case 6. Patient R. M. (Fig. 12), a 65-year-old

was admitted with a 12-hour history of

fection. Del Guercio and coworkers 4 have

described a hyperdynamic circulation in

man

bacteremia.11 Ebert and Stead6 described

dry extremities and normovolemia
in eight patients with Gram-positive infections and/or bacteremia. Thal and Wilson 12 described five patients with septic
warm,

V'olumne 166
Number 4

PATTERNS OF SEPTIC SHOCK IN MAN

553

TABLE 2. Mleasurements of oxygen Uptake, Lactate Production and Flow in Selected Patients

with Septic Shock

Patient

Normal
1
2
3
4
5
6

02
Utilization

Arteriovenous
Oxygen
Difference

Arterial
Blood
Lactate

12 mg./
250 ml./min. 4.5 Vols. l%1ml.
lIOO
295
5.94
24
110
5.29
113
296
3.3
20
203
3.0
70
260
4.67
21
256
2.33
31

septic shock and believe systemic and pularteriovenous shunting is a prominent feature. Udhoji and Weil13 noted a
hyperdynamic, low resistance circulation
with increased plasma volume in nine patients with cirrhosis of the liver who demonary

veloped Gram-negative bacteremic shock.

Table 2 summarizes oxygen uptake, arteriovenous oxygen difference, arterial blood
lactate, cardiac index and final outcome in
six patients with septic shock from the
present series. It appears possible from
these limited data that a defect in either
oxygen utilization or inadequate blood
flow could account for the elevated arterial
blood lactate encountered. It is possible
that oxygen utilization is not uniform
throughout the body and some organs may
suffer despite a normal arteriovenous difference. Oxygen or flow requirements at
times of great stress, as in septic shock,
remain unknown. Arteriovenous shunting
alone was not regularly found in the few
patients on whom sufficient data were obtained.
Flow Requirements in Septic Shock.
While absolute flow requirements are unknown during serious illness, the impression gained from this study suggests that
cardiac outputs of even two or three times
normal may be necessary to provide adequate tissue blood flow. Albrecht and
Clowes' have clearly shown by controlled
experiments on dogs that uneventful re-

Cardiac
Index

Outcome

Probable Defect

Survived
Died
Died
Died
Died
Died

Inadequate Flow
Inadequate Flow
AV Shunting
AV Shunting
Unknown
AV Shunting

3.2 L./min./
2.39
2.03
5.0
3.5
4.33
5.8

covery from a major operation is accompanied by a cardiac output close to the

basal value. Animals with infection, but
only 10 C. rise in temperature, developed
a progressive and significant increase of
cardiac output from 2.6 L./min./M.2 to 4.7
L./min./M.2. In animals in which the abscess was successfully evacuated the cardiac index returned to normal. However,
all animals in which the cardiac output
failed to rise following the development of
an abscess died.
In the patients herein reported similar
relationships exist (Table 3). In 40 patients
several measurements of cardiac output
were available both before and after treatment, providing the opportunity to document whether there was a sustained rise to
cardiac index of greater than 1 L./min./
M.2. Twenty-one of these 40 survived and
18 responded to treatment by raising the
cardiac index over 1 L./min./M. . Only
TABLE 3. Relationship Between Ability to Raise
Cardiac Index and Survival
Total Patients 40

Survived
21
18

Died

Able to raise cardiac

index over 1 L./min./M.2
Unable to raise cardiac
index over a L./min./M.2

19
11
8

MAcLEAN, MULLIGAN, Isv4cLEAN AND DUFF

554

TABLE 4. Mortality Rate in Septic Shock

(relation to surgical drainage)

TABLE 5. Microorganisms Cultured and Type

of Shock Encountered

Total Patients 53
Survived
20

Annals of Surgery
October 1967

Group I Group II Group III Group VI

Low
Low
High
High

Died

CVP
CVP
CVP
CVP
Alkalosis Acidosis Alkalosis Acidosis

33

Gram15

Amendable to surgical
drainage
Not amendable to surgical
drainage

16

17

negative

positive
Fungus

three survived who were unable to respond in this fashion. Nineteen of the 40
patients died, eight of whom were unable
to raise their cardiac indices. Eleven patients were able to increase their indices
but still died. There are several possibilities for failure in the latter group which
include: 1) cardiac output, even though
elevated, is insufficient to meet the needs
of the body; 2) oxygen and metabolites in
the blood are not reaching the vital tissues
(arteriovenous shunting); or 3) there is a
failure of tissue utilization of oxygen at the
cellular level (death of cells).
Table 4 relates survival to the value of
surgical drainage. In 53 patients a firm
opinion on the potential or demonstrated
value of surgical drainage or extirpation
was possible. Of these, 53, 20 survived. In
15 the source of infection was amenable
to surgery. In only five did survival occur
when the infection was not treated by surgery. Thirty-three patients died, 17 of
whom had lesions not amenable to surgery. In 16, death occurred despite the fact
that surgery was potentially useful. In
these patients the source of infection was
discovered late, was missed completely, or
was the result of inadequate surgery. In
several, the process was probably irreversible when the patient was first seen by a

physician.

If a patient, after appropriate surgical

drainage, shows a rising arterial blood lactate, or redevelops shock after a favorable
response, further surgical drainage is usually indicated (e.g., Case 2).

18

8
2

1
1

1
1

0
0

Gram-

Bacteriology. A summary of the organisms encountered, related to the type of

shock seen appears in Table 5. Gram-negative organisms were by far the commonest
cause. High output failure and low output
failure with alkalosis or acidosis were seen
with these organisms. Gram-positive organisms and fungi, with only one exception,
produced a high output snydrome. The
offending fungus was Candida albicans in
all cases.
Some patients dying of septicemia have
negative blood cultures due to massive
doses of antibiotics. It is these same patients from whom one can culture fungi.
Whether or not fungus causes the syndrome of septic shock in these circumstances is questionable. Dennis et al.5 have
reported the typical reaction of septic
shock in dogs using Candida albicans as
the provoking organism.
Hemodynamic-Metabolic Patterns and
Treatment. The natural history of septic
shock (Fig. 13), we believe, is from a state
of respiratory alkalosis to metabolic acidosis. If the patient is normovolemic at the
onset of the bacteremia, as are most patients with septic abortion, a hyperdynamic
circulation develops characterized by 1)
high cardiac index; 2) high central venous
pressure; 3) low peripheral resistance; 4)
hyperventilation; 5) alkalosis; 6) elevated
blood volume; 7) hypotension; 8) warm,
dry extremities; and 9) lactate accumulation. If this is not recognized and promptly
treated by surgical drainage and hemody-

Volume 166
Number 4

PATTERNS OF SEPTIC SHOCK IN MAN

namic support at even a higher level of

output, these patients may pass into an

acidotic phase (e.g., Case 1). The latter

also hyperdynamic but the lacticacidosis is refractory to all present forms
of therapy and death is almost certain.
On the other hand, if the patient has a
low central venous pressure and blood volume at the time of onset of the bacteremia,
a quite different response has been seen
(Fig. 13). These patients characteristically
have fluid losses into strangulated loops of
bowel or into the peritoneal cavity prior to
blood stream infection. Cardiac index is
low, central venous pressure is low, and
peripheral resistance is high. There is additional evidence of adrenergic activity in
that the extremities are cool and cyanotic.
Oliguria, hypotension, alkalosis and lactate
accumulation also occur. While progression
state is

BACTEREM IA

NORMOVOLEMIC MAN
28 patients

HYPOVOLEMIC MAN

ALKALOSIS

13

7/40

BLOOD PRESSURE

4.1

CARDIAC INDEX

CENTRAL VENOUS PRESSURE

75/50 v
2.2

1380

7.52

pH

7.41

61

PO2

73

31

LACTATE

41

V630 TOTALPERIPHERAL RESISTANCE

HIGH OUTPUT
FAIWRE

SEPTIC SHOCK

HIGH CV?P
NORMAL
28
v

or

ALKALOTIC

LOW C. VP
NORMAL or ALKALOTIC

10
survived
24 shock
17 survived

HIGH C.V\ P
ACIDOTIC

survived
shock
5 survived

LOW C.V. I?
ACIDOTIC

11
I survived
shock
0 survived

survived

FiG. 14. Mortality in 56 patients with septic

shock. Only 6 of 38 patients died of shock if treatment was started before the onset of metabolic
acidosis. Only 1 of 18 patients survived when
treatment was started after the onset of metabolic acidosis.

10 patients

HYPERVENTILATION

555

4U
ACI DOSIS

LOW OUTPUT
W FAILURE

FIG. 13. A schematic summary of hemodynamic

changes that occur with bacteremia in normovolemic man. In the former a high output state
exists; in the latter, a low output. Both lead directly to metabolic acidosis which is extremely
refractory to all forms of treatment. The early
recognition of hyperventilation and respiratory
alkalosis promotes early diagnosis.

from alkalosis to acidosis has seldom been

clearly documented in this group, we believe it does occur on the basis of clinical
description of the acidotic patients prior to
our period of observation.
In patients with low output, first efforts
are designed to restore effective blood volume using saline or plasma if the hematocrit is over 45, and with blood first if
under 40. The circulation is further supported with isoproterenol to obtain maximum tissue blood flow after restoration of
cardiac filling pressure. The overall results
in all four groups are summarized in Figure 14.
Massive bacteremia of resistant organisms can lead directly to pulmonary
edema. Figure 15 is the chest film of a patient with Gram-negative bacteremia who
developed sudden pulmonary edema with
a low central venous pressure and low pulmonary arterial wedge pressure. This was
not due to left heart failure, but was, we

MACLEAN, IULLIGAN, McLEAN AND DUFF

556

TA13LE 6. Hyperbaric Oxygen in

Treatment

Patient
Number

Duration
ATA

2
3

3.5 hrs.
1 hr.
1 hr.
1 hr. X 2
1 hr. X 4

Arterial
Blood

October 1967

Septic Shock

Arterial Blood
Lactate mg./lOOml.

pO2

mm.

Hg

1450
16,50
340
1260

believe, the direct effect of bacteria or their

products on the porosity of the pulmonary
capillaries. Hypoalbuminemia must also be
considered a possible cause of pulmonary
edema when associated with normal central venous pressure.
Hyperbar ic Oxygen. Five patients with
septic shock were treated for varying periods of time at 3 atmospheres absolute

FIG. 15. Mr. C. L., aged 54 with E. coli

septicemia. This patient developed early pulmonary edema with a normal right atrial pressure
(R.A.), low pulmonary capillary wedge pressure
(P.C.W.), strongly suggesting that the edema was
due to an increase in porosity of the pulmonary
capillaries. B.A. = brachial artery pressure; H.R.
heart rate; C.O. = cardiac output; S.V. stroke
volume; T.P.R.I. = total peripheral resistance index; C.I. = cardiac index and S.I. = stroke index.
(Included with kind permission of Dr. Maurice

McGregor.)

Annals of Surgery

Before During After

26
64

25
90

32

143

151

194
--

Outcome
Died
Died in Chamber
Died

Died
Died

while breathing 100% oxygen. Elevated

arterial blood oxygen tensions ranging from
340 to 1,650 mm. Hg were achieved. In
three patients arterial blood lactate concentration was followed before, during and
after the treatment. Lactate concentrations
continued to climb (Table 6) despite treatment and all patients died.
The idea of delivering more oxygen to
tissue in shock is appealing. The value of
hyperbaric oxygen in accomplishing this in
clinical septic shock remains to be established.
The present series of patients includes
many who were seen very early in their
course of shock. Shock units, by mistake
or intent, designed to study terminal patients, will miss a wide spectrum of disease. If hemodynamic measurements are to
be of value, it will be early, rather than
late, in the course of disease.
The heart is implicated in all forms of
septic shock whether of high output failure or low output failure. In both instances
output does not meet the needs of the
body and lactate accumulation occurs. Our
policy is to restore effective volume and
strongly support cardiac output using isoproterenol for its positive inotropic effect.
This has produced a drop in arterial blood
lactate, and restoration of urine output and
blood pressure in a large percentage of patients. If this therapy is not successful, we
have found no other support lifesaving.
Methods to prevent or reverse arteriovenous shunting or to increase specifically
blood flow to individual organs are un-

V'olume 166

Number

PATTERNS OF SEPTIC SHOCK IN MAN

45-7

known at the present time. Abscesses and

other sources of bacteremia must be
drained or resected early and adequately.
Patients tolerate the operation better if
normal hemodynamics are restored before,
rather than during or after surgery.
Predisposing Factors. The most important factors predisposing to septic shock in
this group of 56 patients were: long-term
treatment with cortisone; prophylactic antibiotic therapy including preparation for
colon surgery; cirrhosis of the liver; tracheostomy; urethral instrumentation; and
chronic debilitating disease.
Summary
Fifty-six patients with septic shock were
studied by a shock team. Twenty-two patients died of shock and an additional 12
died from other causes before discharge
from the hospital.
A syndrome of early septic shock was
seen in 28 patients who were normovolemic before the onset of the bacteremia or
septic process and include: 1) hyperventilation; 2) respiratory alkalosis; 3) a high
cardiac index; 4) high central venous pressure; 5) low peripheral resistance; 6) elcvated blood volume; 7) hypotension; 8)
oliguria; 9) warm, dry extremities; and
10) arterial blood lactate accumulation. If
recognized while still alkalotic, these patients responded to therapy designed to
maintain cardiac output at an even higher
level. There were only four deaths from
shock among the 28 patients.
If the patient was hypovolemic at the
onset of sepsis, a quite different clinical
picture was presented and consisted of: 1)
low central venous pressure; 2) low cardiac output; 3) high peripheral resistance;
and 4) cold, cyanotic extremities. Again, if
found early, these patients were also alkalotic and responded to treatment which
was primarily volume replacement and surgery. If not seen until they were acidotic,
a low fixed output persisted despite treatment and a high mortality rate ensued.

557

A classification based on central venous

pressure and arterial pH is useful as

guide to treatment and prognosis. The four

possibilities were: Group I-high CVPalkalotic; Group 11-high CVP-acidotic;
Group III-low CVP-alkalotic; Group IV
-lowv CVP-acidotic.
Either high or low cardiac output failure
characterizes septic shock in man. Significaint peripheral pooling which prevented
venous return to the heart, as occurs in the
dog, did not appear in this series of patients.
Gram-negative organisms were cultured
from 42 of the 56 patients and caused high
output as well as low output failure. Grampositive organisms caused shock in 10 patients and was the hyperdynamic type in
all but one. Candida albicans appeared to
cause the shock in four patients. It was
hyperdynamic in three and hypodynamic
in one.
Hyperbaric oxygen was used in five patients but did not lower arterial blood lactate in any and all died.
Patients who wvere able to raise their
cardiac index over 1 L./min./M.2 in response to treatment had a much better
prognosis than those who had a lesion that
could not be treated surgically.
References
1. Albrecht, M. and Clowes, G. H. A.: The Increase of Circulatory Requirements in the
Presence of Inflammation. Surgery, 56:158,
1964.
2. Barker, S. B. and Summerson, W. H.: The
Colorimetric Determination of Lactic Acid
in Biological Material. J. Biol. Chem., 138:
535, 1941.
3. Border, John R., Gallo, E. and Schenk, W. G.,
Jr.: Systemic Arteriovenous Shunts in Patients Under Severe Stress: A Common
Cause of High Output Cardiac Failure?
Surgery, 60:225, 1966.
4. Del Guercio, L. R., Cohn, J. D., Greenspan,
M., Feins, N. R. and Kornitzer, G.: Pulmonary and Systemic Arteriovenous Shunting
in Clinical Septic Shock. Third International
Conference on Hyperbaric Medicine, National Academy of Sciences, Washington,
D. C., 1966.
5. Dennis, D. L. and Peterson, C. G.: Candida
Albicans Shock. Surg. Forum, 15:36, 1964.
6. Ebert, R. V. and Stead, E. A., Jr.: Circulatory

558

MAcLEAN, MULLIGAN, McLEAN AND DUFF

AnnalsOctober
of Surgery
1967

Failture in Acuite Infectionis. J. Clin. Invest.,

20:671, 1941.
7. Gilbert, Robeit P., Honig, Klaas P., Griffin,
Joseph A., Becker, Robert J. and Adelson,
Bernard H.: Hemodynamics of Shock Due
to Infection. Stanford Med. Bull., 13:239,
1955.
8. Hardaway, Robert M. and McKay, Donald G.:
The Syndromes of Disseminated Intravascular Coagulation. Rev. Surg., 20:297, 1963.
9. MacLean, L. D., Duff, J. H., Scott, H. MI.
and Peretz, D. I.: Treatment of Shock in
Mlan Based on Hemodynamic Diagnosis.
Surg. Gynec. Obstet., 120:1, 1965.

10. Sekelj, P. and Oriol, A.: Dyc Curve Errors in

Shock. Fed. Proc., 26:331, 1967.
11. Simmons, Daniel H., Nicoloff, J. and Guze,
L. B.: Hyperventilation and Respiratory
Alkalosis as Signs of Gram-Negative Bacteremia. JAMA, 174:2196, 1960.
12. Thal, Alan P. and Wilson, Robert F.: Shock.
In Current Problems in Surgery. Chicago,
Year Book Medical Publishers Inc., 1965.
13. Udhoji, V. N. and Weil, M. H.: Hemodynamic
and Metabolic Studies on Shock Associated
with Bacteremia. Ann. Int. Med., 62:966,
1965.

DISCUSSION
DR. EDWARD FRANK (Boston): During the
past 5 or 6 years we have been engaged in a bedside effort to study and correct shock due to sepsis.
Our results strongly support Dr. Altemeier's report on the seriousness of this disorder. Also, it is
easier to prevent shock than to reverse the established disorder.
(Slide) Our efforts to control septic shock have
been successful in about half the cases. It is to
be noted that the opportunity for survival seems
to vary with the source of the infection. The most
difficult patients for us have been those with fecal
peritonitis. Here it may be assumed that a lethal
dose of bacterial toxin has preceded the therapeutic effort in many instances. In this regard we
must remember that Dr. Altemeier was among the
first to suggest the use of massive doses of cortocoids in the control of endotoxemia. This has been
very helpful in our experience.
The incidence of positive blood cultures was
30% in the peritonitis group, and variable in the
other groups. It is of interest that all five of the
children had positive blood cultures. Three had
had prior splenectomy, a factor possibly affecting
the decreased resistance to gram-negative bacteria.
After shock has been controlled in any group,
there is still a significant mortality, days or weeks
later, which seems to be related to the reduced
resistance to infection caused by the recent shock
state.
(Slide) Essentials for survival are easy to list,
but very hard to carry out. The words "immediate" and "continuous" are crucial, as has been
commented on by both speakers.
While undertaking the control of the physiologic disturbances, one must be alert to the unpredictable and preventable events that may cause
death. These include aspiration of gastric contents,
pulmonary edema, cardiac arrhythmia and acute
myocardial or cerebral injury. The last two are
commonly the result of transient uncontrolled

that the defects are ever changing and often unpredictable. We do not find such well-defined
patterns of cardiac output. Our experience indicates that isoproterenol may be dangerous in patients with heart rates over 120, and that this
agent is rarely more effective than digitalization
in improving cardiac output.
(Slide) Dr. MacLean has discovered that there
is indeed a significant incidence of hypovolemia
in septic shock. In the management of volume
replacement some recommend a central venous
catheter. Others recoimmend blood volume measurements. These parameters are not interchangeable. Our data -show miiany instances of hypovolemia in the presence of a normal central venous
pressure. There are also many moments, especially in elderly patients with peritonitis, when a
normal blood volume cannot be tolerated by injured heart and lungs. Therefore, in guiding volume replacement, we recommend that both parameters be monitored.

hypotension.
Dr. MacLean has indicated some of the physiologic defects that occur in septic shock. I'm sure
that his data are in agreement with ours, namely

DR. JOHN H. SIEGEL (Bronx, N. Y.): Dr.

Creech, Members and Guests: I would like to
thank Dr. MacLean for allowing me to review his
manuscript and for the privilege of discussing this
excellent paper.
Dr. MacLean has pointed out that in septic
shock we are dealing with a continuum, and that
a patient can progress from one state to the next.
I think we don't realize the extent of this continuum unless we look at a large group of patients
in septic shock.
(Slide) We attempted to examine our experience in septic shock and in so doing to try to
evaluate the vascular tone relationship, which is
the state of vascular vasoconstriction or vasodilatation over the entire range of cardiac output. To
do this we related the cardiac index to the peripheral resistance.
I think the significant fact here is that all patients in septic shock, regardless of cause or bacterial etiology (as Dr. MacLean has pointed out
so well), have a significantly decreased vascular
tone compared to those with nonseptic shock.
This means that at any systemic flow the vascular