Monografı́as del Semin. Matem. Garcı́a de Galdeano. 27: 405–412, (2003).

Classification of shock models in system reliability

F. Mallor, J. Santos
Departamento de Estadı́stica e Investigación Operativa, Universidad Pública de Navarra.

Abstract

Shock models in system reliability are usually defined by the time between two
consecutive shocks, the damage caused by a shock, the system failure and the de-
pendence relationship among the above elements. The main purpose of this work
is to review and classify the large set of shock models defined and studied in the
literature in the last three decades. Furthermore, we introduce a new model which
generalizes some of the classical ones that arise when the system is governed by
independent and identically distributed pairs, {(An , Bn )}∞
n=0 , where An is the mag-
nitude of the nth shock and Bn is the time between the (n − 1)th and the nth
shock.
Keywords: Reliability, Shock model.
AMS Classification: 90B25, 60K10.

1 Introduction
We consider systems subject to shocks that occur randomly in time. Shock models have
been studied by several authors and provide a realistic formulation for modelling certain
reliability systems situated in random environment. Various of the models collected here
are physically motivated. For instance, the extreme and cumulative shock models may
be appropriate descriptions for the fracture of brittle materials, such as glass, and for the
damage due to the earthquakes or volcanic activity, respectively.
The way in which the time between two consecutive shocks, the damage caused by
a shock, the system failure and the relationships among all these elements are modelled,
characterizes a shock model. In the literature, two major types are distinguished depend-
ing on whether the effect of the shock on the system is independent of its arrival time
or not. These principal models are collected in Section 2 and Section 3, respectively. In
Section 4, we introduce a new shock model which generalizes some of the classical ones.
Finally, we end with some remarks and conclusions.

405
2 Classic shock models with independence assump-
tion
When independence between the shock effect and the arrival time is assumed, a sequence
of surviving probabilities {P̄k } is defined, being P̄k the probability that the system still
run after the kth shock. According to the time between consecutive shocks, these models
are divided into four kinds:

- homogeneous Poisson process, that is, the times between two consecutive shocks are
independent, identically distributed exponential random variables;

- non-homogeneous Poisson process, that is, a counting process null at the origin with
independent increments where the probability of a shock in (t+∆t] is λ(t)∆t+o(∆t),
while the probability of more than one shock in (t + ∆t] is o(∆t);

- non-stationary pure birth process, that is, a Markov process where, given that k
shocks have occurred in (0, t], the probability of a shock in (t, t + ∆t] is λk λ(t)∆t +
o(∆t), while the probability of more than one shock in (t, t + ∆t] is o(∆t);

- or renewal process, that is, the times between two consecutive shocks are independent
and identically distributed random variables.

In the simplest case, homogeneous Poisson process, conditions on the prefixed sequence
{P̄k } are obtained to guarantee distribution properties of the survival function H̄(t). For
more details, see Esary et al [6].
Some of these results are extended by A-Hameed and Proschan [1] in the case of the
non-homogeneous Poisson process and by A-Hameed and Proschan [2], Klefsjö [13] and
[14] in the case of the non-stationary pure birth process.
When the shocks occur according to a renewal sequence, Skoulakis [24] describes the
system failure in such a way that generalizes the previous ones. In this model, we assume
that the jth shock, independent of all else, has an intensity x randomly chosen from
a distribution Gj , which is supported in [0, 1] and that it may cause the failure with
probability x. This shock model also has the Ross’ model [20, p. 22], the Råde’s model
[18] and the Nakagawa’s model [17] as particular cases. In the renewal process case, the
interest is focussed on the reliability function for a component and on the extension to
multi-component systems.
We point out that, along these last years, several authors have incorporated elements
to turn the system more realistic. For instance, Finkelstein and Zarudnij [9] add the
concept of recovery to allow the system to eliminate the consequence of each shock in
the following way: a r.v. τ is defined for each shock, which models the recovery time

406
from the shock. Then, if a shock occurs before the recovery time from the previous one
has elapsed, the system fails. For this particular model, Finkelstein and Zarudnij obtain
the reliability function for times between consecutive shocks following a non-homogeneous
Poisson process.
Ageing is another element that has been incorporated to some models. Fan et al
[7] include this ageing notion to a compound Poisson process shock, P (λ, x), that is, a
shock model where the shocks have random magnitudes x and arrive according to an
homogeneous Poisson process of rate λ. In the compound Poisson process, a shock is
fatal to the system with probability 1 − exp(−x), where x is the shock’s magnitude. The
incorporation of ageing is carried out by means of a constant δ, the rate of ageing, in
such a way that the probability of failure due to a shock of magnitude x arriving at
time u is 1 − exp(−δu − x). The reliability function is also obtained and an extension to
multi-component systems is provided.

3 Classic shock models with a dependence structure

When there exists dependence between the effect of the shock and its arrival time, the
damage caused by a shock is modelled in the Fan’s way, that is, by a random variable
representing the shock’s magnitude. Three principal models are considered: extreme
shock model, where the system breaks down as soon as the magnitude of an individual
shock exceeds some given level; cumulative shock model, where the system fails when
the cumulative shock magnitude exceeds some given level and run shock model, where
the system works until k consecutive shocks with critical magnitude occur. However,
Agrafiotis and Tsoukalas [3] define a shock model that is an extension of the cumulative
shock model: the system failure depends on the cumulative damage of those shocks with
a magnitude exceeding some pre-specified threshold.
The general setup in these three main shock models is a family {(An , Bn )}∞
n=0 of i.i.d.
two-dimensional vectors where An represents the magnitude of the nth shock and Bn the
time between the (n − 1)st and the nth shock or, alternatively, the time between the
nth and the (n + 1)st shock, called model I and model II respectively. Model II differs
significantly from model I in that the magnitude An of the nth shock affects future events,
that is, the time interval Bn until the (n + 1)st shock. Moreover, there exists a first shock
at time t = 0 in model II while A0 and B0 are assumed to be zero in the model I.
Let T be the time to the system failure and {N (t), t ≥ 0}, the counting process
generated by the renewal sequence {Bn }∞
n=0 . Then, for a fixed threshold z > 0, we have
that, in the extreme damage case, T ≤ t ⇔ max{An |0 ≤ n ≤ N (t)} > z; in the cumulative
damage case, T ≤ t ⇔ N
P (t)
n=0 An > z; in the run case, where z is the level which defines
a shock as critical, T ≤ t ⇔ min{n|An−j > z, j = 0, 1, . . . , k − 1} ≤ N (t).

407
 Under the model I and model II, the two first failure models were studied by Shanthiku-
mar and Sumita [22], [23], [25] and Gut [10] and [11], providing the reliability function,
two first moments and some results about the asymptotic behaviour of the system failure
time. In the case when the interarrival time Bn has infinite mean, Anderson, [4] and [5],
obtains asymptotic results for the model I.
Igaki et al [12] extend the extreme and cumulative shock model under the model
I incorporating the influence of the external system state after the nth shock, Jn , on
the correlation structure between the shock magnitudes and the shock interarrival times.
More concretely, a trivariate stochastic process {An , Bn , Jn }∞
n=0 is defined satisfying the
following Markov property for all n ∈ {0, 1, 2, . . . } and j ∈ S = {1, 2, . . . , N }:

P {An+1 ≤ a, Bn+1 ≤ b, Jn+1 = j|A0 , . . . , An , B0 , . . . , Bn , J0 , . . . , Jn }

= P {An+1 ≤ a, Bn+1 ≤ b, Jn+1 = j|Jn }

Also, temporally homogeneity is assumed so that the right hand side of the above
equation is independent of n. That is, the system state changes after each shock according
to a Markov process and the joint distribution of {An , Bn } is affected by transitions of
the system state.
The third failure model was recently introduced by Mallor and Omey [15] obtaining
properties of the distribution function of the system failure time and the limit behaviour
when k tends to infinity or when the probability of entering a critical set tends to zero.
All these models are summarized in the Table 1.
System failure
Cumulative damage k consecutive shocks
 Extreme damage / Critical region P
Ai > z with (A, B) ∈ R
(An , Bn )
D.F. of Tz [22] D.F. of Tz [25], [3]
Moments of Tz [22], [11] Moments of Tz [25], [3]
{(An , Bn )}∞
n=0 i.i.d pairs Properties of Tz [23] Properties of Tz [25] D.F. of Tz [15]
of correlated variables Asymptotic behaviour Asymp. behaviour Moments [15]
Model I •E[B] < ∞ [22], [11] •E[B] < ∞ [25], [10], [3] Asymp. behaviour [15]
•E[B] = ∞ [4] •E[B] = ∞ [5]
Random environment [12] Random environment [12]
D.F. of Tz [22] D.F. of Tz [25]
{(An , Bn )}∞
n=0 i.i.d pairs Moments of Tz [22] Moments de Tz [25]
of correlated variables Properties of Tz [23] Properties of Tz [25]
Model II Asymp. behaviour Asymp. behaviour
•E[B] < ∞ [3] •E[B] < ∞ [25], [10]

{(An , Bn )}∞
n=0 independent
but not necessarily
identically distributed pairs Asymp. behaviour [11]
of correlated variables
Model I

Table 1: Correlated effect and interarrival shock time

408
4 Definition of a new general model
We consider a system subject to shocks. Let An denote the magnitude of the nth shock
and Bn the time between the (n − 1)st and the nth shock. Let R ⊆ R be a prefixed real
subset. We say that the nth shock is a critical shock if An ∈ R. Also, we say that k
consecutive shocks form a critical run of length k if all of them are critical and they are
not contained in any sequence of k + 1 consecutive critical shocks. We define a complete
run of length k + 1 as a critical run of length k immediately followed by a non critical
shock.
In order to model the damage caused by a shock, we introduce a new set of random
variables dj , j = 0, 1, . . . . The variable d0 represents the damage due to a non critical
shock and we assume it to be zero. For j ≥ 1, the variable dj represents the damage
caused by a shock when it occupies the jth place in a critical run. That is, the nth shock
causes a damage dj if

An−i ∈ R, for i = 0, 1, . . . , j − 1 and An−j ∈

/ R, for n ≥ j ≥ 1;
An ∈
/ R, for j = 0.

The system fails as soon as the accumulated damage due to the random variables dj ’s
exceeds a fixed threshold z > 0.
For our model we suppose that the defined random variables verify the following
stochastic assumptions:

a) {dj }∞
j=0 is a family of nonnegative and independent but not necessarily identically
distributed random variables. We also assume that d0 = 0;

b) for each j ≥ 0, {(An , Bn , dj )}∞

n=1 are nonnegative, independent random vectors, all
of them equally distributed as the random vector (A, B, dj );

c) we do not impose any condition of independence among the variables A, B and dj

for all j ≥ 0.

In brief, our model is governed by a sequence of random vectors of three correlated

variables which represent the magnitude of the shock, the intershock time and the damage
caused by the shock, respectively. Note that this general shock model extends the model
I in the cases of cumulative damage, extreme damage and run damage.
The distribution function of the system failure time and its mean value are provided
via Laplace transforms in Mallor and Santos [16].

409
5 Final remarks and conclusions
The models where a probability is attached to each shock bring together the cumulative
and extreme shock models defining adequately the sequence {P̄k } and are studied as par-
ticular cases by A-Hameed and Proschan [1] and Esary et al [6]. Let Fj be the distribution
function of the damage caused by the jth shock, then for the cumulative shock model
P̄k = F1 ∗ F2 ∗ · · · ∗ Fk (z) and for the extreme shock model P̄k = kj=1 Fj (z).
Q

As before, different elements are incorporated to get a more realistic model such as the
assumption of a random threshold instead of a prefixed z and the stochastically decrease
of the sequence {Fk }∞
k=1 .

System General failure model Cumulative shock damage

k Cumulative shock damage
Interarrival  failure Y independent Xi and Extreme shock damage
P̄k = (1 − pj ) Xi i.i.d
shock time j=1 Fi (z) decreasing in i

Sufficient conditions on P̄k P̄k = F (k) (z) •Independent Xi and

P̄k = F1 ∗ · · · ∗ Fk (z)
H̄(t) : IF R, IF RA H̄(t) : IF RA, IF R Fi (x) decreas. in i
H̄(t) : IF R, IF RA [6]
Homogeneous Poisson N BU, N BU E, DM RL h(t) : P F2 [6] H̄(t) : IF R [6]
h(t) : P F2 [6]
process of rate λ h(t) : P F2 , P Fn • Random threshold [6] • Ageing
∞ • Random threshold [6]
X (λt)k −λt and dual [6] H̄(t) : IF R, IF RA, N BU H̄(t) : IF R [6]
H̄(t) = e P̄k H̄(t) : N BU
k=0
k! H̄(t) : HN BU E, HN W U E [14] h(t) : P F2 and dual [6]
• Dependence [6]
h(s + t) : SCn [6] • l kinds of shocks ind. [6] • Random threshold [6]
H̄(t) : IF RA
• Ageing [7] H̄(t) : IF RA h(t) : log-concave
• Recovery [9]

Sufficient conditions on
P̄k and Λ(t) • m components in series
Non-homogeneous H̄(t) : IF R, IF RA H̄(t) : IF RA
Poisson process N BU, N BU E, DM RL • m components in series
∞ H̄(t) : IF RA [19]
X (Λ(t))k −Λ(t) h(t) : P F2 with random threshold
H̄(t) = e P̄k
k=0
k! and dual [1] H̄(t) : IF RA, N BU
H̄(t) : HN BU E, HN W U E [14] and dual [1]
• m components [21]
• Recovery [9]

Non-stationary Pure Conditions on P̄k , λk , λ(t)

birth process H̄(t) : IF R, IF RA
∞
X N BU, N BU E, DM RL
H̄(t) = sk (t)P̄k
k=0 h(t) : P F2
∞
X and dual [2]
h(t) = sk (t)λk λ(t)pk+1
k=0
H̄(t) : HN BU E, HN W U E [13]
sk (t) = P {k shocks in [0, t]} H̄(t) : IF RA, DF RA [13]

Reliability function for pk

• indep. of k [18]
Asymp. behaviour
Renewal process • dep. of k [17]
of Tz [25]
• indep. of k and random [20]
• dep. of k and random [24]

Table 2: Independence between the effect and interarrival shock time

Ross [19] extends these two failure modes defining a new damage function Dt such
that:

- Dt (x1 , . . . , xn , . . . , 0) represents the damage at time t if exactly n shocks having

magnitudes x1 , . . . , xn have occurred by time t, with 0 = (0, 0, . . . );

- Dt is nondecreasing in each of its arguments for t ≥ 0;

410
 - Dt (x1 , . . . , xn , 0) = Dt (xi1 , . . . , xin , 0) whenever (i1 , . . . , in ) is a permutation of 1, 2,
. . . , n for all n.
Pn
By taking Dt (x1 , . . . , xn , 0) = max{x1 , . . . , xn } or Dt (x1 , . . . , xn , 0) = i=1 xi , we
obtain the cumulative and the extreme shock model respectively. All these models are
summarized in the Table 2.
In this work, we have presented the main shock reliability models studied in the
literature which, as far as we know, have not been analysed jointly. So, this task facilitates
us to see what has been done and, what is more important, what is still to be done.

References
[1] A-Hameed, M.S. and Proschan, F. (1973). Nonstationary shock models. Stochastic Processes
and their Applications, Vol. 1, No. Oct.; 383-404.

[2] A-Hameed, M.S. and Proschan, F. (1975). Shock models with underlying birth process. Journal
of Applied Probability 12; 18-28.

[3] Agrafiotis, G.K. and Tsoukalas, M.Z. (1995). On excess-time correlated cumulative processes.
Journal of the Operational Research Society 46; 1269-1280.

[4] Anderson, K.K. (1987). Limit theorems for general shock models with infinite mean intershock
times. Journal of Applied Probability 24; 449-456.

[5] Anderson, K.K. (1988). A note on cumulative shock models. Journal of Applied Probability 25;
220-223.

[6] Esary, J.D., Marshall, A. W. and Proschan, F. (1973). Shocks models and wear processes.
The Annals of Probability Vol. 1, No.17; 627-649.

[7] Fan J., Ghurke S.G. and Levine R.A. (2000). Multicomponent lifetime distributions in the
presence of ageing. Journal of Applied Probability 37, 521-533.

[8] Feller, W. (1968). An Introduction to Probability Theory and its Applications, Vol. 1. New York.
Wiley & Sons.

[9] Finkelstein M.S. and Zarudnij V.I. (2001). A shock process with non-cumulative damage.
Reliability Engineering & System Safety 71, 103-107.

[10] Gut, A. (1990). Cumulative shock models. Advances in Applied Probability 22; 504-507.

[11] Gut, A. (1999). Extreme shock models. Extremes 2:3; 295-307.

[12] Igaki, N., Sumita, U. and Kowada, M. (1995). Analysis of Markov renewal shock models.
Journal of Applied Probability 32; 821-831.

[13] Klefsjö, B. (1981). Survival under the pure birth shock model. Journal of Applied Probability 18;
554-560.

411
[14] Klefsjö, B. (1981). HNBUE survival under some shock models. Scandinavian Journal of Statistics
8; 39-47.

[15] Mallor, F. and Omey, E. (2001). Shocks, Runs and Random Sums. Journal of Applied Proba-
bility 38; 438-448.

[16] Mallor, F. and Santos, J. Reliability of systems subject to shocks with a stochastic dependence
for the damages. Submitted.

[17] Nakagawa, T. (1979). Further results of replacement problem of a parallel system in random
environment. Journal of Applied Probability 16; 923-926.

[18] Råde, L. (1976). Reliabilty systems on random environment. Journal of Applied Probability 34;
407-410.

[19] Ross, S.M. (1981). Generalized Poisson shock models. The Annals of Probability 9; 896-898.

[20] Ross, S.M. (1983). Stochastic Processes. New york; John Wiley & Sons.

[21] Savits T.H. (1988). Some multivariate distributions derived from a non-fatal shock model. J. Appl.
Prob. 25, 383-390.

[22] Shanthikumar, J.G. and Sumita, U. (1983). General shock models associated with correlated
renewal sequences. Journal of Applied Probability 20; 600-614.

[23] Shanthikumar, J.G. and Sumita, U. (1984). Distribution properties of the system failure time
in a general shock model. Journal of Applied Probability 16; 363-377.

[24] Skoulakis, G. (2000). A general shock model for a reliability system. Journal of Applied Probability
37; 925-935.

[25] Sumita, U. and Shanthikumar, J.G. (1985). A class of correlated cumulative shock models.
Advances in Applied Probability 17; 347-366.

412
Indian J.
SETHI, Anaesth.MOHTA,
SHARMA, 2003; 47 (5) : 345-359
TYAGI : SHOCK
SHOCK – A SHORT REVIEW
Dr. A. K. Sethi1 Dr. Prakash Sharma2 Dr. Medha Mohta3 Dr. Asha Tyagi4
Introduction
The syndrome of shock in humans is often the final
pathway through which a variety of pathologic processes
lead to cardiovascular failure and death. As such, shock
is perhaps the most common and important problem with
which the critical care physicians contend. It is one of the
most common causes of death in the United States today
and, together with respiratory failure, accounts for most
emergent intensive care unit (ICU) admissions.1 The
magnitude of the problem of shock is illustrated not only
by absolute numbers of deaths but also in the high mortality
percentages seen with various types of shock.
History
Despite recognition of a post traumatic syndrome
by Greek physicians such as Hippocrates and Galen, the
origin of the term shock is generally credited to the
French surgeon Henri Francois Le Dran, who in 1737
defined the same as “A treatise of reflections drawn from
experience with gunshot wounds” and coined the term
choc to indicate a severe impact or jolt.2 An inappropriate
translation by the English physician Clare, in 1743, led to
the introduction of the word “shock” to the English language
to indicate the sudden deterioration of a patient’s condition
when major trauma has occurred.2 It was Edwin A. Moses,3
who began to popularize the term, using it in his article
“A practical treatise on shock after operations and injuries”
in 1867.
Definition of Shock
The definition of shock has evolved in parallel
with our understanding of the phenomenon and many
definitions of shock have appeared.5 Until the late 1800’s,
the term shock was used to indicate the immediate
response to massive trauma, without regard to a specific
post trauma syndrome. Later, with the introduction of
noninvasive blood pressure monitoring devices, most
clinical definitions of shock added the requirement of
1. M.D., D.A., Professor and Head
2. M.D., D.N.B., Senior Resident
3. M.D., Reader
4. M.D., DNB, Lecturer
Department of Anaesthesiology and Critical Care,
U.C.M.S. and G.T.B. Hospital, Shahdara, Delhi, India - 110095
Correspond to :
E-mail: aksethi@bol.net.in
345
arterial hypotension.4 But current technology, which
allows assessment of perfusion independent of arterial
pressure, has shown that hypotension does not define shock.
The emphasis in defining shock is on tissue perfusion in
relation to cellular function. Thus, the most appropriate
definition of shock is “the state in which profound and
wide spread reduction of effective perfusion leads first to
reversible, and then, if prolonged, to irreversible cellular
injury.5
Classification
A classification based on cardiovascular
characteristics, which was initially proposed in 1972 by
Hinshaw and Cox,6 is the most accepted one amongst
many others that have been given. It divides the syndrome
into four major categories: hypovolemic, cardiogenic,
extracardiac obstructive and distributive (Table 1).
However, this is just an artificial separation and there is
a frequent, considerable initial mixing and overlap within
these categories.
(i) Hypovolemic Shock
It is characterized by a loss in circulatory volume,
which results in decreased venous return, decreased
filling of the cardiac chambers, and hence a decreased
cardiac output which leads to increase in the systemic
vascular resistance (SVR). The haemodynamic
profile on monitoring of flow pressure variables
shows low central venous pressure (CVP), a low
pulmonary capillary wedge pressure (PCWP), low
cardiac output (CO) and cardiac index (CI), and high
SVR. The arterial blood pressure may be normal or
low.
(ii) Cardiogenic Shock
This is primarily dependent on poor pump function.
Cardiogenic shock due to acute catastrophic failure
of left ventricular pump function is characterized by
high PCWP, low CO and CI, and generally a high
SVR.
(iii) Distributive or Vasogenic shock
This type of shock is associated with not only poor
vascular tone in the peripheral circulation but
maldistribution of blood flow to organs within the
body also. The CO varies, but is usually raised. A
common haemodynamic profile is a low or normal
PCWP, a high CO, a low arterial blood pressure,
and a low SVR.
346 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

Table - 1 : Classification of shock6 (iv) Extracardiac obstructive shock

HYPOVOLEMIC (oligemic)
It is associated with a physical impairment to adequate
• Hemorrhagic forward circulatory flow involving mechanisms
- Trauma
- Gastrointestinal different than primary myocardial or valvular
- Retroperitoneal dysfunction. Several hemodynamic patterns may be
• Fluid depletion (nonhemorrhagic)
- External fluid loss
observed, depending on the cause, from frank
Dehydration decrease in filling pressures (as in mediastinal
Vomiting
Diarrhea compressions of great veins); to trends towards
Polyuria
- Interstitial fluid redistribution
equalization of pressures in the case of cardiac
Thermal injury tamponade; or to markedly increased right ventricular
Trauma
Anaphylaxis filling pressures with low PCWP in the case of
• Increased vascular capacitance (venodilatation) pulmonary embolism. Cardiac output is usually
- Sepsis
- Anaphylaxis decreased with increased SVR.
- Toxins/Drugs
CARDIOGENIC Pathophysiology
• Myopathic
- Myocardial infarction Shocks of all form involve common cellular
Left ventricle
Right ventricle metabolic processes that typically end in cell injury, organ
-
-
Myocardial contusion (trauma)
Myocarditis
failure and death.7 The pathogenesis of shock involves
- Cardiomyopathy multiple interrelated factors including (a) cellular ischemia,
- Post ischemic myocardial stunning
- Septic myocardial depression (b) circulating or local inflammatory mediators, and (c)
- Pharmacologic
Anthracycline cardiotoxicity
free radical injury.
Calcium channel blockers
• Mechanical
(a) Ineffective perfusion leading to cellular ischemia plays
- Valvular failure a major role in cellular injury in most forms of
Regurgitant
Obstructive shock. Hypoperfusion decreases the delivery of
-
-
Hypertropic cardiomyopathy
Ventricular septal defect
nutrients to the cells leading to diminished ATP
• Arrhythmic production.8 Essential ATP dependent intracellular
- Bradycardia
Sinus (e.g., vagal syncope)
metabolic processes that may be affected include
Atrioventricular blocks maintenance of transmembrane potential,
- Tachycardia
Supraventricular mitochondrial function9 and other energy-dependent
Ventricular enzyme reactions. Liver and kidney are particularly
EXTRACARDIAC OBSTRUCTIVE
sensitive as intracellular levels of ATP fall and ATP-
• Impaired diastolic filling (decreased ventricular preload)
- Direct venous obstruction (vena cava) dependent processes are impaired.8,10-13 Lysosomal
Intrathoracic obstructive tumors
- Increased intrathoracic pressure disruption is the point of irreparable cell damage
Tension pneumothorax analogous to clinical irreversibility. Worsening of
Mechanical ventilation (with positive end-expiratory pressure
[PEEP], autoPEEP or volume depletion) shock, organ failure, and death may result.
Asthma (with auto PEEP)
- Decreased cardiac compliance
Constrictive pericarditis
(b) The effect of inflammatory mediators on cellular
Cardiac tamponade metabolism is of prime importance in organ
Acute
Post-MI free wall rupture dysfunction resulting from sepsis and septic shock
Traumatic
Hemorrhagic
and also hemorrhagic shock associated with extensive
Chronic trauma.14,18 Generally, it is the endotoxin from gram
Malignant
Uremic negative bacteria that triggers the inflammatory
Idiopathic cascade but bacterial antigens and cell injury it self
• Impaired systolic contraction (increased ventricular afterload)
- Right ventricle can also initiate the cascade. Macrophage production
Pulmonary embolus (massive) of cytokines such as TNF-a and IL-1b appear to be
Acute pulmonary hypertension
- Left Ventricle the prime mediators.19 Other substances involved in
Saddle embolus
Aortic dissection the inflammatory process include IL-2, IL-6,
DISTRIBUTIVE interferon-a, endothelin-1, leukotrienes, thromboxanes,
Septic (bacterial, fungal, viral, rickettsial) prostaglandins and complement fragments C3a and
Toxic shock syndrome
Anaphylactic, anaphylactoid C5a.19,20 Two other mediators, circulating myocardial
Neurogenic (spinal shock)
Endocrinologic depressant substance and nitric oxide have a role to
Adrenal crisis
Toxic (e.g., nitroprusside, bretyllium)
play in septic shock.23,24,25
SETHI, SHARMA, MOHTA, TYAGI : SHOCK
(c) Free radical injury induced by reperfusion or
neutrophil activity is another mechanism by which
cell and organs suffer a damage.26,27 Tissue ischemia
leads to accumulation of adenosine, inosine and
hypoxanthine.28 With resuscutation, reperfusion of
ischemic areas occurs. The availability of O2 generates
superoxide (O2-) by xanthine oxidase which is
converted to hydrogen peroxide (H2O2) which further
reacts to produce the highly reactive tissue damaging
hydroxyl radicals. These inturn interact with critical
cell targets resulting in cell lysis and tissue injury.
Oxidant activity, directly and through endothelial
damage attracts and activates neutrophils causing
amplification of superoxide generation and further
tissue damage due to neutrophil protease release.27
Microvascular function in shock
Microvessels (100-150mm diameter) is one of the
key determinants of appropriate tissue perfusion during
shock. Adequate cardiac output as well as normal local
and systemic microvascular function ensure that specific
tissues are effectively perfused. Distribution of cardiac
output involves local intrinsic autoregulation and extrinsic
regulation mediated by autonomic tone and humoral factors.
Blood flow to individual organs may be affected by system
wide changes in microarteriolar tone or by local alteration
in metabolic activity. It is the precapillary arterioles and
precapillary and postcapillary sphincters that are responsible
for these tasks.
During both irreversible hemorrhagic and septic
shock, peripheral vascular failure results. The potential
mechanisms are (a) tissue acidosis29 (b) catecholamine depletion
and mediator related vascular resistance to catecholamine30,33
(c) release of arachidonic acid metabolites34-36 (d) nitric
oxide generation23,37,38 and (e) decreased sympathetic tone
due to altered central nervous system (CNS) perfusion.39
Other microvascular pathologic processes occurring
in shock include disruption of integrity of endothelial cell
barrier leading to loss of plasma proteins, decrease in
plasma oncotic pressure, interstitial edema and fall in
circulating volumel.40,41 In addition, there is microvascular
clotting and microthrombi leading to further inadequate
distribution of perfusion within tissue.42,43
Compensatory Responses to Shock
With the onset of hemodynamic dysfunction,
homeostatic compensatory mechanisms engage to maintain
adequate tissue perfusion. At this stage, signs and symptoms
of hemodynamic stress may be apparent (i.e., tachycardia,
decreased urine output) but overt evidence of shock (i.e.,
hypotension, altered sensorium, metabolic acidosis) are
347
absent. All compensatory responses to shock, whether
hemodynamic, metabolic or biochemical, support oxygen
delivery to vital organs. These responses are similar for
varying classes of shock and are divided into four categories
(Table 2):
(a) Maintenance of mean circulatory pressure
(b) Maximizing cardiac function
(c) Redistributing perfusion to vital organs
(d) Optimizing unloading of oxygen at tissues
Table - 2 : Cardiovascular/Metabolic compensatory
responses to shock5
Maintain Mean Circulatory Pressure (venous pressure)
• Volume
- Fluid redistribution to vascular space
From interstitium (Starling effect)
From intracellular space (Osmotic effect)
- Decreased renal fluid losses
Decreased glomerular filtration rate (GFR)
Increased aldosterone
Increased vasopressin
• Pressure
- Decreased venous capacitance
Increased sympathetic activity
Increased circulating (adrenal) epinephrine
Increased angiotensin
Increased vasopressin
• Maximize Cardiac Performance
- Increased contractility
Sympathetic stimulation
Adrenal stimulation
• Redistribution of Perfusion
- Extrinsic regulation of systemic arterial tone
- Dominant autoregulation of vital organs (heart, brain)
• Optimize Oxygen Unloading
- Increased RBC 2, 3 DPG
- Tissue acidosis
- Pyrexia
- Decreased tissue PO2
Mean circulatory pressure (and venous return) is
sustained in early shock not only by sympathetic
activation44,45 causing precapillary vasoconstriction but also
by decrease in capillary hydrostatic pressure causing influx
of interstitial fluid into the vascular compartment.46 The
intravascular volume may also be supported by the osmotic
activity of glucose generated by glycogenolysis.47
Intravascular volume is maintained by decreasing
renal fluid looses and by release of rennin from juxta-
glomerular apparatus.48 Rennin converts angiotensinogen
into angiotensin I which is further metabolized to
angiotensin II49 which causes aldosterone release. This in
turn, increases sodium reabsorption in the distal tubules of
the kidney. Angiotensin II is also a potent vasocontrictor
particularly on mesenteric vessels and increases sympathetic
348
out flow and adrenal epinephrine release.49,50 Vasopressin
released also causes water retention and vasoconstriction
particularly of the splanchnic circulation.51 Cardiac functions
are augmented by local release of norepinephrine by
sympathetic nerves and systemic release of epinephrine,
which stimulate cardiac a and b adrenergic receptors.
During shock, increased sympathetic vasoconstrictor
tone, systemic release of epinephrine from the adrenals,
vasopressin and angiotensin II cause vasocontriction in all
sensitive vascular beds, including skin, skeletal muscle,
kidney and splanchnic organs. The vascular supply of the
brain and heart is spared causing effective redistribution
of flow to these vital organs.44,45
Tissue ischemia results in local acidemia, which
causes a decreased affinity between oxygen and
haemoglobin.56,57 Also, systemic alkalemia due to
respiratory alkalosis leads to rapid increases of erythrocytes
2,3 diphosphoglycerate (DPG). Both of these cause
rightward shift of oxyhaemolobin dissociation curve.
Effect of shock on various organ systems (Table 3)
(1) Brain - Though CNS neurons are extremely sensitive
to ischemia, the vascular supply is highly resistant to
extrinsic regulatory mechanisms. Patients without a
primary cerebrovascular impairment, support their
cerebral function well until the mean arterial pressure
falls below approximately 50-60 mmHg.58,59 At this
point, irreversible ischemic injury may occur to the
most sensitive areas of the brain i.e., cerebral cortex
and water shed areas of the spinal cord.58,59 Before
such injury, an altered level of consciousness varying
from confusion to unconsciousness may be seen
depending on the degree of perfusion deficit.
Electroencephalographic (EEG) recordings
demonstrate non-specific changes compatible with
encephalopathy.
(2) Heart - The major clinically apparent manifestations
of shock result from sympatho adrenal stimulation.
Heart rate is usually increased except in case of
severe haemorrhage where vagally mediated
paradoxical bradycardia may occur.60,61 In addition,
catecholamine driven supraventricular tachycardia and
ventricular ectopy with ichaemic ECG changes (in
patients predisposed to myocardia ischaemia) may be
seen. Systemic hypotension compromises coronary
perfusion leading to overt ischemia in high risk
patients.62 Circulating myocardial depressant factors
contribute to myocardial depression in septic21,22 and
haemorrhagic shock. Unless shock is of cardiac origin,
the heart usually plays a participatory role in which
it is unable to compensate fully for arterial
hypotension caused by hypovolemia, vasodilatation,
or other factors.63
INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003
Table - 3 : Organ system dysfunction in shock5
Central Nervous System Encephalopathy (ischemic or septic) Cortical necrosis
Heart Tachycardia, Bradycardia, Supraventricular
tachycardia, Ventricular ectopy, Myocardial
depression
Pulmonary Acute respiratory failure, Adult respiratory distress
syndrome
Kidney Prerenal failure, Acute tubular necrosis
Gastro-Intestinal Ileus Erosive gastritis, Pancreatitis, Acalculous
cholecystitis, Colonic submucosal hemorrhage,
Transluminal translocation of bacteria/antigens
Liver Ischemic hepatitis”Shock” liver intrahepatic
cholestasis
Hematologic Disseminated intravascular coagulation,
Dilutional thrombocytopenia
Metabolic Hyperglycemia, Glycogenolysis, Gluconeogenesis,
Hypoglycemia (late), Hypertriglyceridemia
Immune System Gut barrier function depression, Cellular immune
depression, Humoral immune depression
(3) Respiratory system - Increased respiratory drive
resulting from peripheral stimulation of pulmonary J
receptors and carotid body chemoreceptors, as well
as hypo-perfusion of the medullary respiratory center
results in increased minute volume (tachypnea,
hyperpnea), hypocapnia and primary respiratory
alkalosis.64 With increased minute volume and
decreased cardiac output, the V/Q ratio is increased.
Coupled with an increased workload, respiratory and
diaphragmatic muscle impairment caused by
hypoperfusion may lead to early respiratory failure.65,66
If shock is not promptly reversed and the initiating
condition controlled adult respiratory distress
syndrome (ARDS) may develop.
(4) Kidney - Oliguria, as defined by a urinary output
less than 0.5 mlkg-1hour is a cardinal manifestation
of shock. Sympathetic stimulation, circulating
catecholamines, angiotensin, and locally produced
prostaglandin contribute to afferent arteriolar
vasoconstriction and the redistribution of blood flow
away from cortex to the medulla.63,67,68 The net effect
is a decreased glomerular filtration rate. The three
pathologic changes seen are (a) tubular necrosis (b)
tubular obstruction by casts or debris and (c) tubular
epithelial damage. It is because of these pathologic
changes that restoration of normal hemodynamic
function does not often lead to an immediate
improvement in renal function.
Urine produced during shock often reflects the
pathophysiologic changes occurring in kidney. If
SETHI, SHARMA, MOHTA, TYAGI : SHOCK
reflex vasoconstricting mechanisms predominate
(i.e., hypovolemic and cardiogenic shock), the urine
has an osmolality in excess of 450 mosmlL-1, sodium
concentration of less than 20 mmolL-1, fractional
excretion of sodium less than 1% and a urine to
plasma creatinine ratio of over 40. However, with
acute tubular necrosis the osmolality of urine
decreases to less than 350 mosmlL-1, sodium
concentration gets over 40 mmolL-1 with fractional
excretion of sodium of over 2% and a urine to plasma
creatinine ratio of less than 20.69
(5) Gastrointestinal - Typical clinical manifestations of
hypoperfusion, sympathetic stimulation and
inflammatory injury associated with shock includes
ileus, erosive gastritis, pancreatitis, acalculous
cholecystitis and colonic submucosal hemorrhage.70,71,72
Also, enteric bacteria and antigens translocate from
the gut lumen into the systemic circulation during
gut ischemia causing irreversible shock.73,74
(6) Liver - Centrilobular injury with mild increases of
transaminases and lactate dehydrogenase usually peaks
within 1-3 days of ischemic insult and resolves over
3-10 days. ‘Shock liver’ associated with massive
ischemic necrosis and a major elevation of
transaminases is atypical in the absence of extensive
hepatocellular disease.75 In both, only mild increases
in bilirubin and alkaline phosphatase is seen in early
shock. Though, the clnical manifestations are not
apparent in early stages of shock, as the organ
participates in the release of acute phase reactants
but synthetic functions may be impaired with
decreased generation of prealbumin, albumin and
hepatic coagulation factors.76 Biliary stasis with
increased bilirubin uptake and alkaline phosphatase
may be seen after hemodynamic resolution of the
shock.
(7) Hematologic - Disseminated intravascular coagulation
(DIC) characterized by microangiopathic hemolysis,
consumptive thrombocytopenia, consumptive
coagulopathy and microthrombi with tissue injury is
seen commonly in septic shock. Dilutional
thrombocytopenia after volume replacement is
associated with hemorrhagic shock.77
(8) Metabolic - In early shock, sympathoadrenal activity
is enhanced causing increased release of adreno
corticotrophic hormones (ACTH), glucocorticolds and
glucagons and decreased release of insulin.78 Also,
glycogenolysis and gluconeogensis contribute to
hyperglycemia. Later, glycogen depletion or failure
of hepatic glucose synthesis leads to hypoglycemia.79
349
Fatty acid initially increase but later with hypoperfusion
of adipose containing peripheral tissue, levels fall.80
Increased catecholamines, glucocorticoids and
glucagon increase protein catabolism causing negative
nitrogen balance.78,80 Catecholamine stimulation and
reduced lipoprotein lipase expression also causes
hypertriglyceridemia.78,81
(9) Immune system - Compromised immune functions
are due to injury to barrier mucosa especially of the
gut; parenchymal tissue injury from associated trauma,
or free radical injury; and direct ischemic or mediator
induced dysfunction of cellular and humoral immune
system.82,83
Diagnostic Approach and Evaluation
Shock is an end-stage of a continuum of progressive
physiologic derangements. It is imperative, therefore, that
clinicians recognize the early stages of shock at a time
when it is more responsive to treatment. A monitored
physiologic approach to therapy provides the best
opportunity for successful outcome and avoidance of organ
dysfunction. Not only the initial resuscitative technique
but continuous evaluation of the patient’s condition is
important. (Table 4)
Table - 4 : General Approach to Shock: Initial Diagnosis
and Evaluation5
Clinical Tachycardia, tachypnea, cyanosis, oliguria,
(primary diagnosis) encephalopathy (confusion), peripheral hypoperfusion
(mottled extremities), hypotension (systolic blood
pressure < 90 mm Hg; mean arterial pressure
<65 mm Hg)
Laboratory Hemoglobin, WBC, platelets
(confirmatory) PT/PTT
Electrolytes, arterial blood gases
Ca, MgBUN, creatinine
Serum lactate
ECG
Monitoring Continuous ECG and respiratory monitors
Arterial pressure catheter
Central venous pressure monitor (uncomplicated shock)
Pulmonary artery flotation catheter
Cardiac output
Pulmonary wedge pressure
Mixed venous oxygen saturation (intermittent or
continuous)*
Oxygen delivery (Do2) and oxygen consumption
(VO2)*
Oximetry*
Transcutaneous oxygen tension*
Gastric intramucosal pH*
Echocardiogram (functional assessment)*
Imaging Chest radiograph
Radiographs of abdomen*
Computerized axial tomogram (CT scan),
abdomen or chest*
Echocardiogram (anatomic assessment)*
Pulmonary perfusion scan*
350 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

Clinical presentation detailed sediment analysis, serum amylase level; and arterial
This varies with the previous level of organ function, blood gases (ABG).
compensatory mechanisms, severity of organ dysfunctions Leucocyte count is frequently elevated early in shock
and the cause of shock syndrome. Impending shock is caused by demargination of neutrophils. Leucopenia is
characterized by the typical compensatory response to found in sepsis and late shock. Haemoglobin level varies
cardiovascular stress. Tachycardia, tachypnea and oliguria with the type of shock. Stress of circulatory shock increases
are the hall mark. Cool extremities are seen in hypodynamic platlet count initially but with proression thrombocytopenia
shock. With progression, blood pressure falls and frank occurs. BUN and creatnine rarely change after the acute
hypotension (MAP<60-65mmHg) ensues. With further creatinine onset of shock, even if renal injury is present.
progression, anuria, mottled, dusky extremities and altered ABG determines the adequacy of oxygenation and acid
sensorium occurs. (Table 5) base status. Serial serum lactate levels are used in the
assessment of prognosis and levels of >2meqL-1 represent
Table - 5 : Clinical Recognition of Shock5 tissue ischemia.
ORGAN SYMPTOM CAUSES Pregnancy test should be performed in all females
SYSTEM OR SIGN of child bearing age. A 12 lead ECG is critical for diagnosis
CNS Mental status changes Decreased Cerebral perfusion of ischemic cardiac injury either as a primary cause of
Pinpoint pupils Narcotic overdose cardiogenic shock or secondary to hypotension associated
with other shocks. Chest radiograph is also a must. Other
Circulatory Tachycardia Adrenergic stimulation,
Heart depressed contractility studies should be considered in specific conditions and
may include blood, sputum and urine gram stains and
Other dysrhythmias Coronary ischemia
cultures in all cases of suspected sepsis. More detailed
Hypotension Depressed contractility
secondary to ischemia or MDFs,
imaging studies like CT scans, abdominal radiographs or
right ventricular failure ultrasound, surface or transesophageal echocardiograms84,85
Systemic New murmurs Valvular dysfunction,
ventilation/perfusion scan, angiograms and cardiac
Hypotension VSDDecreased SVR, decreased isoenzymes86 may be ordered for as and when required.
Decreased JVP venous return Hypovolemia,
decreased venous return Typing and crossmatching for several units of packed
Increased JVP Right heart failure
RBC’s and fresh frozen plasma should be asked for when
a significant blood loss is observed, anticipated, or
Disparate peripheral
pulses Aortic dissection suspected.
Respiratory Tachypnea Pulmonary edema, respiratory Invasive hemodynamic monitoring
muscle fatigue, sepsis, acidosis
Arterial pressure catheter is a must for all patient
Cyanosis Hypoxemia
suspected of having circulatory shock. Marked peripheral
Renal Oliguria Decreased perfusion, afferent vasoconstriction may make the assessment of blood pressure
arteriolar vasoconstriction
by manual sphygmomanometry or automated noninvasive
Skin Cool, clammy Vasoconstriction, sympathetic
oscillometric technique inaccurate.87 Also, continuous
stimulation
monitoring of the rapidly changing hemodynamic status of
Other Lactic acidosis Anaerobic metabolism,
hepatic dysfunction
unstable patients and access for ABG samples is available
with arterial catheter in place.
Fever Infection
Central venous pressure monitoring is not an
Laboratory studies accurate means of monitoring volume resuscitation and
There are used not only for confirmation of diagnosis should be used only as a rough guide. An initially low
of shock but also to know the etiologic factors. Initial CVP (i.e., less than 5mmHg) may indicate hypovolemia
laboratory tests should include a complete chemistry profile and a CVP more than 15mmHg with an absent Y descent
with serum electrolytes, creatinine, blood urea nitrogen suggests cardiac tamponade in the appropriate clinical
(BUN), liver function tests, calcium, magnesium and setting. As a rule, CVP monitoring is inadequate for the
phosphate levels, a complete blood count and differential; hemodynamic assessment of critically ill patients and also
a platlet count; serum lactate levels; prothrombin and it does not accurately estimate left ventricular preload in
activated partial thromboplastin times, urinalysis with a critically ill patients.88,89
SETHI, SHARMA, MOHTA, TYAGI : SHOCK
Flow directed ballon tipped pulmonary artery
catheter with thermodilution cardiac output determination
capability have become the standard practice for the
hemodynamic assessment of circulatory shock.90,91,92
Continuous monitoring of central venous and pulmonary
artery waveforms and pressures is also provided by them.
It is also useful for etiologic classification of shock,
determination of optimal management and response to the
therapy.
Mixed venous oxygen saturation provides an
assessment of adequacy of resuscitation of low output states
before the presence of anaerobic metabolism. Normal SVo2
falls within 65%-75% range. SVo2 rises with increases of
perfusion above requirements and falls, with increasing
oxygen extraction ratio, as perfusion become inadequate.
Oxygen delivery and oxygen consumption variables
can also be determined using pulmonary artery catheter-
derived data. But, the utility of this data is controversial
when applied to individual patients. Recent modification
to the standard pulmonary artery floatation catheter
allows continuous monitoring of SVo2 or determination of
right ventricular ejection fractions and volumes though
they have no defined role at this time in clinical shock
management.
Ancillary monitoring techniques
Pulse oximetry has a limited use in the acute
management of circulatory shock and may be more helpful
in the post resuscitation monitoring. Transcutaneous and
transconjunctival oxygen tension measurements are newer
noninvasive techniques for determining tissue oxygen
tensions.93,93,95 Gastric mucosal pH is also a noninvasive
method for assessment of adequacy of tissue oxygenation/
perfusion. It correlates well with systemic and organ oxygen
consumption, organ failure and outcome in critically ill
patients.96,97 Normalization of gastric mucosal pH is also
one of the target during resuscitation of circulatory shock.
Echocardiography in the ICU not only detects the anatomic
lesions but also allows direct measurement of cardiac
output, stroke volume, preload, systolic contractility,
diastolic function and regional motion abnormalities.99
There are other promising noninvasive monitoring
devices i.e, near-infrared spectroscopy to detect oxygen
availability and utilization at tissue level and thoracic
electrical bioimpedance for continuous cardiac output
measurements. These could be used with high risk patients
to detect “compensated states”, before clinical
hemodynamic instability is evident. But, more studies and
refinement are necessary before the ‘golden standard’
(pulmonary artery catheter with a thermistor tip) can be
351
challenged.100,101-105
Management and Therapy
Patients in shock should be managed in ICU with
continuous ECG monitoring and close nursing support.
Invasive hemodynamic monitoring with arterial and
pulmonary artery catheters should be instituted in those
indicated i.e., patients in whom etiologic diagnosis is in
doubt, whose hemodynamic instability does not quickly
resolve with intravenous fluids etc., laboratory tests as
mentioned before should be performed the earliest possible.
Management of shock can be divided into specific therapy
for triggering injury and general therapy of the shock
syndrome. (Table 6)
Table - 6 : General approach to shock: Immediate goals5
Hemodynamic MAP>60-65 mm Hg (higher in the presence of coronary
artery disease or chronic hypertension)
PWP = 12 to 18 mm Hg (may be higher for cardiogenic shock)
CI>2.1 Lmin-1m-2 for cardiogenic and obstructive
shock>3.0 to 3.5 Lmin-1m-2 for septic and resuscitated
traumatic/hemorrhagic shock.
Optimization of Hemoglobin >10 gdL-1
oxygen delivery Arterial saturation>92%
Svo2>60% Normalization of serum lactate
(to <2.2 meqL-1)
Reverse organ Reverse encephalopathy
system Maintain urine output >0.5 mlkg-1hr-1
dysfunction
Aims - The basic goal of circulatory shock therapy
is the restoration of effective perfusion to vital organs and
tissues before the onset of cellular injury. This in turn
depends on cardiac index (CI) and mean blood pressure.
The first specific resuscitative aim should be support of
blood pressure greater than 60-65 mmHg in a baseline
normotensive patient. The second aim, maintainence of CI
greater than 2.1Lmin-1m-2 for cardiogenic and obstructive
shock and greater than 3.0-3.5 Lmin-1m2 for septic and
resuscitated hemorrhagic shock should be then looked after.
Finally, maintaining perfusion sufficiently high to keep
arterial lactate concentration <2.2 meqL-1 avoids anaerobic
metabolism. The concept that augmenting O2 delivery (Do2)
to “supranormal” levels increase oxygen consumption and
thereby, decrease organ failure and mortality remains
controversial. More recent investigations have cast doubts
on this therapeutic approach of augmenting Do2.106-109
(a) Airway management and mechanical ventilation
A critical first step in the treatment of shock is to
ensure adequate alveolar ventilation and oxygenation.
Most patients with the fully developed shock syndrome
require tracheal intubation and mechanical ventilatory
352
support, even if acute respiratory failure has not yet
occurred.
Improvement may occur for several reasons.
Mechanical ventilation allows blood flow to be
redistributed, tends to reverse lactic acidosis and
supports the patient until other therapeutic measures
can be effective. Tracheal intubation also is indicated
if mental status changes make airway unprotected or
for inadequate respiratory compensation for metabolic
acidosis.110 Initial guidelines include using calculated
tidal volumes in the order of 7-10 mlkg-1 of lean
body mass, an O2 concentration that results in arterial
saturation not less than 92%, adequate ventilator rate
and sedation to minimize the work of breathing.63
Positive-pressure ventilation and PEEP may produce
further hemodynamic compromise if volume status
of the patient is not maintained. PEEP may also be
desirable in patients with ARDS or pulmonary edema
to ensure adequate oxygenation.
(b) Acid base Balance
The previous standard practice of administering
bicarbonate to patients with shock and lactic acidosis
has been revised. Recent evidence has demonstrated
that metabolic acidosis of the plasma may infact be
protective in shock states and that bicarbonate
administration may transiently decrease intracellular
and cerebrospinal fluid PH.111 The mechanism being
production of CO2 as a product of the bicarbonate
buffering of hydrogen ion and the rapid diffusion of
this non ionized CO2 across cellular membranes. This
paradoxical intracellular acidosis hinders brain and
cardiac functions. Thus, the optimal approach to the
management of lactic acidosis is to improve organ
and systemic perfusion so that anaerobic metabolisms
is limited and the liver as well as kidney can clear
the accumulated lactate. If not effective, it has been
suggested to restrict the use of sodium bicarbonate to
situations with PH <7.1-7.15.
(c) Fluids
Common to all etiologies of hemodynamic instability
and shock is the need to provide optimal intravascular
volume to ensure adequacy of preload. Thus, it is
appropriate to begin fluid administration in all shock
patients who lack signs of pulmonary edema and left
ventricular overload. Substantial controversy exists
regarding the appropriate use of crystalloid and
colloid fluids for resuscitation.112-114 Several meta-
analyses determined that there is no benefit and even
perhaps mild increased mortality associated with the
use of colloids instead of crystalloids for fluid
INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003
resuscitation.115 Thus, given the much higher cost of
colloids, resuscitation of shock should generally focus
on crystalloid solutions unless speed of resuscitation
is paramount (i.e., acute major trauma or massive
hemorrhage). What is most important when either
type of fluid is used is to determine responses to
these fluid challenges. Optimal therapy generally
means administering the quantity of fluid that
maximizes Do2 while avoiding left ventricular
overload and pulmonary edema. Also, sufficient
preload should be there before or during institution
of pharmacologic therapy for hypoperfusion.
(d) Vasopressor agents
The term pressor refers to any substance that raises
BP. These agents are divided into 3 categories: (i)
lonotropes/chronotropes (i.e., drugs that increase
cardiac output (CO) by increasing cardiac contractility
and heart rate); (ii) vasoconstrictors (i.e., agents that
raise BP by increasing systemic vascular resistance);
and (iii) mixed pressor agents (i.e., drugs that act
through both mechanism).
(i) Ionotropic/chronotropic agents
Dobutamine hydrochloride, a synthetic b1, b2
receptor agonist is often used for ionotropic
support in cardiogenic shock. It increase
myocardial contractility and CO, reduces
afterload through peripheral vasodilatation and
decreases left ventricular filling pressures with
improvement in diastolic coronary blood flow.
It also prevents increase in infarct size in patients
with acute myocardial infarction by improved
collateral blood flow and balance between oxygen
supply and demand.116,117 Because of b2 mediated
vasodilatation caution should be observed if it
administered to hypotensive patients, especially
with coexistent hypovolemia.
Milrinone lactate, a selective phosphodiesterase
III inhibitor increases ionotropy and decreases
systemic vascular resistance by preventing the
degradation of cyclic adenosine monophosphate.
The hemodynamic effects are similar to those of
dobutamine. Amrinone, is rarely used because
of excessive vasodilatation and thrombocytopenia
following long term use. It may be useful for
synergy in patients already taking a-agonists and
for patients receiving b-blocking agents. The
most accepted use of these agents in the ICU in
the management of congestive heart failure,
cardiogenic shock and post-cardiopulmonary by
pass myocardial dysfunction.
SETHI, SHARMA, MOHTA, TYAGI : SHOCK 353

Dopexamine, a synthetic catecholamine, induced increases in renal vascular resistance

augments cardiac performance through both during vasoconstrictor infusion.123,124,125 Nor-
b2 mediated afterload reduction and baroreceptor epinephrine exerts both powerful ionotropic
reflex mediated ionotropy. Also, added benefit (cardiac a and b1 adrenoreceptors) and peripheral
is its dopaminergic mediated increase in renal vasoconstriction effects (a adrenoceptors). It can
blood flow. Isoproterenol hydrochloride, a pure be used for persistent hypotension despite high
b receptor agonist produces CO augmentation dose dopamine during septic and obstructive
by increasing both HR and contractility. shock.126 It may also improve splanchnic oxygen
Dysrythmias and increased myocardial oxygen dynamics in patients with sepsis.127
requirement limit the use. Digitatis has limited
Epinephrine is occasionally used when other
use in treating acute states of hypoperfusion due
ionotropes/vasopressors have failed to support
to its slow onset of action and lower potency.
blood pressure and/or cardiac output in
(ii) Vasoconstrictor agents circulatory shock.128 It is the first line agent for
Phenylephrine is a pure adrenergic agonist. It management of anaphylactic shock.
causes vasoconstriction thereby increasing BP,
All currently used vasopressors agents ultimately
generally decreasing CO and often reflex slowing
produce their effects by increasing intracellular
of HR. It should be used as a first line agent in
ionized calcium concentration. Thus normal
neurogenic shock. It can also be useful in patients
ionized calcium concentration should be
who, despite maximal fluid and ionotropic
maintained in patients who are on vasopressor
support, remain hypotensive with evidence of
support.
organ hypo perfusion. Pure vasoconstrictors may
compromise flow and perfusion, thus attention (e) Vasodilator agents
to renal function, acid-base balance, serum These drugs reduce afterload and improve CO in
lactate and Do2 is imperative. acute and chronic ventricular failure. For acute
vasodilatation and preload reduction, nitroglycerin is
Vasopressin is used as an alternative therapy for
the agent of choice; for afterload reduction, sodium
vasodilator shock especially where a stimulation
nitroprusside, hydralazine hydrochloride, anggiotensin
does not produce a satisfactory vasoconstrictor
converting enzyme inhibitors and fenoldopam are
response.118,119 Most studies have used doses
preferable. Patients with right-sided heart failure may
between 0.01 and 0.1U per minute.120,121 Other
benefit from pulmonary vasodilators i.e., prostacyclin,
vasoconstrictors are nor-epinephrine and
prostaglandin E1 and inhaled nitric oxide.
bitartrate.
(f) Steroids
(iii) Mixed Pressor Agents
Prospective, double-blind, randomized, multicenter
Dopamine, a precursor of norepinephrine, is
studies have demonstrated no benefit of steroid
commonly used as an initial pressor agent,
administration in hyperdynamic/septic shock. Thus,
acting at several receptors in a dose related
the practice of routine administration of high dose
manner. It can be titrated towards achieving
steroids was abandoned. Stress doses of
different aims of therapy : dopaminergic effects
glucocorticoids are appropriate for treating shock
at less than 4-5 mgkg-1min-1 (e.g., vasodilatation
when it is associated with adrenal insufficiency,
of renal and splanchnic vascular beds), b effect
hypothyroidism, in patients with impaired adrenal
at 5-10 mgkg-1min-1 (e.g., augmentation of cardiac
pituitary axis, or in those who require steroids for
contractility and HR) and a effects at more than
treatment of an underlying immunologic disease (e.g.,
10 mgkg-1min-1 (e.g., vasoconstriction). Debate
vasculitis). Conversely, steroids are relatively
continues, however, as to whether dopamine truly
contraindicated in patients with cardiogenic shock as
improves renal function or merely increases urine
they alter the healing process of the myocardium and
output through diuretic effect. There has been a
predispose to myocardial rupture.133 But recent reports
decreased enthusiasm for its routine use to protect
also suggest a decrease in the endogenous production
the kidneys from hypoperfusion insults or as a
of stress steroids in sepsis, causing vasopressor
means to promote urine output in post
dependence and failure to respond to therapy.131,132
hypoperfusion oliguria.122 However, at dose of
Administration of 100 mg of hydrocortisone 8 hourly
2-3 mgkg-1min-1 it can reverse vasoconstrictor
indicates benefit. The mechanism for benefit may be
354
reversal of catecholamine receptor down regulation
or prevention of inflammatory mediated induction of
nitric oxide synthase. Patients of shock, who require
increasing doses of vasopressors or do not respond
within 24 hrs of therapy may be administered steroids.
However, the topic still remains controversial.
Experimental Therapies
A number of promising new agents have begun to
undergo experimental and clinical study for the treatment
of ischemia and circulatory shock. The release of pro-
inflammatory cytokines is one of the pathway to MODS in
shock.134 The use of receptor and enzymatic blockers as
well as immunotherapy to minize the effect of these agents
is of little use.135 Antibodies to endotoxin, platlet activating
factor, tumor necrosis factor, receptor blockers to
interleukin-1, administration of the anti-inflammatory
cytokine interleukin1, and inhibition of nitric oxide synthase
have not been effective in randomized studies of patients
with SIRS.136-140
Magnesium chloride complexed adenosine
triphosphate (ATP-Mgcl2),141 pentoxifylline,142 oxygen free
radical scavengers143 (i.e., superoxide dismutase,
allopurinol), calcium channel blockers,144,145 haemoglobin
based blood substitutes (i.e., diaspirin-linked hemoglobin,
bovine hemoglobin) are being assessed in experimental
hemorrhagic and septic shock models.146,147
Studies of activated protein (APC) have supported
its role as an endogenous anti-inflammatory compound
that also blocks thrombin induced microcoagulation.148 APC
levels are decreased in 85% of patients with sepsis and
SIRS. The recommendation is for the early (within 24
hours of diagnosis) administration to all patients with three
of four indices of SIRS, known or suspected infection, and
single-organ dysfunction.
Other agents that may hold some promise for the
management of circulatory shock of varying causes include
novel buffers of acidemia (i.e., disodium carbonate/sodium
bicarbonate),149 bacteriocidal increasing permeability protein
(BPI)150 and chloroquine.151
Recently, terlipressin, a long acting vasopressin
analogue has also been studied in cases with septic shock
who did not respond to corticosteroids and methylene blue.
This agent has been suggested to be an effective rescue
therapy and was able to restore blood pressure in patients
with catecholamine-resistant septic shock without obvious
complications including rebound hypotension as has been
reported with vasopressin.152
INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003
Summary
Produced by multiple interacting mechanisms, shock
is a complex, dynamic disorder of tissue and cellular hypo-
perfusion that may lead to MODS and death. Successful
treatment of patients with shock requires prompt recognition
of the shock state and a thorough understanding of the
pathophysiology of various types of shock. Fluids and
pharmacologic agents are the mainstay in the treatment of
shock. Response to therapy can be monitored by indicators
of both total systemic and individual organ perfusion.
Considering the ongoing research and documentation of
the advances in relation to the subject of shock, it
worthwhile to mention that this brief review shall need
revisions repeatedly in the future times.
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147. Manning JE, Katz LM, Brownstein MR, etal: Bovine
hemoglobin-based oxygen carrier (HBOC-201) for
resuscitation of uncontrolled, exsanguinating liver injury in
swine. Carolina Resuscitation Research Group. Shock 2000;
13: 152.
148. Bernard GR, Vincent JL, Laterre PE, et al. Efficacy and
safety of recombinant human activated protein C for severe
sepsis. N Engl J Med 2001; 344: 699-709.
149. Rhee KH, Toro LO, McDonald GG, et al. Carbicarb, sodium
bicarbonate, and sodium chloride in hypoxic lactic acidosis:
SETHI, SHARMA, MOHTA, TYAGI : SHOCK 359

effect on arterial blood gases, lactate concentrations,
hemodynamic variables,and myocardial intracellular PH.
Chest 1993; 104: 913.
150. Hansbrough J, Tenenhaus M, Wikstrom T, et al. Effects of
recombinant bactericidal/permeability-increasing protein
(rBP123) on neutrophil activity in burned rats. J Trauma
1996; 40: 886.
151. Ertel W, Morrison MH, Ayala A, et al. Chloroquine attenuates
hemorrhagic shock induced immunosuppression and
decreases susceptibility to sepsis. Arch Surg 1992; 127: 70.
152. Alastair O’Brien, Lucie Clapp, Mervyn Singer. Terlipressin
for noreplnephrine-resistant septic shock. Lancet 2002; 359:
1209-1210.

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Shock
Alan E. Jones Jeffrey A. Kline
PERSPECTIVE

In philosophic terms, shock can be viewed as a transition between life and death. Whether shock results
from hemorrhage, sepsis, or cardiac failure, mortality rates exceed 20%. [1] [2] In scientific lexicon, shock
results from the widespread failure of the circulatory system to oxygenate and nourish the body
adequately. In the laboratory, the scientist defines the metabolic effect of shock quantitatively, by
examining the mechanisms by which shock alters mitochondrial energy transfer, evokes the production of
toxic chemicals, and reduces their removal. At the bedside, the clinician identifies shock by linking the
clinical impression, synthesized from the patient's history of present illness, age, underlying health status,
and general appearance, to quantitative data, including vital signs, blood chemistry, urine output, and
direct measurements of oxygenation. When the clinical impression and the quantitative data suggest
widespread inadequate organ perfusion, emergent resuscitation must restore normal tissue oxygenation
and substrate delivery to prevent deterioration into systemic inflammation, organ dysfunction, and death.

Classification

For years, shock has been classified into four broad categories based on Blalock's 1934 description:
hematological, neurologic, vasogenic, and cardiogenic. [3] Although it seems archaic to classify a gunshot
wound as “hematologic” shock, this basic organization scheme remains useful today. Box 4-1 outlines
five categories of shock that generally have specific mechanisms and treatments.

BOX 4-1
Categories of Shock According to Primary Treatment
Causes That Require Primarily the Infusion of Volume

Hemorrhagic shock
Traumatic
Gastrointestinal
Body cavity
Hypovolemia
Gastrointestinal losses
Dehydration from insensible losses
Third-space sequestration from inflammation

Causes That Require Improvement in Pump Function by Either Infusion of Inotropic Support or
Reversal of the Cause of Pump Dysfunction

Myocardial ischemia
Coronary artery thrombosis
Arterial hypotension with hypoxemia
Cardiomyopathy
Acute myocarditits
Chronic diseases of heart muscle (ischemic, diabetic, infiltrative, endocrinologic,
congenital)
Cardiac rhythm disturbances
 Atrial fibrillation with rapid ventricular response
Ventricular techycardia
Supraventricular tachycardia
Hypodynamic septic shock (late sepsis)
Overdose of negative inotropic drug
β-blocker
Calcium channel antagonist overdose (e.g., verapamil)
Structural cardiac damage
Traumatic (e.g., flail mitral valve)
Ventriculoseptal rupture
Papillary muscle rupture

Causes That Require Volume Support and Vasopressor Support

Hyperdynamic sepsis syndrome (early sepsis)

Anaphylactic shock
Central neurogenic shock
Drug overdose (dihydropyridines, α1-antagonists)

Problems That Require Immediate Relief from Obstruction to Cardiac Output

Pulmonary embolism
Cardiac tamponade
Pneumothorax
Valvular dysfunction
Acute thrombosis of prosthetic valve
Critical aortic stenosis
Congenital heart defects in newborn (e.g., closure of patent ductus arteriosus with critical aortic
coarctation)
Critical idiopathic subaortic stenosis

Cellular Poisons That Require Specific Antidotes

Carbon monoxide
Methemoglobinemia
Hydrogen sulfide
Cyanide
Epidemiology
The epidemiology of shock in the emergency department remains speculative because shock rarely is
listed as a primary coding diagnosis and usually is hidden within another diagnosis. Patients presenting
with traumatic, cardiogenic, or septic shock constitute about 1% of all emergency department visits. This
chapter reviews the metabolic, systemic, and inflammatory responses that occur in all types of circulatory
shock and discusses specific pathophysiology of the major causes of shock.

PATHOPHYSIOLOGY

At the subcellular level, shock first affects the mitochondria. Mitochondria function at the lowest oxygen
tension in the body, but paradoxically, they consume almost all the oxygen used by the body. More than
95% of aerobic chemical energy comes from mitochondrial combustion of fuel substrates (fats,
carbohydrates, ketones) plus oxygen into carbon dioxide and water. Mitochondria have been referred to
as the “canaries in the coal mine” because they are affected first in conditions of inadequate tissue
perfusion. [4] [5] When mitochondria have inadequate oxygen, the cell converts fuels to lactate ( Figure 4-1
), which accumulates and diffuses into the blood.

Figure 4-1 Energy metabolism with special reference to the development of lactic acidosis in shock. At site A, oxygen
availability to the mitochondrial electron transport system decreases. In the tricarboxylic acid (TCA) cycle (site B), intermediary
metabolites accumulate, including acetyl coenzyme A (AcCoA), which causes the pyruvate dehydrogenase enzyme complex (site
C) to shut down, leading to accumulation in pyruvate. At site D, pyruvate is reduced to lactate, which generates oxidized
+
nicotinamide adenine dinucleotide (NAD ) to permit anaerobic glycolysis to generate a marginal supply of adenosine triphosphate
(ATP). Lactate can diffuse across the cell membrane through a specific monocarboxylase transporter in the cytosolic membrane
(dotted horizontal line). ADP, adenosine diphosphate; NADH, reduced nicotinamide adenine dinucleotide.

Most cellular energy transfer derives from combustion of acetyl coenzyme A (CoA) in the
tricarboxylic acid (TCA) cycle to form reduced pyridine and flavin nucleotides, which pass
electrons along a series of proteins in the inner mitochondrial membrane, culminating in the
reduction of molecular oxygen to form water. The mitochondrion harnesses energy from this
process in an electromotive (proton) gradient to form adenosine triphosphate (ATP) from
adenosine diphosphate plus inorganic phosphate. Acetyl CoA is primarily formed by one of two
pathways: β-oxidation or decarboxylation of pyruvate. Either fatty acids or ketones are processed
by β-oxidation. Pyruvate derives from either glycolysis or lactate dehydrogenation. In addition,
almost every cell in the body possesses its own internal reserve of chemical energy in the form of
triacylglycerol (fat) and glucose (glycogen), which it can expend in times of stress and
inadequate tissue perfusion to allow continuous supply of acetyl CoA into the mitochondria.
In the early stage of shock, the skeletal muscle and splanchnic organs are affected more by oxygen
deprivation than by a lack of delivery of fuel substrate. As a result, shock rapidly stalls transfer of
electrons in the mitochondria and “jams” the pathways of acetyl CoA input into the TCA. The main
byproduct of this jam in oxidative metabolism is lactic acid, which can exit the cell across the cell
membrane by way of a specific protein transporter. In the resuscitated sepsis syndrome[6] and in
resuscitated hemorrhagic shock,[7] skeletal muscle may produce lactate not entirely because of low
mitochondrial oxygenation, but because the delivery of pyruvate from glycolysis overwhelms the ability of
dehydrogenase enzymes in the TCA to dispose of pyruvate, which is converted to lactate. This scenario
has been termed aerobic glycolysis.[8] Regardless of etiology, elevated concentrations of lactate in the
blood serve as a sentinel marker of widespread inadequate tissue perfusion and disappear when
adequate resuscitation has been achieved.

At the whole-body level, shock from any etiology initiates a sequence of stress responses that are
intended to preserve flow to vital organs and to signal cells to expend internal energy stores ( Figure 4-2
). Shock initially reduces wall tension in the large intrathoracic arteries, which activates their
baroreceptors, which activate adrenergic reflexes that have neural and circulating hormonal components.
The two major arms of the neural component include sympathetic fibers from the stellate ganglion, which
stimulates the heart, and sympathetic fibers from regional ganglia, which cause peripheral arterial
vasoconstriction. Exceptions include certain toxic causes of shock (e.g., septic shock) and many drug
overdoses, which can block these reflex sympathetic actions on the heart and vascular smooth muscle.
The circulating “stress hormones” derive mainly from the hypothalamic-pituitary-adrenomedullary axis,
which leads to secretion of epinephrine and norepinephrine from the adrenal medulla and corticosteroids
from the adrenal cortex, renin from the kidney, and glucagon from the pancreas. These hormones signal
the liver to break down glycogen to release glucose into the plasma and alert adipose tissue to release
fatty acids via lipolysis. As a result, stress hormones increase the input of carbon substrates into the TCA
throughout the body, often overwhelming the mitochondrial ability to oxidize them and leading to an
increase in lactic acid production and release into the bloodstream.

Figure 4-2 Overview of whole-body hormonal stress response to shock. Upper left, Stress hormones (catecholamines,
glucagons) stimulate the liver to increase glucose output, derived from glycogen breakdown and by synthesis from lactate and
alanine, which are released from skeletal muscle catabolism (right side). Lower left, Adrenal medulla secretes
glucocorticosteroids and catecholamines, which induce glycogenolysis, insulin resistance, hypokalemia, and lipolysis.
Juxtaglomerular cells of the kidney release renin, which activates the renin-angiotensin-aldosterone (RAA) system. Upper right,
Skeletal muscle becomes more resistant to substrate uptake and continues to release lactate, which becomes the main fuel
source for the heart in shock. FFA, free fatty acids.
Although lactic acidosis is a unifying feature of shock, its exact source may depend on the cause of
shock. Lactic acidosis from hemorrhagic shock probably arises largely from skeletal muscle during
hypotension and after resuscitation,[9] whereas with sepsis the skeletal muscle probably extracts lactate
until the late stage. Some evidence suggests that the viscera and the lung are the primary sources of
lactic acidosis in septic shock.[10]

Initiation of inflammatory events constitutes a third unifying feature of shock. Shock causes neutrophil
activation and liberation of adhesion molecules, which promote binding of neutrophils to vascular
endothelium. Activated, sticky neutrophils can damage organs directly by liberating toxic reactive oxygen
species, N-chloramines, and proteolytic enzymes. Neutrophils also can plug capillaries and cause
microischemia.[11] Although much of the knowledge about the inflammatory responses in shock has
evolved from the study of septic shock, the consensus is that any low-perfusion state that produces
widespread cellular hypoxia can trigger systemic inflammation. Early in sepsis, multiple tissues (e.g.,
macrophages, endothelial and epithelial cells, muscle cells) are signaled to upregulate transcription of
messenger RNA (mRNA) coding for cytokines, including tumor necrosis factors (TNF-α, TNF-β) and
interleukins (IL-1, IL-6).

Figure 4-3 is a brief overview of some of the inflammatory changes that can occur in shock, using the
action of TNF-α on a heart muscle cell as the prototype. Cytokines bind to surface receptors and cause
changes that lead to the activation of nuclear factor κ B (NFκB), a protein that travels to the cell nucleus.
NFκB upregulates the transcription of mRNA needed to synthesize inflammatory cytokines and leads to
production of inducible nitric oxide (NO) synthase, which liberates high concentrations of NO. NO causes
vascular smooth muscle relaxation. Under healthy conditions, NO is produced in small amounts by a
native enzyme, constitutive NO synthase. Constitutive NO synthase provides enough NO to help balance
against naturally produced vasoconstrictors to maintain blood flow to autoregulated organs. When
inducible NO synthase becomes upregulated, however, too much NO is produced, leading to pathologic
vasodilation and eventually conversion of NO to a highly reactive free radical, peroxynitrite, which can
damage cell membranes, DNA, and organelles and contribute to organ failure during shock. [12]

Figure 4-3 Overview of selected inflammatory mechanisms of shock, using the muscle cell as a prototype. Tumor necrosis
factor α (TNF-α) causes upregulation of inducible nitric oxide synthase (iNOS), which overproduces nitric oxide (NO). In
- -
conditions of low oxygen tension, NO reacts with superoxide (O 2 ) generated from the mitochondria to form peroxynitrite (ONOO ),
which can damage mitochondria and decrease adenosine triphosphate (ATP) production. TNF-α also binds to a surface receptor
and causes a shift of nuclear factor κ B (NFκB) protein into the nucleus, which further increases production of TNF-α and other
inflammatory cytokines. TNF-α also causes production of sphingosine, which can directly block release of calcium from the
sarcoplasmic reticulum (SR) and depress cardiac contraction. cGMP, cyclic guanosine monophosphate; IL, interleukin.

Heart Function
During resuscitation from shock, the heart must transition rapidly from a low-work, low-flow state to a
higher workload and maintain adequate cardiac output in the presence of inflammatory injury to the
cardiac myocyte. The degree to which the heart is affected by shock depends on the cause of shock, but
the pathophysiologic effect of cytokine exposure, arterial hypotension, and acidosis on cardiac function
can be generalized.

The heart generates its pumping power during systole by interaction of actin and myosin in the
myofilament. For this interaction to occur, the contractile apparatus has two basic needs, calcium and
chemical energy (ATP or creatine phosphate). Calcium reaches troponin C in the contractile apparatus by
the mechanism of excitation-contraction. In this model, intracellular calcium release starts with an external
electrical signal on the myocyte surface, which opens voltage-dependent calcium channels on the
membrane. These slow, or L-type, channels conduct the current of calcium that causes the plateau phase
(II) of the ventricular myocyte action potential. This relatively small influx of calcium triggers a larger
release of calcium from the sarcoplasmic reticulum by way of a connection between involutions of the
plasma membrane, called the T tubules. This connection is the ryanodine-sensitive pathway; the alkaloid
agent ryanodine is used experimentally to evoke calcium release from the sarcoplasmic reticulum. The
force of cardiac contraction varies in proportion to the amount of calcium bound to troponin C during
systole. To increase strength of cardiac contraction, or cardiac contractility, the clinician either must
increase calcium entry through the L channel or must increase calcium release from the sarcoplasmic
reticulum. In almost all cases, clinically available inotropic drugs work by the former mechanism, by
binding to cardiac membrane β1-receptors (catecholamines), or by inhibition of cyclic adenosine
monophosphate (cAMP) breakdown (phosphodiesterase inhibitors), which leads to phosphorylation of the
L channel via the stimulatory G protein. Phosphorylation of the L channel increases its probability of
opening, increasing calcium entry and myocardial contractility.

The other component of cardiac contraction, chemical energy, comes almost entirely from mitochondrial
oxidative phosphorylation. Myocardial mitochondria must remain highly active to meet the mechanical
energetic needs of the heart. The heart lives on a thin margin of high-energy phosphate supply; it has
been estimated that the heart completely turns over its reserve of ATP and creatine phosphate every 5 to
10 beats.[13]

Cardiac function may be indirectly depressed in shock conditions by coronary hypotension. In an isolated
working heart, the strength of cardiac contraction varies in proportion to the coronary perfusion pressure
(the Gregg phenomenon). The cellular basis for the link between contractile strength and coronary
perfusion pressure seems to be independent of the L-type calcium current.[14] Although decreased
coronary perfusion aggravates cardiac performance in shock,[15] it is more difficult to determine if coronary
hypotension causes myocardial ischemia in shock. While myocardial oxygen delivery decreases as
coronary flow diminishes in shock, the oxygen requirement for the heart decreases in proportion to
coronary flow because the external workload on the heart diminishes. With respect to oxygen, the heart
[16]
seems to obtain what it needs during hypotensive shock. Whether shock is caused by hemorrhage,
[17] [18]
sepsis, or drug-induced cardiogenic shock, the heart extracts lactate, indicating the absence of
global myocardial hypoxia. A substantial body of evidence now suggests that specific actions of cytokines
may decrease cardiac function, especially in hyperinflammatory causes of shock, such as sepsis (see
Figure 4-3 ). [12] [19] [20] In addition, intracellular and extracellular acidosis can depress cardiac contraction,
but in the whole picture of shock, the contribution of acidosis to depressed heart function is probably
minimal.

Specific Causes
Hemorrhagic Shock

Hemorrhagic shock results from a rapid reduction in blood volume, which causes baroreceptor activation
and leads to vasoconstriction, increased strength of cardiac contraction, and increased heart rate (HR).
Cardiovascular response to hemorrhage can vary with underlying cardiopulmonary status, age, and
presence of ingested drugs. Responses of HR and blood pressure (BP) are notoriously variable in
hemorrhage, so no firm conclusion can be made at the bedside about the presence or absence of
hemorrhagic shock simply by evaluating HR and BP.[21] In general, hemorrhage first increases pulse and
cardiac contraction, then increases vasoconstriction. The first clinical manifestations of hemorrhage are
tachycardia, then a slight increase in the diastolic BP, causing the pulse pressure (difference between
systolic and diastolic BP) to narrow. With worsened bleeding, ventricular filling is compromised, and
cardiac output decreases, followed by a reduction in systolic BP. Before the total cardiac output begins to
decrease, blood flow to noncritical organs and tissues (e.g., skin, skeletal muscle, viscera) begins to
decrease, and these tissues produce lactic acid.

Consequently a change in arterial acid-base status often precedes any significant decrease in cardiac
output with hemorrhage.[22] The base deficit is defined as the amount of strong base that would have to
be added to 1 L of blood to normalize the pH. In the clinical setting, the base deficit is indirectly calculated
from the pH and arterial carbon dioxide partial pressure (PaCO2) and is normally more positive than -2
mEq/L. Accordingly the arterial and venous blood base deficit worsens (the numeric measurement
becomes more negative) early in hemorrhage even while pH and BP remain in the normal range. It can
be scientifically rationalized that the threshold to distinguish simple hemorrhage from hemorrhagic shock
occurs when the base deficit worsens (the total body base deficit increases, but the laboratory numeric
measurement becomes more negative), indicating widespread tissue hypoperfusion. To maintain a
normal arterial pH, the brainstem chemoreceptor responds to acidemia by increasing minute ventilation,
leading to reduced PaCO2. After approximately one third of the total blood volume is acutely lost,
cardiovascular reflexes no longer can cause adequate filling of the arterial circuit, and frank hypotension
supervenes. Arterial hypotension is generally and arbitrarily defined as a systolic arterial BP less than 90
mm Hg, but this threshold should be increased to 100 mm Hg in patients with known systemic
hypertension and in patients older than age 60 years. Usually coincident with the development of
hypotension, the patient no longer can hyperventilate sufficiently to maintain a normal arterial pH, and
acidemia occurs. Hemorrhagic shock causes a large activation of the hypothalamic-pituitary-
adrenomedullary axis, with release of stress hormones that cause glycogenolysis, lipolysis, and mild
hypokalemia (see Figure 4-2 ). In the emergency department, patients sustaining traumatic hemorrhage
generally have an arterial lactate concentration greater than 4 mmol/L, a PaCO2 less than 35 mm Hg, and
mild hyperglycemia (150 to 170 mg/dL) and hypokalemia (3.5 to 3.7 mEq/L). Although hemorrhagic
hypotension does significantly alter ventilation-perfusion relationships in the lung, hemorrhagic
hypotension seldom produces arterial hypoxemia if the airway is clear, the lungs are not injured, and
respiratory effort is adequate.

The second phase of organ injury from hemorrhagic shock occurs during resuscitation. Many experts
assert that the period of hemorrhage “cocks the gun,” and resuscitation “pulls the trigger” to cause organ
injury from hemorrhagic shock. During resuscitation, neutrophils become most aggressive, binding to the
lung endothelium and initiating capillary leak, which can produce acute respiratory distress syndrome
(ARDS). Inflammatory cytokines are liberated during resuscitation, and membrane injury occurs in many
cells. In the liver, damage from inflammation and reactive oxygen species from neutrophils is
compounded by persistent microischemia. During resuscitation from hemorrhagic shock, the normal
balance of vasodilation by NO versus vasoconstriction by endothelins becomes distorted, producing
patchy centrilobular ischemic damage in the liver, which may produce an immediate increase in blood
transaminase levels. A growing body of evidence suggests that retransfusion from hemorrhage exerts
greater injury to the heart than the actual hypotensive insult. [23] [24] Depending on the degree of
hypotensive insult, the kidney may manifest acute spasm of the preglomerular arterioles, causing acute
tubular necrosis. Systemic metabolic changes can impair fuel delivery to the heart and brain, secondary
to depressed hepatic glucose output, impaired hepatic ketone production, and inhibited peripheral
lipolysis.[25]

Septic Shock

Septic shock can be produced by infection with any microbe. Previously, gram-negative aerobic bacteria
were the primary organisms that caused septic shock; however, more recently the incidence of gram-
[1]
positive infections has increased to a frequency equal to that of gram-negative infections. In one third of
cases of septic shock, no organism is identified. One of the chief mediators of sepsis is
lipopolysaccharide, which is contained in the cell wall of gram-negative bacteria. Infusion of
lipopolysaccharide into humans or animals produces cardiovascular, immunologic, and inflammatory
changes identical to the changes observed with microbial infection. In recent years, multicenter trials have
suggested the emergence of gram-positive organisms as the chief cause of sepsis in hospitalized
patients. Further growth in primarily gram-positive sepsis occurs for two main reasons:

1. More patients are being treated at home for chronic immunocompromising diseases with indwelling
catheters, which serve as excellent portals of entry into the vascular space for Staphylococcus
aureus and coagulase-negative staphylococci.
2. The frequency of community-acquired infections caused by antibiotic-resistant, gram-positive
organisms has increased greatly, including infections caused by S. aureus, Streptococcus
 pneumoniae, and Streptococcus pyogenes.

Septic shock causes three major effects that must be addressed during resuscitation: hypovolemia,
cardiovascular depression, and induction of systemic inflammation. Septic shock always produces
relative hypovolemia from increased venous capacitance, which reduces right ventricular filling. Septic
shock often causes absolute hypovolemia from gastrointestinal volume losses, tachypnea, sweating, and
decreased ability to drink during development of the illness. Sepsis also induces capillary leak, which
leads to relative loss of intravascular volume into third spaces. Evidence has shown that septic shock
causes myocardial depression simultaneously with vasodepression and capillary leak. For years it was
thought that septic shock depressed the heart only in the later, hypodynamic stages because sepsis
induces hyperdynamic heart function, characterized by an increase in cardiac output.[26] More
sophisticated and direct measurements of cardiac contractility have shown, however, that cardiac
mechanical function becomes impaired early in the course of septic shock, even in the hyperdynamic
stages.[27] Evidence for multiple mechanisms may explain depressed heart function in sepsis, including
actions of specific cytokines (most notably TNF-α and IL-1β),[20] overproduction of NO by inducible NO
synthase,[12] and possibly impairment in mitochondrial oxidative phosphorylation[28] coincident with
reduced mechanical efficiency.[29] Evidence indicates that circulating mediators, myocellular injury from
inflammation, and deranged metabolism interact synergistically to injure the heart during septic shock.
Systemic inflammation causes capillary leak in the lung, which may cause alveolar infiltration
characteristic of ARDS early in the treatment of septic shock in 40% of patients.[1] With the potential for
early development of ARDS, more profound ventilation-perfusion mismatching, and pneumonia or
pulmonary aspiration, hypoxemia is more severe with septic shock than hemorrhagic shock.

Cardiogenic Shock

Cardiogenic shock results when more than 40% of the myocardium becomes necrosed from ischemia,
inflammation, toxins, or immune destruction. The primary cause of cardiogenic shock is pump failure.
Otherwise, cardiogenic shock essentially produces the same circulatory and metabolic alterations that are
observed with hemorrhagic shock. Impaired baseline cardiac function can contribute to the development
of circulatory shock state secondary to infection, hemorrhage, or vasodilatory drug overdose. When shock
results from a pure cardiac cause, however, severe left ventricular dysfunction is evident on
echocardiography early in the course. Patients with severe left ventricular dysfunction are far more likely
to have a cardiogenic cause of shock than patients with normal or moderate left ventricular dysfunction.[30]

Acute massive pulmonary embolism produces circulatory shock by obstruction of the pulmonary
vasculature, which leads to right ventricular overload and impairs left ventricular filling. Echocardiogram
and electrocardiogram (ECG) observations suggest that selective right ventricular ischemia occurs with
[31]
massive pulmonary embolism. A pulmonary embolism large enough to cause shock always results in
pulmonary ventilation-perfusion mismatching, so arterial hypoxemia becomes a significant problem.
Hypoxemia, together with coronary hypoperfusion from arterial hypotension, and systemic acidosis may
produce synergistic effects on cardiac function, resulting in a “stunning” effect on right and left
ventricles.[32]

Anaphylactic Shock

Anaphylactic shock results from an IgE-mediated systemic response to an allergen. The mast cell plays a
central role in the etiology of anaphylactic shock. IgE causes mast cells to release histamine, which
results in vascular smooth muscle relaxation, bronchial smooth muscle constriction, and capillary leak of
plasma into interstitial spaces. Platelets also participate in anaphylaxis by secreting platelet-activating
factor (PAF), which is derived from membrane phospholipid. PAF causes peripheral vasodilation,
bronchial constriction, and pulmonary arterial and coronary vasoconstriction. Antagonists to PAF can
[33]
reverse the negative inotropy and vasodilation observed with experimental anaphylaxis. As such, PAF
may be an important mediator of anaphylaxis that is refractory to antihistamine treatments.

CLINICAL FEATURES

Patients frequently present to the emergency department in shock with no obvious etiology. Rapid
recognition of shock requires the integration of information from immediate history and physical
examination. Shock can be strongly supported by the presence of a worsening base deficit or lactic
acidosis. In general, patients in shock exhibit a stress response: They are ill appearing, pale, often
sweating, usually tachypneic or grunting, and often with a weak and rapid pulse ( Box 4-2 ). HR can be
normal or low in shock, especially in cases complicated by prescribed drugs or profound hypoxemia that
can depress HR. BP can be normal because of adrenergic reflexes or because of measurement errors
from cuff sphygmomanometry.[21] As a result, arterial BP as a sole measurement remains an unreliable
marker of circulatory status. The HR-to-systolic BP ratio may provide a better marker of shock than either
measurement alone; a normal ratio is less than 0.8.[34] Urine output provides an excellent indicator of
organ perfusion and is readily available with insertion of a Foley catheter into the bladder. Measuring
urine output requires at least 30 minutes, however, to determine accurately if output is normal (>1
mL/kg/hr), reduced (0.5 to 1 mL/kg/hr), or severely reduced (<0.5 mL/kg/hr). Measurements of the arterial
lactate concentration and the base deficit can be performed rapidly and provide accurate assessment of
global perfusion status. An arterial lactate concentration greater than 4 mM/L or an arterial base deficit
more negative than -4 mEq/L predicts the presence of circulatory insufficiency severe enough to cause
subsequent multiple organ failure.[35]

BOX 4-2
Empiric Criteria for Diagnosis of Circulatory Shock[*]

▪ Ill appearance or altered mental status

▪ Heart rate >100 beats/min
▪ Respiratory rate >22 breaths/min or PaCO2 <32 mm Hg
▪ Arterial base deficit <-5 mEq/L or lactate >4 mM/L
▪ Urine output <0.5 mL/kg/hr
▪ Arterial hypotension >20 minutes duration
* Regardless of cause. Four criteria should be met.

When the empiric criteria for circulatory shock are discovered, the next step is to classify the cause of
shock ( Figure 4-4 ). Although the questions in Figure 4-4 are connected in sequence to allow logical
organization, parallel processing of all these questions is required to determine a cause rapidly in
practice. The history, vital signs, and physical examination documented by prehospital providers
represent a valuable insight into a patient's physiologic status before any medical intervention and can be
useful in emergency department management. A study found that nontrauma patients with symptoms
consistent with circulatory insufficiency and prehospital hypotension (systolic BP <100 mm Hg) have a
threefold increase in in-hospital mortality than patients without hypotension. [36]
Figure 4-4 Flow diagram to classify undifferentiated shock.

The primary survey must ensure presence of a patent airway and sufficient respiratory effort to ensure
adequate oxygenation and ventilation. The physical examination should be performed on an undressed
patient and should begin with general inspection of the body for visual or tactile evidence of trauma; odor
of ethanol or other toxins; presence of any indwelling devices; and evidence of soft tissue or bone
infection, rashes, or extremity edema. Dry mucous membranes suggest dehydration, whereas distended
jugular veins suggest cardiac failure or obstruction from pulmonary embolism or cardiac tamponade.
Muffled heart sounds suggest cardiac tamponade, whereas a loud machine-like systolic murmur indicates
acute rupture of a papillary muscle or rupture of the interventricular septum. Bilateral pulmonary rales in a
patient with a normal rectal temperature help to define the presence of left ventricular failure. Wheezing
suggests bronchospasm from anaphylaxis or, less likely, cardiac failure or pulmonary embolism.
Abdominal tenderness may indicate peritoneal inflammation or occult trauma. Rectal and pelvic
examinations may disclose occult gastrointestinal hemorrhage or an unexpected adnexal mass or
tenderness indicating an ectopic pregnancy. Rectal temperature should be performed on every patient
with suspected shock.

The initial neurologic examination may be extremely helpful, especially to providers later during
hospitalization, and should include notation of speech fluency and content, ability to follow one-step
commands, pupillary function and cardinal eye movements, symmetry of extremity movements, and
strength. In children, documentation should include level of alertness, response to parents,
appropriateness of crying, pupillary function, symmetry of grimace, and symmetry of extremity
movements (and motor tone in infants).

Laboratory, radiographic, and other ancillary data should be ordered (1) to assess tissue and vital organ
perfusion and (2) to diagnose injury from trauma, find the source of infection with sepsis, or identify the
cause of cardiac failure. A chest radiograph can identify significant thoracic trauma, pulmonary infection,
pulmonary edema, or tension pneumothorax. In adults, an ECG helps to identify myocardial ischemia,
cardiac failure from dysrhythmia, or pulmonary embolus. A finger-stick glucose measurement can identify
unsuspected hyperglycemia or hypoglycemia, which might prompt further evaluation for myocardial
ischemia or a source of infection. A hemoglobin level less than 8 g/dL strongly suggests the need for
blood transfusion if other criteria for shock are present (see Box 4-2 ). Serum electrolytes can help
identify a metabolic acidosis indicating lactic acidosis, an elevated blood urea nitrogen-to-creatinine ratio
suggests dehydration or chronic gastrointestinal bleeding, and combined electrolyte abnormalities of
hyponatremia and hyperkalemia suggest adrenal insufficiency. The complete blood count helps to
diagnose anemia or identify neutropenia. Arterial blood gases are ordered for a base deficit calculation; a
normal arterial oxygen partial pressure (PaO2) from a patient breathing room air can rule out hypoxemia.
Serum lactate measurement should be performed as early as possible in patients with suspected shock.
Urinalysis can reveal dehydration (specific gravity >1.025 with ketones present) and can identify urinary
infection as a cause of sepsis. Some emergency departments have bedside ultrasound capability, and
cardiac and abdominal scanning can be performed rapidly at the bedside to screen for inadequate central
venous volume, occult hemoperitoneum, abdominal aortic aneurysm, left ventricular failure, and cardiac
tamponade. A systematic ultrasound protocol can improve significantly the physician's ability to diagnose
accurately the etiology of undifferentiated shock in emergency department patients.[37]

Consensus definitions of shock show the spectra of hypoperfusion for the following three common causes
of shock ( Box 4-3 ):

1. Septic shock. The American College of Chest Physicians and Society for Critical Care Medicine[38]
developed a consensus to distinguish septic shock from its precursor conditions, systemic
inflammatory response syndrome and sepsis syndrome. Although this particular consensus
requires persistent hypotension to define septic shock, initiation of treatment for empirically
diagnosed septic shock should not await the onset of hypotension.
2. Hemorrhagic shock. The American College of Surgeons has divided hemorrhagic shock into four
stages, depending on the severity of blood loss and the physiologic response to this loss, but such
arbitrary divisions are of little value. A more useful approach defines hemorrhagic shock as being
present when systemic hypoperfusion manifests as lactic acidosis with organ dysfunction.
3. Cardiogenic shock. Many experts reserve the definition of cardiogenic shock for cardiac failure with
arterial hypotension that is refractory to inotropic/vasopressor therapy.[39] Cardiogenic shock should
be thought to be present, however, whenever cardiac failure (ischemic, toxic, or obstructive)
causes systemic hypoperfusion that manifests as lactic acidosis with organ dysfunction.
BOX 4-3
Definitions and Criteria for Septic, Hemorrhagic and Cardiogenic Shock
Septic Shock

▪ Systemic inflammatory response syndrome (SIRS)

Two or more of the following:
1. Temperature >38° C or <36° C
2. Heart rate >90 beats/min
3. Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg
4. While blood cell count >12,000/mm 3, <4000/mm3, or >10% band neutrophilia
▪ Sepsis syndrome
SIRS associated with organ dysfunction or hypotension; organ dysfunction may include
presence of lactic acidosis, oliguria, or altered mental status
▪ Septic shock
SIRS with hypotension despite adequate fluid resuscitation; septic shock should still be
diagnosed if vasopressor therapy has normalized blood pressure

Hemorrhagic Shock
 ▪ Simple hemorrhage
Suspected bleeding with pulse <100 beats/min, normal respiratory rate, normal blood pressure,
and normal base deficit
▪ Hemorrhage with hypoperfusion
Suspected bleeding with base deficit <-5 mEq/L or persistent pulse >100 beats/min
▪ Hemorrhagic shock
Suspected bleeding with at least four criteria listed in Box 4-2

Cardiogenic Shock

▪ Cardiac failure
Clinical evidence of impaired forward flow of the heart, including presence of dyspnea,
tachycardia, pulmonary rales, peripheral edema, or cyanosis
▪ Cardiogenic shock
Cardiac failure plus four criteria listed in Box 4-2

MANAGEMENT
Monitoring Perfusion Status

In the effort to resuscitate a patient with circulatory shock, the clinician must follow specific indices of
systemic perfusion and organ function to know if the resuscitation effort is working. In all patients with
shock, circulation must be monitored by continuous ECG and pulse oximetry to follow HR and to maintain
arterial oxygenation. BP should be measured by cuff sphygmomanometer every 2 to 5 minutes during
resuscitation. Because cuff sphygmomanometer measurement may be inaccurate in severe hypotensive
states, the use of an arterial pressure monitoring line should be considered. Clinicians should remember
that BP and HR correlate poorly with cardiac index in shock and often underestimate the severity of
systemic hypoperfusion.[21] Children with hypovolemic shock frequently have a normal BP until they
rapidly deteriorate to a near-arrest hemodynamic state.[40] Urine output should be measured as an index
of vital organ perfusion in patients (about 1 mL/kg/hr in persons without renal disease). Normalization of
the serum lactate concentration or the base deficit, when observed with improving vital signs and urine
output, can gauge reliably the adequacy of resuscitation and prognosis in shock from any etiology. [41]
[35]

An increasing lactate concentration (or refractory hypotension with worsening base deficit) with ongoing
volume resuscitation portends high mortality and mandates more aggressive resuscitation or specific
procedural intervention.

The method of achieving intravenous access in a patient with suspected shock has been controversial.
Most patients with shock can be fully resuscitated and adequately monitored with peripheral venous
access established either with two catheters of size 18-gauge or smaller or with one catheter 16-gauge or
larger. Patients with cardiac failure or renal failure may require closer measurement of the central venous
pressure (CVP) and insertion of a central venous catheter. An 8.5F central venous catheter allows for
accurate measurement of the CVP and insertion of a pulmonary artery catheter or other monitoring
device if needed. In children, a 3F or 5F bi-lumen catheter can be placed in the femoral vein with few
[42]
complications. To reduce the potential for limb damage from extravasation from a peripheral
intravenous catheter, vasoactive medications optimally are administered through a central venous
catheter. If vasoactive medications are administered, additional peripheral intravenous catheters are
required for infusion of crystalloid and other treatments. Many patients with renal disease or cancer have
indwelling catheters in place. In patients with empiric criteria for shock, this catheter should be used for
intravenous access, unless satisfactory access already has been established. In emergency departments,
where the standard practice is not to use these ports at the request of other physicians, a specific hospital
policy and training session should be developed to make an exception in the case of circulatory shock. If
such a policy does not exist, the threat to the patient from failure to administer fluids rapidly and in
sufficient quantity outweighs considerations about preservation of the line for future therapy.
Goal-Directed Therapy

Goal-directed therapy refers to the practice of resuscitating patients to a defined physiologic endpoint
indicating that systemic perfusion and vital organ function have been restored. [35] For many years in the
intensive care unit (ICU), physicians have relied on the use of the pulmonary artery catheter to help
optimize left ventricular filling indices. At present, the use of the pulmonary artery catheter is
controversial, based on evidence suggesting that its insertion was associated with increased morbidity in
ICU populations. One multicenter randomized, controlled trial evaluated using pulmonary artery catheters
in ICU patients with shock or ARDS (or both), and there were no differences in the use of vasoactive
agents, number of days of organ failure, or mortality.[43] When data from 16 randomized, controlled trials
were aggregated in a meta-analysis, however, pulmonary artery catheterization was associated with
significantly reduced morbidity in ICU populations.[44] Insufficient data have been published to support the
use or avoidance of pulmonary artery catheters in emergency department patients.

Several alternative methods to the pulmonary artery catheter have been proposed as endpoints to
resuscitation in the emergency department. The lactate clearance index refers to serial measurements of
arterial lactate.[41] Lactate clearance involves measuring the blood lactate concentration at two or more
times. If the lactate concentration has not decreased by 50% 1 hour after resuscitation has begun,
additional steps must be taken to improve systemic perfusion. Resuscitation should continue until the
lactate concentration decreases to less than 2 mM/L. Enthusiasm for lactate measurement as an
endpoint must be tempered by the relative lack of data from emergency department studies and the lack
of availability of the test.

Mixed venous oxygen saturation (SvO2) measurements reflect the balance between oxygen delivery and
oxygen consumption. Previous studies suggested that the SvO2 can be used as a surrogate to cardiac
index when targeting normalization of endpoints (SvO2 70% or cardiac index 2.5 to 3.5 L/min/m2) for
therapeutic intervention in critically ill patients.[45] Although SvO2 requires the use of a pulmonary artery
catheter, the central venous oxygen saturation (ScvO2) drawn from the central circulation has been
shown to parallel the SvO2 closely, especially when tracking changes or trends in the values.[46]

Gastric or rectal tonography also has been studied extensively in ICU populations. A buffer-filled balloon
consisting of a permeable membrane is inserted into the stomach or rectum. The balloon has an
electrode in the buffer solution and can estimate the intramucosal pH. Mucosal pH is used to estimate the
perfusion status of the gut. Use of gastric tonography as an endpoint failed to predict organ dysfunction
and mortality in one randomized, controlled study of heterogeneous ICU patients admitted from an
emergency department.[47]

Goal-directed therapy incorporates multiple indices of circulatory status and oxygenation status. One
study found that goal-directed therapy significantly reduced mortality and morbidity in emergency
department patients with systemic inflammatory response syndrome and several criteria for severe sepsis
[48]
or septic shock. Patients were resuscitated within the first 6 hours of care to achieve several
hemodynamic parameters and to maintain central venous oxygen saturation greater than or equal to 70%
( Figure 4-5 ). This new treatment strategy has not been tested in other causes of shock, but it shows the
value of using defined physiologic endpoints to measure systemic perfusion during resuscitation from
shock in the emergency department. This approach also further substantiates the view that the real
“make-or-break” time to treat shock occurs during the first 6 hours of resuscitation.
Figure 4-5 Flow diagram outlining the protocol for early goal-directed therapy when treating patients with severe sepsis or
septic shock. This protocol outlines specific hemodynamic and physiologic parameters the clinician should seek to achieve within
the first 6 hours of care. This protocol is focused on resuscitation and should be used in conjunction with standard clinical care for
patients with suspected infection, such as appropriate diagnostic studies to determine the focus of infection and appropriate
antimicrobial agents to treat the infection. CVP, central venous pressure; MAP, mean arterial pressure; Scvo2, central venous
oxygen saturation. (Redrawn from Rivers E, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med 345:1368, 2001.)

Ventilation

Rapid sequence intubation is the preferred method in most patients with shock (see Chapter 1 ).
Anesthetic agents with a high degree of cardiovascular stability, such as ketamine or etomidate, should
be used in reduced dosages (half of normal induction dose) with a full dose of succinylcholine to achieve
intubation while minimizing cardiovascular depression. Intubation prevents aspiration, increases
oxygenation, treats acute respiratory failure, provides initial treatment for metabolic or hypercarbic
acidemia, and protects the patient who will be sent to an uncontrolled environment (e.g., for tests).
Intubation also reduces the work of breathing, which, in the hypoperfused patient, further exacerbates
lactic acidemia. Strenuous use of accessory respiratory muscles can increase oxygen consumption by
50% to 100% and decrease cerebral blood flow by 50%. [49] [50] More importantly, if the patient has
increased airway resistance (e.g., bronchospasm with anaphylaxis) or a decrease in lung compliance
(e.g., pulmonary edema, ARDS), a more negative intrathoracic pressure must be generated to fill the
lungs with each inspiration. The greater suction effect also is exerted on the left ventricle, impeding its
ability to eject and increasing functional afterload. Positive-pressure ventilation removes this impedance
and can improve ventricular function and cardiac output 30%.[49]

All intubated shock patients require at least 5 cm H2O of positive end-expiratory pressure to prevent
alveolar consolidation. In acute respiratory failure, ventilation at zero positive end-expiratory pressure can
cause widespread alveolar collapse and lead to severe ventilation-perfusion mismatch and hypoxemia
(see Chapter 2 ).

Volume Replacement

The next imperative in shock is to decide when “the tank is full.” The goal in volume replacement is
slightly elevated left ventricular end-diastolic volume, which is a difficult measurement to make in the
emergency department. The CVP is used most often to estimate right ventricular filling pressure and is
used in some goal-directed algorithms. Because both ventricles tend to stiffen during shock, a high CVP
(10 to 15 cm H2O) is often needed to produce adequate filling volume. It is a long way, however, from the
CVP measurement to actual knowledge of left ventricular end-diastolic volume; a presumed adequate
CVP must be substantiated by increases in urine output and BP and decreasing lactate concentrations. [51]

Treating Specific Causes

Box 4-4 summarizes the general treatment approach for the four common causes of shock.

BOX 4-4
Clinical Management Guidelines for Four Common Causes of Shock
Hemorrhagic Shock

▪ Ensure adequate ventilation/oxygenation

▪ Provide immediate control of hemorrhage, when possible (e.g., traction for long bone fractures,
direct pressure)
▪ Initiate judicious infusion of lactated Ringer's solution (10-20 mL/kg) or 5% hydroxyethyl starch
(5 mL/kg)
▪ With evidence of poor organ perfusion and 30-minute anticipated delay to hemorrhage control,
begin packed red blood cell (PRBC) infusion (5-10 mL/kg)
▪ With suspected central nervous system trauma or Glasgow Coma Scale score <9, immediate
PRBC transfusion may be preferable as initial resuscitation fluid
▪ Treat severe acidosis (pH <6.8) with THAM
▪ Treat coincident dysrhythmias (e.g., atrial fibrillation with synchronized cardioversion)

Cardiogenic Shock

▪ Ameliorate increased work of breathing; provide oxygen and positive end-expiratory pressure
(PEEP) for pulmonary edema
▪ Begin inotropic support; dobutamine (5μg/kg/min) is common empiric agent
▪ Seek to reverse the insult (e.g., initiate thrombolysis, arrange percutaneous transluminal
angioplasty, or administer charcoal for drug overdose)
▪ Consider intra-aortic balloon pump counterpulsation for refractory shock

Septic Shock

▪ Ensure adequate oxygenation; remove work of breathing.

 ▪ Administer 20 mL/kg of crystalloid or 5 mL/kg of colloid, and titrate infusion to adequate urine
output
▪ Begin antimicrobial therapy; attempt surgical drainage or debridement
▪ If volume restoration fails to improve organ perfusion, begin vasopressor support; initial choice
includes dopamine, infused at 5-15μg/kg/min, or norepinephrine, infused at 0.1-1μg/kg/min

Anaphylactic Shock

▪ Control airway and ventilation

▪ Administer 10-20 mL/kg of crystalloid
▪ Test an intravenous bolus of epinephrine (50-100μg), then mix 5 mg of epinephrine in 500 mL of
normal saline. Begin infusion at 10 cc/hr, and titrate to arterial blood pressure response
▪ Administer 5-10 mg/kg of hydrocortisone or 1-2 mg/kg of methylprednisolone
Hemorrhagic Shock

Standard treatment for hemorrhagic shock consists of rapidly infusing several liters of isotonic crystalloid
in adults or three successive 20-mL/kg boluses in children. Colloids, including albumin and hydroxyethyl
hetastarch (Hespan), also can be used but at considerable increase in cost and without substantial effect
on morbidity or mortality. Colloids offer the theoretical advantage of a high osmotic pressure, which
should help to maintain a normal intravascular volume after retransfusion from hemorrhage. If criteria for
shock persist despite crystalloid infusion (see Box 4-2 ), packed red blood cells should be infused (5 to 10
mL/kg). Type-specific blood should be used when the clinical scenario permits, but uncrossmatched
blood should be used immediately for patients with arterial hypotension and uncontrolled hemorrhage. O-
negative blood is used in women of childbearing age, and O-positive blood is used in all other patients
(see Chapter 5 ). Substantial evidence supports the use of leukodepleted blood, which has been filtered
to remove donor neutrophils.[52] Leukodepleted blood is used in countries outside the United States
because it produces less retransfusion-related organ damage.[53]

The infusion of hemoglobin-based oxygen carriers as alternatives to packed red blood cells for
resuscitation of hemorrhagic shock patients has been studied extensively. In a large randomized,
controlled trial, diaspirin cross-linked hemoglobin, a purified and chemically modified human hemoglobin
substrate, was compared with crystalloid for initial resuscitation in critically injured patients, and its use
[54]
resulted in a higher mortality at interim analysis resulting in termination of the trial. Other artificial
hemoglobin substitutes may be available in the future but at present show no benefit over packed red
blood cells.

More recent studies have endorsed the concept of either delayed resuscitation or hypotensive
resuscitation for hemorrhagic shock. Bickell and associates[55] showed improved mortality among patients
with penetrating torso trauma in whom all resuscitation was withheld until they reached the operating
room compared with patients who received standard resuscitation in the prehospital and hospital setting.
Other studies have found no mortality difference in patients with hemorrhagic shock who were
resuscitated to either standard clinical parameters (systolic BP >100 mm Hg) or hypotensive parameters
(systolic BP 70 mm Hg).[56] Although interesting concepts, further prospective controlled studies are
needed before the concept of withholding or limiting volume resuscitation in patients with severe bleeding
can be endorsed. Controlling hemorrhage remains the cornerstone of treating hemorrhagic shock, and
evidence continues to support immediate surgery when direct vascular control cannot otherwise be
obtained (see Chapter 34 ).

In rare instances, hypodynamic hemorrhagic shock may be treated with a positive inotropic drug.
Amrinone and dopamine decrease mortality in crystalloid-resuscitated animals with hemorrhage. [57]

Septic Shock
Septic shock begins as an infectious nidus, which triggers a domino effect of cellular, microvascular,
hematologic, and cardiovascular dysfunction. Treatment begins by establishing adequate ventilation to
correct hypoxia and pH and to reduce systemic oxygen consumption and left ventricular work.
Endotracheal intubation and sedation with or without chemical paralysis are often required.

The second goal is to achieve adequate ventricular filling. The choice of fluids in treating septic shock is
probably less important than scrupulous monitoring for adequate tissue perfusion. Colloid solutions may
decrease the incidence of postresuscitative pulmonary edema and degree of ARDS.[58] Choices for fluid
resuscitation involve consideration of availability and the cost-to-benefit ratio. The initial volume
replacement should include rapid infusion of 20 to 25 mL/kg of crystalloid, followed by 5- to 10-mL/kg
boluses of the least expensive colloid available (usually 6% hydroxyethyl hetastarch) for persistent
hypoperfusion. Blood should be transfused in the emergency department to restore hematocrit to at least
30% to 35%.

The third directive is to eradicate the infection with antimicrobial therapy and, when necessary, surgical or
percutaneous drainage. If an infectious focus is found, the choice of antimicrobial agent can be directed
by clinician experience and institutional minimal infective concentration data. When no focus can be found
in septic shock, a semisynthetic penicillin with a β-lactamase inhibitor, in combination with an
aminoglycoside plus vancomycin, or monotherapy with imipenem-cilastatin is a rational empiric choice.
When neutropenia is suspected in a patient with sepsis syndrome, the progression to refractory, fatal
septic shock can be cataclysmic. Neutropenia should be suspected in patients who have recently
undergone chemotherapy. Chemotherapy patients with sepsis represent a special challenge because the
pathophysiology may be complicated by anemia, thrombocytopenia, dehydration from vomiting, and the
effect of adjunctive steroid therapy. Chemotherapy patients often have indwelling catheters, which
predispose them to more unusual causes of sepsis, including gram-positive bacteria and fungi.[59]

Septic shock refractory to volume restoration (urine output or BP remains low; lactate increases) requires
vasopressor support. The primary goal of vasopressor support is to increase cardiac output and oxygen
delivery to vital organs. Dopamine is a rational first-line therapy in septic shock at 5 to 15 μg/kg/min and
titrated to urine output greater than 1 mL/kg/hr and mean arterial BP (two thirds diastolic plus one third
systolic) greater than 70 mm Hg. Dopamine primarily stimulates HR and cardiac contractility in doses
ranging from 3 to 8 μg/kg/min, then produces peripheral arterial vasoconstriction at doses greater than 10
μg kg/min. Dopamine also may improve splanchnic, renal, and systemic perfusion. If urine output remains
low with high doses of dopamine (>10 μg/kg/min), dobutamine should be started at 5 μg/kg/min to
increase cardiac output and increased to 20 μg/kg/min to maintain urine output.

Multiple agents have been directed against the biologic actions of lipopolysaccharide. Cytokines and
autocoids have been investigated in animal studies and human trials of septic shock, but no
antichemokine has been adopted for routine clinical use in the emergency department.[1] It seems that no
single cytokine or mediator is the sole cause of septic shock, and no single agent treats it. Evidence has
emerged to suggest that derangements in the coagulation cascade in addition to a robust inflammatory
response contribute substantially to the development of organ dysfunction in the setting of sepsis.
Drotrecogin alfa activated (or activated protein C), a recombinant human activated protein with anti-
inflammatory, antithrombotic, and profibrinolytic properties, has shown promising preliminary results in the
[60]
treatment of patients with systemic inflammation and organ failure from acute infection. Patients who
receive activated protein C have a lower 28-day mortality, but the use of activated protein C is associated
with a greater risk of serious bleeding. Certain subgroups may derive additional benefit from the use of
activated protein C, including patients older than 50 years, patients with more than one dysfunctional
organ system, patients with an Acute Physiologic and Chronic Health Evaluation (APACHE) II score
greater than 24, and patients with shock at the time of drug infusion.[61] In general, the institution of
activated protein C therapy is not part of the routine emergency department management of sepsis
because there is a large window of time for treatment initiation (within 24 hours of meeting criteria). If this
therapy is considered, consultation with an ICU physician who would assume care of the patient is
recommended because the therapy is continued for 96 hours.

The use of corticosteroids in the treatment of sepsis and septic shock has been investigated with mixed
results. The results of two large randomized, controlled trials confirm that there is no role for high-dose,
short-course corticosteroid therapy in septic shock. [62] [63] Evidence has suggested, however, that some
patients with septic shock have relative adrenal insufficiency when the hypothalamic-pituitary axis is
tested with a corticotropin stimulation test. One multicenter randomized, controlled trial of patients with
septic shock showed a reduction in the mortality rate and number of days on vasoactive medications in
nonresponders to a corticotropin stimulation test (defined as an increase of serum cortisol ≤9 μg/dL after
stimulation) who received low-dose hydrocortisone (50 mg every 6 hours for 7 days) versus placebo. [64]
More trials are needed to investigate the potential benefit of low-dose hydrocortisone in subgroups of
patients with septic shock, and specifically to identify any potential hazards from use of this agent, before
any firm recommendations can be made.

Cardiogenic Shock

The immediate treatment of cardiogenic shock focuses on improving myocardial contractility and pump
function. Cardiogenic shock traditionally is defined as the combination of systemic signs of hypoperfusion
with arterial systolic BP less than 90 mm Hg (or 30% below a known baseline). If work of breathing is
tiring the patient, if severe pulmonary edema is causing significant hypoxemia, or if respiratory failure is
imminent, intubation and mechanical ventilation should be initiated, followed by emergent treatment of
bradydysrhythymia or tachydysrhythmia and inotropic support. For sedation or anxiety, barbiturates,
morphine, and benzodiazepines should be avoided in cardiogenic shock; when perfused into a failing
heart, their negative inotropism is exaggerated.[65] Cautious doses of fentanyl may be used to manage
pain, but the best approach to calm anxiety and restlessness is to improve perfusion. Etomidate has
excellent hemodynamic stability and should be used (but in reduced doses) for intubation, accompanied
by a full dose of succinylcholine. To improve myocardial contractility, dobutamine and dopamine are the
agents of choice begun in order at the same doses used for septic shock. For refractory hypotension and
shock, amrinone or milrinone may improve cardiac output. Amrinone and milrinone are biperiden
derivatives that increase cAMP by inhibiting phosphodiesterase (complex F-III). These drugs exhibit little
tachyphylaxis with no measurable increase in myocardial oxygen consumption.[66] A loading dose of 0.75
mg/kg for amrinone or 50 μg/kg for milrinone is necessary, followed by a titrated constant infusion for
either drug (5 to 10 μg/kg/min for amrinone and 0.5 μg/kg/min for milrinone).

When pharmacologic support fails to improve indices of perfusion, the next step is to initiate intra-aortic
balloon pump counterpulsation (IABPC). IABPC requires the facilities and personnel of a high-level ICU
or critical care unit. IABPC can augment diastolic coronary perfusion by 30% and may interrupt the
vicious cycle of hypotension-induced myocardial hypoperfusion.[67] Controlled trials have shown IABPC to
improve short-term survival, improve post-thrombolytic patency rates, and reduce stroke morbidity.
IABPC increases cardiac output by a mean of 30% in refractory cardiogenic shock and can prolong
survival until interventional procedures can be performed. IABPC may be contraindicated in patients with
aortic insufficiency or severe peripheral vascular disease.

The dismal outcome of cardiogenic shock complicating acute myocardial infarction has been improved in
recent years. Evidence from a randomized trial suggests that emergent revascularization is not superior
to medical management in reducing short-term mortality; however, significant improvements in mortality
are seen at 6 months and 1 year (see Chapter 77 ). [68] [69] At present, the management of acute
myocardial infarction with cardiogenic shock proceeds as follows and constitutes optimal therapy: (1)
ensure adequate ventilation and oxygenation, (2) treat emergent dysrhythmias, (3) initiate inotropic
support, (4) administer aspirin if the patient is not allergic, and (5) begin heparin anticoagulation (in
absence of contraindications) and arrange for emergent percutaneous transluminal coronary angioplasty.

Anaphylactic Shock

Therapy for anaphylactic shock is aimed at reversing the effect of its mediators. Aggressive volume
resuscitation with isotonic fluid should be initiated rapidly in any patient with suspected anaphylactic
shock. Epinephrine effectively counteracts the vasodepression, bronchoconstriction, fluid transudation,
and reduced cardiac function in anaphylaxis. Epinephrine should be administered intravenously in
patients with hypotension, even in the presence of coronary artery disease. Initially, 1 mL of 1:10,000
epinephrine (100 μg) can be injected slowly and the response monitored. Afterward, 5 mg of epinephrine
can be diluted in 500 mL of saline, with a starting infusion rate of 10 mL/hr (about 0.02 μg/kg/min) and
titrated to maintain perfusion. Corticosteroids are integral to arresting synthesis and release of
anaphylaxis mediators. Corticosteroids inhibit phospholipase A2 and decrease prostanoid, leukotriene,
and PAF synthesis. Corticosteroids also quench T-cell and mast cell triggering and reduce late-phase
bronchial inflammation. Hydrocortisone (5 to 10 mg/kg intravenously) or methylprednisolone (1.5 to 2
mg/kg intravenously) are good choices in anaphylaxis. Histamine receptor antagonists (H1 and H2)
prevent urticaria, aid in reducing bronchoconstriction, reduce fluid transudation, and may improve
myocardial function. Diphenhydramine (0.5 mg/kg intravenously) and cimetidine (2 to 5 mg/kg
intravenously) may be used. Nebulized β2-agonists can be used to help reduce bronchospasm. For
patients with profound bronchospasm, obvious increased work of breathing, and hypotension, mechanical
ventilation is indicated. Ketamine is a logical agent to use for sedation during rapid sequence intubation
with succinylcholine (see Chapter 1 ).

KEY CONCEPTS

▪ Circulatory shock often occurs with normal arterial BP, and not all patients with arterial hypotension
have circulatory shock.
▪ A base deficit more negative than -4 mEq/L or a serum lactate greater than 4 mmol/L indicates the
presence of widespread circulatory insufficiency in suspected shock.
▪ Urine output is a reliable index of vital organ perfusion in patients with suspected shock.
▪ Ill patients with tachycardia, a worsening base deficit, and low urine output should be diagnosed
with circulatory shock.
▪ Use of defined physiologic endpoints to measure systemic perfusion during resuscitation (goal-
directed therapy) is a valuable approach to optimal resuscitation in emergency department patients
with shock.
 SHOCK!

Munish Goyal, MD
David F. Gaieski, MD
Co-Directors
Early Goal-Directed Therapy Program
Department of Emergency Medicine
University of Pennsylvania

Outline
• Definition of Shock
• Oxygen Delivery
• Initial Examination of Patients in Shock
• Classification of Shock
• Septic Shock
• Early Goal-Directed Therapy for Severe
Sepsis and Septic Shock

1
 “I’m all congested up here”
• 53 y/o African American Male
• HPI
– 1 week chest congestion, cough, f/c
• PMH
– Seizures, thrombocytopenia
• SH
– Heavy EtOH, 1 ppd tobacco

Triage Vital Signs

Temp: 101.6° F
BP: 97/65
HR: 135
SpO2: 86% on RA
RR: 32

2
 Physical Exam
Gen: WDWN male in respiratory distress
HEENT: Sclerae icteric; MM dry
Lungs: Decreased BS at left base, dullness
to percussion; rhonchi R mid lung field
CVS: Tachy nl. S1, S2; - obvious murmur
ABD: NT, ND, + BS
EXT: - C, C, E
Skin: No rash, hot to touch
Neuro: Alert, but fatigued

Initial Management
IV access
Fluid resuscitation
Supplemental oxygen
Cardiac monitor
Labs, cultures, CXR
Antibiotics

Is this patient in shock?

3
 What is Shock?
• A physiologic state characterized by
– Decrease in tissue perfusion
– Inadequate oxygen delivery
• Delivery isn’t keeping up with demand

What is Shock?
• First clinical definition in 1800s by John
Collins Warren
– “A momentary pause in the act of death”
» Warren JC. Surgical pathology and therapeutics. Philadelphia: 1895.

• 1872 - Samuel Gross

– “A rude unhinging of the machinery of life”
» Gross SG. System of surgery: Pathological diagnostic, therapeutique, and
operative. Philadelphia: Lea & Febiger; 1872

4
 States of Shock
• Compensated Shock (Warm/Early)
– Organ function maintained
– BP remains normal
• Uncompensated Shock (Cold/Late)
– Microvascular perfusion decreases
– Organ and cellular function deteriorate
– Hypotension develops

Compensatory Mechanisms
• Baroreceptors
– In aortic arch and carotid sinus
– Hypotension stimulates vasoconstriction,
increased HR, BP and CO
• Chemoreceptors
– Respond to cellular acidosis with
vasoconstriction and respiratory stimulation

5
 Compensatory Mechanisms
• Renin-angiotensin system
kidney perfusion leads to renin secretion
– Renin Anigiotensin II leading to
vasoconstriction and aldosterone release
– Aldosterone leads to sodium and water
reabsorption
• Humoral Response
– Catecholamine release leading to
increased contractility and vasoconstriction

Organ Dysfunction
• Uncompensated Shock Organ Dysfunction
– Decreased urine output ARF
– Restlessness agitation obtundation coma
– Tachypnea Respiratory muscle hypoxia
worsening acidosis respiratory failure
– Tachycardia increased myocardial oxygen
demand increased catecholamines
tachycardia myocardial ischemia
• Initially reversible, becomes irreversible

6
 Irreversible Changes
Cell membrane ion pump dysfunction

Intracellular edema

Leakage of intracellular contents into the

extracellular space

This triggers inflammatory cascade

Cascade of Damage
Cell Death

End-Organ Damage

Failure of Multiple Organ Systems

Death
Early interventions prevent progression of Shock

7
 Oxygen Delivery

The amount of O2 delivered to tissue (DO2)

DO2 = CaO2 x CO
CaO2 = Content of O2 in arterial blood
CaO2 = (Hgb x SaO2 x 1.34) + (PaO2 x 0.0031)

CaO2 = Hgb x SaO2

Hgb

CaO2 A-a gradient

DPG
Acid-Base Balance
Influenced By Blockers
Competitors
SaO2 Temperature

DO2 Drugs
Influenced By Conduction System
HR
CVP
CO EDV Venous Volume
Venous Tone

SV Ventricular
Compliance
Influenced By
ESV Contractility

Afterload
Influenced By Temperature
Drugs Autono

8
 Oxygen Delivery

DO2

75%

VO2

Delivery vs. Consumption

Supply independant
VO2
Supply dependant

DO2

9
 Hypoperfusion
• A patient can be in shock with
– High or low SVR
– High or low CO
– High, low or normal blood pressure

Shock is inadequate oxygen delivery to

meet metabolic needs

Determinants of BP
Myocardial
Contractility

Stroke Volume Preload

Cardiac Output Afterload

Blood
Pressure Heart Rate
Systemic Vascular
Resistance

Textbook of Pediatric Advanced Life Support, 1988

10
 Hemodynamic Response to
Hemorrhage
% of Vasc Resistance
Control

100

Blood
Pressure

Cardiac
Output
25% 50%
% Plasma Loss

Common Features of Shock

• Hypoxia acts at cellular level
• S/S - manifestations of cellular response
– Fever
– Tachycardia
– Oliguria
– Change in mental status
– Metabolic acidosis
– Hypotension

Oxygen Delivery is always inadequate

11
 Common Features of Shock
• Hypotension: SBP < 90 or MAP < 65
– Cryptic shock
• normal SBP despite profound tissue hypoxia
– Baseline Hypertension
• drop of > 40mmHg in SBP is highly suggestive
of shock
– Baseline Hypotension
• Some patients live in 80s/50s

Initial Examination
• History and Physical often limited by
patient’s condition
• Exam
– quick
– high yield for finding source of shock
• Often in conjunction with treatment

12
 Physical Exam (cont’d)
• Gen: Distress?, mentating?, LETHARGIC
• HEENT: Sclera; mucous membranes; pupils
• NECK: JVD; meningeal signs
• LUNGS: Tachypnea; accessory muscle use;
Kussmaul respirations; abnormal or absent
breath sounds
• CVS: Tachycardia; dysrhythmias; murmurs;
muffled heart sounds; strength of pulses
• Abdomen: Scars; bowel sounds; guarding;
rebound; peritoneal signs; ascites

Physical Exam (cont’d)

• Rectal: Decreased tone, blood
• Extremities: Swollen calf; palpable
cord; pulse differentials
• Neuro: Agitation; confusion; delirium;
coma; focal deficits; seizure activity
• Skin: Temperature; hyperemic; rashes;
petechiae; urticaria; cellulitis; embolic
stigmata

13
 Limb hypoperfusion

www.aic.cuhk.edu

Classification of Shock

1. Hypovolemic Shock
2. Cardiogenic Shock
3. Distributive Shock
4. Neurogenic Shock
Oxygen Delivery is always inadequate

14
 Cardiovascular Changes

Type Preload Afterload Contractility

Hypovolemic -- /
Cardiogenic -- /
Distributive
Neurogenic

Hypovolemic Shock
• Problem: Decreased Preload
preload SV CO DO2
• Initial response is to increase HR in
attempt to maintain CO
• Result of:
– Hemorrhage
– Dehydration
– Fluid loss

15
 Cardiogenic Shock
• Problem: Contractility
• Pump failure alters Frank-Starling curve;
results in SV and CO
• Multiple causes:
1. Myopathies: ischemia; dilated cardiomyopathy;
myocardial depression of sepsis
2. Arrhythmias: atrial or ventricular
3. Mechanical: acute MR; acute AI; critical AS
4. Obstructive: Extracardiac causes including
tamponade, tension pneumothorax, massive PE

Distributive Shock
• Essential derangement: SVR, functional
hypovolemia
• Multiple causes:
– SIRS Inflammatory cascade: pancreatitis;
burns; trauma; infection
– TSS
– Anaphylaxis
– Addisonian Crisis
– Myxedema Coma

16
 Neurogenic Shock
• Problem: Functional
hypovolemia with lack of
compensation
• Paralysis of the sympathetic
chain which controls vascular
tone from injury to thoracic or
cervical level spinal cord injury
• Produces SVR from loss of
vascular tone and bradycardia
from unopposed
parasympathetic input to SA
node

Septic Shock
• Combination
– Distributive
– Cardiogenic
– Hypovolemic
• Most common form of Shock
• On a continuum from SIRS to Septic
Shock

17
 The Continuum of Sepsis

SIRS Sepsis Severe Sepsis Septic Shock

Systemic Inflammatory Response Syndrome

SIRS criteria
• Temp < 96.8° or > 100.4° F
• HR > 90
• RR > 20 or PCO2 < 32
• WBC < 4 or > 12 or bands > 10%
Bone et al. Chest 1992;101:1644

The Continuum of Sepsis

SIRS Sepsis Severe Sepsis Septic Shock

Systemic Inflammatory Response to Infection

• Suspected or confirmed infection
• 2 or more SIRS criteria

Bone et al. Chest 1992;101:1644;

Balk, RA

18
 The Continuum of Sepsis
SIRS Sepsis Severe Sepsis Septic Shock

Sepsis plus Organ Dysfunction

• Elevated Creatinine
• Elevated INR
• Altered Mental Status
• Elevated Lactate
• Hypotension that responds to fluid
Bone et al. Chest 1992;101:1644

The Continuum of Sepsis

SIRS Sepsis Severe Sepsis Septic Shock

Severe Sepsis and Hypotension

• Hypotension that does NOT
respond to fluid (30 cc/kg bolus)

Bone et al. Chest 1992;101:1644

19
 Why is this so Important?
• 750,000 cases/yr of severe sepsis in US
• 215,000 deaths/yr directly related to sepsis
• Tenth leading cause of death in USA
• Rate of sepsis cases is increasing faster
than the population
• 37% of severe sepsis patients come
through the ED

Why so Important? (cont’d)

Mortality of Severe Sepsis

250,000

200,000
Deaths/Year

150,000

100,000

50,000

0
AIDS* Breast AMI† Severe
Cancer§ Sepsis‡

†National Center for Health Statistics, 2001. §American Cancer Society, 2001.

*American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001 (In Press).

20
 Early Interventions in
Medicine
• AMI – “Time is Muscle”
– ACC/AHA guidelines for STEMI
• Door-to-needle time for initiation of fibrinolytic therapy
should be achieved within 30 minutes
• Door-to-balloon (or medical contact–to-balloon) time
for PCI can be kept under 90 minutes.
• Stroke – “Time is Brain”
– ASA
• IV rtPA is strongly recommended within 3 hours of onset
of ischemic stroke (grade A).
• Trauma
– Golden Hour – …the lives of severely injured
people could be saved if treated by trauma
specialists

Early Goal-Directed Therapy

(EGDT)

21
 EGDT
• Design
– Randomized, Blinded, Controlled trial
• Patients
– 263 adults with severe sepsis and lactate > 4 or
septic shock
• Intervention
– 6 hours of algorithmic care which optimized
• CVP 8-12
• MAP > 65
• ScvO2 > 70%
• Outcome
– Mortality in house, 28 day, and 60 day

Rivers, E. et al. N Engl J Med 2001;345:1368-1377

22
 Rivers, E. et al. N Engl J Med 2001;345:1368-1377

EGDT Results
28-day Mortality
60
49.2%
50 P = 0.01*

40
33.3%
30

20

10

0
Standard Therapy EGDT
n=133 n=130
*Key difference was in sudden CV collapse, not MODS
Rivers E. N Engl J Med 2001;345:1368-77.

23
 Insert CVC in IJV or SCV
Send ScvO2 if not Presep® catheter
Notify Super SAR about need for MICU Bed, measure Apache II score

CVP 8
Yes No

Bolus 500 ml NS q15-20

MAP 65
Yes baseline No

1. Start/Titrate norepi 2 mcg/min or dopamine 5 mcg/kg/min*

2. Dexamethasone 4 mg IV Q6 for refractory hypotension
3. Place arterial line if time permits *If patient requires vasopressor:
Serum cortisol just prior to giving ACTH
ScvO2 70% Give 250 mcg ACTH IV
Yes No Serum cortisol 1 hour after ACTH given

Transfuse PRBC’s until HgB 10

www.sfar.org/scores2/apache22.html
Consider activated protein C if Apache II > 25

ScvO2 70%
Yes No

Start/Titrate Dobutamine 2.5 mcg/kg/min (increase by 2.5

mcg/kg increments; hold for hr > 120, map < 65)

ScvO2 70%
Yes No

CVP, MAP, ScvO2 goals achieved. Re-evaluate to achieve goals.

What is Central Venous

Pressure (CVP)?
Pressure in the thoracic vena cava

Estimates right atrial pressure

Estimates right ventricular pressure

Estimates right ventricular volume

Estimates preload

24
 CVP Values
• Normal in a healthy human
– 0-8 mmHg
• Goal if spontaneously breathing
– 8-12 mmHg
• Goal with positive pressure ventilation
– Increases 3-5 mmHg (11-16mmHg)

CVP Values
• Low CVP (<8)
– Volume depleted
– Negative pressure inspiration
• High CVP (>12)
– Heart failure
– Volume overload
– Obstructed flow (pulmonary htn, TS)
– Increased intrathoracic pressure

25
 CVP Monitoring
• CVP is first physiologic parameter in
EGDT
– CVP < 8 = volume resuscitation
– CVP normal or elevated, proceed to MAP

Mean Arterial Pressure

• MAP = [(2 x diastolic)+systolic] / 3
• Goal MAP - 65
• Measured directly or indirectly
– Arterial Catheters
• Direct measurements
• Most accurate technique in shock states
• Continuous hemodynamic information
• Facilitates ABG measurement
Hollenberg SM. Crit Care Med 1999; 27:639-660.
Bellomo R. Lancet 2000; 356: 2139-2143.
Kellum J. Crti Care Med 2001; 29: 1526-1531.

26
 Mean Arterial Pressure
• If MAP < 65 after fluid challenge start
Vasopressors
• Should be used transiently in the face of life-threatening
hypotension, while fluid challenge is in progress
• Norepinephrine or dopamine in septic shock
• Norepinephrine may be more effective at reversing hypotension
in septic shock patients
• Dopamine may be useful in patients with compromised systolic
function but causes more tachycardia and arrhythmias

LeDoux D. Crit Care Med 2000;28:2729-2732. Regnier B. Intensive Care Med 1977;3:47-53.
Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765.
DeBacker D. Crit Care Med 2003;31:1659-1667. Hollenberg SM. Crit Care Med 1999; 27: 639-660.
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

SvO2
• Oxygen Saturation of Venous
hemoglobin

• Amount of oxygen left over after the

body removes what it needs

• Represents the balance between

oxygen delivery and consumption

27
 SvO2

Rivers et al, 2001

Continuous ScvO2 Catheter

28
 SvO2 v. ScvO2

100%

75%
75%

VO2

SvO2

Rivers et al, 2001

29
 Return to our Patient
Temp: 101.6° F
BP: 97/65
HR: 135
SpO2: 86% on RA
RR: 32

Physical Exam
Gen: WDWN male in respiratory distress
HEENT: Sclerae icteric; MM dry
Lungs: Decreased BS at left base, dullness
to percussion; rhonchi R mid lung field
CVS: Tachy nl. S1, S2; - obvious murmur
ABD: NT, ND, + BS
EXT: - C, C, E.
Skin: No rash, hot to touch
Neuro: Alert, but fatigued

30
 How’s Our Patient Doing?
• SpO2 91%, RR 36, HR 130, BP 138/74
• Notable labs:
– WBC: 5.3
– Hgb: 15 (Hct - 43)
– Platelet: 19
– BMP 131/3.5/94/16/23/2.0/116
– INR – 1.8, PTT – 46.2
– Tbili=6.6; direct=5.3
– Lactate 8.4 Cryptic Shock
• CXR: Left Lower Lobe pneumonia

www.aic.cuhk.edu

31
 ED Course
• Cefepime 1 gm IV
• Intubated for hypoxemia, AMS, WOB
• ScvO2 catheter placed
• Arterial line placed
• Initial ABG – on 100% FiO2
– 7.27/42/126/-6.6
P/F ratio = 126

ED Course
• CVP – 8 (intubated)
– 500 cc NS bolus q 30 min until CVP – 12
– Total intake – 9L
• MAP
– Initially 70s, dropped to 60
– Norepinephrine started at 1 mcg/min
– Maintained MAP >65 with norepi @ 2
• ScvO2
– Remained 70-80%

32
 ED Course
• Repeat Labs
– Creatinine – 1.1 (2.0)
– Lactate – 5.8 (8.4)
– Base Deficit – 1.0 (6.6)
– pH – 7.38 (7.27)
• Transferred to MICU
– Continued Goal-Directed Therapy

Case Conclusion
• Blood and Sputum Cx
– Streptococcus pneumoniae
• Weaned off vasopressors HD # 5
• Self-extubated at HD # 5
• D/c’ed home on hospital day # 14

33
 Topics Covered
• Definition of Shock
• Oxygen Delivery
• Initial Examination of Patients in Shock
• Classification of Shock
• Septic Shock
• Early Goal-Directed Therapy for Severe
Sepsis and Septic Shock

34