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.
References
1. Rodriguez RM., Rosenthal MH. Etiology & Pathophysiology
of shock. In: Murray MJ, Coursin DB, Pearl RG, Prough
DS. eds. Critical care medicine - Perioperative management.
Lippincott William & Wilkins, London. 2003; 192-205.
2. Le Dran HF: A treatise, or reflections drawn from practice
on gun-shot wounds. London. 1737 (Translated and self-
published by J Clarke. 1743).
3. Morris EA: A practical treatise on shock after operations
and injuries. London, 1867. Hardwicke.
4. Blalock A. Acute circulatory failure as exemplified by shock
and haemorrhage. Surg Gynecol Obstet. 1934; 58: 551-566.
5. kumar A, Parrillo JE. Shock: Classification, pathophysiology,
and approach to management. In: Parrillo JE, Dellinger RP.
eds. Critical Care medicine. Principles of Diagnosis and
management in the adult. Mosby. London. 2001; 291-339.
6. Hinshaw LB, Cox BG. The fundamental mechanisms of
shock, New York, 1972. Plenum Press.
7. Jimenez EJ. Shock. In: Civetta JM, Taylor RW, Kirby RR
eds. Critical Care. Lippincott, Raven publishers.
Philadelphia. 1997; 359-385.
8. Mela L, Bacalaz OL, Miller L. Defective oxidative
metabolism of rat mitochondria in hemorrhage and endotoxin
shock. Am J Physiol 1971; 220: 571.
9. Vogt MT, Fraber E. The effects of ethionine treatment on
the metabolism of liver mitochondria. Arch Biochem Biophys
1970; 141: 162.
10. Horpacsy G, Schnells G. Metabolism of adenine mucleotides
in the kidney during hemorrhagic hypotension and after
recovery. J Surg Res 1980; 29: 11.
11. Chaudry IH, Sayeed MM, Baue AE. Alteration in high-energy
phosphates in hemorrhagic shock as related to tissue and
organ function. Surgery 1976; 79: 666.
12. Chaudry IH, Sayeed MM, Baue AE. Effect of adenosine
triphosphate-magnesium chloride administration in shock.
Surgery 1974; 75: 220.
SETHI, SHARMA, MOHTA, TYAGI : SHOCK
13. Chaudry IH, Sayeed MM, Baue AE. Effect of hemorrhagic
shock on tissue adenine nucleotides in conscious rats. Can
J Physiol Pharmacol 1974; 52: 131.
14. Ayala A, Perrin MM. Meldrum DR, et al. Hemorrhage
induces an increase in serum TNF which is not associated
with elevated levels of endotoxin. Cytokine 1990; 2: 170.
15. Calandra T, Baumgartner J, Grau GE, et al. Prognostic
values of tumor necrosis factor/cachectin, interleukin-1, and
interferon-g in the serum of patients with septic shock. JID
1990; 151: 982.
16. Giroir BP. Mediators of septic shock: new approaches for
interrupting the endogenous inflammatory cascade. Crit Care
Med 1993; 21: 780.
17. Levine B, Kalman J, Mayer L, et al. Elevated circulating
levels of tumor necrosis factor in severe chronic heart failure.
N Engl J Med 1990; 323: 236.
18. Pinsky MR, Vincent JL, Deviere J, et al. Serum cytokine
levels in human septic shock: relation to multiple system
organ failure and mortality. Chest 1993; 103: 565.
19. Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991;
115: 457.
20. Bone RC. Inflammatory Mediators in Sepsis and Septic
Shock. Ann Intern Med 1991; 115: 457.
21. Reilly JM, Cunnion RE, Burch-Whitman C, et al. A
circulating myocardial depressant substance is associated
with cardiac dysfunction and peripheral hypoperfusion (lactic
acidemia) in patients with septic shock. Chest 1989; 95:
1072.
22. Parrillo JE, Burch C, Shelhamer JH, et al. A circulating
myocardial depressant substance in humans with septic
shock. Septic shock patients with a reduced ejection fraction
have a circulating factor that depresses in vitro myocardial
cell perormance. J Clin Invest 1985; 76: 1539.
23. Lorente JA, Landin L, Renes E, et al. Role of nitric oxide
in the hemodynamic changes of sepsis. Crit Care Med 1993;
21: 759.
24. Nathan C. Nitric oxide as a secretory product of mammalian
cells. FASEB J 1992; 6: 3051.
25. Kilbourn RG, Gross SS, Jubran A, et al. N-methyl-L-arginine
inhibits tumor necrosis factor-induced hypotension:
implications for the involvement of nitric oxide. Proc Natl
Acad Sci 1990; 87: 3629.
26. Granger DN, Rutili G, McCord JM. Super-oxide radicals in
feline intestinal ischemia. Gastroenterology 1981; 81: 22.
27. McCord JM. Oxygen-derived free radicals. New Horiz 1993;
1: 70.
28. Saugstad OD, Ostrem T. Hypoxanthine and urate levels of
plasma during and after hemorrhagic hypotension in dogs.
Due Surg Res 1977; 9: 48.
29. Cryer HM, Kaebrick H, Harris PD, Et al. Effect of tissue
acidosis on skeletal muscle microcirculatory responses to
hemorrhagic shock in unanaesthetized rats. J Surg Res 1985;
39: 59.
355
30. Hollenberg SM, Cunnion RE, Parrillo JE. The effect of
tumor necrosis factor on vascular smooth muscle. In vitro
studies using rat aortic rings. Chest 1991; 100: 1133.
31. Coleman B, Glaviano VV. Tissue levels of norepinephrine
in hemorrhagic shock. Science 1963; 139: 54.
32. Beasley D, Cohen RA, Levinsky NG. Interleukin-1 inhibits
contraction of vascular smooth muscle. J Clin Invest 1989;
83: 331.
33. McKenna TM, Reusch DW, Simpkins CO. Macrophage
conditioned medium and interleukin-1 suppress vascular
contractility. Circ Shock 1988; 25: 187.
34. Chernow B. Roth BL. Pharmacologic manipulation of the
peripheral vasculature in shock: clinical and experimental
approaches. Circ Shock 1986; 18: 141.
35. Bond RF, Bond CH, Peissner LC, et al. Prostaglandin
modulation of adrenergic vascular control during
hemorrhagic shock. Am J Physiol 1981; 241: H85.
36. Slotman GJ, Burchard KW, Williams JJ, et al. Interaction of
prostaglandins in clinical sepsis and hypotension. Surgery
1986; 99: 744.
37. Thiemermann C, Szab C, Mitchell JA et al. Vascular
hyporeactivity to vasoconstrictor agents and hemodynamic
decompensation in hemorrhagic shock is mediated by nitric
oxide. Proc Natl Acad Sci 1993; 30: 267.
38. Zingarelli B, Squadrito F, Altavilla D, et al. Evidence for a
role of nitric oxide in hypovolemic hemorrhagic shock. J
Cardiovas Pharmacol 1992; 19: 982.
39. Koyama S, Aibiki M, Kanai K, et al. Role of the central
nervous system in renal nerve activity during prolonged
hemorrhagic shock in dogs. Am J Physiol 1988; 254.
40. Carden DI, Smith JK. Zimmerman BJ, et al. Reperfusion
injury following circulatory collapse: the role of reactive
oxygen metabolites. J Crit Care 1989; 4: 294.
41. Shasby DM, Shasby SS, Peach MJ, et al. Granulocytes and
phorbolyristate acetate increase permeability to albumin of
cultured endothelial monolayers and isolated perfuse lungs-
role of oxygen radicals and granulocyte adherence. Am Rev
Resp Dis 1983; 127: 72.
42. Thijs LG. Groenveld ABJ. Peripheral circulation in septic
shock. Appl Cardiopul Path 1998; 2: 203.
43. Shah DM, Dutton RE, Newell JC, et al. Vascular
autoregulatory failure following trauma and shock. Surg
Forum 1977; 28: 11.
44. Chien S. Role of the sympathetic nervous system in
hemorrhage. Physiol Rev 1967; 47: 214.
45. Bond RF, Green HD. Cardiac output redistribution during
bilateral common carotid artery occlusion. Am J Physiol
1969; 216: 393.
46. Haupt MT. The use of crystalloidal and colloidal solution
for volume replacement in hypovolemic shock. Crit Rev
Clin Lab Sci 1989; 27: 1.
47. Gann DS, Carlson DE, Byrnes GJ, et al. Role of solute in
the early restitution of blood volume after hemorrhage.
Surgery 1983; 94: 439.
356
48. Davis JO, Freeman RH. Mechanisms regulating rennin
release. Physiol Rev 1976; 56: 1.
49. Peach MJ. Renin-angiotensin system: biochemistry and
mechanisms of action. Physiol Rev 1977; 57: 313.
50. Klingbeil CK, Keil LC, Chang D, et al. Role of vasopressin
in stimulation of ACTH secretion by angiotensin II in
conscious dogs. Am J Physiol 1986; 251: E52.
51. Liard JF. Vasopressin in cardiovascular control: role of
circulating vaspressin. Clin Sci 1984; 67: 473.
52. Bond RF. Peripheral macro-and microcirculation. In: Schlag
G, Redl H. eds: Pathophysiology of shock, sepsis and organ
failure, Springer-Verlag Berlin. 1993.
53. Higgins CB, Vatner SF, Franklin D, et al. Pattern of
differential vasoconstriction in response to acute and chronic
low output states in the conscious dog. Cardiovasc Res 1974;
8: 92.
54. Kaihara S, Rutherford RB, Schwentker EP, et al. Distribution
of cardiac output in ex-perimental hemorrhagic shock in
dogs. J Appl Physiol 1969; 27: 218.
55. Forsyth RP, Hoffbrand BI, Melmon KL. Redistribution of
cardiac output during hemorrhage in the unanesthetized
monke. Circ Res 1970; 27: 311.
56. Kalter ES, Henning J, Thijs L, et al. Effects of
methylprednisolone on P50, 2, 3-diphosphoglycerate and
arteriovenous oxygen difference in acute myocardial
infarction, Circulation 1980; 62: 970.
57. du Luz PL, Cavanilles JM, Michaels S, et al. Oxygen
delivery, anoxic metabolism and hemoglobin-oxygen affinity
in patients with acute myocardial infarction and shock. Am
J Cardiol 1975; 36: 148.
58. Autoregulation of cerebral blood flow: Influence of the
arterial blood pressure on the blood flow though the cerebral
cortex. J Neurol Neurosurg Psychiatry 1966; 29: 398.
59. Lindenberg R. Patterns of CNS vulnerability in acute
hypoxemia including anaesthesia accidents. In: Schade JP,
McMeney WH. eds: Selective Vulnerability of the brain in
hypoxemia: a symposium. Philadelphia, 1963, FA Davis.
60. Sander-Jenson K, Secher NH, Bie P, et al. Vagal slowing of
the heart during hemorrhage: observations from twenty
consecutive hypotensive patients. Br Med J 1986; 295: 364.
61. Barriot P, Riou B. Hemorrhagic shock with paradoxical
bradycardia. Intensive Care Med 1987; 13: 203.
62. Sarnoff SJ, Case RB, Waitag PE, et al. In-sufficient coronary
flow and myocardial failure as a complicating factor in late
hemorrhagic shock. Am J Physiol 1954; 176: 439.
63. Hallstrom S, Vogl C, Redl H, et al. Net inotropic plasma
activity in canine hypovolemic traumatic shock: low
molecular weight plasma fraction after prolonged
hypotension depresses cardiac muscle performance in vitro.
Circ Shock 1990; 30: 129.
64. Douglas ME, Downs JB, Dannemiller FB, et al. Acute
respiratory failure and intravascular coagulation. Surg
Gynecol Ostet 1976; 143: 555.
INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003
65. Roussos C, Macklem PT. The respiratory muscles. N Engl
J Med 1982; 307: 786.
66. Johnson G, Henderson D, Bond RF. Morphological
differences in cutaneous and skeletal muscle vasculature
during compensatory and decompensatory hemorrhagic
hypotension. Circ Shock 1985; 15: 111.
67. Myer B, Moran S. Hemodynamically mediated acute renal
failure. N Engl J Med 1986; 314: 97.
68. Badr KF, Ichikawa E Prerenal failure. adeleterious shift from
renal compensation to decompensation. N Engl J Med 1988;
319: 623.
69. Rose BD. Meaning and application of urine chemistries. In:
clinical physiology of acid-base and electrolyte disorders.
McGraw-Hill ed 2, New York. 1984,.
70. Astiz ME, Rackow EC, Weil MH. Pathophysiology and
treatment of circulatory shock. Crit Care Clin 1993; 9: 183.
71. Bhagwat AG, Hawk WA. Terminal hemorrhagic necrotizing
enteropthy. Am J Gastroenteral 1966; 45: 163.
72. Robert A, Kaufman G. Stress ulcers erosions, and gastric
mucosal injury. In: Sleisenger M. Fortran J. eds.
Gastrointestinal disease. WB Saunders Philadelphia. 1989,.
73. Deitch E, Bridges W, Baker J, et al. Hemorrhagic shock-
induced bacterial translocation is reduced by xanthine
oxidase inhibition or inactivation. Surgery 1988; 104: 191.
74. Lillehei RC, MacLean LD. The intestinal factor in irreversible
endotoxin shock. Ann Surg 1958; 148: 513.
75. Champion HR, Jones RT, Trump BF, et al. A
clinicopathologic study of hepatic dysfunction following
shock. Surg Gynecol Obster 1976; 142: 657.
76. Bor NM, Alvur M, Erean MT, et al. Liver blood flow rate
and glucose metabolism in hemorrhagic hypotension and
shock. J Trauma 1982; 22: 753.
77. Counts HB, Haisch C, Simon TL, et al. Hemostasis in
massively transfused trauma patients. Ann Surg 1979; 190:
91.
78. Arnold J, Leinhardt D, Little RA. Metabolic response ot
trauma. In Schlag G, Redl H. eds: Pathophysiology of shock
sepsis and organ failure. Springer-Verlag Berlin. 1993.
79. Naylor JM, Kronfeld DS. In-vivo studies of hypoglycemia
and lactic acidosis in endotoxic shock. Am J Physiol 1985;
248.
80. Daniel AM, Pierce CH, Shizgal HM, et al. Protein and fat
utilization in shock. Surgery 1978; 84: 588.
81. Bagby GJ, Spitzer JA. Decreased myocardial extracellular
and muscle lipoprotein lipase activities in endotoxin-treated
rats. Proc Soc Exp Biol Med 1981; 168: 395.
82. Hoyt DB, Junger WG, Ozkan AN. Humoral mechanisms. In:
Schlag G, Redl H. eds. Pathophysiology of shock, sepsis
and organ failure. Springer-Verlag. Berlin. 1993.
83. Stephan R, Ayala A, Chaudry IH. Monocyte and lymphocyte
responses following trauma. In: Schlag G, Redl H. eds.
Pathophysiology of shock, sepsis and organ failure. Springer-
Verlag Berlin. 1993.
SETHI, SHARMA, MOHTA, TYAGI : SHOCK
84. Milne ENC. Impact of imaging in the intensive care unit.
Curr Opin Critical Care 1995; 1: 43.
85. Khoury AF, Afridi I, Quinones MA, et al. Transesophageal
echocardiography in critically ill patients: feasibility, safety
and impact on management. Am Heart J 1994; 127: 1363.
86. Kinch JW, Ryan TJ. Right ventricular infarction. N Engl J
Med 1994; 330: 1211.
87. Cohn J. blood pressure measurement in shock: Mechanisms
of inaccuracy in auscultatory and palpatory methods. JAMA,
1967; 199: 118.
88. Packman MI, Rackow EC. Optimum left heart filling pressure
during fluid resuscitation of patients with hypovolemic and
septic shock. Crit Care Med 1983; 11: 165.
89. Weisul RD, Vito L, Dennis RC, et al. Myocardial depression
during sepsis. Am J Surg, 1977; 133: 512.
90. Tuchschmidt J, Fried J, Astiz M, et al. Elevation of cardiac
output and oxygen delivery improves outcome in septic
shock. Chest 1992; 102: 216.
91. Fleming A, Bishop M, Shoemaker W, et al. Prospective trial
of supranormal values as goals of resuscitation in severe
trauma. Arch Surg 1992; 127: 1175.
92. Naylor CD, Sibbald WJ, Sprung CL, et al. Pulmonary artery
catheterization: can there be an integrated strategy of guideline
development and research promotion? JAMA 1993; 269.
93. Abraham E, Smith M, Silver L. Continuous monitoring of
critically ill patients with transcutaneous oxygen and carbon
dioxide, and conjunctival oxygen sensors. Ann Emerg Med
1984; 13: 1021.
94. Tremper KK, Keenan B, Applebaum R, et al. Clinical and
experimental monitoring with transcutaneous PO2 during
hypoxia, shock, cardiac arrest, and CPR. J Clin Invest 1981;
6: 149.
95. Abraham E, Smith M, Silver S. Conjunctival and
transcutaneous oxygen monitoring during cardiac arrest and
cardiopulmonary resuscitation. Crit Care Med 1984; 12: 419.
96. Gutierrez G, Bismar H, Dantzker D, et al. Comparison of
gastric intramucosal pH with measures of oxygen transport
and consumption in critically ill patients. Crit Care Med
1992; 20: 451.
97. Maynard N, Bihari D, Beal R, et al. Assessment of
splanchnic oxygenation by gastric tonometry in patients with
acute circulatory failure. JAMA 1993; 270: 1203.
98. Fiddian-Green RG, Haglung U, Gutierrez G, et al. Goals
for the resuscitation of shock. Crit Care Med 1993; 21
(suppl): 25.
99. Porembka DT. Transesophageal echocardiography. Crit Care
Clin 1996; 12: 875.
100. Shoemaker WC. Invasive and noninvasive cardiopulmonary
monitoring of acute circulatory dysfunction and shock. Curr
Opin Critical Care 1995; 1: 189.
101. Simonson SG, Piantadosi CA. Near-infrared spectroscopy
for monitoring tissue oxygenation in the critical care setting.
Curr Opin Critical Care 1995; 1: 197.
357
102. Wo CC, Shoemaker WC, Bishop MH, et al. Noninvasive
estimations of cardiac output and circulatory dynamics in
critically ill patients. Curr Opin Critical Care 1995; 1: 211.
103. Shoemaker WC, Wo CC, Bishop MH, et al. Multicenter trial
of a new thoracic electrical bioimpedance device for cardiac
output estimation. Crit Care Med 1994; 22: 1907.
104. Groeneveld AB, Kolkman JJ: Splanchnic tonometry. a review
of physiology, methodology, and clinical applications. J Crit
Care 1994; 9: 198.
105. Arnold J, Hendriks J, Ince C, et al. Tonometry to assess the
adequacy of splanchnic oxygenation in the critically ill
patient. Intensive Care med 1994; 20: 452.
106. Hayes MA, Timmins AC, Yau EHS, et al. Elevation of
systemic oxygen delivery in the treatment of critically ill
patients. N Engl J Med 1994; 330: 1717.
107. Gattinoni L, SVO2 Collaborative Group. A trial of goal-
oriented hemodynamic therapy in critically ill patients. N
Engl J Med 1995; 333: 1025.
108. Durham RM, Neunaber K, Mazuski JE, et al. The use of
oxygen consumption and delivery as end points for
resuscitation in critically ill patients. J Trauma 1996; 41:
32.
109. Yu M, Takanishi D, Mayers SA, et al: Frequency of mortality
and myocardial infarction during maximizing oxygen
delivery: a prospective, randomized trial. Crit Care Med
1995; 23: 1025.
110. Johnson TJ, Stothert JC. Respiratory evaluation and support
in the ICU. Curr Opin Critical Care 1995; 1: 306.
111. Cooper DJ, Walley KR, Wiggs BR, et al. Bicarbonate does
not improve hemodynamics in critically ill patients who
have lactic acisosis. A prospective, controlled clinical Study.
Ann Intern Med 1990; 112: 492.
112. Haupt MT, Kaufman BS, Carlson RW. Fluid resuscitation in
patients with increased vascular permeability. Crit Care Clin
1992; 8: 341.
113. Bissoni RS, Holtgrave DR, Lawler R, et al. Colloids versus
crystalloids in fluid resuscitation: an analysis of randomized
control trials. J Fam Pract 1991; 32: 387.
114. Velanovich V. Crystalloid versus colloid fluid resuscitation:
a meta-analysis of mortality. Surgery 1989; 105: 65.
115. Human albumin administration in critically ill patients:
systematic review of randomized controlled trials. Cochrane
Injuries Group Albumin Reviewers. Br Med J 1998; 317:
235.
116. Gillespie TA, Ambos HD, Sobel Be, et al. Effects of
dobutamine in patients with acute myocardial infarction.
Am J Cardiol 1977; 39: 588-594.
117. Leier CA. Acute inotropic support. In: Leier CV, ed.
Cardiotonic drugs: a clinical survey. Marcel Dekker. New
York: 1986.
118. Rozenfeld V, Cheng JW. The role of vasopressin in the
treatment of vasodilation in shock states. Ann Pharmacother
2000; 34: 250-254.
358
119. Landry DW, Levin HR, Gallant EM, et al. Vasopressin
deficiency contributes to the vasodilation of septic shock.
Circulation 1997; 95: 1122-1125.
120. Argenziano M, Choudhri AF, Oz MC, et al. Aprospective
randomized trial of arginine vasopressin in the treatment of
vasodilatory shock after left ventricular assist device
placement. Circulation 1997; 96: 286-290.
121. Malay MB, Ashton RC, Landry DW, et al. low-dose
vasopressin in the treatment of vasodilatory shock. J Trauma
1999; 47: 699-703.
122. Bellomo R, Chapman M, Finfer S, et al. Low-dose dopamine
in patients with early renal dysfunction: a placebo-controlled
randomized trial: Australian and New Zealand Intensive Care
Society (ANZICS) Clinical Trials Group. Lancet 2000; 356:
2139-2143.
123. Hoogenberg K, Smit AJ, Girbes ARJ. Effects of low-dose
dopamine on renal and systemic hemodynamics during
incremental norepinephrine infusion in healthy volunteers.
Crit Care Med 1998; 26: 260-265.
124. Duke GJ, Briedis JH, Weaver RA. Renal support in critically
ill patients: low-dose dopamine or low-dose dobutamine?
Crit Care Med 1994; 22: 1919-1925.
125. Sachaer GL, Fink MP, Parillo JE. Norepinephrine alone
versus nor-epinephrine plus low-dose dopamine enhanced
renal blood flow with combined pressor therapy. Crit Care
Med 1985; 13: 492-496.
126. Martin C, Papzian L, Perrin G, et al. Norepinephrine or
dopamine for the treatment of hyperdynamic septic shock?
Chest 1993; 103: 1826-1831.
127. Marik PE, Mohedin M. The contrasting effects of dopamine
and nor-epinephrine on systemic and splanchnic oxygen
utilization in hyperdynamic sepsis. JAMA 1994; 272: 1354-
1357.
128. Harari A, Martin E. Decreased dopamine beta hydroxylase
activity in septic shock. Anesthesiology 1979; 51: S155.
129. Bone RC, Fisher CJ, Clemmer TP, et al. A controlled clinical
trial of high-dose methylprednisolone in the treatment of
severe sepsis and septic shock. N Engl J Med 1987; 317:
653-658.
130. The Vterans Administration systemic Sepsis Cooperative
Study Group Effect of high-dose glucocorticoid therapy on
mortality in patients with clinical signs of systemic sepsis.
N Engl J Med 1987; 317: 659-665.
131. Bollaert PE, Charpentier C, Levy B, et al. Reversal of late
septic shock with supraphysiologic doses of hydrocortisone.
Crit Care Med 1998; 26: 645-650.
132. Briegel J, Forst H, Hummel T, et al. Stress doses of
hydrocortisone: reverse hyperdynamic septic shock: a
prospective randomized, double-blind, single-center study.
Crit Care Med 1999; 27: 723-732.
133. Roberto R, DeMillo V, Sobel BE. Deleterious effects of
methylprednisolone in patients with myocardial infarction.
Circulation 1976; 53: 204.
INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003
134. Bone RC. Towards a theory regarding the pathogenesis of
systemic inflammatory response syndrome: what we do and
do not know about cytokine regulation. Crit Care Med 1996;
24: 163-172.
135. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies
to treat sepsis and septic shock: a reassessment. Crit Care
Med 1997; 25: 1095-1100.
136. Angus DC, Birmingham MC, Balk RA, et al. F5 murine
monoclonal anti endotoxin antibody in gram-negative sepsis:
a randomized controlled trial. JAMA 2000; 283: 1723-1730.
137. Cohen J, Carlet J. INTERSEPT: an international,
multicenter, placebo-controlled trail of monoclonal antibody
to human tumor necrosis factoralpha in patients with sepsis.
International Sepsis Trial Study Group. Crit Care Med 1996;
24: 1431-1440.
138. Opal SM, Fisher CJ, Dhainaut JFA. Confirmatory
interleukin-I receptor antagonist trial in severe sepsis: a phase
III, randomized, double-blind, placebo-controlled,
multicenter trial. Crit Care Med 1997; 25: 1115-1124.
139. Remick DG, Garg SJ, Newcomb De, et al. Exogenous
interleukin-1 fails to decrease the mortality and morbidity
of sepsis. Crit Care Med 1998; 26: 895-904.
140. Avontaur JAM, Nothenius RPT, Bujik SLCE, et al. Effect of
L-Name, an inhibitor of nitric oxide synthesis, on
cardiopulmonary function in human septic shock. Chest
1998; 113: 1640-1646.
141. Harkema JM, Chaudry IH. Magnesium-adenosine
triphosphate in the treatment of shock, ischaemia, and sepsis.
Crit Care Med 1992; 20: 263.
142. Ward A, Clissold SP: Pentoxifylline; a review of its
pharmacodynamic and pharmcokinetic properties and its
therapeutic efficacy. Drugs 1987; 34: 50.
143. Karkema JM, Singh G, Wang P, et al. Pharmacologic agents
in the treatment of ischemia, hemorrhagic shock and sepsis.
J Crit Care 1992; 7: 189.
144. Maitra SR, Krikhely M, Dulchavsky SA, et al. Beneficial
effects of diltizem in hemorrhagic shock. Circ Shock 1991;
33: 121.
145. Sayeed MM, Maitra SR. Effect of diltiazem on altered cellular
calcium regulation during endotoxic shock. Am J Physiol
1987; 253: R549.
146. Soltero RG, Hansbrough JF. The effects of diaspirin cross-
linked hemoglobin on hemodynamics, metabolic acidosis,
and survival in burned rats. J Trauma 1999; 46: 286-291.
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.

ISA NEWS : Election - ISA - 2004 - Vaccancies - Notification

Election to the Governing Council ISA-2004 will be held at the Conference venue of ISACON 2003, on 28.12.2003
at Bhuvaneshwar. The vacancies open for the year - 2004 are:
(a) President - (one post)
(b) Vice-President - (one post)
(c) Editor - (one post)
(d) Governing Council Members - (3 posts)
The rules and regulations regarding the election to the Governing Council of ISA are as per the Constitution of ISA
(Article No.VII) published in 2002. Nomination in the proper format may be forwarded to the Secretary ISA, at Society’s
office by registered post/courier/in person, on or before 27th November 2003.

Secretary ISA (National)

$ $
INDIAN SOCIETY OF ANAESTHESIOLOGISTS : Elections - 2003
PROFORMA
(For Nomination of Office - Bearers to the Governing Council ISA National)
I propose the name of Dr……………..................................................……...............………………………………………..

of …………….................................…………City Branch/Direct Member …………..............…..............……………………………

.....................……as President / Vice President / Editor / Governing Council Member of Indian Society of Anaesthesiologists.
Candidate’s Name & Qualification Address ISA No.

Proposer’s Name Address ISA No.

Signature

I second the above proposal

Seconder’s Name Address ISA No.

Signature

I give my consent to the above proposal

Conference Attended: 1998 - Kathmandu 2001 - Ahmedabad
1999 - Cochin 2002 - Coimbatore
2000 - Nagpur

Signature of the candidate ……………………………

Place:
Date: