Review Article

Hemorrhagic shock: The “physiology approach”

Fabrizio Giuseppe Bonanno
Trauma Directorate, Chris Hani Baragwanath Hospital, Johannesburg, South Africa

ABSTRACT
A shift of approach from ‘clinics trying to fit physiology’ to the one of ‘physiology to clinics’, with interpretation of the
clinical phenomena from their physiological bases to the tip of the clinical iceberg, and a management exclusively based
on modulation of physiology, is finally surging as the safest and most efficacious philosophy in hemorrhagic shock. ATLS®
classification and recommendations on hemorrhagic shock are not helpful because antiphysiological and potentially
misleading. Hemorrhagic shock needs to be reclassified in the direction of usefulness and timing of intervention: in particular
its assessment and management need to be tailored to physiology.

Key Words: Classification, hemorrhagic shock, management

INTRODUCTION management of a scenario or of a problem [Table 1]. ATLS®

It has always been puzzling trying to understand and accept the
rationale and benefits of the ATLS classification[1] especially after
having replaced Holcroft more sensible classification,[2] as for the
difficulty of practical implementation with reference to timing and
optimal management. Both classifications were consequences of
experiments done on animals that do not have the same adrenergic
receptors distribution and amount on humans, which further varies
from individual to individual,[3,4] and a misinterpretation of Shires
studies in the 1960s,[5,6] deceptively corroborated by the improvement
in renal failure statistics in the Vietnam war with the overload of
crystalloids, incidental with a coincidental increase of ARDS.[7,8]
A more useful classification of hemorrhagic shock (HS), individual
physiology-tailored and therapeutic/decision-making friendly, which is
based on the above two classifications of shock, has been elaborated.
CLASSIFICATION OF HEMORRHAGIC SHOCK
Classifications are meant to summarize the assessment and
Address for correspondence:
Dr. Fabrizio Giuseppe Bonanno, E-mail: f.g.bonanno@gmail.com
classification of hemorrhagic shock (HS)[1] is not sensitive
and specific enough to help decision-making in reference to
the timing of management, being based only on the amount
of blood loss that may or may not be rightly estimated, and
it is unhelpful and difficult to apply too. [9] The previous
physiological classification[2] had advantages overlooked and not
re-captured by the ATLS® one, namely the progression of the
effects of a hemorrhage on the different organs and systems,
a more reliable indicator than the amount of blood itself in
guiding timing of intervention. Nevertheless, the physiological
classification, despite being more functional and useful does not
keep in account the pre-existent different organ physiological
reserves or can foresee the level at which hypotension, crucial
parameter signaling decompensation, occurs. By recommending
the fluid-load of 2 L crystalloids load for adult patients to test
the reliability of compensatory mechanisms, as recommended
up to recently, classical ATLS® guidelines actually delay the
timing of intervention as source control when testing is not
required and more crucially end up increasing the ongoing
or spontaneously stopped bleeding. The only novelty of the
classification is the cutoff at 30% blood loss as level of blood
loss always manifesting with hypotension, per se not enough
useful information to guide decision making.

The new classification [Table 2], which may well be called

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the “physiological HS classification” or “therapeutical HS
Quick Response Code:
Website: classification’, is based on a decision-making that keeps in account
www.onlinejets.org hard practice and basic physiological considerations, such as
the significance of fluid-blood resistant hypotension and body
DOI:
natural hemostatic mechanisms, the right definition of shock
10.4103/0974-2700.102357 nonetheless the relevance that hemorrhage triggered I-R and SIR
have in critical illness scenarios as secondary insult from ischemia.
Journal of Emergencies, Trauma, and Shock I 5:4 I Oct - Dec 2012 285
Bonanno: Hemorrhagic shock
Table 1: Classical clinical classifications of
haemorrhagic shock
Holcroft*
Mild <20% Skin changes
Mod >20% <40% Kidney, Gut, Lung, Liver dysfunction - Hypotension
Severe >40% Brain and Heart involvement
ATLS**
I: blood loss <15%
II: blood loss >15% <30%
III: blood loss >30% <40%
IV: blood loss >40%
*BV diverted towards noble organs in a reverse hierarchy response; **Hypotension is
consistently present when > 30% TBV loss. It may or may not be present with blood
loss of < 30% TBV. Hypotension signals decompensation.; ***Persisting Tachycardia with
normalised systolic after fluid load signals partial compensation (stably unstable);
****Persisting Tachycardia and hypotension after fluid load signals severe life
threatening Physiology (unstably unstable); BV: Blood volume; ATLS®: Advanced trauma
life support; TBV: Total blood volume
Table 2: Therapeutical/physiological classification of
HS and first line management of source control
Critical HS Shock with heart and brain involvement or > 40% TBV loss
(impending CV collapse) → Stand-by surgery for source
control
Severe HS Shock with hypotension not responding to blood/fluid load-test
(unstably unstable) → Rapid surgery for source control
Moderate/ Moderate shock is hypotensive shock responding with
Mild HS normotension and reverse tachycardia trend to blood/
fluid overload (unstably stable); mild shock is normotensive
tachycardic from start → Investigate, Ponder surgery,
Interventional radiology/ Non-operative intervention
*hypotension may occur at ≥ 20% and is always present at ≥ 30% TBV loss; **by response
is meant reverse tachycardia trend and normalization of pressure; HS: Haemorrhagic
shock; TBV: Total blood volume; CV: Cardiovascular
In “critical shock”, in fact there is no much of circulating volume,
and brain and heart internal circulations are barely holding as a
result of the systemic vasoconstriction from chemoreceptor and
central nervous system receptors stimulation, while in “severe
shock” there is sufficient blood volume to potentially maintain
perfusion despite endogenous compensatory capacity in terms of
vasomotion/vasoconstriction has been lost; in moderate shock
compensatory capacity instead has not been lost; and mild shock
indicates only some blood loss.
The ‘physiological–therapeutical’ classification must be
distinguished from the prognostic one, i.e. reversible or
irreversible shock and implicitly photographs the levels of shock
within a time-frame of reversibility. It must also not be confused
with the two hit-model of physiological deterioration either,
which describe the time-peaks of clinical downfall.
RATIONALE: TIMING OF INTERVENTION—THE
“RESUSCITATION PARADOX”
Timing is everything. The main stem of treatment of shock is
removal of the causa prima (source optimization in cardiogenic
shock (CS), source control in HS, and source elimination in
inflammatory shock (IS). The timing for treatment of HS can
be summarized in a “therapeutic paradox”: Intervene soon in a
very sick patient to prevent death and accepting the inevitable
286
complications; improve the healthy or moderately sick patient
before surgery by optimizing or reinforcing patient physiology
with a view to reduce or prevent complications. So, sicker the
patient, the earlier more rapid and aggressive the intervention
has to be; the less sick the patient more time has to be taken
for improvement before intervention. Patient biological and
physiological reserves (immunity, nutrition, exercise and age-
related cardiovascular reflexes and specific organs homeostatic
autoregulatory compensatory mechanisms), pre-existing
systemic diseases or derangements (chronic renal failure,
hypertension, diabetes, chronic liver disease, and chronic heart
disease), and concurrent drug intake (alcohol, antihypertensive,
anti-arrhythmic, β-blockers, steroids, vasodilators, inotrops, and
insulin) play different significant roles in the overall prognosis
of the critical illness by delaying detection, limiting the
physiological reserve of the different organs and complicating
recovery.
Timing of intervention for source control in HS depends on
the clinical severity and degree of compensation that in normal
individuals reflects the level of blood loss, and on the response
to fluids load. TBV is 70 ml/kg body weight in adults, 80 ml/kg
in infant age and 80–90 ml/kg in newborns. HS at the extremes
of life is more serious than at the age in between as for the not
developed (newborns and infants) or less responsive (elderly)
vascular reflexes. Elderly patients as a matter of fact can have
shock at seemingly normal blood pressure of 120 mmHg due
to atherosclerosis, hypertension, and less functional reflexes
maintaining relatively high pressures for perfusion.[10,11]
HS in pregnant women does not manifest with shock signs until
30–35% TBV is lost due to the increase of plasma and cardiac
output. The supine position neutralizes the advantages of those
preparatory changes to forthcoming intravascular volume-losses
as for the uterus compressing on the IVC and impairing VR,
phenomenon avoidable by always maintaining a left-oblique
positioning when lying down.
Acute blood loss and hypotension with brain and heart
disturbances or a blood loss >40% of TBV (critical HS, unstably
unstable) require stand-by surgery to stop bleeding; persisting
hypotension not responding to blood or fluids load (severe
shock) with stable normalization of systolic and reversed HR
trend (stably unstable), also requires emergency surgery to stop
bleeding.
Heart and brain circulation in “critical shock” are holding because
of still functional regional vasomotion, but they have already
passed the critical extraction point as by definition ischemic
signs are already present.
No response to small volumes of hypertonic/colloid fluid load
in “severe shock” signifies a deranged vasomotion due to loss of
endogenous compensation as the beginning of a physiological
slope with continuing hemorrhage at a rate in which reflex
compensatory vasoconstriction cannot maintain pressures.
Journal of Emergencies, Trauma, and Shock I 5:4 I Oct - Dec 2012

Anything else other than a fast run to theater and swift anesthesia
induction will kill patients in the above two scenarios. To push
extra fluids fast or in great quantity will disrupt the balance by
counteracting life-saving hypotension, vasoconstriction, vessel
retraction, and clot formation, with the end-result of killing the
patient or in the less pessimistic scenario causing heart attack or
a cerebrovascular accident.[12]
The mechanisms accounting for the worsening of the situation
before or in the absence of source control in critical and severe
HS are multiple and act in combination evolving in a vicious
circle of accelerated exitus.
The chemoreceptor response to low PaO2 at levels of pulse
pressure of 70–80 mmHg increases BP by direct stimulation of
the vasomotor centers in the reticular activating substance of the
medulla oblongata and lower pons, increasing arterioles tone via
sympathetic nervous system stimulation. At some stage, without
or before source control and in the presence of supplementary
fluids and oxygen or hyperoxia, the vasoconstricting reflex gets
dampened; eventually, with HbO2 reduced to minimal terms from
the unarrested bleeding and CO reduced from the decreased
venous return, and with dissolved PaO2 that cannot sustain CaO2
at a level to maintain sufficient perfusion (DO2), the reflex gets
triggered. By the time the chemoreceptor is triggered though,
HbO2 will have reached minimal levels, and so the DO2, and brain
and heart are already suffering of relative hypoxia (critical shock).
Coronaries have a very high O2ER at basal conditions (75% vs.
25% of most of the other organs) and are already in pathological
supply dependence in critical shock, dangerously near the
critical extraction level beyond which anaerobic metabolism and
potentially devastating further ischemia ensues.[13] Adjunctive
hyperoxia will paradoxically accelerate the physiological slope,
particularly if combined with blood or fluids increasing bleeding
rate before source control.
As importantly, the ischemic CNS response to pressures <60
mmHg with decreased DO2 delivery, as signaled by an already
clinically impalpable level of systolic pressure, would also be
counteracted by fluid administration with the paradox of having a
situation, otherwise kept compensated by the two reflexes, being
instead decompensated by fluids and oxygen administration.
Moreover, the increase of intravascular volumes with fluid
transfusion before source control previously advised would
further decrease perfusion as it counteracts the three natural
physiological mechanisms of hemosthasis, i.e. arterial retraction/
spasm, hypotension, and clot, ending up increasing bleeding and
decreasing pressures.
Since World War I in fact it has been known that: hypotension,
vasoconstriction, vessel retraction, and clot formation prevented
continuation of bleeding after wounding; blood or plasma
transfusion before surgery was a wasted resource that could
cause re-bleeding; and surgery with control of hemorrhage
was the most effective resuscitation. The insight of war surgery
Journal of Emergencies, Trauma, and Shock I 5:4 I Oct - Dec 2012
Bonanno: Hemorrhagic shock
experience had told us that hypotension, clot formation, and
vessels retraction were the reasons for patients’ survival after
arterial damage or injury, that an untreated arterial injury or
killed rapidly or was savageable if spontaneously stopped, while
a venous injury had to rely only on clot formation to stop.
This implies, paradoxically, that major venous injury can be
more lethal than arterial one in sites such as mediastinum and
retroperitoneum where it cannot be compressed.[14-17]
Thus, pushing fluids and hyperoxia and the maintenance—
though temporary—of the actual mean arterial pressure (MAP)
in critical shock and severe shock before source control, is in
principle and de facto deleterious to patient’s physiology and
outcome. Delay and standard resuscitation with oxygen and
fluids will paradoxically result in an earlier ischemia of the two
organs than the one that would occur if no transfusion and early
surgery were instead implemented.
The fluid-load test is consequently a wasteful and damaging
exercise in ‘critical hemorrhagic shock’ as is any delay to fast
source control.
In all other cases of hypotensive shock with no heart or brain
ischemia the fluid-load test should be carried out as it tells us
on the status of compensation present and, importantly, allows
distinction between severe and moderate shock, i.e. between
a rush to theater or temporizing on further diagnostic or
therapeutic strategies. Hypotensive shock without heart or brain
involvement, independently whether the loss is 20% (not always
accompanied by hypotension) or 30% (always accompanied by
hypotension) of TBV, which responds to blood/fluids overload
test with normalization of blood pressure and reverse trend in
tachycardia (moderate shock), indicates reliably the presence
still of a certain physiological reserve in terms of compensatory
mechanisms. Such scenarios do not require immediate or rapid
surgery but can be investigated before surgery or interventional
radiology and considered for conservative management. No
investigation should be entertained in the presence of critical
or severe shock.
Investigations should be allowed only in not-hypotensive,
compensated mild-to-moderate HS, and should be aimed only to
identify the origin of the bleeding/s and concomitant pathologies
worthy or essential to be picked up before surgery. History,
clinical assessment, logistics and equipment dictate the timing
of intervention and investigations in compensated shock or
consideration for conservative not-operative management. Blood
transfusion in these not emergency cases should be given within
maximum 4–6 h from insult to prevent I-R complications, till a
level judged satisfactory (Hb ≥ 7 g/dL with Hct >21–24%) in
healthy patients and ≥9–10 mg/dL with Hct ≥27–30% in cardiac
patients, keeping in account SvO2 minimal levels of 70%, and
normalized values of BE and LA in the absence of infection.[18-19]
Moderate HS responds well to crystalloids and PRBC i.v.; mild
shock can be treated with oral fluids, or i.v. fluids.
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Bonanno: Hemorrhagic shock
For stabilization to be considered established, besides normal BP
and reverse or normal pulse, patients must be seen with normal
or improved complexion, mental status, urinary output, and
comforting indirect signs of perfusion such as PaO2 and SaO2.
PITFALLS IN HEMORRHAGIC SHOCK RESUSCITATION
The loading fluid test of 2 L of crystalloids previously
recommended by ATLS® was de facto antiphysiological and
deleterious especially when indiscriminately implemented and
did not bring increase of survival,[20] but an increase in mortality
and postoperative complications when compared to no-fluids or
less-fluids resuscitation.[21-24] Experimental evidence confirmed
the deleterious effects of the crystalloid bolus.[25,26]
At normal heart conditions and healthy valves and myocardium,
any increase of venous return will effectively increase MAP
which will increase actual bleeding by counteracting hypotension,
the physiological vasoconstriction, and the clotting attempts,
which are the three natural mechanisms the organism uses to
stop hemorrhage. Vasodilatation and decreased viscosity from
hemodilution also trigger the same chain of events, leading to
increased, continuous or recurrent bleeding. These considerations
and observations were tested in animals,[25-36] humans,[20-22,37,38]
and computer simulations[39] and confirmed that (i) too much
fluid infusion causes hemodilution of platelets and clotting
factors, increase of blood pressure, decrease of blood viscosity,
vasodilatation, all factors thus leading to a blow out of the
hemostatic plug with accentuation of ongoing hemorrhage or/
and secondary hemorrhage; (ii) blood loss causes hypothermia,
which causes coagulopathy; (iii) in patients with penetrating
trunk injury and hypotension and uncontrolled vascular injury,
if no fluids in standard fashion are given in prehospital setting
before theater, survival is increased, complications decreased and
hospital stay shortened compared to standard fluid resuscitation;
(iv) surgical hemosthasis is the key therapeutic act for uncontrolled
hemorrhage; and (v) limited or moderate resuscitation is superior
to aggressive resuscitation in uncontrolled vascular injury. Same
hemodynamic and hemostasis derangements occur if hypertonic
saline instead of crystalloids is used [Figure 1].[25-27,30,33-34,36]
Moreover, the principle first-crystalloids-then-blood, even
worse in a 3:1 ratio, was based on the assumption that
noncorpuscolated plasma, the fluid part of plasma, has
first to replace the interstitial–intracellular shifts occurring
during hemorrhage. Shires studies[5,6] were accurate on the
assessment of fluids shifts, not in the way to manage them. The
homeostasis of water bidirectionally in the cell-interstitia-blood
pathways will be obviously deranged in not-compensated shock
whereby definition the grasp on maintaining blood pressure by
arteriolar vasoconstriction fails and the ratios in the Starling
equilibrium in the capillaries default. It is intuitive that only
by restoring vasoconstriction capacity the shifts can re-occur.
This assumption was missed when the 3:1 ratio was postulated
as the right one, confirming the need to categorize shock for
288
Figure 1: Effects of VR manipulations on haemodynamics in
patients with normal cardiac reserve
any experiment or study in a more physiological manner. The
real message from Shires works is that replenishment to be
effective and accurate can only be done after source control
where the solution of continuity is repaired and compensatory-
physiology restored. Only then fluids infusion will equilibrate
the three fluid compartments. It is true that combinations of
crystalloids, plasma, and blood in the Vietnam war, increased
survival and decreased renal failure at expenses of ARDS
(former Da-Nang lung), but that cannot be attributed to the
combination fluids blood 3:1 more that it can be attributed
to blood only.[7,8] The ratio 3:1 is not only inaccurate in its
conception, amount and priority of transfusion but also for its
indiscriminate use, i.e. whether shock is compensated and with
or without source control. Moreover, patients’ selection was
not done in terms of categorizing them with different classes
of shock and the decrease of renal failure is likely to have
represented a natural selection occurred in survivors with not
critical/severe shock cases, eventually some of them evolving in
ARDS. Besides the negative effects on bleeding and on viscosity
of microcirculation, the classical approach does not make sense
intuitively either. If blood loss is the primitive derangement, it is
expected blood replacement to be the main and most important
corrective action. In other words, blood should be given first
and crystalloids should follow once the fluid component of the
plasma shifts toward interstitial-intracellular spaces and increases
blood hematocrit.[40] The infusion of crystalloids would then
replace the lost intravascular component and restore hematocrit.
It is simple deduction that unless there is a loss of continuity left
unrepaired in the circulation system, which is a closed system,
any fluid shift from cells-to-interstitia-to-intravascular space
would be reversed in the opposite direction by reproducing the
dynamics backwards (Claude Bernard homeostasis concept).
In hemorrhage it is blood that is lost and blood needs to be
replaced, at least to minimum physiological levels when blood
loss trespasses them. An indirect advantage of this shift of policy
would be the shortening of time of clot formation compared to
the first fluids—then blood current policy that has dominated
decades of practice in trauma with deleterious effects.[41]
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In hypotensive shock Ringer’s lactate should therefore be used
only after blood or blood components therapy in an amount
tailored to balance osmolality electrolytes and hemathocrit.
Another drawback of an excess of fluid transfusion is RV/LV
cardiac failure or CS if the two halves of the heart have pre-
existent decreased functional reserve due to valvular or myocardial
pathology. Two problems would then be faced—overload and
low cardiac output—with treatment of one condition worsening
the other one [Figure 2]. Direct inotropic support would then be
required in conjunction with blood replenishment and aggressive
ICU monitoring of the cardiac output.
Furthermore, excess treatment with fluid or blood overload
is deleterious whether is effected before source control
or afterwards, as it may cause secondary intra-abdominal
compartment syndrome, [42-44] with changes that trigger a
second hit SIR or I-R syndromes and ALI helped by SIR and
vasodilatation, if resuscitation is done late, or worsened by
vasoconstriction with serious effects on abdominal organs
perfusion, ventilation, kidney function and venous return, if
resuscitation is done early and in excess. Gut edema and increased
intraabdominal pressure till abdominal compartment syndrome
level will ensue, due the increase of capillary net-filtration-
pressure (cNFP) secondary to increased intracapillary pressure
result of the increased pressure upstream from increased volume.
Starling law ruling the permeable capillaries net filtration pressure
states: NFP = [capillary pressure – (interstitial fluid pressure
+ plasma colloid-osmotic pressure) + interstitial fluid colloid-
osmotic pressure].
Inadequate or delayed resuscitation is the other side of
inappropriate treatment of HS. Cardiac arrest can occur as a
primary hit for insufficient venous return and coronary ischemia
due to the dependence of coronary perfusion from blood flow
during the diastole phase, which is decreased following the
decrease of the stroke volume. The compensatory tachycardia
only worsens the situation accelerating heart ischemia. Post-HS
SIR or I-R phenomenon is the second serious consequence
of inadequate or deficient resuscitation leading to increased
morbidity and mortality.[45,46]
STRATEGIES AND TACTICS
Adjuncts in treatment
Compensation of HS occurs by reflex arteriolar vasoconstriction
sympathetic-mediated with catecholamines acting on α1 receptors.
At some stage hyporeactivity to endogenous catecholamines
installs, signaling decompensation, which becomes paralysis when
a complete lack of responsiveness occurs even to exogenous
vasoconstrictors signaling irreversible shock.
Besides its proven benefits in septic shock (SS), vasopressin alias
arginine vasopressin (AVP) alias anti-diuretic hormone (ADH)
has shown beneficial effects in CS and in cardiac arrest. [47-51]
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Bonanno: Hemorrhagic shock
Figure 2: Effects of VR manipulations on haemodynamics in
patients with diminished cardiac reserve
In HS AVP has been found to reduce the fluid requirement
and improve neurological outcome and cardiopulmonary
parameters. [52] Vasopressin as bolus (0.4 U once or twice) and/
or infusion (0.04–0.1 U/min) reverses intractable or prolonged
hypotension in the late phase HS or intraoperative HS with and
without cardiac arrest.[53-59] Vasopressin vasoconstrictive effect
results from inhibition of KATP channels and inhibition of nitric
oxide-induced accumulation of cGMP. Replacement of depleted
stores of vasopressin in the neurohypophysis may also contribute
to reversal of shock.[60] ADH may cause problems at higher
dosages or when given for several hours.[61]
Noradrenaline (NE) is a potent alpha-adrenergic agonist with
minimal β-adrenergic agonist effects. NE increases MAP due
to its vasoconstrictive effects with little change in the heart
rate and stroke volume, and by doing so increases indirectly
the cardiac output as well. Doses of NE going from 0.2 µg/
kg/min titrated to response up to 3.3 µg/kg/min are used to
maintain CO and BP. Its drawbacks are an increase of workload
and oxygen consumption plus coronary vasoconstriction. NE
should be used early as neurohormonal augmentation therapy
supporting hemodynamic function, rather than as a late rescue
therapy to treat shock.[62]
Both NE and ADH combined with hydroxyethyl starch improve
cerebral perfusion pressure, oxygenation and metabolism in HS,
with AVP being the faster of the two.[63,64] The combination AVP
+ NE is an effective treatment for uncontrolled HS at the early
stage after hemostasis, if blood is unavailable.[65]
NE should be added to AVP if the latter is ineffective, and must
be discontinued before ADH.[66]
Likewise in SS, the combination of low doses NE and ADH,
or ADH on its own, can be administered from presentation
and categorization of critical or severe HS till before source
control as a vasoconstriction-maintaining, vasomotor collapse-
delaying, drug.
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Bonanno: Hemorrhagic shock
Once arterial pressure is brought to a systolic of at least 90
mmHg and a MAP >65–70 mmHg, and CO still would be low,
intravenous dobutamine may take over. In normal hearts there is
however scarce need for inotropic support in the postoperative
ICU phase.
Dopamine may also be useful in patients with compromised
systolic function, low CO, and MAP. At doses of approximately
10–20 µg/kg/min, the prevailing α-adrenergic effect leads to
arterial vasoconstriction and elevation in blood pressure. The
problem with dopamine however is that before the cardio-vascular
system responds to vasoconstricting high dosages it has to pass
through low and medium concentrations that may temporarily
worsen the situation by increasing the heart rate and regional
vasodilatation in a moment where there is not much blood in
circulation; furthermore dopamine predisposes to dys-rhythmias.
Titrated hypotensive resuscitation
Too late, too little, too early too much, too late and too much
are all harmful resuscitation strategies. To which level then
should resuscitation be maintained before imminent surgery
or temporarily before surgery or as the only treatment if a
conservative nonoperative approach is adopted? This should
be a level of blood pressure sufficient enough to maintain
perfusion without risking either continuation of bleeding or re-
bleeding. These targets are reached with “Titrated Hypotensive
Resuscitation” [Table 3].
“Hypotensive resuscitation” is an old concept introduced by
Cannon around the First World War,[14-17] but implemented
only by Crawford in late 1980s for the treatment of ruptured
abdominal aortic aneurysm before surgery, [38] recently re-
introduced as “permissive or titrated hypotension” by the Israeli
Defense Force[67,68] for transported patients with HS where
resuscitation monitoring and titration are difficult to achieve
and a small volume of infusion is logistically convenient. The
systolic pressure was kept less than 90 mmHg to maintain a
consciousness level or at the palpable pulse level, i.e. ≥70 and
Table 3: HS: too much too early, too little and too
late. What is the ideal or perfect resuscitation?
Resuscitation in defect or delayed or omitted
• Primary cardiac arrest for insufficient venous return, massive heart or
cerebrovascular accident
• “Primary hit” IHD, CVA, acute overlapping ischemic cardiogenic shock or
failure
• “Secondary hit” ischemia-reperfusion, SIR, endotoxaemia and bacterial
translocation (hitting lungs and kidneys)
Resuscitation in excess
• Secondary compartment syndrome, cardiac failure, cardiogenic shock,
pulmonary oedema, persistent or recurrent bleeding
What is then the Ideal or Perfect Resuscitation?
• “Standard Resuscitation?”. No, not any more flat resuscitation! It is just a guess
work and increases morbidity and mortality.
• Titrated Hypotensive Resuscitation? Yes! It should be the standard for transport
of patients with critical or severe HS.
• Damage Control? Yes! In specific situations.
• Conservative /Non-operative intervention ? Yes! In specific situations. NOI is a
form of DC
IHD: Ischemic heart disease; CVA: Cerebro-vascular accident; SIR: Systemic inflammatory
response; NOI: Non-operative intervention; DC: Damage control
290
<90 mmHg by titrated prn hourly bolus of 250 ml of RL or HTS;
skin complexion and consciousness level direct resuscitation in
a conscious patient.
The presence of associated head injury that is not mild
(GCS  ≤  12) compounds the clinical picture because of the
difficulty or impossibility to use level of consciousness as
an indicator of the level of blood loss and compensatory
mechanisms efficacy, and the unpredictable loss of the capacity
of flow self-regulation following trauma. Patients with HS and
HI need therefore a moderate resuscitation in between permissive
hypotension and standard resuscitation, i.e. systolic of ≥100
mmHg particularly in view of the fact that the brain loses its
circulation self-regulatory capacity at variable levels of HI.[69,70]
Experimental evidence and clinical experience in civilian and
military setting have shown benefits and safety of boluses of
250 ml of fluids, whether crystalloids, colloids, or hypertonic
saline at different concentrations, as effective and safe initial
management of patients with HS[67,68,71-73] HTS should be given
not more than 250, maximum 375, ml/h to maximize its merits
and diminish its drawbacks on bleeding by interference with
coagulation and more importantly following increase of pressure
as direct hemodynamic effect.
In a recent study on humans, the no-difference of mortality in
patients who received either HTS 7.5%–Dextran 70 at 6% or
HTS 7.5% administration boluses of 250 ml compared to NS
0.9% 250 ml as initial fluid treatment before source control,[74]
associated to an increase of mortality in the subgroup who
did not receive blood transfusion in the first 24 h, appears to
contradict some of the conclusions of previous experiences. The
inclusion, in the study, of patients in HS with SBP ≤70 mmHg
or with SBP between 70 and 90 mmHg + HR ≥110 bpm would
fit the profile of critical and severe shock categories if brain or
heart were involved and a known loss <40% had occurred, or
no consistent response to the fluid bolus was noted; moreover,
the observations made in the group with no-blood transfusion
indicate patients in whom type and amount of fluids would not
have made difference. The study only emphasizes the need of a
more accurate and useful categorization of HS.
“Hypotensive resuscitation” and “permissive hypotension
on demand” or “titrated hypotension”, more accurately
“Titrated Hypotensive Resuscitation” (THR), remains the ideal
resuscitation and the way to go as standard initial resuscitation
particularly during transport of patients with critical or severe HS
independently on the scenario, whether civil or rural or military.
Emergency protocols: The “physiology approach”
In ‘critical shock’ with a known TBV loss of ≥40% or the
presence of brain and heart ischemic changes there is no
proven effective strategy of resuscitation out-of-hospital that
would not contemplate heroics like in situ extreme-outdoor-
resuscitation (EOR) by small operative units with or without
suspended animation-fastly induced hypothermia techniques.
Journal of Emergencies, Trauma, and Shock I 5:4 I Oct - Dec 2012

Such techniques with portable femoro-femoral CPBP/ECMO
without hypothermia have given dismal results outdoors in CA
or CS before refractory CA in normovolemic not-exhanguinating
patients even when applied with beating heart, and a survival
of 20-30% indoors.[75-76] In trauma scenarios with solution of
continuity in the vascular tree and decreased blood volume
EOR with the method of suspended animation can only be
effective with hypothermia induced by cold saline aortic flush
via emergency sternotomy/thoracotomy.[77]
Until methods and techniques of EOR and suspended
animation- hypothermia are optimized or perfected, only three
options are so far available. ‘One’ is a life-saving run to the
nearest medical facility for rapid source control with continuous
blood transfusion running in high capacity/flow cannulae, well
knowing it is destined to get lost. ‘Two’ is to run at the nearest
medical facility with no fluid-treatment whatsoever at all leaving
to the patient natural balancing mechanisms to do their best
without iatrogenic interference until rapid/swift anesthesia/
surgery for source control. “Three” is THR. In the author’s
view no-resuscitation or THR are the most sensible options to
use as initial resuscitation before source control in patients with
hypotensive HS both indoor and outdoor while rushing on the
way to a medical facility. The no-resuscitation option may indeed
be the best option.[21]
THR should also be used in ‘severe’ HS after the initial bolus
of the fluid-load test discriminates it from the ‘moderate’ one;
if shock turns out to be moderate with normalized systolic and
reversed tachycardia trend, no further fluid should be given until
source control.
Which fluid to use in “critical HS” in pre-hospital phase and
which fluid should be used for load-test in severe HS?
It should be the fluid one would like to use as bridge infusion
until source control if blood were unavailable: hyperosmotic–
hyperviscous solutions (HHS), HTS or RL combined with
alginates, and conjugated albumin solutions appear so far to
be excellent choice. There is overwhelming evidence on the
importance of maintaining microcirculation function with aim
to optimize perfusion in HS by using apt fluid with specific
characteristics and composition, particularly viscosity more than
colloid-osmotic and oncotic properties, and, in parallel, on the
irreplaceable function of blood from microhemodynamics and
oxygen-transport end-points.[78-94]
To show predictable benefits of THR on mortality and
morbidity, [85,95] specifically in preventing the installing of
cryptic shock abutting in a I-R MOD/S clinical picture in the
postoperative period, trials[96] should be done on patients in
hypotensive shock classifiable as ‘severe’ or ‘critical’.[97]
It is under the same principle of the least interference with
physiology during resuscitations that tactics and strategies such
as THR, damage control, and damage control resuscitation, have
Journal of Emergencies, Trauma, and Shock I 5:4 I Oct - Dec 2012
Bonanno: Hemorrhagic shock
been conceptualized. Likewise general anesthesia should too be
titrated to pain/autonomic stimulation response (autonomic
controlled—anesthesia) under the comprehensive concept of
‘physiology approach’.
Etomidate, S(+)-ketamine or alfentanyl induction and S(+)
ketamine or remifentanyl continuous-intravenous anesthesia
(CIVA) titrated to response is the author’s suggested method for
anesthetizing critical and severe shock patients.[98-100]
Emergency protocols based on a “Physiology approach”
comprehensive strategy, i.e. the “Therapeutical Classification
Table 4: Decision making in Critical HS: A
comprehensive management
Critical HS
Out-of hospital: NO-resuscitation until source control - or titrated hypotensive
resuscitation ± AVP iv boluses x max 2 followed by AVP infusion, +
NE infusion if ADH on its own is ineffective.
In-hospital: Stand-by surgery for source control under CIVA with Etomidate
or S(+)-Ketamine or Alfentanyl as induction followed by Ketamine
and/or Remifentanyl infusion for maintenance.
Followed after source control
by
Fresh whole blood transfusion (0 neg or 0 pos or grouped or cross-matched blood,
according to immediate availability)
or
PRC/FFP/Platelets + Anticoagulopathy regimen (rFVIIa, Cryoprecipitates,
Fibrinogen, Prothrombin Complex concentrates, antifibrinolitics, Desmopressin)
empirically or ad hoc following routine coagulation tests and thromboelastometry
within 10-15 minutes from the blood sample
and
Crystalloids as Ringer’s Lactate to balance osmolality, electrolytes and
hemathocrit after blood/blood components transfusion in an inverse ratio from
previous recommendations i.e. blood or blood components/fluids ratio > 1
HS: Haemorrhagic shock; NE: Noradrenaline; ADH: Anti-diuretic hormone, alias AVP:
Arginine vasopressin; CIVA: Continuous intravenous anaesthesia; PRC: Packed red cells;
FFP: Fresh frozen plasma; rVIIa: Reconbinant factor viia; prn: Pro re nata (when there is
need, when need rises); ad hoc: (specifically, for a specific situation)
Table 5: Decision making in Severe HS: A
comprehensive management
Severe HS
Out-of hospital: Titrated hypotensive resuscitation + AVP iv boluses x max 2
followed by AVP infusion, + NE infusion if ADH on its own is
ineffective.
In-hospital: Rapid surgery for source control under CIVA with Etomidate or
S(+)-Ketamine or Alfentanyl as induction followed by Ketamine
and/or Remifentanyl infusion for maintenance.
Followed after source control
by
Fresh whole blood transfusion (0 neg or 0 pos or grouped or cross-matched blood,
according to immediate availability)
or
PRC/FFP/Platelets + Anticoagulopathy regimen (rFVIIa, Cryoprecipitates, Fibrinogen,
Prothrombin Complex concentrates, antifibrinolitics, Desmopressin) empirically or ad
hoc following routine coagulation tests and thromboelastometry within 10-15 minutes
from the blood sample
and
Crystalloids as Ringer’s Lactate to balance osmolality, electrolytes and hemathocrit
after blood/blood components transfusion in an inverse ratio from previous
recommendations i.e. blood or blood components/fluids ratio > 1
HS: Haemorrhagic shock; NE: Noradrenaline; ADH: Anti-diuretic hormone, alias AVP:
arginine vasopressin; CIVA: Continuous intravenous anaesthesia; PRC: Packed red cells;
FFP: Fresh frozen plasma; rVIIa: Reconbinant factor viia; prn: Pro re nata (when there is
need, when need rises): ad hoc: (specifically, for a specific situation)
291
Bonanno: Hemorrhagic shock
of HS”, “THR”, “exogenous vasoconstrictive support”,
autonomic-control CIVA, and blood and blood components
replenishment, [101-108] are suggested in Tables 4 and 5. In
hypotensive shock Ringer’s lactate should be used only after
blood or blood components therapy in an amount tailored to
balance osmolality electrolytes and hematocrit.
CONCLUSIONS
The standard ATLS classification of HS is unhelpful, confusing
and misleading as it focuses on the amount of blood loss instead
of individual physiological response to hemorrhage, which is the
core by definition of the derangement we call ‘shock’. A new
classification was needed and centered on physiology like the
classical classification of Holcroft emphasized.
The era of flat anesthetics and surgery is over and it is time
we go toward a tailored-to-individual physiology restoration
and reprioritize all critical illness management from the
microcirculation stand-point.
Fluids as first modality of treatment, particularly in excess as
recommended till recently, are deleterious in hypotensive shock and
should be considered second line modality; moreover should be
given after blood, and in an amount based on adjusting osmolarity.
Exogenous vasoconstrictors are a valid therapeutic strategy once
endogenous vasoconstriction has failed to maintain the grip on
the flow-controlling arterioles.
“Save life” is the Commandment in decompensated hypotensive
shock not responding to fluid-load test or with a calculated TBV
loss > 40% or with brain heart signs of ischemia, accepting
inevitable and obligatory I-R and a phase of Cryptic Shock.
“Prevent complications”, namely I-R, is the Commandment in
compensated mild or moderate shock.
Playing with the enemy in its own way is the key word of the
game. Do not alter the physiological compensatory mechanisms
but keep them and reinforce them. Let the body run the orchestra
and follow it.
Without the right convenient and physiological classification
of HS, we will still continue to generate controversies and
contradictory investigator-appeasing results.
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How to cite this article: Bonanno FG. Hemorrhagic shock: The
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Received: 30.03.11. Accepted: 13.04.11.
Source of Support: Nil. Conflict of Interest: None declared.

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