Hypovolemic shock

Hypovolemic shock
Dr Shaurya Pratap Singh

 Shock:
 Systemic state of low perfusion that is inadequate for normal cellular respiration.
 Types:
 Hypovolemic
 Cardiogenic
 Distributive
 Septic
 Anaphylactic
 Spinal cord injury
 Obstructive
 Endocrine

 Modified Shock Index
 MSI is defined as heart rate divided by mean arterial pressure. High MSI indicates
a value of stroke volume and low systemic vascular resistance, a sign of
hypodynamic circulation. In contrast, low MSI indicates a hyperdynamic state.

 Dynamic fluid response
 The shock status can be determined dynamically by the car diovascular response
to the rapid administration of a fluid bolus. In total, 250–500 mL of fluid is
rapidly given (over 5–10 minutes) and the cardiovascular responses in terms
heart rate, blood pressure and central venous pressure are observed.
can be divided into ‘responders’, ‘transient respond ers’ and ‘nonresponders’.
 Responders have an improvement in their cardiovascular status that is
These patients are not actively losing f luid but require filling to a normal
volume status.
 Transient responders have an improvement, but this then reverts to the
state over the next 10–20 min utes. These patients have moderate ongoing fluid
losses (either overt haemorrhage or further fluid shifts reducing intravascular
volume).
 Non-responders are severely volume depleted and are likely to have major
ongoing loss of intravascular volume, usually through persistent uncontrolled
haemorrhage.

 CENTRAL VENOUS PRESSURE
 There is no ‘normal’ central venous pressure (CVP) for a shocked patient, and
reliance cannot be placed on an indi vidual pressure measurement to assess
volume status. Some patients may require a CVP of 5 cmH2O, whereas some
require a CVP of 15 cmH2O or higher. Further, ventricular compliance can
from minute to minute in the shocked state, and CVP is a poor reflection of end
diastolic volume (preload).
 CVP measurements should be assessed dynamically as response to a fluid
challenge (see above). A fluid bolus (250500 mL) is infused rapidly over 5–10
minutes. The normal CVP response is a rise of 2–5 cmH2O which gradually
drifts back to the original level over 10–20 minutes. Patients with no change
their CVP are empty and require further fluid resuscitation.
 Patients with a large, sustained rise in CVP have high preload and an element of
cardiac insuffi ciency or volume overload.

 Cellular:
 As perfusion to the tissues is reduced, cells are deprived of oxygen and must switch from
aerobic to anaerobic metabolism.
 Microvascular:
 Hypoxia and acidosis activate complement and prime neutrophils, resulting in the
generation of oxygen free radicals and cytokine release. These mechanisms lead to
injury of the capillary endothelial cells.

 Systemic:
 Cardiovascular: As preload and afterload decrease, there is a compensatory baroreceptor
response resulting in increased sympathetic activity and release of catecholamines into the
circulation. This results in tachycardia and systemic vasoconstriction (except in sepsis).
 Respiratory: The metabolic acidosis and increased sympathetic response result in an
increased respiratory rate and minute ventilation to increase the excretion of carbon dioxide
(and so produce a compensatory respiratory alkalosis).
 Renal: Decreased perfusion pressure in the kidney leads to reduced filtration at the
glomerulus and a decreased urine output. The renin–angiotensin–aldosterone axis is
stimulated, resulting in further vasoconstriction and increased sodium and water
reabsorption by the kidney.

 Endocrine: As well as activation of the adrenal and renin–angiotensin systems, vasopressin
(antidiuretic hormone) is released from the hypothalamus in response to decreased preload
and results in vasoconstriction and resorption of water in the renal collecting system.
Cortisol is also released from the adrenal cortex contributing to the sodium and water
resorption and sensitizing the cells to catecholamines.
 Ischaemia–reperfusion syndrome:
 The cellular and humoral elements activated by the hypoxia (complement, neutrophils,
microvascular thrombi) are pushed back into the circulation where they cause further
endothelial injury to organs such as the lungs and the kidneys. This leads to acute lung
injury, acute renal injury, multiple organ failure and death.
 Re-perfusion injury can currently only be attenuated by reducing the extent and duration of
tissue hypoperfusion.

 Acidosis
 The best fundamental approach to metabolic acidosis from shock is to treat the
underlying cause of shock. In the surgeon’s case, it is blood loss or ischemic tissue.
However, some clinicians believe that treating the pH has advantages because the
enzymes necessary for the coagulation cascade work better at an optimal
temperature and optimal pH. Coagulopathy can contribute to uncontrolled bleeding,
so some have recommended treating acidosis with bicarbonate infusion for patients
in dire scenarios. Treating acidosis with sodium bicarbonate may have a benefit in
an unintended and unrecognized way. Rapid infusion of bicarbonate is usually
accompanied by a rise in BP in hypotensive patients. This rise is usually attributed
to correcting the pH; however, sodium bicarbonate in most urgent scenarios is given
in ampules. The 50-mL ampule of sodium bicarbonate has 1 mEq/ mL—in essence,
similar to giving a hypertonic concentration of sodium, which quickly draws fluid
into the vascular space. Given its high sodium concentration, a 50-mL bolus of
sodium bicarbonate has physiologic results similar to 325 mL of normal saline or
385 mL of LR. Essentially, it is like giving small doses of HTS. Sodium bicarbonate
quickly increases CO2 levels by its conversion in the liver, so if the minute
ventilation is not increased, respiratory acidosis can result.

 THAM (tromethamine; tris[hydroxymethyl] aminomethane) is a biologically inert
amino alcohol of low toxicity that buffers CO2 and acids. It is sodium free and
limits the generation of CO2 in the process of buffering. At 37° C, the pKa of
THAM is 7.8, making it a more effective buffer than sodium bicarbonate in the
physiologic range of blood pH. In vivo, THAM supplements the buffering capacity of
the blood bicarbonate system by generating sodium bicarbonate and decreasing the
partial pressure of CO2. It rapidly distributes to the extracellular space and slowly
penetrates the intracellular space, except in the case of erythrocytes and
hepatocytes, and it is excreted by the kidney. Unlike sodium bicarbonate, which
requires an open system to eliminate CO2 to exert its buffering effect, THAM is
effective in a closed or semiclosed system, and it maintains its buffering ability
during hypothermia. THAM acetate (0.3 M, pH 8.6) is well tolerated, does not
cause tissue or venous irritation, and is the only formulation available in the United
States. THAM may induce respiratory depression and hypoglycaemia, which may
require ventilatory assistance and the administration of glucose.
 The initial loading dose of THAM acetate (0.3 M) for the treatment of acidemia
may be estimated as follows:
 THAM (in mL of 0.3M solution) = lean body weight ( in kilogram) X the base deficit (in
mmol/liter)

 Hypothermia, although potentially beneficial, is detrimental in trauma patients
mainly because it causes coagulopathy. Cold affects coagulopathy by decreasing
enzyme activity, enhancing fibrinolytic activity, and causing platelet dysfunction.
Platelets are affected by the inhibition of thromboxane B2 production, resulting in
decreased aggregation. A heparin-like substance is released, causing diffuse
intravascular coagulation–like syndrome. Hageman factor and thromboplastin are
some of the enzymes most affected. Even a drop in core temperature of just a few
degrees results in 40% inefficiency in some of the enzymes.
 Heat affects the coagulation cascade so much that when blood is drawn in cold
patients and sent to the laboratory, the sample is heated to 37° C, because even 1°
or 2° of cold delays clotting and renders test results inaccurate. Thus, in a cold and
coagulopathic patient, if the coagulation profile obtained from the laboratory shows
an abnormality, the result represents the level of coagulopathy if the patient (and
not just the sample) had been warmed to 37° C. Therefore, a cold patient is always
even more coagulopathic than indicated by the coagulation profile. A normal
coagulation profile does not necessarily represent what is going on in the body.

 If an average man (weight, 75 kg) consisted of pure water, it would take 75 kcal to
raise his temperature by 1° C. However, we are not made of pure water, and blood
has a specific heat coefficient of 0.87. Thus, the human body as a whole has a
specific heat coefficient of 0.83. Therefore, it actually takes 62.25 kcal (75 kg ×
0.83) to raise body temperature by 1° C. If a patient were to lose 62.25 kcal, body
temperature would drop by 1° C.
 The normal basal metabolic heat generation is about 70 kcal/ hr. Shivering can
increase this to 250 kcal/hr. Heat is transferred to and from the body by contact or
conduction (as in a frying pan and Jacuzzi), air or convection (as in an oven and
sauna), radiation, and evaporation. Convection is an extremely inefficient way to
transfer heat as the air molecules are so far apart compared with liquids and
solids. Conduction and radiation are the most efficient ways to transfer heat.
However, heating the patient with radiation is fraught with inconsistencies and
technical challenges, and thus it is difficult to apply clinically, so we are left with
conduction to transfer energy efficiently.

 Warming or cooling through manipulation of the temperature of IV fluids is useful
as it uses conduction to transfer heat. Although IV fluids can be warmed, the U.S.
Food and Drug Administration (FDA) allows fluid warmers to be set at a maximum of
40° C. Therefore, the differential between a cold trauma patient (34° C) and warmed
fluid is only 6°. Thus, 1 liter of warmed fluids can transfer only 6 kcal to the
patient. As previously calculated, one needs about 62 kcal to raise the core
temperature by 1°. Therefore, we need 10.4 liters of warmed fluids to raise the
core temperature by 1° to 35° C. Once that has been achieved, the differential is
now only 5° between the patient and the warmed fluid, so it actually takes 12.5
liters of warmed fluids to raise the patient from 35° C to 36° C. A cold patient at
32° C needs to be given 311 kcal (75 kg × 0.83) to be warmed to 37° C. Note that
a liter of fluid must be given at the highest rate possible because if the infusion
rate is slow, it cools to room temperature as the IV line is exposed to ambient
room temperature. To avoid IV line cooling, devices that warm fluids up to the
point of insertion into the body should be used.

 Warming of patients by infusion of warmed fluids is difficult, but fluid warmers are
still critically important; the main reason to warm fluids is so that patients are not
cooled. Cold fluids can cool patients quickly. The fluids that are typically infused are
either at room temperature (22° C) or 4° C if the fluids were refrigerated. T he
internal temperature of a refrigerator is 4° C, and this is where PRBCs are stored.
Therefore, it takes 5 liters of 22° C fluid or 2 liters of cold blood products to cool a
patient by 1°. Again, the main reason for using fluid warmers is not necessarily to
warm patients but to prevent cooling them during resuscitation.
 The most important way to prevent heat loss is to treat haemorrhagic shock by
controlling bleeding. Once shock has been treated, metabolism will heat the patient
from his or her core. This point cannot be overemphasized.

Classification of warming techniques

 Forced air heating increases only the patient’s ambient temperature, but it can
actually cool the patient initially because it increases evaporative heat loss if the
patient is wet from blood, fluids, clothes, or sweat. Warming the skin may feel
good to the patient and the surgeon, but it actually decreases shivering (a highly
efficient method of internal warming that tricks the thermoregulatory nerve input on
the skin). Because forced-air heating uses convection, the actual amount of active
warming is estimated to be only 10 kcal/hr.
 Active external warming is better performed by placing patients on heating pads,
which use conduction to transfer heat. Beds are available that can warm patients
faster, such as the Clinitron bed (Hill-Rom, Batesville, Ind), which uses heated air-
fluidized beads. Such beds are not practical in the operating room but are
applicable in the ICU. Removal of wet sheets and wet clothes remains an essential
aspect of rewarming. Heating pads that use heated water use countercurrent heat
exchange; placed under the patient during surgery, they can be effective in
minimizing mild hypothermia. The amount of kilocalories per hour depends on the
extent of dilation or vasoconstriction of the blood vessels in the skin. This counter
current heat exchange system can also be used to cool the patient if so desired.

 The best method to warm patients is to deliver the calories internally (Table 4-4).
Heating the air used for ventilators is technically internal active warming, but it is
inefficient because, again, the heat transfer method is convection. The surface area
of the lungs is massive, but the energy is mainly transferred through humidified
water droplets, mostly by convection and not conduction. The amount of heat
transferred through warmed humidified air is also minimal by comparison to
methods that use conduction. Body cavities can be lavaged by infusing warmed
fluids through chest tubes or by merely irrigating the abdominal cavity with hot
fluids. Other means written about but rarely used in practice include gastric lavage
and esophageal lavage with special tubes. If gastric lavage is desired, one method is
continuous lavage by infusion of warmed fluids through the sump port while the
fluid is sucked out of the main tube. Bladder irrigation with an irrigation Foley
catheter is also useful. Instruments to warm the hand through conduction show
much promise but are not yet readily available.

 The best means to deliver heat is through a countercurrent exchange system, using
conduction to transfer calories. Again, heating the IV fluids and then infusing the
warmed fluids is technically active internal warming, but again, because of the
limitations of how hot we can heat the fluids, it is relatively inefficient. Heating
fluids before infusion is to minimize cooling rather than to actively warm. Full
cardiopulmonary bypass is unmatched; it delivers more than 5 litres/min of heated
blood to every place in the body where there are capillaries. If full cardiopulmonary
bypass is not available or not desired, alternatives include continuous venous or
arterial rewarming. Venous-venous rewarming is most easily accomplished using the
roller pump of a dialysis machine (which is often more available to the average
surgeon). A prospective study showed arterial-venous rewarming to be highly
effective. It can warm patients to 37° C in about 39 minutes, compared with an
average warming time of 3.2 hours with standard techniques. Special Gentilello
arterial warming catheters are inserted into the femoral artery, and a second line is
inserted into the opposite femoral vein. The pressure from the artery produces
flow, which is then directed to a fluid warmer and back into the vein. This method
depends highly on the patient’s BP because flow is directly related to BP. There are
also commercially available central line catheters that directly heat the blood; a
countercurrent exchange system heats the tip of the catheter with warmed fluids,
and as blood passes over this warmed catheter, it can directly transfer kilocalories.

 During the last decades, with the changes in resuscitation methods, the incidence
of hypothermia has decreased, and it is now less of a problem. Dilutional
coagulopathy also occurs less frequently as the volume of crystalloids has been
minimized, and particular attention has been paid to ensure that all resuscitation
fluids and blood are warmed before infusion.

Trauma inflammation and immunology

 Coagulopathy in surgical patients is multifactorial. In addition to acidosis and
hypothermia, the other main usual cause of coagulopathy is decreased clotting factors.
This decrease is caused by consumption (from the innate attempt to stop bleeding),
dilution (from infused fluids devoid of clotting factors), and genetic (haemophilia) factors.
 Thromboelastography and rotational thromboelastometry have emerged as dynamic
measures of coagulation that provide a more sensitive and accurate measure of the
coagulation changes seen in trauma patients. Thromboelastography and rotational
thromboelastometry are based on similar principles of detecting clot strength, which is
the final product of the coagulation cascade. They are also performed on whole blood,
so they take into account the functional interaction of coagulation factors and platelets.
Thromboelastography parameters include R, reaction time; α, alpha angle; and MA,
maximum amplitude. The R time reflects the latent time until fibrin formation begins. An
increase in this time may result from factor deficiency or decreased factor activity,
whereas a decrease in R time reflects a hypercoagulable state. The steepness of the α
angle reflects the rate of fibrin formation. T he measure of clot strength is MA, which
reflects clot elasticity. T he value of MA is a measure of the strength of interaction
between the coagulation factors and platelets. Qualitative or quantitative defects in either
of these would result in decreased MA. Thromboelastography provides the additional
ability to measure the fibrinolytic arm of the coagulation cascade. LY30 and LY60 indices
provide a measure of the fibrinolysis rate by calculating the decrease in clot strength at
30 and 60 minutes, respectively. A large lysis index reflects rapid fibrinolysis and may
help guide the use of antifibrinolytic therapy in these patients, which has been shown to
reduce mortality if it is used within 3 hours of injury. These tests are routinely used in
cardiac surgery and are becoming more popular in trauma in the form of point-of-care
testing, but they are not widely available in most hospitals.

 The military began using rFVIIa during the war in Iraq and reported a decreased
30-day mortality rate without an increased risk of severe thrombotic events. Caution
started to emerge as thromboembolic events were being reported. It seems that
injured vessels were at risk for thrombosis. The ideal dose of the drug is still
unclear, as is the optimal timing of administration.
 The average cost for the drug is $1/µg/kg; for a 75-kg person, that equates to
$7500 per dose.
 Although rFVIIa is not yet shown to be beneficial in traumatic shock, it may be
particularly useful in patients with TBI.
 Factor IX or prothrombin complex concentrate (PCC) has become popular for the
treatment of surgical coagulopathy. For patients taking warfarin, PCC is the
recommended treatment of choice. T his is of particular benefit in elderly patients
with TBI, in whom treatment with fresh-frozen plasma (FFP) can potentially be a
problem if the patient has comorbid cardiac disease and could induce cardiac heart
failure from volume overload. Additional benefit of using PCC is that the time to
reversal of coagulopathy is shorter than when FFP is used.26 PCC actually has many
factors (factors II, VII, IX, X) in it, including variable amounts of factor VIIa,
depending on the brand of PCC used. It also has the advantage of costing only
one-tenth the cost of rFVIIa.

 Tranexamic acid (TXA) is a synthetic analogue of the amino acid lysine. It is an
antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin.
Thus, it prevents degradation of fibrin, which is a protein that forms the
framework of blood clots. TXA has about eight times the antifibrinolytic activity of
an older analogue, ε-aminocaproic acid. It is used to treat or to prevent excessive
blood loss during surgical procedures, such as on the heart, liver, and vascular
system, and in large orthopaedic procedures. It seems that topical TXA is effective
and safe after total knee and hip replacement surgery, reducing bleeding and the
need for blood transfusions. Studies have shown similar results in children
undergoing craniofacial surgery, spinal surgery, and others.
 It is even used for heavy menstrual bleeding in oral tablet form and in dentistry as
a 5% mouthwash. Recently, it is advocated for use in trauma. It seems to be
effective in reducing rebleeding in spontaneous intracranial bleeding.
 A small double blinded, placebo-controlled, randomized study of 238 patients
resulted in reducing progressive intracranial bleeding after trauma, but because of
the small sample size, it was not statistically significant. TXA is used to treat
primary fibrinolysis, which is integral in the pathogenesis of the acute coagulopathy
of trauma.

 The CRASH-2 (Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage)
trial, a multicenter randomized controlled civilian trial of 20,211 patients, showed
that TXA reduced all-cause mortality versus placebo (14.5% versus 16.0%).27 The risk
of death caused by bleeding was also reduced (4.9% versus 5.7%). CRASH-2 also
suggested that TXA was less effective and could even be harmful if treatment was
delayed more than 3 hours after admission. This was confirmed in the retrospective
MATTERs (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation)
study.

Monitoring
 The minimum standard for monitoring of the patient in shock are:
 1. continuous heart rate and oxygen saturation monitoring,
 2. frequent non-invasive blood pressure monitoring and
 3. hourly urine output measurements.
 Monitors for organ/systemic perfusion

 MIXED VENOUS OXYGEN SATURATION
 The percentage saturation of oxygen returning to the heart from the body is a measure of
the oxygen delivery and extraction by the tissues. Accurate measurement is via analysis of
blood drawn from a long central line placed in the right atrium. Estimations can be made
from blood drawn from lines in the superior vena cava, but these values will be slightly
higher than those of a mixed venous sample (as there is relatively more oxygen extraction
from the lower half of the body).
 Normal mixed venous oxygen saturation levels are 50–70%. Levels below 50% indicate
inadequate oxygen delivery and increased oxygen extraction by the cells. This is consistent
with hypovolaemic or cardiogenic shock.
 High mixed venous saturations (>70%) are seen in sepsis and some other forms of
distributive shock. In sepsis, there is disordered utilisation of oxygen at the cellular level,
and arteriovenous shunting of blood at the microvascular level. Therefore, less oxygen is
presented to the cells, and those cells cannot utilise what little oxygen is presented. Thus,
venous blood has a higher oxygen concentration than normal.
 Systemic and organ perfusion:
 Base deficit
 Lactate
 Mixed venous oxygen saturation

 Haemorrhage types:
 Revealed and concealed haemorrhage:
 Revealed haemorrhage is obvious external haemorrhage, such as exsanguination from an
open arterial wound or from massive haematemesis from a duodenal ulcer. Concealed
haemorrhage is contained within the body cavity and must be suspected, actively
investigated and controlled.
 Primary, reactionary and secondary haemorrhage
 Primary haemorrhage is haemorrhage occurring immediately due to an injury (or
surgery).
 Reactionary haemorrhage is delayed haemorrhage (within 24 hours) and is usually due to
dislodgement of a clot by resuscitation, normalisation of blood pressure and
vasodilatation. Reactionary haemorrhage may also be due to technical failure, such as
slippage of a ligature.
 Secondary haemorrhage is due to sloughing of the wall of a vessel. It usually occurs 7–14
days after injury and is precipitated by factors such as infection, pressure necrosis (such as
from a drain) or malignancy.
 Surgical and non-surgical haemorrhage:
 Surgical haemorrhage is due to a direct injury and is amenable to surgical control (or other
techniques such as angio-embolization). Non-surgical haemorrhage is the general ooze
from all raw surfaces due to coagulopathy and cannot be stopped by surgical means (except
packing). Treatment requires correction of the coagulation abnormalities.

Management
 Remember the ABCs
 Airway and cervical spine control
 Breathing and ventilation
 Circulation and haemorrhage control
 Disability and GCS
 Exposure and Environment control
 And AMPLE history
 A = Allergy
 M = Medications
 P = Past illness
 L = Last meal
 E = Events leading to current condition

 External haemorrhage may be obvious, but the diagnosis of concealed haemorrhage
may be more difficult. Any shock should be assumed to be hypovolemic until proved
otherwise, and similarly, hypovolaemia should be assumed to be due to haemorrhage
until this has been excluded.

 Immediate resuscitative manoeuvres:
 Direct pressure should be placed over the site of external haemorrhage. Airway and
breathing should be assessed and controlled as necessary. Large-bore intravenous access
should be instituted, and blood drawn for cross-matching. Emergency blood should be
requested if the degree of shock and ongoing haemorrhage warrants this.
 Transfusion trigger:

 Identify the site of haemorrhage:
 Once haemorrhage has been considered, the site of haemorrhage must be rapidly identified. Note
this is not to definitively identify the exact location, but rather to decide the next step in
haemorrhage control (operation, angio-embolization, endoscopic control).
 Haemorrhage control:
 The bleeding, shocked patient must be moved rapidly to a place of haemorrhage control. This
will usually be in the operating room but may be the angiography or endoscopy suites. These
patients require surgical and anaesthetic support and full monitoring and equipment must be
available. Haemorrhage control must be achieved rapidly so as to prevent the patient entering the
triad of coagulopathy–acidosis-hypothermia and physiological exhaustion. There should be no
unnecessary investigations or procedures prior to haemorrhage control to minimize the duration
and severity of shock.
 A. Initial Transfusion of Red Blood Cells (RBCs):
 1. Notify blood bank immediately of urgent need for RBCs. O negative uncrossmatched
(available immediately).
 As soon as possible, switch to O negative for females and O positive for males.
 Type-specific uncrossmatched (available in approximately 5–10 min).
 Completely crossmatched (available in approximately 40 min).
 2. A blood sample must be sent to blood bank for a type and cross.
 3. The Emergency Release of Blood form must be completed. If the blood type is not known
and blood is needed immediately, O-negative RBCs should be issued.
 4. RBCs will be transfused in the standard fashion. All patients must be identified (name and
number) prior to transfusion.
 5. Patients who are unstable or receive 1–2 RBCs and do not rapidly respond should be
considered candidates for the massive transfusion (MT) guideline.

 B. Adult Massive Transfusion Guideline:
 1. The Massive Transfusion Guideline (MTG) should be initiated as soon as it is anticipated
that a patient will require massive transfusion. The blood bank should strive to deliver
plasma, platelets, and RBCs in a 1:1:1 ratio. To be effective and minimize further dilutional
coagulopathy, the 1:1:1 ratio must be initiated early, ideally with the first 2 units of
transfused RBCs. Crystalloid infusion should be minimized.
 2. Once the MTG is activated, the blood bank will have 6 RBCs, 6 FFP, and a 6-pack of
platelets packed in a cooler available for rapid transport. If 6 units of thawed FFP are not
immediately available, the blood bank will issue units that are ready and notify
appropriate personnel when the remainder is thawed. Every attempt should be made to
obtain a 1:1:1 ratio of plasma:platelets:RBCs.
 3. Once initiated, the MT will continue until stopped by the attending physician. MT
should be terminated once the patient is no longer actively bleeding.4. No blood
components will be issued without a pickup slip with the recipient’s medical record
number and name.
 5. Basic laboratory tests should be drawn immediately on ED arrival and optimally
performed on point-of-care devices, facilitating timely delivery of relevant information to
the attending clinicians. These tests should be repeated as clinically indicated (e.g., after
each cooler of products has been transfused). Suggested laboratory values are:
 • CBC
 • INR, fibrinogen
 • pH and/or base deficit
 • TEG, where available

 Component therapy administration during massive transfusion

 Components of crystalloids:

 Permissive Hypotension
 The idea of permissive hypotension was slow to catch on. The argument against
allowing anything besides aggressive resuscitation was dismissed. Critics continued
to emphasize that the Mattox trial focused only on penetrating injuries and should
not be extrapolated to blunt trauma. Clinicians feared that patients with traumatic
blunt head injuries would be harmed without a normalized BP. However, Shafi and
Gentilello examined the National Trauma Data Bank and found that hypotension was
an independent risk factor for death, but it did not increase the mortality rate in
patients with TBIs any more than in patients without TBIs.
 Everything that surgeons had been taught before 1994 stressed that not treating
hypotensive patients with fluids would certainly and surely lead to death, yet
Mattox’s study showed the opposite.
 That 1994 article popularized the concept of permissive hypotension, that is,
allowing hypotension during uncontrolled haemorrhage. The fundamental rationale
for permissive hypotension was that restoration of BP with fluids would increase
bleeding from uncontrolled sources.
 The idea was that increasing BP would dislodge the clot that had formed. The
study also found that the pressure that would cause rebleeding was a mean arterial
pressure of 64 ± 2 mm Hg, with a systolic pressure of 94 ± 3 mm Hg and diastolic
pressure of 45 ± 2 mm Hg. Other animal studies have confirmed these concepts.

 Surgical intervention may need to be limited to the minimum necessary to stop bleeding
and control sepsis. More definitive repairs can be delayed until the patient is
haemodynamically stable and physiologically capable of sustaining the procedure. This
concept of tailoring the operation to match the patient’s physiology and staged procedures
to prevent physiological exhaustion is called ‘damage control surgery’ .

 Damage control surgery
 Arrest haemorrhage
 Control sepsis
 Protect from further injury
 Nothing else

 Damage control resuscitation
 These concepts have been combined into a new paradigm for the management of trauma
patients with active haemorrhage called damage control resuscitation (DCR). The four
central strategies of DCR are:
 Anticipate and treat acute traumatic coagulopathy
 Permissive hypotension until haemorrhage control
 Limit crystalloid and colloid infusion to avoid dilutional coagulopathy
 Damage control surgery to control haemorrhage and preserve physiology.
 Damage control resuscitation strategies have been shown to reduce mortality and morbidity
in patients with exsanguinating trauma and may be applicable in other forms of acute
haemorrhage

 Complications of blood transfusion
 Complications from a single transfusion:
 incompatibility haemolytic transfusion reaction
 febrile transfusion reaction
 allergic reaction
 infection–
 bacterial infection (usually due to faulty storage)
 hepatitis
 HIV
 malaria
 air embolism
 thrombophlebitis
 transfusion-related acute lung injury (usually from FFP).

 Complications from massive transfusion
 Coagulopathy
 hypocalcaemia
 hyperkalaemia
 hypokalaemia
 hypothermia.
 In addition, patients who receive repeated transfusions over long periods of time (e.g.
patients with thalassaemia) may develop iron overload. (Each transfused unit of red blood
cells contains approximately 250 mg of elemental iron.)

 Management of coagulopathy
 Correction of coagulopathy is not necessary if there is no active bleeding or haemorrhage is
not anticipated (not due for surgery). However, coagulopathy following or during massive
transfusion should be anticipated and managed aggressively.
 Standard guidelines are as follows:
 FFP if prothrombin time (PT) or partial thromboplastin time (PTT) >1.5 times normal
 cryoprecipitate if fibrinogen <0.8 g/L
 platelets if platelet count <50 × 10^9/L

 Topical haemostatic agents:
 Topical Hemostatic Agents: They can play an important role in helping to facilitate
surgical hemostasis. These agents are classified based on their mechanism of action, and
many act at specific stages in the coagulation cascade and take advantage of natural
physiologic responses to bleeding. The ideal topical hemostatic agent has significant
hemostatic action, minimal tissue reactivity, nonantigenicity, in vivo biodegradability, ease
of sterilization, low cost, and can be tailored to specific needs.
 Achneck et al have published a comprehensive overview of absorbable, biologic, and
synthetic agents. Absorbable agents include gelatin foams (Gelfoam), oxidized cellulose
(Surgicel), and microfibrillar collagens (Avitene). Both gelatin foam and oxidized cellulose
provide a physical matrix for clotting initiation, while microfibrillar collagens facilitate
platelet adherence and activation.
 Biologic agents include topical thrombin, fibrin sealants (FloSeal), and platelet sealants
(Vitagel).
 Human or recombinant thrombin derivatives, which facilitate the formation of fibrin clots
and subsequent activation of several clotting factors, take advantage of natural
physiologic processes, thereby avoiding foreign body or inflammatory reactions.

 Caution must be taken in judging vessel caliber in the wound because thrombin
entry into larger caliber vessels can result in systemic exposure to thrombin with a risk of
disseminated intravascular clotting or death. They are particularly effective in
controlling capillary bed bleeding when pressure or ligation is insufficient; however, the
bovine derivatives should be used with caution due to the potential immunologic
response and worsened coagulopathy.
 Fibrin sealants are prepared from cryoprecipitate (homologous or synthetic) and have the
advantage of not promoting inflammation or tissue necrosis.
 A recent study by Koea et al demonstrated in a prospective multicenter randomized trial
that a fibrin sealant patch was safe and highly effective in controlling parenchymal
bleeding following hepatectomy regardless of the type of resection.
 Platelet sealants are a mixture of collagen and thrombin combined with plasma-derived
fibrinogen and platelets from the patient, which requires the additional need for
centrifugation and processing.
 A direct current also can result in hemostasis. Because the protein moieties and cellular
elements of blood have a negative surface charge, they are attracted to a positive pole
where a thrombus is formed. Direct currents in the 20- to 100-mA range have
successfully controlled diffuse bleeding from raw surfaces, as has argon gas.

Monitoring adequacy of resuscitation
 The state of normal vital signs and continued underperfusion is termed ‘occult
hypoperfusion’. With current monitoring techniques, it is manifested only by a
persistent lactic acidosis and low mixed venous oxygen saturation. The time spent by
patients in this hypoperfused state has a dramatic effect on outcome. Patients with occult
hypoperfusion for more than 12 hours have two to three times the mortality of patients
with a limited duration of shock. Resuscitation algorithms directed at correcting global
perfusion end points (base deficit, lactate, mixed venous oxy gen saturation) rather than
traditional end points have been shown to improve mortality and morbidity in high risk
surgical patients. However, it is clear that, despite aggressive regimes, some patients
cannot be resuscitated to normal parameters within 12 hours by fluid resuscitation
alone.

 Lactate:
 Lactate is generated by conversion of pyruvate to lactate by lactate dehydrogenase in
the setting of insufficient O2. Lactate is released into the circulation and is predominantly
taken up and metabolized by the liver and kidneys. The liver accounts for
approximately 50% and the kidney for about 30% of whole body lactate uptake. Elevated
serum lactate is an indirect measure of the O2 debt, and therefore an approximation
of the magnitude and duration of the severity of shock.
 Elevated serum lactate is an indirect measure of the O2 debt, and therefore an
approximation of the magnitude and duration of the severity of shock. The admission
lactate level, highest lactate level, and time interval to normalize the serum lactate are
important prognostic indicators for survival.
 However individual variability of lactate may be too great to permit accurate prediction of
outcome in any individual case. Base deficit and volume of blood transfusion required in
the first 24 hours of resuscitation may be better predictors of mortality than the
plasma lactate alone.

 Base Deficit:
 Base deficit is the amount of base in millimoles that is required to titrate 1 L of whole
blood to a pH of 7.40 with the sample fully saturated with O2 at 37°C (98.6°F)
and a partial pressure of CO2 of 40 mmHg. It usually is measured by arterial blood gas
analysis in clinical practice as it is readily and quickly available.
 Base deficit can be stratified into mild (3 to 5 mmol/L), moderate (6 to 14 mmol/L), and
severe (15 mmol/L) categories, with a trend toward higher mortality with worsening base
deficit in patients with trauma. Both the magnitude of the perfusion deficit as indicated
by the base deficit and the time required to correct it are major factors determining
outcome in shock.
 Indeed, when elevated base deficit persists (or lactic acidosis) in the trauma patient,
ongoing bleeding is often the etiology. Trauma patients admitted with a base deficit
greater than 15 mmol/L required twice the volume of fluid infusion and six times more
blood transfusion in the first 24 hours compared to patients with mild acidosis.
Transfusion requirements increased as base deficit worsened and ICU and hospital
lengths of stay increased. Mortality increased as base deficit worsened; the frequency of
organ failure increased with greater base deficit. The probability of trauma patients
developing ARDS has been reported to correlate with severity of admission base deficit
and lowest base deficit within the first 24 hours postinjury.
 Monitoring base deficit in the resuscitation of trauma patients assists in assessment of O2
transport and efficacy of resuscitation.

 Near Infrared Spectroscopy:
 The optimal device for monitoring the adequacy of resuscitation should be noninvasive,
simple, cheap, and portable. NIR spectroscopy uses the NIR region of the
electromagnetic spectrum from about 800 nm to 2500 nm. Typical applications are wide
ranging: physics, astronomy, chemistry, pharmaceuticals, medical diagnostics, and food and
agrochemical quality control. The main attraction of NIR is that light, at those
wavelengths, can penetrate skin and bone.
 A common device using NIR technology that has now become standard in the medical
industry is the pulse oximeter. Using slightly different light waves, it yielded correlations
with such variables as the cytochrome aa3 status by adding a third light wave in the
800-nm region. When the oxygen supply is less than adequate, the rate of electron
transport is reduced, and oxidative phosphorylation decreases, leading ultimately to
anaerobic metabolism. Optical devices that use NIR wavelengths can determine the redox
potential of copper atoms on cytochrome aa3 and have been used to study intracellular
oxidative processes noninvasively. Thus, with NIR technology, the metabolic rate of tissue
can be directly determined to assess whether it is being adequately perfused. Animal
models of haemorrhagic shock have validated the potential use of NIR technology in that
they showed changes in regional tissue beds (Fig. 4-11). The superiority of NIR results
over conventional measurements of shock has been shown in animal and human studies.
 The NIR probe was found to be as sensitive as base deficit in predicting death and
MODS in hypotensive trauma patients.33 T he receiver operating characteristic curves
show that it also may be somewhat better than BP in predicting outcome. More
important, the negative predictive value was 90% (Fig. 4-12). The noninvasive and
continuous NIR probe was able to demonstrate perfusion status. Note, however, that
MODS developed in only 50 patients in that study. This was probably because the
method of resuscitating trauma patients changed during this period, and this reduced
MODS and death rates.

 NIR technology may be able to show when a patient is in shock or even when a
patient is doing well. Occult hypoperfusion can be detected or even ruled out
reliably with NIR. In the trauma setting, a noninvasive method that can continuously
detect trends in parameters such as regional oxygenation status, base deficit, or BP
will surely find a role.
 Will this technology change how patients are treated? The debate now centers on
this issue and raises some questions. Once a patient’s hypoperfusion status has been
determined, whether by BP, NIR technology, or some other device, what should we
do with that information? Is it necessary to increase oxygen delivery to regional
tissue beds that are inadequately oxygenated? Previous studies have shown that
optimizing global oxygen delivery is not useful and that regional tissue monitoring
with gastric tonometry has also failed to show benefit, so will NIR technology be
helpful or harmful? An example of harm is over-resuscitating a patient to fix an
abnormal value that may or may not mean much clinically. The end point of
resuscitation is constantly being debated. Because NIR results correlate well with
base deficit, we may one day use NIR technology to infer the base deficit value
indirectly.
 NIR technology has other promising uses in surgery, such as direct monitoring of
flow and tissue oxygenation in high-risk patients (e.g., in those undergoing organ
transplantation; for free f lap perfusion; for classification of burn injuries; in
intraoperative assessment of bowel ischemia; with compartment syndrome or even
subdural and epidural hematomas). Perhaps the most useful application will be in
the ICU in septic shock patients at risk for multiple-organ failure.

 Detrimental Impact of Fluids
 It was shown that neutrophils are activated after a 40% blood volume haemorrhage
when followed by resuscitation with LR. That finding was not surprising. What was
enlightening was that the level of neutrophil activation was similar in control animals that
did not undergo haemorrhagic shock but merely received LR (Fig. 4-15). In other control
animals that did not receive LR but instead were resuscitated with shed blood or HTS
after haemorrhagic shock, the neutrophils were not activated. The implication was that
the inflammatory process was not caused by shock and resuscitation but by LR itself.
 Experiments with the isomers have shown that D(−)-lactate causes significant
inflammatory changes in rats and swine as well as activation of human neutrophils.
 The U.S. military also requested Baxter, among others manufacturers of LR, to eliminate
D(−)-lactate in LR, which it has done. The LR from Baxter currently contains only the
L(+)lactate isomer.
 HTS has a long record of research and development. It has been used in humans for
decades and has been consistently shown to be less inflammatory than LR. This showed
from an immunologic point of view that HTS is better than LR and that LR is worse
than HTS. Although this is stating the same thing, it is a paradigm shift in recognizing
that LR and normal saline may be detrimental. Again, blood is complex, and the fluids
used in the past were a poor replacement.
 Hetastarch
 Hydroxyethyl starch, sold under the brand name Voluven among others, is a nonionic
starch derivative, used as a volume expander in intravenous therapy. The use of HES
on critically ill patients is associated with an increased risk of death and kidney
problems.

 The Committee on Tactical Combat Casualty Care was formed in 2000 by the U.S.
Navy and now sets policy on the prehospital management of combat casualties.
Their recommendations and algorithm for resuscitation were revolutionary compared
with the civilian recommendations. The algorithm was formed with the following
points in mind:
 1. Most combat casualties do not require fluid resuscitation.
 2. Oral hydration is an underused option as most combat casualties require
resuscitation.
 3 Aggressive resuscitation has not been shown to be beneficial in civilian victims of
penetrating trauma.
 4. Moderate resuscitation in animal models of uncontrolled haemorrhage offers the
best outcome.
 5. Large volumes of LR are not safe.
 6. Colloid or HTS offers a significant advantage in terms of less weight and cube for
the military medic or corpsman.

 Crystalloids
 The mechanism responsible for acidosis, after large volumes of normal saline are infused,
is the dilution of serum bicarbonate (HCO3−) through the replacement of lost plasma
with fluids that do not contain bicarbonate. Normally, chloride and bicarbonate ions are
reciprocated up or down with each other. Often, the result of massive normal saline
infusion is a hyperchloremic anion gap metabolic acidosis. At extreme levels, acidosis can
impair cardiac performance and decrease responsiveness to cardiac inotropic drugs. Many
would argue that for cellular protection, the human body offloads oxygen more easily
from haemoglobin in the acidotic state and that acidosis, at least to a degree, is actually
better for a patient than alkalosis.
 Regardless of the theoretical advantages and disadvantages of induced metabolic acidosis,
no clinical evidence exists that it makes a difference. Surgeons with experience using HTS
sometimes encounter induced metabolic acidosis but have found it to be of minimal
clinical consequence. Induced metabolic hyperchloremic acidosis is different from
spontaneous metabolic acidosis and from hypovolemic lactic acidosis. No evidence exists
that hyperchloremic acidosis does anything more than confuse the interpretation of the
metabolic state. Given the lack of any significant proven benefit of one crystalloid over
another, many trauma systems use normal saline in the prehospital setting. This is
because stocking just one form of fluid is convenient. Another reason is that when
transfusion is required, the LR has to be switched to normal saline as LR contains
calcium and is contraindicated. This is a regulatory policy even though studies have
shown that the use of LR as a carrier in the same IV line as blood has no relevant side
effects.
 In most institutions, the costs of LR, normal saline, and Plasma-Lyte are similar, which is
about $3.00. If LR is to be used, it should be the LR manufactured by Baxter, which
currently makes LR with only the L(+)lactate isomer, and it does not contain the D(−)-
lactate isomer.

 Hypertonic Saline:
 In an animal model of hemorrhagic shock, if 1 liter of normal saline is required to
achieve a BP of 120 mm Hg, the same result can be obtained with an infusion of 120
mL of 7.5% normal saline. For 5% HTS, only 182 mL would be needed. In animal
studies, HTS draws water into the intravascular space from the intracellular and
interstitial spaces.
 HTS has consistently been shown to reduce the inflammatory response and is thus
considered to be immunomodulatory. Immunosuppression from HTS may thus be
beneficial and detrimental, depending on when and how it is used.
 One of the main problems with 7.5% HTS is that there is no manufacturer that makes
and sells it. This is because it is extremely difficult and expensive to obtain FDA approval,
and there is probably no profit in selling salt water. In Europe, 7.5% HTS with dextran is
available.
 HTS infusion is highly effective in decreasing ICP and can do this while increasing blood
volume, BP, and blood f low to the brain. Compared with mannitol, which is customarily
used for lowering ICP, HTS might do this without dehydrating patients or putting them at
further risk for secondary brain injury caused by hypotension or renal failure from
mannitol.
 HTS injected rapidly into human volunteers causes pain at the infusion site. Thus, the
preferred route is through the central vein.
 In animal studies, if 7.5% HTS is given through the interosseous route, osteomyonecrosis
and compartment syndrome can ensue.
 The sodium content of 250 mL of 5% HTS is equivalent to 1645 mL of LR. Thus, a bolus
can be given quickly, without having to use hypotonic solutions such as LR. If 500 mL of
5% HTS is used in acute trauma patients, some believe that can resuscitate patients
without having to give 3 liters of a crystalloid solution. That belief complies with the
concept of damage control resuscitation, in which one of the goals is to minimize
crystalloid use.

 Colloids:
 Albumin:
 Human albumin (4% to 5%) in saline is considered to be the reference colloidal
solution. It is fractionated from blood and heat treated to prevent transmission of
viruses. It has many theoretical advantages, especially in animal studies, but clinical
studies have not been able to show outcome differences. Its main theoretical
advantage is that compared with crystalloids, it is less inflammatory. This may be
because it is a natural molecule, not artificial. Other than its dilutional effect,
albumin is associated with minimal coagulopathy. No clinical evidence has shown
that albumin is better than other colloids, but the SAFE study in Australia has
shown 4% albumin to be safe, compared with normal saline, in ICU patients.60 The
SAFE study, whose main intent was to show equivalency, found no difference in the
primary outcome (28-day mortality rate) or in any secondary outcome
 There are still other advantages of 25% albumin over artificial colloids. It has a
proven immunologic anti-inflammatory effect and five times less volume than
current artificial colloids. Unlike artificial colloids, it does not potentially lead to
coagulopathic side effects. It has been proven safe from infectious and clinical
standpoints. The volume of fluid that has to be carried is obviously much less (Fig.
4-21). Albumin costs approximately 30 times more than crystalloids and three times
more than dextran or Hextend, but those comparisons were made against 5%
human albumin. The cost of 100 mL of 25% albumin, compared with 500 mL of
Hextend on a physiologic basis, is only approximately three times as much. During
the Vietnam War, 25% albumin was first made available, and it seemed to have
worked well. It was packaged in a green can that could be transported without
damage, had a long shelf life, and was easy to use.

 Hetastarch:
 Hetastarch, particularly the high-molecular-weight preparations, is associated with
alterations in coagulation, specifically resulting in changes in the viscoelastic
measurements and fibrinolysis. Studies have questioned the safety of concentrated
(10%) hetastarch solutions with a molecular weight of more than 200 and a molar
substitution ratio of more than 0.5 in patients with severe sepsis, citing increased
rates of death, acute kidney injury, and use of renal replacement therapy. To
prolong intravascular expansion, a high degree of substitution on glucose molecules
protects against hydrolysis by nonspecific amylases in the blood. However, this
results in accumulation in reticuloendothelial tissues such as skin, liver, and kidneys.
Because of the potential for accumulation in tissues, the recommended maximal
daily dose of hetastarch is 33 to 55 mL/kg/day. Thus, it would be prudent to limit
the use of Hextend to 1 liter in trauma patients, who are often harmed if they
have coagulopathy from increased bleeding. Studies in trauma patients have shown
an association between acute kidney injury and death after blunt trauma.
 Whole Blood:
 Whole blood is now rarely available in civilian practice because it has been seen as an
inefficient use of the limited resource. However, whole blood transfusion has significant
advantages over packed cells as it is coagulation factor rich and, if fresh, more
metabolically active than stored blood.

 Hextend
 HEXTEND® (6% Hetastarch in Lactated Electrolyte Injection) is a sterile,
nonpyrogenic solution for intravenous administration.
Hetastarch 6 g
Sodium Chloride, USP 672 mg
Sodium Lactate Anhydrous, USP 317 mg
Dextrose Hydrous, USP 99 mg
Calcium Chloride Dihydrate, USP 37 mg
Potassium Chloride, USP 22 mg
Magnesium Chloride Hexahydrate, USP 9 mg
Water for Injection, USP qs
Sodium 143
Chloride 124
Lactate 28
Calcium 5
Potassium 3
Magnesium 0.9

 Packed red cells:
 Packed red blood cells are spundown and concentrated packs of red blood cells. Each unit is
approximately 330 mL and has a haematocrit of 50–70%. Packed cells are stored in a SAGM
solution (saline–adenine–glucose–mannitol) to increase shelf life to 5 weeks at 2–6°C. (Older
storage regimes included storage in CPD: citrate–phosphate–dextrose solutions, which have a
shelf life of 2–3 weeks.)
 Fresh frozen plasma:
 Fresh frozen plasma (FFP) is rich in coagulation factors and is removed from fresh blood and
stored at −40 to −50°C with a 2year shelf life. It is the first line therapy in the treatment of
coagulopathic haemorrhage (see below under Management of coagulopathy). Rhesus D
positive FFP may be given to a rhesus D negative woman although it is possible for sero
conversion to occur with large volumes owing to the presence of red cell fragments, and RhD
immunisation should be considered.
 Cryoprecipitate:
 Cryoprecipitate is a supernatant precipitate of FFP and is rich in factor VIII and fibrinogen. It
is stored at −30°C with a 2year shelf life. It is given in low fibrinogen states or factor VIII
deficiency.
 Platelets:
 Platelets are supplied as a pooled platelet concentrate and contain about 250 × 109/L.
Platelets are stored on a special agitator at 20–24°C and have a shelf life of only 5 days. Plate
let transfusions are given to patients with thrombocytopenia or with platelet dysfunction who
are bleeding or undergoing surgery. Patients are increasingly presenting on antiplatelet therapy
such as aspirin or clopidogrel for reduction of cardiovascular risk. Aspirin therapy rarely poses a
problem but control of haemorrhage on the more potent platelet inhibitors can be
extremely difficult. Patients on clopidogrel who are actively bleeding and undergoing major
surgery may require almost continuous infusion of platelets during the course of the
procedure. Arginine vasopressin or its analogues (DDAVP) have also been used in this patient
group, although with limited success.

 Prothrombin complex concentrates:
 Prothrombin complex concentrates (PCC) are highly purified concentrates prepared from
pooled plasma. They contain factors II, IX and X. Factor VII may be included or produced
separately. It is indicated for the emergency reversal of anti coagulant (warfarin) therapy
in uncontrolled haemorrhage.
 Autologous blood:
 It is possible for patients undergoing elective surgery to predonate their own blood up to
3 weeks before surgery for retransfusion during the operation. Similarly, during surgery
blood can be collected in a cell saver which washes and collects red blood cells which can
then be returned to the patient.

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