CASE 17-1, QUESTION 3: A large-bore IV catheter is inserted into N.G.’s arm and STAT blood samples
should be monitored to determine the success of fluid replacement?
Isotonic crystalloids equilibrate rapidly between the interstitial and the intravascular
spaces at a ratio of 3:1. For every liter of fluid infused, approximately 750 mL will
pass into the interstitium, whereas 250 mL will remain in the plasma. Based on
estimated blood loss, the “three-to-one rule” may be applied as a general guideline:
for each 1 mL of blood loss, 3 mL of crystalloid is infused. Because this
determination of blood loss is based solely on clinical assessment and not on
quantitative measurements, treatment is best directed by the response to initial
therapy rather than the initial classification. Close observation of hemodynamic status
with consideration of the patient’s age, particular injury, and pre-hospital fluid
therapy is essential to avoid inadequate or excessive fluid administration.
A safe and effective resuscitative approach for crystalloids in hemorrhagic shock
is to give 2 L of fluid as an initial bolus as rapidly as possible for an adult or 20
mL/kg for a pediatric patient.
13 Additional fluid boluses may be necessary, depending
on the patient’s response. Between boluses, fluids are slowed to maintenance rates
(150–200 mL/hour for adults, weight-based up to 100 mL/hour for children
ongoing evaluation of the patient’s physiologic response for signs of continued blood
loss or inadequate perfusion that would indicate the need for additional volume
replacement. The fluid boluses given to N.G. are an appropriate initial measure, then
assessment of her perfusion is vital to determine the need for additional boluses.
Normalization of BP, HR, and pulse pressure (difference between SBP and
diastolic blood pressure [DBP]) indicate improved circulation. Signs that actual
organ perfusion is normalizing and that fluid resuscitation is adequate include
improvements in mental status, warmth and color of skin, improved acid–base
balance, and increased urinary output. The minimal acceptable urine output is 0.5
mL/kg/hour for an adult, 1 mL/kg/hour for a child, and 2 mL/kg/hour in an infant
13 Persistent metabolic acidosis in normothermic shock usually
indicates the need for additional fluid resuscitation; sodium bicarbonate
administration is controversial but is not recommended unless the pH is less than
14 Monitoring serum lactate and base deficit is important to determine adequate
resuscitation. As perfusion improves, lactate and base deficit will decrease; thus, the
actual values are not as important as the trend. It is important to note that
resuscitation is not defined by just one value or number, such as BP, but by the
constellation of indicators of overall perfusion.
Lactated Ringer’s Versus Normal Saline
CASE 17-1, QUESTION 4: Is there an advantage to using LR solution versus NS solution?
The choice of replacement fluid varies widely in clinical practice. Normal saline
solution has a supraphysiologic chloride content, while LR contains a more balanced
chemical composition (Table 17-4). Large volumes of NS can cause hyperchloremic
metabolic acidosis, thereby worsening the tissue acidosis from hypovolemic shock.
This may also cause immune and renal dysfunction, but survival differences have not
been seen and the clinical significance is unknown.
28,29 LR, in contrast, is a buffered
solution designed to simulate the intravascular plasma electrolyte concentration. It
contains 28 mEq/L of lactate, which is metabolized to bicarbonate in patients with
normal circulation and liver function. In situations in which hepatic perfusion is
reduced (20% of normal) or hepatocellular damage is present, lactate clearance may
be significantly decreased, particularly in combination with hypoxia (SaO2 50% of
In patients with shock and those having cardiopulmonary bypass during
surgery, the half-life of lactate, normally 20 minutes, increases to 4 to 6 hours and 8
hours, respectively. Because unmetabolized lactate can be converted to lactic acid,
prolonged infusion of LR could cause tissue acidosis in predisposed patients.
Concern about the high sodium and chloride content in NS has led to the first-line
selection of more balanced resuscitative solutions (e.g., LR) in patients at high risk of
acidosis, including those with trauma, burns, diabetic ketoacidosis, or undergoing
28 LR, however, should be avoided in patients with metabolic alkalosis,
lactic acidosis, or hyperkalemia. In practice, NS and LR solutions typically are used
interchangeably because neither solution appears to be superior to the other.
The advantage of HS (3% to 7.5% NaCl) solution as a resuscitative fluid is the
smaller volume of fluid required to expand the intravascular compartment compared
with isotonic solutions. This could be a particular advantage in the pre-hospital
setting (e.g., field rescue by emergency medical technicians) given the large volumes
of fluids necessary to restore ongoing blood loss.
With a high concentration of sodium, HS solution exerts an osmotic effect,
translocating fluid from the interstitial and intracellular compartments to the
intravascular space. Consequently, plasma volume is rapidly expanded to a greater
extent than similar volumes of crystalloid solutions, and systemic BP, CO, and ḊO2
are readily increased. HS solution also improves myocardial contractility, causes
peripheral vasodilation, and redistributes blood flow preferentially to the splanchnic
and renal circulations. In addition, intracranial pressure is reduced, but to date HS
has not been shown to improve outcomes in trauma patients with concomitant head
31 Other recent studies have shown that HS may have beneficial effects on
circulation, inflammation, and endothelial function, which may be beneficial in
patients with septic shock and acute lung injury.
31,32 More robust clinical trials are
needed to determine if these preliminary findings translate into improved clinical
It is difficult to make conclusions about the utility of HS for fluid resuscitation
because of the heterogeneity of studies and solutions. The majority of data regarding
patients with hypovolemic shock, but as with isotonic saline the effects are transient
and it has not been shown to improve mortality.
These clinical trials suggest that HS solution may be safe and effective for the
initial resuscitation of hemorrhagic shock. Despite these positive findings, HS
used by clinicians who are unfamiliar with the product. The osmolarity of HS can
range from 1,026 to 2,567 mOsm/L (3%–7.5% NaCl), so infusion through a central
line is preferred to minimize phlebitis. HS may cause hypernatremia and
hyperchloremic metabolic acidosis, resulting in rapid fluid shifts between cellular
compartments and potentially devastating effects such as osmotic demyelination
syndrome. However, most studies have not reported such events, which may be
because of a lack of power or the relatively small volumes of HS used for
CASE 17-1, QUESTION 6: N.G. has received 4 L of LR solution to maintain hemodynamic stability. Her
and is becoming more agitated and combative. Urine
output has been only 30 mL in the past 30 minutes. Laboratory results include the following:
Hematocrit (Hct), 21% (down from 26%)
Hemoglobin (Hgb), 7.1 g/dL (down from 8.9 g/dL)
Two units of packed red blood cells (PRBCs) are now available, and N.G. is being prepared for the GI
N.G. is still exhibiting signs of inadequate tissue perfusion. Although her BP has
improved and her HR has decreased, her mental status has declined, she is oliguric,
and her ABG indicates metabolic acidosis. N.G. has not been adequately resuscitated
from her hemorrhage, is still actively bleeding, and should receive available blood at
The prior conventional approach to the transfusion of critically ill patients was to
maintain the hemoglobin greater than 10 g/dL or the hematocrit greater than 30%. It
has been argued that these liberal transfusion goals are justified in acutely ill
patients, particularly those with cardiovascular disease, because the compensatory
mechanisms to maintain tissue ḊO2 are impaired. However, randomized, controlled
trials have shown that a restrictive transfusion strategy (target hemoglobin 7 to 8 g/dL
or transfused if symptomatic) is associated with equivalent or better outcomes in
hemodynamically stable critical care, surgical, and medical patients.
In acute hemorrhage, the actual degree of blood loss is not accurately reflected by
the hemoglobin and hematocrit values, and it also does not take into account the
body’s ability to compensate for the loss of oxygen-carrying capacity. Because it
takes at least 24 hours for all fluid compartments to come to equilibrium, a normal
hematocrit (or hemoglobin concentration) in the setting of hemorrhagic shock does
not rule out significant blood loss or indicate adequacy of transfusion. Only when
equilibrium has been reached can these measures be used reliably to gauge blood
loss. On the other hand, if cardiopulmonary function is normal and volume status is
maintained, an increase in CO can compensate for a reduction in hemoglobin (O2
content) to a certain degree (Fig. 17-1).
Because inadequacy of tissue perfusion, and hence ḊO2
abnormality in shock, the need for transfusion therapy is more accurately determined
by the patient’s symptoms and oxygen demand, rather than an arbitrary hematocrit or
15 Calculation of ḊO2 and O2 can be used to determine the
adequacy of perfusion. Although these values can be determined by use of a PA
catheter and arterial and venous blood samples, for practical purposes the patient’s
response to initial fluid resuscitation and clinical signs of inadequate tissue perfusion
are the primary determinants for blood transfusion. Patients who are not acutely
bleeding and who do not respond to initial volume resuscitation or who transiently
respond but remain tachycardic, tachypneic, and oliguric clearly are underperfused
and will likely require blood transfusion. Patients who have acute bleeding or who
demonstrate signs of underperfusion should be considered for transfusion much
sooner; thus, N.G. should receive a transfusion.
Adverse Effects of Transfusion
CASE 17-1, QUESTION 7: After the transfusion, N.G. has a serum potassium concentration of 4.7 mEq/L
potential acute transfusion-related complications are associated with PRBC administration?
Possible risks of blood transfusions include febrile and allergic reactions,
hemolytic reactions, electrolyte abnormalities, infectious disease transmission,
coagulopathies, and immunosuppression.
35 Febrile non-hemolytic and allergic
transfusion reactions are the most common adverse reactions. Transfusions can also
cause acute lung injury from activation of recipient neutrophils, which cause
capillary endothelial damage. Transfusion-associated circulatory overload results in
pulmonary edema in patients with limited cardiac reserve (elderly, infant, renal
failure, heart failure) or after massive transfusions. Recognition of donor-recipient
ABO incompatibility and the signs and symptoms of a transfusion reaction (e.g.,
anxiety, infusion site pain, chills, rigors, fever, hypotension, tachycardia, hemolysis,
hemoglobinuria) can prevent unnecessary morbidity and mortality by stopping the
infusion and providing supportive therapy.
Hemolytic transfusion reactions are the most common cause of fatalities from
blood transfusions; however, it is unlikely that N.G. is having a true hemolytic
reaction. Banked blood is stored with a citrate anticoagulant additive. With multiple
transfusions, the large amount of citrate can cause hypocalcemia and acid–base
abnormalities. Hyperkalemia also can occur because transfusion of stored blood
causes the release of potassium from hemolyzed (ruptured) red blood cells. The
increase in serum potassium observed in N.G. may be from the blood product;
although, the average amount of extracellular potassium ranges from less than 0.5 to 7
mEq/unit of blood, so the transfusion is unlikely the culprit. The increased potassium
may simply reflect hemolysis of blood cells in the test tube after the blood draw. In
either case, the measured serum concentration of 4.7 mEq/L is not sufficiently high to
warrant immediate treatment but should be monitored.
Blood products and donors are screened for disease; thus, transmission of
bacterial or viral illness is rare. It is estimated that the transmission of hepatitis C is
1:1,149,000, and human immunodeficiency virus is 1:1,467,000.
infection and prion disease are also transmissible through infusion but are an even
lower risk. Hemostatic abnormalities, specifically coagulopathies and
thrombocytopenia, may be transiently related to dilution from administration of large
volumes of crystalloids, colloids, or banked blood, but they are more likely caused
by the extent of injury and the development of disseminated intravascular
coagulopathy (DIC). Banked whole blood is usually reserved for massive
transfusions and contains sufficient coagulation factors (including labile factors V
and VIII) to maintain hemostasis during the life span of the unit; however, it does not
contain platelets because they do not survive the temperatures required for red blood
Immunosuppression has also been associated with blood transfusions as evidenced
by enhanced graft survival in renal transplant recipients, tumor recurrence in patients
with colorectal carcinoma, and postoperative infections. Transfusion-related
immunosuppression is multifactorial, but it is most likely caused by the infusion of
donor white blood cells (WBCs), which creates a competition between the donor and
the recipient leukocytes. Transfusion-related immunomodulation can be limited by
leukoreducing PRBCs prior to transfusion. The majority of blood in the United States
is leukoreduced, but it is not a universal practice primarily because of cost. Patients
who are immunosuppressed, undergoing cardiac surgery, or receiving chronic
transfusions should receive leukoreduced blood. This mechanism is not, however, the
only cause because immunosuppression is associated with autologous blood
transfusions as well as the infusion of plasma alone.
Because of the limited supply and potential adverse effects associated with blood,
research is ongoing to develop blood substitutes. The ideal agent would have a
longer shelf life, a reduced risk of disease transmission, and less risk of transfusion
reactions. The agents in various stages of clinical research include
the modified hemoglobins and the perfluorocarbons.
with some of the products thus far, such as short half-life, vasoconstriction, GI
disturbances, and flu-like symptoms. The exact role the blood substitutes would play
in transfusions is unclear. No agents are approved, but research is continuing.
HYPOVOLEMIA VERSUS PUMP FAILURE
QUESTION 1: P.T. is a 58-year-old man who arrives to the ED via ambulance after a motor vehicle
follows (initial parameters in parentheses):
BP (S/D/MAP), 86/44/58 mm Hg (100/52/68 mm Hg)
HR, 96 beats/minute (88 beats/minute)
CO, 3.2 L/minute (4.8 L/minute)
PA pressure (S/D), 18/8 mm Hg (24/14 mm Hg)
Urine output, 0.4 mL/kg/hour (1.2 mL/kg/hour)
Most of P.T.’s hemodynamic changes are consistent with hypovolemia. These
include a drop in BP, CVP, PA pressure (PAP), PCWP, CO, and urine output. The
decrease in CVP and PCWP suggest that preload is reduced, resulting in a lower CO.
The pulse pressure is narrowed, suggesting either blood flow or ventricular
contractility has decreased. (Decreases in pulse pressure correlate with decreases in
SV or left ventricular stroke work index [LVSWI]). P.T.’s HR increased slightly, but
it is unclear whether he was taking any medications, such as a β-blocker, before his
injury. As body temperature rises postoperatively, vasodilation decreases SVR and
increases the intravascular space. If intravascular volume is inadequate and
increased sympathetic tone cannot generate a sufficient CO, mean BP falls. The
decline in urine output reflects a compensatory drop in renal perfusion. The most
likely explanation for the hemodynamic change in P.T. is hypovolemia. The PCWP
would be higher if P.T. was in cardiogenic shock; although he also should be
evaluated for the occurrence of a perioperative cardiac event (myocardial infarct).
His ABG should be checked to assess oxygen requirements.
CASE 17-2, QUESTION 2: What are the most likely causes of hypovolemia in P.T.?
Common causes of hypovolemia in surgical patients are postoperative bleeding,
third spacing, and temperature-related vasodilation. Postoperative bleeding can
produce hypovolemia; however, P.T.’s initial and 2-hour postoperative Hct of 31%
and 32%, respectively, do not support bleeding as a cause.
After major vascular or bowel surgery and in cases of burns or peritonitis, patients
have an internal redistribution of fluids, called third spacing, which can result in
intravascular volume depletion. It is not unusual for patients to third-space significant
amounts of intravascular volume. The interstitial space and bowel walls can
sequester large amounts of fluid, and this can produce a state of relative hypovolemia
as is occurring with P.T. This is likely in the first 12 to 24 hours after the surgical
procedure. P.T. is receiving 150 mL/hour of LR solution, but this is apparently not
sufficient to maintain his intravascular volume.
Mild hypothermia is common during operative procedures. Vasodilation occurs as
patients warm postoperatively, expanding the intravascular space. If the amounts of
IV fluids administered are insufficient to compensate for the increased venous
capacitance, BP and CO will decline during the rewarming phase, which can range
from 1 to 6 hours. P.T. has rewarmed from 34.8°C to 37.4°C in 2 hours, which is not
unusual after a major operative procedure. His temperature could conceivably rise to
as high as 38°C to 38.5°C during the first 12 to 24 hours after surgery.
Other considerations include inadequate fluid administration during the operative
procedure and the effects of drugs given in the operating room or in the immediate
postoperative period (e.g., opioids, sedatives, inhaled anesthetics) that cause
VOLUME REPLACEMENT AND VENTRICULAR FUNCTION
CASE 17-2, QUESTION 3: How will volume replacement improve P.T.’s CO and perfusion pressure?
The Frank–Starling mechanism indicates that the volume of blood returned to the
heart is the main determinant of volume pumped by the heart. Therefore, as venous
return is increased, the CO also will increase within physiologic limits until the
optimal preload is achieved at which point further volume has minimal effect on SV
(Fig. 17-1). The PCWP, the best indicator of LV preload, and the CVP, a marker of
RV preload and overall estimate of volume status, are low because of declining
A ventricular function curve can be constructed by plotting a measure of cardiac
pumping (CO, SV, or LVSWI) against a measure of preload ( Fig. 17-3). Two hours
after surgery, P.T.’s CVP has fallen from 12 to 6 mm Hg and his CO has fallen from
4.8 to 3.2 L/minute. Therefore, additional volume replacement is warranted.
following hemodynamic profile:
Cardiac Index (CI), 2.4 L/minute/m
Assess P.T.’s response to the fluid challenge (see Table 17-2 for normal values).
According to the Frank–Starling curve, a small change in preload in response to a
volume challenge with a minimal change in CO represents a ventricle on the flat
portion of the ventricular function curve (Fig. 17-3). Additional fluid therapy given to
these patients can increase their risk for pulmonary edema without improving CO. In
contrast, a large change in preload in response to a fluid challenge with a significant
increase in CO represents a ventricle on the steep portion of the curve. In P.T., the
PCWP indicates he does not have pulmonary edema and the change in CVP from 6 to
10 mm Hg along with the increase in CO show that he is still responsive to fluid.
Thus, it is reasonable to administer more fluid to enhance CO and renal perfusion.
CASE 17-2, QUESTION 5: One hour after the 500-mL NS bolus, P.T.’s hemodynamic profile returns to his
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