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28-1
HYPOVOLEMIC SHOCK
A Glass Half Full. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Level II
Brian L. Erstad, PharmD, FCCP, MCCM, FASHP
Yvonne C. Huckleberry, PharmD, BCPS
CASE SUMMARY
A 20-year-old man with a history of Crohn disease, ankylosing
spondylitis, and pulmonary coccidioidomycosis is hospitalized
because of vomiting, diarrhea, fatigue, decreased oral intake, and
fever. The patient has clinical signs of hypotension (volume depletion) that indicate the early stages of hypovolemic shock. The hypovolemia was apparently caused by a flare-up of Crohn disease that
contributed to the patient’s abdominal pain, vomiting, and diarrhea
and resulted in lost plasma volume. The gastrointestinal problems
precluded adequate fluid intake that ultimately led to extracellular
depletion. When considering alternatives for intravascular volume repletion, the reader must weigh the benefits and limitations
of crystalloids versus colloids. The potential need for adjunctive
therapies, such as inotropic agents and vasopressors, should also
be considered. Dosage adjustment of concomitant medications
(eg, fluconazole) in the face of acute kidney injury would not be
warranted unless the process continues to worsen or does not
improve with fluid resuscitation alone. Monitoring parameters
should be directed toward achieving successful fluid resuscitation
while minimizing the likelihood of fluid overload.
The use of a TNF-blocker such as infliximab in a patient with
a history of pulmonary coccidioidomycosis is very controversial,
and some would consider its use to be contraindicated in this
patient. However, this scenario was based on an actual case where
the benefits were thought to exceed the risks, given the small cocci
lesion noted in one lung on CXR, the relative lack of pulmonary
symptoms (only cough was present in this patient on initial presentation), and the rapid decrease in cocci titers. Given the cocci
concern, it is important that the fluconazole not be discontinued;
additionally, the dose should only be decreased if the acute kidney
injury is sustained or worsens despite fluid resuscitation.
QUESTIONS
Problem Identification
1.a. Create a list of the patient’s drug-related problems.
• This patient is in early stages of shock (as noted by physical
examination, vital signs, decreased urine output, and elevated
creatinine), which initially requires treatment with fluids.
• The patient will need dosage adjustments of renally eliminated
medications (fluconazole) if the renal dysfunction is not
reversed within the next 24–48 hours.
• Medication nonadherence.
• Possible infectious disease (including reactivation of pulmonary coccidioidomycosis, but seems unlikely with negative
• A possible acid-base disorder is suggested by the elevated
serum CO2 and increasing serum creatinine in the setting
of hypotension without tachypnea. The elevated serum CO2
would argue against metabolic acidosis with lactic acid production that would be expected in septic shock and/or metabolic
acidosis associated with acute kidney injury. Instead, a loss of
acidic gastric contents with vomiting in excess of alkaline loss
with persistent diarrhea might explain this patient’s increase
in serum CO2.
• Anemia is apparent as this patient has a decreased hemoglobin
and hematocrit, even in the setting of significant hypovolemia.
This may be due to subtle blood loss with Crohn ulcerations,
overall malnutrition, or specific nutrient deficiencies. A workup for anemia would be warranted as part of outpatient
follow-up.
• Active flare-up of Crohn disease as indicated by elevated
CRP and ESR and abdominal pain; azathioprine may cause
gastrointestinal adverse effects, but this seems much less
likely to be the primary etiology of the patient’s abdominal
symptoms, given the indicators of a Crohn’s flare-up and the
patient’s admission that he has not been routinely taking the
medication.
• Ankylosing spondylitis (does not appear to be cause of elevated
CRP and ESR given gastrointestinal complaints consistent
with Crohn’s flare-up).
1.b.What information (signs, symptoms, laboratory values)
indicates the presence or severity of hypovolemic shock?
• The presence of the early stages of shock is determined
from inadequate oral intake of fluids, vomiting and diarrhea,
decreased blood pressure, skin pallor, tachycardia, weak pulse,
and acute kidney injury leading to decreased urine output
and impending renal failure. Also, sodium and chloride concentrations tend to increase and decrease together in fluid
disorders, and their elevation is not unexpected in a patient
with hypovolemia.
• Acute kidney injury is evidenced by the elevated BUN/
creatinine and decreased urine output. The relatively normal
creatinine value is likely to be misleadingly low in early stages
of renal dysfunction and in patients with decreased lean
tissue mass (this patient is 13 kg below his ideal body weight
of 73 kg).
Desired Outcome
2.What are the goals of pharmacotherapy in this case?
• Prevent progression of shock to a potentially life-threatening
situation.
• Reverse organ dysfunction (eg, acute kidney injury) related
to shock.
• Eliminate the patient’s symptoms of volume depletion and
shock.
• Resolve infectious process, if found.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Hypovolemic Shock
Brian J. Kopp, PharmD, BCPS, FCCM
• Malnutrition as reflected by low albumin actual, weight less
than ideal weight, and physical examination.
CHAPTER 28
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CXR) as evidenced by increased temperature and white blood
cell count. If an infectious process is suspected, broad spectrum antibiotics should be administered as soon as possible
considering the patient’s immunosuppression. Delay in antibiotic therapy has been associated with increased mortality for
patients with septic shock.1
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SECTION 2
• Treat underlying Crohn disease flare and optimize maintenance therapy.
• Maintain long-term control of ankylosing spondylitis.
Therapeutic Alternatives
3.a. What nondrug therapies might be useful for this patient?
Cardiovascular Disorders
• Subacutely: Parenteral nutrition is not indicated at this time
since oral feedings should resume once the acute disease state
resolves. Once feedings have resumed, the patient’s protein
requirements will need to be evaluated in light of his decreased
albumin and weight.
• Chronically: Dietary compliance. Calorie requirements are
approximately 15–20% above basal energy expenditure with
<30% of calories obtained from saturated fat. Protein requirements typically average 0.8 g/kg per day, but should be
increased in this patient to at least 1 g/kg per day by insuring
adherence to whey protein shakes. Although the patient is
underweight, he should be questioned about physical activity
as a way of increasing lean weight and to relieve stress that
is likely aggravating the Crohn disease. Stretching exercises
would also be beneficial for his ankylosing spondylitis since he
was found to have some limited mobility of his hips and knees
on physical examination. After evaluation of anemia, nutrient
supplementation, such as ferrous sulfate, may be warranted.
3.b.What feasible pharmacotherapeutic alternatives are available for treatment of shock and the associated laboratory
alterations?
Treatment of shock:
• Oral rehydration solutions are appropriate and usually adequate therapy for acute diarrhea since they contain sodium,
potassium, and glucose in addition to the fluid needed to
replace losses. However, IV fluids are needed in cases such
as this when the patient cannot drink the required volume to
replace losses or when shock occurs.
• Ringer’s lactate and normal saline solution are crystalloids that
are near-isotonic, salt-containing fluids given intravenously
for the treatment of shock. These fluids fill the extracellular
space (all 1,000 mL of 1,000 mL infused), which is more important than intracellular filling in symptomatic patients with
obvious intravascular depletion. Ringer’s lactate does contain
small amounts of potassium that could accumulate in patients
with ongoing acute kidney injury; thus, serum potassium concentrations should be monitored.
• Balanced salt solutions (eg, Plasmalyte) are crystalloids that
are isotonic and have physiologic amounts of sodium and
chloride. In recent years, multiple studies have evaluated
differences in outcomes between those that received chlorideliberal (normal saline, 4% albumin) and those that received
chloride-restrictive (Plasmalyte, Hartmann solution) fluid
resuscitation strategies in various critically ill patient populations. In addition to causing hyperchloremia and metabolic
acidosis, fluid resuscitation with chloride-liberal solutions
appears to increase the risk of acute kidney injury and need
for renal replacement therapy.2 A meta-analysis that included
21 trials and more than 6200 critically ill and perioperative
patients found similar results.3 While these results are preliminary and directly applicable to critically ill and perioperative
patient populations, balanced salt solutions are a reasonable
fluid resuscitation strategy in this patient.
• Dextrose solutions for patients with intravascular depletion are
not appropriate because only a small amount of the solution is
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
retained in the extracellular space (eg, one third of the amount
infused for 5% dextrose in water).
• Colloids (eg, 5% albumin) may be considered if at least
2 L of crystalloid solution has been administered without
an adequate response in monitoring parameters, although
this use is controversial. Albumin has been compared with
normal saline in a randomized multicenter study involving
6,997 patients admitted to intensive care units for fluid resuscitation.4 In this landmark trial, there were no statistically
significant differences in overall mortality, length of stay,
days of mechanical ventilation, or days of renal replacement
therapy between 4% albumin and normal saline solution
used for acute intravascular volume repletion. In addition,
while albumin infusion is initially restricted to the intravascular space, substantial differences in the ratio of albumin to
saline administration (1:1.4) were not demonstrated likely as
a result of substantial leakage into the interstitial space that
occurs within hours, even in patients without altered capillary permeability. Although clinicians need to be cautious
in extrapolating the results of this multicenter trial to other
patient populations and settings, it is increasingly difficult to
justify the use of colloid products for hypovolemia given their
higher cost and lack of increased efficacy or safety compared
with crystalloid solutions.
Starch solutions have been studied as an initial resuscitative strategy, although concerns related to coagulation
abnormalities and acute kidney injury have limited their use
historically.5 In recent years, newer starch solutions with lower
molecular weights and less starch substitution (eg, 130/0.4)
have been developed with the hope that they would alleviate
some of the concerns related to the development of acute
kidney injury. However, large randomized trials conducted
in critically ill patients with or without sepsis demonstrated
that patients receiving 6% hydroxyethyl starch 130/0.4 were
more likely to require renal replacement therapy compared
with patients receiving crystalloid solutions. Mortality rates
at 90 days were also higher in the starch groups, although the
differences were only statistically significant in patients with
sepsis.6,7 Therefore, resuscitation with starch solutions should
generally be avoided unless subsequent data from large, randomized controlled trials demonstrate that these products are
safe to administer.
• Albumin therapy may also be considered (albeit with a lack of
published data) if the patient develops dyspnea, rales, or radiographic evidence of substantial interstitial fluid accumulation,
assuming such findings are consistent with interstitial fluid
accumulation caused by crystalloid administration despite
inadequate responses in monitoring parameters (eg, blood
pressure, urine output). If such problems develop, oxygen
therapy, titrated by arterial blood gas determinations and/or
oximetric recordings, will also be indicated.
• Vasopressors (eg, norepinephrine, epinephrine, vasopressin)
are used when continued evidence of shock persists despite
adequate fluid resuscitation, particularly in patients with septic
shock.1 These agents increase systemic blood pressure through
vasoconstriction in desired and undesired vessels and may lead
to ischemic adverse events such as tissue necrosis of extremities especially if fluid resuscitation is inadequate.
• Inotropic agents (eg, dobutamine) are occasionally considered if there is an inadequate response to plasma expanders
and/or vasopressor, particularly in specific patient populations
(eg, heart failure) as determined by vital signs, hemodynamic
indices, urine output, and physical examination.
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Treatment of laboratory alterations:
Optimal Plan
4.What drug, dosage form, dose, schedule, and duration of
therapy are best for this patient?
• Plasma expansion using a crystalloid solution is necessary
for preventing the progression of shock. Begin by infusing
15 mL/kg of crystalloid solution (such as 0.9% sodium chloride
or Ringer’s lactate) over approximately 2 hours. Administration of additional fluids is based on physical examination
findings, heart rate, blood pressure (arterial if not rapidly
responding to fluid resuscitation), and urine output in patients
with urinary catheters.
• Because the patient does not have a history of renal failure, it
is possible that the patient’s acute kidney injury will reverse
relatively quickly with adequate fluid resuscitation. Therefore,
rather than immediately adjusting doses of renally eliminated
medications, it may be more appropriate to wait until adequate
resuscitation has been performed (within the first 24–48 hours)
and see whether renal function improves quickly.
• No specific interventions for the laboratory alterations are
needed at this time other than replacement doses of electrolytes for low values such as potassium.
• Empiric antimicrobials are not needed on admission since the
temperature elevation is not substantial and the hypotension is
likely due to extracellular fluid depletion associated with diarrhea
and inadequate oral intake. Furthermore, some infectious forms
of diarrhea (eg, C. difficile) may be caused or aggravated by antimicrobial agents. The scheduled infliximab infusion will need to
be held until an infectious process, including possible reactivation of the patient’s pulmonary coccidioidomycosis, has been
ruled out (which appears to be the case given the negative CXR).
• Assuming an infectious disease process is ruled out, consideration could be given to short-course corticosteroid therapy to
get the patient’s Crohn disease under control.
Outcome Evaluation
5.What clinical and laboratory parameters are necessary to
evaluate the therapy for achievement of the desired therapeutic
outcome and to detect or prevent adverse events?
• Initially, physical examination findings (eg, skin turgor),
heart rate, blood pressure (preferably arterial), urine output
(by bladder catheterization), and mental status should be
monitored every 10–15 minutes and then with decreasing
frequency as compensation for fluid losses is achieved. In
addition, monitoring for clearance of elevated lactate levels,
performing passive leg raises and using bedside ultrasonography to look for indicators that the patient has been adequately
• As successful resuscitation occurs, one would expect the skin
to have normal turgor. The heart rate and blood pressure
recordings should return to normal pretreatment values.
Urine output in healthy adults should be at least 0.5 mL/kg/
hour (assuming the patient is catheterized). Other signs and
symptoms related to volume depletion (eg, fatigue, dry oral
mucosa) should abate with successful resuscitation. Note that
blood pressure alone is not adequate to monitor the progression or regression of shock. Normal blood pressure recordings,
particularly from cuff measurements, do not necessarily imply
adequate tissue perfusion and oxygenation.
• Basic laboratory parameters (electrolytes including calcium,
phosphorus, and magnesium, BUN, and creatinine) should be
monitored at least once daily until stable. Admission cultures
and a titer for C. difficile were ordered on admission; subsequent testing should be based on the patient’s clinical course.
• Fluid intake and output should be monitored at least every
nursing shift until stable, and then decreased to daily.
• The most likely adverse effects of crystalloid and colloid therapies are fluid overload as a result of interstitial space expansion
such as increasing ascitic fluid accumulation, leg edema or pulmonary edema as noted by physical exam, auscultation, and/or
radiographic evidence. Development of congestive heart failure
is a concern in patients with poor left ventricular function.
• All medications that are renally eliminated will need to be
adjusted as acute kidney injury improves or worsens (as noted
by changes primarily in serum creatinine concentrations and
urine output).
• For the Crohn disease, control would include lack of abdominal pain, vomiting, and diarrhea and ability to achieve adequate oral intake without reoccurrence of these problems.
• Monitoring for ankylosing spondylitis disease control would
include improved range of motion, normalization or reduction
in CRP and ESR, and lack of pain or swelling.
Patient Education
6.What information should be provided to the patient to
enhance adherence, ensure successful therapy, and minimize
adverse effects?
• With your Crohn disease, it is essential that you maintain
appropriate fluid and food intake. When you do not drink
enough liquids, your body cannot work properly and it may
be harmful to many organs including your kidneys. We will
have a dietitian see you regarding a healthy diet for your Crohn
disease and ankylosing spondylitis.
• If you have problems such as vomiting, diarrhea, or fatigue in
the future contact your healthcare provider or me for helpful
advice, which may prevent you from having to be hospitalized.
• Finally, it is very important that you take your medications
exactly as ordered. If you feel you are having a problem related
to a medication, contact your healthcare provider or me for
further instructions. Do not take any other medication, even
over-the-counter products such as aspirin or antacids, without
consulting one of us first.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Hypovolemic Shock
• Treatment of the underlying problems (shock, malnutrition,
Crohn’s, and possibly infection) will lead to a normalization
of the laboratory parameters, so no other interventions are
needed other than replacement of electrolytes if low values
are present. Arterial blood gases have been ordered, since the
vomiting could have led to an acute metabolic alkalosis due to
loss of stomach acid. The single episode of diarrhea would be
unlikely to lead to substantial changes in the blood gases.
fluid resuscitated can be useful, particularly in more critically
ill patients where it may be difficult to determine when the end
point of resuscitation has occurred. Daily weights and intake/
output should be monitored as other indicators of fluid status.
In general, an adult patient will require 30–35 mL/kg per day
of fluids to maintain euvolemia, so even larger amounts are
required for patients with hypovolemia.
CHAPTER 28
• Antimotility agents should not be considered for the diarrhea
until an infectious cause has been ruled out, which would take
approximately 2–3 days for the cultures and Clostridium difficile titer results to be reported by the clinical laboratory. In
this case, the C. difficile titer result was negative.
28-4
■■ FOLLOW-UP QUESTION
SECTION 2
1.Explain why hypotonic IV fluids such as 5% dextrose are not
indicated in a patient with overt hypovolemia who is going
into shock.
Cardiovascular Disorders
• Hypovolemia is associated with extracellular, not intracellular,
fluid depletion. For each 1 L of 5% dextrose administered by
the IV route, only 333 mL is retained in the extracellular space.
Furthermore, just over 80 mL is retained in the intravascular
space where it is most needed for maintaining blood pressure
and perfusion of organs.
REFERENCES
1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign:
International guidelines for management of severe sepsis and septic
shock: 2012. Crit Care Med 2013;41:580–631.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
2. Yunos NM, Bellomo R, Hegarty C, et al. Association between chlorideliberal vs chloride-restrictive intravenous fluid administration strategy
and kidney injury in critically ill adults. JAMA 2012;308:1566–1572.
3. Krajewski ML, Raghunathan K, Paluszkiewicz SM, et al. Meta-analysis
of high- versus low-chloride content in perioperative and critical care
fluid resuscitation. BJS 2015;102:24–36.
4. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and
saline for fluid resuscitation in the intensive care unit. N Engl J Med
2004;350:2247–2256.
5.Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med
2008;358:125–139.
6. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for
fluid resuscitation in intensive care. N Engl J Med 2012;367:1901–1911.
7.Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch
130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med
2012;367:124–134.