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2011 BRS5

Board Review Session V
Saturday, August 20, 2011
Questions With Answers and Rationales
64. A 55-year-old woman receiving warfarin for atrial fibrillation is transferred to your
ICU with a left thalamic bleed. At an outside hospital she was awake and aphasic, with a
right facial droop and right-sided weakness. She had onset of somnolence and irregular
breathing and was placed on invasive mechanical ventilation. On arrival to the ICU, her
pulse rate is 60/min and BP is 200/90 mm Hg. She does not follow commands and has no
eye opening. Pupils are 6 mm on the left and 3 mm on the right with extensor posturing
in all extremities. Which of the following is the most appropriate next step in her
management?
a. Antiepileptics
b. Mannitol
c. Corticosteroids
d. Reversal of coagulopathy
65. A 26-year-old woman taking oral contraceptives presents to the emergency
department with a 1-day history of headache, nausea, and vomiting. Two hours ago she
had a generalized seizure lasting 2 minutes. On examination she is awake and alert, with
BP of 120/70 mm Hg, HR of 72/min, RR of 18/min, and temperature of 39.2°C
(102.5°F). Her fundoscopic examination shows papilledema. The rest of the neurological
exam is unremarkable. Meningitis is suspected and a lumbar puncture is planned. As the

physician prepares to leave the room, the patient has a seizure. Five minutes after onset,
which of the following would be the most effective initial therapy in her management?
a. Phenytoin
b. Diazepam
c. Lorazepam
d. Phenobarbital
66. A 55-year-old woman with hypertension is admitted to the ICU with slurred speech
and unsteadiness, with a tendency to fall to the left. On examination her BP is 150/90 mm
Hg and pulse rate is 96/min. She has dysarthria, limited abduction of the left eye, leftsided weakness, and ataxia on finger-nose testing and knee-heel testing on the left side.
Brain CT reveals a 3.4-cm left cerebellar bleed, with compression of the ambient cistern
and brainstem and hydrocephalus.
Which of the following therapies would help the patient the most?
a. Corticosteroids
b. Controlling blood pressure
c. Posterior fossa decompression


d. Conservative management
67. A 65-year-old man presents with ascending paralysis of his lower extremities. The
paralysis increases subacutely over several days, accompanied by only minor sensory
defects. A diagnosis of Guillain-Barre syndrome is made. The patient has significant
exertional angina despite coronary artery stenting and aggressive medical care. Which of
the following would be the best choice for management of his Guillain-Barre syndrome?
a. Observation
b. Plasma exchange
c. IV immunoglobulin
d. Prednisone
e. Cyclophosphamide
68. A previously healthy, 67-year-old man presents with a 2-day history of increasing
dyspnea, tingling in the extremities, and difficulty arising from a chair or turning in bed.
His examination shows profound weakness, absent reflexes, and normal sensory
examination findings. The most likely diagnosis is:
a. Botulism
b. Syringomyelia
c. Guillain-Barré syndrome
d. Cervical cord metastasis from lung cancer
e. Myasthenia gravis
69. Which of the following patients is most likely to benefit from therapeutic
hypothermia (temperature 32°C–34°C [89.6°F–93.2°F])?
a.20-year-old man with blunt head injury secondary to car crash, diffuse axonal injury on
CT, and Glasgow Coma Scale score of 8 on ICU admission
b. 65-year-old woman with acute left hemiplegia, altered mental status, and acute
ischemia in the right middle cerebral artery territory on CT
c. 55-year-old man with anterior acute myocardial infarct who was admitted to the ICU
after percutaneous coronary intervention, intubated and in cardiogenic shock
d. 43-year-old woman with out-of-hospital cardiac arrest who arrives to the hospital with
restored spontaneous circulation and has Glasgow Coma Scale score of 15
e. 58-year-old man admitted to the hospital with pneumonia who has an in-hospital
cardiac arrest from ventricular tachycardia and is transferred to the ICU with return of
spontaneous circulation, intubated and unconscious
70. A 53-year-old woman is evaluated in the emergency department after 1 day of severe
right flank pain, fever, and mild nausea. Urinalysis shows many leukocytes and leukocyte


casts. Gram stain of her urine shows gram-positive cocci, and therapy with vancomycin
and gentamicin is started. Despite therapy, the patient develops progressive hypoxemia
and requires mechanical ventilation. On examination, she appears very anxious but is not
trying to remove the endotracheal tube or any other support devices. Her temperature is
37.5°C (99.5°F), pulse rate is 130/min, and blood pressure is 120/60 mm Hg.
Electrocardiography shows sinus tachycardia. Blood and urine cultures grow
Enterococcus faecalis. While the patient is on mechanical ventilation, which of the
following is the most appropriate sedation strategy?
a. Sedation with intermittent paralytics as tolerated
b. Deep continuous sedation
c. Intermittent bolus dosing with daily awakening
d. No sedation
71. A 28-year-old man is admitted to the ICU after sustaining a large aneurysmal
subarachnoid bleed and is intubated for airway protection and ventilatory support.
Because of increased intracranial pressure and patient-ventilator dyssynchrony, propofol
infusion is started at 100 μg/kg/min. The patient’s medical course is complicated by
gram-positive sepsis and adrenal insufficiency on day 3 in the ICU, for which he is
treated with appropriate broad-spectrum antibiotic therapy, volume resuscitation,
norepinephrine, and hydrocortisone with the goal of maintaining a mean arterial pressure
greater than 65 mm Hg. On day 4, the patient remains sedated on mechanical ventilation
and appears to be improving. On day 5, he develops acute kidney injury, hyperkalemia,
metabolic acidosis, rhabdomyolysis, and jugular venous distension with cardiac failure.
ECG shows no signs of an acute myocardial infarction or ischemia, and no peaked T
waves or conduction disturbances. Which of the following is the most urgent next step in
the management of this patient?
a. Noncontrast CT of the head
b. Discontinuation of propofol
c. Plasmapheresis
d. IV heparinization
72. A 75-year-old man comes to the ICU after surgical repair of an infected aortic graft.
He is still intubated and requires mechanical ventilation for poor oxygenation and
ventilation. He is febrile, agitated, hypertensive, and tachycardic. He has a history of
coronary artery disease and had a stroke in the distant past. The nurse asks about choice
of sedation in this patient.
The goals are to minimize the potential for delirium and optimize the ability to follow the
patient’s neurologic status and maintain his blood pressure. Minimizing the cost of the
patient’s hospitalization is also important.
Which of the following medications is most appropriate?


A. Lorazepam
B. Midazolam
C. Propofol
D. Dexmedetomidine
E. Remifentanil
73. A 75-year-old man who is intubated and mechanically ventilated is breathing at a rate
of 40/min despite IV sedation. The physician decides to use a neuromuscular blocker.
The nurse hands the physician a drug and the physician administers it intravenously.
When the physician asks for the name of the drug, the nurse is not sure whether it was
succinylcholine or rocuronium. The physician can most accurately determine which drug
it is by:
A. Evaluating the tetanic fade with a neuromuscular monitor
B. Timing the initiation of paralysis after drug administration
C. Evaluating the response of the diaphragm to the drugs
D. Evaluating the response to reversal agents immediately after the administration of the
neuromuscular blocker
74. Intubation is required for an 80-year-old woman who is hypotensive, tachycardic, and
still hypoxic despite wearing a 100% rebreathing mask for sepsis and adult respiratory
distress syndrome Which of the following estimates of the likelihood of complications
including cardiac arrest during intubation is most likely to be correct?
A. 100%
B. 75%
C. 50%
D. 30%
E. 5%
75. An 82-year-old woman enters the ICU with fever and hypotension. She has a history
of intermittent bowel obstruction from adhesions secondary to a ruptured appendix more
than 10 years ago. Ceftazidime, vancomycin, and clindamycin are begun, and 2 L of fluid
administration results in a BP of 70/40 mm Hg. An arterial and pulmonary artery catheter
are inserted. Baseline and post-therapy hemodynamics are as follows:
HR, per min
BP, mm Hg (systolic/diastolic/mean)
Right atrial pressure, mm Hg (mean)
Right ventricular pressure,
mm Hg (systolic/diastolic)

Baseline
82
70/40/50
3

Following Therapy
90
105/60/70
4

25/3

26/3


Pulmonary artery pressure,
mm Hg (systolic/diastolic)
Pulmonary artery occlusion pressure,
mm Hg (mean)
Cardiac output, L/min
Urine output, mL/h
Splanchnic blood flow
Blood lactate concentrations, mg/dL

27/18

26/18

16
3.5
0
decreased
6.8

16
4.8
30
increased
2.7

Which of the following medications was most likely administered?
a. Vasopressin, high dose (0.1–0.4 U/min)
b. Vasopressin, low dose (0.01–0.03 U/min)
c. Dopamine
d. Norepinephrine
76. A 66-year-old man enters the ICU with severe dyspnea due to acute heart failure. He
has a long-standing history of coronary artery disease with 2 coronary artery bypass graft
surgeries, the first 15 years ago, and again 5 years ago. An echocardiography performed 2
months ago showed multiple wall motion abnormalities with a left ventricular ejection
fraction of 25%. His dyspnea continues despite high doses of IV furosemide, and a
pulmonary artery catheter is placed with baseline and post-therapy values shown below:
Hemodynamic profile
Heart rate, beats/min
Blood pressure, mm Hg (systolic/diastolic/mean)
Right atrial pressure, mm Hg (mean)
Right ventricular pressure, mm Hg
(systolic/diastolic)
Pulmonary artery pressure, mm Hg
(systolic/diastolic/mean)
Pulmonary artery occlusion pressure, mm Hg (mean)
Cardiac output, L/min
Urine output, mL/min

Baseline
84
98/60/70
18
50/20

Following Therapy
86
95/60/68
8
40/10

50/28/30

40/18/20

28
2.8
10

16
2.9
40

Which of the following medications were administered to this patient?”
a. Nitroglycerin
b. Nitroprusside
c. Milrinone
d. Dobutamine

Formatted: Italian (Italy)
Formatted: Italian (Italy)
Formatted: Italian (Italy)
Formatted: English (U.S.)
Formatted: English (U.S.)
Formatted: English (U.S.)


77. A 69-year-old man with HIV infection was evaluated one year ago with a CD4 cell
count of 30/µL and a viral load of 100,000 RNA copies per microliter. He was treated
with lopinavir/ritonavir and lamivudine/zidovudine, and 1 month ago his CD4 cell count
was 210/µL and his viral load was less than 50 RNA copies per microliter. This morning,
he had a seizure and was brought to the emergency department. CT of his head shows a
single 4-cm mass with surrounding edema in his right frontal lobe. He is transferred
comatose to the ICU. His laboratory results are as follows: WBCs, 500/µL (90%
neutrophils); bilirubin, 2.1 mg/dL; alkaline phosphatase, 310 U/L; aspartate
aminotransferase and alanine aminotransferase, twice the normal range.
Which of the following is the most likely diagnosis of this lesion?
a. Toxoplasmosis
b. Lymphoma
c. Mycobacterium tuberculosis
d. Malignant glioblastoma
e. Cytomegalovirus
78. A patient with a stool toxin assay positive for Clostridium difficile colitis is treated
with IV metronidazole. The patient improves during 10 days of therapy, but 1 week after
completing therapy, the diarrhea recurs.
Which of the following is the most appropriate next step?
a. Treatment with oral vancomycin
b. Treatment with IV vancomycin
c. Treatment with oral Saccharomyces boulardii
d. Treatment with nitazoxanide
e. Antibiotic susceptibility testing of a stool isolate of Clostridium difficile


Responses and Rationales:
64. Correct Answer: B. Mannitol
Rationale: The patient has warfarin-associated intracranial hemorrhage. She is
manifesting signs of herniation with left third nerve palsy and Cushing triad (bradycardia,
irregular respiratory pattern, and systemic hypertension) from increased intracranial
pressure (ICP). These findings should prompt the physician to immediately take steps to
reduce the ICP. Mannitol is an osmotic diuretic, used emergently to reduce ICP. It
reduces the rate of cerebrospinal fluid formation and blood viscosity by making red blood
cells more flexible.
Other measures which can be used to reduce ICP are elevation of the head of the bed,
hyperventilation, hypertonic saline (3%, 23.4%), and paralytics. Emergent reversal of
coagulopathy is indicated, but she needs immediate management of elevated ICP, so
option D is incorrect. Prophylactic antiepileptics have been shown to have worse
outcomes following intracerebral hemorrhage, so option A is incorrect. However, patients
who develop clinical or electrographic seizures need to be treated with antiepileptics.
Corticosteroids are beneficial in vasogenic edema from intracranial tumors (primary and
metastatic). Steroids have not been shown to be beneficial in intracerebral hemorrhage.
Thus option C is incorrect.
65. Correct Answer: C. Lorazepam
Rationale: A double-blind study conducted by Veterans Affairs of 384 patients with
generalized status epilepticus showed that initial treatment with lorazepam was more
effective than phenytoin in controlling seizures. It was not more efficacious than
phenobarbital or diazepam, but was easier to use. Another trial comparing lorazepam to
diazepam showed that lorazepam was a better therapy than diazepam with regard to rate
of termination of status epilepticus.
66. Correct Answer: C. Posterior fossa decompression
Rationale: The patient is having signs of brainstem compression (left sixth nerve palsy)
from a cerebellar bleed. Patients with large cerebellar hemorrhages (>3 cm) who are
deteriorating neurologically or having signs of brainstem compression or hydrocephalus
should undergo surgical decompression (option C). Corticosteroids (option A) have not
been shown to benefit patients with hematoma. The patient’s blood pressure is fairly
controlled, so option B is incorrect. Conservative management would lead to worsening
of brainstem compression and poor outcome, so option D is incorrect.
67. Correct Answer: B. Plasma exchange


Rationale: Plasma exchange and IV immunoglobulin (Ig) are equivalently effective in
randomized trials. IV Ig is usually chosen for children because of venous access
problems. Patients with coronary artery or carotid artery disease tolerate plasma exchange
better than the hyperviscosity of IV Ig. Autonomic instability is not a contraindication to
plasma exchange.
68. Correct Answer: C. Guillain-Barré syndrome
Rationale: Guillain-Barré syndrome fits all of the points here. Sensory complaints are
common, but objective sensory findings very rare. Botulism usually has prominent
cranial nerve findings on presentation. Syringomyelia would have sensory loss. A
cervical cord metastasis would produce a sensory level and hyperreflexia. Myasthenia
does not affect reflexes and lacks sensory concerns.
69. Correct Answer: E. 58-year-old man admitted to the hospital with pneumonia who
has an in-hospital cardiac arrest from ventricular tachycardia and is transferred to the ICU
with return of spontaneous circulation, intubated and unconscious
Rationale: Based on results from clinical trials, the Advanced Life Support Task Force
of the International Liaison Committee on Resuscitation and the American Heart
Association have recommended the use of therapeutic hypothermia after cardiac arrest.
Unconscious patients with return of spontaneous circulation after out-of-hospital cardiac
arrest should be cooled to 32º-34°C (89.6°-93.2°F) for 12-24 hours (class IIa
reccomendation). Similar therapy may be beneficial in patients with non-ventricular
tachycardia arrest (out-of-hospital) or for in-hospital arrest (class IIb recomendation).
Clinical trials in other areas such as traumatic brain injury, ischemic stroke, and
myocardial infarct have been disappointing. Current available literature does not support
the routine use of therapeutic hypothermia in these clinical scenarios. Based on these
recommendations, patients in options D and E are the most likely to benefit. The patient
in option D is awake with a Glasgow Coma Scale score of 15 and therefore would not be
considered a candidate for therapeutic hypothermia. Hence, the patient in option E is the
most likely to benefit from therapeutic hypothermia (intrahospital, ventriculartachycardia arrest, unconscious with return of spontaneous circulation).
70. Correct Answer: C. Intermittent bolus dosing with daily awakening
Rationale: A randomized, controlled trial by Girard et al in critically ill patients showed
that intermittent bolus dosing of sedatives titrated against a validated sedation scale and
with a daily spontaneous awakening trial with total cessation of sedatives yielded a 4-day
reduction in ICU and hospital length-of-stay and an improvement in 1-year survival. In
critically ill patients, this method allows enough drug for comfort and reduces the
likelihood of excess use of these potent psychoactive medications such as lorazepam. A
sedative drip with propofol would also be a consideration, as long as daily interruption of
sedation was undertaken. The newer-generation sedation scales are being widely adopted
by ICUs to aid in drug titration and ease of communication. The use of sedation with


intermittent paralytics as tolerated has the potential for harming the patient via use of an
agent (paralytics) that will increase risk of ICU-acquired weakness or paralysis without
adequate sedation, and is generally reserved for patients demonstrating severe ventilator
dyssynchrony (which is not mentioned as a current issue). Deep sedation until the patient
is extubated would lead to unnecessarily prolonged and pronounced sedation. The notion
of trying to “eliminate” memories from the ICU appears to be a risk factor for
posttraumatic stress disorder, which occurs in about 15% to 20% of ICU survivors.
Neuromuscular blockade with paralytic agents should be avoided unless absolutely
necessary because of problems such as myopathy and prolonged paralysis.
71. Correct Answer: B. Discontinuation of propofol
Rationale: This patient has the propofol infusion syndrome, and the drug should be
discontinued and replaced by fentanyl and midazolam. The propofol infusion syndrome is
a rare and often fatal syndrome originally described in critically ill children undergoing
long-term propofol infusion at high doses. Recently, several cases have been reported in
adults, mostly in patients with acute neurologic illnesses or acute inflammatory diseases
complicated by severe infections or even sepsis, and receiving catecholamines and/or
corticosteroids in addition to propofol.
The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe
metabolic acidosis, and renal failure associated with hyperkalemia. Central nervous
system activation with production of catecholamines and corticosteroids, and systemic
inflammation with cytokine production are priming factors for cardiac and peripheral
muscle dysfunction. High-dose propofol, but also supportive treatments with
catecholamines and corticosteroids, act as triggering factors. At the subcellular level,
propofol impairs free fatty acid utilization and mitochondrial activity. Imbalance between
energy demand and utilization is a key pathogenetic mechanism, which may lead to
cardiac and peripheral muscle necrosis. The syndrome can be lethal if not identified
early, and caution should be exercised when using prolonged (>48 hours) propofol
sedation at doses higher than 75 μg/kg/min, particularly in patients with acute neurologic
or inflammatory illnesses. In these cases, alternative sedative agents should be considered
immediately and monitoring of the plasma levels of troponin I, creatine kinase, and
myoglobin should be undertaken.
There is no need to obtain a CT of the head, which would pose added risk of transport for
the patient. Beyond immediate discontinuation of the drug, the treatment of propofol
infusion syndrome is supportive. Supportive treatment may ultimately include
bicarbonate infusion, hemodialysis, treatment of heart failure, and cardiac pacing for
profound bradycardia. There is no indication for IV heparin at this time. Plasmapheresis
has no role in managing the propofol infusion syndrome.
72. Correct Answer: D. Dexmedetomidine
Rationale: An infusion of dexmedetomidine would meet most of the stated goals. Data
regarding dexmedetomidine as a sedative in critical care patients suggests it might


decrease length of ICU stay. Continuous sedation with dexmedetomidine results in
significantly lower total ICU costs than midazolam infusions by decreasing length of ICU
stay and duration of mechanical ventilation. Dexmedetomidine appears to allow more
normal cognition in patients, whereas infusions of propofol (option C) or
benzodiazepines (options A and B) decrease cognition.
Infusions of dexmedetomidine have also been shown to be associated with decreased
time in coma, allowing more neurologic status checks. Dexmedetomidine does not affect
respiratory rate but can cause bradycardia when given as a large bolus or in a large
quantity during maintenance therapy.
Dexmedetomidine was shown to be particularly beneficial in improving brain
dysfunction in patients with sepsis.
Lorazepam is an independent risk factor for the development of delirium in the ICU.
Thus, option A is incorrect.
When patients who were given midazolam were compared to those who had received
dexmedetomidine, dexmedetomidine patients were extubated earlier by about 2 days,
with significantly less delirium and fewer infections. Therefore, option B is incorrect.
Increased infections have been found in patients receiving remifentanil infusions (option
E). There is no advantage to this type of sedation in terms of delirium, and it may be less
advantageous given the issues of cost and possible immunomodulation.
73. Correct Answer: A. Evaluating the tetanic fade with a neuromuscular monitor
Rationale: “A more accurate description of the effects of relaxants recognizes that the
neuromuscular junction is a complex and dynamic system in which the phenomena
produced by drugs are composites of actions that vary with drug, dose, activity in the
junction and muscle, time after administration and presence of anesthetics or other drugs,
and the age and condition of the patient.” It is now appreciated that there are nicotinic
acetylcholine receptors [nAChRs] in the carotid body and on macrophages; thus, it is
clear that the administration of these drugs can cause more effects than muscle paralysis.
Finally, neuromuscular function can also be affected by drugs that affect the
conformational state of the nAChR, such as volatile anesthetics, cocaine, neostigmine,
succinylcholine, calcium-channel blockers, phenothiazines, alcohol, and barbiturates.
These can cause desensitization of the receptors in that they bind to the receptors, but the
sodium channel does not open and fewer receptor-channel units are available to carry
transmembrane current.
Nicotinic autoreceptors are localized at the presynaptic nerve terminal and are
responsible for the release of acetylcholine [ACh] into the synaptic cleft during highfrequency stimulation of the presynaptic nerve terminal. These presynaptic cholinergic
receptors are only inhibited by nondepolarizing neuromuscular blockers such as
rocuronium and hexamethonium, and are nAChRs with alpha3-beta2 subunits.


Pharmacologic inhibition of these presynaptic alpha3-beta2 subunits during highfrequency, repetitive, tetanic stimulation causes a tetanic fade. These receptors are not
inhibited by succinylcholine, so a train-of-4 fade is not seen during the depolarizing block
associated with the administration of succinylcholine.
Succinylcholine is like two molecules of ACh and it binds to the AChRs, opens the
channel, passes current, and depolarizes the end plate; hence, it is a depolarizing
neuromuscular blocker .
Increasing the dose of rocuronium from 0.6 mg/kg to 1.2 mg/kg shortens the onset time
of complete neuromuscular blockade from 89 seconds to about 55 seconds. This is a very
similar amount of time for the initiation of complete blockade from an intubating dose of
succinylcholine. Thus, option B is incorrect.
Neuromuscular blockade, from both depolarizing and nondepolarizing neuromuscular
blockers, develops more quickly in centrally located muscles, including the laryngeal
muscles, the jaw muscles, and the diaphragm (option C), but the blockade also recovers
more quickly.
Although it is true that reversal agents would typically have no effect after a depolarizing
agent, whereas they should reverse a block from a nondepolarizing agent, timing is
everything. Reversal agents are usually administered when nondepolarizing
neuromuscular agents have been given and there has been a recovery of the train of 4 to a
ratio of about 0.7. Reversal of neuromuscular blockade cannot be achieved immediately
after the administration of neuromuscular blockers because the high doses of
nondepolarizing neuromuscular blockers prevent the action of the reversal agent at the
receptors. Therefore, administration of a reversal agent immediately after the
administration of the neuromuscular blocking drug would not help one discern whether a
depolarizing or nondepolarizing agent was given, as it would have no effect. Thus, option
E is incorrect.
74. Correct Answer: D. 30%
Rationale: This patient is at very high risk for complications during an emergent
intubation. She is elderly, she has severe underlying disease, she is unstable
hemodynamically, and she is severely hypoxic despite receiving maximal supplemental
oxygen. Her chances of complications, according to the literature on this subject, are
about 30%, and if she has complications, she has an increased chance of dying. Longterm survival in patients who require emergent intubations is about 45-55%. Furthermore,
if the intubation is not achieved after one attempt, there is an increased rate of
complications and mortality.
Therefore, to optimize the outcomes of emergent intubations in this high-risk population,
paralytic agents should be utilized, skilled personnel (third-year anesthesia residents
and/or anesthesia faculty) should be in attendance, and attempts at laryngoscopic
intubation should be minimized prior to utilizing different devices or a surgical airway.


75. Correct Answer: C. Dopamine
Rationale: This patient has septic shock from a probable abdominal source. The
therapeutic intervention produces an increase in heart rate, blood pressure, cardiac output,
urine output, and splanchnic blood flow; a decrease in blood lactate; and no change in
right atrial, right ventricular, pulmonary artery, and pulmonary artery occlusion pressures.
This pattern of hemodynamic effects is most consistent with dopamine administration, so
choice C is correct.
Dopamine is a common choice for an initial vasopressor in circulatory shock. A central
and peripheral nervous system neurotransmitter and the biological precursor of
norepinephrine, dopamine stimulates three different receptors: vascular dopaminergic,
cardiac beta1-adrenergic, and vascular alpha-adrenergic. At infusion rates of 1-3
µg/kg/min, dopaminergic effects usually dominate with vasodilation of renal, mesenteric,
myocardial, and cerebral vascular beds. At infusion rates of 5-10 µg/kg/min, cardiac
output is preferentially augmented by increased cardiac contractility via cardiac beta1
stimulation. At doses higher than 10 µg/kg/min, vascular alpha-adrenoreceptor effects
become most pronounced, with increasing blood pressure. If an adequate blood pressure
is not achieved with up to 20 µg/kg/min of dopamine, norepinephrine should be initiated.
There is substantial interindividual response to dopamine, and all three effects —
dopaminergic, cardiac beta1-adrenergic, and vascular alpha-adrenergic—commonly all
exist at all dose levels of the drug. Dopamine produces an increase in splanchnic flow and
urine output via its dopaminergic effects, increase in cardiac output and heart rate via its
cardiac beta1-adrenergic effects, and increase in blood pressure and decrease in lactate
(due to increased tissue perfusion) via both its vascular alpha-adrenergic and its cardiac
beta1-adrenergic effects.
Norepinephrine, another endogenous catecholamine, exerts powerful peripheral
vasoconstrictive (via alpha-adrenergic receptors) and moderate inotropic cardiac effects
(via cardiac beta1-adrenoreceptors). It causes an increase in blood pressure and (usually)
a decrease in heart rate and cardiac output due to its predominant ability to increase
afterload and blood pressure out of proportion to its ability to increase cardiac output via
the cardiac beta-adrenoreceptors. Norepinephrine administration in septic shock
commonly results in increased urine output and decreased blood lactate due to
improvement in blood pressure and tissue perfusion. Norepinephrine does not cause an
increase in splanchnic blood flow, so choice D is incorrect.
Vasopressin has vasoconstrictive and antidiuretic properties. Vasopressin constricts
vascular smooth muscle directly via V1 receptors. In septic shock, vasopressin levels are
reduced, and administration of exogenous vasopressin can produce a substantial
vasopressor effect. Prior to 10 years ago, vasopressin was used therapeutically at doses of
0.2 to 0.4 U/min to treat gastrointestinal hemorrhage from varices and other sources. At
this high dose, vasopressin produced profound systemic vasoconstriction with
particularly profound constriction seen in the splanchnic, coronary, and peripheral


vasculature. This dose of vasopressin was frequently associated with mesenteric,
coronary, and digital ischemia and infarction (choice A is incorrect).
More recently, vasopressin has been used in a lower dose of 0.01 to 0.03 U/min, and at
this dose it produces substantial generalized systemic vasoconstriction. It results in
increased blood pressure, and the increased afterload usually leads to decreased cardiac
output and heart rate; thus, choice B is incorrect. Because of an increase in blood pressure
and tissue perfusion, urine output may increase and lactate may decrease. Vasopressin
does not increase splanchnic blood flow.
76. Correct Answer: A. Nitroglycerin
Rationale: The hemodynamic effects involve little or no changes in heart rate, blood
pressure, cardiac output, and urine output. Substantial decreases are seen in right heart
filling pressures with a decrease in right atrial, right ventricular, pulmonary artery, and
pulmonary artery occlusion pressures. This hemodynamic pattern is most typical of a
predominantly venous vasodilator, and nitroglycerin is the agent most likely to produce
such an effect. Therefore, option A is correct.
Nitroglycerin has major vasodilating effects on the systemic venous circulation and the
coronary circulation, acting directly on vascular smooth muscle cells to produce
relaxation. Although in high doses it may have some effect on the systemic circulation,
its actions are predominantly on the venous circuit, producing a large decrease in preload
and filling pressures. Nitroglycerin has the ability to improve coronary blood flow and
reduce ischemia in patients with coronary artery disease, even when coronary
atherosclerosis is severe. Because of its favorable effects on coronary ischemia,
nitroglycerin is favored as a drug of first choice by cardiovascular physicians when
dealing with severe coronary artery disease. Dosages used intravenously usually range
from 5 to 200 µg/min. A significant limitation of nitroglycerin therapy is the
development of drug tolerance after about 24 hours of administration. Nitroglycerin
dosage will need to be increased to maintain the same therapeutic hemodynamic effect.
Therefore, nitroglycerin is only used for a short duration intravenously (24-48 hours), and
when used chronically, a 6-hour nitrate-free period every 24 hours is necessary in order
to prevent the development of nitrate tolerance.
Nitroprusside is a powerful venous and arterial vasodilator, and it produces a significant
reduction of preload and afterload. Nitroprusside infusions lead to decreases in right heart
and pulmonary artery filling pressures, but they also result in decreased blood pressures
and increased cardiac output in patients with a low cardiac output due to heart failure.
Thus, option B is incorrect. Dosage range is usually 0.3 to 5.0 µg/kg/min. Limitations of
nitroprusside include potentially causing a “coronary steal” syndrome, in which blood
flow may be directed away from ischemic myocardium. Prolonged nitroprusside
infusions in the setting of renal insufficiency may lead to accumulation of thiocyanate
and cyanide toxicity. This possible toxicity needs to be monitored when prolonged
infusions are used.


Milrinone is a phosphodiesterase inhibitor that works downstream from the betaadrenergic receptor. Milrinone has inotropic and vasodilator properties. In addition to a
decrease in filling pressures, it produces a significant increase in cardiac output (making
option C incorrect) with minimal changes in heart rate and either no change or a small
decrease in blood pressure. In severe acute heart failure, milrinone is commonly used if
dobutamine has failed to bring filling pressures and/or cardiac output into adequate range.
A major limitation of milrinone is its ability to cause hypotension, and with a relatively
long elimination half-life of 2.3 hours, this hypotension can represent a prolonged
problem.
Dobutamine is a potent beta1-adrenergic agonist with some beta2-adrenergic and alphaadrenergic agonist properties. Its major effect is to increase myocardial contractility; it
also causes an increase in cardiac output (making option D incorrect) and usually a mild
increase in heart rate. Because a decrease in systemic vascular resistance accompanies the
increase in inotropy, dobutamine does not have a predictable effect on blood pressure:
blood pressure may increase, decrease, or remain unchanged. A major advantage of
dobutamine is that its effective half-life is only a few minutes, so any drug-induced
hypotensive episodes are brief. A major limitation in heart failure is that beta-adrenergic
receptors may be chronically down-regulated, limiting the hemodynamic effects of a
beta1 agonist. Also, many heart failure patients are now receiving long-term betablockade therapy, and this may reduce dobutamine’s effectiveness. In such patients,
milrinone may be a good alternative. Dobutamine’s negatives also include a ventricular
arrhythmia risk and tolerance to the drug, which has been demonstrated with infusions
lasting >24 hours.
77. Correct Answer: B. Lymphoma
Rationale: The differential diagnosis of a central nervous system mass lesion in a patient
with HIV infection is primarily lymphoma versus toxoplasmosis. Many other infections
such as endemic fungi (Cryptococcus in particular) or Mycobacterium tuberculosis could
cause this lesion, but they are less common.
The current CD4 cell count is an excellent indicator of susceptibility to infection. A
recent CD4 cell count of 210/µL makes toxoplasmosis unlikely. This patient could have a
glioblastoma, but lymphoma is more likely. A polymerase chain reaction test of
cerebrospinal fluid for Epstein-Barr virus would strongly support this diagnosis.
78. Correct Answer: A. Treatment with oral vancomycin
Rationale: Therapy for Clostridium difficile colitis fails in 5-25% of cases. Some patients
fail to improve and some relapse. Relapses are due either to failure to eradicate spores
from the stool or to reacquisition of C difficile from the environment. Retreatment could
be approached with oral metronidazole, oral vancomycin, or a combination of both.
Nitazoxanide is active against C difficile, but its role in initial therapy or retreatment has
not been clearly defined, so it is not the best option. More than 95% of oral metronidazole
is absorbed in the proximal small bowel, so there is no real pharmacologic difference


between oral and IV routes of administration: both depend on bloodstream delivery to
inflamed gastrointestinal mucosa.
Vancomycin is effective orally, but IV therapy does not attain high gastrointestinal levels
and is not recommended. The literature is filled with accounts of treatment failures. If
vancomycin must be given, and oral therapy is not feasible, a retention enema is more
likely to be effective, but mechanical complications are a major concern with inflamed
colonic mucosa. Such enemas are rarely used in ICUs.
Gut recolonization with Saccharomyces has been shown to reduce the incidence of
relapses, but recolonization should not be done without a course of oral or IV therapy.
The controlled study that showed efficacy in preventing relapses compared standard oral
or IV antibiotic therapy plus Saccharomyces to antibiotic therapy alone.
Testing stool for fecal leukocytes provides data but is not a sensitive test. Testing of stool
by the lactoferrin test is more sensitive but not specific. Testing stool for toxin after an
initial positive result is not helpful. Even in successfully treated patients, toxin may
persist for many days or weeks and its presence does not distinguish why patients are
failing.
Almost no laboratories routinely perform C difficile susceptibility testing. Metronidazole
resistance does occur in about 7% of cases, but the clinical significance of this resistance
is uncertain given the high levels of drug that are attained in stool, particularly when the
colon is inflamed. Thus, the almost universal approach is to retreat the patient with oral
or IV metronidazole or oral vancomycin.



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