Supportive and Preventive

Medicine
Amy L. Dzierba, Pharm.D., BCPS, FCCM
NewYork-Presbyterian Hospital
New York, New York
 Supportive and Preventive Medicine

Supportive and Preventive

Medicine
Amy L. Dzierba, Pharm.D., BCPS, FCCM
NewYork-Presbyterian Hospital
New York, New York

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-107
 Supportive and Preventive Medicine

Learning Objectives C. If appropriate, discontinue sedation, and

ensure that the patient’s head is 30 degrees
1. Identify the importance of key components of above the bed.
intensive care medicine that can be applied to all D. Assess the need for VTE prophylaxis in
critically ill patients. patients admitted to the ICU, and initiate an
2. Recommend therapeutic options to prevent stress- insulin infusion to maintain a blood glucose of
related mucosal disease. 120 mg/dL.
3. Recommend therapeutic options to prevent venous
thromboembolism in a critically ill patient. 2. Regarding pharmacologic prophylaxis for stress-
4. Discuss therapeutic options for patients with related mucosal injury, which would be the most
heparin-induced thrombocytopenia. appropriate statement?
5. Discuss medications that can be used to provide A. Sucralfate neutralizes gastric pH.
comfort to a critically ill patient at the end of life. B. Proton pump inhibitors (PPIs) are superior to
histamine-2 receptor antagonists (H2RAs) in
preventing clinically significant bleeding.
Abbreviations in This Chapter C. Tolerance will occur with continued
administration of H2RAs.
aPTT Activated partial thromboplastin time D. Antacids are effective when used up to three
CDI Clostridium difficile infection times daily.
DVT Deep venous thrombosis
ELISA Enzyme-linked immunosorbent assay 3. A 66-year-old man is admitted to the ICU with
H2RA Histamine-2 receptor antagonist abdominal pain, nausea, and altered mental status.
HIT Heparin-induced thrombocytopenia He has a history of alcoholic cirrhosis, atrial
ICU Intensive care unit fibrillation, and erosive esophagitis. He is intubated
NGT Nasogastric tube and stabilized on the ventilator. A nasogastric tube
PF4 Platelet factor-4 (NGT) is placed, and the patient is tolerating enteral
PPI Proton pump inhibitor tube feedings. Which would be best to recommend
SRMD Stress-related mucosal disease for preventing stress-related bleeding?
SUP Stress ulcer prophylaxis A. Pantoprazole 40 mg intravenously twice daily.
VTE Venous thromboembolism B. Ranitidine 50 mg intravenously three times
daily.
C. Famotidine 20 mg twice daily by NGT.
Self-Assessment Questions D. Omeprazole suspension 20 mg once daily by
Answers and explanations to these questions may be NGT.
found at the end of this chapter.
4. A 51-year-old woman is admitted to the ICU for
1. On rounds, you have a “checklist” of interventions hypovolemic shock secondary to severe dehydration.
that will benefit all critically ill patients in an inten- She reports a 5-day history of diarrhea and malaise.
sive care unit (ICU). Which checklist would be most She has no recent history of illnesses or contact with
effective to implement? health care personnel. Her medical history includes
A. Initiate stress ulcer prophylaxis (SUP) in hypothyroidism and gastroesophageal reflux
patients who are admitted to the ICU, and if disease. Her medications include levothyroxine
appropriate, discontinue sedation. 25 mcg orally daily and famotidine 20 mg orally
B. Initiate enteral nutrition when appropriate, and at bedtime. Recently, her primary care physician
initiate mechanical venous thromboembolism changed famotidine to omeprazole 20 mg orally
(VTE) prophylaxis. at bedtime for increased gastroesophageal reflux
disease symptoms. While she is in the ICU, testing
for Clostridium difficile infection (CDI) comes back

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-108
 Supportive and Preventive Medicine

positive. Which would be the most appropriate A. Intermittent pneumatic compression devices.
statement regarding PPI use and CDI? B. Dalteparin 5000 units subcutaneously daily.
A. PPIs are a potential risk factor for CDI by C. Fondaparinux 2.5 mg subcutaneously daily.
producing hypochlorhydria and increasing the D. No VTE prophylaxis is indicated at this time.
host susceptibility to infections.
B. Prospective randomized controlled trials have 7. A 34-year-old man (weight 70 kg) is admitted to
shown that the risk of CDI is associated with the surgical ICU for acute respiratory failure from
PPI use. pancreatitis. He has no pertinent medical history.
C. Studies have shown that an increased risk of His current medications include norepinephrine at
CDI is associated with daily PPI use compared 0.07 mcg/kg/minute, dexmedetomidine at 0.7 mcg/
with PPI administration more frequently. kg/minute, ampicillin/sulbactam 3 g intravenously
D. Studies reporting on CDI and PPI use every 6 hours, famotidine 20 mg intravenously
have used the same definition of CDI and twice daily, and heparin 5000 units subcutaneously
implemented the same infection control three times daily. On day 3 of his ICU admission,
practices. the team suspects heparin-induced thrombocytope-
nia (HIT). The platelet count was 360,000/mm3 on
5. A 50-year-old woman (weight 70 kg) is admitted to admission, and today, it is 180,000/mm3. The 4T’s
the ICU after having an acute myocardial infarction. score is used to determine the probability of HIT.
She has a medical history significant for hypertension, The score is calculated as 3: low risk. The team
tobacco use, and osteoporosis. The next morning, would like to send the heparin–platelet factor 4
she is intubated and stabilized on a ventilator after an (PF4) immunoassay and initiate argatroban. Which
aspiration event. She has an NGT placed. Her current is the most appropriate response?
medications include piperacillin/tazobactam 4.5 g A. Discontinue all heparin products, but do not
intravenously every 8 hours (she has normal renal initiate argatroban.
function), famotidine 20 mg per NGT twice daily, B. Discontinue all heparin products, and initiate
metoprolol 50 mg per NGT every 8 hours, aspirin argatroban.
325 mg per NGT daily, and atorvastatin 80 mg per C. Send the heparin-PF4 immunoassay, and
NGT daily. Which would be the most appropriate continue low-dose unfractionated heparin until
VTE prophylaxis for this patient? the results come back.
A. Intermittent pneumatic compression devices. D. Do not send the heparin-PF4 immunoassay,
B. Enoxaparin 40 mg subcutaneously daily. and do not discontinue low-dose
C. Unfractionated heparin continuous infusion unfractionated heparin.
to maintain a therapeutic activated partial
thromboplastin time (aPTT). 8. Which would be the most important considerations
D. No VTE prophylaxis at this time. in a critically ill patient approaching the end of life?
A. Pain management, tight glucose management,
6. A 34-year-old woman (weight 65 kg) is admitted to and control of secretions.
the ICU with several fractures, a closed-head injury, B. Routine vital sign checks, discontinuation
and a grade 4 liver laceration after sustaining a motor of unnecessary medications, and control of
vehicle crash. Her medical history is not significant. secretions.
She is admitted to the ICU on a ventilator after C. Pain management, control of secretions, and
surgery. Current laboratory values are as follows: discontinuation of unnecessary medications.
sodium 145 mEq/L, potassium 3.1 mEq/L, chloride D. Discontinuation of unnecessary medications,
97 mEq/L, carbon dioxide 18 mEq/L, blood urea insertion of a Foley catheter, and treatment of
nitrogen (BUN) 70 mg/dL, and serum creatinine nausea and vomiting.
(SCr) 3.5 mg/dL. Which would be the most
appropriate VTE prophylaxis for this patient?

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-109
 Supportive and Preventive Medicine

I. KEY ASPECTS IN THE GENERAL CARE OF ALL CRITICALLY ILL PATIENTS

A. FAST-HUG is a mnemonic emphasizing important aspects of ICU medicine that can be applied at least
daily to all critically ill patients to ensure safe, effective, and efficient care (Crit Care Med 2005;33:1225-9).

Table 1. Key Elements of the FAST-HUG Approach

Element Importance Considerations

Malnutrition can lead to impaired
immune function leading to increased • Initiate oral or enteral feeding
susceptibility to infection, inadequate (preferred to parenteral feedings) as
Feeding
wound healing, bacterial overgrowth soon as possible, typically within the
in the GI tract, and increased first 24–72 hours after stabilization
propensity for decubitus ulcers

• Pain should be regularly assessed with

a validated tool such as the Behavioral
Pain Scale or the Critical-Care Pain
Analgesia Observation Tool
Analgesic and sedative administration • Preemptive analgesia should be
optimizes patient comfort and considered for invasive or potentially
minimizes the acute stress response painful clinical procedures
(hypermetabolism, increased oxygen • Sedation should be assessed and
consumption, hypercoagulability, and reassessed with a validated tool such
alterations in immune function) as the Richmond Agitation-Sedation
Sedation Scale or the Sedation Agitation Scale
• Maintain light levels of sedation
• If appropriate, execute sedative
interruption

• Initiate appropriate prophylaxis,

considering VTE and bleeding risks
• Mechanical prophylaxis (graduated
Most ICU patients carry at least one
Thromboembolic prophylaxis compression stockings or intermittent
risk factor for VTE
pneumatic compression devices) are
alternative nonpharmacologic options
in patients at high risk of bleeding

Elevating the head and thorax above

bed to a 30–45 degree angle reduces • Ensure patient position periodically
the occurrence of GI reflux and throughout the day, especially after
Head of bed elevation
nosocomial pneumonia in patients procedures that require the patient to
who are receiving mechanical lie flat
ventilation

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-110
 Supportive and Preventive Medicine

Table 1. Key Elements of the FAST-HUG Approach (continued)

Element Importance Considerations

Critically ill patients develop stress-
• Consider discontinuing acid-
related mucosal damage, potentially
Stress Ulcer prophylaxis suppressive medications when risk
leading to clinically significant
factors are no longer present
bleeding
• Continuous insulin infusions to
Glycemic control is necessary in maintain blood glucose between 140
critically ill patients to decrease the and 180 mg/dL should be considered
incidence of complications such as in the acutely ill patient when blood
Glycemic control
decreased wound healing, increased glucose levels are ³ 150 mg/dL or
infection risk, and increased risk of greater
polyneuropathy • Transition to subcutaneous basal/bolus
insulin once the patient is stabilized
GI = gastrointestinal; ICU = intensive care unit; VTE = venous thromboembolism.

B. Daily Checklists
1. Checklists aim to provide a framework of standardization and regulation of interventions in a
systematic manner, allowing individuals to assess the presence or absence of the items.
2. Provides structure to important ICU-related interventions in an effort to reduce errors of omission and
increase compliance with evidence-based practices to improve outcomes in the ICU patient population
(N Engl J Med 2006;355:2725-32; N Engl J Med 2009;360:491-9)

Patient Case
1. A 68-year-old man (weight 85 kg) is admitted to the ICU for management of severe hypoxemic respiratory
failure associated with community-acquired pneumonia. He is endotracheally intubated and placed on
mechanical ventilation. His medical history consists of Child-Pugh class B cirrhosis secondary to alcohol
abuse, heart failure, and myocardial infarction. His laboratory values show a white blood cell count
(WBC) of 15 x 103 cells/mm3, platelet count 75,000/mm3, BUN 15 mg/dL, SCr 1.1 mg/dL, potassium 4.5
mEq/L, international normalized ratio (INR) 1.0, aspartate aminotransferase (AST) 58 IU/mL, and alanine
aminotransferase (ALT) 49 IU/mL. His current medications include ceftriaxone 1 g intravenously daily,
vancomycin 1250 mg intravenously every 12 hours, heparin 5000 units subcutaneously every 8 hours,
fentanyl drip at 50 mcg/hour, midazolam drip at 1 mg/hour titrated to a Richmond Agitation Sedation Scale
(RASS) of 0 to -1, and a regular insulin drip at 1.5 units/hour titrated to maintain blood glucose 140–180
mg/dL. Currently, the patient’s head is 30 degrees above the bed, his RASS is documented as -4, he is on
minimal ventilator settings, and he has an NGT placed. As the clinical pharmacist rounding on this patient,
you go through the FAST-HUG mnemonic. Which are the best recommendations to make to the team?
A. Initiate enteral nutrition by NGT, add SUP, and discontinue fentanyl and midazolam drips.
B. Initiate enteral nutrition by NGT, discontinue deep venous thrombosis (DVT) prophylaxis, and transition
insulin drip to sliding scale.
C. Transition insulin drip to sliding scale, add SUP, and discontinue fentanyl and midazolam drips.
D. Discontinue fentanyl and midazolam drips, discontinue DVT prophylaxis, and add SUP.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-111
 Supportive and Preventive Medicine

II. STRESS ULCER PROPHYLAXIS

A. Epidemiology of Stress-Related Mucosal Disease (SRMD)

1. Endoscopic evidence of superficial mucosal damage occurs in 75%–100% of patients within 1–2 days
after ICU admission.
2. Mortality from stress-related bleeding ranges from 50% to 70% in the critically ill, with a 20%
mortality rate attributable to SRMD.
3. Clinically significant stress-related bleeding has decreased during the past decade because of many
factors, including early resuscitation and SUP.

B. Characteristics of SRMD
1. Multiple superficial erosive lesions occurring early in the course of critical illness, potentially
progressing to deep ulcers.
2. Stress ulcers are diffuse in nature and are not amenable to endoscopic therapy; they generally heal over
time, without intervention, as the patient’s clinical status improves.

Table 2. Clinical Presentation of Stress vs. Peptic Ulcers

Stress Ulcers Peptic Ulcers

Multiple superficial lesions at the proximal stomach Few deep lesions in the duodenum; typically involves a
bulb; involves superficial capillaries single vessel

C. Pathophysiology of SRMD
1. Decreased splanchnic blood flow is the primary cause of stress ulcer-related bleeding.
2. Reduced splanchnic blood flow is caused by mechanisms common to critical illness:
a. Hypovolemia
b. Reduced cardiac output
c. Proinflammatory mediator release
d. Increased catecholamine release
e. Visceral vasoconstriction
3. Additional factors leading to stress ulcer-related bleeding:
a. Decreased gastric mucosal bicarbonate production
b. Decreased gastric emptying of irritants and acidic contents
c. Acid back-diffusion
d. Reperfusion injury that may occur following restoration of blood flow after prolonged periods of
hypoperfusion

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-112
 Supportive and Preventive Medicine

Table 3. Categories of Stress-Related Bleeding

Outcome Incidence in ICU Patients Definition
Endoscopically evident mucosal
75%–100% Superficial lesions identified on endoscopy
damage
Presence of guaiac-positive stools or
Occult bleeding 15%–50%
nasogastric aspirate
Appearance of coffee grounds in
Overt or clinically evident bleeding 5%–25% nasogastric aspirate, hematemesis, melena,
or hematochezia
Bleeding with hemodynamic instability
Clinically significant bleeding 1%–5%
and/or blood transfusion

D. Risk Factors for Stress-Related Bleeding

1. Significant independent risk factors for SRMD and bleeding include respiratory failure requiring
mechanical ventilation for 48 hours or longer OR coagulopathy (platelet count less than 50,000/mm3,
INR greater than 1.5, or aPTT greater than 2 times the control) (N Engl J Med 1994;330:377-81).
a. Patients with at least one risk factor had a 3.7% incidence of bleeding compared with 0.1% if risk
factors were absent.
b. Most of the 2252 patients enrolled in this study were cardiothoracic patients, potentially making
extrapolations to other ICU settings inaccurate.
2. Other risk factors for SRMD and bleeding include:
a. Severe brain injury
b. Major surgery
c. Thermal injury affecting more than 20% total body surface area
d. Acute kidney injury
e. Acute hepatic failure
f. Severe sepsis
g. Hypotension
h. History of gastrointestinal (GI) bleed within the past year
i. Postoperative transplantation
j. Ulcerogenic medications (nonsteroidal anti-inflammatory drugs, aspirin, corticosteroids)
3. Risk factors associated with GI bleeding while receiving prophylaxis (all patients on mechanical
ventilation):
a. Renal failure (Crit Care Med 1999;27:2812-7)
b. Age (50 years or older), male sex, diagnosis with acute respiratory failure or myocardial
infarction, acute kidney injury, neurologic injury, sepsis, shock, acute or chronic hepatic failure,
and coagulopathy (JAMA Intern Med 2014;174:564-74)

E. Pharmacologic Therapy for Preventing Stress Ulcers

1. Antacids
a. Dose-dependent neutralization of gastric acid
b. Not recommended for routine use because of frequency of administration (up to every hour),
adverse effects (diarrhea, constipation, electrolyte abnormalities), and interactions (interferes with
absorption of some drugs)

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-113
 Supportive and Preventive Medicine

2. Sucralfate (Carafate)
a. Complexes with albumin and fibrinogen to form a viscous, adhesive substance that adheres to
ulcers in the presence of a pH less than 4
b. Not recommended for routine use because of adverse effects (constipation, aluminum toxicity,
hypophosphatemia) and interactions by chelation
c. Sucralfate is less efficacious than H2RAs
3. Histamine-2 receptor antagonists
a. Competitive blockers of histamine subtype 2 receptor on the basolateral membrane of the parietal
cells. In addition, H2RAs inhibit gastrin secretion to reduce acid production; however, they do not
reliably inhibit vagally induced acid secretion.
b. In animal models, H2RAs may also attenuate reperfusion injury by decreasing interleukin-6 and
neutrophil activation, reducing inflammation by enhancing cell-mediated immunity, and acting as
a weak free radical scavenger.
c. Dose-dependent increase in gastric pH
d. Data against SRMD-related bleeding are primarily with the intravenous route of administration.
i. Previous studies used either continuous-infusion H2RAs or combined H2RAs with intermittent
antacids to maintain pH greater than 4.
ii. Current practice is to use intermittent administration of H2RAs without pH monitoring.
May offer reduction in bacterial overgrowth and thereby less aspiration pneumonia and less
tachyphylaxis
e. Adverse effects
i. Mental status changes such as confusion, hallucinations, agitation, and headaches (mainly
associated with cimetidine)
ii. Thrombocytopenia (occurs over several days from hapten formation; may occur within hours
if patient is sensitized)
iii. Rapid infusion-related hypotension
iv. Sinus bradycardia
v. Risk of nosocomial pneumonia
f. Drug interactions
i. Cimetidine inhibits cytochrome P450 (CYP) isoenzymes 3A4, 2D6, 2C9, 2C19, and 1A2.
ii. pH-dependent interactions

Table 4. Available H2RAs

Drug Name Dosea
Cimetidineb
300 mg IV/PO every 6 hours or continuous infusion at 37.5–50 mg/hour
(Tagamet)
Famotidine
20 mg IV/PO every 12 hours
(Pepcid)
Nizatidine
150 mg PO every 12 hours
(Axid)
Ranitidine
150 mg PO every 12 hours or 50 mg IV every 8 hours
(Zantac)
a
Dose based on clinical data (cimetidine as a continuous infusion is the only H2RA approved by the U.S. Food and Drug Administration for SUP).
All H2RAs are renally eliminated and require dose adjustments for renal dysfunction.
b
Competitively inhibits tubular secretion of creatinine.
H2RA = histamine-2 receptor antagonist; IV = intravenously; PO = oral.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-114
 Supportive and Preventive Medicine

4. Proton pump inhibitors

a. Prodrugs activated in the acidic environment of the parietal cell inhibiting both histamine-induced
and vagally mediated gastric acid by binding and inhibiting active proton pumps
b. Dose-dependent increase in gastric pH, with maximal activity reached 3 days after initiation
c. Most trials had evaluated the effectiveness of enteral PPIs; however, they may be administered
intravenously.
d. Despite short elimination half-lives, PPIs suppress acid secretion for 20 hours or more, permitting
once-daily dosing without requiring gastric pH monitoring.
e. Tachyphylaxis does not occur with PPIs.
f. Rebound acid hypersecretion may occur after discontinuation; however, clinical relevance is
unknown.
g. Adverse effects
i. GI such as diarrhea, abdominal pain, constipation, nausea
ii. Headaches
iii. Rash
iv. Interstitial nephritis
v. Hypomagnesemia (3 months or more of therapy)
vi. Neurologic effects with high-dose intravenous omeprazole (hearing and vision disturbances)
vii. Hypophosphatemia and metabolic alkalosis when administered with sodium bicarbonate
viii. Increased risk of fractures (hip, waist, and spine)
ix. C. difficile infection (definitive cause-effect relationship is not well established)
x. Risk of nosocomial pneumonia
h. Drug interactions
i. All agents are hepatically metabolized by CYP isoenzymes 3A4 and 2C19.
ii. Omeprazole is an inhibitor of 3A4, 2C19, 2C9, and 1A2.
iii. Lansoprazole may induce CYP1A2.
iv. pH-dependent interactions

Table 5. Available Proton Pump Inhibitors

Alternative Routes of Administration
Agent Dose a
(NGT/OGT) Alternative Dosage Forms
Intact capsule granules sprinkled on applesauce Delayed-release oral
Esomeprazole 40 mg daily suspension granules
Suspend granules in a syringe with 50 mL of
water; flush with 10 mL of water Intravenous
Intact capsule granules sprinkled on applesauce,
pudding, cottage cheese, or yogurt Packet for oral suspension
Suspend granules in a syringe with 40 mL of Delayed-release orally
apple juice; flush with 20 mL of apple juice disintegrating tablet
Lansoprazole 30 mg daily
Dissolve granules in 10 mL of 8.4% sodium Delayed-release suspension
bicarbonate; flush with 10 mL of sodium (xanthan gum will clog NGT
bicarbonate or water (simplified lansoprazole or OGT)
suspension)

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-115
 Supportive and Preventive Medicine

Table 5. Available Proton Pump Inhibitors (continued)

Alternative Routes of Administration

Agent Dosea (NGT/OGT) Alternative Dosage Forms
Intact capsule granules sprinkled on applesauce
Suspend granules in a syringe with 40 mL of
apple juice; flush with 20 mL of apple juice Powder for oral suspension
Omeprazole 20 mg daily
Dissolve granules in 10 mL of 8.4% sodium
bicarbonate; flush with 10 mL of sodium
bicarbonate or water (simplified omeprazole
suspension)
Crush and dissolve enteric-coated tablet in 10 mL
Packet for oral suspension
of 4.2% sodium bicarbonate and add 10 mL
Pantoprazole 40 mg daily for a total volume of 20 mL; flush with 10 mL Intravenous
of sodium bicarbonate or water (pantoprazole
suspended in sodium bicarbonate solution)
Dose based on clinical data (only omeprazole powder for oral suspension is approved by the U.S. Food and Drug Administration for SUP).
a

NGT = nasogastric tube; OGT = orogastric tube.

F. Clinically Significant Bleeding

1. Most trials define clinically significant bleeding as overt bleeding accompanied by one of the
following:
a. Decrease in blood pressure of 20 mm Hg within 24 h of the first GI bleeding episode
b. Decrease in blood pressure of 10 mm Hg and an increase in heart rate of 20 beats/minute on
orthostatic change
c. Decrease in hemoglobin of 2 g/dL and transfusion of 2 units of blood within 24 hours of bleeding
OR failure of the hemoglobin concentration to increase after transfusion by at least the number of
units transfused minus 2 g/dL
2. Antacids, sucralfate, H2RAs, and PPIs have all reduced clinically significant SRMD-related bleeding
compared with placebo.
3. Results of meta-analyses assist in providing a comparative estimate of treatment on bleeding rates.
4. Three meta-analyses favored PPIs to H2RAs for GI bleeding; however, the studies that were included
lacked methodological quality with unexpectedly high baseline bleeding rates, a disproportionate
number of risk factors between patient groups, inconsistent definitions of bleeding, and different routes
and dosing of agents.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-116
 Supportive and Preventive Medicine

Table 6. Results of Meta-analyses on Clinically Important Bleeding Ratesa

Antacids vs. H2RAs vs. H2RAs vs. PPIs vs.
Sucralfate Antacids Sucralfate H2RAs
Am J Med 0.65 0.84 0.95
—
1991;91:519-27 (0.16–2.49) (0.45–1.56) (0.06–15.40)
Infect Control
1.39 0.84 1.05
Hosp Epidemiol —
(0.67–3.21) (0.45–1.56) (0.12–16.36)
1994;15:437-42
JAMA 1996; 1.49 0.86 1.28
—
275:308-14 (0.42–5.27) (0.46–1.59) (0.27–6.11)
Crit Care Med 0.87 0.53 (0.3–0.93)
— —
1991;19:942-9b (0.45–1.67) favoring sucralfate
Crit Care 0.87
— — —
2010;14:R194 (0.49–1.53)
-0.04
Crit Care Med
— — — (-0.09–0.01)
2010;38:1197-1205
favoring PPIs
0.30
Am J Gastroenterol
— — — (0.17–0.54)
2012;107:507-20
favoring PPIs
0.36
Crit Care Med
— — — (0.19–0.68)
2013;41:693-705
favoring PPIs
a
All results reported as odds ratio or risk difference (95% confidence interval)
b
Macroscopic hemorrhages only; meta-analysis directly contradicts findings from a landmark study (N Engl J Med 1998;338:791-7) in which
intermittent administration of intravenous ranitidine resulted in a lower rate of clinically significant bleeding compared with sucralfate.
H2RA = histamine-2 receptor antagonist; PPI = proton pump inhibitor.

G. Infectious Complications
1. Increases in gastric pH promote bacterial overgrowth, potentially leading to infectious complications.
Both H2RAs and PPIs will cause changes in gastric pH; however, because tachyphylaxis occurs with
H2RAs, PPIs have a greater propensity to maintain a sustained higher pH.
2. Pneumonia
a. Meta-analyses showed lower pneumonia rates with sucralfate compared with H2RAs alone or
H2RAs combined with antacids and no differences in pneumonia rates when H2RAs were compared
with PPIs. Many of the trials included in the analysis have variable definitions of pneumonia.
b. An observational study of cardiac surgical patients detected a higher rate of pneumonia with PPIs
than with H2RAs (relative risk [95% confidence interval {CI}]) 1.19 [1.03–1.38] after propensity
score adjustment (BMJ 2013;347:f5416).
3. C. difficile infection
a. A cohort study observed incremental increases in the risk of nosocomial CDI as the level of
acid suppression increased. After adjustment, the CDI increased from an odds ratio of 1 (1 =
reference of no acid suppression) to 1.53 (95% CI, 1.12–2.10) for H2RA to 1.74 (1.39–2.18) with
daily PPI use, and to 2.36 (1.79–3.11) for more frequent administration of PPI (Arch Intern Med
2010;170:784-90).

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-117
 Supportive and Preventive Medicine

b. There are no prospective trials evaluating the risk of CDI in ICU patients. Furthermore, many
published trials have different definitions of CDI, unclear association of antisecretory therapy
initiation and CDI diagnosis, and variable infection control practices.

H. Duration of SUP: Continued as long as one or more risk factors are present

I. Pharmacoeconomics
1. According to the landmark trial comparing H2RAs with sucralfate, H2RAs may be more cost-effective
because of reduced incidence of bleeding without an increase in pneumonia rates.
2. Cost-effectiveness models have compared H2RAs with PPIs in relation to clinically important bleeding
and adverse effects (ventilator-associated pneumonia [VAP] and CDI), yielding discordant results:
a. Use of PPI therapy for SUP resulted in a $1250 net cost savings per patient compared with H2RAs.
Univariate sensitivity analysis showed that with changing the probability of VAP rates, PPI
therapy would not be as cost-effective (Value Health 2013;16:14-22).
b. Use of H2RA therapy for SUP resulted in a $1095 net cost savings compared with PPIs. Univariate
sensitivity analysis showed that assumptions of pneumonia and bleeding rates were the primary
drivers of incremental costs (Crit Care Med 2014;42:809-15).
3. Cost minimization is best practiced by initiating SUP in patients at risk and appropriately discontinuing
SUP when a patient no longer possesses any of the risk factors for stress-induced bleeding.

J. Guideline Recommendations: The Surviving Sepsis Guidelines published in 2012 recommend PPIs over
H2RAs for SUP (weak/low quality evidence) (Crit Care Med 2013;41:580-637).

Patient Cases

Questions 2–4 pertain to the following case.

A 72-year-old woman is admitted to the ICU for severe respiratory failure from community-acquired pneumonia.
She is endotracheally intubated and placed on mechanical ventilation. An NGT is placed to begin enteral nutrition.
She is currently receiving fluid boluses, norepinephrine and vasopressin infusions, and appropriate antimicrobial
agents. Her WBC is 20 x 103 cells/mm3, platelet count 45,000/mm3, BUN 70 mg/dL, SCr 4.5 mg/dL (baseline 0.9
mg/dL), potassium 4.5 mEq/L, INR 1.4, AST 30 IU/mL, and AST 46 IU/mL.

2. Which best reflects this patient’s number of risk factors for stress-related bleeding?
A. One.
B. Two.
C. Four.
D. Five.

3. Which would be most appropriate for preventing stress-related bleeding?

A. Sucralfate 1 g four times daily by NGT.
B. Magnesium hydroxide 30 mL every 4 hours by NGT.
C. Pantoprazole 40 mg intravenously twice daily.
D. Famotidine 20 mg intravenously daily.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-118
 Supportive and Preventive Medicine

Patient Cases (continued)

4. One week later, the patient’s respiratory status has greatly improved. She has been off sedation and
vasopressors for the past 4 days, working with physical therapy, and is now extubated. Her only medications
include ceftriaxone, heparin subcutaneously, and SUP from above. Her current laboratory values are as
follows: WBC 6 x 103 cells/mm3, platelet count 256,000/mm3, BUN 10 mg/dL, SCr 1.1 mg/dL, potassium
4.0 mEq/L, INR 0.8, AST 15 IU/mL, and ALT 10 IU/mL. Which would be the most appropriate
recommendation to make regarding this patient’s SUP regimen?
A. SUP should be continued until hospital discharge.
B. SUP should be continued until ICU discharge.
C. SUP should be discontinued now.
D. SUP should be discontinued once the patient is off antimicrobials.

III. PROPHYLAXIS AGAINST DEEP VENOUS THROMBOSIS OR PULMONARY EMBOLISM

A. Risk Factors
1. Malignancy, previous VTE, immobility, known thrombophilia, recent (1 month or less) surgery or
trauma, older age (70 years or older), heart or respiratory failure, sepsis, obesity (body mass index of
30 kg/m2 or more), pregnancy, erythropoiesis-stimulating agents with hemoglobin 12 g/dL or more,
hormonal therapy, recent transfusions of concentrated clotting factors, central venous lines, and long-
distance travel.
2. Additional VTE risk factors in critically ill patients:
a. Single-center prospective cohort (n=261) identified four independent risk factors for ICU-acquired
VTE, including personal or family history of VTE (multivariate hazard ratio [HR] 4.0; 95%
CI, 1.5–10.3; p=0.004), end-stage renal failure (HR 3.7; 95% CI, 1.2–11.1; p=0.02), platelet
transfusion (HR 3.2; 95% CI, 1.2–8.4; p=0.02), and vasopressor use (HR 2.8; 95% CI, 1.1–7.2;
p=0.03) (Crit Care Med 2005;33:1565-71).
b. In the critically ill patient population, there are no validated risk assessment models to estimate the
risk of VTE.

B. Prevention of VTE in the General Critically Ill Patient Population – Summary of recommendations (Chest
2012;141:S195-226)
1. Routine ultrasound screening is not recommended.
2. Either low-dose unfractionated heparin or low-molecular-weight heparin should be initiated in a
critically ill patient over no prophylaxis.
3. Mechanical VTE prophylaxis should be used in a critically ill patient if bleeding or at high risk of
bleeding. Once bleeding risk abates, initiate pharmacologic VTE prophylaxis.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-119
 Supportive and Preventive Medicine

Table 7. Randomized Trials of VTE Prophylaxis in Critically Ill Patients

Major
Screening Bleeding
Citation Study Type Population Intervention Methods VTE Rates Rates
Crit Care Single-center 119 medical- LDUH 5000 Daily 13% in Not reported
Med surgical ICU units SC 125
I-labeled LDUH vs.
1982;10: patients twice daily vs. fibrinogen leg 29% in
448-50 placebo scanning placebo;
p<0.05
Am J Multicenter, 221 MV Nadroparin Weekly Doppler 15% in 6% in
Respir Crit double-blind patients with (weight ultrasonography nadroparin nadroparin
Care Med COPD based) SC and day 21 group vs. 28% group and 3%
2000;161: daily vs. in placebo in placebo
1109-14 placebo group; group; p=0.28
p=0.045
Thromb Multicenter, 1935 patients LDUH 5000 Doppler 5.6% in Not reported
Haemost double-blind with severe units SC ultrasonography LDUH group
2009;101: sepsis twice daily vs. between days vs. 5.9% in
139-44 receiving enoxaparin 40 4 and 6 enoxaparin
drotrecogin mg SC daily group vs.
alfa vs. placebo 7.0% in
(activated) placebo
group; p=NS
Blood Single-center, 156 surgical LDUH 5000 Doppler 2.7% in 2.7% in the
Coagul double-blind patients units SC ultrasonography LDUH group LDUH group
Fibrinolysis undergoing twice daily vs. 5–7 days after vs. 1.2% in vs. 1.2% in
2010;21: major elective enoxaparin 40 surgery and enoxaparin enoxaparin
57-61 surgery mg SC daily when clinically group; p=0.51 group; p=0.48
indicated

N Engl Multicenter, 3746 medical- LDUH 5000 Doppler 9.9% in 5.6% in

J Med double-blind surgical units SC ultrasonography LDUH group LDUH group
2011;364: ICU patients twice daily 2 days after vs. 8.2% in vs, 5.5% in
1305-14 expected to vs. dalteparin admission, dalteparin dalteparin
remain in the 5000 twice weekly, group; p=0.24 group; p=0.98
ICU for ≥ 3 international and as clinically
days (90% units SC daily indicated
medical, 76%
MV)
ICU = intensive care unit; LDUH = low-dose unfractionated heparin; SC = subcutaneously; VTE = venous thromboembolism.
COPD = chronic obstructive pulmonary disease; ICU = intensive care unit; MV = mechanically ventilated; NS = not significant.

C. Prevention of VTE in the Non-Orthopedic Surgical Patent (Chest 2012;141:S227-77)

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-120
 Supportive and Preventive Medicine

Table 8. VTE Prophylaxis Recommendations in Trauma Patents

Risk Level for VTE Risk of Bleeding Prophylaxis

Low-moderate Low LMWH,a LDUH,a or IPCD (all preferred to no prophylaxis)

Highb Low LMWHa or LDUHa with elastic stockings or IPCD

a
If LDUH or LMWH is contraindicated, mechanical prophylaxis with IPCD is preferred to no prophylaxis in the absence of lower extremity injury.
b
Includes acute spinal cord injury, traumatic brain injury, and spinal surgery from trauma.
IPCD = intermittent pneumatic compression device; LDUH = low-dose unfractionated heparin; LMWH = low molecular weight heparin; VTE =
venous thromboembolism.
LMWH = low molecular weight heparin; VTE = venous thromboembolism.

Table 9. VTE Prophylaxis Recommendations in the General and Abdominal-Pelvic Surgical Patient
Risk Level for VTE Risk of Bleeding Prophylaxis
Very low Low Early ambulation
Low Low IPCD
Low LMWH, LDUH, or IPCD
Moderate
High IPCD
Low LMWH or LDUH with elastic stockings or IPCD
Low with contraindications to
Low-dose aspirin, fondaparinux, or IPCD
High LMWH or LDUH
IPCD until risk of bleeding abates, then pharmacologic
High
prophylaxis should be initiated
IPCD = intermittent pneumatic compression device; LDUH = low-dose unfractionated heparin; LMWH = low molecular weight heparin; VTE =
venous thromboembolism.

Table 10. Available Agents and Dosing

Dose in Patients with Normal
Renal Function Dose in Patients with Renal Impairmenta
Enoxaparin 40 mg SC daily 30 mg SC daily
Specific dosage adjustments have not been
recommended; accumulation was not observed in
Dalteparin 5000 units SC daily critically ill patients with severe renal insufficiency. No
adjustment needed for CrCl ³ 20 mL/minute or greater.
(Arch Intern Med 2008;168:1805-12)
5000 units SC every 8–12 hours: choosing between every 8 and every 12 hours should be based
LDUH
on the patient’s risk of thrombosis and bleeding
2.5 mg once daily for patients Contraindicated; however, doses of 2.5 mg SC every 48
Fondaparinux
weighing 50 kg or more hours have been used
a
Estimated CrCl 20–30 mL/minute.
CrCl = creatinine clearance; LDUH = low-dose unfractionated heparin; SC = subcutaneously.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-121
 Supportive and Preventive Medicine

D. Considerations for Critically Ill Patients

1. Inability to communicate symptoms (impaired consciousness) and altered physical examination
(edema) makes diagnosis of symptomatic VTE challenging in the critically ill patient population.
Routine screening for VTE with ultrasonography is not recommended.
2. Dosing frequency of low-dose unfractionated heparin (twice vs. thrice daily)
a. Large randomized controlled trials have only assessed twice-daily dosing, and no direct
comparisons have been made in any population, including the critically ill.
b. Indirect comparisons from a meta-analysis suggest no difference in thrombosis or major bleeding
rates with twice- compared with thrice-daily regimens (Chest 2011;140:374-81).
3. The bioavailability of subcutaneously administered drugs is reduced in critically ill patients with the
concomitant use of vasoactive drugs or the presence of edema, thereby potentially providing a reduced
effect.
4. Renal impairment
a. Critically ill patients (n=138) administered prophylactic subcutaneous dalteparin with an estimated
creatinine clearance (CrCl) less than 30 mL/minute were evaluated in a prospective study.
b. No evidence of accumulation or an increased risk of bleeding (Arch Intern Med 2008;168:1805-12)
5. Bleeding
a. Bleeding rates in critically ill patients are variable, depending on the type of pharmacologic
prophylaxis.
b. Patients at high risk of bleeding are often excluded from studies.
c. Patients at high risk of bleeding with a moderate to high risk of VTE may be considered for
mechanical VTE prophylaxis; however, pharmacologic prophylaxis should be reassessed when
bleeding risk is no longer present.

E. Novel Oral Anticoagulants for VTE Prophylaxis

1. No studies to date conducted in critically ill ICU patients.
2. Rivaroxaban has been shown to be noninferior to standard treatments in other settings such as
orthopedic surgery.
3. Rivaroxaban 10 mg orally once daily (35-day regimen) was compared with enoxaparin 40 mg
subcutaneously daily for 10 days, followed by placebo in acutely ill, hospitalized patients
(N Engl J Med 2013;368:513-23).
a. Rates of composite end point (asymptomatic or symptomatic VTE, pulmonary embolism, or death):
i. Day 10: 2.7% in both the rivaroxaban and enoxaparin group, p=0.003; met criteria for
noninferiority
ii. Day 35: 4.4% in the rivaroxaban group vs. 5.7% in the enoxaparin/placebo group, p=0.02;
met criteria for superiority
b. Clinically relevant bleeding events
i. Day 10: 2.8% in the rivaroxaban group vs. 1.2% in the enoxaparin group, p<0.001
ii. Day 35: 4.1% in the rivaroxaban group vs. 1.7% in the enoxaparin/placebo group, p<0.001

F. Heparin-Induced Thrombocytopenia (Chest 2012;141(2 suppl):495S-530S)

1. HIT is a severe, immune-mediated reaction potentially leading to life-threatening complications such
as myocardial infarction, skin necrosis, stroke, and VTE (around 50%–75% of patients with HIT
develop symptomatic thrombosis).
2. A rare manifestation is delayed-onset HIT, affecting patients exposed to heparin in the recent past
(prior 2 weeks) that present with new thrombosis and low platelet counts.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-122
 Supportive and Preventive Medicine

3. Frequency of HIT
a. Higher in patients receiving unfractionated heparin compared with low molecular weight heparin,
occurring in 1%-5% of patients versus less than 1%, respectively.
b. Occurs in less than 1% of ICU patients
c. Higher risk in cardiac or orthopedic surgical patients receiving unfractionated heparin (1-5) than in
medical patients (0.1-1)
4. Alternative causes of thrombocytopenia in critically ill patients include extracorporeal devices,
intra-aortic balloon pumps, sepsis, disseminated intravascular coagulation, bleeding, and medications.
Platelets may decrease post-cardiac bypass surgery and subsequently recover. A secondary drop in
platelets may signal potential HIT.
5. The clinical diagnosis of HIT
a. Suspected when a patient has a decrease in absolute platelet count to less than 150,000/mm3
or a relative decrease of at least 50%, skin lesions at injection sites, or systemic reactions after
intravenous boluses.
b. The typical onset is 5–10 days after heparin exposure, though it can be delayed and occur up to
3 weeks after cessation of therapy.
c. Recent heparin exposure may result in rapid-onset HIT, occurring within hours after rechallenge.
d. Patients with recent unfractionated heparin/low molecular weight heparin exposure and new
thrombosis should have their platelet counts checked before starting anticoagulant therapy.
6. Probability of HIT
a. The 4T’s pretest clinical scoring system has a high negative predictive value; however, it requires
further investigation in ICU patients.
b. The HEP (HIT Expert Probability) score has not been assessed in ICU patients.
7. Laboratory testing
a. Platelet factor 4 (PF4): ELISA
b. Antibody present if sample from patient binds to the heparin-PF4–coated wells, leading to a
color-producing reaction. A higher antibody concentration leads to more color production and a
higher optical density reading. Optical density readings of 0.4 or greater are considered positive
and indicate the presence of HIT antibodies.
c. High sensitivity (greater than 90%)
d. Low to moderate specificity
i. As low as 20%, depending on the patient population studied
ii. Clinically insignificant HIT antibodies are often detected among patients who have received
heparin 5-100 days earlier.
iii. Detects a range of immunoglobulin (Ig) A and IgM antibodies that are not pathogenic
e. Heparin-induced platelet aggregation (HIPA) and C14 serotonin release assay (SRA): Functional
assays
i. Patient serum is mixed with washed platelets from healthy volunteers and low and high
concentrations of heparin. In the presence of HIT antibodies, platelets are activated in low
concentrations of heparin and detected using radioactive serotonin (SRA) or visually (HIPA).
ii. High sensitivity and specificity
iii. Technically challenging and not readily available
8. Treatment of HIT
a. Immediately discontinue all sources of heparin and initiate an alternative non-heparin anticoagulant.
b. Parenteral direct thrombin inhibitors are the agents of choice for anticoagulation in the setting
of acute HIT because they have no cross-reactivity with heparin. Some studies support the use
of the factor Xa inhibitor, fondaparinux for the treatment of HIT, although there are reports of
fondaparinux-induced HIT.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-123
 Supportive and Preventive Medicine

c. Parenteral direct thrombin inhibitors are associated with a higher rate of major bleeding
complications compared with unfractionated heparin, and no antidote is available for excessive
anticoagulation.
d. Initiate warfarin once the platelet count has recovered and is within normal limits (at least
150,000/mm3) and after at least 5 days of therapy with an alternative anticoagulant. Alternatively,
conservative warfarin dosing may begin once platelet count is recovering. If a patient is on
warfarin at the time of HIT diagnosis, reversing with vitamin K is recommended.
e. Argatroban dosing in the critically ill population (Crit Care 2010;14:R90; Ann Pharmacother
2007;41:749-54)
i. Mean dose in critically ill patients was 0.24 (±0.16) mcg/kg/minute.
ii. Mean dose in critically ill patients with multiple organ dysfunction was 0.22 (±0.15) mcg/kg/
minute.
iii. Lower doses, 0.5 mcg/kg/min should be considered in severe liver impairment.
iv. Target aPTT is 1.5–3 times baseline.
f. Bivalirudin dosing in the critically ill population (Pharmacotherapy 2006;26:452-60)
i. Dose reduced to 0.05–0.1 mg/kg/hour, depending on renal function and bleeding risks.
ii. Slightly higher doses may be necessary with continuous renal replacement therapy
(0.07 mg/kg/hour).
iii. Target aPTT is 1.5–2.5 times baseline.

Table 11. Parenteral Agents for the Treatment of HIT

Desirudin Bivalirudin Fondaparinux

Argatroban (Iprivask) (Angiomax) (Arixtra)
Percutaneous
FDA approved for coronary
Yes No No
the treatment of HIT intervention
with HIT
Mechanism Direct thrombin Direct thrombin Direct thrombin
Factor Xa inhibitor
of action inhibitor inhibitor inhibitor
Elimination
40–50 minutes 120 minutes 25 minutes 17–20 hours
half-life
80% enzymatic;
Elimination Hepatobiliary Renal Renal
20% renal

Unlabeled dose for Unlabeled dose for

2 mcg/kg/minute HIT: 0.15–0.2 mg/
Unlabeled dose for HIT: 5–10 mg SC
kg/hour
Dosing HIT: 15–30 mg SC daily (dependent on
(see above for dosing
every 12 hours weight); 2.5 mg/day
in critically ill) (see above for dosing
for prophylaxis
in critically ill)

Monitoring aPTT aPTT aPTT Anti-factor Xa level

Effect on INR Excessive Minimal Moderate None
aPTT = activated partial thromboplastin time; FDA = U.S. Food and Drug Administration; HIT = heparin-induced thrombocytopenia; SC =
subcutaneously.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-124
 Supportive and Preventive Medicine

Patient Cases
5. A 93-year-old bedbound man (weight 45 kg) is admitted from a nursing home with a chronic obstructive
pulmonary disease exacerbation requiring mechanical ventilation. He has a history of diabetes mellitus and
heart failure. His laboratory values are all within normal limits except for a BUN of 35 mg/dL and an SCr
of 2.8 mg/dL (baseline 0.5). Which would be the most appropriate recommendation for VTE prophylaxis in
this patient?
A. Intermittent pneumatic compression devices.
B. Enoxaparin 30 mg subcutaneously once daily.
C. Heparin 5000 units subcutaneously twice daily.
D. Fondaparinux 2.5 mg subcutaneously daily.

Questions 6 and 7 pertain to the following case.

A 55-year-old man (weight 60 kg) with a medical history of diabetes mellitus, hyperlipidemia, and a DVT
2 months ago secondary to trauma to the lower extremity is admitted today to the ICU for acute respiratory
failure from influenza virus. His current laboratory values are as follows, WBC 13.1 x 103 cells/mm3, platelet
count 250,000/mm3, BUN 13 mg/dL, SCr 0.9 mg/dL, INR 1.2, AST 22 IU/mL, and AST 11 IU/mL. His current
medication regimen includes fentanyl and midazolam boluses for pain and agitation, piperacillin/tazobactam,
vancomycin, regular insulin infusion, SUP, and a heparin drip. Five days later, the patient remains intubated on
the same medications. At this time, it is noted that his platelet count has dropped to 112,000/mm3, and his BUN
and SCr have increased to 45 mg/dL and 2.7 mg/dL, respectively. The team sends a heparin-PF4 immunoassay;
however, the results will not come back for 48 hours.

6. Which would be the best course of action?

A. Discontinue heparin drip, and initiate argatroban continuous infusion at 0.5 mcg/kg/minute.
B. Do nothing because the patient has several other reasons to be thrombocytopenic.
C. Discontinue heparin drip, and initiate fondaparinux at 10 mg subcutaneously daily.
D. Do nothing until the heparin-PF4 immunoassay results.

7. Three days later, both the heparin-PF4 immunoassay and the SRA (serotonin release assay) return positive,
and the patient has a new DVT. The team would like to initiate warfarin. The patient’s current platelet count
is 130,000/mm3. Which would be the most appropriate response?
A. Discontinue argatroban and initiate warfarin at 5 mg orally daily.
B. Discontinue argatroban and initiate warfarin at 10 mg orally daily.
C. Warfarin should never be used in patients with HIT.
D. Warfarin should not be initiated now.

IV. END-OF-LIFE CARE

A. Clinicians commonly provide end-of-life and palliative care in ICUs.

B. The World Health Organization describes palliative care as “an approach that improves the quality of life of
patients and their families facing the problems associated with life-threatening illness, through the prevention
and relief of suffering by means of early identification and impeccable assessment and treatment of pain and
other problems, physical, psychosocial, and spiritual” (Global Atlas of Palliative Care at the End of Life).

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-125
 Supportive and Preventive Medicine

C. Goals of Palliative Care

1. To improve the quality of life for individuals who have severe diseases.
2. To offer a diverse array of assistance and care to the patient.

D. Categories of Support
1. Pain management is of paramount importance for comfort and reduction of distress. Providers and
families can collaborate to identify the sources of pain and relieve them with drugs and other forms of
therapy.
2. Symptom management involves treating symptoms other than pain such as nausea, thirst, bowel and
bladder problems, depression, anxiety, dyspnea, and secretions.
3. Emotional and spiritual support is important for both the patient and the family in dealing with the
emotional demands of critical illness.

E. General Considerations
1. Minimization of uncomfortable or unnecessary procedures, tests, or treatments.
2. Minimizing or discontinuing routine vital sign checks, patient weights, cardiac or other electronic
monitoring, fingersticks, and intermittent pneumatic compression devices.
3. Consider discontinuing routine blood draws, radiologic imaging, and other diagnostic procedures.
4. Consider discontinuing all medications not necessary for patient comfort.

F. Symptom Management
1. Pain
a. Opioids are the mainstay of treatment for patients experiencing pain at the end of life.
b. Administer opioid as an intravenous bolus dose and begin an intravenous continuous infusion,
adjusting rates to maintain comfort; avoid using subcutaneous or enteral routes because the onset
is delayed.
c. No evidence that unconscious patients do not experience pain; therefore, opioid administration
should be initiated or continued
d. Bolus and titrate infusions to control labored respirations; specific dosages of medications are less
important than the goal of symptom relief. Optimal dose is determined by assessing the patient
and rapidly increasing it as needed until symptoms are no longer present. Dose determined by
symptom relief and adverse effects (excessive sedation, respiratory depression [rare])
e. Suggested goals include keeping the respiratory rate at or below 30 breaths/minute and eliminating
grimacing and agitation.
f. Never use neuromuscular blocking agents to treat pain.
g. Morphine most commonly used; hydromorphone and fentanyl are alternatives.
h. In addition, opiates will reduce dyspnea.
i. Tolerance may develop over time.
j. Evidence is good that pain can be improved with correct dosing and titration without causing
respiratory depression or hastening death (JAMA 1992;267:949-53; Crit Care Med 2004;32:1141-8).
2. Anxiety/agitation/delirium
a. Symptoms at the end of life can relate to acute or chronic anxiety, delirium, or terminal delirium.
b. Nonpharmacologic treatments for agitation and anxiety can include frequent reorientation to the
environment and reduction in noise and other bothersome or stimulating environmental factors.
c. Intravenous haloperidol may be used without electrocardiographic (ECG) monitoring because the
benefits outweigh the risks of prolonged QTc (corrected QT interval), given the goals of care.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-126
 Supportive and Preventive Medicine

d. Benzodiazepines (midazolam and lorazepam)

i. Dose is determined by assessing the patient and increasing as needed until symptoms are no
longer present if haloperidol fails to relieve significant agitation.
ii. Determining what would be perceived as an acceptable level of sedation with the patient and/
or family or surrogate decision-maker is important before initiating sedatives.
iii. Tolerance may develop over time.
3. Fever
a. Acetaminophen is an effective therapy for improving comfort and decreasing the incidence of
fever. If patient is unable to swallow, this agent may be administered per rectum.
b. A nonsteroidal anti-inflammatory drug may be used when acetaminophen is ineffective.
c. Dexamethasone, which is also known to have antipyretic properties, could be considered.
4. Nausea and vomiting
a. Underlying causes such as medications, uremia, ascites, gastroparesis, and intestinal or gastric
obstruction should be treated or eliminated, if possible.
b. Agents to consider include haloperidol, metoclopramide, ondansetron, and dexamethasone.
c. Lorazepam can be considered as an adjunct, especially with anticipatory vomiting.
d. Use of more than one agent may be necessary for symptom relief.
5. Cough
a. Excessive coughing can lead to exacerbation of dyspnea, and spells of nausea and vomiting, in
addition to disturbing sleep and exacerbating pain.
b. Non-opioid antitussives such as benzonatate and dextromethorphan may be considered.
c. All opioids have intrinsic antitussive action by inhibiting the brain stem cough center; however,
if the patient is on an opioid for other reasons, adding another opioid has not shown additional
benefit.
d. For refractory cough, consider nebulized lidocaine.
6. Secretions
a. Near the end of life, the ability to clear oral and tracheobronchial secretions diminishes.
b. Secretions are usually too low in the tracheobronchial tree for gentle oral suctioning to be of help,
and suctioning can be disturbing.
c. The mainstay of treatment includes anticholinergic and antimuscarinic medications.
i. Scopolamine and atropine cross the blood-brain barrier and can be more sedating than
glycopyrrolate.
ii. Glycopyrrolate (0.1 mg intravenously every 4 hours) or atropine (1% ophthalmic solution
2 drops sublingually every 4 hours as needed) should be used to manage acute symptoms.
iii. Scopolamine patch is more gradual in onset (12 hours).
iv. More than one scopolamine patch may be used for unrelieved symptoms.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-127
 Supportive and Preventive Medicine

Patient Case
8. An 88-year-old woman is admitted to the ICU for decompensated heart failure and acute kidney injury.
This is her fourth admission to the ICU in the past 5 months. Speaking with the patient, you find that she
wishes not to be resuscitated or intubated but only to be comfortable. In a meeting with the patient’s family,
all members agree that they do not want to see their loved one suffer any longer. It is decided to initiate a
morphine drip at 2 mg/hour. Titration parameters include giving a bolus dose equivalent to the current rate
and increasing the infusion by 25%. The nurse taking care of the patent believes that the titration parameters
are too aggressive. Which would be the most appropriate change in titration parameters?
A. Change the parameters to increase only the morphine drip when the patient shows signs of discomfort,
such as an increase in blood pressure or heart rate.
B. Discontinue titration parameters, keeping the morphine infusion at the current rate.
C. Discontinue titration parameters, keeping the morphine infusion at the current rate and adding a
midazolam infusion at 2 mg/hour.
D. Do not change the titration parameters at this time.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-128
 Supportive and Preventive Medicine

REFERENCES

Key Aspects in the General Care of All Critically Ill 7. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors
Patients for gastrointestinal bleeding in critically ill patients.
1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Canadian Critical Care Trials Group. N Engl J Med
Sepsis Campaign: international guidelines for 1994;330:377-81.
management of severe sepsis and septic shock: 8. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer
2012. Crit Care Med 2013;41:580-637. prophylaxis in critically ill patients. Resolving
2. Haynes AB, Weiser TG, Berry WR, et al. A surgical discordant meta-analyses. JAMA 1996;275:308-14.
safety checklist to reduce morbidity and mortality in 9. Cook DJ, Reeve BK, Scholes LC. Histamine-2-
a global population. N Engl J Med 2009;360:491-9. receptor antagonists and antacids in the critically
3. Pronovost P, Needgam D, Berenholtz S, et al. ill population: stress ulceration versus nosocomial
An intervention to decrease catheter-related pneumonia. Infect Control Hosp Epidemiol
bloodstream infections in the ICU. N Engl J Med 1994;15:437-42.
2006;355:2725-32. 10. Cook DJ, Witt LG, Cook RJ, et al. Stress ulcer
4. Vincent JL. Give your patient a fast hug (at least) prophylaxis in the critically ill: a meta-analysis. Am
once a day. Crit Care Med 2005;33:1225-9. J Med 1991;91:519-27.
11. Dellinger RP, Levy MM, Rhodes A, et al. Surviving
Stress Ulcer Prophylaxis Sepsis Campaign: international guidelines for
1. Alhazzani W, Alenezi F, Jaeschke RZ, et al. Proton management of severe sepsis and septic shock:
pump inhibitors versus histamine 2 receptor 2012. Crit Care Med 2013;41:580-637.
antagonists for stress ulcer prophylaxis in critically 12. Howell MD, Novack V, Grgurich P, et al. Iatrogenic
ill patients: a systematic review and meta-analysis. gastric acid suppression and the risk of nosocomial
Crit Care Med 2013;41:693-705. Clostridium difficile infection. Arch Intern Med
2. Barkun AN, Adam V, Martel M, et al. Cost- 2010;170:784-90.
effectiveness analysis: stress ulcer bleeding 13. Huang J, Cao Y, Liao C, et al. Effect of histamine-2-
prophylaxis with proton pump inhibitors, H2 receptor antagonists versus sucralfate on stress ulcer
receptor antagonists. Value Health 2013;16:14-22. prophylaxis in mechanically ventilated patients: a
3. Barkun AN, Bardou M, Pham CQ, et al. Proton meta-analysis of 10 randomized controlled trials.
pump inhibitors vs. histamine 2 receptor antagonists Crit Care 2010;14:R194.
for stress-related mucosal bleeding prophylaxis 14. Lin P, Chang C, Hsu P et al. The efficacy and safety
in critically ill patients: a meta-analysis. Am J of proton pump inhibitors vs histamine-2 receptor
Gastroenterol 2012;107:507-20. antagonists for stress ulcer bleeding prophylaxis
4. Bateman BT, Bykov K, Choudhry NK, et al. Type among critical care patients: A meta-analysis. Crit
of stress ulcer prophylaxis and risk of nosocomial Care Med 2010;38:1197-1205.
pneumonia in cardiac surgical patients: cohort 15. MacLaren R, Campbell J. Cost-effectiveness of
study. BMJ 2013;347:f5416. histamine receptor-2 antagonist versus proton pump
5. Cook D, Guyatt G, Marshall J, et al. A comparison inhibitor for stress ulcer prophylaxis in critically ill
of sucralfate and ranitidine for the prevention of patients. Crit Care Med 2014;42:809-15.
upper gastrointestinal bleeding in patients requiring 16. MacLaren R, Reynolds PM, Allen RR. Histamine-2
mechanical ventilation. Canadian Critical Care receptor antagonists vs proton pump inhibitors on
Trials Group. N Engl J Med 1998;338:791-7. gastrointestinal tract hemorrhage and infectious
6. Cook D, Heyland D, Griffith L, et al. Risk factors for complications in the intensive care unit. JAMA
clinically important upper gastrointestinal bleeding Intern Med 2014;174:564-74.
in patients requiring mechanical ventilation. 17. Tryba M. Sucralfate versus antacids or
Canadian Critical Care Trials Group. Crit Care Med H2-antagonists for stress ulcer prophylaxis: a meta-
1999;27:2812-7. analysis on efficacy and pneumonia rate. Crit Care
Med 1991;19:942-9.

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-129
 Supportive and Preventive Medicine

Prophylaxis Against Deep Venous Thrombosis or in critically ill patients with hepatic and/or renal
Pulmonary Embolism dysfunction. Pharmacotherapy 2006;26:452-60.
1. Beiderlinden M, Treschan TA, Görlinger K, et al. 12. Linkins LA, Dans AL, Moores LK, et al.
Argatroban anticoagulation in critically ill patients. Treatment and prevention of heparin-induced
Ann Pharmacother 2007;41:749-54. thrombocytopenia: Antithrombotic Therapy and
2. Cade JF. High risk of the critically ill for venous Prevention of Thrombosis, 9th ed: American
thromboembolism. Crit Care Med 1982;10:448-50. College of Chest Physicians Evidence-Based
3. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban Clinical Practice Guidelines. Chest 2012;141(2
for thromboprophylaxis in acutely ill medical suppl):495S-530S.
patients. N Engl J Med 2013;368:513-23. 13. Phung OJ, Kahn SR, Cook DJ, et al. Dosing frequency
4. Cook D, Crowther M, Meade M, et al. Deep venous of unfractionated heparin thromboprophylaxis: a
thrombosis in medical-surgical critically ill patients: meta-analysis. Chest 2011;140:374-81.
prevalence, incidence, and risk factors. Crit Care 14. Saugel B, Phillip V, Moessmer G, et al. Argatroban
Med 2005;33:1565-71. therapy for heparin-induced thrombocytopenia
5. Cook D, Meade M, Guyatt G, et al. Dalteparin versus in ICU patients with multiple organ dysfunction
unfractionated heparin in critically ill patients. N syndrome: a retrospective study. Crit Care
Engl J Med 2011;364:1305-14. 2010;14:R90.
6. De A, Roy P, Garg VK, et al. Low-molecular-weight 15. Shorr AF, Williams MD. Venous thromboembolism
heparin and unfractionated heparin in prophylaxis in critically ill patients. Observations from a
against deep vein thrombosis in critically ill randomized trial in sepsis. Thromb Haemost
patients undergoing major surgery. Blood Coagul 2009;101:139-44.
Fibrinolysis 2010;21:57-61.
7. Douketis J, Cook D, Meade M, et al. Prophylaxis End-of-Life Care
against deep vein thrombosis in critically ill patients 1. Brody H, Campbell ML, Faber-Langendoen K, et al.
with severe renal insufficiency with the low- Withdrawing intensive life-sustaining treatment—
molecular-weight heparin dalteparin: an assessment recommendations for compassionate clinical
of safety and pharmacodynamics: the DIRECT management. N Engl J Med 1997;336:652-7.
study. Arch Intern Med 2008;168:1805-12. 2. Global Atlas of Palliative Care at the End of Life.
8. Fraisse F, Holzapfel L, Couland JM, et al. Nadroparin Available at www.who.int/nmh/Global_Atlas_of_
in the prevention of deep vein thrombosis in acute Palliative_Care.pdf. Accessed December 11, 2014.
decompensated COPD. The Association of Non- 3. Treece PD, Engelberg RA, Crowley L, et al.
University Affiliated Intensive Care Specialist Evaluation of a standardized order form for the
Physicians of France. Am J Respir Crit Care Med withdrawal of life support in the intensive care unit.
2000;161:1109-14. Crit Care Med 2004;32:1141-8.
9. Gould MK, Garcia DA, Wren SM, et al. Prevention 4. Truog RD, Campbell ML, Curtis JR, et al.
of VTE in nonorthopedic surgical patients: Recommendations for end-of-life care in the
Antithrombotic Therapy and Prevention of intensive care unit: a consensus statement by the
Thrombosis, 9th ed: American College of Chest American College of Critical Care Medicine. Crit
Physicians Evidence-Based Clinical Practice Care Med 2008;36:953-63.
Guidelines. Chest 2012;141(2 suppl):227S-77S. 5. Wilson WC, Smedira NG, Fink C, et al. Ordering and
10. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE administration of sedatives and analgesics during
in nonsurgical patients: Antithrombotic Therapy the withholding and withdrawal of life support from
and Prevention of Thrombosis, 9th ed: American critically ill patients. JAMA 1992;267:949-53.
College of Chest Physicians Evidence-Based
Clinical Practice Guidelines. Chest 2012;141(2
suppl):195S-226S.
11. Kiser TH, Fish DN. Evaluation of bivalirudin
treatment for heparin-induced thrombocytopenia

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-130
 Supportive and Preventive Medicine

ANSWERS AND EXPLANATIONS TO PATIENT CASES

1. Answer: A 4. Answer: C
The mnemonic FAST-HUG stands for Feeding, Once the risk factors are no longer present, SUP should
Analgesia, Sedation, Thromboembolic prophylaxis, promptly be discontinued (Answer C is correct).
Head of bed elevation, stress Ulcer prophylaxis, and This patient no longer has risk factors (mechanical
Glycemic control. Using this mnemonic as a “checklist” ventilation, coagulopathy acute kidney failure, and
every day for each critically ill patient will assist in severe sepsis). In addition, there is no evidence that SUP
maximizing therapeutic interventions and promote should be continued until hospital or ICU discharge or
patient safety. This patient would benefit from having when antimicrobial therapy is complete (Answers A, B,
enteral nutrition initiated (patient has an NGT already and D are incorrect).
placed and has a working GI tract), a sedative interruption
(current RASS [Richmond Agitation Sedation Scale] is 5. Answer: C
above the designated goal), and the addition of SUP (risk The patient has several risk factors for VTE, including
factors include mechanical ventilation) (Answer A is immobility and respiratory failure, making heparin 5000
correct). Critically ill patients with risk factors for VTE, units subcutaneously twice daily an appropriate choice
should remain on VTE prophylaxis (Answers B and D for VTE prophylaxis (Answer C is correct). Neither
are incorrect); moreover, sliding-scale insulin should enoxaparin nor fondaparinux is appropriate for this
be initiated when the patient is not critically ill, adding patient, who has acute kidney injury with an estimated
another reason why Answer B is incorrect, as well as CrCl of less than 20 mL/minute (Answers B and D are
making Answer C incorrect. incorrect). Intermittent pneumatic compression would
be insufficient in a patient with no contraindication to
2. Answer: C pharmacologic prophylaxis (Answer A is incorrect).
Two independent risk factors for SRMD include
respiratory failure requiring mechanical ventilation for 6. Answer: A
48 hours or longer and coagulopathy (platelet count less Diagnosing HIT is difficult in a critically ill patient
than 50,000/mm3, INR greater than 1.5, or aPTT time because there are many alternative causes of
greater than 2 times the control). This patient has both thrombocytopenia. Clinical assessment is essential
of these risk factors. In addition, this patient has severe in diagnosing HIT because of the immediate need for
sepsis, as evidenced by end-organ dysfunction and acute treatment and the delay in laboratory testing (Answers B
kidney injury (Answer C is correct). Answers A, B, and D and D are incorrect). Clinically, this patient has a greater
are incorrect as this patient has four risk factors for SUP. than 50% drop in platelet count within 5 days of receiving
heparin. This patient had a DVT 2 months ago, when he
3. Answer: D was probably exposed to heparin products. The first step
Antacids are not recommended for routine use because in managing suspected HIT is to ensure that all forms of
of their frequency of administration, adverse effects, heparin are discontinued, including flushes or heparin-
and interactions (Answer B is incorrect). In a large coated catheters. The next step is to initiate an alternative
randomized controlled trial, sucralfate was inferior to form of anticoagulation. Direct thrombin inhibitors are
H2RAs in preventing clinically significant bleeding from the agents of choice for anticoagulation in the setting of
SRMD and is generally not recommended because of acute HIT because they have no cross-reactivity with
its adverse effect profile (Answer A is incorrect). Proton heparin (Answer A is correct). Factor Xa inhibitors have
pump inhibitors are no better than H2RAs in preventing been used in the management of HIT; however, they
SRMD and are associated with increased infectious would not be the best choice in this patient, who has
complications, including pneumonia and CDI (Answer acute kidney injury (Answer C is incorrect).
D is correct). Meta-analyses have favored PPIs to H2RAs
for GI bleeding; however, the individual trials included
lacked methodological quality (Answer C is incorrect).

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-131
 Supportive and Preventive Medicine

7. Answer: D
Warfarin can be initiated (Answer C is incorrect) once
the platelet count has recovered to at least 150,000/mm3
and after at least 5 days of therapy with an alternative
anticoagulant (Answer D is correct). Because this
patient’s platelet counts have not reached 150,000/mm3
and only 3 days of argatroban have been completed,
warfarin therapy should not be initiated at this time
(Answers A and B are incorrect). Argatroban should
be continued, and warfarin may be considered at low
doses (maximum 5 mg) as the platelet count continues to
recover (Answer B is incorrect).

8. Answer: D
Up to 50% of seriously ill, hospitalized patients will
experience moderate or severe pain. Opioids are the
mainstay of treatment for patients experiencing pain and
dyspnea at the end of life. Assessing pain in the ICU can
be particularly challenging because many patients have
impaired cognition and communication. The use of vital
signs alone should not be used alone for pain assessment
(Answer A is incorrect). Evidence suggests that pain can
be improved with correct dosing and titration (Answers
B and C are incorrect) without causing respiratory
depression or hastening death (Answer D is correct).

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-132
 Supportive and Preventive Medicine

ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS

1. Answer: C 4. Answer: A
The FAST-HUG mnemonic can serve as a “checklist” Proton pump inhibitors are potent inhibitors of gastric
for every patient admitted to the ICU. Every patient acid production and are the drug of choice for treatment of
should be assessed for a sedation interruption in an gastroesophageal reflux disease. To date, no prospective
effort to minimize sedative exposure and maintain a randomized controlled trials have evaluated the risk
light level of sedation (Answer C correct). To decrease of CDI with PPI use (Answer B is incorrect). A cohort
the risk of nosocomial pneumonia, each patient should study showed an increased risk of CDI when PPIs were
have his or her head 30–45 degrees above the head of used more frequently than daily (Answer C is incorrect).
the bed (Answer C correct). Enteral nutrition should be All published trials assessing the risk of CDI with PPI
initiated as soon as possible—typically, once the patient use have been limited by the inconsistent definitions of
is stabilized; however thromboprophylaxis should be CDI and the variable infection control practices (Answer
initiated in every patient, using pharmacologic agents D is incorrect). Gastric juice is strongly bactericidal for
preferentially to mechanical prophylaxis (Answer B is microorganisms. Proton pump inhibitors are commonly
incorrect). Stress ulcer prophylaxis should be initiated used to increase the gastric pH; therefore, they act as a
only in patients who have risk factors present and should potential risk factor for CDI (Answer A is correct).
be discontinued when the risk factor does not exist
(Answer A is incorrect). Insulin infusions should be 5. Answer: B
initiated only if blood glucose readings are not within Low-dose unfractionated heparin or low-molecular-
the range of 140–180 mg/dL (Answer D is incorrect). weight heparin should be initiated for VTE prophylaxis
in a critically ill patient over no prophylaxis (Answer
2. Answer: C D is incorrect). Intermittent pneumatic compression
Sucralfate forms a protective barrier over the surface devices would be insufficient prophylaxis in a patient
of the stomach, reducing exposure to acidic gastric with several risk factors for VTE (Answer A is incorrect).
contents; therefore, sucralfate has no effect on gastric pH A continuous infusion of heparin is inappropriate for the
(Answer A is incorrect). Compared with H2RAs, PPIs prevention of VTE (Answer C is incorrect). Enoxaparin
seem to be more effective in reducing gastric acidity, but may be used in a critically ill patient with stable renal
no well-conducted trial has shown PPIs to be superior function for VTE prophylaxis (Answer B is correct).
in preventing clinically significant bleeding (Answer B
is incorrect). Tolerance to any H2RA may occur, but not 6. Answer: A
with PPIs (Answer C is correct). Antacids have some This patient sustained a closed-head injury, placing her
effect on reducing stress ulceration, provided the gastric at high risk of VTE (Answer D is incorrect). The patient
pH is kept above 3.5, but frequent dosing (up to every 2 is at high risk of having major bleeding and experiencing
hours) is required to achieve this goal, making their use acute kidney injury; therefore, use of a low-molecular-
impractical (Answer D is incorrect). weight heparin or a factor Xa inhibitor would not be
the best option in this patient (Answers B and C are
3. Answer: D incorrect). Mechanical prophylaxis with intermittent
The patient has an indication for SUP (mechanical pneumatic compression devices is preferred to no
ventilation). The patient has an NGT in place and is prophylaxis in the absence of lower extremity injury
tolerating tube feedings, indicating a functioning gut; until the bleeding risk is no longer present (Answer A
therefore, intravenous therapy is not required (Answers A is correct).
and B are incorrect). The patient has erosive esophagitis,
for which a PPI will be more effective than an H2RA 7. Answer: D
(Answer C is incorrect). Omeprazole suspension Clinical assessment is essential in the diagnosis of HIT
is effective in the prevention of SRMD; therefore, because of the immediate need for treatment and the
omeprazole suspension would be the most appropriate delay in laboratory testing. Although this patient did
choice for this patient (Answer D is correct). experience a 50% decrease in his platelet count, the

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-133
 Supportive and Preventive Medicine

characteristic onset of the platelet count fall in HIT is

5–10 days after heparin initiation. Clinical prediction
rules to assist in determining the probability of HIT have
been developed such as the 4T’s score. Patients with
a low 4T’s score (0–3) have a very low probability of
HIT (Answer D is correct). Direct thrombin inhibitors
are the agents of choice for anticoagulation in the setting
of acute HIT because they have no cross-reactivity with
heparin. Initiating these agents in the setting of a low
probability of HIT may lead to an unnecessary increase in
bleeding risk (Answer B is incorrect). If HIT were highly
suspected in this patient, the first step in the management
of HIT would be to ensure the discontinuation of all
forms of heparin, including flushes or heparin-coated
catheters (Answer C is incorrect). The next step would
be to initiate an alternative form of anticoagulation
(Answer A is incorrect).

8. Answer: C
General considerations in the critically ill patient at the
end of life include minimization of uncomfortable or
unnecessary procedures, tests, or treatments, including
fingersticks, Foley catheters, and routine vital signs
(Answers A, B, and D are incorrect). Symptom
management of pain and anxiety, fever, cough, secretions,
nausea and vomiting, and delirium should be considered
in the dying patient (Answer C is correct).

ACCP Updates in Therapeutics® 2015: Critical Care Pharmacy Preparatory Review Course

1-134