Prophylaxis in the hospital
a 2009 update
Scott Akin MD
OUTLINE
• Deep vein thrombosis/ pulmonary
embolism prophylaxis (VTE prophylaxis)
• Stress ulcer prophylaxis (SUP)
• Contrast nephropathy (CIN) prevention
Venous Thromboembolism
(DVT and PE)
• Background
– Risk of VTE 130 times greater among hospitalized pts
– 10% of all hospital deaths can be attributed to PE
– Without prophylaxis, medical pt has VTE risk 5-15%
– PE = most common preventable cause of hospital death
– VTE prophylaxis routinely used in surgical patients, but
not widely practiced in medical pts
• 40% eligible medical pts got prophylaxis in ENDORSE study
• 60% in the IMPROVE study
– Around ¾ PE deaths are medical (not surgical) patients
VTE Prophylaxis in Medical
Patients
• There is no formal, validated risk
assessment model for medical patient, as
there is in surgical patients
• Bottom line: generally, medical patients
who have limited mobility for > 3 days and
have one RF should get VTE prophylaxis
2004 ACCP Guidelines for VTE
Prophylaxis in Medical Patients
“In acutely ill medical patients who have been
admitted to the hospital with CHF or severe
respiratory disease, OR who are confined to
bed and have one or more additional risk
factors, we recommend prophylaxis with
unfractionated heparin (UFH) or low
molecular weight heparin (LMWH…aka
enoxaparin/lovenox)”
2004 ACCP Guidelines for VTE
Prophylaxis in Medical Patients
“We recommend, on admission to the ICU, all
patients be assessed for their risk for VTE.
Accordingly, most patients should receive
thromboprophylaxis”
Risk Factors for VTE
• Malignancy (&
myeloprolif. Disorders)
• Indwelling catheter
• CHF
• Pregnancy
• OCPs/HRT
• IBD
• Paralysis
• Nephrotic syndrome
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Vericose veins
Previous VTE
Obesity
Smoking
History of MI
History of Afib
DM
Thrombiphilias (fact 5 L)
What Is the Best Drug and
Dosing for DVT Prophylaxis?
• Short answer: probably low molecular
weight heparin (enoxaparin/lovenox)…but
much more expensive than unfractionated
heparin.
• How about Unfractionated heparin BID vs.
TID?…
2007 Meta-analysis
Wein Et. Al Arch Intern Med 167 (14)
• 36 prospective RCTs including 48,000 pts
• Update on a 2000 meta-analysis with fewer pts
• Conclusions:
– Both UFH and LMWH (enoxaparin/lovenox) reduce
DVT & PE in hospitalized patients, but neither affect
mortality
– LMWH (vs. UFH of any dose or frequency) associated
with reduced risk DVT
Wein’s 2007 Meta-analysis
-Both LMWH & UFH reduce PE risk about
the same
-Both LMWH & UFH increase the risk of
major bleeding about the same
-No difference in thrombocytopenia
-Injection site hematoma less common with
LMWH
Wein’s 2007 Meta-analysis
-Cost of LMWH more, but maybe more cost
effective in the end because decreases
number of DVTs.
-UFH dose of TID was more effective than
the UFH dose of 5000 BID in reducing
DVT …without any increase risk of
bleeding.
Another Meta-analysis
Chest 2007; 131;507-516
• 8000 patients, 12 studies
• BID vs. TID unfractionated heparin
• TID heparin showed a trend toward a
decrease in pulmonary embolism
• Significant decrease in the incidence of the
combined outcome of proximal DVT or PE
• BUT significant increase in major bleeding
events with TID dosing (especially in elderly
and thin)
– Yes, that conflicts with the previous meta-analysis
2008 Chest Guidleines
• “There is no compelling evidence that
unfractionated heparin (UFH) should be
administered three times daily in
preference to twice daily in medical
patients, although these two regimens
have never been directly compared.”
2008 Chest Guidelines
• “In a metaanalysis that included almost
8,000 patients, three-times-daily UFH
was associated with significantly more
major bleeding events, while there was
a nonsignificant trend toward more
thromboembolic events with twice-daily
UFH.”
TID Vs. BID…will We Ever
Really Know?
• Probably not…
• Randomized controlled trial would take
a study of 150,000 to show a
difference...And given heparin is generic
there is no financial incentive to do it.
What Are We Doing at CCRMC?
• First do no harm: “default” order for DVT
prophylaxis will be heparin 5000 units SQ BID
• If patient has multiple DVT risk factors consider
heparin 5000 units SQ TID or Enoxaparin 40 units
daily….But only IF patient is low bleeding risk:
- Not “old” (>65-70??)
- Not “low body weight” (< 50kg…??)
- Stable Hemoglobin
- No history of bleeds
VTE prophylaxis summary
• Assess every patient for VTE prophylaxis based
on their mobility status and risk factors
• Encourage early ambulation
• LMWH may be better than UFH…but $$$$
• Generally stick with BID UFH…unless multiple
DVT risk factors and low bleeding risk
• Stay tuned for guidelines on extended prophylaxis
in the high risk patient
Next topic: Stress ulcer
prophylaxis
• Background:
– Stress ulcers= stomach (but sometimes duodenal or
distal esophagus) erosions that can bleed (usually
“ooze,” but if deeper can cause massive hemorrhage).
– Physiology: Disruption of balance between acid
production (increases) and glycoprotein mucosal
protection barrier (breaks down from refluxed bile
salts/build up of uremic toxins)
– In shock/trauma: Perfusion impaired  ischemia
mucosal barrier breakdown
Stress Ulcer Risk Factors
-Mechanical
ventilation
-coagulopathy
-Shock/sepsis
-Kidney/Liver failure
-Trauma (especially head/spine)
-Severe burns
-Organ transplant
-History of PUD or UGIB
SUP Official Guidelines
• 1999 American Society of Health System
Pharmacists…SUP recommended in:
– All ICU patients with a coagulopathy or pts intubated >
48 hours
– Pts with Hx GIB w/in 1 yr PTA
– Pts with two of the following: Sepsis, ICU stay > 1
week, occult bleeding > 6 days, high dose steroids
– GCS <10
– Burn patients (>35%BSA)
– Consider in: Some trauma pts (ISS >16), Post
transplant pts, Liver failure, Spinal cord injury pt
SUP guidelines (continued)
• 1999 American Society of Health System
Pharmacists:
– “SUP is not recommended for adult patients in
non-ICU settings”
SUP since 1999
• Since then SUP has become much more
common in general medicine (non-ICU)
patients with little evidence to support such
use…why?
– Inadvertently continuing SUP after acute reason
for its initiation has resolved (extubated and
transferred to floor…all meds continued).
– Extrapolating ICU data to no-ICU patients
Downside of inappropriate SUP
meds
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Giving a patient a med that is not indicated
Cost
Increase risk of C-diff related disease
Increase risk of drug-drug interactions
Potential increase risk of Pneumonia
– Rise in gastric PH may promote growth of
bacteria in stomach (GN bacilli in duodenum)
– Studies have been conflicting
10 years since 1999
Who should get SUP???
Generally only critically ill ICU patients who are:
– Intubated > 48 hours
– Coagulopathic
Consider in ICU patient with multiple other risk
factors
Stress Ulcer Risk Factors
Mechanical ventilation
-coagulopathy
-Shock/sepsis
-Kidney/Liver failure
-Trauma (especially head/spine)
-Severe burns
-Organ transplant
-History of PUD or UGIB
OK, so they REALLY qualify for
SUP…what do you give them?
• Antacids: Not ideal because you have to give
them every 1-2 hours
• Sucralfate: The most rigorous RTC comparing to
ranitidine, showed more GIBs with sucralfate (Crit
care medicine 2005 33:760)
• H2 Blockers: Efficacy for SUP well documented,
generally well tolerated**
• PPIs: Data on efficacy less extensive than for the
above, but well tolerated, side effects for short
term use are rare, and PO is now generic.
“expert opinion”
• Oral PPI for those who can take them
(better than H2 blockers for decreasing PH)
• IV H2 Blockers in those who cannot eat
(“expert” opinion that the “far greater cost
of IV PPIs outweighs the nominally greater
efficacy that may exist”)
Don’t forget to feed your patient
• Entral nutrition may reduce incidence of
stress ulcers/GIB
• Protective effect of nutrition is NOT due to
change in gastric PH…it is due to
preventing the loss of energy stores of the
gastric epithelium (suggested by the fact
that TPN patients have less stress ulcers).
Next Topic: Contrast Induced
Nephropathy (CIN) Prevention
• Definition: 0.5mg/dl or 25% increase in creatinine
following contrast administration (within 24
hours, up to 5 days later)
• 3rd most common cause of ARF in hospital
• 4-11% incidence of CIN in mild-mod CRI
• Higher rates in DM patients, or pt with RFs
• Generally no prevention measures necessary when
Cr<1.5 or GFR >50-60…remember, serum Cr
may overestimate GFR in older, thiner, patients
CIN risk factors
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DM
Age >75
Periprocedural volume depletion
CHF
Cirrhosis
CRI
NSAID use
CIN Prevention
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Do they really need contrast?
Can you do a u/s, or MRI?
Avoid high Osmolal agents (1400-1800)
Use “iso-osmolal” (290) agents rather than
“low osmolal” (500-850…still increased
osm compared to plasma)
• AVOID VOLUME DEPLETION, NSAIDS,
and nephrotoxins
CIN Prevention: Meds/IVF prior
• Multiple conflicting studies..here are just 2:
– NEJM 2006; 354:4 “additional fluids should be
given, although the optimal regimen is
uncertain” … “N-acetylcystine is not
recommended…”
– Circulation 2007; 115:1211(REMEDIAL trial):
Bicarb + NAC is superior to saline + NAC or
saline + NAC + ascorbic acid.
7 CIN Studies: Sodium Bicarb
vs. Sodium Chloride
• Five prospective trials (REMEDIAL was
the largest) each concluded that bicarb is
superior to NS
• Two concluded there was no difference
• Differences in design, definitions of CIN,
and patient populations make direct
comparisons difficult
• Overall bicarb comes out ahead…I guess
CIN prevention: UTD
recommendations
• “we recommend isotonic IVF prior to and
continued for several hours after contrast
administration…optimal type of IVF and timing
are not well established”
– Isotonic bicarb (3 amps in 850ml D5W) at 3 ml/kg for
one hr prior, then at rate of 1ml/kg for 6 hours after
procedure OR NS at 1ml/kg for at least 2, ideally 6-12
hrs pre and 6-12 hrs post
AND
– NAC 1200 mg PO BID day before and day of
CIN prevention: Clinical pearl
• Before ordering NAC and/or IVF/Bicarb,
ask yourself: Is this intervention which is
supported by weak evidence (at best) going
to DELAY a study…and possibly DELAY
patient care??
Conclusions
• Assess ALL your patients daily for need of DVT
prophylaxis
• Ditto for Peptic ulcer disease prophylaxis, BUT
ONLY IN YOUR ICU PATIENTS
• PUD prophylaxis should almost always be stopped
once transferred out of ICU
• Prior to contrast CT, check a creatinine, and if
>1.5, consider risks and benefits of the CT scan.
If really needed, make sure they are hydrated and
consider giving them Bicarb+D5W and/or NAC