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

• 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-analysisWein 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-analysisChest 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

• 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 1999Who 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

• DM

• Age >75

• Periprocedural volume depletion

• CHF

• Cirrhosis

• CRI

• NSAID use

CIN Prevention

• 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