APE in Critical Care.leeper

8/7/2019 APE in Critical Care.leeper

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Acute Pulmonary Embolism in theAcute Pulmonary Embolism in theCritical Care Unit: Is it different ?Critical Care Unit: Is it different ?

Kenneth V. Leeper Jr. MDKenneth V. Leeper Jr. MD

Associate Professor of MedicineAssociate Professor of Medicine

Division of Pulmonary, Allergy and Critical Care MedicineDivision of Pulmonary, Allergy and Critical Care Medicine

Emory School of MedicineEmory School of Medicine

Atlanta, GeorgiaAtlanta, Georgia


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Acute Pulmonary Embolism in theAcute Pulmonary Embolism in the

Critical Care Unit: Is it different ?Critical Care Unit: Is it different ? Case PresentationCase Presentation

The incidence of VTE in MICU patientsThe incidence of VTE in MICU patients

Clinical Clues of VTE in MICU PatientsClinical Clues of VTE in MICU Patients

Treatment of VTE in CriticallyTreatment of VTE in Critically Ill PatientsIll Patients

Impact of current prophylaxis on theImpact of current prophylaxis on the

prevention of DVT in MICU patientsprevention of DVT in MICU patients


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The Risk Factor and Incidence of VTE inThe Risk Factor and Incidence of VTE in

MICU patientsMICU patients

Clinical Clues of VTE in MICU PatientsClinical Clues of VTE in MICU Patients Impact of current prophylaxis on theImpact of current prophylaxis on the



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VTE in the ICUVTE in the ICU Case StudyCase Study

5858--yy--o AAM presented to the MICU with ao AAM presented to the MICU with a

RML and RLL pneumoniaRML and RLL pneumonia

Patient required 100% nonPatient required 100% non--rebreather torebreather to

maintain Omaintain O22 saturation > 90%saturation > 90% PMH: History of right lower extremity DVTPMH: History of right lower extremity DVT

after a long car drive 8 years PTAafter a long car drive 8 years PTA No medications, no allergiesNo medications, no allergies


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Physical examPhysical exam

Weight 112 kg, RR 36, BP 142/78 mm Hg,Weight 112 kg, RR 36, BP 142/78 mm Hg,T 38.7T 38.7 C, egophony right posterior chest,C, egophony right posterior chest,2/6 SEM; rest of exam unremarkable2/6 SEM; rest of exam unremarkable

OO22 sat 91% on 100% NRMsat 91% on 100% NRM

Labs: WBC 15,600 (84 PMNs, 10 bands)Labs: WBC 15,600 (84 PMNs, 10 bands)

CXR: RML/RLL pneumoniaCXR: RML/RLL pneumonia Initial Rx: ceftriaxone / azithromycinInitial Rx: ceftriaxone / azithromycin

DVT prophylaxis:DVT prophylaxis: UFH 5,000 SC q 8 hUFH 5,000 SC q 8 h


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MICU courseMICU course

Patient required face mask ventilation with BiPAP forPatient required face mask ventilation with BiPAP for48 hours then weaned to 50% Venturi mask48 hours then weaned to 50% Venturi mask

Day 4: persistent fever with episode of hypotension thatDay 4: persistent fever with episode of hypotension that

responded to fluid therapyresponded to fluid therapy Day 5: persistent fever, WBC normalizing; LE DopplersDay 5: persistent fever, WBC normalizing; LE Dopplers

obtained: right proximal LE DVTobtained: right proximal LE DVT Rx with weightRx with weight--basedbased

UFHUFH Evening of day 5: episode of hypotension requiring fluidsEvening of day 5: episode of hypotension requiring fluids

and brief vasopressor therapyand brief vasopressor therapy spiral CT scan of thespiral CT scan of the

chest obtainedchest obtained


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Spiral CT scan of the chestSpiral CT scan of the chest large bilaterallarge bilateral

PEPE

Both troponin and BNP elevatedBoth troponin and BNP elevated

Cardiology fellow performedCardiology fellow performedechocardiogram: Severe RV enlargementechocardiogram: Severe RV enlargement

with RV wall motion abnormalitieswith RV wall motion abnormalities Management options?Management options?


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The Risk Factor and Incidence of VTE inThe Risk Factor and Incidence of VTE in

MICU patientsMICU patients

Diagnosis of VTE in MICU PatientsDiagnosis of VTE in MICU Patients Impact of current prophylaxis on theImpact of current prophylaxis on the



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The Challenge of VTE in Critically IllThe Challenge of VTE in Critically Ill

PatientsPatients Critically ill patients commonly develop DVTCritically ill patients commonly develop DVT

Rate varies from 22Rate varies from 22 60% depending on60% depending on

patient characteristicspatient characteristics

Methods of prophylaxis are not universalMethods of prophylaxis are not universal In highIn high--risk groups more effectiverisk groups more effective

prophylaxis regimens are neededprophylaxis regimens are needed


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Clinical Risk Factors for VTE inClinical Risk Factors for VTE in

Critically Ill PatientsCritically Ill Patients

Factors before ICU admissionFactors before ICU admission

Recent surgeryRecent surgery Trauma, burnsTrauma, burns

Malignancy and treatmentMalignancy and treatment

SepsisSepsis Immobilization / bed rest,Immobilization / bed rest,

stroke, spinal cord injurystroke, spinal cord injury

Increasing ageIncreasing age

Heart / respiratory failureHeart / respiratory failure

Previous VTEPrevious VTE

Pregnancy / puerperiumPregnancy / puerperium

EstrogensEstrogens

Additional factors acquired in ICUAdditional factors acquired in ICU

Central venous linesCentral venous lines SepsisSepsis

Pharmacologic interventions:Pharmacologic interventions:

sedation, paralysissedation, paralysis Mechanical venti lationMechanical ventilation

An autopsy study revealed that 20%of patients who died in the ICU

had evidence of PE. Moser KM.

JAMA 1981.


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Prevalence of of DVTPrevalence of of DVT

Among Patients in the MICUAmong Patients in the MICU

Ultrasound in 100 patients admitted to MICU forUltrasound in 100 patients admitted to MICU for> 48 hours> 48 hours

Incidence of DVTIncidence of DVT 33%33%

61% received DVT prophylaxis61% received DVT prophylaxis

Patients with DVTPatients with DVT more likely to have a historymore likely to have a history

prior VTEprior VTE Hospital MRHospital MR 36% w/ DVT vs. 24% w/o DVT (36% w/ DVT vs. 24% w/o DVT (PP==

0.028)0.028)

Hirsch DR, et al.Hirsch DR, et al. JAMAJAMA. 1995;274:335. 1995;274:335--7.7.


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VTE on Presentation to the ICUVTE on Presentation to the ICU

Prospective study of 196 COPD patientsProspective study of 196 COPD patients

admitted to a respiratory ICUadmitted to a respiratory ICU Ultrasound on day of admissionUltrasound on day of admission

21/196 (11%)21/196 (11%) had DVT, all above the kneehad DVT, all above the knee 18/2118/21 asymptomaticasymptomatic

No differences in age, ABG, FEVNo differences in age, ABG, FEV11, or dyspnea, or dyspnea Physical exam not helpful to detect DVTPhysical exam not helpful to detect DVT

Schonhofer B, Kohler D.Schonhofer B, Kohler D. RespirationRespiration. 1998;65:175. 1998;65:175--7.7.


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VTE in Decompensated CHF patientsVTE in Decompensated CHF patients

requiring CCU admissionrequiring CCU admission 198 patients admitted with severe198 patients admitted with severe

decompensated CHF over 31 month perioddecompensated CHF over 31 month period 18/19818/198 acute PE / 8 of 18 (44.4%) DVTacute PE / 8 of 18 (44.4%) DVT

Thromboprophylaxis: 12/18 (66.7%) vsThromboprophylaxis: 12/18 (66.7%) vs126/180 (70%) NS126/180 (70%) NS

Independent risk factors associates with PEIndependent risk factors associates with PE

CancerCancer OR 26.9OR 26.9

RV abnRV abn OR 9.7OR 9.7

Prev. VTE OR 9.1Prev. VTE OR 9.1Darze ES.et.al. Chest 2005; 128;2576 - 2580


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DVT in medicalDVT in medical --surgical critically il l patients:surgical critically il l patients:prevalence, incidence and risk factors. Cook D et.al.prevalence, incidence and risk factors. Cook D et.al.Crit. Care Med. 2005 33:1565Crit. Care Med. 2005 33:1565--7171

Prospective cohort study closed universityProspective cohort study closed university

affil iated ICUaffil iated ICU Consecutive patients enrolled, excludedConsecutive patients enrolled, excluded

trauma, orthopedic surgery, pregnancy andtrauma, orthopedic surgery, pregnancy andlife support withdrawnlife support withdrawn

Bilateral LE US within 48 hrs of admissionBilateral LE US within 48 hrs of admission

and twice weekly and if DVT was suspectedand twice weekly and if DVT was suspected Thromboprophylaxis was protocol directedThromboprophylaxis was protocol directed

and universaland universal


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DVT in medicalDVT in medical --surgical critically il l patients:surgical critically il l patients:prevalence, incidence and risk factors. Cook D et.al.prevalence, incidence and risk factors. Cook D et.al.Crit. Care Med. 2005 33:1565Crit. Care Med. 2005 33:1565--7171

261 patients with APII of 25.5261 patients with APII of 25.5

Prevalence of DVT on admissionPrevalence of DVT on admission 2.7%2.7%

Incidence over the ICU stayIncidence over the ICU stay 9.6%9.6%

Independent risk factors for DVTIndependent risk factors for DVT Personal or FH of VTEPersonal or FH of VTE HR 4.0HR 4.0

ESRDESRD HR 3.7HR 3.7

Platelet transfusionsPlatelet transfusions HR 3.2HR 3.2

Vasopressor useVasopressor use HR 2.8HR 2.8

Consequences of DV

Longer ICU stay p=0.0

Longer duration on M

Longer hospitalization


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Ibrahim EH, Iregui M, Prentice D, Sherman G, Kollef M, Shannon WIbrahim EH, Iregui M, Prentice D, Sherman G, Kollef M, Shannon W..

Critical Care Medicine.Critical Care Medicine. 2002;30:7712002;30:771--4.4.

Objective: Determine the prevalence of DVT among patients

requiring prolonged mechanical ventilation in the ICU

Deep Vein ThrombosisDeep Vein Thrombosis

During Prolonged MechanicalDuring Prolonged MechanicalVentilation Despite ProphylaxisVentilation Despite Prophylaxis


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DVT During Prolonged MechanicalDVT During Prolonged Mechanical

Ventilation Despite ProphylaxisVentilation Despite Prophylaxis

MeasurementsMeasurements

Total of 110 patients requiring mechanicalTotal of 110 patients requiring mechanical

ventilation for > 7 days were enrolledventilation for > 7 days were enrolled Prophylaxis against DVT employed in 110Prophylaxis against DVT employed in 110

patients (100%)patients (100%)

26 patients (23.6%) developed DVT26 patients (23.6%) developed DVT

Ibrahim EH, et al.Ibrahim EH, et al. Crit Care MedCrit Care Med. 2002;30:771. 2002;30:771--4.4.


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Ventilation Despite ProphylaxisVentilation Despite Prophylaxis

0

5

10

15

20

1 2 3 4

Risk factors for DVTRisk factors for DVT Underlying malignancyUnderlying malignancy

Renal failureRenal failure

GI disturbancesGI disturbances

Duration of CVP lineDuration of CVP line

Clinical outcomesClinical outcomes

PEPE more common withmore common with

DVT (11.5 vs. 0.0%)DVT (11.5 vs. 0.0%) No difference in LOS orNo difference in LOS or

mortalitymortality

Week DVT detectedWeek DVT detected


Percent

Percent


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Ventilation Despite ProphylaxisVentilation Despite ProphylaxisIncidence and PreventionIncidence and Prevention

19.2

80.8

73.1

26.9

0

10

20

30

40

50

60

70

80

90

UE-DVT LE-DVT UFH SCD

Percent

Percent



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Prevalence of VTE in and LTAC Setting:Prevalence of VTE in and LTAC Setting:

Preliminary Data. VTEPreliminary Data. VTE LTAC Study GroupLTAC Study Group Select LTAC ECLH: July 1 2006Select LTAC ECLH: July 1 2006 June 13,June 13,

20072007 50 admissions to the Emory Pulmonary50 admissions to the Emory Pulmonary

ServiceService

40/50 had screening US of the lower40/50 had screening US of the lowerextremities and upper extremities ( ifextremities and upper extremities ( if

clinically indicated)clinically indicated) 6/40 (15%)6/40 (15%) -- VTE events on screening US. 4VTE events on screening US. 4

LE DVT and 2 UE DVTsLE DVT and 2 UE DVTs


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Vasopressor Administration May Predispose ICUVasopressor Administration May Predispose ICUPatients to DVTPatients to DVT

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

Days in ICU

Vasopressors

DVT

Days in ICU

Patien

ts*

*Patients (9 of261) whoreceviedvasopressorsand developedDVT

Cook D et al. Crit Care Med. 2005;22:1565- 1571.

Multivariable analysis identified vasopressor administration as anindependent risk factor (hazard ratio 2.8, 95% CI 1.1 - 7.2) for DVT


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VTE in Severe Sepsis: Incidence of VTE in Severe sepsisVTE in Severe Sepsis: Incidence of VTE in Severe sepsistreated with Drotrecogin alfa with or without prophylactictreated with Drotrecogin alfa with or without prophylactic

heparin. Levy M. Abstract Chest 2006heparin. Levy M. Abstract Chest 2006

Xpress studyXpress study large phase 3B 28 day mortality andlarge phase 3B 28 day mortality and

the relative incidence of VTE in patients treated withthe relative incidence of VTE in patients treated withdrotrecogin alfa (DAA) with or without heparindrotrecogin alfa (DAA) with or without heparin

Dec 2002Dec 2002 July 2005July 2005

Adult pts with high risk for severe sepsisAdult pts with high risk for severe sepsis

All pts received DAAAll pts received DAA

Study drugs: heparin 5000Usc q 12 hrs, enoxaparin 40mgStudy drugs: heparin 5000Usc q 12 hrs, enoxaparin 40mg

sc qd and placebosc qd and placebo

Randomization: 1:1:2Randomization: 1:1:2

Lower extremity US 4 and 6 daysLower extremity US 4 and 6 days

S S f S


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VTE in Severe Sepsis: Incidence of VTE in Severe sepsisVTE in Severe Sepsis: Incidence of VTE in Severe sepsistreated with Drotrecogin alfa with or without prophylactictreated with Drotrecogin alfa with or without prophylactic

heparin. Levy M. Abstract Chest 2006heparin. Levy M. Abstract Chest 2006

1935 patients were enrolled and received DAA and1935 patients were enrolled and received DAA and

one of the study drugsone of the study drugs 959 placebo959 placebo

976 Heparins ( 498 UFH/478 LMWH)976 Heparins ( 498 UFH/478 LMWH)

Incidence of VTEIncidence of VTE Study periodStudy period heparinsheparins placebo pvalueplacebo pvalue

00--6 days6 days 4.6%4.6% 5.1%5.1% 0.60.6

00 28 days28 days 5.7% 7.0%5.7% 7.0% 0.260.26

Subgroups with highest incidence of VTE: previousSubgroups with highest incidence of VTE: previousVTE, age > 75, recent surgery, pts on baselineVTE, age > 75, recent surgery, pts on baselineheparin randomized to placebo VTE incidenceheparin randomized to placebo VTE incidence8.1%8.1%

S f C


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Sources of Thrombi: Central VeinSources of Thrombi: Central Vein

CatheterCatheter--Related Thrombi in the ICURelated Thrombi in the ICU Prospectively performed duplex scans justProspectively performed duplex scans just

before or within 24 hours after removing thebefore or within 24 hours after removing theIJ or subclavian CVL in ICU patientsIJ or subclavian CVL in ICU patients

208 lines studied208 lines studied Mean duration was 9Mean duration was 9 5 days5 days

CatheterCatheter--related clotrelated clot 33% of patients33% of patients

Timsit JF, et al.Timsit JF, et al. ChestChest. 1998:114;207. 1998:114;207--13.13.

fWh t i th b li t ti l f UE


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What is the embolic potential for UEWhat is the embolic potential for UE--

DVT?DVT?

PE%

S f Th bi HITS f Th bi HIT


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Sources of Thrombi:HITSources of Thrombi:HIT

DiagnosisDiagnosis Suspect if the platelet count drops belowSuspect if the platelet count drops below

150,000/mm150,000/mm33

while patient receiving UFH orwhile patient receiving UFH orLMWHLMWH

Suspect if the platelet count drops 50% fromSuspect if the platelet count drops 50% from

prepre--heparin baseline levelsheparin baseline levels Suspect if new thrombosis while the patientSuspect if new thrombosis while the patient

is receiving UFH or LMWHis receiving UFH or LMWH

Suspect if heparin resistance developsSuspect if heparin resistance develops Confirm with laboratory test (SRA, HIPA orConfirm with laboratory test (SRA, HIPA or

ELISA)ELISA)

I id f HIT d VTE Aft U fI id f HIT d VTE Aft U f


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Incidence of HIT and VTE After Use ofIncidence of HIT and VTE After Use of

UFH and LMWHUFH and LMWH Literature review: Identify studies using UFH orLiterature review: Identify studies using UFH or

LMWH for thromboprophylaxis or treatment in whichLMWH for thromboprophylaxis or treatment in whichnew or recurrent VTE and serologically confirmed HITnew or recurrent VTE and serologically confirmed HIT

10 studies10 studies

386 of 6,219 heparin386 of 6,219 heparin--treated patients had VTEtreated patients had VTE

32 of 386 VTE patients also had HIT32 of 386 VTE patients also had HIT

Among 32 cases of HIT in 386 VTE patientsAmong 32 cases of HIT in 386 VTE patients 17 cases occurred in 129 IV UFH17 cases occurred in 129 IV UFH--treated patients (13.2%)treated patients (13.2%)

14 cases occurred in 113 SC UFH14 cases occurred in 113 SC UFH--treated patients (12.4%)treated patients (12.4%)

1 case occurred in 144 LMWH1 case occurred in 144 LMWH--treated patients (0.7%)treated patients (0.7%)

Levine RL, et al.Levine RL, et al. ChestChest. 2006;130:681. 2006;130:681--7.7.

A t P l E b li i thA t P l E b li i th


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The Risk Factor and Incidence of VTE inThe Risk Factor and Incidence of VTE inMICU patientsMICU patients



Cli i l S t d Si f VTE iCli i l S t d Si f VTE i


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Clinical Symptoms and Signs of VTE inClinical Symptoms and Signs of VTE in

MICU PatientsMICU Patients NonspecificNonspecific

Persistent FeverPersistent Fever

In MV patients, unexplained increase inIn MV patients, unexplained increase in

minute ventilationminute ventilation ET CO2 measurementET CO2 measurement

In MV patientsIn MV patients Paradoxical hypercarbiaParadoxical hypercarbia

Neither baseline tests of molecularNeither baseline tests of molecular


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Neither baseline tests of molecularNeither baseline tests of molecularhypercoagulability nor Dhypercoagulability nor D--dimer levels predict DVTdimer levels predict DVT

in critically ill medical surgical patientsin critically ill medical surgical patients

Predicting patients who are harboringPredicting patients who are harboring

asymptomatic DVT or PE is a desirableasymptomatic DVT or PE is a desirableclinical goalclinical goal

Prospective study of 197 patients in a medProspective study of 197 patients in a med--

surg ICUsurg ICU

6 commercial D6 commercial D--dimer test and markers ofdimer test and markers of

hypercoagulabiltyhypercoagulabilty Conclusion: None of the test patients at riskConclusion: None of the test patients at risk

for DVTfor DVT

Crowther MA. Et.al intensive Care Med 2005;31: 48-55

Which diagnostic tests for VTEWhich diagnostic tests for VTE


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Which diagnostic tests for VTEWhich diagnostic tests for VTE

evaluation in the ICU patients?evaluation in the ICU patients? Depends upon clinical stability and renalDepends upon clinical stability and renal

function.function. Suspect VTESuspect VTE

Clinically stable + normal renal function orClinically stable + normal renal function orESRD: Spiral CT scan of the chest and eitherESRD: Spiral CT scan of the chest and either

CTV or Doppler US the extremitiesCTV or Doppler US the extremities

Clinically stable + ongoing renal insufficency: USClinically stable + ongoing renal insufficency: USof the extremities and TTE/TEEof the extremities and TTE/TEE

Clinically unstableClinically unstable

unable to move off the unit:unable to move off the unit:

US of the extremities and TEE ( esp in the MV pt.)US of the extremities and TEE ( esp in the MV pt.)

A t P l E b li i thAcute Pulmonary Embolism in the


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The Risk Factor and Incidence of VTE inThe Risk Factor and Incidence of VTE inMICU patientsMICU patients



ACCP Recommendations 2004ACCP Recommendations 2004


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ACCP Recommendations 2004ACCP Recommendations 2004Critical Care UnitCritical Care Unit

Upon admission to aUpon admission to a criticalcritical

care unitcare unit, all patients should, all patients shouldbe assessed for their risk ofbe assessed for their risk ofDVT/PEDVT/PE Accordingly, most should receiveAccordingly, most should receive

thromboprophylaxis (grade 1A)thromboprophylaxis (grade 1A)

LowLow--molecularmolecular--weight heparin (LMWH)weight heparin (LMWH)

LowLow--dose unfractionated heparin (UFH)dose unfractionated heparin (UFH)(q 12 h or q 8 h)(q 12 h or q 8 h)

Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S.

ACCP=American College of Chest Physicians

Initial Prophylaxis Considerations inInitial Prophylaxis Considerations in


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Initial Prophylaxis Considerations inInitial Prophylaxis Considerations in

Critical Care PatientsCritical Care PatientsHigh bleeding riskHigh bleeding risk

MechanicalMechanicalprophylaxisprophylaxis

Delay prophylaxis untilDelay prophylaxis until

high bleeding riskhigh bleeding risk

resolvesresolves

Screen for proximalScreen for proximalDVT with DUS in highDVT with DUS in high

risk patientsrisk patients

Usual bleeding riskUsual bleeding risk

LowLow--dose UFHdose UFH5,000 U q 8 h5,000 U q 8 h

LMWHLMWH

Combine AC andCombine AC and

mechanicalmechanical

prophylaxisprophylaxis

Geerts W, et al.Geerts W, et al. J Crit CareJ Crit Care. 2002;. 2002;1:951:95--104104


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Trials for VTE prophylaxis in the ICUTrials for VTE prophylaxis in the ICU

Study/YearStudy/Year Size, nSize, n Type of ICUType of ICU

PatientPatientMethod ofMethod of

DetectionDetectionControlControl Active TxActive Tx ResultsResults

CadeCade

19821982

119119 GeneralGeneral

ICUICUFUT for 14dFUT for 14d PlaceboPlacebo UFH 5000UFH 5000

bidbid29 v. 13%29 v. 13%

KapoorKapoor

1999abst1999abst

791791 MedicalMedical

ICUICU

DUS on q 3DUS on q 3

daysdays

PlaceboPlacebo UFH 5000UFH 5000

bidbid

31 v. 11%31 v. 11%

FraisseFraisse

20002000

223223 VentilatedVentilated

COPDCOPDVenographVenograph

by day 21by day 21PlaceboPlacebo NadroparinNadroparin

65 U/kg SC65 U/kg SC

q dayq day

28 v. 15%28 v. 15%

GoldhaberGoldhaber2000abst2000abst

325325 MedicalMedicalICUICU

DUS onDUS onday 3,7,10day 3,7,10

UFH 5000UFH 5000bidbid

Enoxapar.Enoxapar.300 mg bid300 mg bid

13 v. 16%13 v. 16%

CookCook 129129 MedMed--SurgSurg

ICUICUCUSCUS UFH 5000UFH 5000

bidbidDalteparinDalteparin

5000 IU/d5000 IU/d

NR v NRNR v NR

Do mechanical prophylaxis devicesDo mechanical prophylaxis devices


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Do mechanical prophylaxis devicesDo mechanical prophylaxis devices

reduce DVT incidence in ICU patients?reduce DVT incidence in ICU patients? Stimulates endogenous fibrinolysisStimulates endogenous fibrinolysis

production of plasminogen activatorproduction of plasminogen activator More efficacious in moderate risk postMore efficacious in moderate risk post--

operative patientsoperative patients Robust data lacking efficacy in medical ICURobust data lacking efficacy in medical ICU

patientspatients

INTERMITTENT PNEUMATIC COMPRESSION


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INTERMITTENT PNEUMATIC COMPRESSION

Indication: contraindication

to anticoagulation

Evidence: limited

Compliance: poor

Cost: $56.00 per day

equipment rental

Bleeding risk: NONE

Combination StrategyCombination Strategy


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Combination StrategyCombination Strategy

Randomized trial of 2,551 consecutiveRandomized trial of 2,551 consecutive

cardiac surgical patients. SCDs + LDUHcardiac surgical patients. SCDs + LDUH62% reduction in post62% reduction in post --surgical PE ( 1.5% vssurgical PE ( 1.5% vs

4%) *4%) *

Nonhemorrhagic StrokeNonhemorrhagic Stroke 40 fold reduction40 fold reduction

risk of DVT**risk of DVT**

*Ramos R. et.al. Chest 1996

**Kamran SL. Et.al. Neurology 1998

Role of Mechanical prophylaxis in preventing DVTRole of Mechanical prophylaxis in preventing DVT


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Role of Mechanical prophylaxis in preventing DVTRole of Mechanical prophylaxis in preventing DVTin high risk populations: Stannard JP. J Bone andin high risk populations: Stannard JP. J Bone and

Joint Surgery 2006: 88; 261Joint Surgery 2006: 88; 261 --266266 224 patients with blunt trauma224 patients with blunt trauma prospective studyprospective study

investigating VTEinvestigating VTE

Group A (97)Group A (97) enoxaparin SQ BID starting 24enoxaparin SQ BID starting 24 4848hrs after blunt traumahrs after blunt trauma

Group B (103)Group B (103) pulsatile foot pumps at time ofpulsatile foot pumps at time ofadmission and delayed enoxaparinadmission and delayed enoxaparin

Group AGroup A 13 DVTs (13.4%) and 2 PEs (2.1%)13 DVTs (13.4%) and 2 PEs (2.1%)

Group BGroup B 9 DVTs ( 8.7%) no PEs9 DVTs ( 8.7%) no PEs Group AGroup A 11 large and occulsive clots (11.3%)11 large and occulsive clots (11.3%)

Group BGroup B 3 large and occlussive clots (2.9%)3 large and occlussive clots (2.9%)p=0.025p=0.025


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Prevention of VTE in the Obese MICU PatientPrevention of VTE in the Obese MICU Patient


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Prevention of VTE in the Obese MICU PatientPrevention of VTE in the Obese MICU Patient

AntiAnti--Xa levels with fixed dose LMWH regimens correlateXa levels with fixed dose LMWH regimens correlatenegatively with BMI in crit ically il l patients (Priglinger Unegatively with BMI in crit ically il l patients (Priglinger U2003)2003)

Standard prophylactic regimens are twice as l ikely to fail inStandard prophylactic regimens are twice as l ikely to fail inorthopedic patients with BMI >32orthopedic patients with BMI >32

BMI > 32 VTE rate 32% vs 17% BMI 32 VTE rate 32% vs 17% BMI


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MICU Patient with Renal Insufficiency:MICU Patient with Renal Insufficiency:

VTE PreventionVTE Prevention Delayed renal clearance of LMWHs andDelayed renal clearance of LMWHs and

Fondaparinux very problematicFondaparinux very problematic Lack of outcomes based dataLack of outcomes based data

FDA approvedFDA approved enoxaparin 30 mg sq qd forenoxaparin 30 mg sq qd forpatients with CCL


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Elderly Patient in the MICUElderly Patient in the MICU

Mahe et.al. monitored antiMahe et.al. monitored anti --Xa levels in 68Xa levels in 68

consecutive hospitalized elderly patients (mean ageconsecutive hospitalized elderly patients (mean age82) receiving enoxaparin 40mg sq qd for82) receiving enoxaparin 40mg sq qd for

prophylaxisprophylaxis

Day 2 >50% had levels >0.5IU/ml ( optimal range)Day 2 >50% had levels >0.5IU/ml ( optimal range) Day 8 69.4 levels >0.5 IU/mlDay 8 69.4 levels >0.5 IU/ml

BE CAREFUL: consider empiric reduction ofBE CAREFUL: consider empiric reduction ofenoxaparin or use mechanical devices alone inenoxaparin or use mechanical devices alone in

elderly with low body weight < 45 kg or marginalelderly with low body weight < 45 kg or marginal

creatinine clearanecreatinine clearane

Patients with Prior HITPatients with Prior HIT


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Patients with Prior HITPatients with Prior HIT

Treatment of HIT is a thrombin inhibitorTreatment of HIT is a thrombin inhibitor

bridge to warfarin therapybridge to warfarin therapy Optimal future VTE prevention strategies areOptimal future VTE prevention strategies are

lacking in this populationlacking in this population

Avoid UFH and LMWHAvoid UFH and LMWH

DTIs are impractical for primary VTE prophylaxisDTIs are impractical for primary VTE prophylaxis

FondaparinuxFondaparinux indirect antiindirect anti --Xa inhibitor may beXa inhibitor may bea promising prophylaxis schemea promising prophylaxis scheme

Fondaparinux does not bind platelet factor 4Fondaparinux does not bind platelet factor 4

No apparent in vitro cross reactivity to HIT antibiodiesNo apparent in vitro cross reactivity to HIT antibiodies

Prophylactic Anticoagulation WithProphylactic Anticoagulation With


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Priglinger U, Delle Karth G, Geppert A, Joukhadar C, Graf S, BerPriglinger U, Delle Karth G, Geppert A, Joukhadar C, Graf S, Berger R,ger R,

HHlsmann M, Spitzauer S, Pabinger I, Heinz Glsmann M, Spitzauer S, Pabinger I, Heinz G

Critical Care MedicineCritical Care Medicine. 2003. 31:1405. 2003. 31:1405--409409

Objective: Determine antiObjective: Determine anti --Xa activit ies in crit ically il lXa activit ies in crit ically il l

patients and in noncritically i ll patients receivingpatients and in noncritically i ll patients receiving

prophylactic doses of subcutaneous enoxaparinprophylactic doses of subcutaneous enoxaparin

p y gp y gEnoxaparin: Is the Subcutaneous RouteEnoxaparin: Is the Subcutaneous Route

Appropriate in the Critically Ill?Appropriate in the Critically Ill?

Prophylactic Anticoagulation With Enoxaparin:Prophylactic Anticoagulation With Enoxaparin:


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y gIs the SC Route Appropriate in the Critically Ill?Is the SC Route Appropriate in the Critically Ill?

FF over timeover time = 39,= 39, PP= 0.001= 0.001

FF between groupsbetween groups = 23,= 23, PP= 0.001= 0.001

00 33 66 99 1212

1.01.0

0.80.8

0.60.6

0.40.4

0.20.2

00

Time (hours)Time (hours)

A

nti

A

nti--Xaactivity(U/mL)

Xaactivi

ty(U/mL)

ICU patients (n = 16)ICU patients (n = 16)

General ward (n = 13)General ward (n = 13)

Priglinger U, et al.Priglinger U, et al. Crit Care MedCrit Care Med. 2003. 31:1405. 2003. 31:1405--409.409.

Prophylactic Anticoagulation With Enoxaparin:Prophylactic Anticoagulation With Enoxaparin:I h SC R A i i h C i i ll Ill?


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Is the SC Route Appropriate in the Critically Ill?Is the SC Route Appropriate in the Critically Ill?

ICU patients (n = 16)ICU patients (n = 16)

General ward (n = 13)General ward (n = 13)FF over timeover time = 43.2,= 43.2, PP= 0.001= 0.001

FFbetween groupsbetween groups

= 1.5,= 1.5, PP= 0.2= 0.2

00 2424 4848 7272 9696 120120

1.01.0

0.80.8

0.60.6

0.40.4

0.20.2

00

Time (hours)Time (hours)

A

nti

A

nti--Xaactivity(U/mL)

Xaactivi

ty(U/mL)


Prophylactic Anticoagulation With Enoxaparin:Prophylactic Anticoagulation With Enoxaparin:I h SC R A i i h C i i ll Ill?I th SC R t A i t i th C iti ll Ill?


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Is the SC Route Appropriate in the Critically Ill?Is the SC Route Appropriate in the Critically Ill?

Conclusion: Critically i ll patients with normalConclusion: Critically i ll patients with normal

renal function demonstrated significantlyrenal function demonstrated significantlylower antilower anti --Xa levels in response to a singleXa levels in response to a single

daily dose of subcutaneous enoxaparin whendaily dose of subcutaneous enoxaparin when

compared with medical patients in the normalcompared with medical patients in the normal

ward.ward.


THE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY INTHE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY INAAMEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .MEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .H. Patel,H. Patel,

A V l D Sh K L P l /C it i l C M di iA V l D Sh K L P l /C iti l C M di i E H lthE H lth


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A. Velasquez, D. Shaz, K. Leeper, Pulmonary/Crit ical Care MediciA. Velasquez, D. Shaz, K. Leeper, Pulmonary/Critical Care Medici ne, Emory Healthcare,ne, Emory Healthcare,Atlanta, GA;Atlanta, GA;

Introduction : Patients in a medical intensive care unit (MICU)Introduction : Patients in a medical intensive care unit (MICU) are often atare often at

very high risk of developing a venous thromboembolism (VTE). Hepvery high risk of developing a venous thromboembolism (VTE). Heparinarinand low molecular weight heparins (LMWHs) are pharmacological agand low molecular weight heparins (LMWHs) are pharmacological agentsents

used for prevention of VTE.used for prevention of VTE.

Hypothesis: Current dosing guidelines for VTE prophylaxis may beHypothesis: Current dosing guidelines for VTE prophylaxis may beinadequate in MICU patients who often have altered pharmacokinetinadequate in MICU patients who often have altered pharmacokinet ic andic and

pharmacodynamic profi les.pharmacodynamic profiles.

Methods : Patients in the MICU receiving VTE prophylaxis with heMethods : Patients in the MICU receiving VTE prophylaxis with heparinparinor LMWH had antior LMWH had anti --Xa levels monitored in this prospective, observationalXa levels monitored in this prospective, observational

study. Antistudy. Anti --Xa levels were drawn at least after 4 doses and 4 hours afterXa levels were drawn at least after 4 doses and 4 hours after

subcutaneous administration of medication.subcutaneous administration of medication.

THE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY INTHE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY INA MEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .A MEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .H.H.


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Patel,Patel, A. Velasquez, D. Shaz, K. Leeper, Pulmonary/Critical Care MediA. Velasquez, D. Shaz, K. Leeper, Pulmonary/Critical Care Medi cine, Emorycine, Emory

Healthcare, Atlanta, GA;Healthcare, Atlanta, GA;

Results : From March 2007 to August 2007, 50 patients had antiResults : From March 2007 to August 2007, 50 patients had anti --Xa levelsXa levels

monitored. Among the 50 patients, 12 patients (24%) acheivedmonitored. Among the 50 patients, 12 patients (24%) acheived

appropriate antiappropriate anti --Xa levels compared to 38 patients (76%) who were nonXa levels compared to 38 patients (76%) who were non--therapeutic. Among those in the appropriate range, 8 patients (6therapeutic. Among those in the appropriate range, 8 patients (67%) were7%) were

receiving LMWH. ICU length of stay and days on the ventilator wereceiving LMWH. ICU length of stay and days on the venti lator werere

longer in patients with nonlonger in patients with non--therapeutic antitherapeutic anti --Xa levels.Xa levels.

Conclusions : Current dosing guidelines of heparin for VTE prophConclusions : Current dosing guidelines of heparin for VTE prophylaxisylaxis

are inadequate in an MICU setting. Weight based dosing of hepariare inadequate in an MICU setting. Weight based dosing of heparinn

should be considered in future patients. The LMWHs may have a beshould be considered in future patients. The LMWHs may have a bettertter

predictabil ity. Future studies should evaluate whether subtherappredictabil ity. Future studies should evaluate whether subtherapeuticeuticVTE prophylaxis correlates to a higher incidence of VTE comparedVTE prophylaxis correlates to a higher incidence of VTE compared toto

therapeutic dosing.therapeutic dosing.

Strategies to ImproveStrategies to Improve


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g pg

ThromboprophylaxisThromboprophylaxis

No special complianceNo special compliance

interventionintervention38%38%

Education provided toEducation provided to

physiciansphysicians62%62%

Education and mandatoryEducation and mandatory

computer order entrycomputer order entry97%97%

Comparison of strategies among 1,827 patients in 3 similar CCUsComparison of strategies among 1,827 patients in 3 similar CCUs

Levi et al. Chest. 1998;114(Suppl):392S.Levi et al. Chest. 1998;114(Suppl):392S.

SummarySummary


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y

Critically il l patients are at high risk of VTECritically il l patients are at high risk of VTE Low rate of clinical diagnosisLow rate of clinical diagnosis

Prevalence 10Prevalence 10 60%60%

Predominant test: ultrasoundPredominant test: ultrasound ProphylaxisProphylaxis

UFH 5000 U q 8 hUFH 5000 U q 8 h

LMWH (enoxaparin 40 mg SC/d)LMWH (enoxaparin 40 mg SC/d) Dalteparin 5000 IU SC dailyDalteparin 5000 IU SC daily

Fondaparinux 2.5 mg SQ dailyFondaparinux 2.5 mg SQ daily

Intermittent compression devicesIntermittent compression devices

Utilization of prophylaxis is inadequate AND or prophylacticUtilization of prophylaxis is inadequate AND or prophylacticregimens may be inadequateregimens may be inadequate

New sources of thrombiNew sources of thrombi HIT induced thrombosisHIT induced thrombosis

We can do better !!!We can do better !!!


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Treatment of VTE in the Critical CareTreatment of VTE in the Critical CarePatientsPatients

Kenneth V. Leeper Jr. MDKenneth V. Leeper Jr. MD

Associate Professor of MedicineAssociate Professor of Medicine

Division of Pulmonary, Allergy and Critical Care MedicineDivision of Pulmonary, Allergy and Critical Care Medicine

Emory School of MedicineEmory School of MedicineAtlanta, GeorgiaAtlanta, Georgia

Summary of Sixth American College of Chest PhysiciansSummary of Sixth American College of Chest Physicians(ACCP) Guidelines for Antithrombotic Therapy in the Treatment(ACCP) Guidelines for Antithrombotic Therapy in the Treatment


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( ) py( ) pyof Venous Thromboembolismof Venous Thromboembolism

Recommendations Guidelines for Treatment

Grade 1A i.v. LMWH/UFH or adjusted-dose s.c. heparin

initially for at least 5 daysOverlap with oral anticoagulation for at least 4-5 days

Discontinue LMWH/UFH on day 5/6 if INR is

therapeutic for 2 consecutive days

Grade 2B LMWH preferred over UFH

Grade 1C Massive pulmonary embolism/severe iliofemoral

thrombosis: LMWH/UFH for approximately 10 days

Grade 1C+ LMWH: dose based on manufacturers instructions

UFH: adjust to correspond to a plasma heparin level

of 0.2-0.4 IU/mL (protamine sulfate) or 0.3-0.4

IU/mL (amidolytic anti-Xa assay).Turpie AGG et al..Turpie AGG et al. Sem Thromb & HemostSem Thromb & Hemost. 2002;28(Suppl 3):3. 2002;28(Suppl 3):3--11.11.

56 y.o man with a history of alcoholism admitted to the MICU in56 y.o man with a history of alcoholism admitted to the MICU inrespiratory failure secondary to pneumonia. He is on norespiratory failure secondary to pneumonia. He is on no


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p y y pp y y pvasopressors and renal function is normal and on heparin 5000 unvasopressors and renal function is normal and on heparin 5000 unitsits

sq BIDsq BID

On day 5 his WBC count is normal butOn day 5 his WBC count is normal but

temperature is 38.6Ctemperature is 38.6C Differential Dx: 1.Slow resolution of theDifferential Dx: 1.Slow resolution of the

pneumonia. 2. VAP. 3 Possible DVTpneumonia. 2. VAP. 3 Possible DVT Evaulation: Mini BAL negative, LE dopplersEvaulation: Mini BAL negative, LE dopplers

Positive for DVT right deep femoralPositive for DVT right deep femoral

Treatment: No contraindications to heparinTreatment: No contraindications to heparin

therapy: Treat with UFU or LMWHtherapy: Treat with UFU or LMWH

Therapeutic peak antiTherapeutic peak anti --Xa levels withXa levels with


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LMWHs for the treatment of VTELMWHs for the treatment of VTE Enoxaparin 1mg/kg q 12 hrsEnoxaparin 1mg/kg q 12 hrs 0.60.6--1.0IU/ml1.0IU/ml

Enoxaparin 1.5mg/kg qdEnoxaparin 1.5mg/kg qd 1.01.01.5 IU/ml1.5 IU/ml Tinzaparin 175 IU/kg qdTinzaparin 175 IU/kg qd 0.850.85 1.0 IU/ml1.0 IU/ml

Dalteparin 100IU/kg q 12 hrsDalteparin 100IU/kg q 12 hrs 0.40.4 1.1 IU/ml1.1 IU/ml Dalteparin 200 IU/kg qdDalteparin 200 IU/kg qd 1.01.0--2.0 IU/ml2.0 IU/ml

ProphylaxisProphylaxis 0.10.1 0.6 IU/ml0.6 IU/ml

Chromogenic anti-Xa level assay drawn 4 hours after the subq dose

This is a 62 y.o woman with diabetes and ESRD, admitted to theThis is a 62 y.o woman with diabetes and ESRD, admitted to theMICU with MRSA bacteriemia. The patient is placed on SCDs for DVMICU with MRSA bacteriemia. The patient is placed on SCDs for DVTT


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p pprophylaxis. On MICU day 4 she developes a sudden onset ofprophylaxis. On MICU day 4 she developes a sudden onset of

dyspnea ,hypoxemia and SPB of 98 mmHg .dyspnea ,hypoxemia and SPB of 98 mmHg .

Evaluation: Spiral CT scan of the chestEvaluation: Spiral CT scan of the chest large rightlarge right

main pulmonary embolism. LE dopplersmain pulmonary embolism. LE dopplers RightRightpopliteal DVT.popliteal DVT.

TEETEE Moderate RV dilation with parodoxical septalModerate RV dilation with parodoxical septal

shift.shift. ManagementManagement

Hypotension responded to fluid therapyHypotension responded to fluid therapy

Pharmacologic management and other optionsPharmacologic management and other options UFH infusionUFH infusion UFH infusion and retrieveable filterUFH infusion and retrieveable fi lter

ThrombolysisThrombolysis

Pulmonary embolectomyPulmonary embolectomy

51 y.o man underwent coronary artery bypass surgery51 y.o man underwent coronary artery bypass surgerycomplicated by a hemopericardium, requiring pericardialcomplicated by a hemopericardium, requiring pericardial


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complicated by a hemopericardium, requiring pericardialcomplicated by a hemopericardium, requiring pericardial

window drainage.window drainage.

Fifth postFifth post op day prophylactic therapy withop day prophylactic therapy with

enoxaparin was started.enoxaparin was started. 99thth postpost--op day fever to 39C and hypotensionop day fever to 39C and hypotension

with BP 90/70, abdominal tenderness andwith BP 90/70, abdominal tenderness and

distention.distention.

Admission platelet countAdmission platelet count 182X109 cells/l182X109 cells/l

postpost--op day 3, nowop day 3, now 40 X109 cells cells/l40 X109 cells cells/l



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complicated by a hemopericardium, requiring pericardialp y p , q g p

window drainagewindow drainage Differential Diagnosis: Sepsis with DICDifferential Diagnosis: Sepsis with DIC

ManagementManagement Moved to the ICUMoved to the ICU

Antibiotics and fluids startedAntibiotics and fluids started

DIC profile negativeDIC profile negative

Serum cortisol orderedSerum cortisol ordered Argatroban startedArgatroban started

HITHIT ELISA for heparinELISA for heparin induced PF 4 antibodies strongly positiveinduced PF 4 antibodies strongly positive

CTscan of abdomenCTscan of abdomen revealed bilateral adrenal necrosisrevealed bilateral adrenal necrosis

Serum cortisol < 1ug/mlSerum cortisol < 1ug/ml Patient improvedPatient improved discharged on adrenal replacement and warfarindischarged on adrenal replacement and warfarin



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p y p , q g pp y p , q g p

window drainage:window drainage: CommentComment

If there is a moderate suspicion of HITIf there is a moderate suspicion of HIT -- treat withtreat with

DTIDTI

Large amount of heparin during bypass wasLarge amount of heparin during bypass was

sensitizing along with the LMWH.sensitizing along with the LMWH.

When heparin was stopped greatest risk period forWhen heparin was stopped greatest risk period fornew thromboembolic complicationsnew thromboembolic complications

Adrenal necrosis is a microthrombotic lesion withAdrenal necrosis is a microthrombotic lesion with

secondary necrosis and hemorrhagesecondary necrosis and hemorrhage

Diagnosis: HIT with acute adrenal crisisDiagnosis: HIT with acute adrenal crisis

Incidence of HIT and VTE After Use ofIncidence of HIT and VTE After Use ofUFH and LMWHUFH and LMWH


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UFH and LMWHUFH and LMWH

Literature review: Identify studies using UFH or LMWH forLiterature review: Identify studies using UFH or LMWH for

thromboprophylaxis or treatment in which new or recurrentthromboprophylaxis or treatment in which new or recurrentVTE and serologically confirmed HITVTE and serologically confirmed HIT

10 studies10 studies

386 of 6,219 heparin386 of 6,219 heparin--treated patients had VTEtreated patients had VTE

32 of 386 VTE patients also had HIT32 of 386 VTE patients also had HIT

Among 32 cases of HIT in 386 VTE patientsAmong 32 cases of HIT in 386 VTE patients

17 cases occurred in 129 IV UFH17 cases occurred in 129 IV UFH--treated patients (13.2%)treated patients (13.2%)

14 cases occurred in 113 SC UFH14 cases occurred in 113 SC UFH--treated patients (12.4%)treated patients (12.4%)

1 case occurred in 144 LMWH1 case occurred in 144 LMWH--treated patients (0.7%)treated patients (0.7%)

Levine RL, et al.Levine RL, et al. ChestChest. 2006;130:681. 2006;130:681--7.7.

Pretest Scoring System for HIT. WarkenteninPretest Scoring System for HIT. Warkenteninand Heddle Curr Hematol Rep 2003and Heddle Curr Hematol Rep 2003


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4Ts 2 Points 1 point 0 points

Thrombocytopenia Platelet count >50%

and platelet nadir>20 X109/L

Platelet count> 30-

50%

Platelet count < 30%

Timing of platelet

count decrease

Clear onset between

days 5 -10 or platelet

dec with one day

Consistent with

immunization but

unclear history

Platelet count


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