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DVT Prophylaxis in Neurosurgery “Seek simplicity and distrust it” Alfred North Whitehead

DVT Prophylaxis in Neurosurgery - Medical School · DVT and PE may be undetected In some studies as many as 50% of PE have no associated DVT Therefore, VTE probably overestimates

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Text of DVT Prophylaxis in Neurosurgery - Medical School · DVT and PE may be undetected In some studies as...

  • DVT Prophylaxis in

    Neurosurgery

    “Seek simplicity and distrust it”

    Alfred North Whitehead

  • 54

  • VTE Prophylaxis in Critically Ill Patients with:

    Intracranial Hemorrhage

    Aneurysmal Subarachnoid Hemorrhage

    Traumatic Brain Injury (TBI)

    Brain Tumors

    Spinal Cord Injury

  • Recommendations for Prevention of VTE

    in Patients Undergoing Neurosurgical and

    Neurovascular Interventions in:

    Elective Spine Surgery

    Complicated Spinal Surgery

    Elective Craniotomy

    Elective Intracranial/Intra-arterial

    Procedures

    Intracranial Endovascular Procedures

  • DVT, PE or VTE?

    DVT is the most common, but is not

    always serious

    PE is the most serious, but is much less

    common

    If PE were always preceded by DVT, the

    DVT would be a reasonable surrogate

    measure, but it is not

    Therefore most researchers use VTE as

    the measure of choice for analysis

  • Is VTE a Reasonable Choice ?

    It lumps minor superficial DVT with death

    due to massive pulmonary embolism

    DVT may be independent of PE, precede

    PE, not be identified in patients with PE,

    be disabling without leading to PE

    DVT and PE may be undetected

    In some studies as many as 50% of PE

    have no associated DVT

    Therefore, VTE probably

    overestimates the risk of DVT and/or

    PE with serious consequences

  • Soooo Much Data

    By my count, there at least 20

    randomized trials involving more than

    8,000 patients assessing some

    component of VTE prophylaxis

    predominantly in intracranial surgery

    There are also at least 4 systematic

    reviews with meta analysis of the

    subject(s)

  • REF 18

    RCT

    refs refer to "Beyond…" paper

    Ns

    Pooled N

    4UFH vs LMWH

    23, 24 247 2Craniotomy23UFH + ICD 75LMWH + ICD 75 24UFH + ICD 48LMWH + ICD 49

    25, 26 379 2Spinal surgery25200UFH + ICD LMWH + ICD 26UFH + CS 92LMWH + CS 87

    19, 20 792 2CS to LMWH Mostly craniotomy19LMWH + CS 153placebo + CS 154 20LMWH + CS 241placebo + CS 244

    5, 27 188 2ICD to LMWH Mostly craniotomy27ICD 60LMWH 60 5ICD 22LMWH 23ICD+LMWH 23

    21, 28 203 3UFH to placebo 2Craniotomy21UFH 50placebo 50 28UFH 55placebo 48

    29 50 1Spinal surgery29N=50 UFH placebo

    30-32 309 4CS to ICD 3Craniotomy Can’t confirm 3rd ref Wautrecht

    30N=70 ICD CS 31CS + ICD 78CS 80placebo 81

    33 117 1Spinal surgery33ICD 57CS 60

    34 95 1ICD to placebo Mixed craniotomy and spine

    34N=95 ICD placebo

    35

    104 1ICD to electrical stim Mixed craniotomy and spine 35UFH 58

    Calf stim +

    dextran 46

    Used as cohort

    36 134 1Thigh ICD to foot ICD Spinal surgery Used as cohort36

    ICD foot75ICD thigh 59

    12Cohort

    37, 38 247 7Pharmacologic 2LMWH alone Craniotomy37

    LMWH150 38

    LMWH97

    39 2823 1LMWH and CS Craniotomy39LMWH + CS 2823

    40 150 1UFH alone Craniotomy40

    UFH150

    41-43

    1116 3UFH and ICD

    Craniotomy43UFH + ICD 872 42UFH + ICD 106

    Frim is used in both RCT and

    cohort

    41

    UFH + ICD

    138ICD 473

    44-46 370 5Mechanical 3ICD alone Spinal surgery 44ICD 31 45ICD 200 46 139

    47, 48 392 2CS and ICD Spinal Surgery 47ICD + CS 75 48ICD + CS 317

    7716

  • Meta AnalysisShould simplify by pooling data

    Cannot make all the included trials have

    the same:

    Eligibility and exclusion criteria

    Choice of prophylactic method

    Choice of outcome measure

    and yet, pooling the data assumes that all

    of these things are so similar that the

    differences among the studies don’t matter

  • Khan, et al. J Neurosurg 129:906–915, 2018

  • Assumptions Underlying Meta Analyses

    The risk of VTE and Intracranial

    Hemorrhage is the same in cranial and

    spinal patients

  • Comparing Meta Analyses

    Author Number of studies RCT Cohort Spine Included DVT PE VTE

    Iorio 4 no yes no yes

    Collen 12 RCT, 18 cohort yes yes yes no

    Hamilton 6 no no no yes

    Khan 9 yes yes no no

    Outcomes

    Separately

    Analyzed

    Author Number of studies RCT Cohort Spine Included DVT PE VTE

    Iorio 4 no yes no yes

    Collen 12 RCT, 18 cohort yes yes yes no

    Hamilton 6 no no no yes

    Khan 9 yes yes no no

    Outcomes

    Separately

    Analyzed

  • Assumptions Underlying Meta Analyses

    Is the risk of VTE and Intracranial

    Hemorrhage is the same in cranial and

    spinal patients ?

    Is it OK to include non-randomized cohorts ?

    Is it OK to assume that DVT and VTE

    outcomes are similar enough to pool?

  • Comparing Meta Analyses

    All methods used inconsistently across studies

    Author venography echo fibrinogen angio CT V/Q

    Iorio

    Collen

    Hamilton

    Khan

    Methods of Diagnosis for VTE

  • Assumptions Underlying Meta Analyses

    Is the risk of VTE and Intracranial

    Hemorrhage is the same in cranial and

    spinal patients ?

    Is it OK to include non-randomized cohorts ?

    Is it OK to assume that DVT and VTE

    outcomes are similar enough to pool?

    Is it OK to assume that using different

    diagnostic methods doesn’t affect outcome?

  • Comparing Meta Analyses

    All methods used inconsistently across studies

    Author placebo

    compression

    stockings

    intermittent

    compression

    devices

    unfractionated

    heparin enoxaparin nadroparin

    Iorio

    Collen

    Hamilton

    Khan

    Methods of Prophylaxis

  • Assumptions Underlying Meta Analyses

    Is it OK to assume that using different

    methods and combinations of prophylaxis

    doesn’t affect outcome?

    In addition, many studies mix populations of

    patients known to have different risk of VTE

    (brain tumor patients subarachnoid

    hemorrhage patients and other elective

    intracranial surgery patients)

  • Well, let’s just assume that all those assumptions are OK

  • 0.00

    0.10

    0.20

    0.30

    0.40

    0.50

    0.60

    0.70

    0.80

    0.90

    Iorio Collen Hamilton Khan

    Odds Ratio for DVT

    lower 95% ci

    Odds Ratio

    upper 95% ci

    Odds Ratio for DVT

    Iorio Collen Hamilton Khan0.00

    0.90

    0.50

  • Odds Ratio for ICH or Maj. Hem.

    0.00

    0.50

    1.00

    1.50

    2.00

    2.50

    3.00

    3.50

    4.00

    Iorio Collen Hamilton Khan

    lower 95% ci

    Odds Ratio

    upper 95% ci

    Iorio Collen Hamilton Khan0.00

    3.00

    1.00

    2.00

    4.00

  • NNT

    Author

    Number of

    studiesnon-pharm

    prophylaxis

    chemo-

    prophylaxis

    absolute

    risk

    reduction

    Number

    Needed

    to Treat

    Agnelli 4 RCT 0.290 0.161 0.129 7.74

    Collen 12 RCT, 18 cohort 0.061 0.033 0.029 34.59

    Hamilton 6 RCT 0.260 0.148 0.112 8.93

    Khan 9 RCT 0.215 0.126 0.089 11.24

    proportion with VTE

    Another View

  • NNH

    Author

    Number of

    studiesnon-pharm

    prophylaxis

    chemo-

    prophylaxis

    absolute

    risk

    increase

    Number

    Needed to

    Harm

    Agnelli 4 RCT 0.0137 0.0235 0.0098 102.20

    Collen 12 RCT, 18 cohort 0.0630 0.1244 0.0888 11.26

    Hamilton 6 RCT 0.0400 0.0500 0.0100 100.00

    Khan 9 RCT 0.0240 0.0330 0.0090 111.11

    proportion with ICH or

    major hemorrhage

    Another View

  • NNT NNH

    Author

    absolute risk

    reduction

    Number

    Needed to

    Treat

    absolute

    risk increase

    Number

    Needed to

    Harm

    Collen 0.03 35 0.09 11

    Iorio 0.13 8 0.01 102

    Hamilton 0.11 9 0.01 100

    Khan 0.09 11 0.01 111

    trying to simplify the comparison

  • Agnelli

    Nurmohamed

    Cerrato

    Collen

    Hamilton

    KhanIorio

    Constantini

    Goldhauber

    MacDonald

    Bostrom

    Bucci

    Nelson

    Prestar

    Skillman

    Turpie

    Voth

    Wautrecht

    Wood

    Dickinson

    MelonGruber

    Kurtoglu

    Hamidi

  • Conclusions

    Meta-analysis does not fix flaws in the

    included studies

    Different approaches to inclusion and

    exclusion lead to wildly different results

    It isn’t clear which is right

    More than 3 decades of uncoordinated

    underpowered randomized trials have

    failed to provide clear guidance on this

    issue