als 450: prognostication in hypothermia · claudio sandroni: first author of two systematic reviews...

Dallas 2015

TFQO: Clifton Callaway

EVREVs: Claudio Sandroni (COI #134); Eyal Golan (COI #61)

Taskforce: ALS

ALS 450: Prognostication in Hypothermia

Dallas 2015 COI Disclosure (specific to this systematic review)

Commercial/industry

Claudio Sandroni: none

Eyal Golan: none

Potential intellectual conflicts Claudio Sandroni: first author of two systematic reviews on prognostication after cardiac arrest and of the ERC-ESICM Advisory Statement on prognostication in comatose survivors of cardiac arrest

Eyal Golan: first author of a systematic review on prognostication after cardiac arrest in patients receiving targeted temperature management and author of the Canadian Guidelines on the use of targeted temperature management after cardiac arrest

Dallas 2015

2010 CoSTR

No reviews in 2010

Dallas 2015

C2015 PICO

Population: Adults with ROSC who are treated with targeted temperature management (TTM)

Intervention: any clinical variable when normal (e.g. 1. Clinical Exam, 2. EEG or SSEP, 4. Imaging, 5. Other)

Comparison: any clinical variable when abnormal

Outcomes Survival with Favorable neurological or functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year

Dallas 2015 Inclusion/Exclusion & Articles Found

Inclusion: adult (≥16 years) pts, comatose (unconscious, unresponsive, or GCS≤8)

Exclusion: Studies including pts. in hypoxic coma from causes other than CA (e.g., respiratory arrest, CO poisoning) except when a subpopulation of cardiac arrest patients could be evaluated separately.

Included: 44 articles were included in final analysis

Dallas 2015

Grading: risk of bias

Serious = treating team aware of the results of the index test

Very serious = index test used for WLST

Other variables

Sedation, paralysis (when applicable)

Best CPC reported

Length of follow-up

Interobserver agreement

Dallas 2015

Imprecision

Serious = upper limit of the 95%CIs of the estimate of the false positive rate (FPR) was greater than 5%

Very serious = upper 95%CI limit was greater than 10%

Dallas 2015

Risk of Bias in studies

Author, year Index Blinding (treating

team)

Blinding (index or outcome

evaluators)

Excludes sedation

or paralysis

Best CPC

Excludes previous neurol.

diseases

Interobserv. agreement assessed

Length of follow-up

Index test used for

WLST Overall

Al Thenayan, 2008

PLR, CR, MR no No No no no No 90 days Not reported Very serious

Bisschops 2011 PLR+CR+MR, myoclonus, EEG

no No Yes no no No 90 days Yes (BR) Very serious

Bisschops 2011 SSEP no No N/A no no No 90 days Yes Very serious

Bouwes 2009 SSEP (TH) limited Yes N/A no yes No 30 days No Serious

Bouwes 2012 PLR, CR, M1-2, myoclonus

no No uncertain no yes No 180 days Uncertain Serious

Bouwes 2012 SSEP (TH) limited No N/A no no No 180 days No Serious

Bouwes 2012 SSEP (after RW) no No N/A no no No 180 days Yes Very serious

Bouwes, 2012 NSE yes No N/A no no N/A 180 days Uncertain Serious

Choi 2012 SSSEP, CT, MRI no No N/A no no No Discharge Not reported Very serious

Choi, 2012 PLR no No No no no No Discharge Not reported Very serious

Cloostermans 2012

cEEG no Yes No no yes No 180 days No Serious

Cloostermans 2012

SSEP no No N/A no yes No 180 days Yes Very serious

Crepeau 2013 cEEG, myoclonus no Yes No no no No Discharge Yes Very serious

Cronberg 2011 SSEP no No N/A yes no Yes 180 days Yes Very serious

Cronberg 2011 EEG no Yes Yes yes no No 180 days No Serious

Cronberg, 2011 PLR, CR, MR, myoclonus

no No Yes yes no No 180 days Yes (PLR,

MR) Very serious

Cronberg, 2011 NSE no No N/A yes no N/A 180 days No Serious

Cronberg, 2011 MRI DWI no Yes N/A yes no No 180 days No Serious

Dallas 2015



team)


evaluators)

Excludes sedation

or paralysis

Best CPC


diseases


Length of follow-up

Index test used for

WLST Overall

Fugate 2010 PLR, CR, MR, myoclonus

no No No no no No Discharge Yes Very serious

Fugate 2010 NSE, CT no No N/A no no No Discharge No Serious

Huntgeburth 2014

NSE no No N/A no no No 60 days Not reported Very serious

Inamasu 2010 CT no Yes N/A no no Yes 180 days Not reported Very serious

Kawai 2011 EEG no No No no no No 180 days Not reported Very serious

Kim, 2012 NSE, MRI no No N/A no no no (MRI) N/A (NSE)

180 days Not reported Very serious

Kim 2013 MRI no No N/A no no No 180 days Uncertain Serious

Kim S 2013 CT no Yes N/A no no No Discharge Not reported Very serious

Leary 2010 BIS no No No no no N/A Discharge Not reported Very serious

Lee 2013 NSE, CT no Yes N/A No No No Discharge No

withdrawal Serious

Legriel 2009 EEG no Yes No no no No Discharge Not reported Very serious

Legriel 2013 Myoclonus no No No no no No 1 year Uncertain Serious

Legriel 2013 EEG no No No no no No 1 year No Serious

Leithner 2010 SSEP no No N/A no no No Discharge Not reported Very serious

Mani 2012 EEG no Yes No no no Yes Discharge Uncertain Serious

Mlynash, 2010 MRI no Yes N/A yes no Yes 180 days Not reported Very serious

Mortberg, 2011 NSE, S-100B no No N/A no no N/A 180 days Not reported Very serious

Oddo 2014 BR, Myoclonus no No Yes no no No 90 days Yes Very serious

Dallas 2015



team)


evaluators)

Excludes sedation

or paralysis

Best CPC


diseases


Length of follow-up

Index test used for

WLST Overall

Okada 2012 PLR, MR no No No no yes No Discharge Not reported Very serious

Oksanen, 2009 NSE no No No no no N/A 180 days No Serious

Rittenberger 2012

EEG, myoclonus no No No no no No Discharge Not reported Very serious

Rossetti 2010 BR, MR, myoclonus, EEG

no No Yes no no No 180 days Yes (BR, EEG) Very serious

Rossetti 2010 SSEP no No N/A no no No 180 days Yes Very serious

Rossetti 2012 BR, MR, myoclonus, EEG

no No Yes no no No 90 days Yes (BR,

myoclonus, EEG)

Very serious

Rossetti, 2012 SSEP, NSE yes No N/A no no no (SSEP); N/A (NSE)

90 days Yes (SSEP) Very serious

Rundgren 2010 EEG no Yes No no no No 180 days No Serious

Rundgren, 2009 NSE, S-100B no No N/A yes yes N/A 180 days No Serious

Sakurai 2006 BAEP wave V absent

no No N/A no yes No 60 days Not reported Very serious

Samaniego 2011 BR, MR, myoclonus no No No no no No 90 days Yes Very serious

Samaniego, 2011 SSEP no No N/A no no N/A 90 days Yes Very serious

Samaniego, 2011 NSE no No N/A no no N/A 90 days No Serious

Schefold 2009 GCS ≤ 4 no No No no no No Discharge Yes Very serious

Seder 2010 BIS no No N/A no no N/A Discharge Not reported Very serious

Stammet 2009 BIS limited Yes N/A yes no N/A 180 days No Serious

Stammet 2013 BIS no No Yes no no N/A 180 days Not reported Very serious

Stammet 2013 S-100B no No N/A no no N/A 180 days Not reported Very serious

Dallas 2015



team)


evaluators)

Excludes sedation

or paralysis

Best CPC


diseases


Length of follow-up

Index test used for

WLST Overall

Tiainen 2005 SSEP limited No N/A no yes No 180 days No Serious

Tiainen, 2003 NSE, S-100B no Yes N/A no no N/A 180 days Not reported Very serious

Wennervirta 2009

EEG no Yes No no yes No 180 days Not reported Very serious

Wennervirta, 2009

NSE, S-100B no No N/A no yes N/A 180 days Not reported Very serious

Wijman, 2009 MRI (ADC) limited Yes N/A yes no No 180 days No Serious

Zanatta 2012 SSEP, MLCEP no No N/A no no No 90 days Not reported Very serious

Zellner 2013 NSE, S-100B No No No No No No 180 days Not reported Very serious

Dallas 2015

Clinical examination

For the critical outcome of survival with unfavorable neurological status or death at discharge, we identified four studies on corneal reflex, pupillary reflex, motor response, Glasgow Coma Score, or myoclonus (295 patients, very low quality of evidence).

For the critical outcome of survival with unfavorable neurological status or death at 90 days, we identified five studies on corneal reflex, pupillary reflex, motor response, brainstem reflexes, or myoclonus (388 patients, very low quality of evidence).

For the critical outcome of survival with unfavorable neurological status or death at 180 days, we identified four studies on corneal reflex, pupillary reflex, motor response, brainstem reflexes, or myoclonus (642 patients, low or very low quality of evidence).

Dallas 2015

Evidence profile table

Predictor

(studies) Timing

Risk of

bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

Corneal

reflex (4) At 72-120h

Very

serious No Serious Serious Very low 43 3 132 123 25 [18-32] 2 [0-7] 5 [2-16]

Pupillary

reflex (5) at 72-108h

Very

serious No No No Low 42 1 180 160 19 [14-26] 1 [0-3] 7 [2-22]

GCS Motor

1-2 (6) At 36-108h

Very

serious No No

very

serious very low 257 28 111 239 70 [65-74] 10 [7-15] 6 [4-9]

Myoclonus

(5) At 24-72h

Very

serious No Serious serious very low 182 16 249 274 41 [36-46] 6[3-9] 6 [4-10]

Status

myoclonus

(3)

≤72h Very

serious No No No Low 25 0 137 78 16 [11-22] 0 [0-4] 4 [2-10]

Dallas 2015 Draft Treatment Recommendations

Clinical Examination - 1

We recommend using bilaterally absent pupillary light reflexes or the combined absence of both pupillary and corneal reflexes at ≥72 h from ROSC to predict poor outcome (Strong recommendation, low QOE)

We suggest against using an absent or extensor motor response to pain (M≤2) alone to predict poor outcome, given its high false positive rate (weak recommendation, very low QOE). However, due to its high sensitivity, this sign may be used to identify the population with poor neurological status needing prognostication or to predict poor outcome in combination with other more robust predictors.

We suggest using the presence of a status myoclonus within 72 h from ROSC in combination with other predictors for prognosticating a poor neurological outcome (weak recommendation, low QOE).


Clinical Examination - 2

We suggest prolonging the observation of clinical signs when interference from residual sedation or paralysis is suspected, so that the possibility of obtaining false positive results is minimized (weak recommendation, very low QOE).

We recommend that the earliest time to prognosticate a poor neurological outcome using clinical examination is 72hrs after ROSC, and should be extended longer if the residual effect of sedation and/or paralysis confounds the clinical examination.

Dallas 2015

Myoclonus

Is a clinical sign

Sudden, brief, shock-like, involuntary movements caused by muscular contractions or inhibitions

Focal = involving only a few adjacent muscles

Generalized = involving most of the muscles in the body, often not synchronously

Dallas 2015

Status myoclonus

A prolonged period of frequent myoclonic jerks

There is no universal consensus on the duration or frequency of the myoclonic jerks necessary to qualify them as a status myoclonus

Proposed definition = generalised continuous myoclonus persisting for ≥30 minutes

Dallas 2015

Myoclonus and epilepsy

Myoclonus is only inconsistently associated with EEG epileptiform activity

Most frequent EEG correlate of post-anoxic myoclonus is burst-suppression

Status epilepticus = continuous and prolonged epileptiform activity on EEG

It may or may not be associated with clinical manifestations, including myoclonus

Dallas 2015

Status epilepticus

Status myoclonus MSE

Dallas 2015

Knowledge Gaps

In comatose resuscitated patients who have been treated with TTM, prospective studies are needed to investigate:

the pharmacokinetics of sedative and NMB drugs

the reproducibility of clinical signs used to predict

outcome.

There is no universally accepted definition of status myoclonus

Recently proposed definition = generalised myoclonus persisting for ≥30 minutes.

Dallas 2015

Electrophysiology

For the critical outcome of survival with unfavorable neurological status or death at discharge, we identified 8 studies on SSEP, EEG or BIS (571 patients, very low QOE).

For the critical outcome of survival with unfavorable neurological status or death at 30 days, we identified one study on SSEP (77 patients, very low QOE).

For the critical outcome of survival with unfavorable neurological status or death at 60 days we identified one study on BAEPs (26 patients, very low QOE).

For the critical outcome of survival with unfavorable neurological status or death at 90 days, we identified five studies on SSEP or EEG (362 patients, low or very low QOE).

For the critical outcome of survival with unfavorable neurological status or death at 180 days, we identified ten studies on SSEP, EEG or BIS (921 patients, moderate, low, or very low QOE).

For the critical outcome of survival with unfavorable neurological status or death at 1 year, we identified one study on EEG (106 patients very low QOE).

Dallas 2015


Predictor

(studies) Timing

Risk of

bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

Absent N20

SSEP (4) During TTM Serious No No No Moderate 60 3 164 194 28 [22-34] 2 [1-4] 12 [5-32]

Absent N20

SSEP (10) After RW

Very

serious No Serious No Very low 42 1 180 160 45 [41-50] 1 [0-3] 14 [6-32]

Unreactive

EEG (3) During TTM

Very

serious No No Serious Very low 80 3 46 120 63 [54-72] 2 [1-7] 18 [5-61]

Unreactive

EEG (3) After RW

Very

serious no no No Low 85 0 52 86 62 [53-70] 0 [0-3] 33 [7-163]

Burst-

suppression

EEG (4)

During TTM Very

serious no serious Serious Very low 55 3 57 111 49 [40-58] 3 [1-7] 11 [4-30]

Burst-

suppression

EEG (1)

After RW Serious no very

serious Very low 7 0 31 57 18 [8-34] 0 [0-5] 22 [1-379]

Dallas 2015


Predictor

(studies) Timing

Risk of

bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

EEG

seizures,

nonreactive

During TTM Very

serious No -

Very

serious Very low 10 0 23 28 30 [16-49] 0 [0-10] 18 [1-293]

EEG

seizures After RW

Very

serious No -

Very

serious Very low 9 0 17 12 35 [17-56] 0 [0-22] 9 [1-145]

EEG

seizures

During TTM

and RW

Very

serious No - Serious Very low 5 0 16 33 24 [8-47] 0 [0-9] 17 [1-292]

Status

epilepticus During TTM

Very

serious no - no Low 5 0 34 12 13 [4-27] 0 [0-22] 4 [0,2-60]

Status

epilepticus After RW

Very

serious no - serious Very low 4 0 5 21 44 [14-79] 0 [0-13] 20 [1-334]

Status

epilepticus

(2)

≤72h Very

serious No serious

Very

serious Very low 43 2 131 31 25[18-32] 6 [1-20] 3 [0-23]

Dallas 2015


Predictor

(studies) Timing

Risk of

bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

Flat During

TTM Serious No -

Very

serious Very low 10 21 26 17 31 55 [38-71] 46 [32-59]

Flat or low-

voltage

During

TTM Serious No -

Very

serious Very low 9 8 0 12 26 40 [19-64] 0 [0-11]

Flat After RW Serious No - Serious Very low 5 6 3 32 54 16 [6-31] 5 [1-15]

BIS=0 During

TTM

Very

serious no -

Very

serious Very low 14 0 14 17 50 [31-69] 0 [0-16] 18 [1-284]

Lowest mean

BIS≤ 5,5

During

TTM

Very

serious no -

Very

serious Very low 29 7 5 34 85 [69-95] 17 [7-32] 5 [3-10]

Lowest

BIS=0

During

TTM

Very

serious No -

Very

serious Very low 26 4 8 37 76 [59-89] 10 [3-23] 8 [3-30]


Electrophysiology

We recommend using bilateral absence of N20 SSEP wave at ≥72h after ROSC to predict poor outcome (strong recommendation, low QOE).

We suggest using EEG-based predictors such as absence of EEG reactivity (weak recommendation, low QOE), presence of burst-suppression (weak recommendation, very low QOE) or status epilepticus (weak recommendation, very low QOE) at ≥72h after ROSC in combination with other predictors for prognosticating a poor neurological outcome.

We suggest against using BIS to predict poor outcome (weak recommendation, very low QOE).

Dallas 2015

Knowledge Gaps

In most prognostication studies on TTM-treated patients, SSEPs have been used as a criterion for WLST

Blinded studies on SSEPs are needed to assess the relevance of self-fulfilling prophecy for SSEP.

Definitions of EEG-based predictors are inconsistent among prognostication studies.

Future studies should comply with recently recommended definitions (Hirsch and coll., 2013).

The stimulation modalities for eliciting EEG reactivity have not been standardised.

Dallas 2015

Biomarkers

For the critical outcome of survival with unfavorable neurological status or death at discharge, we identified 4 studies on NSE (354 patients, moderate, low or very low quality of evidence).

For the critical outcome of survival with unfavorable neurological status or death at 60 days, we identified one study on NSE (73 patients, very low quality of evidence)

For the critical outcome of survival with unfavorable neurological status or death at 90 days, we identified 3 studies on NSE (248 patients, very low quality of evidence)

For the critical outcome of survival with unfavorable neurological status or death at 180 days, we identified 8 studies on NSE or S-100B (810 patients, moderate, low, or very low quality of evidence).

Dallas 2015


Predictor,

timing,

studies

Th

resh

old

(mcg

L-1)

Risk of bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

NSE

24 h

(6)

31.2 Very serious no - very

serious very low 2 1 8 24 20 [3-56] 4 [0-20] 5 [1-49]

41 Serious no - very

serious very low 7 2 32 48 18 [8-34] 4 [0-14] 4 [1-20]

49.6 Very serious no - very

serious very low 20 0 5 9 80 [59-93] 0 [0-29] 15 [1-229]

52.4 Very serious no very

serious very low 1 0 9 20 10 [0-45] 0 [0-14]

6 [0,3-

129]

80.8 Serious no No Moderate 22 0 60 60 27 [18-37] 0 0-4][ 33 [2-535]

151.4 Very serious No Very

serious Very low 8 0 54 41 13 [6-24] 0 [0-7] 11 [1-191]

Dallas 2015


Predictor,

timing,

studies

Th

resh

old

(mcg

L-1)

Risk of bias

In

dire

ctn

ess

In

co

nsis

ten

cy Imprecision

Quality of

evidence TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

NSE

48 h

(13)

4.97 Very serious no - Very serious very low 2 1 8 24 20 [3-56] 4 [0-20] 5 [1-49]

25 Very serious no very serious very low 2 0 7 24 22 [3-60] 0 [0-12] 13 [1-238]

33 Serious No S Serious Very low 122 11 107 191 53 47-60] 5 [3-10] 9 [5-16]

44.3 Very serious no - Very serious Very low 19 0 3 7 86 [64-97] 0 [0-34] 14 [1-209]

52.7 Very serious no - No Low 49 0 33 60 60 [48-70] 0 [0-5] 73 [5-1157]

54.5 Very serious no Very serious Very low 14 0 10 9 10]0-45] 0 [0-28] 12 [1-176]

58.3 Serious no Very serious Very low 43 11 116 140 27 [10-35] 7 4-13][ 4 [2-7]

59.25 Very serious No Very serious Very low 1 0 9 20 10 [0-45] 0 [0-14] 6 [0-129]

81.8 Serious No Np Moderate 29 0 130 151 18 [13-25] 0 [0-2] 56 [3-909]

112.4 Very Serious No Serious Very low 9 0 21 33 30 [15-49] 0 [0-9] 21 [1-343]

151.5 Very Serious No Serious Very low 14 0 48 41 23 [13-35] 0 [0-7] 19 [1-343]

Dallas 2015


Predictor,

timing

Th

resh

old

(mcg

L-1)

Risk of

bias

In

dire

ctn

ess

In

co

nsis

ten

cy

Im

pre

cis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

NSE 72h

(4)

33 Serious No - Very

serious Very low 18 4 6 14 75 [53-90] 22 [6-48] 3 [1-8]

57.2 Very

serious No -

Very

serious Very low 11 0 13 9 46 [26-67] 0 [0-28] 9 [1-142]

65.4 Very

serious No - Serious Very low 23 0 7 33 77 [58-90] 0 [0-9] 52 [3-813]

78.9 Very

serious no Serious Very low 21 0 23 53 48 [32-63] 0 [0-5] 52 [3-828]

Dallas 2015

Huntgeburth et al., Neurocrit Care 2014; 20: 358-66

Dallas 2015

Oksanen T et al Resuscitation 2009; 80: 165-70

Dallas 2015

Lee BK et al Resuscitation 2013; 84: 1387-92


Biomarkers

We suggest using high serum values of NSE at 48h-72h from ROSC in combination with other predictors for prognosticating a poor neurological outcome (weak recommendation, from moderate to very low QOE). However, no threshold enabling prediction with zero FPR can be recommended.

We suggest using utmost care and preferably sampling at multiple time-points when assessing NSE, to avoid false positive results due to hemolysis (weak recommendation, very low QOE).

Dallas 2015

Knowledge Gaps

There is a need for standardisation of the measuring techniques for NSE and S-100 in cardiac arrest patients.

Little information is available on the kinetics of the blood concentrations of biomarkers in the first few days after cardiac arrest.

Dallas 2015

Imaging

For the critical outcome of survival with unfavorable neurological status or death at discharge, we identified 3 studies on CT (273 patients, low or very low quality of evidence).

For the critical outcome of survival with unfavorable neurological status or death at 180 days, we identified 6 studies on CT or MRI (246 patients, very low quality of evidence).

Dallas 2015


CT Index

Timing

from

ROSC

Risk of

bias

Ind

irectn

ess

Inco

nsis

ten

cy

Imp

recis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

GWR BG <1.22 < 1 h Very

serious Serious

Very

serious Very low 5 0 0 3 100 [55-100] 0 [0-63] 7 [1-99]

Average GWR

<1.14

(BG/cerebrum)

<1 h Very

serious No

Very

serious Very low 4 0 26 21 13 [4-31] 0 [0-13] 6 [0-113]

GWR CN/PIC <

1.10 ≤2 h Serious No No Low 16 0 66 60 20 [12-30] 0 [0-5] 24 [1-396]

GWR P/CC

< 1.17 ≤2 h Serious No No Low 43 0 39 60 52 [41-64] 0 [0-5] 64 [4-1018]

GWR≤1.18

CN/IC < 1 h

Very

Serious No

Very

serious Very low 51 1 12 11 81[69-90] 8[0-38] 10 [1-64]

Global cerebral

oedema

Median

day 1

(1-7)

Serious No Serious Low 11 0 34 57 24 [13-40] 0 [0-5] 29 [2-479]

BG = Basal ganglia; CC= Corpus callosum; CN = Caudate nucleus; PIC = Posterior limb of the internal capsule; P = Putamen

Dallas 2015


MRI Index

Timing

from

ROSC

Risk of

bias

Ind

irectn

ess

Inco

nsis

ten

cy

Imp

recis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

Extensive cortical

lesion pattern

80H (IQR

55-117)

Very

serious No

Very

serious Very low 9 1 1 10 90 [55-100] 9 [0-41] 10 [2-65]

DWI changes in BG 80H (IQR

55-117)

Very

serious No

Very

serious Very low 8 1 2 10 80 [44-97] 9 [0-41] 9 [1-58]

DWI changes in BS 80H (IQR

55-117)

Very

serious No

Very

serious Very low 3 0 7 11 30 [7-65] 0 [0-24] 8 [0-132]

Changes in cortex +

BG

74h (IQR

61-86) Serious Serious

Very

serious Very low 11 0 8 3 58 [33-80] 0 [0-63] 5 [0-63]

Changes in cortex +

BG < 5 days

Very

serious No

Very

serious Very low 5 0 0 3 100 [55-100] 0 [0-63] 7 [1-99]

Dallas 2015


MRI Index

Timing

from

ROSC

Risk of

bias

Ind

irectn

ess

Inco

nsis

ten

cy

Imp

recis

ion

Quality of

evidence

TP FP FN TN

Sensitivity

[95%CI]

FPR

[95%CI]

LR+

[95%CI]

ADC < 650 ▪ 10-6

mm2/sec in >10%

of brain volume

49-108 h Serious No Very

serious Very low 10 0 3 9 77 [46-95] 0 [0-28] 15 [1-227]

Occipital cortex

ADC < 616 ▪ 10-6

mm2/sec

45.8

(IQR

36,8-

52,4))

Very

serious No

Very

serious Very low 29 0 3 11 91 [75-98] 0 [0-24] 21 [1-324]

Putamen ADC < 590

▪ 10-6 mm2/sec

Very

serious No

Very

serious Very low 25 0 7 11 78 [60-91] 0 [0-24] 19 [1-281]

Thalamus ADC <

660 ▪ 10-6 mm2/sec

Very

serious No

Very

serious Very low 20 0 12 11 63 [44-79] 0 [0 24] 15 [1-228]


Imaging

We suggest using the presence of a marked reduction of the GM/WM ratio on brain CT within 2 h after ROSC or the presence of extensive reduction in diffusion on brain MRI at 2-6 days after ROSC in combination with other predictors for prognosticating a poor neurological outcome (weak recommendation, very low QOE).

We suggest using brain imaging studies for prognostication only in centers where specific experience is available (weak recommendation, very low QOE).

Dallas 2015

Knowledge Gaps

Prospective studies in unselected patient populations and including inter-rater agreement are needed for evaluating the prognostic accuracy of imaging studies in comatose patients resuscitated from cardiac arrest.

Dallas 2015

Final comments

Bilaterally absent PLR or SSEP are the most robust predictors (FPR <5%, narrow Cis)

No index predicts poor outcome with absolute certainty

Multimodality is the most reasonable approach

(1) At ≥24h after ROSC in patients not treated with targeted temperature

(2) See text for details.

Poor outcome very likely

(FPR <5%, narrow 95%CIs)

Two or more of the following: - Status myoclonus ≤48h after ROSC - High NSE levels (2) - Unreactive burst-suppression or status epilepticus on EEG - Diffuse anoxic injury on brain CT/MRI (2)

One or both of the following: - No pupillary and corneal reflexes - Bilaterally absent N20 SSEP wave (1)

Yes

No

Indeterminate outcome Observe and re-evaluate

No

Exclude confounders, particularly residual sedation

Unconscious patient, M=1-2 at ≥72h after ROSC

Rewarming

Days 1-2

Days 3-5

EEG

- N

SE

Poor outcome likely

Yes

Controlled temperature

Cardiac arrest

SSEP

Stat

us

Myo

clo

nu

s

Use multimodal prognostication whenever possible

CT

Wait at least 24h

Mag

net

ic R

eso

nan

ce Im

agin

g (M

RI)

Dallas 2015

Next Steps

Consideration of interim statement

Person responsible

Due date

als 450: prognostication in hypothermia · claudio sandroni: first author of two systematic reviews...

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