Conflict of Interest Declaration
The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: none applicable.
The following Task Force members and other authors declared an intellectual conflict of interest, and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: Claudio Sandroni, Karen Hirsch, Jerry Nolan and Jasmeet Soar were coauthors of the systematic review used for adolopment. They did not participate in assessment of the systematic review for quality for adolopment.
CoSTR Citation
Insert citation for ILCOR.org posting of CoSTR
Sandroni C, Skrifvars M, Humaloja J, Hirsch K, on behalf of the ILCOR ALS Task Force, Imaging for Prediction of Good Neurologic Outcome, Consensus on Science with Treatment Recommendations. Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force, 2022 December 15. Available from: http://ilcor.org
Methodological Preamble and Link to Published Systematic Review
The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of prognostication after cardiac arrest (PROSPERO: CRD 420 1914 1169). This review was conducted by a systematic review team with the involvement of clinical content experts from the ILCOR ALS Task Force and consisted of two parts. The first part was about prediction of poor neurological outcome and provided evidence for the 2021 ILCOR CoSTR. The second part was about prediction of good neurological outcome and it was completed after the publication of the 2021 ILCOR CoSTR. The two parts of this review have been published separately in 2020 and 2021 respectively (Sandroni C et al, DOIs 10.1007/s00134-020-06198-w and 10.1007/s00134-022-06618-z, respectively). As the recent systematic review on prognostication of favorable outcome met ILCOR criteria for being of sufficient quality, the TF deemed it appropriate to use the adolopment process for systematic reviews. Additionally, an updated search including the dates October 31, 2021-May 20, 2022, to capture any papers published since the search for the original systematic review was conducted. Task force members screened and selected all newly identified papers, extracted data and performed bias assessment using the QUIPS tool, which was also used in the original systematic review. The totality of this identified evidence was considered by the Advanced Life Support task force and used to determine the certainty of evidence and formulate the Consensus on Science and Treatment Recommendations.
Systematic Review
(Sandroni C, D'Arrigo S, Cacciola S, Hoedemaekers CWE, Westhall E, Kamps MJA, Taccone FS, Poole D, Meijer FJA, Antonelli M, Hirsch KG, Soar J, Nolan JP, Cronberg T. Prediction of good neurological outcome in comatose survivors of cardiac arrest. A systematic review. DOI: 10.1007/s00134-022-06618-z.)
PICOST
Population: Adults (≥16 y) who are comatose after resuscitation from cardiac arrest (either in-hospital or out-of-hospital), regardless of target temperature.
Intervention: Imaging studies assessed within one week from cardiac arrest.
Comparators: none.
Outcomes: Prediction of good neurological outcome defined as Cerebral Performance Categories (CPC) 1-2 or modified Rankin Score (mRS) 0-3 at hospital discharge/1 month or later. CPC 1-3 or mRS 1-4 was accepted as an indirect outcome.
Study Designs Prognostic accuracy studies where the 2 x 2 contingency table (i.e., the number of true/false negatives and positives for prediction of poor outcome) was reported, or where those variables could be calculated from reported data, are eligible for inclusion. Unpublished studies, reviews, case reports, case series, studies including less than 10 patients, letters, editorials, conference abstracts, and studies published in abstract form were excluded.
Timeframe: In 2015 and 2020, ILCOR evidence reviews identified four categories of predictors of poor neurological outcome after cardiac arrest, namely clinical examination, biomarkers, electrophysiology, and imaging. However, the prediction of good neurological outcome has never been systematically reviewed to date.
In the systematic review DOI: 10.1007/s00134-022-06618-z we searched studies published from January 1, 2001 to October 13, 2021. We updated this review for this CoSTR. Our last search was on20/05/2022.
Consensus on Science
The original systematic review identified 37 studies on prediction of good neurological outcome, of which five investigated imaging. The updated review identified 6 studies, of which one investigated imaging.
For the outcome of long-term favorable neurological outcome, we identified six studies (Lee 2017, 1628; Park, 2020, 39; Oh, 2019, 224; Jang, 2019, 142; Mlynash, 2010, 1665, Wouters, 2021, e2611). The certainty of evidence for all studies included in this CoSTR was rated as very low, with the common reasons for downgrading the certainty of evidence being moderate to serious risk of bias, imprecision in sensitivity and specificity, and in some cases inconsistency between studies. The individual studies were all at moderate risk of bias, mainly due to confounding and low study participation. In one study (Mlynash, 2010, 1665), good neurological outcome was measured as CPC 1-3 instead of 1-2. Because of a high degree of heterogeneity between the studies, we did not perform meta-analyses. None of the included predictors had the maximum 1% rate of falsely optimistic prediction that most clinicians would consider appropriate based on a survey conducted in 2019 (Steinberg, 2019, 190). However, the panel also considered that achieving a 0% false positive rate with narrow confidence intervals when predicting good outcome is less important than when predicting poor outcome since good outcome predictors are not used to withdraw life-sustaining treatment.
Grey matter to white matter ratio (GWR) on brain CT
Hypoxic-ischemic changes due to cardiac arrest were quantified using the ratio between the densities (measured in Hounsfield units) of the grey and the white matter (Grey matter/White matter ratio: GWR). In the normal brain, grey matter has a higher density than white matter. The occurrence of brain oedema reduces GWR.
The ability of brain CT performed at one to three hours after ROSC to predict good neurological outcome was assessed in one study [Lee, 2017 1628] of 67 patients. In the included study, a GWR >1.25 at 124.5 min (±59.9 min) after ROSC predicted good neurological outcome at 1 month with 77% [95%CI, 62.0–87.7%] specificity and 25% [95%CI, 8.7–49.1%] sensitivity (very-low certainty of evidence).
Quantitative regional abnormality (QRA)
QRA is the sum of hypoattenuations in 12 parenchymal areas on brain CT and is calculated bilaterally (lower scores indicate fewer hypoattenuation, maximum score of 24).
In one study [Lee, 2017 1628] on 67 patients, a QRA ≤5 at 124.5 min (±59.9 min) after ROSC predicted good neurological outcome at 1 month with 77% [95%CI, 62.0–87.7%] specificity and 25% [95% CI, 8.7–49.1%] sensitivity (very-low certainty of evidence).
Alberta Stroke Program Early CT Score (ASPECTS-b)
ASPECTS-b provides a semiquantitative assessment of early ischemic changes on brain CT in the middle cerebral artery territory, bilaterally. ASPECTS-b score is calculated by subtracting 1 per each change from the maximum score of 20 points. Lower scores indicate more abnormalities.
In one study [Lee, 2017 1628] of 67 patients, ASPECTS-b≥15 at 124.5 min (±59.9 min) after ROSC predicted good neurological outcome at 1 month with 89% [95% CI, 76.9–96.0%] specificity and 75% [95% CI, 50.9–91.3%] sensitivity (very-low certainty of evidence).
Diffusion-weighted imaging (DWI)
DWI on magnetic resonance imaging (MRI) was investigated in five observational studies [Park, 2020, 39; Oh, 2019, 142; Jang, 2019, 142; Mlynash, 2010, 1665; Wouters, 2021, e2611].
In one study [Oh, 2019] on 134 patients, the absence of restricted diffusion in the cortex or the deep grey matter on DWI immediately after rewarming predicted good neurological outcome at 6 months with 94.5% [95% CI 88.5-98.3%] specificity and 72% [95% CI 54.8–85.8%] sensitivity (very-low certainty of evidence).
In one study [Oh, 2019] on 134 patients, the presence of no areas or a single area of restricted diffusion in the cortex or the deep grey matter immediately after rewarming predicted good neurological outcome at 6 months with 91.8% [84.5–96.4] specificity) and 94.4% [81.3–99.3] sensitivity (very-low certainty of evidence).
In one study [Park, 2020] on 36 patients, the absence of restricted diffusion at 3.1 [2.4–4] h after ROSC predicted good outcome at 6 months with 60% [32.3–83.7] specificity and 100% [86.7–100] sensitivity (very-low certainty of evidence).
In one study [Park, 2020] on 36 patients, the absence of restricted diffusion on MRI at 77.6 (75.9–80) h after ROSC predicted good outcome at 6 months with 93.3% [68.1–99.8] specificity and 100 [86.7–100] sensitivity (very-low certainty of evidence).
In one study (Jang, 2019, 142) on 39 patients, the absence of restricted diffusion on MRI at 77.6 (75.9–80) h after ROSC predicted good outcome at 6 months with 93.3% [68.1–99.8] specificity and 100% [86.7–100] sensitivity (very-low certainty of evidence).
In one study (Mlynash, 2010, 1665) on 33 patients, the absence of areas of restricted diffusion or changes in fluid-attenuated inversion recovery (FLAIR) in the cortex on MRI within 8 days from ROSC predicted good outcome at 6 months with 80% [51.9–95.7] specificity and 77.8% [52.4–93.6] sensitivity (very-low certainty of evidence).
In one study (Mlynash, 2010, 1665) on 33 patients, the absence of areas of restricted diffusion or changes in fluid-attenuated inversion recovery (FLAIR) in the deep grey nuclei on MRI within 8 days from ROSC predicted good outcome at 6 months with 86.7% [59.5–98.3] specificity and 50% [26–74] sensitivity (very-low certainty of evidence).
In one study (Mlynash, 2010, 1665) on 33 patients, the absence of areas of restricted diffusion or changes in fluid-attenuated inversion recovery (FLAIR) in the cerebellum and pons on MRI within 8 days from ROSC predicted good outcome at 6 months with 20% [4.3–48.1] specificity and 100% [84.7–100] sensitivity (very-low certainty of evidence).
In one study (Wouters, 2021, e2611) on 58 patients, an average apparent diffusion coefficient (ADC) value >931 x 10-6 mm2/s on day 5 (IQR 4-6) after ROSC predicted good outcome with 100% [86-100] sensitivity and 38% [23-58] specificity (very-low certainty of evidence).
In one study (Wouters, 2021, e2611) on 58 patients, a percentage <6.5% of brain voxels with an ADC value <450 x 10-6 mm2/s on day 5 (IQR 4-6) after ROSC predicted good outcome with 100% [86-100] sensitivity and 26% [13-46] specificity (very-low certainty of evidence).
Gradient-Recalled Echo (GRE)
The T2-weighted GRE sequence was investigated in one study (Jang, 2019, 142) on 39 patients. The absence of GRE changes measured as a summary GRE score = 0 at 74.5±16.1 h after ROSC predicted good neurological outcome at six months with 100% [89.5–100] specificity and 75% [42.8–94.5] sensitivity (very-low certainty of evidence).
Treatment Recommendations
- We suggest using the absence of diffusion restriction on MRI between 72h and 7 days after ROSC, in combination with other tests, for predicting good neurological outcome of adults who are comatose after cardiac arrest (weak recommendation, very-low-certainty evidence).
- We suggest against using GWR, QRA, or ASPECTS-b on brain CT to predict good neurological outcome in patients who are comatose after cardiac arrest (weak recommendation, very-low certainty of evidence).
- We suggest against using ADC on brain MRI to predict good neurological outcome in patients who are comatose after cardiac arrest (weak recommendation, very-low certainty of evidence).
- We suggest against using GRE on brain MRI to predict good neurological outcome in patients who are comatose after cardiac arrest (weak recommendation, very-low certainty of evidence).
Justification and Evidence to Decision Framework Highlights
- ● Evidence from five studies consistently suggests that the absence of visible cytotoxic oedema, assessed as the absence of cortical DWI changes on brain MRI, predicts good neurological outcome with high specificity at 72h or later after cardiac arrest.
- ● Apparent diffusion coefficient (ADC) allows a quantification of the diffusion changes on brain MRI. However, the evidence is limited to one study, and no ADC threshold for prediction of good neurological outcome has been established.
- ● Evidence showing that a high grey matter to white matter ratio (GWR), a low quantitative regional attenuation (QRA) score, or a high Alberta Stroke Program Early CT (ASPECTS-b) score predicts good neurological outcome after cardiac arrest is limited to one study, and the certainty of the evidence is very low. There is a wide heterogeneity of measurement techniques (sites and calculation methods) for GWR in medical literature.
- ● Evidence for GWR and GRE was limited to small, single-center studies.
- ● Lack of blinding was a limitation in all included studies. The supporting evidence had very low certainty.
Knowledge Gaps
- ● A consistent GWR threshold for predicting good neurological outcome after cardiac arrest should be identified.
- ● A standardization of the methods for GWR calculation is warranted.
- ● The optimal timing for prognostication using brain CT after cardiac arrest is still unknown. Studies assessing serial brain CT after cardiac arrest to predict good outcome are desirable.
- ● The criteria for defining a normal MRI after cardiac arrest must be standardized
- A standardization of the methods for calculating ADC is warranted.
Attachments:
References
Jang J, Oh SH, Nam Y, Lee K, Choi HS, Jung SL, Ahn KJ, Park KN, Kim BS. Prognostic value of phase information of 2d t2*-weighted gradient echo brain imaging in cardiac arrest survivors: A preliminary study. Resuscitation. 2019; 140:142-149.
Lee KS, Lee SE, Choi JY, Gho YR, Chae MK, Park EJ, Choi MH, Hong JM. Useful computed tomography score for estimation of early neurologic outcome in post-cardiac arrest patients with therapeutic hypothermia. Circulation journal: official journal of the Japanese Circulation Society. 2017; 8:1628-1635
Mlynash M, Campbell DM, Leproust EM, et al. Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest. Stroke 2010; 41:1665–1672.
Oh SH, Park KN, Choi SP, et al. Beyond dichotomy: patterns and amplitudes of SSEPs and neurological outcomes after cardiac arrest. Crit Care 2019; 23:224.
Park JS, In YN, You YH, et al. Ultra-early neurologic outcome prediction of out-of-hospital cardiac arrest survivors using combined diffusion-weighted imaging find- ings and quantitative analysis of apparent diffusion coefficient. Resuscitation 2020; 148:39–48
Wouters A, et al., Added Value of Quantitative Apparent Diffusion Coefficient Values for Neuroprognostication After Cardiac Arrest, Neurology, 2021; 96: e2611.