Prognostication with Point-of-Care Echocardiography during Cardiac Arrest (ALS): Systematic Review

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: none applicable.

CoSTR Citation

Reynolds JC, Nicholson TC, Drennan I, O’Neil BJ, Scholefield B, Soar J, Andersen LW, Böttiger BW, Callaway CW, Deakin CD, Donnino M, Hsu CH, Morley PT, Neumar RW, Nolan JP, Paiva EF, Parr MJ, Sandroni C, Wang TL, Welsford M. Prognostication with Point-of-Care Echocardiography During Cardiac Arrest: Consensus on Science with Treatment Recommendations [Internet]. Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force, 20193 January 2020. Available from: http://ilcor.org

Methodological Preamble

The continuous evidence evaluation process for the production of the Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review (PROSPERO Submission No. 150677; Final Registration No. Pending) conducted by Joshua C. Reynolds, Mahmoud Issa, Tonia Nicholson, Katherine Berg, Ian Drennan, and Brian O’Neil with involvement of methodologic and clinical content experts. Evidence from adult literature was sought and considered by the Advanced Life Support Adult Task Force.

In addition to standardized risk of bias assessment with the QUIPS tool, we especially considered two sources of bias unique to prognostication during resuscitation of cardiac arrest. Firstly, ‘self-fulfilling prophecy’, when clinicians involved with the decision to terminate resuscitation are not blinded to the results of point-of-care echocardiography, was a key consideration when reviewing studies for risk of bias. It was considered a critical risk of bias and precluded pooling studies. Second, the timing of point-of-care echocardiography during resuscitation was another key confounder since restoring cardiac motion is a primary goal of resuscitative therapies. For example, resuscitative interventions could lead to the restoration of cardiac motion, or cardiac motion could cease over the course of an unsuccessful resuscitation. The timing of a prognostic test assessing cardiac motion could artificially improve or lower its prognostic estimates.

Although the Cochrane Prognosis Working Group recommends estimating odds ratios or risk ratios in a prognostic factor systematic review, the binary nature of the clinical outcomes lends itself well to consideration in a standard 2x2 tabular format. While this was not a systematic review of diagnostic test accuracy, elements of test performance have clinical applications in the prognostication of clinical outcomes (i.e. ROSC) with a bedside tool (i.e. point-of-care echocardiography). In addition, we believe that consideration of the true- and false-positive rates of point-of-care echocardiography is more useful to clinicians than traditional measures of association.

Upon reviewing the included articles, we discovered wide variability in the definitions of ‘cardiac motion’ pertaining to anatomy (i.e. left ventricular contractions, any ventricular movement, any myocardial movement, any movement [including isolated valvular fluttering], or unspecified) and timing (initial, every, or any point-of-care echocardiogram; or unspecified). Ultimately, we classified studies describing cardiac motion as organized contractility or in a non-organized and/or unspecified motion. We classified studies describing echocardiogram timing as the initial echocardiogram, every echocardiogram, any echocardiogram, or unspecified timing. We grouped sonographic evidence of potentially treatable pathology (i.e. evidence of hypovolemia, pericardial effusion, cardiac tamponade, or right ventricular dilation) into one category. Finally, we describe several other miscellaneous sonographic findings.

PICOST

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Adults in any setting (in-hospital [IHCA] or out-of-hospital [OHCA]) with non-traumatic cardiac arrest.

Intervention: A particular finding on point-of-care echocardiography during CPR

Comparators: The absence of that finding or a different finding on point-of-care echocardiography during CPR

Outcomes: Clinical outcomes, including, but not necessarily limited to, return of spontaneous circulation, survival to hospital admission, survival/survival with a favorable neurological outcome at hospital discharge, and survival/survival with a favorable neurological outcome beyond hospital discharge. The final included outcomes will depend on the available data and subsequent outcome prioritization by the ILCOR task forces.

Study Designs: Randomized trials, non-randomized controlled trials, observational studies (cohort studies and case-control studies), registries, and prognosis studies. Ecological studies, case series, case reports, reviews, abstracts, editorials, comments, letters to the editor, or unpublished studies will not be included.

Timeframe: All years and all languages were included as long as there is an English abstract. Literature search updated to September 18, 2019.

PROSPERO Submission No. 150677; Final Registration No. Pending

Consensus on Science

The overall certainty of evidence was rated as very low for all outcomes primarily to risk of bias, inconsistency, or imprecision. The individual studies were at substantial risk of bias due to prognostic factor measurement, outcome measurement, adjustment for prognostic factors, or confounding. Because of this and a high degree of clinical heterogeneity, no meta-analyses could be performed and individual studies are difficult to interpret.

Organized Cardiac Motion (Unspecified Echocardiogram Timing)

For the critical outcome survival to 180 days, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Flato 2015 1) enrolling 49 adult IHCA subjects, which estimated sensitivity 1.00 (95% CI 0.40-1.00), specificity 0.49 (95% CI 0.34-0.64), and OR 8.62 (95% CI 0.44-169.38).

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Atkinson 2019 e4456, Flato 2015 1) enrolling 229 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.67 to 1.00, specificities ranging from 0.51 to 0.89, and OR ranging from 13.60 to 16.63.

For the important outcome survival to hospital admission, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Atkinson 2019 e4456, Blaivas 2001 616) enrolling 330 adult OHCA subjects, which estimated sensitivities ranging from 0.39 to 1.00, specificities ranging from 0.91 to 0.91, and OR ranging from 6.73 to 414.56 .

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Atkinson 2019 e4456, Flato 2015 1) enrolling 229 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.34 to 0.79, specificities ranging from 0.68 to 0.96, and OR ranging from 8.07 to 13.21.

Unspecified Cardiac Motion on Initial Echocardiogram

For the critical outcome favorable neurologic outcome at hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Aichinger 2012 251) enrolling 42 adult OHCA subjects, which estimated sensitivity 1.0 (95% 0.03-1.00), specificity 0.78 (95% CI 0.62-0.89), and OR 10.26 (95% CI 0.39-273.09).

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 3 observational studies (Gaspari 2016 33, Varriale 1997 1717, Zengin 2016 105) enrolling 1,171 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.06 to 0.91, specificities ranging from 0.49 to 0.94, and OR ranging from 0.38 to 17.00.

For the important outcome survival to hospital admission, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 4 observational studies (Aichinger 2012 251, Gaspari 2016 33, Salen 2001 459, Zengin 2016 105) enrolling 1,295 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.11 to 0.92, specificities ranging from 0.55 to 0.85, and OR ranging from 0.75 to 27.56.

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 3 observational studies (Gaspari 2016 33, Kim 2016 21, Varriale 1997 1717) enrolling 861 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.25 to 0.64, specificities ranging from 0.78 to 1.00, and OR ranging from 6.33 to 16.11.

Unspecified Cardiac Motion on Every Echocardiogram

For the important outcome survival to hospital admission, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Aichinger 2012 251, Salen 2001 459) enrolling 141 adult OHCA subjects, which estimated sensitivities ranging from 0.46 to 0.80, specificities ranging from 0.92 to 1.00, and OR ranging from 46.67 to 148.20.

Unspecified Cardiac Motion (Unspecified Echocardiogram Timing)

For the critical outcome favorable neurologic outcome at 180 days, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Flato 2015 1) enrolling 49 adult IHCA subjects , which estimated sensitivity 1.0 (95% CI 0.4-1.0), specificity 0.49 (95% CI 0.34-0.64), and OR 8.62 (95% CI 0.44-169.38).

For the critical outcome favorable neurologic outcome at hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Salen 2005 610) enrolling 70 adult OHCA subjects, which estimated sensitivity 1.0 (95% 0.03-1.00), specificity 0.86 (95% CI 0.75-0.93), and OR 17.00 (95% CI 0.65-446.02).

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Lien 2018 125) enrolling 177 adult OHCA subjects, which estimated sensitivity 0.48 (95% CI 0.28-0.69), specificity 0.77 (95% CI 0.69-0.83), and OR 3.09 (95% CI 1.29-7.37).

For the important outcome survival to hospital admission, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 3 observational studies (Breitkreutz 2010 1527, Chua 2017 310, Salen 2001 459) enrolling 291 adult OHCA subjects, which estimated sensitivities ranging from 0.72 to 0.86, specificities ranging from 0.60 to 0.84, and OR ranging from 9.14 to 14.00.

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 4 observational studies (Chardoli 2012 284, Lien 2018 125, Salen 2005 610, Tayal 2003 315) enrolling 307 adult OHCA subjects, which estimated sensitivities ranging from 0.62 to 1.00, specificities ranging from 0.33 to 0.98, and OR ranging from 23.18 to 289.00.

Return of Organized Cardiac Motion on Subsequent Echocardiogram

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Varriale 1997 1717) enrolling 21 adult IHCA subjects, which estimated sensitivity 0.50 (95% CI 0.01-0.99), specificity 0.79 (95% CI 0.54-0.94), and OR 3.75 (95% CI 0.19-74.06).

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Varriale 1997 1717) enrolling 20 adult IHCA subjects, which estimated sensitivity 0.67 (95% CI 0.22-0.96), specificity 1.00 (95% CI 0.77-1.00), and OR 52.50 (95% CI 2.10-1,300.33).

Coalescent Echo Contrast (i.e. visible clotted intra-cardiac blood) after 20-30 min CPR

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Varriale 1997 1717) enrolling 20 adult IHCA subjects, which estimated sensitivity 0.00 (95% CI 0.00-0.84), specificity 0.45 (95% CI 0.23-0.68), and OR 0.13 (95% CI 0.01-3.11).

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and imprecision) from 1 observational study (Varriale 1997 1717) enrolling 20 adult IHCA subjects, which estimated sensitivity 0.00 (95% CI 0.00-0.46), specificity 0.21 (95% CI 0.05-0.51), and OR 0.02 (95% CI 0.00-0.53).

Sonographic Evidence of Treatable Pathology

For the critical outcome survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias) from 3 observational studies (Gaspari 2016 33, Varriale 1997 1717, Zengin 2016 105) enrolling 20 adult IHCA and OHCA 1,190 subjects, which estimated sensitivities ranging from 0.00 to 0.15, specificities ranging from 0.89-0.98, and OR ranging from 1.32 to 4.25.

For the important outcome survival to hospital admission, we have identified very low certainty evidence (downgraded for risk of bias) from 1 observational study (Zengin 2016 105) enrolling 531 adult IHCA and OHCA subjects , which estimated sensitivities ranging from 0.03 to 0.04, specificities ranging from 0.95 to 0.99, and OR ranging from 0.61 to 4.70.

For the important outcome ROSC, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 4 observational studies (Chardoli 2012 284, Lien 2018 125, Tayal 2003 315, Varriale 1997 1717) enrolling 317 adult IHCA and OHCA subjects, which estimated sensitivities ranging from 0.00 to 1.00, specificities ranging from 0.84 to 0.94, and OR ranging from 0.38 to 125.00.

Treatment Recommendations

We suggest against using point-of-care echocardiography for prognostication during cardiopulmonary resuscitation (weak recommendation, very low certainty of evidence).

Justification and Evidence to Decision Framework Highlights

This topic was prioritized by the ALS Task Force based on the high prevalence of point-of-care echocardiography during cardiac arrest without recognizing the potential pitfalls for misinterpretation as an adjunct prognostic tool. Given the increasing popularity of point-of-care echocardiography during cardiac arrest into current clinical practice, a comprehensive and rigorous summary of its intra-arrest prognostic capabilities provides valuable information to both the resuscitation science community and bedside clinicians.

In making these recommendations, the ALS Task Force considered the following:

• There were inconsistent definitions and terminology around sonographic evidence of cardiac motion. This included wide variation in the classification of anatomy, type of motion, and timing of point-of-care echocardiogram. We strongly encourage the establishment of uniform definitions and terminology to describe sonographic findings of cardiac activity during cardiac arrest.

• Most of the identified studies suffer from high risk of bias related to prognostic factor measurement, outcome measurement, lack of adjustment for other prognostic factors, and confounding from self-fulfilling prophecy and unspecified timing of point-of-care echocardiography. Due to the risk of bias and heterogeneity between studies, no meta-analyses were performed. The evidence supporting use of point-of-care echocardiography as a prognostic tool during cardiac arrest is uniformly of very low certainty. Clinicians should interpret sonographic findings during cardiac arrest in light of these limitations. We strongly encourage subsequent investigations of point-of-care echocardiography during cardiac arrest to employ methodology that mitigates these risks of bias.

• Only 2 studies (Flato 2015 1; Gaspari 2016 33) reported estimates of inter-rater reliability (Kappa 0.63 and 0.93). We strongly encourage subsequent investigations of point-of-care echocardiography during cardiac arrest to estimate inter-rater reliability.

• No sonographic finding had sufficient and/or consistent sensitivity for any clinical outcome to be used a sole criterion to terminate resuscitative efforts, but the certainty of this evidence is very low.

• Some sonographic findings had higher ranges of specificity for clinical, but the certainty of this evidence is very low.

• The impact of extracorporeal CPR (ECPR) on the prognostic accuracy of point-of-care echocardiography is uncertain.

• Point-of-care echocardiography may still have utility to diagnose treatable etiologies of cardiac arrest or to intermittently assess response to resuscitative treatments. These applications are not within the scope of this particular PICOST question. We do caution against over-interpreting the finding of right ventricular dilation in isolation as a diagnostic indicator of massive pulmonary embolism. Right ventricular dilation begins a few minutes after onset of cardiac arrest as blood shifts from the systemic circulation to the right heart along its pressure gradient. (Querellou 2009 769, Blanco 2016 15) Right ventricular dilation was uniformly observed in a porcine model of cardiac arrest across etiologies of hypovolemia, hyperkalemia, and primary arrhythmia. (Aagaard 2017 e963)

• Clinicians should be cautious about introducing additional interruptions in chest compressions with a transthoracic approach to point-of-care echocardiography during cardiac arrest. (Huis In’t Veld 2017 95, Clattenburg 2018 65).

• Point-of-care echocardiography is subject to availability of equipment and skilled operators.

Knowledge Gaps

There is no standardized or uniform definition of cardiac motion visualized on point-of-care echocardiography during cardiac arrest.

There are very few prognostic factor studies of point-of-care echocardiography during cardiac arrest performed with methodology that minimizes risk of bias.

The inter-rater reliability of point-of-care echocardiography during cardiac arrest is uncertain.

There were no studies identified that provided data on resource requirement, cost-effectiveness, equity, acceptability, or feasibility.

Attachments

Evidence-to-Decision Table: POCUS

References

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