Cardiac Arrest Centers versus Non-Cardiac Arrest Centers – Adults (ALS & EIT): Systematic Review

Cardiac Arrest Centers versus Non-Cardiac Arrest Centers – Adults

Citation

Yeung J, Bray J, Reynolds J, Matsuyama T, Skrifvars M, Lang E, Singletary E, Lockey A, Pellegrino J, Gilfoyle E, Duff J, Hsieh M Monsieurs K, Breckwoldt J, Iwami T, Bigham B Okamoto D, Ma M, Ong M Bhanji F, Greif R on behalf of the ALS and EIT Task Forces. Cardiac Arrest Centers versus Non-Cardiac Arrest Centers – Adults. Consensus on Science and Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) EIT and ALS Task Forces, 2019 January 3023. 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 cardiac arrest centers (Yeung, 2018, - PROSPERO - CRD 42018093369) conducted by two ILCOR evidence reviewers (Yeung and Matsuyama) with involvement of clinical content experts (Bray, Reynolds, Skrifvars). Evidence for adult literature was sought and considered by the Education, Implementation and Teams (EIT) Task Force and the Advanced Life Support (ALS) Task Force groups. Additional scientific literature was published (Elmer 2018 48) after the completion of the systematic review and identified by the EIT Task Force and is described before the Justifications and Evidence to Decision Highlights section of this CoSTR. These data were taken into account when formulating the Treatment Recommendations.

CACs were considered hospitals providing evidence-based post-resuscitation treatments, namely targeted temperature management and cardiac intervention (e.g. cardiac angiogram) (Callaway 2015 S84; Soar 2015 e71). The majority of the included studies compared outcomes in OHCA patients who were cared for at a CAC compared to those cared for at non-CACs; however the description of prehospital triage practices in the studies varied between transport to: closest hospital (n=5), triage of select patients to CACs (n=4), triage of all patients to CACs (n=3) or were not described (n=5). Furthermore, some studies used the characteristics of the first treating centers, whereas others used last or did not define.
Given the potential for confounding, data were only included in the meta-analysis from studies reporting adjusted outcomes. Individual studies reporting unadjusted data are identified but not pooled

Systematic review

Yeung J, Matsuyama T, Bray J, Reynolds J, Skrifvars MB. Does care at a cardiac arrest center improve outcome after out-of-hospital cardiac arrest? – A systematic review. Link to come.

PICOST

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

Population: Adults with attempted resuscitation after non-traumatic in-hospital (IHCA) or out-of-hospital (OHCA) cardiac arrest.

Intervention: Care at a specialized cardiac arrest center (CAC).

Comparators: Care in an institute not designated as a specialized cardiac arrest center.

Outcomes: Primary outcomes were: survival at 30 days with favorable neurological outcome (defined as Cerebral Performance Category [CPC] 1 or 2, modified Rankin Scale [mRS] 0-3); and Survival at hospital discharge with favorable neurological outcome (defined as CPC 1 or 2, mRS 0-3). Secondary outcomes were: Survival at 30 days; Survival at hospital discharge and Return of spontaneous circulation (ROSC) after hospital admission.

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) were eligible for inclusion. Unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Studies reporting pediatric cardiac arrests (≤18 years old) and cardiac arrest secondary to trauma were excluded.

Timeframe: All years and all languages were included provided there was an English abstract. Literature search updated to the 1st August 2018.

PROSPERO registration: CRD42018091427

Consensus on Science

OHCA

For the critical outcome (O) of survival to 30 days with favorable neurologic outcome, we identified very-low-certainty evidence (downgraded for risk of bias, inconsistency, and imprecision) from 2 observational studies (Matsuyama 2017 146, Tagami 2012 589) reporting adjusted analyses involving 45,956 OHCA subjects and 1 observational study (Seiner 2018 e234) reporting unadjusted analyses involving 208 OHCA subjects (P). The adjusted data showed no difference in survival to 30 days with favorable neurologic outcome in patients cared for at CACs (I) compared with those care for at non-CACs (C) (OR 2.92, 95% CI 0.68 to 12.48).

For the critical outcome of survival to hospital discharge with favorable neurologic outcome at discharge, we identified very-low-certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Kragholm 2017 e003414, Spaite 2014 496) reporting adjusted analyses involving 3,673 adult OHCA subjects and 2 observational studies (Couper 2018 49, Soholm 2015 268) reporting unadjusted analyses involving 18,682 OHCA subjects. The adjusted data showed improved neurological outcome in patients cared for at CACs (I) compared with those care for at non-CACs (C) (OR 2.22 95% CI 1.74 to 2.84).

For the critical outcome of survival to 30 days, we identified very-low-certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Harnold 2013 216, Soholm 2013 162) reporting adjusted analyses involving 2,693 adult OHCA subjects and 4 observational studies (Elmer 2018 48, Matsuyama 2017 146, Seiner 2018 e234, Tranberg 2017 1645) reporting unadjusted analyses involving 47,590 adult OHCA subjects. The adjusted data showed no difference in survival to 30-days in patients cared for at CACs (I) compared with those care for at non-CACs (C) (OR 2.14 95% CI 0.73 to 6.29).

For the critical outcome of survival to hospital discharge, we identified very-low-certainty evidence (downgraded for risk of bias and inconsistency) from 5 observational studies (Cournoyer 2018 28, Kragholm 2017 e003414, Lick 2011 26, Spaite 2014 496, Stub 2011 1489) reporting adjusted analyses involving 11,662 adult OHCA subjects and 5 observational studies (Couper 2018 49, Chocron 2017 63, Lai 2018 e0191954, Soholm 2015 162, McKenzie 2018 76) reporting unadjusted analyses involving 31,653 adult OHCA subjects. The adjusted data showed improved survival to hospital discharge in patients cared for at CACs (I) compared with those care for at non-CACs (C) (OR 1.85 95% CI 1.46 to 2.34).

For the important outcome of ROSC after hospital admission in subjects with ongoing resuscitation, we identified very-low-certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies reporting unadjusted analyses involving 41,447 adult OHCAs (Matsuyama 2017 146, Tagami 2012 589). The pooled adjusted data showed no difference in rates of ROSC in patients cared for at CACs (I) compared with those cared for at non-CACs (C) (OR 1.24 95% CI 0.93 to 1.66).

IHCA

Only one observational study (Elmer 2016 108) reported combined data on IHCA and OHCA. No data on isolated IHCA were identified.

Subgroups

We pre-planned subgroup analyses of subjects with shockable vs. non-shockable initial cardiac rhythm, and primary transport vs. secondary transfer to CAC. Heterogeneity in reported outcomes and lack of adjusted analyses precluded meta-analysis for either subgroup.

Shockable versus non-shockable

There were eight studies that reported outcomes in CACs versus non-CACs stratified by shockable or non-shockable rhythms (Chocron 2017, Cournoyer 2018 28, Elmer 2018 48, Lick 2018 26, Mumma 2015, Seiner 2018 e234, Spaite 2014 496, Tagami 2012 589).

In patients with shockable rhythm, five studies reported improved outcomes at CACs (Elmer 2018 48, Lick 2018 26, Mumma 2015, Spaite 2014 496, Tagami 2012 589), and three studies reported no difference (Chocron 2017, Cournoyer 2018 28, Seiner 2018 e234).

In patients with non-shockable initial rhythms, CACs were associated with improved outcomes in one study (Mumma 2015) and no difference in two studies (Cournoyer 2018 28, Spaite 2014 496).

Primary versus secondary transfers

Only four studies examined outcomes in OHCA patients who were transferred to a CAC from a non-CAC (Elmer 2018 48, Lai 2018 e0191954, McKenzie 2018 76, Tagami 2012 589). Two studies reported no difference in (unadjusted) outcomes in patients transferred compared to patients directly transported (Elmer 2018 48, Tagami 2012 589). One study (McKenzie 2018 76) reported higher (adjusted) survival in patients who were transferred directly to a CAC compared to secondary transfers (OR 1.97 95%CI 1.13 to 3.43). Another study (Lai 2018 e0191954) reported higher (adjusted) survival among patients secondarily transferred to a CAC compared to patients remaining at initial treating non-CACs (OR 1.59 95%CI 1.30 to 1.93). One study (Kragholm 2017 e003414) reported higher (adjusted) survival in patients who bypassed the nearest non-CAC compared to patients transported to non-CACs (OR 3.01 95%CI 2.01 to 4.53).

Treatment Recommendations

We suggest adult non-traumatic OHCA cardiac arrest patients (P) be cared for in cardiac arrest centers (I) rather than in non-cardiac arrest centers (C) (weak recommendation, very low certainty of evidence).

We cannot make a recommendation for or against regional triage of OHCA patients to a cardiac arrest center by primary EMS transport (bypass protocols) or secondary interfacility transfer. The current evidence is inconclusive and confidence in the effect estimates is currently too low to support an EIT and ALS Task Force recommendation.

For patients with in-hospital cardiac arrest, we found no evidence to support an EIT and ALS Task Force recommendation.

For patients with shockable or non-shockable initial cardiac rhythm, the current evidence is inconclusive and confidence in the effect estimates is currently too low to support an EIT and ALS Task Force recommendation.

Justification and Evidence to Decision Highlights

• This PICO was prioritized for review by the EIT and ALS Task Forces based on several large registry studies comparing outcomes of patients treated at cardiac arrest centers (CACs) compared with non- cardiac arrest centers (non-CACs) published after the previous CoSTR in 2015 (Bhanji 2015 S242; Finn 2015 e203).
• In considering the importance of this topic, we note the wide variability in survival (8-16%) among hospitals caring for patients after resuscitation from OHCA. In most countries, post resuscitation care is not regionalized to specialized hospitals and there is wide variation among hospitals in the availability and type of post-resuscitation care, as well as clinical outcomes.

In making this recommendation, the EIT and ALS Task Force concluded that the potential benefits in clinical outcomes outweighed the potential risks and logistical issues with implementation. We also considered the following:

• We considered the consistency of improved outcomes in patients treated at CACs across most studies; even though the certainty of the evidence is very low, studies were all observational and the heterogeneity of included studies was high.
• We placed a high value on the importance of patients receiving evidence based post-resuscitation care that contributes to improving outcomes that are important to patients.
• We noted other evidence demonstrating benefits of specialized acute care for other emergency conditions such as trauma, stroke and ST-elevation myocardial infarction.
• We note the lack of evidence suggesting clinical harm due to longer transport time. (Geri 2017 96).
• We considered the limited available data on regional triage of OHCA patients to cardiac arrest centers via primary EMS transport or secondary inter-facility transfer. We considered the potential for referral bias (transporting patient likely to survive) in this evidence. The ideal regional triage scheme of OHCA patients to cardiac arrest centers is likely region-dependent. The impact of primary EMS transport or secondary inter-facility transfer is identified as a knowledge gap.
• We considered the uncertainties and implications of feasibility, costs, impact on health care systems and resource use. We recognize that the implementation of this recommendation may not be feasible in all regions due to resources, costs, and inherent differences in health care delivery.
• We considered that regionalized cardiac arrest care may remove patients from their local social support networks.
• It remains unclear whether specific patient subgroups (e.g. shockable or nonshockable initial cardiac rhythm) benefit to a different extent from regionalized cardiac arrest care. This is identified as a knowledge gap.
• We did not find any studies on in-hospital cardiac arrest and have identified this as a knowledge gap.

Knowledge Gaps

Current knowledge gaps include but are not limited to:

• There are currently no randomized data on this topic beyond a single, small, feasibility trial.
• There is no high-quality evidence surrounding primary EMS transport compared to secondary inter-facility transfer to CACs.
• There is no evidence regarding IHCA.
• There is no universal definition of a cardiac arrest center. The precise aspects of post-cardiac arrest care that improve outcomes is unclear.
• Evidence of the impact on other clinical outcomes such as cognitive recovery and quality of life are lacking.
• Evidence in certain subgroups of cardiac arrest patients (e.g. cardiac etiology, shockable rhythm, and witnessed collapse) is currently insufficient.
• There is no evidence of the cost-effectiveness of caring for OHCA patients at specialized cardiac arrest centers.
• More evidence is needed on the risks of bypassing a local hospitals and transferring patients to specialized cardiac arrest centers (e.g. re-arrest).
• More evidence is needed on whether OHCA subjects should be transported primarily to a specialized cardiac arrest center by prehospital services, or through secondary inter-facility transport after initial evaluation and stabilization at a local hospital.
• Studies are needed to assess the hospital- and clinician-level effects on bypassed hospitals (e.g. degrading skill set in post-resuscitation management and downgrading of services).
• The impact of transporting subjects away from their local social support networks is unknown.

Attachments

EtD: Should adults with cardiac arrest be cared for at cardiac arrest centers vs. non-cardiac arrest centers?

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