Value of Blood Pressure monitoring during pediatric cardiac arrest (PLS #814): Scoping 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

Task Force Scoping Review Citation

Van de Voorde P, Atkins DL, Maconochie I, Aicken R, Bingham R, Couto TB, de Caen A, Guerguerian AM, Nadkarni V, Ng KC, Nuthall G, Ong G, Reis A ,Schexynader S, Tijssen J , Scholefield B on behalf of the International Liaison Committee on Resuscitation Paediatric Life Support Task Force. on behalf of the International Liaison Committee on Resuscitation Paediatric Life Support Task Force. Value of Blood Pressure Monitoring during pediatric cardiac arrest. Scoping Review and Task Force Insights [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Life Support Task Force, 2020 Jan 09. Available from: http://ilcor.org

Methodological Preamble and Link to Published Scoping Review

The continuous evidence evaluation process started with a scoping review of blood pressure and haemodynamic resuscitation in paediatric cardiac arrest, conducted by the ILCOR PLS Task Force Scoping Review team. Evidence from adult and pediatric literature was sought and considered by the PLS Task Force.

Scoping Review

Pending

The PICOST

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

Population: Infants & Children in any setting (in-hospital or out-of-hospital) with cardiac arrest

Intervention: the presence of variables -images, cut-off values or trends- during CPR (intra-arrest) that can provide physiologic feedback to guide resuscitation efforts, namely:

2/ Arterial blood pressure

Comparators: the absence of such factors -images, cut-off values or trends.

Outcomes: Any clinical outcome.

Study Designs: STEP 1: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies). If there are insufficient studies from which to draw a conclusion, case series may be included in the initial search. Unpublished studies (e.g., conference abstracts, trial protocols) will be excluded.
STEP 2: the same study designs and/or existing systematic or scoping reviews not directly concerning the population or intervention defined above but considered informative as additional evidence – taking into account severe indirectness- for the development of the final taskforce insights.

Timeframe: For STEP 1, all languages are included, as long as there is an English abstract. We searched articles from 2015 onwards. For STEP 2, if a systematic or scoping review of high quality (as per AMSTAR 2 tool) is identified, search can be limited to beyond data and/or scope of that review.

Active and Reposed PICOs Related to scope of work for this PICOST:

P 826 Invasive Blood Pressure Monitoring During CPR

2015 Consensus on Science:

For the critical outcome of survival to 180 days and good neurologic outcome, we identified no studies. For the critical outcome of survival to 60 days and good neurologic outcome, we identified no studies. For the critical outcome of survival to hospital discharge and good neurologic outcome, we identified no studies. For the critical outcome of the likelihood of survival to discharge, we identified very-low-quality evidence (downgraded for risk of bias, very serious inconsistency, indirectness, and imprecision) from 2 pediatric animal RCTs {Friess 2013 2698-2704; Sutton 2013 696-701} involving 43 subjects, which showed benefit. For the important outcome of ROSC, we identified very-low-quality evidence (downgraded for risk of bias, inconsistency, very serious indirectness, and imprecision) from 2 pediatric animal RCTs {Friess 2013 2698-2704; Sutton 2013 696-701} involving 43 subjects, which showed benefit.

2015 Treatment Recommendation:

The confidence in effect estimates is so low that the panel decided a recommendation was too speculative.

Search Strategies

We searched PUBMED and Embase with the predefined inclusion criteria (13/09/2019 – final review 10/01/2020) and combined the following terms using Bolean operators: life support care, cardiopulmonary resuscitation, ROSC, heart arrest, cardiac arrest using both individual (ti,ab,kw) and related MESH terms, as well as exploded terms within Embase. We combined these with the terms: blood pressure, diastolic, systolic, (mean) arterial pressure, coronary perfusion pressure, hemodynamic-directed, haemodynamic-directed (again both individual and MESH terms, and Embase exploded terms). Detailed search strategies are listed at the end of this document.

We identified 689 articles after elimination of duplicates. For the subsequent screening by title, we excluded those studies that clearly did not have blood pressure as study focus, were not focussed on values during cardiac arrest or obviously had one of the other pre-defined exclusion criteria.

We accepted only 19 abstracts for full text review (with exclusion of 1 duplicate paper). 100% consensus was reached after a first blinded individual review (Rayyan.qrci.org) and a subsequent discussion about 1 abstract. After subsequent full text review, two studies met criteria for inclusion in this review (step 1). In step 2, we withheld 1 adult study, 1 SR of 6 animal studies and 4 additional animal studies (from 2014 onwards). Finally, a follow-up review (10/01/2020) identified 1 additional animal study.

Inclusion and Exclusion criteria

Inclusion: Studies that evaluate the population and intervention in the PICOST. Studies evaluating those variables that can be measured or monitored during the provision of ALS and before ROSC and that have potential to provide (physiologic and/or haemodynamic) feedback to the resuscitating team, potentially guiding their actions to improve outcome, and which might predict outcome.

Exclusions include:

1/ Newborn at Delivery

2/ Pre-arrest features, not influenced by ALS: time of day, location, bystander CPR, gasping, age, etiology, initial rhythm, unwitnessed…

3/ Standard ALS interventions e.g. ventilation strategies, fluids, firm surface, medications given, eCPR, length and Quality of CPR….

4/ Post-ROSC parameters such as lactate clearance, post-arrest rhythm, hypotension nor any actions to provide neuroprotective care post-ROSC.

Adult data are only considered in step 2 as both the etiology and pathophysiology of paediatric arrest differs substantially (serious indirectness). Moreover, the complexity or impact of obtaining the variable under study will likely differ e.g. placing an arterial line… Finally, animal data are considered in step 2 but -as human data are available- mostly to inform the knowledge gaps and possible future research agenda.

Outcomes considered include: Quality of CPR, ROSC, survival to discharge, (changes in) functional outcome at discharge or other time points.

Data tables

Task Force Insights

1. Why this topic was reviewed.

Ideally, physiologic monitoring and feedback to the clinician during cardiac arrest resuscitation would allow rescuers to monitor and adjust the quality of CPR, and to predict and influence the likelihood of return of spontaneous circulation and subsequent neurologic recovery. As such, this physiologic monitoring could lead to a form of ‘individualised’ CPR, where actions are altered to match with individual needs and responses of the victim in cardiac arrest.

Arterial blood pressure (systolic (SBP), diastolic (DBP) or mean blood pressure (MBP)) drive coronary and brain perfusion and therefore certain levels of systolic, diastolic or mean blood pressure might be associated with improved outcome. This observation has been supported by both pre-clinical data and expert experience. However, it is unknown if CPR with an individualized BP-goal directed protocol rather than the standard one-size-fits-all protocol could change outcome. Given the need for invasive monitoring this question currently seems limited to the IHCA subpopulation, and more specifically to those in an intensive care environment

2. Narrative summary of evidence identified

We identified 2 observational studies from the same group (describing essentially the same population). Wolfe et al {Wolfe 2019 57} did not find any association between any BP and neurological outcome in a cohort of survivors from (PICU-PCICU) IHCA. Berg et al {Berg 2018 174} did find, in a very preselected population, a significant association between the mean diastolic BP during the first 10 minutes (or less) of CPR and outcome. Although the test performance as such was less than optimal, Berg et al were able to define ROC curve threshold optimums. The optimal ROC curve thresholds without covariable consideration were 27 mmHg (infants) and 31.75 mmHg (children). These correlated with predicted survival rates of 63% [35-84] and 67% [48-82]. Survival rapidly dropped with thresholds below 20 mmHg (infant) and 25 mmHg (child). The lowest mean DBP with survival to discharge was 16mmHg (infants) resp. 18 mmHg (children).

To further explore the topic, we also looked at indirect evidence from adult and animal studies (STEP 2). Chopra et all {Chopra 2016 102} performed a systematic review on hemodynamic-directed feedback during resuscitation and identified 6 animal studies (from 2 research groups and published between 2011 and 2014; only studies with a control group were included). The 4 studies looking at survival showed a significant advantage of hemodynamic [HD]-directed CPR, but given the limited sample sizes, the authors did not feel the evidence to be sufficient to draw any conclusions.

This identified trend was also confirmed in more recent pediatric animal studies (mostly form the same research group).

Morgan et al {Morgan 2016 6} compared HD-directed CPR with standard CPR in a 3-month swine model of either asphyxia-associated or primary VF. They had 37/60 animals (61.7%) surviving to 45 minutes. Diastolic blood pressure was superior to ETCO2 in discriminating survivors (AUC 0.82 vs 0.6) with an optimal cut-off of 34.1 mmHg. Still the test performance was only moderate (sensitivity 0.78, specificity 0.81, PPV 0.64, NPV 0.89).

Naim et al {Naim 2016 e1111} also compared HD-directed CPR with standard CPR in a 3-month old swine model. Again, survival was higher in the HD-directed CPR group (24h survival 5 out of 8 vs. no survivors 0/8 in the standard group). The mean coronary perfusion pressure was higher, and the HD-directed group received more doses of vasopressor and had slightly less compression depth than the standard group.

Morgan et al {Morgan 2017 41} compared HD-directed CPR with standard CPR in an asphyxia VF piglet model. The 4-hour survival was 100% in the HD-directed group, vs. 6 / 10 for the standard group. Tthe mean coronary perfusion pressure was higher and the HD-directed group received more doses of vasopressor and had less compression depth (-14mm) than the standard group.

Lautz et al {Lautz 2019 e241} compared HD-directed CPR with standard CPR in a piglet model of asphyxia VF (N=28, with 6 sham animals). Favourable neurological outcome was observed in 7/10 HD-directed CPR animals, compared to 1/12 with standard CPR). Coronary perfusion pressure and brain tissue oxygenation were markedly higher in the piglets with HD-directed CPR.

Manrique et al (Manrique 2019 e0219660) randomised 60 piglets to compare between synchronized and non-synchronized BVMV with chest compressions (CC), and between guided and non-guided CC with a real-time feedback-device (Group A: guided-CC and synchronized ventilation; Group B: guided-CC and non-synchronized ventilation; Group C: non-guided CC and synchronized ventilation; Group D: non-guided CC and non-synchronized ventilation). Twenty-six (46.5%) achieved ROSC: A (46.7%), B (66.7%), C (26.7%) and D (33.3%). Survival rates were higher in group B than in groups A+C+D (66.7% vs 35.6%, p = 0.035). ROSC was higher with guided-CC (A+B 56.7% vs C+D 30%, p = 0.037). No differences were found in arterial pH and pO2, mean arterial pressure (MAP) or cerebral blood flow between groups. Chest compressions were shallower in surviving than in non-surviving piglets (4.7 vs 5.1 cm, p = 0.047). There was a negative correlation between time without CC and MAP (r = -0.35, p = 0.038).

Finally, there is one adult study using data from the AHA’s Get with the Guidelines-Resuscitation™ registry. Sutton et al {Sutton 2016 76} performed a prospective observational propensity-matched cohort study of adult IHCA. 3032 physiologic monitored patients (either by ETCO2 or diastolic BP) were compared to 6064 patients without monitoring. Those monitored showed a higher rate of ROSC (OR 1.22 [1.04; 1.43]) but not survival to discharge (OR 1.04 [0.91; 1.18]) nor survival with favourable neurological outcome. The study did not specifically look at diastolic BP and even for those with an arterial line in place only about 1/3 reported using the diastolic BP to guide their CPR efforts. Importantly most of the data in this register were collected before 2010.

3. Narrative Reporting of the task force discussions
Cardiac arrest still has an overall poor prognosis. High quality CPR improves outcome, but what constitutes the best possible CPR for an individual patient is still based on limited evidence and may be different for different etiological factors. Having parameters to guide CPR and adjust it to the need of the individual patient is therefore essential.
Adequate myocardial and brain tissue perfusion is fundamental to outcome and (diastolic) blood pressure could be useful as a clinically measurable surrogate for this. The identified evidence reports a possible relation between diastolic BP and patient outcome. Only IHCA events were studied because of the need for invasive BP monitoring.
Although Berg et al were able to identify optimal ROC curve thresholds with regard to test performance, and also identified thresholds below which no child survived, the evidence is too limited to consider diastolic BP in itself sufficient to identify CPR futility.

The potential value of truly personalised hemodynamic-directed CPR, where CPR efforts (chest compressions, vasopressor doses, etiological treatments) are adjusted in view of pre-defined (diastolic) BP goals and not limited by current ‘standard’ guidelines, has yet to be defined. Animal studies suggest a positive impact on outcome of such an approach but can only be seen as exploratory and hypothesis-generating.

This scoping review has not identified sufficient new evidence to prompt either a new systematic review or reconsideration of current resuscitation guidelines/treatment recommendations.

Knowledge Gaps

Clear need for RCTs to assess potential value of truly personalised hemodynamic-directed CPR, where CPR efforts (chest compressions, vasopressor doses, etiological treatments) are adjusted in view of pre-defined (diastolic) BP goals and not limited by current ‘standard’ guidelines.

References

1. Berg RA, Sutton RM, Reeder RW, Berger JT, Newth CJ, Carcillo JA, McQuillen PS, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) PICqCPR (Pediatric Intensive Care Quality of Cardio-Pulmonary Resuscitation) Investigators. Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival. Circulation. 2018 24; 137:1784-1795
2. Chopra AS, Wong N, Ziegler CP, Morrison LJ. Systematic review and meta-analysis of hemodynamic-directed feedback during cardiopulmonary resuscitation in cardiac arrest. Resuscitation. 2016; 101:102-7
3. Lautz AJ, Morgan RW, Karlsson M, Mavroudis CD, Ko TS, Licht DJ, Nadkarni VM, Berg RA, Sutton RM, Kilbaugh TJ. Hemodynamic-Directed Cardiopulmonary Resuscitation Improves Neurologic Outcomes and Mitochondrial Function in the Heart and Brain. Crit Care Med. 2019; 47(3):e241-e249
4. Manrique G, García M, Fernández SN, González R, Solana MJ, López J, Urbano J, López-Herce J. Comparison between synchronized and non-synchronized ventilation and between guided and non-guided chest compressions during resuscitation in a pediatric animal model after asphyxial cardiac arrest. PLoS One. 2019; 14(7):e0219660
5. Morgan RW, French B, Kilbaugh TJ, Naim MY, Wolfe H, Bratinov G, Shoap W, Hsieh TC, Nadkarni VM, Berg RA, Sutton RM. A quantitative comparison of physiologic indicators of cardiopulmonary resuscitation quality: Diastolic blood pressure versus end-tidal carbon dioxide. Resuscitation. 2016; 104:6-11
6. Morgan RW, Kilbaugh TJ, Shoap W, Bratinov G, Lin Y, Hsieh TC, Nadkarni VM, et al; Pediatric Cardiac Arrest Survival Outcomes PiCASO Laboratory Investigators. A hemodynamic-directed approach to pediatric cardiopulmonary resuscitation (HD-CPR) improves survival. Resuscitation. 2017; 111:41-47
7. Naim MY, Sutton RM, Friess SH, Bratinov G, Bhalala U, Kilbaugh TJ, Lampe JW, Nadkarni VM, Becker LB, Berg RA. Blood Pressure- and Coronary Perfusion Pressure-Targeted Cardiopulmonary Resuscitation Improves 24-Hour Survival From Ventricular Fibrillation Cardiac Arrest. Crit Care Med. 2016; 44(11): e1111-e1117
8. Sutton RM, French B, Meaney PA, Topjian AA, Parshuram CS, Edelson DP, Schexnayder S, et al; American Heart Association’s Get With The Guidelines–Resuscitation Investigators. Physiologic monitoring of CPR quality during adult cardiac arrest: A propensity-matched cohort study. Resuscitation. 2016; 106:76-82
9. Wolfe HA, Sutton RM, Reeder RW, Meert KL, Pollack MM, Yates AR, Berger JT, et al; Eunice Kennedy Shriver National Institute of Child Health; Human Development Collaborative Pediatric Critical Care Research Network; Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Investigators. Functional outcomes among survivors of pediatric in-hospital cardiac arrest are associated with baseline neurologic and functional status, but not with diastolic blood pressure during CPR. Resuscitation. 2019; 143:57-65