1. Νέες μελέτες & νέες τεχνολογίες στην αναζωογόνηση
CAAM Study
Μαρία Δρακοπούλου
Α’ Καρδιολογική Κλινική
Ιπποκράτειο Νοσοκομείο

2. Aim
To improve the management of patients in cardiac arrest, and this by comparing two initial airway management methods: Tracheal intubation and bag-valve-mask ventilation

3. European Resuscitation Council Guidelines
J. Soar et al. / Resuscitation 95 (2015) 100–147

4. Hypothesis
Basic airway management (i.e. bag-valve-mask ventilation) is safe and may avoid the deleterious effects of tracheal intubation including interruption of chest compressions
Question
Is bag-mask ventilation noninferior to endotracheal intubation for initial airway management during advanced resuscitation of patients with out-of-hospital cardiac arrest?
Jabre P et al, JAMA. 2018 Feb 27;319(8):779-78

5. Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest
Design, Setting, and Participants Prospective, nationwide, population-based study
(All-Japan Utstein Registry) involving consecutive adult patients in Japan who
had an OHCA and in whom resuscitation was attempted by emergency responders with
subsequent transport to medical institutions from January 2005 through December 2010.
Main Outcome Measures Favorable neurological outcome 1 month after an OHCA,
defined as cerebral performance category 1 or 2.
Results Of the eligible patients with OHCA, (57%) underwent bagvalve-
mask ventilation and (43%) advanced airway management, including
(6%) with endotracheal intubation and (37%) with use of supraglottic
airways. In the full cohort, the advanced airway group incurred a lower rate of favorable
neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%;
odds ratio [OR], 0.38; 95% CI, ). In multivariable logistic regression, advanced
airway management had an OR for favorable neurological outcome of 0.38
(95% CI, ) after adjusting for age, sex, etiology of arrest, first documented
rhythm, witnessed status, type of bystander cardiopulmonary resuscitation, use of public
access automated external defibrillator, epinephrine administration, and time intervals.
Similarly, the odds of neurologically favorable survival were significantly lower
both for endotracheal intubation (adjusted OR, 0.41; 95% CI, ) and for supraglottic
airways (adjusted OR, 0.38; 95% CI, ). In a propensity score–
matched cohort ( patients), the adjusted odds of neurologically favorable survival
were significantly lower both for endotracheal intubation (adjusted OR, 0.45;
95% CI, ) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI,
). Both endotracheal intubation and use of supraglottic airways were similarly
associated with decreased odds of neurologically favorable survival.Among adult patients with OHCA, any type of advanced
airway management was independently associated with decreased odds of neurologically
favorable survival compared with conventional bag-valve-mask ventilation
A large Japanese observational study of patients demonstrated a significant decrease in favorable functional survival associated with tracheal intubation vs ventilation by bag mask (1.1% vs 2.9%).
Hasegawa K et al, JAMA Jan 16;309(3):257-66

6. Advanced Cardiac Life Support in Out-of-Hospital Cardiac Arrest
The addition of ALS interventions did not improve the rate of survival after out-of-hospital CA
background
The Ontario Prehospital Advanced Life Support (OPALS) Study tested the incremental effect on the rate of survival after out-of-hospital cardiac arrest of adding a program of advanced life support to a program of rapid defibrillation.
methods
This multicenter, controlled clinical trial was conducted in 17 cities before and after advanced-life-support programs were instituted and enrolled 5638 patients who had had cardiac arrest outside the hospital. Of those patients, 1391 were enrolled during the rapid-defibrillation phase and 4247 during the subsequent advanced-life-support phase. Paramedics were trained in standard advanced life support, which includes endotracheal intubation and the administration of intravenous drugs.
results
From the rapid-defibrillation phase to the advanced-life-support phase, the rate of admission to a hospital increased significantly (10.9 percent vs percent, P<0.001), but the rate of survival to hospital discharge did not (5.0 percent vs. 5.1 percent, P=0.83). The multivariate odds ratio for survival after advanced life support was 1.1 (95 percent confidence interval, 0.8 to 1.5); after an arrest witnessed by a bystander, 4.4 (95 percent confidence interval, 3.1 to 6.4); after cardiopulmonary resuscitation administered by a bystander, 3.7 (95 percent confidence interval, 2.5 to 5.4); and after rapid defibrillation, 3.4 (95 percent confidence interval, 1.4 to 8.4). There was no improvement in the rate of survival with the use of advanced life support in any subgroup.
conclusions
The addition of advanced-life-support interventions did not improve the rate of survival after out-of-hospital cardiac arrest in a previously optimized emergency-medical-services system of rapid defibrillation. In order to save lives, health care planners should make cardiopulmonary resuscitation by citizens and rapid-defibrillation responses a priority for the resources of emergency-medical-services systems
Stiell et,al N Engl J Med 2004;351:647-56

7. The association between timing of tracheal intubation and outcomes of adult in-hospital cardiac arrest: A retrospective cohort study
Aim: Resuscitation guidelines indicate the ideal timing of tracheal intubation during in-hospital cardiac arrest (IHCA) has not been adequately studied. Methods: A retrospective observational study in a single medical centre was conducted that evaluated patients with IHCA between 2006 and Multivariable logistic regression analysis was used to evalu-ate associations between independent variables and outcomes. Time to intubation was defined as elapsed time from the first chest compression to the time of completion of endotracheal intubation, tracheostomy, or cricothyroidotomy. Results: A total of 702 patients were included. The mean time to intubation was 8.8 min. Ninety-five (13.5%) patients survived to hospital discharge, and 44 (6.3%) patients displayed favourable neurological status at discharge. Time to intubation was shown to be inversely associated with favourable neurolog-ical outcome (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.80–0.93; p-value <0.001). Delayed time to intubation was noted to be particularly unfavourable for survival outcome in patients with non-shockable rhythms (OR: 0.95, 95% CI: 0.91–0.98; p-value = 0.005). Intubation within 8.8 min of arrest was demonstrated to be positively associated with both favourable neurological outcome (OR: 7.28, 95% CI: 2.98–20.52; p-value <0.001) and survival to hospital discharge (OR: 2.09, 95% CI: 1.27–3.52; p-value = 0.004). Conclusion: Earlier tracheal intubation during cardiopulmonary resuscitation might be beneficial for clinical outcomes following IHCA. Intubation within 8.8 min appears favourable for both neurological and survival outcomes. Nevertheless, this goal should be attempted by clinicians who experienced in intubation to avoid potential complications and harm.
Logit (p), where p represented the probability for favorable neurological outcome, and time to intubation
Chih-Hung Wang et al, Resuscitation 105 (2016) 59–65

8. Survival was higher among OHCA receiving ETI
Airway management and out-of-hospital cardiac arrest outcome in the CARES registry
Survival was higher among OHCA receiving ETI
Termination of resuscitation occurred in approximately 30% of patients and was least frequent in the ETI group
Unadjusted outcomes were highest for patients who did not receive successful advanced airway placement. Compared with those receiving successful SGA placement, unadjusted outcomes were better with ETI.
Background: Optimal out of hospital cardiac arrest (OHCA) airway management strategies remain unclear. We compared OHCA outcomes between patients receiving endotracheal intubation (ETI) versus supra-glottic airway (SGA), and between patients receiving [ETI or SGA] and those receiving no advanced airway. Methods: We studied adult OHCA in the Cardiac Arrest Registry to Enhance Survival (CARES). Primary exposures were ETI, SGA, or no advanced prehospital airway placed. Primary outcomes were sustained ROSC, survival to hospital admission, survival to hospital discharge, and neurologically-intact survival to hospital discharge (cerebral performance category 1–2). Propensity scores characterized the probability of receiving ETI, SGA, or no advanced airway. We adjusted for Utstein confounders. Multivariable random effects regression accounted for clustering by EMS agency. We compared outcomes between (1) ETI vs. SGA, and (2) [no advanced airway] vs. [ETI or SGA]. Results: Of 10,691 OHCA, 5591 received ETI, 3110 SGA, and 1929 had no advanced airway. Unadjusted neurologically-intact survival was: ETI 5.4%, SGA 5.2%, no advanced airway 18.6%. Compared with SGA, ETI achieved higher sustained ROSC (OR 1.35; 95%CI 1.19–1.54), survival to hospital admission (1.36; 1.19–1.55), hospital survival (1.41; 1.14–1.76) and hospital discharge with good neurologic outcome (1.44; 1.10–1.88). Compared with [ETI or SGA], patients receiving no advanced airway attained higher survival to hospital admission (1.31; 1.16–1.49), hospital survival (2.96; 2.50–3.51) and hospital discharge with good neurologic outcome (4.24; 3.46–5.20). Conclusion: In CARES, survival was higher among OHCA receiving ETI than those receiving SGA, and for patients who received no advanced airway than those receiving ETI or SGA.
McMullan et al, Resuscitation 85 (2014) 617–622

9. Study Setting
randomized, parallel-group, noninferiority, 2-country (Belgium and France)
20 pre-hospital emergency medical services centers(ambulance base stations equipped with 1 or more mobile intensive care units, consisting of an ambulance driver, a nurse, and an emergency physician as the minimum team)
15 in France and 5 in Belgium. 3/2015 – 3/2017 (22months enrollment)
1000 patients per arm is required to have 80% power to demonstrate non-inferiority with margin fixed at 1%

10. Study Population Inclusion criteria Exclusion criteria
Adults≥18 years old with OHCA who received resuscitation performed by clinicians from participating centers
Exclusion criteria
Suspected massive aspiration before resuscitation,
Presence of a DNR order,
Known pregnancy, and/or
Imprisonment

11. Patients were resuscitated according to international recommendations:
Study Intervention
Out-of-Hospital Period (time of randomization- hospital admission):
Spontaneous circulation intubation in the out-of-hospital setting
If standard BMV was impossible ETI as a rescue procedure
In instances where the primary rescuers (ie, firefighters) arrived at the scene before the medical team ventilation with the bag mask was performed as part of basic life support.
Patients were resuscitated according to international recommendations:
a chest compression to breath ratio of 30:2 before ETI attempt and attention to ensure continuous compressions
Patients were transported to the hospital only if they were successfully resuscitated at the scene

12. Study Intervention
In-hospital Period (time of hospital admission - hospital discharge):
No procedures or treatments relevant to the research protocol occurred during hospitalization.
If the patient’s condition improved during hospitalization, the investigator was required to inform the patient about his or her enrollment in the study.
Data collected during this period were death from any cause and vital status at day 28

13. Outcomes
Primary end point: survival at day 28 with favorable neurological function (Glasgow-Pittsburgh Cerebral Performance Categories (CPCs) of≤ 2 or less
Secondary study end points: rate of survival to hospital admission, rate of survival at 28 days, rate of ROSC, intubation difficulty assessed by the Intubation Difficulty Scale score, difficult intubation (defined by Intubation Difficulty Scale score >5), BMV difficulty assessed by a visual analog scale ranging from 0 mm to 100 mm and by the Han mask ventilation classification, and rate of BMV or ETI failure.

14. Flow Chart of Patient Inclusion
Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, −1.64% to infinity]; P for noninferiority = .11).
Jabre P et al, JAMA. 2018 Feb 27;319(8):779-78

15. Baseline Characteristics
Patient characteristics and the process of resuscitation were well balanced between the 2 groups except for age and history of psychiatric disorder

16. Primary outcome (ITT analysis)
In the ITT population, favorable functional survival (ie, CPC 1-2) in the 2 groups at day 28 were 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, −1.64% to infinity]; P for noninferiority = .11). The lower limit of the confidence interval was greater than the threshold of noninferiority, thus noninferiority was not demonstrated. Very similar estimates were obtained using a hierarchical modeling including center as a random effect (difference, 0.05% [1-sided 97.5% CI, −1.70% to infinity]). This result was consistent in the per-protocol population: 4.3% vs 4.2% in the BMV and ETI groups, respectively (difference, 0.08% [1-sided 97.5% CI, −1.74% to infinity]; P for noninferiority = .12).
The lower limit of the confidence interval was greater than the threshold of noninferiority, thus noninferiority was not demonstrated
Jabre P et al, JAMA. 2018 Feb 27;319(8):779-78

17. Secondary outcomes
In ITT analysis, the rate of ROSC was significantly greater in the ETI group (397/1022 [38.9%]) vs in the BMV group (348/1018 [34.2%]) (difference, −4.7% [95% CI, −8.8% to −0.5%]; P = .03). The survival to hospital admission and survival at day 28 were not, however, significantly different between the 2 groups (BMV vs ETI: 294/1018 [28.9%] vs 333/1022 [32.6%]; difference, −3.7% [95% CI, −7.7% to 0.3%] and 55/1018 [5.4%] vs 54/1022 [5.3%]; difference, 0.1% [95% CI, −1.8% to 2.1%]
Although there was a significantly higher rate of ROSC in
the ETI group vs the BMV group, overall 28-day survival was
not different. Thismay be related to differences in ventilationassociated
complications (hyperoxia, overventilation, and hypotension)
between the 2 randomized groups and these factors
would need to be considered in future trials

18. Airway management adverse events analysis
Complications that were significantly more frequent in the BMV group compared with the ETI group included airway management difficulty (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001)

19. Limitations
The use of ETI in the BMV group either after ROSC or when difficulty with airway management was encountered may question the BMV-only strategy in the intervention group.
This trial did not include comparison of inpatient management after cardiac arrest.
2. However, post-hoc analysis with removal of patients with protocol violations did not change results in terms of survival. After successful resuscitation of patients included in the BMV group, it is expected that all these patients were intubated (in the out-of-hospital setting or in the hospital). The principal aim of this trial was to identify the better airway management strategy in ACLS of patients with OHCA rather than post-ROSC care.
3. which could vary considerably. However, because this study was randomized, the 2 groups should be comparable in terms of in-hospital management.

20. Conclusion
Patients with out of hospital CA, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result.
The authors conclude that a “determination of equivalence or superiority between these techniques requires further research.”. On the other hand, BMV is associated with increased complications and difficulty.
Although this trial was hampered by sample size limitations, these data could prove useful for other investigators in designing future trials tomore definitively address the relative efficacy of BMV vs ETI for adults with out-of-hospital cardiac arrest

21. Discussion
Even if BMV were an equivalent strategy to ETI, BMV would be the preferred strategy due to greater ease in implementation and training.
Considerations regarding: training burden associated with ETI equipment costs, maintenance of skills, and the potential for unrecognized complications