Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: a randomised trial

Abstract

Background: Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest.

Methods: In our randomised trial of 46 emergency medical service agencies (serving 2·3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age ≥18 years) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of ≤3). All investigators apart from initial rescuers were masked to treatment group assignment. This trial is registered with ClinicalTrials.gov, number NCT00189423.

Findings: 2470 provisionally enrolled patients were randomly allocated to treatment groups. 813 (68%) of 1201 patients assigned to the standard CPR group (controls) and 840 (66%) of 1269 assigned to intervention CPR received designated CPR and were included in the final analyses. 47 (6%) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 (9%) of 840 patients in the intervention group (odds ratio 1·58, 95% CI 1·07-2·36; p=0·019]. 74 (9%) of 840 patients survived to 1 year in the intervention group compared with 48 (6%) of 813 controls (p=0·03), with equivalent cognitive skills, disability ratings, and emotional-psychological statuses in both groups. The overall major adverse event rate did not differ between groups, but more patients had pulmonary oedema in the intervention group (94 [11%] of 840) than did controls (62 [7%] of 813; p=0·015).

Interpretation: On the basis of our findings showing increased effectiveness and generalisability of the study intervention, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest.

Funding: US National Institutes of Health grant R44-HL065851-03, Advanced Circulatory Systems.

Figure 1. Utstein Guidelines Patient Flow Chart

Intervention Group received active compression decompression cardiopulmonary resuscitation with an impedance threshold device; S-CPR Group received standard cardiopulmonary resuscitation. Abbreviations: DNR= Do Not Resuscitate, ED= emergency department, EMS= emergency medical services, F/U= follow-up. ¹Patients were finally excluded from the S-CPR (Control) Group for the following: presumed or known non-cardiac etiology (256); pre-existing DNR order discovered or had efforts terminated prematurely (68); signs of obvious clinical death or condition that precluded the use of CPR (23); complete airway obstruction that could not be cleared or advanced airway that could not be placed (17); leaky or uncuffed advanced airway or patient with stoma, tracheotomy, or tracheostomy (12); received <1 minute of CPR (8); recent sternotomy (3); prisoner (1). ²Patients were finally excluded from the Intervention Group for the following: presumed or known non-cardiac etiology (296); pre-existing DNR order discovered or had efforts terminated prematurely (54); signs of obvious clinical death or condition that precluded the use of CPR (22); leaky or uncuffed advanced airway or patient with stoma, tracheotomy, or tracheostomy (21); complete airway obstruction that could not be cleared or advanced airway that could not be placed (18); received <1 minute of CPR (13); recent sternotomy (3); known/presumed age <18 years (1); prisoner (1). ³Public death record search was performed at one year for all patients who withdrew or were lost to follow-up at any interval.

Figure 2. Disabilities Rating Scores 90 and 365 days after OOHCA. There were no significant differences between study groups at 90 and 365 days after cardiac arrest

The Disabilities Rating Scale (DRS) is based on a scale of 0–29 where 0=no disability (category 1), 1=mild (2), 2–3=partial (3), 4–6=moderate (4), 7–11=moderately severe (5), 12–16=severe (6), 17–21=extremely severe (7), 22–24=vegetative state (8), and 25–29=extreme vegetative state (9).

Figure 3

Age Distribution of Patients Surviving to Hospital Discharge with a Favorable Neurologic Function. Results are shown as percent of patients/age group. Favorable Neurologic function was defined as MRS ≤ 3.

Figure 4

Analyses were performed to determine the effects of age, study site, gender, and date of treatment, on the primary study endpoint. Consistent differences between study groups were observed throughout the entire study, independent of age, study site, gender, and date of treatment.

Figure 5

Cumulative Rates of Achieving the Primary Endpoint (mRS ≤3 at Hospital Discharge). Results are shown for pivotal phase enrollment (N=1653) by quarter. Consistent results in both groups were demonstrated throughout the entire duration of the study. Enrollment in Site 6 was initiated in the 4^th Quarter (Q) of 2007 and in Site 7 in the 1^st Quarter of 2009.

Figure 6. Survival to Hospital Discharge with Favorable Neurologic Function by Time to CPR Treatment. Survival to hospital discharge with MRS ≤ 3 was significantly increased in the Intervention Group [p = 0.019, OR 1.58 (CI = 1.07, 2.36)]. There no survivors in either group if CPR was initiated > 10 min after the 911 call. Values above the bars are number of patients that survived to hospital discharge with favorable neurologic function, defined as mRS ≤3

Abbreviations: mRS = Modified Rankin Scale, Intervention= impedance threshold device plus active compression decompression cardiopulmonary resuscitation, S-CPR= standard cardiopulmonary resuscitation.