Outcome of patients receiving CPR in the ED of an urban academic hospital

    Outcome of patients receiving cardiopulmonary resuscitation (CPR) in the Emergency Department of an urban academic hospital Nalin Chokengarmwong MD, Luis Alfonso Ortiz BSc, Ali Raja MD, Joshua N. Goldstein MD, PhD, Fei Huang PhD, D. Dante Yeh MD PII: DOI: Reference:

S0735-6757(16)30193-0 doi: 10.1016/j.ajem.2016.05.060 YAJEM 55839

To appear in:

American Journal of Emergency Medicine

Received date: Revised date: Accepted date:

28 March 2016 22 May 2016 24 May 2016

Please cite this article as: Chokengarmwong Nalin, Ortiz Luis Alfonso, Raja Ali, Goldstein Joshua N., Huang Fei, Yeh D. Dante, Outcome of patients receiving cardiopulmonary resuscitation (CPR) in the Emergency Department of an urban academic hospital, American Journal of Emergency Medicine (2016), doi: 10.1016/j.ajem.2016.05.060

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ACCEPTED MANUSCRIPT Outcome of patients receiving cardiopulmonary resuscitation (CPR) in the Emergency Department of an urban academic hospital

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Nalin Chokengarmwong, MD1,2; Luis Alfonso Ortiz, BSc2; Ali Raja, MD3; Joshua N. Goldstein, MD, PhD3; Fei Huang, PhD4; D. Dante Yeh, MD2

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1. King Chulalongkorn Memorial Hospital, Thai Red cross society and Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 2. Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 4. Department of Medicine, Massachusetts General Hospital

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Corresponding author: D. Dante Yeh, MD 165 Cambridge St. #810 Boston, MA 02114

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Support: none

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Key words: resuscitation, CPR, asystole, ventricular fibrillation, ventricular tachycardia

Short Running Head: Outcomes with closed chest CPR by resuscitation duration

ACCEPTED MANUSCRIPT Introduction Cardiac arrest is a common public health problem and a leading cause of death

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in developed nations. Approximately 37 adults suffer out of hospital cardiac arrest

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(OHCA) per hour in the United States [1]. Closed chest cardiopulmonary resuscitation (CC-CPR) with Advanced Cardiac Life Support (ACLS) has been the standard method

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of resuscitation since 1960. Despite initial reports of high survival rates, currently the

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survival rate of CC-CPR is only 6.7% [1].

Prior to widespread adoption of CC-CPR, however, open chest-CPR (OC-CPR),

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the act of compressing the heart directly between the hands via thoracotomy or sternotomy, was the prevailing method of cardiac resuscitation [2]. When performed

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expeditiously by an experienced surgeon, OC-CPR can be beneficial [3], but

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widespread application is limited by lack of training and concerns about unnecessary invasive procedures. After its initial description in 1960, CC-CPR became widely

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adopted because it could be performed by anyone (including laypersons) and does not

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require surgical instruments [4]. However, CC-CPR has not been adequately compared to OC-CPR in a rigorous manner and it is possible that in appropriately selected patients, OC-CPR can lead to superior outcomes. Given the risks of this procedure, the patients most likely to benefit are those who will not be successfully resuscitated with CC-CPR. In order to best define this population, we performed a retrospective study of patients receiving CC-CPR at our hospital to determine a time threshold beyond which continuing CC-CPR is likely futile (probability of survival <1%).

ACCEPTED MANUSCRIPT Methods Study Design and Setting

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This retrospective study was approved by our local institutional review board

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(IRB). The study institution is an urban academic Level 1 trauma center hospital. The Emergency Department (ED) records more than 100,000 visits annually. Using ICD-9

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codes (427.1, 427.41, 427.42, 427.5), we screened all adult patients (age ≥ 18 years

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old) diagnosed with cardiac arrest, ventricular fibrillation (VF), ventricular tachycardia (VT) or asystole from January 1, 2010 through December 31, 2014. We excluded

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trauma patients and patients with known pre-stated limitations of life-sustaining

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treatments (i.e., do-not-resuscitate orders).

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Data Collection

Data collected included patient demographics, cardiac rhythm, resuscitation

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duration, survival to hospital discharge and neurological outcomes. Shockable rhythm

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was defined as VF and VT and all other rhythms were defined as a non-shockable rhythm. Initiation of CPR was defined as the initiation of chest compressions by a professional rescuer and duration of CPR was calculated until ROSC or termination of resuscitative efforts. The ability to follow commands was used to define a good neurological outcome.

Statistical Analysis Normally distributed variables are presented as mean (standard deviation, SD) while non-normally distributed data are presented as median (interquartile ranges, IQR). Comparisons were performed using two-sample t-tests or Wilcoxon rank sum tests as

ACCEPTED MANUSCRIPT appropriate. Categorical data are presented as frequency and percentage and compared using chi-square tests. A two-sided p value of <0.05 was considered

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statistically significant.

Results

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During the 5-year study period, 869 patients were treated in our institution’s ED

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for cardiac arrest, ventricular fibrillation, ventricular tachycardia or asystole. After exclusion of pediatric and trauma patients, the final cohort comprised 242 cases.

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Demographic characteristics, initial cardiac rhythm, and outcomes of the cohort are summarized in TABLE 1. Of the 242 patients, 205 (85%) suffered OHCA and received

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pre-hospital CPR for a median duration of 30 min (20-44min); overall, 46/242 (19%)

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achieved ROSC. However, only 29/242 (12%) survived for 24 hours and 20/242 (8.3%) survived to hospital discharge. All 20 patients surviving to hospital discharge had good

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neurological outcomes.

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Age and gender were not significantly different when comparing patients suffering OHCA to those with witnessed arrest in the ED, nor were the relative frequencies of shockable vs. non-shockable initial cardiac rhythm. In both groups, the majority of patients had initially non-shockable cardiac rhythm. However, patients with OHCA had a significantly higher incidence of asystole and lower incidence of pulseless electrical activity (PEA). Patients with witnessed arrest in the ED had significantly higher rates of ROSC (54.1% vs. 12.7%, p<0.001), 24 hour survival rate (45.9% vs. 5.9% p<0.001), survival to hospital discharge rate (37.8% vs. 2.9%, p<0.001), and good neurological outcome (37.8% vs. 2.9%, p<0.001) when compared to those receiving pre-hospital CPR.

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Pre-hospital CPR

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TABLE 2 summarizes the demographics, CPR duration, and initial cardiac

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rhythm for only those patients suffering OHCA. We excluded cases with unknown CPR duration and were left with 177 remaining subjects. Patients who achieved ROSC had

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a median time of 10 minutes of pre-hospital CPR and 18 minutes of total CPR duration.

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Patients without ROSC had significantly longer pre-hospital CPR duration (median 35 vs. 10 minutes), ED CPR duration (median 10 vs. 6 minutes), and total CPR duration

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(median 47 vs. 18 minutes), and asystole accounted for nearly half of all initial cardiac rhythms.

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Among the OHCA patients, the percentage achieved ROSC, the percentage of

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patients with survival to hospital discharge and good neurological outcomes decreased with increasing duration of ED CPR (FIGURE 1). No OHCA patient receiving

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prehospital CPR and who then underwent CPR in the ED for more than 10 minutes had

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a good neurological outcome (0/99, 95%CI 0-3.7%). Likewise, among patients suffering witnessed arrest in the ED, the cumulative percentage for achieving ROSC or survival to hospital discharge and good neurological outcomes had minimal increase after 10 minutes of ED CPR (FIGURE 2). No patient requiring CPR for more than 10 minutes of CPR (total CPR duration = ED CPR duration) survived to hospital discharge with a good neurological outcome (0/19, 95%CI 0-17.7%).

Discussion In this retrospective review of patients receiving CC-CPR in the ED of an urban academic hospital, we report that overall, ROSC was achieved in 19%, but the rate of

ACCEPTED MANUSCRIPT survival to hospital discharge with a good neurologic outcome was only 8.3%. Not surprisingly, ED witnessed arrests had significantly better rates of ROSC (54.1%) and

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survival to hospital discharge with good neurologic outcome (37.8%), a finding

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consistent with other reports. For example, Brooks et al reported a survival to hospital discharge rate in OHCA of 8.3% while Kayser et al reported patients suffering witnessed

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arrest in the ED had a 22.2% rate of survival to hospital discharge [5, 6]. Goldberger et

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al also reported that 49% of in-hospital cardiac arrest patients had ROSC, with 15% overall survival to hospital discharge [7]. Recognizing that ROSC alone is not an

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adequate patient-centered outcome, we chose to consider survival to hospital discharge with good neurologic outcome as a meaningful endpoint. Using this metric and

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reviewing 5 years’ worth of outcomes, we can define 10 minutes of CPR in the ED as

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the limit of futility for continuing ongoing resuscitative efforts with standard closed-chest compressions. A recent study by Grunau et al. have also attempted to address the

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question of how long to persist with resuscitation efforts [8]. In a post-hoc analysis of

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the Resuscitation Outcomes Consortium database, the investigators examined outcomes according to the initial rhythm (shockable or non-shockable) taking into consideration the time-to-ROSC. In their cohort of 1617 patients with OHCA, nearly half (49%) achieved ROSC (the remainder were not transported to the hospital), but only 10% had a neurologically favorable outcome. Time-to-ROSC was independently associated with the probability of survival and good neurological outcome. It is worth emphasizing that Grunau et al. counted total CPR time, including pre-hospital CPR time. For both shockable and non-shockable initial rhythms, the percentage of patients surviving with good neurological outcome was <1% at 34 min into the resuscitation. However, the median time-to-ROSC was approximately 15 min for all patients; for those

ACCEPTED MANUSCRIPT patients who achieved a favorable neurological outcome, median time-to-ROSC was 8 min and 6 min for shockable and non-shockable, respectively. In their study, only 82

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(5.1%) arrived in the ED without previously achieving ROSC. Those authors conclude

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that resuscitation efforts should continue up to 48 min of total CPR time, especially for younger patients with initial shockable rhythms. Our study, by definition, enrolled only

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patients arriving in the ED with CPR ongoing after a median of 30 min of prehospital

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CPR. We found that those patients who achieved ROSC in the ED did so after a median of 6 min of ED CPR and the longest duration of ED CPR time for a favorable

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neurological outcome was 10 min. Our total CPR time, thus, is very similar to the limit of futility reported by Grunau.

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CPR is associated with high rates of survival if several conditions are met: 1)

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favorable etiology (e.g., ventricular fibrillation vs. asystole) [9], 2) early initiation of chest compressions by medical professionals (as in witnessed arrests in the ED) or

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bystanders, and 3) high-quality resuscitation efforts [10-12]. Outside of this confluence

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of factors, meaningful outcomes after CPR are dismal, usually ~5% [13]. While etiology and early initiation are beyond the control of the ED physician, high-quality cardiac compressions are a potentially modifiable factor. The principal purpose of cardiac compression is to maintain adequate coronary and cerebral perfusion, as higher pressures are associated with higher likelihood of ROSC and good neurologic outcome, respectively. It is commonly believed that external compressions maintain cardiac output by directly compressing the heart between the sternum and the spine. However, studies have discounted this theory and it is now accepted that the forward flow of blood is a result of the recoil of the thoracic cavity, with the heart acting as a passive conduit [14-18]. This results in, at best, a cardiac output of only 25-33% of normal cardiac

ACCEPTED MANUSCRIPT output and oxygen delivery. There is, however, a way to drastically improve cardiac output by restoring the heart-pump function: resuscitative thoracotomy with direct

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cardiac massage, aka open-chest CPR (OC-CPR).

OC-CPR

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Animal studies of medical cardiac arrest have shown that OC-CPR results in

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higher cardiac output, dramatic improvements in coronary perfusion pressure and cerebral blood flow, and higher rates of ROSC when compared to CC-CPR [2, 19-25].

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In one randomized study, cardiac arrest was induced by potassium chloride injection and dogs were randomized to receive either CC-CPR or OC-CPR after 5 minutes of

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non-intervention. All subjects receiving OC-CPR were successfully resuscitated and

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behaviorally normal at 72 h. In contrast, only 43% of dogs receiving CC-CPR survived, and the majority of survivors had incapacitating neurologic deficits [26]. Another study

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in dogs demonstrated that OC-CPR was an effective “rescue” technique after CC-CPR

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was unable to achieve adequate coronary perfusion pressures after 15 minutes. 80% of subjects receiving OC-CPR survived, compared to none in the continued CC-CPR group [27]. However, time to initiation of OC-CPR is a critical factor. Sanders et al. demonstrated that 75% of animals were resuscitated when OC-CPR was initiated within 15 minutes. If the procedure was delayed to 20 minutes, ROSC rates dropped to 40% [28, 29]. This intervention should be ideally initiated within 20-25 minutes of cardiac arrest in order to be successful [23], though there have been case reports of successful resuscitation (with good neurologic outcome) after up to 75 minutes of unsuccessful CC-CPR [30].

ACCEPTED MANUSCRIPT Human studies of OC-CPR are sparse, yet encouraging [31, 32]. In one study, Boczar et al performed OC-CPR a median 45 minutes of unsuccessful standard CC-

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CPR for non-traumatic out-of-hospital cardiac arrest [33]. It is interesting to note that

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30% of patients achieved ROSC with OC-CPR, despite being previously declared unsalvageable. It must be stressed that the purpose of this exploratory study was not to

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assess clinical efficacy, but rather to measure hemodynamic parameters in a human

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model. The lack of long term survival after ROSC in this pilot study was likely due to the prolonged delay before initiating OC-CPR. In a Japanese case series of 33 patients

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receiving OC-CPR for OHCA after unsuccessful CC-CPR (median 25 min) [34], ROSC was achieved in 13/33 (39%), a significantly higher rate than the 12.7% we reported for

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OHCA in our series. No wound infections were noted and there was only one case of

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iatrogenic heart damage, which was subsequently successfully repaired. Another case series from Japan reported that 15 of 26 (58%) of patients receiving OC-CPR for OHCA

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achieved ROSC, with the likelihood of success highest amongst those undergoing

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thoracotomy within 5 minutes of hospital arrival. Overall, 12% were discharged alive, compared to 1% of contemporaneous patients receiving standard CC-CPR [35]. Acceptability of OC-CPR by laypersons and surviving family members is high, with nearly 80% unconditionally agreeing with the use of OC-CPR [36]. However, at this time, no strong recommendations can be made regarding the routine use of OC-CPR due to the lack of evidence of benefit or harm [37].

Extracorporeal Life Support Another invasive option which may be considered in select institutions is extracorporeal life support (ECLS), which encompasses both extracorporeal membrane

ACCEPTED MANUSCRIPT oxygenation (ECMO) and cardiopulmonary bypass [37]. While there are no randomized trials comparing ECLS to continuing CC-CPR, small case series and single-center

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observational studies have reported encouraging results [38, 39]. A recently published

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meta-analysis combined 14 publications (2008-2014) describing the use of ECLS in both in-hospital and OHCA patients and concluded that overall survival and neurologic

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seemed to be improved at 3-6-months in ECLS patients, though the benefits for OHCA

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patients were less robust [40]. As with OC-CPR, the American Heart Association acknowledges that there is insufficient evidence to recommend routine use of ECLS in

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cardiac arrest patients, though it may be considered, if readily available, in select

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circumstances [37].

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Limitations

Our study has several limitations. Firstly, this was a retrospective medical record

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review and therefore we were unable to record important data points such as whether

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the OHCA was witnessed and whether bystanders initiated CC-CPR. Secondly, we were unable to assess the quality (depth and rate) of chest compressions nor the adherence of the overall resuscitation with ACLS best practices. Thirdly, we acknowledge that therapeutic hypothermia was not performed in the six OHCA patients surviving >24 hours. However, all six patients were discharged with a good neurologic outcome and therefore we do not feel that addition of therapeutic hypothermia would have altered our findings (according to our definition of good neurologic outcome) or conclusions regarding the limitations of CC-CPR. While the median pre-hospital CPR time was 30 min overall, no patient receiving >10 minutes of CPR in the ED survived to hospital discharge. These data suggest that

ACCEPTED MANUSCRIPT alternative rescue options such as OC-CPR should be considered after ten minutes of

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CC-CPR in the ED in patients with OHCA.

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Conclusion

In our urban, academic Emergency Department, the overall rate of survival to

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hospital discharge and survival with good neurological outcome in patients receiving

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CPR in the ED is 8.3%. Patients with witnessed arrests have significantly improved outcomes compared to patients suffering out-of-hospital cardiac arrest. Given the

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universally poor survival and neurologic outcomes in patients without ROSC after 10

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unnecessary thoracotomy.

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minutes of CC-CPR in the ED, OC-CPR could potentially be attempted with low risk of

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FIGURE 1 –Out of Hospital Cardiac Arrest and ED CPR duration

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CPR = cardiopulmonary resuscitation; ED = Emergency Department; ROSC = return of spontaneous circulation

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FIGURE 2 –Witnessed ED arrest and Total (ED) CPR duration

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CPR = cardiopulmonary resuscitation; ED = Emergency Department; ROSC = return of spontaneous circulation

ACCEPTED MANUSCRIPT Table 1 - Demographics and Outcomes

47 (22.9%) 38 (18.5%) 4 (2%) 158 (77.1%) 63 (30.7%) 90 (43.9%) 26 (12.7%) 1 (IQR 1-5) 1 (IQR 1-6) 12 (5.9%) 6 (2.9%) 6 (2.9%)

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55 (22.7%) 42 (17.4%) 8 (3.3%) 187 (77.3%) 89 (36.8%) 93 (38.4%) 46 (19%) 2.5 (IQR 1-6) 4 (IQR 1-12) 29 (12%) 20 (8.3%) 20 (8.3%)

Arrested in ED (n=37) 63 (IQR 59-75) 12 (32.4%)

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Pre-hospital CPR (n = 205) 63 (IQR 52-78) 60 (29.3%)

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Age female Initial Cardiac rhythm Shockable VF VT Non-shockable PEA Asystole ROSC ICU LOS (days)* Hospital LOS (days)* 24 hour survival Survival to hospital discharge Good neurological outcome

All (n = 242) 63 (IQR 53-77) 72 (29.8%)

8 (21.6%) 4 (10.8%) 4 (10.8%) 29 (78.4%) 26 (70.3%) 3 (8.1%) 20 (54.1%) 3 (IQR 1-8) 5 (IQR 4-20) 17 (45.9%) 14 (37.8%) 14 (37.8%)

p value 0.55 0.70 <0.0001

<0.0001 0.37 0.032 <0.0001 <0.0001 <0.0001

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LOS = length of stay; PEA = pulseless electrical activity; ROSC = return of spontaneous circulation; VF = ventricular fibrillation; VT = ventricular tachycardia ** limited only to those patients with ROSC

ACCEPTED MANUSCRIPT Table 2 – OHCA only (limited to those with pre-hospital CPR duration available) ROSC (n=22)

No ROSC (n=155)

p value

Age

62 (50-77)

Female

49 (27.7%)

58 (IQR 50-63)

64 (50-78)

0.18

7 (31.8%)

42 (27.3%)

0.64

Pre-hospital CPR duration (min)

30 (20-44)

10 (IQR 4-30)

35(IQR 25-45)

<0.0001

ED-CPR duration (min)

10 (5-16)

6 (IQR 3-10)

10 (IQR 6-16)

0.03

Total CPR duration (min)

45 (36-55)

18 (IQR 8-44)

47 (IQR 37-57)

<0.0001

VT

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0.007

39 (22%)

6 (27.3%)

33 (21.3%)

33 (18.6%)

4 (18.2%)

29 (18.7%)

2 (1.1%) 138 (78%)

PEA

57 (32.2%)

Asystole

77 (43.5%)

1 (4.5%)

1 (0.6%)

16 (72.7%)

122 (78.7%)

11 (50%)

46 (29.7%)

3 (13.6%)

74 (47.7%)

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Non-shockable

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VF

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Initial Cardiac rhythm Shockable

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All (n = 177)

** Includes only subjects with known duration of pre-hospital CPR

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CPR = cardiopulmonary resuscitation; ED = Emergency Department; PEA = pulseless electrical activity; ROSC = return of spontaneous circulation; VF = ventricular fibrillation; VT = ventricular tachycardia