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Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy
Resuscitation 93 (2015) 74–81
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Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy夽 Graham Nichol a,b,∗ , Danielle Guffey a , Ian G. Stiell c , Brian Leroux a , Sheldon Cheskes d , Ahamed Idris e , Peter J. Kudenchuk f , Renee S. Macphee g , Lynn Wittwer h , Jon C. Rittenberger i , Thomas D. Rea f , Kellie Sheehan a , Val E. Rac j , Keitki Raina i , Kyle Gorman k , Tom Aufderheide l , the Resuscitation Outcomes Consortium Investigators a
Clinical Trial Center, Department of Biostatistics, University of Washington, Seattle, WA, United States University of Washington-Harborview Center for Prehospital Emergency Care, Department of Medicine, University of Washington, Seattle, WA, United States c Department of Emergency Medicine, University of Ottawa, Ottawa Health Research Institute, Ottawa, ON, Canada d Rescu, Li Ka Shing Knowledge Institute, St Michael’s Hospital and Sunnybrook Center for Prehospital Medicine, Division of Emergency Medicine, Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada e Departments of Emergency Medicine and Internal Medicine, University of Texas Southwestern, Dallas, TX, United States f King County EMS, Seattle and King County Public Health, and Department of Medicine, University of Washington, Seattle, WA, United States g Wilfrid Laurier University, Waterloo, ON, Canada h Clark County Emergency Medical Services, Vancouver, WA, United States i Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, United States j Toronto Health Economics and Technology Assessment Collaborative, Institute of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, ON, Canada k Clackamas Fire District #1, Clackamas, OR, United States l Medical College of Wisconsin, Milwaukee, WI, United States b
a r t i c l e
i n f o
Article history: Received 13 February 2015 Received in revised form 16 May 2015 Accepted 17 May 2015 Keywords: Cardiac arrest Prognosis Quality of life Depression Cognition Functional status
a b s t r a c t Importance: Assessment of morbidity is an important component of evaluating interventions for patients with out-of-hospital cardiac arrest (OHCA). Objective: We evaluated among survivors of OHCA cognition, functional status, health-related quality of life and depression as functions of patient and emergency medical services (EMS) factors. Design: Prospective cohort sub-study of a randomized trial. Setting: The parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium. Participants: Consenting survivors to discharge. Main outcome measures: Telephone assessments up to 6 months after discharge included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), health-related quality of life (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS). Results: Of 15,794 patients enrolled in the parent trial, 729 (56% of survivors) consented. About 644 respondents (88% of consented) completed ≥ 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most respondents had MRS ≤ 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no severe impairment in health (71.6%, HUI3 ≥ 0.7) and no depression (90.1% T-GDS ≤ 10). Outcomes did not differ by trial intervention or time from hospital discharge. Conclusions and relevance: The majority of patients in this large cohort who survived cardiac arrest and were interviewed had no, mild or moderate health impairment. Concern about poor quality of life is not a valid reason to abandon efforts to improve an EMS system’s response to cardiac arrest. © 2015 Published by Elsevier Ireland Ltd.
夽 A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2015.05.011. ∗ Corresponding author at: University of Washington-Harborview Center for Prehospital Emergency Care, Department of Medicine, Box 359727, 325 Ninth Ave, Seattle, WA 98104, United States. E-mail address: [email protected] (G. Nichol). http://dx.doi.org/10.1016/j.resuscitation.2015.05.011 0300-9572/© 2015 Published by Elsevier Ireland Ltd.
G. Nichol et al. / Resuscitation 93 (2015) 74–81
1. Objective Assessment of cognition, functional status, health-related quality of life (HRQL) and mood are important components of evaluating the effects of interventions for patients with out-of-hospital cardiac arrest (OHCA).1 Survivors of OHCA may have HRQL that is similar to that of age- and sex-matched peers.2 Depression is observed in those with cardiovascular disease3 or who have survived cardiac arrest,4 and is difficult to differentiate from cognitive impairment. Thus, resuscitation interventions may be associated with subtle differences in neurologic status, HRQL, or depression after discharge. Therefore this prospective sub-study of the Prehospital Resuscitation IMpedance valve and Early vs. Delayed analysis (ROC PRIMED) trial sought to: describe post-discharge neurological status, cognition, HRQL and depression as functions of baseline characteristics, EMS process, and study interventions; compare the characteristics of patients with complete vs. missing postdischarge measures; and correlate post-discharge outcomes with each other after OHCA. 2. Design and methods 2.1. Overview of randomized trial This study was a prospective cohort sub-study of a randomized trial. The methods and results for the parent ROC PRIMED trial were previously reported.5–8 The Resuscitation Outcomes Consortium (ROC) is a clinical trial network that includes 10 U.S. and Canadian universities and their regional emergency medical services (EMS) systems. This trial used a partial factorial design to study two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in ROC. The first comparison randomly allocated persons to undergo cardiopulmonary resuscitation (CPR) with an active or sham impedance threshold device (ITD). The second comparison randomly allocated clusters of individuals with OHCA grouped by EMS agency or geographic boundaries or defibrillator device, vehicle, station or battalion to Analyze Early or Analyze Later. The former strategy consisted of about 30 s of manual CPR by EMS providers before first rhythm analysis; the latter strategy consisted of about 2 min of CPR by EMS providers before first rhythm analysis. All episodes of OHCA in a cluster were allocated to one CPR strategy. After a set period of time, ranging from three to 12 months, each cluster was re-randomized to either CPR strategy. The primary outcome for either comparison was survival to hospital discharge with a modified Rankin score (MRS) of 3 or less. Patient enrollment began in June 2007. It concluded in November 2009 when the data and safety monitoring board recommended that the trial be stopped early because continuing recruitment was unlikely to change the outcome of the study. The ROC PRIMED trial qualified for exception from informed consent for emergency research. Participants in this substudy consented for follow up and survived to discharge (Fig. 1). 2.2. Prospective sub-study of health-related quality of life All research staff were trained in instrument administration before study enrollment began. Post-discharge assessments were made periodically by telephone interview (Appendix Fig. 1). Neurologic disability or dependence in daily activities was measured with modified Rankin scale (MRS) which was assessed from the clinical record prior to discharge.9 MRS is an ordinal scale from 0 (no symptoms) to 6 (dead), with MRS ≤ 3 interpreted as indicating satisfactory neurologic function. Neurological status was measured at 1, 3 and 6 months after discharge by using the adult lifestyle and function interview (ALFI)
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version of the mini-mental status exam (MMSE).10,11 The ALFIMMSE has 23 items. It is scored from 0 to 22, with lower scores interpreted as being worse. A cutoff of 16/17 is used to determine cognitive impairment. Generic HRQL was measured 3 and 6 months after discharge by administering the Health Utilities Index Mark 3 system (HUI3).12–14 The interview-administered version of HUI3 requires completion of a maximum of 39 questions. (http://www.healthutilities.com accessed on 14 October 2014) The HUI3 consists of eight attributes of general health (vision, hearing, speech, mobility, dexterity, emotion, cognition, and pain) with five or six levels per attribute. For each attribute, no, or mild impairment in health has been defined as better than level 3 function (or level 4 function in the cognition attribute). For each respondent, health status is described as a vector that combines the levels of each attribute. This information is then converted into a utility score of HRQL on a scale from perfect health (1.0) to death (0).13,15 A cutoff of 0.7 is used to determine severe impairment.16 Depression was assessed 3 and 6 months after discharge by using a shortened version of the Geriatric Depression Scale administered by telephone (T-GDS).17 This instrument has 15 items answered either ‘yes’ or ‘no’. It is scored from 0 to 15, with higher scores interpreted as being worse. A cutoff of 10/11 is used for the diagnosis of depression. This sub-study was approved by relevant institutional review boards or research ethics boards. Consent was obtained from subjects or their legally authorized representative prior to enrollment. 2.3. Statistical analysis Patients included in this sub-study were those enrolled in the intent-to-treat population for either ROC PRIMED treatment comparisons who survived to hospital discharge (Fig. 1). Descriptive statistics compared the baseline characteristics of patients who consented vs. not, and among those who consented, compared those interviewed vs. lost to follow up vs. died before interview. Logistic regression was used to build a predictive model for successful follow-up as compared to no post-discharge follow-up using baseline patient or EMS characteristics. Descriptive statistics compared outcomes at 1-, 3- and 6-month outcomes, assessed correlations between them, and also examined best and worst scores. This analysis led to the use of the last available score for each of the four post-discharge measures in subsequent analyses. Linear regression was used to assess associations between patient or EMS characteristics and each of the four outcome measures and also to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. The site with the largest sample size was the reference group. All regression analyses used robust standard errors to accommodate non-constant variances. Analyses were repeated using two methods to assess sensitivity to missing-data bias: multiple imputation with 20 hot-deck imputations using deciles of predicted values from regression models based on baseline characteristics; and inverse-probability weighting with weights based on the logistic regression analysis. Patients who consented to participate but subsequently died were assigned scores of 6 for MRS, 0 for ALFI-MMSE, 0 for HUI3, and 15 for T-GDS. 3. Results 3.1. Baseline characteristics and ems process according to follow-up status 18,036 treated OHCA were screened in ROC PRIMED, of which 15,794 were enrolled in the intent-to-treat sample for either the
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Fig. 1. Patient flow diagram.
active vs. sham ITD comparison or the Analyze Early vs. Analyze Later comparison. Of these, 1303 (8.3%) survived to hospital discharge. About 729 (56% of survivors) consented to participate in this post-discharge sub-study. About 644 (49% of survivors; 88% of consented) completed at least one post-discharge assessment. Eighteen (1.4% of survivors; 2.4% of consented) died before completing a post-discharge assessment. The proportions of missing baseline characteristics among those who consented (Table 1) were low (0–2.2%). Compared with patients who did not consent, those who consented and were interviewed were less likely to be female (24.5 vs. 31.0%) or have an obvious cause of arrest (1.2 vs. 6.0%), but were more likely to have arrested in a public location (41.2 vs. 31.0%), been witnessed by a bystander (72.8 vs. 66.7%), or received bystander CPR (55.0 vs. 48.6%). There were large differences in the distribution of initial rhythm, with higher percentages of shockable rhythm in the group followed (79.7 vs. 55.1%) while percentages of all other rhythms were higher in the group not followed. There were also differences in likelihood of follow-up by study site (Table 1).
3.2. Descriptive statistics and group comparisons on post-discharge outcomes The proportion of patients who were deceased at 1, 3, and 6 months, were 1.2, 3.2, and 5.4%, respectively (Table 2). Participants who survived to discharge after resuscitation from OHCA and completed at least one assessment after discharge had last available MRS of mean 1.7 ± SD 1.8; ALFI-MMSE of mean 18.4 ± SD 5.7; HUI3 of mean 0.74 ± SD 0.34; and T-GDS of mean 3.2 ± SD 4.3 (Table 2 and Appendix Fig. 2). The majority of survivors who were interviewed had satisfactory neurologic function (82.7% MRS ≤ 3), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no, mild or moderate impairment in general health (71.6% HUI3 ≥ 0.7, and no depression (90.1% T-GDS ≤ 10) at their last follow-up. Although most survivors had good quality of life, a minority had severe impairment (Appendix Fig. 3). Neurologic function, HRQL and depression of patients did not change significantly over time from hospital discharge (Table 2). The last available score of each post-discharge outcome was highly correlated with both its’ best and worst scores, with correlations above 0.9 for all measures.
Table 1 Characteristics of patients who survived to hospital discharge.
a
All patients
Consent obtained
Consent not obtained
Consented and interviewed
N = 1303
N = 1303
N = 729
N = 574
0 (0.0) 0 (0.0) 26 (2.0) 0 (0.0)
59.6 (15.4) 374 (28.7) 45 (3.5) 472 (36.2)
59.2 (14.1) 181 (24.8) 12 (1.7) 294 (40.3)
60.0 (16.9) 193 (33.6) 33 (6.0) 178 (31.0)
97 (7.5) 893 (69.9) 664 (51.2) 5.4 (2.4) 8.4 (4.8) 1275 (97.9)
56 (7.7) 525 (72.4) 388 (53.2) 5.4 (2.4) 8.1 (4.7) 716 (98.2)
880 (67.5) 219 (16.8) 86 (6.6) 52 (4.0) 66 (5.1)
2 (0.2) 26 (2.0) 6 (0.5) 11 (0.8) 28 (2.1) 0 (0.0)
N = 644
Consented and lost to follow-up N = 67
Consented, died before interview N = 18
59.1 (14.1) 158 (24.5) 8 (1.2) 265 (41.2)
58.5 (14.5) 18 (26.9) 3 (4.7) 26 (38.8)
65.9 (11.6) 5 (27.8) 1 (5.6) 3 (16.7)
41 (7.2) 368 (66.7) 276 (48.6) 5.4 (2.4) 8.7 (5.0) 559 (97.4)
49 (7.6) 468 (72.8) 354 (55.0) 5.4 (2.4) 8.1 (4.6) 632 (98.1)
5 (7.5) 45 (70.3) 30 (44.8) 5.1 (2.3) 8.1 (5.1) 66 (98.5)
2 (11.1) 12 (66.7) 4 (22.2) 5.4 (3.0) 6.9 (4.1) 18 (100.0)
564 (77.4) 84 (11.5) 36 (4.9) 25 (3.4) 20 (2.7)
316 (55.1) 135 (23.5) 50 (8.7) 27 (4.7) 46 (8.0)
513 (79.7) 65 (10.1) 30 (4.7) 20 (3.1) 16 (2.5)
42 (62.7) 13 (19.4) 5 (7.5) 4 (6.0) 3 (4.5)
9 (50.0) 6 (33.3) 1 (5.6) 1 (5.6) 1 (5.6)
15 (1.2) 40 (3.1) 88 (6.8) 163 (12.5) 36 (2.8) 134 (10.3) 49 (3.8) 359 (27.6) 253 (19.4) 166 (12.7) 2.2 (1.7)
14 (1.9) 24 (3.3) 51 (7.0) 109 (15.0) 24 (3.3) 103 (14.1) 14 (1.9) 169 (23.2) 140 (19.2) 81 (11.1) 1.9 (1.6)
1 (0.2) 16 (2.8) 37 (6.4) 54 (9.4) 12 (2.1) 31 (5.4) 35 (6.1) 190 (33.1) 113 (19.7) 85 (14.8) 2.6 (1.8)
13 (2.0) 14 (2.2) 46 (7.1) 105 (16.3) 11 (1.7) 86 (13.4) 14 (2.2) 148 (23.0) 134 (20.8) 73 (11.3) 1.8 (1.5)
1 (1.5) 5 (7.5) 4 (6.0) 4 (6.0) 9 (13.4) 13 (19.4) 0 (0.0) 19 (28.4) 5 (7.5) 7 (10.4) 2.2 (1.6)
0 (0.0) 5 (27.8) 1 (5.6) 0 (0.0) 4 (22.2) 4 (22.2) 0 (0.0) 2 (11.1) 1 (5.6) 1 (5.6) 4.2 (1.3)
282 (22.1) 313 (24.6) 73 (5.7) 260 (20.4) 193 (15.1) 153 (12.0)
175 (24.1) 210 (28.9) 47 (6.5) 164 (22.6) 91 (12.5) 39 (5.4)
107 (19.5) 103 (18.8) 26 (4.7) 96 (17.5) 102 (18.6) 114 (20.8)
164 (25.5) 191 (29.7) 39 (6.1) 150 (23.3) 76 (11.8) 23 (3.6)
11 (16.9) 17 (26.2) 8 (12.3) 13 (20.0) 11 (16.9) 5 (7.7)
0 (0)
29 (2.2)
G. Nichol et al. / Resuscitation 93 (2015) 74–81
Age, mean (SD) Female, N (%) Obvious cause of arrest, N (%)a Public location, N (%) Witness status, N (%) EMS witnessed arrest Bystander witnessed arrest Bystander CPR, N (%) Dispatch to first EMS arrival (min), mean (SD) Dispatch to first ALS arrival (min), mean (SD) Treated by ALS, N(%) First known rhythm, N(%) VT/VF/shockable PEA Asystole AED no shock advised, no strip Cannot determine/unknown Site, N (%) A B C D E F G H I J Modified Rankin scale at discharge, mean (SD) Modified Rankin scale category, N (%) 0 1 2 3 4 5
Missing data, n (%)
0 (0.0) 2 (11.1) 0 (0.0) 1 (5.6) 4 (22.2) 11 (61.1)
Included but not limited to drug or chemical poisoning and mechanical suffocation (foreign body or hanging.)
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Table 2 Unadjusted post-discharge outcomes.
Alive, n (%) MRS Mean (SD) Prop. ≤3 (%) ALFI-MMSE Mean (SD) Prop. ≥17 (%) HUI Mark 3 Mean (SD) Prop. ≥0.7 (%) T-GDS Mean (SD) Prop. ≤10 (%)
1 month N = 684
3 months N = 664
6 months N = 591
Worst score N = 689
Best score N = 689
Last available score N = 689
676 (98.8)
643 (96.8)
559 (94.6)
657 (95.4)
676 (98.1)
657 (95.4)
1.8 (1.7) 459/550 (83.5)
1.8 (1.8) 463/564 (82.1)
2.1 (1.8) 504/636 (79.2)
1.5 (1.7) 546/636 (85.8)
1.7 (1.8) 526/636 (82.7)
19.1 (4.7) 443/509 (87.0)
18.7 (5.7) 449/527 (85.2)
17.5 (5.6) 489/637 (76.8)
19.2 (5.2) 552/637 (86.7)
18.4 (5.7) 527/627 (82.7)
0.75 (0.33) 295/409 (72.1)
0.74 (0.35) 307/429 (71.6)
0.71 (0.35) 370/549 (67.4)
0.77 (0.33) 414/549 (75.4)
0.74 (0.34) 393/549 (71.6)
3.0 (4.0) 463/505 (91.7)
3.2 (4.3) 469/521 (90.0)
3.7 (4.3) 523/587 (89.1)
2.7 (4.1) 537/587 (91.5)
3.2 (4.3) 529/587 (90.1)
18.6 (5.0) 376/452 (83.2)
Post-discharge outcomes were not significantly different between Analyze Early vs. Analyze Later strategies or active vs. sham ITD after adjustment for other factors (Table 3).
3.3. Independent predictors of post-discharge outcomes Post-discharge outcomes were associated with some baseline characteristics as well as EMS process factors (Table 4). Patients who arrested in a public location had significantly better cognition (difference in ALFI-MMSE score, mean (95% confidence interval) 0.76 (0.01, 1.50) as well as HRQL after discharge (difference in HUI3 score, mean (95% confidence interval) 0.07 (0.02, 0.13) and less depression (difference in T-GDS, −0.67 (−1.30, −1.004) as compared to private location. Those who received bystander CPR had better cognitive function after discharge (difference in ALFI-MMSE, 1.02 (0.21, 1.84) and less depression (difference in T-GDS, −0.81 (−1.52, −0.10) as compared to those who did not receive bystander CPR. An initial shockable rhythm was associated with better post-discharge neurologic status, cognitive function, HRQL and depression (difference in MRS, ALFI-MMSE, HUI3 and TGDS scores compared to non-shockable rhythms of −0.72 (−1.10, −0.34), 2.39 (1.09, 3.68), 0.13 (0.05, 0.20), −1.39 (−2.42, −0.37) respectively). After addition of post-discharge outcomes to the models, all of these associations with baseline characteristics and EMS process variables were no longer significant. MRS at discharge was independently associated with post-discharge neurologic status, cognition, HRQL and depression (difference in MRS score of 0.41 (0.32, 0.50), −1.30 (−1.64, −0.96), −0.07 (−0.09, −0.05), 0.67 (0.41, 0.93) for post-discharge MRS, ALFI-MMSE, HUI3, and T-GDS
Table 3 Adjusted group comparisons of post-discharge outcomes. Outcome
Active vs. sham ITD difference N = 460 Difference (95% CI)
Analyze late vs. early difference N = 605 Difference (95% CI)
Alive, % MRS MRS ≤ 3, % ALFI-MMSE ALFI-MMSE≥17, % HUI3 HUI3 ≥0.7, % T-GDS T-GDS ≤10, %
−1.7 (−5.2, 1.9) 0.14 (−0.17, 0.44) −0.76 (−5.36, 3.85) −0.66 (−1.61, 0.28) −6.06 (−12.22, 0.10) −0.02 (−0.08, 0.05) −1.15 (−9.95, 7.64) −0.11 (−0.92, 0.71) −1.08 (−6.80, 4.63)
0.72 (−2.31, 3.74) 0.07 (−0.20, 0.34) 0.31 (−3.17, 3.78) 0.06 (−0.71, 0.83) −1.25 (−7.21, 4.70) 0.00 (−0.06, 0.05) 0.49 (−7.66, 8.63) −0.46 (−1.06, 0.15) 0.75 (−3.94, 5.44)
Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, and site location
respectively). Some site differences remained after adjustment for baseline characteristics as well as MRS at discharge. Greater post-discharge HRQL was significantly associated with less neurologic impairment, cognitive impairment or depression after adjustment for baseline characteristics and EMS process (difference in post-discharge HUI3 score of −0.06 (−0.08, −0.04), −0.05 (−0.06, −0.04) for post-discharge MRS and T-GDS respectively). 3.4. Assessment of non-participation and missing data Post-discharge follow-up was significantly associated with some baseline characteristics and EMS process as well as site (see online Appendix Table 1). Accounting for missing data by using multiple imputation or inverse-probability weighting changed the assessment of neurologic status, cognitive impairment, and HRQL in the direction of worse outcomes for each measure. However, associations with baseline characteristics and comparisons of outcomes by treatment group with accounting for missing data generally changed the results quantitatively but not qualitatively (see online Appendix Tables 2 and 3). 4. Comment Most patients who were resuscitated from OHCA, survived to discharge and completed at least one assessment in this prospective sub-study of a large trial had satisfactory neurologic function, no cognitive impairment, and no depression. Most did not have severe impairment of HRQL. Ratings were relatively robust to whether and how the analysis accounted for missing data. Also ratings were robust to adjustment for differences in most but not all baseline characteristics or EMS process variables. Experts recommend post-discharge assessments of neurologic function as the primary measure of the effectiveness of resuscitation interventions.1 But such post-discharge assessments are logistically difficult and prolong study duration compared to assessment of outcomes prior to discharge from hospital, so potentially delay adoption of effective resuscitation interventions. Importantly, they are also subject to selection bias as demonstrated by the present study as well as prior work.18 As the majority of survivors who were interviewed in this study were not impaired, such efforts may not be warranted so that effective resuscitation interventions can be identified quickly, then disseminated into common practice. Prior studies of cognition and HRQL after OHCA provide conflicting evidence of the degree of impairment in this population, due in part to their differences in baseline and treatment characteristics, small sample size as well as use of multiple different measures at multiple different time points.2,19–28 Importantly,
Table 4 Independent predictors of post-discharge outcomes. Prediction using pre-hospital and post-discharge variablesb , point estimate (95% confidence intervals)
Predictor variables
MRS
ALFI-MMSE
HUI3
T-GDS
MRS
ALFI-MMSE
HUI3
T-GDS
Baseline variables Age, years
0.008 (−.001, 0.02)
−0.048 (−0.08, −0.02)
−0.008 (−0.034, 0.017)
−0.001 (−0.008, 0.005)
−0.03 (−0.87, 0.82) 3.09 (−0.91, 7.08)
−0.04 (−0.24, 0.16) −0.49 (−1.52, 0.53)
−0.046 (−0.068, −0.024) −0.74 (−1.49, −0.002) 0.50 (−3.36, 4.37)
−0.001 (−0.002, −0.0002) −0.01 (−0.05, 0.03) −0.08 (−0.32, 0.16)
−0.02 (−0.04, −0.01)
−0.73 (−1.72, 0.26) −1.26 (−4.36, 1.84)
−0.001 (−0.003, 0.0004) −0.01 (−0.08, 0.06) −0.29 (−0.63, 0.06)
−0.22 (−0.69, 0.26) 1.45 (−0.76, 3.66)
0.76 (0.01, 1.50)
0.07 (0.02, 0.13)
−0.67 (−1.30, −0.04)
0.16 (−0.02, 0.34)
0.36 (−0.22, 0.94)
0.04 (−0.0003, 0.07)
−0.04 (−0.44, 0.35)
−0.79 (−2.87, 1.29)
0.004 (−0.12, 0.13)
0.62 (−1.02, 2.25)
−0.10 (−0.50, 0.30)
0.24 (−1.28, 1.76)
0.036 (−0.04, 0.12)
0.76 (−0.15, 1.68)
−0.66 (−1.71, 0.39)
0.03 (−0.05, 0.10)
−0.05 (−0.95, 0.85)
0.001 (−0.20, 0.20)
−0.61 (−1.40, 0.18)
0.008 (−0.04, 0.05)
−0.16 (−0.66, 0.33)
1.02 (0.21, 1.84) −0.086 (−0.30, 0.13)
0.05 (−0.005, 0.11) −0.004 (−0.02, 0.01)
−0.81 (−1.52, −0.10) 0.012 (−0.159, 0.183)
−0.03 (−0.21, 0.15) −0.02 (−0.06, 0.01)
0.28 (−0.34, 0.89) −0.11 (−0.27, 0.04)
0.002 (−0.04, 0.04) −0.004 (−0.01, 0.003)
−0.13 (−0.57, 0.30) −0.02 (−0.10, 0.06)
−0.12 (−2.16, 1.93) 2.39 (1.09, 3.68)
−0.004 (−0.16, 0.15) 0.13 (0.05, 0.21)
0.15 (−1.48, 1.78) −1.39 (−2.42, −0.37)
−0.21 (−0.68, 0.27) −0.05 (−0.28, 0.18)
−0.11 (−1.99, 1.77) 0.39 (−0.51, 1.28)
−0.01 (−0.12, 0.10) 0.03 (−0.02, 0.07)
0.18 (−1.18, 1.53) −0.01 (−0.53, 0.52)
−1.30 (−1.64, −0.96)
−0.07 (−0.09, −0.05)
0.67 (0.41, 0.93)
0.08 (0.02, 0.15)
−0.39 (−0.64, −0.14)
−0.01 (−0.03, −0.001)
−0.13 (−0.27, 0.02)
−1.08 (−3.95, 1.79) −5.37 (−9.06, −1.69) 0.01 (−2.07, 2.08) −0.88 (−2.03, 0.27) −4.08 (−8.46, 0.30) −0.36 (−1.66, 0.94) 1.99 (0.55, 3.43) Reference −0.31 (−1.35, 0.72) −0.30 (−1.62, 1.03)
−0.23 (−0.41, −0.04) −0.11 (−0.27, 0.04) 0.05 (−0.07, 0.17) −0.02 (−0.1, 0.06) −0.31 (−0.50, −0.11) −0.09 (−0.18, 0.01) −0.09 (−0.30, 0.12) Reference 0.01 (−0.07, 0.08) 0.01 (−0.09, 0.11)
0.34 (−2.22, 2.91) 3.35 (0.16, 6.54) −1.35 (−2.88, 0.19) 1.24 (0.15, 2.33) 5.69 (2.85, 8.53) 0.96 (−0.08, 2.00) 1.15 (−1.36, 3.67) Reference 0.46 (−0.46, 1.37) −0.15 (−1.28, 0.99)
−0.01 (−0.64, 0.62) −0.10 (−0.48, 0.28) −0.15 (−0.47, 0.17) −0.20 (−0.49, 0.10) −0.50 (−1.06, 0.07) 0.39 (0.09, 0.68) 0.13 (−0.51, 0.78) Reference 0.31 (0.03, 0.58) −0.42 (−0.69, −0.14)
−0.56 (−2.96, 1.83) −3.76 (−5.89, −1.63) −0.14 (−1.39, 1.11) −0.20 (−1.21, 0.82) −1.19 (−4.46, 2.08) 0.33 (−0.71, 1.37) 2.36 (0.34, 4.38) Reference 0.63 (−0.17, 1.43) −0.86 (−1.84, 0.11)
−0.10 (−0.23, 0.03) 0.01 (−0.05, 0.07) −0.02 (−0.09, 0.05) 0.04 (−0.01, 0.1) −0.01 (−0.12, 0.11) 0.001 (−0.06, 0.06) −0.06 (−0.17, 0.06) Reference 0.06 (0.01, 0.11) −0.03 (−0.09, 0.03)
−0.82 (−2.28, 0.64) 0.01 (−0.81, 0.84) −0.32 (−1.07, 0.43) 0.91 (0.19, 1.62) 2.03 (0.50, 3.56) −0.12 (−0.73, 0.49) 0.22 (−0.98, 1.41) Reference 0.34 (−0.17, 0.84) 0.04 (−0.53, 0.61)
−1.16 (−1.61, −0.71)
−0.06 (−0.08, −0.04) −0.01 (−0.01, 0.0003)
0.59 (0.36, 0.93) −0.22 (−0.29, −0.15) −6.01 (−7.26, −4.75)
Female, % 0.11 (−0.20, 0.43) Obvious cause of 0.28 (−0.94, 1.50) arrest, % Public location, % −0.21 (−0.45, 0.04) Witness status, % EMS witnessed −0.06 (−0.66, 0.54) arrest Bystander −0.02 (−0.35, 0.31) witnessed arrest Bystander CPR, % −0.18 (−0.45, 0.09) Dispatch to First 0.001 (−0.06, 0.06) EMS arrival, per min Treated by ALS, % −0.01 (−0.63, 0.61) −0.72 (−1.10, −0.34) First known shockable rhythm, % Modified Rankin 0.41 (0.32, 0.50) scale at discharge Site 0.72 (−0.21, 1.64) A B 0.95 (0.15, 1.75) C −0.41 (−1.01, 0.19) D 0.11 (−0.28, 0.50) 1.02 (−0.07, 2.11) E F 0.63 (0.21, 1.05) G 0.19 (−0.75, 1.12) Reference H I 0.44 (0.09, 0.80) J −0.43 (−0.90, 0.04) Post-discharge variables MRS ALFI-MMSE HUI3 T-GDS
−0.09 (−0.12, −0.06) −1.65 (−2.15, −1.15) 0.12 (0.07, 0.16)
−1.88 (−3.94, 0.17) −0.56 (−0.76, −0.36)
G. Nichol et al. / Resuscitation 93 (2015) 74–81
Prediction using baseline characteristics and EMS process variablesa , point estimate (95% confidence intervals)
−0.05 (−0.06, −0.04)
a
Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, and site location. b Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, site location and post-discharge outcomes.
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resuscitation interventions associated with good survival are also associated with good HRQL.29–31 Thus the results of this large prospective cohort study are consistent with prior assessments of functional outcomes after cardiac arrest. Our observation that the presence of a shockable first recorded rhythm after the onset of cardiac arrest was a strong predictor of post-discharge outcome is consistent with prior evidence that demonstrated that the presence of a shockable rhythm is a strong correlate of the likelihood of survival to discharge.32 Provision of bystander CPR was associated with better cognition after discharge. Although rhythm is not modifiable, the likelihood of bystander CPR being performed could be modified by implementing dispatcher instructions in CPR,33,34 or by increased training of laypersons in recognition and response to cardiac arrest.35,36 Thus communitybased interventions could improve the cognition, depression status and HRQL of survivors after cardiac arrest. Our observation of differences in post-discharge outcome by site is new and warrants cautious interpretation. Self-reported HRQL varies by geography and culture.37 Baseline differences in HRQL among subjects in the present study were not assessed because such retrospective assessments are of unknown reliability or validity in this population. A difference of 0.03 on a scale of 0–1 was previously defined as the minimum clinically important difference in a generic HRQL score such as HUI3.14,38 Others suggested that a difference of 0.1 on a HRQL scale of 0–1 was probably clinically important.39 We observed such differences between sites after conditioning on survival to discharge (since only patients who consented to participate in the study were assessed after discharge), and after adjusting for baseline and EMS covariates. These differences were consistent with trends in other post-discharge outcomes across sites. But there were differences in the proportion of patients followed up across sites. If these inter-site differences in HRQL are true, some of them appear to be large enough to be clinically important. These differences warrant further exploration in a future study. Some argue that attempts to resuscitate patients after OHCA may not be appropriate because both survival and quality of life are poor.40 If outcomes after cardiac arrest are indeed poor, then treatments for this disorder may not be economically attractive.41 Conversely, if the quality of life of survivors is good, then even a small improvement in survival would be important to patients and policymakers. Our observation that a minority of patients who survive to discharge are severely impaired reemphasizes the need for ongoing efforts to improve survival after cardiac arrest. Limitations of this study included the rate of non-consent among survivors. The association between consent for participation and site as well as other factors suggests that participation in this sub-study was not random. Importantly neurologic function at discharge differed significantly between those who were and were not followed. Imputation and inverse-probability weighting were used to adjust for these data which were not missing at random but associated with predictors of poorer functional outcome. Use of imputation changed the results in the direction of worse outcomes for each measure. However, associations and treatment group comparisons were generally not sensitive to whether or how missing data was accounted for among consenting survivors. Despite the rate of non-consent among survivors, this is the largest study reported to date of post-discharge outcomes in patients resuscitated from cardiac arrest. The proportion of survivors interviewed after discharge was similar to or better than prior studies in this population.4,31,42 Another limitation is that hospital care and post-resuscitation prognosis assessment and withdrawal of care were not standardized. Combinations of hospital-based treatments improved outcomes in patients resuscitated from cardiac arrest compared with historical controls.43–48 Collectively, these studies
demonstrate that hospital-based care of those resuscitated from OHCA is associated with patient outcomes and potentially modifies the effect of interventions for cardiac arrest. Outcomes were assessed by telephone rather than face-toface interview. Each of these measures was previously used to detect impairment. ALFI-MMSE correlates strongly with face-toface MMSE across all patients or when grouped by clinical dementia rating scale class.10 The HUI3 was used in several studies of interventions for individuals resuscitated from cardiac arrest2,31 and is reliable and valid in other populations.49–51 Although the T-GDS was initially designed for use in older adults, it is also valid in younger adults.52 Thus, each of the measures we used to assess impairment after discharge has acceptable performance characteristics for telephone administration, as used in this study. Strengths of this study include that multiple measures were used to describe multiple dimensions of functional status and HRQL in a large cohort of survivors of OHCA. Prior to the design of the ROC PRIMED trial, MRS was used to assess survivors of cardiac arrest in a cohort of neurosurgical patients with in-hospital cardiac arrest53 and a cohort of survivors of OHCA.42 MRS has concurrent validity with other measures of neurological recovery after stroke and brain injury.54,55 Use of a structured interview in a recent study of stroke patients improved the measure’s reliability.9 The present study demonstrated that MRS prior to discharge is strongly correlated with multiple post-discharge outcomes, which reinforces the former as being a valid measure of resuscitation success. Importantly these performance characteristics are such that we believe it is unlikely that we failed to detect significant impairment present in this population.
5. Conclusion The majority of patients in this large cohort who survived cardiac arrest and were interviewed had satisfactory neurologic function, no cognitive impairment, no or mild impairment in health and no depression. Concerns about the likelihood of poor quality of life after resuscitation are not a valid reason to abandon efforts to improve a health care system’s response to victims of cardiac arrest.
Conflict of interest statement Dr. Nichol receives salary support from the University of Washington via the Leonard A. Cobb Medic One Foundation Endowed Chair in Prehospital Emergency Care. He holds Research Grants from the following: (1) National Heart Lung Blood Institute, Bethesda, MD. Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004–2015; Co-PI; (2) Food and Drug Administration, Silver Spring, MD; Cardiac Science Corp, Waukesha, WI; Heartsine Technologies Inc., Newtown, PA; Philips Healthcare Inc., Bothell, WA; Physio-Control Inc., Redmond, WA; ZOLL Inc., Chelmsford, MA. University of Washington Dynamic AED Registry, PI. 2013–2015; (3) Velomedix Inc., Menlo Park, CA. Velocity Pilot Study of Ultrafast Hypothermia in Patients with ST-Elevation Myocardial Infarction, National Co-PI. 2014–2015. *Waived personal compensation. He did not receive any other Research Support. He is not a member of Speakers Bureau and does not hold an Honorary post in any company. He received travel reimbursement from Abiomed Inc., Danvers, MA in 2015. He has no other conflict of interest to declare. Dr. Cheskes has received speaking honorarium from Zoll Medical and Physio-Control Inc. He has received grant funding as Co-PI, Toronto site, Resuscitation Outcomes Consortium. The other authors disclosed no conflict of interest.
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Health-related quality of life is better for cardiac arrest survivors who received citizen cardiopulmonary resuscitation. Circulation 2003;108:1939–44. 32. Rea TD, Cook AJ, Stiell IG, et al. Predicting survival after out-of-hospital cardiac arrest: role of the Utstein data elements. Ann Emerg Med 2010;55:249–57. 33. Hallstrom A, Cobb L, Johnson E, Copass M. Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilation. N Engl J Med 2000;342:1546–53. 34. Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med 2010;363:423–33. 35. Bobrow BJ, Spaite DW, Berg RA, et al. Chest compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA 2010;304:1447–54. 36. Wissenberg M, Lippert FK, Folke F, et al. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest. 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Clinical Paper
Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy夽 Graham Nichol a,b,∗ , Danielle Guffey a , Ian G. Stiell c , Brian Leroux a , Sheldon Cheskes d , Ahamed Idris e , Peter J. Kudenchuk f , Renee S. Macphee g , Lynn Wittwer h , Jon C. Rittenberger i , Thomas D. Rea f , Kellie Sheehan a , Val E. Rac j , Keitki Raina i , Kyle Gorman k , Tom Aufderheide l , the Resuscitation Outcomes Consortium Investigators a
Clinical Trial Center, Department of Biostatistics, University of Washington, Seattle, WA, United States University of Washington-Harborview Center for Prehospital Emergency Care, Department of Medicine, University of Washington, Seattle, WA, United States c Department of Emergency Medicine, University of Ottawa, Ottawa Health Research Institute, Ottawa, ON, Canada d Rescu, Li Ka Shing Knowledge Institute, St Michael’s Hospital and Sunnybrook Center for Prehospital Medicine, Division of Emergency Medicine, Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada e Departments of Emergency Medicine and Internal Medicine, University of Texas Southwestern, Dallas, TX, United States f King County EMS, Seattle and King County Public Health, and Department of Medicine, University of Washington, Seattle, WA, United States g Wilfrid Laurier University, Waterloo, ON, Canada h Clark County Emergency Medical Services, Vancouver, WA, United States i Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, United States j Toronto Health Economics and Technology Assessment Collaborative, Institute of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, ON, Canada k Clackamas Fire District #1, Clackamas, OR, United States l Medical College of Wisconsin, Milwaukee, WI, United States b
a r t i c l e
i n f o
Article history: Received 13 February 2015 Received in revised form 16 May 2015 Accepted 17 May 2015 Keywords: Cardiac arrest Prognosis Quality of life Depression Cognition Functional status
a b s t r a c t Importance: Assessment of morbidity is an important component of evaluating interventions for patients with out-of-hospital cardiac arrest (OHCA). Objective: We evaluated among survivors of OHCA cognition, functional status, health-related quality of life and depression as functions of patient and emergency medical services (EMS) factors. Design: Prospective cohort sub-study of a randomized trial. Setting: The parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium. Participants: Consenting survivors to discharge. Main outcome measures: Telephone assessments up to 6 months after discharge included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), health-related quality of life (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS). Results: Of 15,794 patients enrolled in the parent trial, 729 (56% of survivors) consented. About 644 respondents (88% of consented) completed ≥ 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most respondents had MRS ≤ 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no severe impairment in health (71.6%, HUI3 ≥ 0.7) and no depression (90.1% T-GDS ≤ 10). Outcomes did not differ by trial intervention or time from hospital discharge. Conclusions and relevance: The majority of patients in this large cohort who survived cardiac arrest and were interviewed had no, mild or moderate health impairment. Concern about poor quality of life is not a valid reason to abandon efforts to improve an EMS system’s response to cardiac arrest. © 2015 Published by Elsevier Ireland Ltd.
夽 A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2015.05.011. ∗ Corresponding author at: University of Washington-Harborview Center for Prehospital Emergency Care, Department of Medicine, Box 359727, 325 Ninth Ave, Seattle, WA 98104, United States. E-mail address: [email protected] (G. Nichol). http://dx.doi.org/10.1016/j.resuscitation.2015.05.011 0300-9572/© 2015 Published by Elsevier Ireland Ltd.
G. Nichol et al. / Resuscitation 93 (2015) 74–81
1. Objective Assessment of cognition, functional status, health-related quality of life (HRQL) and mood are important components of evaluating the effects of interventions for patients with out-of-hospital cardiac arrest (OHCA).1 Survivors of OHCA may have HRQL that is similar to that of age- and sex-matched peers.2 Depression is observed in those with cardiovascular disease3 or who have survived cardiac arrest,4 and is difficult to differentiate from cognitive impairment. Thus, resuscitation interventions may be associated with subtle differences in neurologic status, HRQL, or depression after discharge. Therefore this prospective sub-study of the Prehospital Resuscitation IMpedance valve and Early vs. Delayed analysis (ROC PRIMED) trial sought to: describe post-discharge neurological status, cognition, HRQL and depression as functions of baseline characteristics, EMS process, and study interventions; compare the characteristics of patients with complete vs. missing postdischarge measures; and correlate post-discharge outcomes with each other after OHCA. 2. Design and methods 2.1. Overview of randomized trial This study was a prospective cohort sub-study of a randomized trial. The methods and results for the parent ROC PRIMED trial were previously reported.5–8 The Resuscitation Outcomes Consortium (ROC) is a clinical trial network that includes 10 U.S. and Canadian universities and their regional emergency medical services (EMS) systems. This trial used a partial factorial design to study two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in ROC. The first comparison randomly allocated persons to undergo cardiopulmonary resuscitation (CPR) with an active or sham impedance threshold device (ITD). The second comparison randomly allocated clusters of individuals with OHCA grouped by EMS agency or geographic boundaries or defibrillator device, vehicle, station or battalion to Analyze Early or Analyze Later. The former strategy consisted of about 30 s of manual CPR by EMS providers before first rhythm analysis; the latter strategy consisted of about 2 min of CPR by EMS providers before first rhythm analysis. All episodes of OHCA in a cluster were allocated to one CPR strategy. After a set period of time, ranging from three to 12 months, each cluster was re-randomized to either CPR strategy. The primary outcome for either comparison was survival to hospital discharge with a modified Rankin score (MRS) of 3 or less. Patient enrollment began in June 2007. It concluded in November 2009 when the data and safety monitoring board recommended that the trial be stopped early because continuing recruitment was unlikely to change the outcome of the study. The ROC PRIMED trial qualified for exception from informed consent for emergency research. Participants in this substudy consented for follow up and survived to discharge (Fig. 1). 2.2. Prospective sub-study of health-related quality of life All research staff were trained in instrument administration before study enrollment began. Post-discharge assessments were made periodically by telephone interview (Appendix Fig. 1). Neurologic disability or dependence in daily activities was measured with modified Rankin scale (MRS) which was assessed from the clinical record prior to discharge.9 MRS is an ordinal scale from 0 (no symptoms) to 6 (dead), with MRS ≤ 3 interpreted as indicating satisfactory neurologic function. Neurological status was measured at 1, 3 and 6 months after discharge by using the adult lifestyle and function interview (ALFI)
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version of the mini-mental status exam (MMSE).10,11 The ALFIMMSE has 23 items. It is scored from 0 to 22, with lower scores interpreted as being worse. A cutoff of 16/17 is used to determine cognitive impairment. Generic HRQL was measured 3 and 6 months after discharge by administering the Health Utilities Index Mark 3 system (HUI3).12–14 The interview-administered version of HUI3 requires completion of a maximum of 39 questions. (http://www.healthutilities.com accessed on 14 October 2014) The HUI3 consists of eight attributes of general health (vision, hearing, speech, mobility, dexterity, emotion, cognition, and pain) with five or six levels per attribute. For each attribute, no, or mild impairment in health has been defined as better than level 3 function (or level 4 function in the cognition attribute). For each respondent, health status is described as a vector that combines the levels of each attribute. This information is then converted into a utility score of HRQL on a scale from perfect health (1.0) to death (0).13,15 A cutoff of 0.7 is used to determine severe impairment.16 Depression was assessed 3 and 6 months after discharge by using a shortened version of the Geriatric Depression Scale administered by telephone (T-GDS).17 This instrument has 15 items answered either ‘yes’ or ‘no’. It is scored from 0 to 15, with higher scores interpreted as being worse. A cutoff of 10/11 is used for the diagnosis of depression. This sub-study was approved by relevant institutional review boards or research ethics boards. Consent was obtained from subjects or their legally authorized representative prior to enrollment. 2.3. Statistical analysis Patients included in this sub-study were those enrolled in the intent-to-treat population for either ROC PRIMED treatment comparisons who survived to hospital discharge (Fig. 1). Descriptive statistics compared the baseline characteristics of patients who consented vs. not, and among those who consented, compared those interviewed vs. lost to follow up vs. died before interview. Logistic regression was used to build a predictive model for successful follow-up as compared to no post-discharge follow-up using baseline patient or EMS characteristics. Descriptive statistics compared outcomes at 1-, 3- and 6-month outcomes, assessed correlations between them, and also examined best and worst scores. This analysis led to the use of the last available score for each of the four post-discharge measures in subsequent analyses. Linear regression was used to assess associations between patient or EMS characteristics and each of the four outcome measures and also to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. The site with the largest sample size was the reference group. All regression analyses used robust standard errors to accommodate non-constant variances. Analyses were repeated using two methods to assess sensitivity to missing-data bias: multiple imputation with 20 hot-deck imputations using deciles of predicted values from regression models based on baseline characteristics; and inverse-probability weighting with weights based on the logistic regression analysis. Patients who consented to participate but subsequently died were assigned scores of 6 for MRS, 0 for ALFI-MMSE, 0 for HUI3, and 15 for T-GDS. 3. Results 3.1. Baseline characteristics and ems process according to follow-up status 18,036 treated OHCA were screened in ROC PRIMED, of which 15,794 were enrolled in the intent-to-treat sample for either the
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Fig. 1. Patient flow diagram.
active vs. sham ITD comparison or the Analyze Early vs. Analyze Later comparison. Of these, 1303 (8.3%) survived to hospital discharge. About 729 (56% of survivors) consented to participate in this post-discharge sub-study. About 644 (49% of survivors; 88% of consented) completed at least one post-discharge assessment. Eighteen (1.4% of survivors; 2.4% of consented) died before completing a post-discharge assessment. The proportions of missing baseline characteristics among those who consented (Table 1) were low (0–2.2%). Compared with patients who did not consent, those who consented and were interviewed were less likely to be female (24.5 vs. 31.0%) or have an obvious cause of arrest (1.2 vs. 6.0%), but were more likely to have arrested in a public location (41.2 vs. 31.0%), been witnessed by a bystander (72.8 vs. 66.7%), or received bystander CPR (55.0 vs. 48.6%). There were large differences in the distribution of initial rhythm, with higher percentages of shockable rhythm in the group followed (79.7 vs. 55.1%) while percentages of all other rhythms were higher in the group not followed. There were also differences in likelihood of follow-up by study site (Table 1).
3.2. Descriptive statistics and group comparisons on post-discharge outcomes The proportion of patients who were deceased at 1, 3, and 6 months, were 1.2, 3.2, and 5.4%, respectively (Table 2). Participants who survived to discharge after resuscitation from OHCA and completed at least one assessment after discharge had last available MRS of mean 1.7 ± SD 1.8; ALFI-MMSE of mean 18.4 ± SD 5.7; HUI3 of mean 0.74 ± SD 0.34; and T-GDS of mean 3.2 ± SD 4.3 (Table 2 and Appendix Fig. 2). The majority of survivors who were interviewed had satisfactory neurologic function (82.7% MRS ≤ 3), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no, mild or moderate impairment in general health (71.6% HUI3 ≥ 0.7, and no depression (90.1% T-GDS ≤ 10) at their last follow-up. Although most survivors had good quality of life, a minority had severe impairment (Appendix Fig. 3). Neurologic function, HRQL and depression of patients did not change significantly over time from hospital discharge (Table 2). The last available score of each post-discharge outcome was highly correlated with both its’ best and worst scores, with correlations above 0.9 for all measures.
Table 1 Characteristics of patients who survived to hospital discharge.
a
All patients
Consent obtained
Consent not obtained
Consented and interviewed
N = 1303
N = 1303
N = 729
N = 574
0 (0.0) 0 (0.0) 26 (2.0) 0 (0.0)
59.6 (15.4) 374 (28.7) 45 (3.5) 472 (36.2)
59.2 (14.1) 181 (24.8) 12 (1.7) 294 (40.3)
60.0 (16.9) 193 (33.6) 33 (6.0) 178 (31.0)
97 (7.5) 893 (69.9) 664 (51.2) 5.4 (2.4) 8.4 (4.8) 1275 (97.9)
56 (7.7) 525 (72.4) 388 (53.2) 5.4 (2.4) 8.1 (4.7) 716 (98.2)
880 (67.5) 219 (16.8) 86 (6.6) 52 (4.0) 66 (5.1)
2 (0.2) 26 (2.0) 6 (0.5) 11 (0.8) 28 (2.1) 0 (0.0)
N = 644
Consented and lost to follow-up N = 67
Consented, died before interview N = 18
59.1 (14.1) 158 (24.5) 8 (1.2) 265 (41.2)
58.5 (14.5) 18 (26.9) 3 (4.7) 26 (38.8)
65.9 (11.6) 5 (27.8) 1 (5.6) 3 (16.7)
41 (7.2) 368 (66.7) 276 (48.6) 5.4 (2.4) 8.7 (5.0) 559 (97.4)
49 (7.6) 468 (72.8) 354 (55.0) 5.4 (2.4) 8.1 (4.6) 632 (98.1)
5 (7.5) 45 (70.3) 30 (44.8) 5.1 (2.3) 8.1 (5.1) 66 (98.5)
2 (11.1) 12 (66.7) 4 (22.2) 5.4 (3.0) 6.9 (4.1) 18 (100.0)
564 (77.4) 84 (11.5) 36 (4.9) 25 (3.4) 20 (2.7)
316 (55.1) 135 (23.5) 50 (8.7) 27 (4.7) 46 (8.0)
513 (79.7) 65 (10.1) 30 (4.7) 20 (3.1) 16 (2.5)
42 (62.7) 13 (19.4) 5 (7.5) 4 (6.0) 3 (4.5)
9 (50.0) 6 (33.3) 1 (5.6) 1 (5.6) 1 (5.6)
15 (1.2) 40 (3.1) 88 (6.8) 163 (12.5) 36 (2.8) 134 (10.3) 49 (3.8) 359 (27.6) 253 (19.4) 166 (12.7) 2.2 (1.7)
14 (1.9) 24 (3.3) 51 (7.0) 109 (15.0) 24 (3.3) 103 (14.1) 14 (1.9) 169 (23.2) 140 (19.2) 81 (11.1) 1.9 (1.6)
1 (0.2) 16 (2.8) 37 (6.4) 54 (9.4) 12 (2.1) 31 (5.4) 35 (6.1) 190 (33.1) 113 (19.7) 85 (14.8) 2.6 (1.8)
13 (2.0) 14 (2.2) 46 (7.1) 105 (16.3) 11 (1.7) 86 (13.4) 14 (2.2) 148 (23.0) 134 (20.8) 73 (11.3) 1.8 (1.5)
1 (1.5) 5 (7.5) 4 (6.0) 4 (6.0) 9 (13.4) 13 (19.4) 0 (0.0) 19 (28.4) 5 (7.5) 7 (10.4) 2.2 (1.6)
0 (0.0) 5 (27.8) 1 (5.6) 0 (0.0) 4 (22.2) 4 (22.2) 0 (0.0) 2 (11.1) 1 (5.6) 1 (5.6) 4.2 (1.3)
282 (22.1) 313 (24.6) 73 (5.7) 260 (20.4) 193 (15.1) 153 (12.0)
175 (24.1) 210 (28.9) 47 (6.5) 164 (22.6) 91 (12.5) 39 (5.4)
107 (19.5) 103 (18.8) 26 (4.7) 96 (17.5) 102 (18.6) 114 (20.8)
164 (25.5) 191 (29.7) 39 (6.1) 150 (23.3) 76 (11.8) 23 (3.6)
11 (16.9) 17 (26.2) 8 (12.3) 13 (20.0) 11 (16.9) 5 (7.7)
0 (0)
29 (2.2)
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Age, mean (SD) Female, N (%) Obvious cause of arrest, N (%)a Public location, N (%) Witness status, N (%) EMS witnessed arrest Bystander witnessed arrest Bystander CPR, N (%) Dispatch to first EMS arrival (min), mean (SD) Dispatch to first ALS arrival (min), mean (SD) Treated by ALS, N(%) First known rhythm, N(%) VT/VF/shockable PEA Asystole AED no shock advised, no strip Cannot determine/unknown Site, N (%) A B C D E F G H I J Modified Rankin scale at discharge, mean (SD) Modified Rankin scale category, N (%) 0 1 2 3 4 5
Missing data, n (%)
0 (0.0) 2 (11.1) 0 (0.0) 1 (5.6) 4 (22.2) 11 (61.1)
Included but not limited to drug or chemical poisoning and mechanical suffocation (foreign body or hanging.)
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Table 2 Unadjusted post-discharge outcomes.
Alive, n (%) MRS Mean (SD) Prop. ≤3 (%) ALFI-MMSE Mean (SD) Prop. ≥17 (%) HUI Mark 3 Mean (SD) Prop. ≥0.7 (%) T-GDS Mean (SD) Prop. ≤10 (%)
1 month N = 684
3 months N = 664
6 months N = 591
Worst score N = 689
Best score N = 689
Last available score N = 689
676 (98.8)
643 (96.8)
559 (94.6)
657 (95.4)
676 (98.1)
657 (95.4)
1.8 (1.7) 459/550 (83.5)
1.8 (1.8) 463/564 (82.1)
2.1 (1.8) 504/636 (79.2)
1.5 (1.7) 546/636 (85.8)
1.7 (1.8) 526/636 (82.7)
19.1 (4.7) 443/509 (87.0)
18.7 (5.7) 449/527 (85.2)
17.5 (5.6) 489/637 (76.8)
19.2 (5.2) 552/637 (86.7)
18.4 (5.7) 527/627 (82.7)
0.75 (0.33) 295/409 (72.1)
0.74 (0.35) 307/429 (71.6)
0.71 (0.35) 370/549 (67.4)
0.77 (0.33) 414/549 (75.4)
0.74 (0.34) 393/549 (71.6)
3.0 (4.0) 463/505 (91.7)
3.2 (4.3) 469/521 (90.0)
3.7 (4.3) 523/587 (89.1)
2.7 (4.1) 537/587 (91.5)
3.2 (4.3) 529/587 (90.1)
18.6 (5.0) 376/452 (83.2)
Post-discharge outcomes were not significantly different between Analyze Early vs. Analyze Later strategies or active vs. sham ITD after adjustment for other factors (Table 3).
3.3. Independent predictors of post-discharge outcomes Post-discharge outcomes were associated with some baseline characteristics as well as EMS process factors (Table 4). Patients who arrested in a public location had significantly better cognition (difference in ALFI-MMSE score, mean (95% confidence interval) 0.76 (0.01, 1.50) as well as HRQL after discharge (difference in HUI3 score, mean (95% confidence interval) 0.07 (0.02, 0.13) and less depression (difference in T-GDS, −0.67 (−1.30, −1.004) as compared to private location. Those who received bystander CPR had better cognitive function after discharge (difference in ALFI-MMSE, 1.02 (0.21, 1.84) and less depression (difference in T-GDS, −0.81 (−1.52, −0.10) as compared to those who did not receive bystander CPR. An initial shockable rhythm was associated with better post-discharge neurologic status, cognitive function, HRQL and depression (difference in MRS, ALFI-MMSE, HUI3 and TGDS scores compared to non-shockable rhythms of −0.72 (−1.10, −0.34), 2.39 (1.09, 3.68), 0.13 (0.05, 0.20), −1.39 (−2.42, −0.37) respectively). After addition of post-discharge outcomes to the models, all of these associations with baseline characteristics and EMS process variables were no longer significant. MRS at discharge was independently associated with post-discharge neurologic status, cognition, HRQL and depression (difference in MRS score of 0.41 (0.32, 0.50), −1.30 (−1.64, −0.96), −0.07 (−0.09, −0.05), 0.67 (0.41, 0.93) for post-discharge MRS, ALFI-MMSE, HUI3, and T-GDS
Table 3 Adjusted group comparisons of post-discharge outcomes. Outcome
Active vs. sham ITD difference N = 460 Difference (95% CI)
Analyze late vs. early difference N = 605 Difference (95% CI)
Alive, % MRS MRS ≤ 3, % ALFI-MMSE ALFI-MMSE≥17, % HUI3 HUI3 ≥0.7, % T-GDS T-GDS ≤10, %
−1.7 (−5.2, 1.9) 0.14 (−0.17, 0.44) −0.76 (−5.36, 3.85) −0.66 (−1.61, 0.28) −6.06 (−12.22, 0.10) −0.02 (−0.08, 0.05) −1.15 (−9.95, 7.64) −0.11 (−0.92, 0.71) −1.08 (−6.80, 4.63)
0.72 (−2.31, 3.74) 0.07 (−0.20, 0.34) 0.31 (−3.17, 3.78) 0.06 (−0.71, 0.83) −1.25 (−7.21, 4.70) 0.00 (−0.06, 0.05) 0.49 (−7.66, 8.63) −0.46 (−1.06, 0.15) 0.75 (−3.94, 5.44)
Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, and site location
respectively). Some site differences remained after adjustment for baseline characteristics as well as MRS at discharge. Greater post-discharge HRQL was significantly associated with less neurologic impairment, cognitive impairment or depression after adjustment for baseline characteristics and EMS process (difference in post-discharge HUI3 score of −0.06 (−0.08, −0.04), −0.05 (−0.06, −0.04) for post-discharge MRS and T-GDS respectively). 3.4. Assessment of non-participation and missing data Post-discharge follow-up was significantly associated with some baseline characteristics and EMS process as well as site (see online Appendix Table 1). Accounting for missing data by using multiple imputation or inverse-probability weighting changed the assessment of neurologic status, cognitive impairment, and HRQL in the direction of worse outcomes for each measure. However, associations with baseline characteristics and comparisons of outcomes by treatment group with accounting for missing data generally changed the results quantitatively but not qualitatively (see online Appendix Tables 2 and 3). 4. Comment Most patients who were resuscitated from OHCA, survived to discharge and completed at least one assessment in this prospective sub-study of a large trial had satisfactory neurologic function, no cognitive impairment, and no depression. Most did not have severe impairment of HRQL. Ratings were relatively robust to whether and how the analysis accounted for missing data. Also ratings were robust to adjustment for differences in most but not all baseline characteristics or EMS process variables. Experts recommend post-discharge assessments of neurologic function as the primary measure of the effectiveness of resuscitation interventions.1 But such post-discharge assessments are logistically difficult and prolong study duration compared to assessment of outcomes prior to discharge from hospital, so potentially delay adoption of effective resuscitation interventions. Importantly, they are also subject to selection bias as demonstrated by the present study as well as prior work.18 As the majority of survivors who were interviewed in this study were not impaired, such efforts may not be warranted so that effective resuscitation interventions can be identified quickly, then disseminated into common practice. Prior studies of cognition and HRQL after OHCA provide conflicting evidence of the degree of impairment in this population, due in part to their differences in baseline and treatment characteristics, small sample size as well as use of multiple different measures at multiple different time points.2,19–28 Importantly,
Table 4 Independent predictors of post-discharge outcomes. Prediction using pre-hospital and post-discharge variablesb , point estimate (95% confidence intervals)
Predictor variables
MRS
ALFI-MMSE
HUI3
T-GDS
MRS
ALFI-MMSE
HUI3
T-GDS
Baseline variables Age, years
0.008 (−.001, 0.02)
−0.048 (−0.08, −0.02)
−0.008 (−0.034, 0.017)
−0.001 (−0.008, 0.005)
−0.03 (−0.87, 0.82) 3.09 (−0.91, 7.08)
−0.04 (−0.24, 0.16) −0.49 (−1.52, 0.53)
−0.046 (−0.068, −0.024) −0.74 (−1.49, −0.002) 0.50 (−3.36, 4.37)
−0.001 (−0.002, −0.0002) −0.01 (−0.05, 0.03) −0.08 (−0.32, 0.16)
−0.02 (−0.04, −0.01)
−0.73 (−1.72, 0.26) −1.26 (−4.36, 1.84)
−0.001 (−0.003, 0.0004) −0.01 (−0.08, 0.06) −0.29 (−0.63, 0.06)
−0.22 (−0.69, 0.26) 1.45 (−0.76, 3.66)
0.76 (0.01, 1.50)
0.07 (0.02, 0.13)
−0.67 (−1.30, −0.04)
0.16 (−0.02, 0.34)
0.36 (−0.22, 0.94)
0.04 (−0.0003, 0.07)
−0.04 (−0.44, 0.35)
−0.79 (−2.87, 1.29)
0.004 (−0.12, 0.13)
0.62 (−1.02, 2.25)
−0.10 (−0.50, 0.30)
0.24 (−1.28, 1.76)
0.036 (−0.04, 0.12)
0.76 (−0.15, 1.68)
−0.66 (−1.71, 0.39)
0.03 (−0.05, 0.10)
−0.05 (−0.95, 0.85)
0.001 (−0.20, 0.20)
−0.61 (−1.40, 0.18)
0.008 (−0.04, 0.05)
−0.16 (−0.66, 0.33)
1.02 (0.21, 1.84) −0.086 (−0.30, 0.13)
0.05 (−0.005, 0.11) −0.004 (−0.02, 0.01)
−0.81 (−1.52, −0.10) 0.012 (−0.159, 0.183)
−0.03 (−0.21, 0.15) −0.02 (−0.06, 0.01)
0.28 (−0.34, 0.89) −0.11 (−0.27, 0.04)
0.002 (−0.04, 0.04) −0.004 (−0.01, 0.003)
−0.13 (−0.57, 0.30) −0.02 (−0.10, 0.06)
−0.12 (−2.16, 1.93) 2.39 (1.09, 3.68)
−0.004 (−0.16, 0.15) 0.13 (0.05, 0.21)
0.15 (−1.48, 1.78) −1.39 (−2.42, −0.37)
−0.21 (−0.68, 0.27) −0.05 (−0.28, 0.18)
−0.11 (−1.99, 1.77) 0.39 (−0.51, 1.28)
−0.01 (−0.12, 0.10) 0.03 (−0.02, 0.07)
0.18 (−1.18, 1.53) −0.01 (−0.53, 0.52)
−1.30 (−1.64, −0.96)
−0.07 (−0.09, −0.05)
0.67 (0.41, 0.93)
0.08 (0.02, 0.15)
−0.39 (−0.64, −0.14)
−0.01 (−0.03, −0.001)
−0.13 (−0.27, 0.02)
−1.08 (−3.95, 1.79) −5.37 (−9.06, −1.69) 0.01 (−2.07, 2.08) −0.88 (−2.03, 0.27) −4.08 (−8.46, 0.30) −0.36 (−1.66, 0.94) 1.99 (0.55, 3.43) Reference −0.31 (−1.35, 0.72) −0.30 (−1.62, 1.03)
−0.23 (−0.41, −0.04) −0.11 (−0.27, 0.04) 0.05 (−0.07, 0.17) −0.02 (−0.1, 0.06) −0.31 (−0.50, −0.11) −0.09 (−0.18, 0.01) −0.09 (−0.30, 0.12) Reference 0.01 (−0.07, 0.08) 0.01 (−0.09, 0.11)
0.34 (−2.22, 2.91) 3.35 (0.16, 6.54) −1.35 (−2.88, 0.19) 1.24 (0.15, 2.33) 5.69 (2.85, 8.53) 0.96 (−0.08, 2.00) 1.15 (−1.36, 3.67) Reference 0.46 (−0.46, 1.37) −0.15 (−1.28, 0.99)
−0.01 (−0.64, 0.62) −0.10 (−0.48, 0.28) −0.15 (−0.47, 0.17) −0.20 (−0.49, 0.10) −0.50 (−1.06, 0.07) 0.39 (0.09, 0.68) 0.13 (−0.51, 0.78) Reference 0.31 (0.03, 0.58) −0.42 (−0.69, −0.14)
−0.56 (−2.96, 1.83) −3.76 (−5.89, −1.63) −0.14 (−1.39, 1.11) −0.20 (−1.21, 0.82) −1.19 (−4.46, 2.08) 0.33 (−0.71, 1.37) 2.36 (0.34, 4.38) Reference 0.63 (−0.17, 1.43) −0.86 (−1.84, 0.11)
−0.10 (−0.23, 0.03) 0.01 (−0.05, 0.07) −0.02 (−0.09, 0.05) 0.04 (−0.01, 0.1) −0.01 (−0.12, 0.11) 0.001 (−0.06, 0.06) −0.06 (−0.17, 0.06) Reference 0.06 (0.01, 0.11) −0.03 (−0.09, 0.03)
−0.82 (−2.28, 0.64) 0.01 (−0.81, 0.84) −0.32 (−1.07, 0.43) 0.91 (0.19, 1.62) 2.03 (0.50, 3.56) −0.12 (−0.73, 0.49) 0.22 (−0.98, 1.41) Reference 0.34 (−0.17, 0.84) 0.04 (−0.53, 0.61)
−1.16 (−1.61, −0.71)
−0.06 (−0.08, −0.04) −0.01 (−0.01, 0.0003)
0.59 (0.36, 0.93) −0.22 (−0.29, −0.15) −6.01 (−7.26, −4.75)
Female, % 0.11 (−0.20, 0.43) Obvious cause of 0.28 (−0.94, 1.50) arrest, % Public location, % −0.21 (−0.45, 0.04) Witness status, % EMS witnessed −0.06 (−0.66, 0.54) arrest Bystander −0.02 (−0.35, 0.31) witnessed arrest Bystander CPR, % −0.18 (−0.45, 0.09) Dispatch to First 0.001 (−0.06, 0.06) EMS arrival, per min Treated by ALS, % −0.01 (−0.63, 0.61) −0.72 (−1.10, −0.34) First known shockable rhythm, % Modified Rankin 0.41 (0.32, 0.50) scale at discharge Site 0.72 (−0.21, 1.64) A B 0.95 (0.15, 1.75) C −0.41 (−1.01, 0.19) D 0.11 (−0.28, 0.50) 1.02 (−0.07, 2.11) E F 0.63 (0.21, 1.05) G 0.19 (−0.75, 1.12) Reference H I 0.44 (0.09, 0.80) J −0.43 (−0.90, 0.04) Post-discharge variables MRS ALFI-MMSE HUI3 T-GDS
−0.09 (−0.12, −0.06) −1.65 (−2.15, −1.15) 0.12 (0.07, 0.16)
−1.88 (−3.94, 0.17) −0.56 (−0.76, −0.36)
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Prediction using baseline characteristics and EMS process variablesa , point estimate (95% confidence intervals)
−0.05 (−0.06, −0.04)
a
Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, and site location. b Adjusted for age, gender, obvious cause of arrest, public location, EMS witnessed arrest, bystander witnessed arrest bystander CPR, dispatch to first EMS arrival, treatment by ALS, first known shockable rhythm, discharge MRS, site location and post-discharge outcomes.
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resuscitation interventions associated with good survival are also associated with good HRQL.29–31 Thus the results of this large prospective cohort study are consistent with prior assessments of functional outcomes after cardiac arrest. Our observation that the presence of a shockable first recorded rhythm after the onset of cardiac arrest was a strong predictor of post-discharge outcome is consistent with prior evidence that demonstrated that the presence of a shockable rhythm is a strong correlate of the likelihood of survival to discharge.32 Provision of bystander CPR was associated with better cognition after discharge. Although rhythm is not modifiable, the likelihood of bystander CPR being performed could be modified by implementing dispatcher instructions in CPR,33,34 or by increased training of laypersons in recognition and response to cardiac arrest.35,36 Thus communitybased interventions could improve the cognition, depression status and HRQL of survivors after cardiac arrest. Our observation of differences in post-discharge outcome by site is new and warrants cautious interpretation. Self-reported HRQL varies by geography and culture.37 Baseline differences in HRQL among subjects in the present study were not assessed because such retrospective assessments are of unknown reliability or validity in this population. A difference of 0.03 on a scale of 0–1 was previously defined as the minimum clinically important difference in a generic HRQL score such as HUI3.14,38 Others suggested that a difference of 0.1 on a HRQL scale of 0–1 was probably clinically important.39 We observed such differences between sites after conditioning on survival to discharge (since only patients who consented to participate in the study were assessed after discharge), and after adjusting for baseline and EMS covariates. These differences were consistent with trends in other post-discharge outcomes across sites. But there were differences in the proportion of patients followed up across sites. If these inter-site differences in HRQL are true, some of them appear to be large enough to be clinically important. These differences warrant further exploration in a future study. Some argue that attempts to resuscitate patients after OHCA may not be appropriate because both survival and quality of life are poor.40 If outcomes after cardiac arrest are indeed poor, then treatments for this disorder may not be economically attractive.41 Conversely, if the quality of life of survivors is good, then even a small improvement in survival would be important to patients and policymakers. Our observation that a minority of patients who survive to discharge are severely impaired reemphasizes the need for ongoing efforts to improve survival after cardiac arrest. Limitations of this study included the rate of non-consent among survivors. The association between consent for participation and site as well as other factors suggests that participation in this sub-study was not random. Importantly neurologic function at discharge differed significantly between those who were and were not followed. Imputation and inverse-probability weighting were used to adjust for these data which were not missing at random but associated with predictors of poorer functional outcome. Use of imputation changed the results in the direction of worse outcomes for each measure. However, associations and treatment group comparisons were generally not sensitive to whether or how missing data was accounted for among consenting survivors. Despite the rate of non-consent among survivors, this is the largest study reported to date of post-discharge outcomes in patients resuscitated from cardiac arrest. The proportion of survivors interviewed after discharge was similar to or better than prior studies in this population.4,31,42 Another limitation is that hospital care and post-resuscitation prognosis assessment and withdrawal of care were not standardized. Combinations of hospital-based treatments improved outcomes in patients resuscitated from cardiac arrest compared with historical controls.43–48 Collectively, these studies
demonstrate that hospital-based care of those resuscitated from OHCA is associated with patient outcomes and potentially modifies the effect of interventions for cardiac arrest. Outcomes were assessed by telephone rather than face-toface interview. Each of these measures was previously used to detect impairment. ALFI-MMSE correlates strongly with face-toface MMSE across all patients or when grouped by clinical dementia rating scale class.10 The HUI3 was used in several studies of interventions for individuals resuscitated from cardiac arrest2,31 and is reliable and valid in other populations.49–51 Although the T-GDS was initially designed for use in older adults, it is also valid in younger adults.52 Thus, each of the measures we used to assess impairment after discharge has acceptable performance characteristics for telephone administration, as used in this study. Strengths of this study include that multiple measures were used to describe multiple dimensions of functional status and HRQL in a large cohort of survivors of OHCA. Prior to the design of the ROC PRIMED trial, MRS was used to assess survivors of cardiac arrest in a cohort of neurosurgical patients with in-hospital cardiac arrest53 and a cohort of survivors of OHCA.42 MRS has concurrent validity with other measures of neurological recovery after stroke and brain injury.54,55 Use of a structured interview in a recent study of stroke patients improved the measure’s reliability.9 The present study demonstrated that MRS prior to discharge is strongly correlated with multiple post-discharge outcomes, which reinforces the former as being a valid measure of resuscitation success. Importantly these performance characteristics are such that we believe it is unlikely that we failed to detect significant impairment present in this population.
5. Conclusion The majority of patients in this large cohort who survived cardiac arrest and were interviewed had satisfactory neurologic function, no cognitive impairment, no or mild impairment in health and no depression. Concerns about the likelihood of poor quality of life after resuscitation are not a valid reason to abandon efforts to improve a health care system’s response to victims of cardiac arrest.
Conflict of interest statement Dr. Nichol receives salary support from the University of Washington via the Leonard A. Cobb Medic One Foundation Endowed Chair in Prehospital Emergency Care. He holds Research Grants from the following: (1) National Heart Lung Blood Institute, Bethesda, MD. Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004–2015; Co-PI; (2) Food and Drug Administration, Silver Spring, MD; Cardiac Science Corp, Waukesha, WI; Heartsine Technologies Inc., Newtown, PA; Philips Healthcare Inc., Bothell, WA; Physio-Control Inc., Redmond, WA; ZOLL Inc., Chelmsford, MA. University of Washington Dynamic AED Registry, PI. 2013–2015; (3) Velomedix Inc., Menlo Park, CA. Velocity Pilot Study of Ultrafast Hypothermia in Patients with ST-Elevation Myocardial Infarction, National Co-PI. 2014–2015. *Waived personal compensation. He did not receive any other Research Support. He is not a member of Speakers Bureau and does not hold an Honorary post in any company. He received travel reimbursement from Abiomed Inc., Danvers, MA in 2015. He has no other conflict of interest to declare. Dr. Cheskes has received speaking honorarium from Zoll Medical and Physio-Control Inc. He has received grant funding as Co-PI, Toronto site, Resuscitation Outcomes Consortium. The other authors disclosed no conflict of interest.
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