Peditric Criticl Cre Incidence nd Outcomes of Crdiopulmonry Resuscittion in PICUs Robert A. Berg, MD, FCCM, FAHA, FAAP 1 ; Viny M. Ndkrni, MD, FCCM, FAHA, FAAP 1 ; Amy E. Clrk, MS 2 ; Frnk Moler, MD 3 ; Kthleen Meert, MD 4 ; Rick E. Hrrison, MD, FCCM 5 ; Christopher J. L. Newth, MD, FRCPC 6 ; Robert M. Sutton, MD, FCCM 1 ; Dvid L. Wessel, MD 7 ; John T. Berger, MD 7 ; Joseph Crcillo, MD, FCCM 8 ; Heidi Dlton, MD, FCCM 9 ; Sbrin Heidemnn, MD 4 ; Thoms P. Shnley, MD 3 ; Athen F. Zupp, MD, MSCE 1 ; Alln Doctor, MD, FCCM 10 ; Robert F. Tmburro, MD 11 ; Tmmr L. Jenkins, MSN, RN 11 ; J. Michel Den, MD, FCCM, FAAP 2 ; Richrd Holubkov, PhD 2 ; Murry M. Pollck, MD, FCCM 12 ; for the Eunice Kennedy Shriver Ntionl Institute of Child Helth nd Humn Development Collbortive Peditric Criticl Cre Reserch Network 1 Deprtment of Anesthesiology nd Criticl Cre, the Children s Hospitl of Phildelphi nd University of Pennsylvni Perelmn School of Medicine, Phildelphi, PA. 2 Deprtment of Peditrics, University of Uth School of Medicine, Slt Lke City, UT. 3 Deprtment of Peditrics, University of Michign, Ann Arbor, MI. 4 Deprtment of Peditrics, Children s Hospitl of Michign, Detroit, MI. 5 Deprtment of Peditrics, University of Cliforni t Los Angeles, Los Angeles, CA. 6 Deprtment of Anesthesiology nd Criticl Cre Medicine, Children s Hospitl Los Angeles, Los Angeles, CA. 7 Deprtment of Peditrics, Children s Ntionl Medicl Center, Wshington DC. 8 Deprtment of Criticl Cre Medicine, Children s Hospitl of Pittsburgh, Pittsburgh, PA. 9 Deprtment of Child Helth, Phoenix Children s Hospitl nd University of Arizon College of Medicine-Phoenix, Phoenix, AZ. 10 Deprtments of Peditrics nd Biochemistry, Wshington University School of Medicine, St. Louis, MO. 11 Brnch of Trum nd Criticl Illness of the Eunice Kennedy Shriver Ntionl Institutes of Child Helth nd Humn Development, the Ntionl Institutes of Helth, Bethesd, MD. 12 Deprtment of Peditrics, Children s Ntionl Medicl Center, George Wshington University School of Medicine, Wshington DC. This work ws performed t the Children s Hospitl of Phildelphi, University of Michign, Children s Hospitl of Michign, University of Cliforni, Los Angeles, Children s Hospitl Los Angeles, Children s Ntionl Medicl Center, Children s Hospitl of Pittsburgh, nd Phoenix Children s Hospitl. Supported, in prt, by coopertive greements from the Deprtment of Helth nd Humn Services, Eunice Kennedy Shriver Ntionl Institute of Child Helth nd Humn Development (NICHD), Ntionl Institutes of Helth (NIH): U10HD050096, U10HD049981, U10HD049983, U10HD050012, U10HD063108, U10HD063106, U10HD063114, nd U01HD049934. The content is solely the responsibility of the uthors nd does not necessrily represent the officil views of the NIH. Copyright 2016 by the Society of Criticl Cre Medicine nd Wolters Kluwer Helth, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000001484 Dr. Berg received support for this rticle reserch from the NIH. His institution received funding from NICHD nd support from coopertive greements from the Deprtment of Helth nd Humn Services, Eunice Kennedy Shriver NICHD, NIH (U10HD050096, U10HD049981, U10HD049983, U10HD050012, U10HD063108, U10HD063106, U10HD063114, nd U01HD049934). Drs. Clrk nd Moler received support for this rticle reserch from the NIH. Their institutions received funding from the NIH (NICHD). Drs. Meert, Hrrison, nd Newth received support for this rticle reserch from the NIH. Their institution received funding from the NIH. Dr. Sutton received support for this rticle reserch from the NIH nd received funding from the Zoll Medicl Corportion. His institution received funding from the NICHD. Dr. Wessel received support for this rticle reserch from the NIH. His institution received funding from the NIH. Dr. Berger received support for this rticle reserch from the NIH. His institution received funding from the NIH nd the Assocition for Peditric Pulmonry Hypertension. Dr. Crcillo received support for this rticle reserch from the NIH. His institution received grnt support from the NICHD. Dr. Dlton consulted for Innovtive ECMO concepts, is employed by the Alskn Ntive Tribl Helth Center, lectured for Mquet Inc, received roylties from the Society of Criticl Cre Medicine (Rogers Text of Peditric Criticl Cre), nd received support for this rticle reserch from the NIH. Her institution received grnt support from the NIH. Dr. Heidemnn received support for this rticle reserch from the NIH. Her institution received funding (Dr. Heidemnn s slry is prtilly supported through the Collbortive Peditric Criticl Cre Network grnt sponsored by the NIH). Dr. Shnley received funding from the University of Minnesot, Cse Western Reserve University, nd Springer Publishers. He received support for this rticle reserch from the NIH. His institution received funding from the NIH. Dr. Zupp received support for this rticle reserch from the NIH. Her institution received funding from the NICHD nd the NIH. Dr. Doctor received support for this rticle reserch from the NIH. His institution received funding from the NIH nd the Children s Discovery Institute. Dr. Tmburro received support for this rticle reserch from the NIH, disclosed government work, nd disclosed other support (he hs two potentil finncil conflicts, neither of which seems relevnt to this mnuscript submission. First, his institution received grnt from the U.S. Food nd Drug Administrtion Office of Orphn Product Development to study the use of exogenous surfctnt in children with cute lung injury who hd undergone stem cell trnsplnt or hd leukemi/ lymphom. ONY supplied the mediction for the tril. Also, he ws n ssocite editor on textbook nd study guide nd received roylties from Springer Publishers). Dr. Jenkins disclosed government work (she is federl employee. The work ws completed s prt of officil duties t the NIH. The NIH funded the work through coopertive greement). 798 www.ccmjournl.org April 2016 Volume 44 Number 4
Peditric Criticl Cre Dr. Den received support for this rticle reserch from the NIH. His institution received funding from the NICHD. Dr. Holubkov received funding from St. Jude Medicl, Inc (Biosttisticl Consulting reltionship terminted s of My 1, 2015), Pfizer Inc (Dt nd Sfety Monitoring Bord [DSMB] membership), nd Physicins Committee for Responsible Medicine (Biosttisticl Consulting). He disclosed other support (he is DSMB member for the Ntionl Burn Assocition nd for Fibrocell, Inc), nd he received support for this rticle reserch from the NIH. His institution received funding from the NIH/NICHD. Dr. Pollck disclosed other support (occsionl honorri nd occsionl consultncy) nd received support for this rticle reserch from the NIH. His institution received funding from the NIH/NICHD under U wrd. Dr. Ndkrni hs disclosed tht he does not hve ny potentil conflicts of interest. For informtion regrding this rticle, E-mil: bergr@emil.chop.edu Objectives: To determine the incidence of crdiopulmonry resuscittion in PICUs nd subsequent outcomes. Design, Setting, nd Ptients: Multicenter prospective observtionl study of children younger thn 18 yers old rndomly selected nd intensively followed from PICU dmission to hospitl dischrge in the Collbortive Peditric Criticl Cre Reserch Network December 2011 to April 2013. Results: Among 10,078 children enrolled, 139 (1.4%) received crdiopulmonry resuscittion for more thn or equl to 1 minute nd/or defibrilltion. Of these children, 78% ttined return of circultion, 45% survived to hospitl dischrge, nd 89% of survivors hd fvorble neurologic outcomes. The reltive incidence of crdiopulmonry resuscittion events ws higher for crdic ptients compred with non-crdic ptients (3.4% vs 0.8%, p <0.001), but survivl rte to hospitl dischrge with fvorble neurologic outcome ws not sttisticlly different (41% vs 39%, respectively). Shorter durtion of crdiopulmonry resuscittion ws ssocited with higher survivl rtes: 66% (29/44) survived to hospitl dischrge fter 1-3 minutes of crdiopulmonry resuscittion versus 28% (9/32) fter more thn 30 minutes (p < 0.001). Among survivors, 90% (26/29) hd fvorble neurologic outcome fter 1-3 minutes versus 89% (8/9) fter more thn 30 minutes of crdiopulmonry resuscittion. Conclusions: These dt estblish tht contemporry PICU crdiopulmonry resuscittion, including long durtions of crdiopulmonry resuscittion, results in high rtes of survivl-to-hospitl dischrge (45%) nd fvorble neurologic outcomes mong survivors (89%). Rtes of survivl with fvorble neurologic outcomes were similr mong crdic nd noncrdic ptients. The rigorous prospective, observtionl study design voided the limittions of missing dt nd potentil selection bises inherent in registry nd dministrtive dt. (Crit Cre Med 2016; 44:798 808) Key Words: crdic rrest; crdiopulmonry resuscittion; children; incidence; intensive cre; survivl Bsed on registry nd dministrtive dt, more thn 6,000 children in the United Sttes receive in-hospitl crdiopulmonry resuscittion (CPR) ech yer, mostly in PICUs (1, 2). In prospective study from the erly 1990s, CPR ws provided for 1.8% of 11,165 dmissions t 32 North Americn multidisciplinry PICUs, nd 13.7% survived to hospitl dischrge (3). More recent dt from three single-center peditric crdic ICU studies demonstrte crdic rrests in 3 6% of children dmitted, suggesting higher incidence in this popultion (4 6). Although there hve been mny chnges in criticl cre nd incresed focus on CPR qulity since the 1990s, the current incidence nd outcome from CPR in PICUs re not known. Published outcomes from CPR in PICUs vry (7). Although the survivl rte following PICU CPR ws 13.7% in the 1990s (3), more recent PICU CPR dt from the Get With The Guidelines-Resuscittion (GWTG-R) in-hospitl crdic rrest registry of the Americn Hert Assocition found tht 22% of children survived to hospitl dischrge (8). In contrst, single-center peditric crdic ICU study in n overlpping time period reported survivl rte of 46%, suggesting tht post-cpr outcomes my be better mong children with crdic disese (4). Similrly, GWTG-R registry dt suggest tht crdic rrest outcomes re superior mong the children post crdic surgery compred with others (9). Much of the published PICU CPR outcome dt re bsed on registry or dministrtive dtbses, which re limited by chllenges of missing neurologic outcome dt nd potentil ptient enrolment scertinment bis. The Eunice Shriver Kennedy Ntionl Institute of Child Helth nd Humn Development s Collbortive Peditric Criticl Cre Reserch Network (CPCCRN) embrked on n intensive prospective study of more thn 10,000 dmissions to its lrge cdemic PICUs with the primry im to investigte the reltionship of physiologic instbility with the development of morbidity nd mortlity (10). As prt of this effort, we prospectively evluted the incidence nd outcomes of PICU CPR events to ccurtely determine the current overll incidence of CPR occurring in the PICU, the chrcteristics of children who received CPR in the PICU, their survivl rtes, nd the neurologic nd functionl outcomes of the survivors. We lso sought to determine whether incidences nd outcomes vry between crdic nd noncrdic criticlly ill children. We hypothesized tht CPR events would be more common mong children with medicl or surgicl crdic disese thn those with medicl or surgicl noncrdic disese nd tht outcomes would be better for those crdic ptients. METHODS The current investigtion ws performed t the seven sites prticipting in the CPCCRN during the study period. These sites combined hve pproximtely 17,000 PICU dmissions per yer. The detils of ptient selection nd dt collection hve been previously published (10, 11). Ptients rnging in ges from newborn to younger thn 18 yers were rndomly selected from both the generl/medicl PICUs nd the crdic/crdiovsculr PICUs. There were no seprte generl surgicl or neurologicl PICUs. Only the first PICU dmission ws included, nd ptients were excluded if their vitl signs were incomptible with life for t lest the first 2 hours fter PICU dmission (i.e., moribund ptients). Ptients were enrolled from December 4, 2011, to April 7, 2013. The protocol ws pproved by the Institutionl Review Bords t ll prticipting institutions. Criticl Cre Medicine www.ccmjournl.org 799
Berg et l A CPR event ws defined s chest compressions for t lest 1 minute nd/or defibrilltion. The resons for initition of chest compressions were ctegorized s pulseless crdic rrest or poor perfusion with brdycrdi nd/or hypotension, s per Americn Hert Assocition Guidelines (12). Immedite outcomes from the CPR event were ctegorized s return of spontneous circultion (ROSC) for more thn 20 minutes, return of circultion (ROC) by extrcorporel life support (ECLS), or no ROC (12, 13). Survivl-to-hospitl dischrge ws reported for the index (or first) CPR event of ech ptient becuse ptient cn only survive to dischrge once per hospitliztion (13). Dignostic, demogrphic, nd functionl sttus dt, including Peditric Cerebrl Performnce Ctegory (PCPC) nd Functionl Sttus Scle (FSS) scores, were determined t PICU dmission. The functionl sttus evlution included documenttion of preillness bseline sttus (i.e., prior to the event tht brought the child to the hospitl) nd lter determintion t PICU dischrge nd hospitl dischrge (10, 11, 13, 14). Dignoses were clssified by the system of dysfunction ccounting for the primry reson for PICU dmission. Opertive sttus included both operting room nd interventionl ctheteriztion procedures but not dignostic ctheteriztion procedures. Ptients were clssified s surgicl or medicl bsed on opertive sttus prior to the CPR event nd then further clssified into four subgroups bsed on cute dmission dignoses nd opertive type: crdic surgicl, crdic medicl, noncrdic surgicl, nd noncrdic medicl. Physiologic sttus ws ssessed with the Peditric Risk of Mortlity III score with shortened observtion time period (10). Investigtors, reserch coordintors, nd reserch ssistnts were trined in dt collection with inperson trining on multiple occsions; bi-weekly teleconference clls were lso conducted (10, 11). Functionl sttus ws ssessed by the PCPC nd FSS scores. The FSS ws developed to provide ssessment of functionl sttus suitble for lrge studies. It is composed of six domins (mentl sttus, sensory, communiction, motor function, feeding, nd respirtory) with domin scores rnging from 1 (norml) to 5 (very severe dysfunction). Therefore, totl scores my rnge from 6 to 30 with lower scores indicting better function. The opertionl definitions nd mnul for the clssifictions hve been published (14). The FSS vlidtion consisted of comprison with the Adptive Behviorl Assessment Scle II, vlidted mesure of peditric dptive behvior, nd comprison with the PCPC (10, 14, 15). A PCPC score of 1 describes children with norml ge-pproprite neurodevelopmentl functioning, 2 for mild cerebrl disbility, 3 for moderte disbility, 4 for severe disbility, 5 for com/vegettive stte, nd 6 for brin deth. As previously reported, fvorble neurologic outcome ws defined s PCPC score of 1 3 t dischrge or no increse compred with dmission PCPC sttus (1, 8, 9, 16, 17). In ddition, we ctegorized FSS scores of 6 7 s good, 8 9 s mildly bnorml, 10 15 s modertely bnorml, 16 21 s severely bnorml, nd more thn 21 s very severely bnorml (10, 11, 14). These ctegory rnges were chosen bsed on the dysfunction reflected in the score. This ctegoriztion ws designed such tht the equivlent FSS groups would pproximtely correspond to the PCPC ctegories (9, 13, 14). Newborns who hd never chieved stble bseline function were ssigned n FSS score of 6; this ws opertionlized by ssigning bseline FSS score of 6 to ll dmissions for infnts 0 2 dys old nd to trnsfers from nother fcility for infnts 3 6 dys old (10, 15). As previously reported, new morbidity ws defined s n increse in the FSS totl score t lest 3 (10). The primry study outcomes were the rte of CPR events nd survivl-to-hospitl dischrge with fvorble neurologic outcomes. Secondry outcomes included ROC for more thn 20 minutes, 24-hour survivl, survivl-to-hospitl dischrge, nd survivl without new morbidities. All descriptive nd inferentil nlyses re bsed on the index (i.e., first) qulifying CPR event. Ctegoricl dt re expressed s counts nd percentges or rte per 100 dmissions. Continuous dt re expressed s medin nd interqurtile rnge (IQR, 25th nd 75th percentiles). Associtions of ptient nd event chrcteristics with ptient type were ssessed using the Person chi-squre or the Fisher exct test for ctegoricl vribles nd the Wilcoxon signed rnk test for continuous vribles. Observed ssocitions between durtion of compressions nd outcome were evluted using the Cochrn-Armitge trend test. Univrible ssocitions of other key ptient nd event chrcteristics with outcome were evluted using modified Poisson regression, method tht implements generlized estimting equtions to fcilitte direct estimtion of rte rtios with robust vrince estimtes (18). Differences between crdic nd noncrdic subgroups were further evluted in multivrible model. This model djusted for ptient ge nd whether compressions were strted for poor perfusion or pulselessness, fctors determined priori to be potentil covrites. In ddition, ny vribles with p vlue less thn 0.15 in univrible nlyses were included in the finl model. Reltive risks nd ssocited 95% CIs re reported. Anlyses were performed using SAS version 9.4 (SAS Institute, Cry, NC). RESULTS Enrolment t ech of the seven CPCCRN sites vried from 1,252 (12%) to 1,617 (16%) of the 10,078 dmissions in the overll study. The PICU mortlity rte for these 10,078 dmissions ws 2.3% (227 PICU deths), nd overll hospitl mortlity rte ws 2.7% (275 hospitl deths). A totl of 139 (1.4%) received CPR for t lest 1 minute nd/or defibrilltion within the initil PICU dmission (Fig. 1). Only four hd defibrilltion without chest compressions. Twenty-eight (20%) of these children received CPR on multiple occsions for totl of 182 CPR events (1.8 CPR events per 100 dmissions). Demogrphic nd event dt re displyed in Tbles 1 nd 2. The seven CPC- CRN sites ech contributed nywhere from 8 (6%) to 30 (22%) of the 139 children with CPR events. The incidence of index CPR events (i.e., the number of index CPR events per 100 ICU dmissions) rnged cross sites from 0.6 to 2.3 per 100 dmissions (p < 0.001). Among the 139 children with CPR event, 31 (22%) filed to ttin ROC during the initil CPR event, 91 (65%) ttined ROSC for more thn 20 minutes, nd 17 (12%) ttined ROC vi ECLS instituted during CPR. 800 www.ccmjournl.org April 2016 Volume 44 Number 4
Peditric Criticl Cre Figure 1. Flow digrm of ptients evluted, crdiopulmonry resuscittion (CPR) events, overll outcomes, nd outcomes mong mjor subgroups. PCPC = Peditric Cerebrl Performnce Ctegory, ROC = return of circultion. Following their 139 index CPR events, 89 (64%) children survived for 24 hours, 64 (46%) survived to PICU dischrge, 63 (45%) survived to hospitl dischrge, nd 56 (40%) survived to hospitl dischrge with fvorble neurologic outcome (Tble 3). Importntly, 56 of 63 survivors (89%) hd fvorble neurologic sttus t hospitl dischrge, nd 48 of 63 (76%) hd PCPC score of 1 or no chnge from bseline. Notbly, 35 of 63 (56%) hd dischrge PCPC score of 1, 13 (21%) hd dischrge PCPC score of 2, nd five (8%) hd PCPC score of 3. Ten (16%) survivors were severely disbled or in vegettive stte t hospitl dischrge, but three of these hd no chnge from the bseline PCPC. Only four survivors (6%) hd chnge in the PCPC score of 2 ctegories or more. Among the 63 who survived to hospitl dischrge, 46 (73%) hd no new morbidities, s defined by n FSS score increse of t lest 3 (10), wheres 17 (27%) hd n FSS score increse of t lest 3. The medin chnge in FSS scores ws 1 (IQR, 0 3), nd 26 of 63 (41%) hd no chnge or slight improvement in the FSS score from bseline. Seventy-three (53%) children with ICU CPR were crdic ptients (51 surgicl/22 medicl), nd 66 (47%) were noncrdic (20 surgicl/46 medicl). Twenty-one hd open-chest CPR; of whom, 19 were crdic surgicl ptients, one ws crdic medicl ptient, nd one ws noncrdic surgicl ptient. Bsed on disese clssifiction t PICU dmission, the crdic group hd higher incidence of index CPR events thn the noncrdic group (3.4% vs 0.8%; p < 0.001). However, mong those with CPR event, there were no pprent differences in survivl-to-hospitl dischrge or survivl with fvorble neurologic outcome between the crdic nd noncrdic groups (Tble 3; nd Appendix Tble 1). The medin durtion of the initil CPR event ws 9 minutes (IQR, 3 30) for the 135 CPR events with chest compressions t lest 1 minute (rnge, 1 122 min). Among the 90 ptients receiving CPR for poor perfusion with brdycrdi nd/or hypotension, the medin durtion of the initil CPR event ws 8 minutes (IQR, 3 30); 17 (19%) did not ttin ROC, 61 (68%) ttined ROSC for more thn 20 minutes, nd 12 (13%) hd ROC by ECLS during CPR. Among the 45 ptients receiving CPR for pulselessness, the medin durtion of the initil CPR event ws 14 minutes (IQR, 3 28); 14 (31%) did not ttin ROC, 28 (62%) ttined ROSC for more thn 20 minutes, nd 3 (7%) hd ROC vi ECLS during CPR. Shorter durtion CPR ws ssocited with higher survivl rtes (Tble 4). Among the 44 children with CPR for 1 3 minutes (12 crdic surgicl, 6 crdic medicl, 6 noncrdic surgicl, nd 20 noncrdic medicl), only one filed to ttin ROC (becuse of withdrwl of technologicl support), 41 hd ROSC, 2 hd ROC vi ECLS, nd 29 of 44 (66%) survived to hospitl dischrge. In contrst, mong 32 children with CPR for more thn 30 minutes, 14 (44%) filed to ttin ROC, 9 (28%) hd ROSC, 9 (28%) hd ROC vi ECLS, nd only 9 of 32 (28%) survived to hospitl dischrge. However, the durtion of CPR ws not ssocited with fvorble neurologic outcomes for children who survived to hospitl dischrge. Among the 29 survivors with 1 3 minutes of CPR, 26 (90%) hd fvorble neurologic outcome. Similrly, 8 of 9 (89%) children Criticl Cre Medicine www.ccmjournl.org 801
Berg et l Tble 1. Chrcteristics of Ptients Who Received Crdiopulmonry Resuscittion Vrible Overll, n = 139 Crdic, n = 73 Noncrdic, n = 66 p Women (%) 69 (50) 36 (49) 33 (50) 0.94 Age t time of crdiopulmonry resuscittion event (%) < 1 mo 24 (17) 22 (30) 2 (3) < 0.001 1 mo to < 1 yr 58 (42) 33 (45) 25 (38) 1 yr to < 8 yr 36 (26) 10 (14) 26 (39) 8 yr to < 18 yr 21 (15) 8 (11) 13 (20) Rce (%) Blck or Africn Americn 34 (24) 15 (21) 19 (29) 0.49 White 56 (40) 31 (42) 25 (38) Other 10 (7) 4 (5) 6 (9) Unknown or not reported 39 (28) 23 (32) 16 (24) Ethnicity (%) Hispnic or Ltino 25 (18) 13 (18) 12 (18) 0.92 Not Hispnic or Ltino 76 (55) 39 (53) 37 (56) Unknown or not reported 38 (27) 21 (29) 17 (26) Pyer (%) Commercil 47 (34) 24 (33) 23 (35) 0.23 Government 79 (57) 39 (53) 40 (61) Other 5 (4) 3 (4) 2 (3) Unknown 8 (6) 7 (10) 1 (2) Bseline Functionl Sttus Scle score (%) Good (6 7) 93 (67) 54 (74) 39 (59) 0.04 Mild (8 9) 21 (15) 12 (16) 9 (14) Moderte (10 15) 20 (14) 6 (8) 14 (21) Severe (16 21) 2 (1) 1 (1) 1 (2) Very severe (> 21) 3 (2) 0 (0) 3 (5) Bseline Peditric Cerebrl Performnce Ctegory (%) 1 (norml) 87 (63) 48 (66) 39 (59) 0.16 2 (mild disbility) 30 (22) 17 (23) 13 (20) 3 (moderte disbility) 12 (9) 3 (4) 9 (14) 4 (severe disbility) 8 (6) 3 (4) 5 (8) 5 (com/vegettive) 2 (1) 2 (3) 0 (0) Primry disorder for ICU dmission (%) Respirtory 41 (29) 11 (15) 30 (45) < 0.001 b Cncer 3 (2) 0 (0) 3 (5) Crdiovsculr disese, cquired c 21 (15) 9 (12) 12 (18) Crdiovsculr disese, congenitl 53 (38) 52 (71) 1 (2) Gstrointestinl disorder 5 (4) 0 (0) 5 (8) Hemtologic disorder 1 (1) 0 (0) 1 (2) Musculoskeletl condition 1 (1) 0 (0) 1 (2) Neurologic 8 (6) 0 (0) 8 (12) Renl 1 (1) 0 (0) 1 (2) Miscellneous 5 (4) 1 (1) 4 (6) Peditric Risk of Mortlity III, medin (IQR) 8 (3 15) 8 (3 12) 8 (3 17) 0.50 IQR = interqurtile rnge. p vlue reflects the Wilcoxon signed rnk test for the ssocition between Peditric Risk of Mortlity III nd crdic versus noncrdic ptient type nd the chi-squre or Fisher exct test for ll other vribles. b All primry disorders with overll count of up to 5 were combined with miscellneous prior to p vlue clcultion. c Crdiovsculr disese (cquired) includes septic shock, systemic inflmmtory response syndrome, nd postcrdic rrest syndrome. 802 www.ccmjournl.org April 2016 Volume 44 Number 4
Peditric Criticl Cre Tble 2. Chrcteristics of the Crdiopulmonry Resuscittion Events Vrible Overll, n = 139 Crdic, n = 73 Noncrdic, n = 66 p CPR performed (%) Chest compressions only 122 (88) 60 (82) 62 (94) 0.03 Defibrilltion only 4 (3) 2 (3) 2 (3) Chest compressions nd defibrilltion 13 (9) 11 (15) 2 (3) Reson chest compressions strted (%) Poor perfusion (i.e., brdycrdi nd 90 (67) 50 (70) 40 (63) 0.33 hypotension) Pulselessness 45 (33) 21 (30) 24 (38) CPR performed open or closed chest (%) Open chest 21 (16) 20 (28) 1 (2) < 0.001 Closed chest 114 (84) 51 (72) 63 (98) Chest compression durtion (min) (%) 1 3 44 (33) 18 (25) 26 (41) 0.03 4 9 26 (19) 12 (17) 14 (22) 10 30 33 (24) 17 (24) 16 (25) > 30 32 (24) 24 (34) 8 (13) Time from PICU dmission to index CPR event (%) < 1 hr 9 (6) 4 (5) 5 (8) 0.25 1 to < 6 hr 17 (12) 5 (7) 12 (18) 6 to < 24 hr 21 (15) 11 (15) 10 (15) 24 hr to < 1 wk 50 (36) 27 (37) 23 (35) 1 wk or more 42 (30) 26 (36) 16 (24) CPR = crdiopulmonry resuscittion. p vlue reflects the Wilcoxon signed rnk test for the ssocition between Peditric Risk of Mortlity III nd crdic versus noncrdic ptient type nd the chisqure or Fisher exct test for ll other vribles. Tble 3. Outcomes of Children Following PICU Crdiopulmonry Resuscittion Vrible Overll, n = 139 (%) Crdic, n = 73 (%) Noncrdic, n = 66 Reltive Risk (95% CI) Return of circultion chieved 108 (78) 57 (78) 51 (77) 0.89 (0.74 1.08) Alive 24 hr following the first event 89 (64) 50 (68) 39 (59) 1.00 (0.76 1.32) Alive t the time of hospitl dischrge 63 (45) 32 (44) 31 (47) 0.84 (0.57 1.24) Fvorble neurologic outcome t hospitl dischrge (Peditric Cerebrl Performnce Ctegory score of 1 3 or no chnge) 56 (40) 30 (41) 26 (39) 0.91 (0.60 1.38) Reltive risk nd 95% CI bsed on modified Poisson regression model (n = 135) with djustment for ptient ge, Peditric Risk of Mortlity III score, time from PICU dmission to index crdiopulmonry resuscittion event, nd whether compressions strted for poor perfusion or pulselessness. The four ptients who hd defibrilltion without chest compressions were excluded from the reltive risk model becuse of vribles tht re only pplicble to ptients with chest compressions. who survived fter more thn 30 minutes of CPR hd fvorble neurologic outcome. Among the 139 children with CPR event, six (4%) hd crdic rrest prior to hospitl dmission nd nother four (3%) hd n in-hospitl crdic rrest prior to PICU dmission. Of these 10 ptients with CPR events prior to the ICU dmission, four (40%) survived to hospitl dischrge, nd ll four hd fvorble neurologic outcomes with PCPC score of 1 t dischrge or no chnge from dmission. Seventy-six ptients died prior to hospitl dischrge; 48 (63%) did not ttin ROC during resuscittion event (the initil resuscittion or subsequent resuscittion), 23 (30%) Criticl Cre Medicine www.ccmjournl.org 803
Berg et l Tble 4. Outcomes by Durtion of Chest Compressions Vribles 1 3 min, n = 44 (%) 4 9 min, n = 26 (%) 10 30 min, n = 33 (%) > 30 min, n = 32 (%) p Return of circultion chieved 43 (98) 23 (88) 20 (61) 18 (56) < 0.001 Alive 24 hr following the first event 39 (89) 19 (73) 14 (42) 14 (44) < 0.001 Alive t the time of hospitl dischrge 29 (66) 12 (46) 11 (33) 9 (28) < 0.001 Fvorble neurologic outcome t hospitl dischrge (Peditric Cerebrl Performnce Ctegory score of 1 3 or no chnge) 26 (59) 10 (38) 10 (30) 8 (25) 0.001 p vlue reflects Cochrn-Armitge trend test for differences in outcome reltive to the ctegorized length of crdiopulmonry resuscittion. The four ptients who hd defibrilltion without chest compressions could not be included in this tble. hd withdrwl of technologicl support, three (4%) hd limittion of technologicl support, nd two (3%) were declred ded by the bsence of brin function. Among the 23 ptients with withdrwl of technologicl support, 17 (77%) hd withdrwl of mechnicl ventiltion, 10 (45%) hd withdrwl of extrcorporel membrne oxygentor, 12 (55%) hd withdrwl of vsoctive medictions, three (14%) hd withdrwl of renl replcement therpy, nd 2 (9%) hd withdrwl of crdic compressions during CPR. Twenty-eight children hd multiple CPR events during their initil PICU dmission; 20 hd only one dditionl CPR event, nd 8 hd with more thn one dditionl CPR event (Appendix Tble 2). Of these 28 children, 13 (46%) ttined ROC in subsequent CPR event, nd only seven (25%) survived to hospitl dischrge (Appendix Tble 3). Among the seven survivors, six survived to hospitl dischrge with PCPC score of 1 or no chnge from bseline nd the other with PCPC score of 2. Subsequent CPR events were not more common fter ROC from n initil CPR event of more thn 30 minutes versus ROC from n initil CPR event of up to 30 minutes (5/18 [28%] vs 23/86 [27%]; p = 1.0). DISCUSSION In this prospective study of more thn 10,000 peditric dmissions to these lrge cdemic PICUs, 139 children received 1 minute or more of chest compressions nd/or defibrilltion in the PICU, incidence of 1.4%. Among these children, 78% ttined ROC during their initil CPR event, 45% survived to hospitl dischrge, nd 89% of the survivors hd fvorble neurologic outcome; 73% survived without new morbidities. Consistent with previous single-center studies (3 6), the reltive incidence of CPR events in our multicenter study ws higher for crdic ptients compred with noncrdic ptients (3.4% vs 0.8%). In contrst to previous single-center study dt nd multicenter registry dt (4 9), the survivl nd neurologic outcomes did not differ between the crdic nd noncrdic ptients. Although the likelihood of survivl decresed with incresed durtion of CPR, there ws no demonstrble difference in neurologic outcome or new morbidities mong those who survived fter longer durtions of CPR. Peditric nd dult studies suggest tht rpid response tems hve successfully decresed the number of crdic rrests in wrds nd incresed the proportion in ICUs (1, 19). For exmple, over the lst decde, more thn 93% of PICU nd wrd CPR events in the United Sttes occurred in PICU (1). However, rpid increses in the size nd number of PICUs over the lst 2 3 decdes might hve resulted in lower incidence of PICU CPR events (20). Nevertheless, the 1.4% incidence of PICU CPR events mong PICU dmissions in the current study is similr to the 1.8% incidence in 32 North Americn PICUs in the erly 1990s (3). Although our dt suggest tht the incidence of PICU CPR events hs not chnged much over the lst 20 yers, the outcomes re now substntilly better. Only 13.7% of ptients with PICU CPR event survived to dischrge in the erly 1990s (3). In contrst, 45% of the contemporry CPCCRN ptient cohort with PICU CPR events from 2011 to 2013 survived to hospitl dischrge, nd 89% of the survivors hd fvorble neurologic outcomes. The resons for these improved outcomes re not certin. All of the CPCCRN PICU sites hd 24/7 in-house cll with criticl cre ttendings nd/or fellows in 2011 2013 in contrst to the rrity of ttending nd/or fellow in-house cll in the erly 1990s, nd this higher level of in-hospitl expertise hs been ssocited with improved ptient cre (21). Perhps resurgence in focus on CPR qulity, PICU CPR trining, nd CPR implementtion science hs trnslted into superior outcomes (1, 7 9, 12). All of these PICU sites prticipte in the multicenter Therpeutic Hypothermi After Peditric Crdic Arrest tril (22). Therefore, it is plusible tht the better outcomes re in prt due to improvements in CPR nd postcrdic rrest cre mong providers who know tht they re being monitored s prt of tht tril (the Hwthorne effect). Notbly, GWTG-R registry dt hve lso demonstrted tht outcomes from peditric in-hospitl crdic rrests (ICU plus non-icu) hve improved over the lst decde (23). In this study, we defined fvorble neurologic outcomes s PCPC scores t hospitl dischrge of 1 3 or no chnge compred with bseline, consistent with other peditric crdic rrest/cpr investigtions (1, 8, 9, 16, 17). Fvorble neurologic outcomes in most dult studies use dult Cerebrl Performnce Ctegories 1 2 tht re identicl to the PCPC scores of 1 3 (24). Using this definition, 89% of survivors in our cohort hd fvorble neurologic outcomes. This contrsts mrkedly from the 37% to 65% rte of fvorble neurologic outcomes mong peditric 804 www.ccmjournl.org April 2016 Volume 44 Number 4
Peditric Criticl Cre survivors following out-of-hospitl crdic rrest/cpr over the lst decde (25 27). Perhps more importnt outcome is survivl without new functionl morbidities (10, 11). Among the children surviving to hospitl dischrge following PICU CPR in our cohort, 73% hd no new functionl morbidities. In single-center studies, 3 6% of ptients dmitted to peditric crdic ICU hd crdic rrests (4 6). Our dt confirm this higher risk of PICU CPR events for crdic versus noncrdic ptients (3.4% vs 0.8%). However, the bsolute number of CPR events ws similr mong crdic nd noncrdic PICU dmissions becuse noncrdic dmissions were lmost four-fold more common. In contrst to dt from single-center studies nd n in-hospitl crdic rrest registry, rtes of survivl to dischrge nd survivl with fvorble neurologic outcome were quite similr mong crdic nd noncrdic ptients in our cohort (44% vs 47% nd 41% vs 39%, respectively) (4 9). Recent studies from the lrge multicenter GWTG-R in-hospitl crdic rrest registry of the Americn Hert Assocition hve found tht CPR durtions more thn 10 minutes re common mong dults nd children, nd mny ptients survive fter more thn 30 minutes of CPR (9, 28). However, the uthors of those reports noted multiple limittions in the study designs, including potentil scertinment bises, s well s the bsence of neurologic dt for mny of the survivors fter more thn 30 minutes of CPR (9, 28). Consistent with the GWTG-R dt, the likelihood of survivl decresed with longer durtions of CPR in our cohort. The medin durtion of CPR ws 9 minutes (IQR, 3 30), nd 67% of children survived to hospitl dischrge following 1 3 minutes of CPR compred with only 28% following more thn 30 minutes of CPR. Surprisingly, fvorble neurologic outcome ws ttined in 90% of survivors following 1 3 minutes of CPR compred with 89% following more thn 30 minutes of CPR. These dt suggest tht ICU CPR efforts dequte for successful myocrdil resuscittion my lso be dequte for cerebrl resuscittion. Neurologic outcomes seem much better for children with in-hospitl CPR compred with peditric out-of-hospitl CPR where severe neurologic impirments hve been reported to occur in 35 63% of cses (25 27). The differences cn likely be explined by longer periods of untreted crdic rrest with no cerebrl blood flow during out-of-hospitl crdic rrests nd perhps suboptiml bsic nd dvnced life support in the chllenging out-of-hospitl setting. In ddition, difficulty in monitoring nd treting postcrdic rrest hypotension nd myocrdil dysfunction in the prehospitl setting my contribute to the worse outcomes. The findings in this multicenter study re limited becuse of the lck of dt regrding CPR qulity nd postcrdic rrest cre (7, 29). It is possible tht the qulity of CPR nd postcrdic rrest cre re superior in these lrge, cdemic CPCCRN PICUs. If so, outcomes my not be generlizble to institutions with less effective CPR qulity nd/or postcrdic rrest cre. These dt my differ from registry dt or dt from dministrtive dtbses becuse our reserch tem reviewed the cre of ech ptient in this PICU outcome study on dily bsis with specific focus on collecting prospectively determined dt from ll children receiving CPR for more thn 1 minute or defibrilltion. Therefore, we re confident tht ll CPR events were documented in this study, voiding scertinment bises inherent in registry dt nd dministrtive dtbses. The neurologic outcome dt do not include long-term outcomes, neurobehviorl outcomes, or detiled neuropsychologic outcomes (30). Nevertheless, this study includes mesures of both neurologic outcomes (PCPC) nd functionl outcomes (FSS) t the time of dischrge for ll surviving ptients. Notbly, dult dt show tht outcomes of individul ptients improve over time, suggesting tht the long-term outcomes of these children my ultimtely be superior to outcomes t dischrge (31). Finlly, the incidence of PICU CPR cn be influenced by differences in the numertor (e.g., decresed by do not ttempt resuscittion orders) nd in the denomintor (ffected by dmission criteri nd illness severity of ptients dmitted to specific PICU). Despite concerns tht the incidence dt might reflect increses in do not ttempt resuscittion orders nd incresed dmissions of children to PICUs with lower severity of illness, the incidence of PICU CPR hs pprently not chnged gretly over the lst two decdes. CONCLUSIONS CPR is provided for mny children dmitted to the PICU despite close monitoring nd mny therpies intended to prevent crdic rrest nd the need for CPR. Fully, 1.4% of children dmitted to lrge cdemic CPCCRN PICU received CPR nd/or defibrilltion. These dt estblish tht contemporry PICU CPR, including long durtions of CPR, results in high rtes of survivl-to-hospitl dischrge (45%), fvorble neurologic outcome mong survivors (89%), nd survivl without new morbidities (73%). Rtes of survivl to dischrge nd survivl with fvorble neurologic outcomes were similr mong crdic nd noncrdic ptients. The rigorous prospective, observtionl study design voided the limittions of missing dt nd potentil selection bises inherent in registry nd dministrtive dt. ACKNOWLEDGMENTS We cknowledge the importnt contributions of the following reserch coordintors nd dt coordinting center stff: Teres Liu, MPH, CCRP, nd Jeri Burr, MS, RN-BC, CCRN, from the University of Uth; Mry Ann DiLiberto, BS, RN, CCRC, nd Crol Ann Twelves, BS, RN, from the Children s Hospitl of Phildelphi; Jen Rerdon, MA, BSN, RN, from Children s Ntionl Medicl Center; Aimee Lbell, MS, RN, from Phoenix Children s Hospitl; Jeffrey Terry, MBA, from Children s Hospitl Los Angeles; Ric Morzov, RN, BSN, from Children s Hospitl Los Angeles; Mrgret Vill, RN, from Children s Hospitl Los Angeles nd Mttel Children s Hospitl; Mry Ann Nyc, BS, from UCLA Mttel Children s Hospitl; Jeni Kwok, JD, from Children s Hospitl of Los Angeles; Ann Pwluszk, BSN, RN, from Children s Hospitl of Michign; Monic S. Weber, RN, BSN, CCRP, from University of Michign; nd Aln C. Abrhm, BA, CCRC, from University of Pittsburgh Medicl Center. Criticl Cre Medicine www.ccmjournl.org 805
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Girotr S, Spertus JA, Li Y, et l; Americn Hert Assocition Get With the Guidelines Resuscittion Investigtors: Survivl trends in peditric in-hospitl crdic rrests: An nlysis from Get With the Guidelines-Resuscittion. Circ Crdiovsc Qul Outcomes 2013; 6:42 49 24. Becker LB, Aufderheide TP, Geocdin RG, et l; Americn Hert Assocition Emergency Crdiovsculr Cre Committee; Council on Crdiopulmonry, Criticl Cre, Periopertive nd Resuscittion: Primry outcomes for resuscittion science studies: A consensus sttement from the Americn Hert Assocition. Circultion 2011; 124:2158 2177 25. Moler FW, Meert K, Donldson AE, et l; Peditric Emergency Cre Applied Reserch Network: In-hospitl versus out-of-hospitl peditric crdic rrest: A multicenter cohort study. Crit Cre Med 2009; 37:2259 2267 26. Nitt M, Iwmi T, Kitmur T, et l; Utstein Osk Project: Age-specific differences in outcomes fter out-of-hospitl crdic rrests. Peditrics 2011; 128:e812 e820 27. Michiels EA, Dums F, Qun L, et l: Long-term outcomes following peditric out-of-hospitl crdic rrest*. Peditr Crit Cre Med 2013; 14:755 760 28. Goldberger ZD, Chn PS, Berg RA, et l; Americn Hert Assocition Get With The Guidelines Resuscittion (formerly Ntionl Registry of Crdiopulmonry Resuscittion) Investigtors: Durtion of resuscittion efforts nd survivl fter in-hospitl crdic rrest: An observtionl study. Lncet 2012; 380:1473 1481 29. Meney PA, Bobrow BJ, Mncini ME, et l; CPR Qulity Summit Investigtors, the Americn Hert Assocition Emergency Crdiovsculr Cre Committee, nd the Council on Crdiopulmonry, Criticl Cre, Periopertive nd Resuscittion: Crdiopulmonry resuscittion qulity: [Corrected] Improving crdic resuscittion outcomes both inside nd outside the hospitl: A consensus sttement from the Americn Hert Assocition. Circultion 2013; 128:417 435 30. Holubkov R, Clrk AE, Moler FW, et l: Efficcy outcome selection in the therpeutic hypothermi fter peditric crdic rrest trils. 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Appendix 1. Univrible Associtions With Fvorble Neurologic Outcome Peditric Criticl Cre Vrible Fvorble Outcome, n (%) Reltive Risk (95% CI) p Sex Femle 29 (42) 1.09 (0.73 1.63) 0.68 Mle 27 (39) Reference Age t time of CPR event < 1 mo 9 (38) Reference 0.46 1 mo to < 1 yr 27 (47) 1.24 (0.69 2.23) 1 to < 8 yr 11 (31) 0.81 (0.40 1.66) 8 to < 18 yr 9 (43) 1.14 (0.56 2.34) Rce Blck or Africn Americn 10 (29) Reference 0.35 White 27 (48) 1.64 (0.91 2.95) Other 4 (40) 1.36 (0.54 3.41) Unknown or not reported 15 (38) 1.31 (0.68 2.52) Ethnicity Hispnic or Ltino 11 (44) Reference 0.84 Not Hispnic or Ltino 31 (41) 0.93 (0.55 1.56) Unknown or not reported 14 (37) 0.84 (0.46 1.54) Pyer Commercil 20 (43) Reference 0.39 Government 29 (37) 0.86 (0.56 1.34) Other 4 (80) 1.88 (1.08 3.26) Unknown 3 (38) 0.88 (0.34 2.29) Ptient type Crdic 30 (41) 1.04 (0.69 1.57) 0.84 Noncrdic 26 (39) Reference Bseline Functionl Sttus Scle score Good/mild (6 9) 45 (39) Reference 0.90 Moderte (10 15) 9 (45) 1.14 (0.67 1.95) Severe/very severe (> 16) 2 (40) 1.01 (0.34 3.04) Bseline Peditric Cerebrl Performnce Ctegory 1 3 (norml, mild, nd moderte) 53 (41) Reference 0.52 4 5 (severe nd com/vegettive) 3 (30) 0.73 (0.28 1.92) Primry disorder for ICU dmission Respirtory 19 (46) Reference 0.34 Crdiovsculr disese (cquired) 9 (43) 0.92 (0.51 1.67) Crdiovsculr disese (congenitl) 22 (42) 0.90 (0.57 1.42) Neurologic 1 (13) 0.27 (0.04 1.74) Miscellneous 5 (31) 0.67 (0.30 1.50) Peditric Risk of Mortlity III, medin (IQR) 8 (3 11) (vs 8 [3 16]) 0.97 (0.95 1.00) b 0.046 (Continued) Criticl Cre Medicine www.ccmjournl.org 807
Berg et l Appendix 1. (Continued ). Univrible Associtions With Fvorble Neurologic Outcome Vrible Fvorble Outcome, n (%) Reltive Risk (95% CI) p Time from PICU dmission to index CPR event <24 hr 19 (40) Reference 0.11 24 hr to <1 wk 25 (50) 1.24 (0.79 1.93) 1 wk or more 12 (29) 0.71 (0.39 1.28) Defibrilltion performed Yes 5 (29) 0.70 (0.33 1.51) 0.37 No 51 (42) Reference Reson chest compressions strted Poor perfusion 39 (43) 1.30 (0.81 2.09) 0.28 Pulselessness 15 (33) Reference CPR performed open or closed chest Open chest 8 (38) 0.94 (0.52 1.70) 0.85 Closed chest 46 (40) Reference CPR = crdiopulmonry resuscittion, IQR = interqurtile rnge. Undjusted reltive risk, 95% CI, nd p vlue bsed on modified Poisson regression model. b Reflects reltive risk of fvorble outcome for one-unit increse in totl Peditric Risk of Mortlity score. Appendix 2. Number of Crdiopulmonry Resuscittion Events Among Ptients No. of Crdiopulmonry Resuscittion Events Ptients, n (%) 1 111 (80) 2 20 (14) 3 4 (3) 4 1 (1) 5 3 (2) Appendix 3. Outcomes Among Ptients With Single Versus Multiple Crdiopulmonry Resuscittion Events Within the Initil PICU Admission Vrible Return of circultion chieved for ll events (%) Alive t the time of hospitl dischrge (%) Fvorble neurologic outcome t hospitl dischrge (Peditric Cerebrl Performnce Ctegory 1 3 or no chnge) (%) One CPR Event, n = 111 Two or More CPR Events, n = 28 80 (72) 13 (46) 56 (50) 7 (25) 49 (44) 7 (25) b CPR = crdiopulmonry resuscittion. 15 (54%) filed to chieve return of circultion during subsequent crdiopulmonry resuscittion event. b 6 survived to dischrge with Peditric Cerebrl Performnce Ctegory score of 1 or no chnge from bseline nd the other with Peditric Cerebrl Performnce Ctegory score of 2. 808 www.ccmjournl.org April 2016 Volume 44 Number 4