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Delayed high-quality CPR does not improve outcomes
Resuscitation 82S (2011) S52–S55
Delayed high-quality CPR does not improve outcomes Fengqing Song a , Shijie Sun a,b , Giuseppe Ristagno a , Tao Yu a , Yi Shan a , Sung Phil Chung a , Max Harry Weil a,b , Wanchun Tang a,b, * a b
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA The Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
A R T I C L E
I N F O
Keywords: Cardiac arrest Cardiopulmonary resuscitation Quality
A B S T R A C T Aim of Study: The quality of cardiopulmonary resuscitation (CPR) is an important factor in the outcome of cardiac arrest. Our objective was to compare outcomes following either immediate low-quality (LQ) CPR or delayed high-quality (HQ) CPR. We hypothesized that delayed HQ CPR will improve the outcomes of CPR in comparison to immediately performing LQ CPR. Methods: Eighteen Sprague-Dawley rats were randomized into two groups: (1) Delayed HQ CPR (HQ group, n = 9). (2) Immediate LQ CPR (LQ group, n = 9). Ventricular fibrillation (VF) was induced and untreated for 8 mins. CPR was immediately performed in LQ group for 5 mins. Compression depth was set at 70% of the “optimal compression depth”. VF was untreated for an additional 5 mins in HQ group. HQ CPR was started together with ventilation (100% oxygen) and external hypothermia for 8 mins in both groups. The “optimal compression depth” was approximately 30% of the anteroposterior chest diameter. Epinephrine was administrated 3 mins prior to defibrillation attempt. Restoration of spontaneous circulation, postresuscitation myocardial function and survival time were monitored. Results: All animals in the LQ group and 7 of 9 animals in the HQ group were resuscitated. Myocardial function, including ejection fraction and cardiac output was better in the LQ group than in the HQ group (p < 0.05) and survival time was longer in the LQ group (p < 0.05). Conclusion: The outcomes after immediate LQ CPR, were better than those after delayed HQ CPR in this rat model of cardiac arrest and resuscitation. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Cardiopulmonary resuscitation (CPR) to revive victims of sudden cardiac arrest, drowning and asphyxia, has been performed for decades. Despite major efforts to improve outcomes, survival rates are still poor. 1 –4 Early and high-quality (HQ) of CPR, especially chest compression, is an important determinant for survival of these victims. 5 –8 CPR by bystanders including chest compressions and mouthto-mouth ventilation prior to the arrival of emergency medical services (EMS) has been documented to save lives. 8 Nevertheless, several studies have shown that the quality of CPR performed by bystanders is sub-optimal. 9 –13 Either lay rescuers allow for long interruptions between chest compressions, 9 which significantly decrease the number of compressions provided per min, or chest compression depth is too shallow and continues to decline as the fatigue increases. 10 –13 The deteriorated quality of CPR during transport has been observed in both manikin investigations 14,15 and clinical studies. 16,17
* Address for correspondence: Wanchun Tang, MD, Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA, 92270, USA. Tel.: +1-760778-4911; fax: +1 760-778-3468. E-mail address: [email protected] (W. Tang). 0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
EMS professionals performing HQ CPR usually arrive after a delayed interval. Since low-quality (LQ) CPR results in poor outcome, it was suggested that waiting for EMS professionals to perform HQ CPR may be preferable rather than immediately performing LQ CPR. Accordingly, whether the low blood flow produced by LQ CPR was better than no flow with delayed HQ CPR remained unclear. We proposed to compare the outcome of immediate LQ CPR with delayed HQ CPR. We hypothesized that delayed HQ CPR would improve the outcomes of CPR in comparison to immediately performing LQ CPR. 2. Methods All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86-32, revised 1985). The protocol was approved by the Institutional Animal Care and Use Committee of the Weil Institute of Critical Care Medicine.
F. Song et al. / Resuscitation 82S (2011) S52–S55
2.1. Animal preparation Eighteen male Sprague-Dawley rats weighing 450–550 g were fasted overnight except for free access to water. The animals were anesthetized by an intraperitoneal injection of pentobarbital (45 mg/kg). Additional doses (10 mg/kg) were administrated at intervals of approximately one hour or when required to maintain anesthesia, except for the 30 mins before induction of cardiac arrest. The trachea was orally intubated with a 14G cannula mounted on a blunt needle with a 145° angled tip. 18 End-tidal CO2 (EtCO2 ) was continuously monitored with a side-stream infrared CO2 analyzer (model 200; Instrumentation Laboratories, Lexington, MA). A conventional lead II EKG was continuously monitored. Animals spontaneously breathed room air. A polyethylene catheter (PE-50; Becton-Dickinson, Franklin Lakes, NJ) was advanced into the descending aorta from the surgically exposed left femoral artery for measurement of arterial pressure and blood gases. Another polyethylene catheter (PE-50; Becton-Dickinson, Franklin Lakes, NJ) was advanced through the left external jugular vein and into the right atrium for measurement of right atrial pressures and the drug treatment. Aortic and right atrial pressures were measured with reference to the midchest with high-sensitivity transducers (model 42584-01, Abbott Critical Care Systems, North Chicago, IL). A thermocouple microprobe, 10 cm in length and 0.5 mm in diameter (9030-12-D-34, Columbus Instruments, Columbus, OH), was inserted into the thoracic aorta for measurement of blood temperature. A 3-French PE catheter (model C-PMS-301J, Cook Critical Care, Bloomington, IN) was advanced through the right external jugular vein into the right atrium. A pre-curved guide wire supplied with this catheter was then advanced through the catheter into the right ventricle for inducing ventricular fibrillation (VF) as confirmed by an endocardial electrocardiogram. All catheters were flushed intermittently with saline containing 2.5 IU/ml of crystalline bovine heparin. 2.2. Experimental procedures Mechanical ventilation was established at a tidal volume of 0.65 ml/100 g of body weight and a frequency of 100 breaths/min. The inspired O2 fraction (FIO2 ) was maintained at 0.21. A progressive increase in 60 Hz current to a maximum of 3 mA was delivered to the right ventricular endocardium and current flow was continued for 3 min such as to prevent spontaneous defibrillation. Mechanical ventilation was stopped after onset of VF. 19 Eighteen animals were randomized into two groups. In the “immediate LQ CPR” group (LQ group), precordial compression with a mechanical chest compressor was begun 8 min after onset of VF. LQ chest compression was performed at a rate of 200 compressions per min with 70% of “optimal compression depth”. Ventilation was started and FIO2 was maintained at 0.21. After 5 min of LQ CPR, HQ CPR with hypothermia, a rapid cooling performed externally with the aid of ice packs and an electrical fan, 20 was started for an additional 8 mins prior to defibrillation and FIO2 was switched to 1.0. In the “delayed HQ CPR” group (HQ group), after 13 mins of untreated VF, HQ CPR was initiated and animals were mechanically ventilated with a FIO2 of 1.0 and
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hypothermia was induced. For the “optimal compression depth”, the HQ precordial compression depth at maximal compression was approximately 30% of the anteroposterior chest diameter. 21 Epinephrine (20 μg/kg) was administered following 5 mins of HQ CPR. Resuscitation was attempted with up to 3 two (2) joule countershocks after 8 mins of HQ CPR. ROSC was defined as the return of supraventricular rhythm with a mean aortic pressure of 50 mm Hg for a minimum of 5 mins (Fig. 1). 22,23 For the hypothermic treatment, upon reaching the target cooling temperature of 32°C ± 0.2 at ROSC, temperature was maintained with the aid of Blanketrol II (CSZ, Cincinnati, OH) until 4 hours after ROSC. After a 4-hour observation, body temperature was gradually increased over 2 hours with a heating lamp to 37°C ± 0.2. Following ROSC, mechanical ventilation was continued with 100% inspired oxygen for 1 hour and then maintained at 21% inspired oxygen for the following 3 hours. Animals were then allowed to recover from anesthesia. All catheters, including the endotracheal tube were then removed. The animals were continuously observed by the investigators for an additional 2 hours. Butorphanol (0.4 mg/kg) was injected intramuscularly if discomfort was identified. The status of the animals was then evaluated at 4-hour intervals by the investigators for a total of 72 hours. Levels of consciousness, brain stem function and overall performance were observed and scored according to the method of Hendrickx et al. 24 (neurological deficit score (NDS) ranged from: normal = 0 to coma = 500). The animals were euthanized by intraperitoneal injection of pentobarbital (150 mg/kg) after 72 hours. At autopsy, organs were inspected for gross abnormalities, including evidence of traumatic injuries consequent to cannulation or precordial compression. 2.3. Measurements Aortic and right-atrial pressures, electrocardiographic tracings, and EtCO2 were continuously recorded on a PC-based dataacquisition system supported by WIND AQ software (DataQ, Akron, OH). Coronary perfusion pressure (CPP) was calculated as the difference between decompression diastolic aortic and time-coincident right-atrial pressure measured at the end of each min of precordial compression. Baseline and hourly interval measurements after ROSC of echocardiographic cardiac output (CO) and ejection fraction (EF) were obtained with a Philips ultrasound system, utilizing a 12.5-Hz transducer (HD 11 XE, Philips Ultrasound, Bothell, WA). EF served as an indicator of myocardial contractility. Blood gas measurements of arterial oxygen partial pressure (PO2 ), CO2 partial pressure (PCO2 ), pH, and lactate were made from 0.2 ml samples at each time point. 3. Results Baseline haemodynamics were not significantly different between the two groups (Table 1), nor was there any between the two groups regarding the duration of HQ CPR (Table 2). Seven of 9 animals were resuscitated in the HQ group and all animals were resuscitated in the LQ group. Animals survived longer in the LQ group than those in the HQ group (p < 0.05, Table 2). CPP and ETCO2 were significantly lower during LQ CPR than
Fig. 1. The experimental procedure. BL = baseline; CA = cardiac arrest; PR = postresuscitation.
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F. Song et al. / Resuscitation 82S (2011) S52–S55
Table 1 Variables at baseline between two groups. Group
Weight (g)
Heart rate (beats/min)
MAP (mm Hg)
RAP (mm Hg)
ETCO2 (mm Hg)
HQ (n = 9) LQ (n = 9)
515 ± 10 516 ± 4
357 ± 24 354 ± 25
137 ± 6 139 ± 8
0.2 ± 0.4 0.4 ± 0.5
42 ± 7 43 ± 6
Table 2 Variables of resuscitation between groups.
Duration of high-quality CPR (s) Survival time (h) Resuscitated animals (n)
HQ
LQ
469 ± 23 5.5 (2.5, 18) 7/9
476 ± 43 18 (12, 51)* 9/9
*p < 0.05 vs HQ group.
during HQ CPR (6 ± 1 and 5 ± 2 mm Hg vs 23 ± 2 and 14 ± 6 mm Hg, p < 0.001). There were no differences at baseline in blood gas between two groups. pH was lower in the HQ group than LQ group at VF 12 min (7.36 ± 0.05 vs 7.49 ± 0.08, p <0.01) and PR 240 min (7.29 ± 0.08 vs 7.37 ± 0.04, p < 0.05). There were no differences in PO2 and PCO2 at PR 240 min. However, lactate was higher in the HQ group at PR 240 min than that of the LQ group (2.99 ± 2.51 vs 0.97 ± 0.32, p < 0.05, Table 3). Myocardial function was significantly impaired after resuscitation from cardiac arrest in both groups. However, at PR 240 mins, EF and CO were higher in the LQ group than those of HQ group (57 ± 10 and 103 ± 26 vs 45 ± 9 and 69 ± 21, p < 0.05, Fig. 2). 4. Discussion The present study demonstrated that with immediate LQ CPR followed by delayed HQ CPR, all animals were successfully resuscitated while only 7 of 9 animals were resuscitated in the delayed HQ CPR group. Cardiac function, including EF and CO was impaired more severely in the delayed HQ group than those in the early LQ group. Consequently survival time was shorter in the HQ group than in the LQ group. Successful treatment of VF becomes increasingly more difficult when the duration of VF exceeds 5 min. When performed immediately after prolonged VF of cardiac arrest, bystander CPR provides a small but critical amount of blood flow to the heart and brain so that it can double or triple the victim’s chance of survival. 25 –27 In the present study, we simulated bystander initiated LQ CPR for 5 mins followed by professional HQ CPR. The delayed HQ CPR did not show benefits in the outcome of cardiac arrest. Optimal chest compressions appear to be the most important factor accounting for the quality of CPR, both in human and animal
Fig. 2. Comparison of ejection fraction and cardiac output between the two groups. *p < 0.05 vs HQ group.
studies. 7,28 However, in the Wik et al. study on 176 victims of out-of-hospital cardiac arrest, 10 only 28% of rescuers performed competent chest compressions, in which the anteroposterior diameter was decreased by approximately 5 cm, according to the international guidelines. Abella et al. 29 also observed inadequate depth of chest compressions based on 67 instances of in-hospital cardiac arrest. In the present study, HQ precordial compression depth was approximately 30% of the anteroposterior chest diameter, 21 while LQ chest compression was defined as precordial compression depth of approximately 70% of the “optimal compression depth”. As expected, CPP generated by LQ compression was significantly lower than that achieved during HQ chest compression. Nevertheless, when LQ chest compression was performed at the onset of CPR followed by HQ CPR, all the animals were succesfully resuscitated and 3 of them survived for more than 24 hours. Seven of 9 animals were resuscitated in the group in which no CPR was performed prior to HQ CPR and none of them survived more than 24 hours. Both ventilations and compressions are important for victims of prolonged VF cardiac arrest. With oxygen deprivation for a long interval, tissue hypoxia will persist until restoration of effective spontaneous perfusion. Tissue hypoxia leads to anaerobic metabolism and metabolic acidosis. In an earlier pig study, CPR without assisted ventilation resulted in profound hypoxemia and respiratory acidosis. 30 In the present study, after 8 mins of untreated cardiac arrest, ventilation was started during LQ chest
Table 3 Comparison of blopd gases variables between the two groups. BL***
VF12
HQPC7
PR5
PR60
PR240
pH HQ LQ
7.46 ± 0.03 7.47 ± 0.01
7.36 ± 0.05 7.49 ± 0.08**
7.06 ± 0.13 7.11 ± 0.11
7.02 ± 0.08 7.07 ± 0.11
7.21 ± 0.08 7.28 ± 0.09
7.29 ± 0.08 7.37 ± 0.04
PO2 (mm Hg) HQ LQ
81 ± 9 83 ± 6
46 ± 5 50 ± 7
55 ± 14 81 ± 39
133 ± 93 143 ± 86
314 ± 73 328 ± 58
99 ± 14 103 ± 7
PCO2 (mm Hg) HQ LQ
35 ± 7 35 ± 4
44 ± 7 23 ± 8**
55 ± 24 53 ± 30
43 ± 7 50_23
33 ± 5 35 ± 4
24 ± 6 27 ± 5
LAC (mmol/l) HQ LQ
0.51 ± 0.17 0.48 ± 0.05
2.47 ± 0.71 3.42 ± 0.73*
7.64 ± 2.59 9.32 ± 1.29
10.65 ± 1.34 10.37 ± 1.31
5.29 ± 1.51 3.07 ± 1.41
2.99 ± 2.51 0.97 ± 0.32*
***Baseline ventilation with 21% oxygen. *p < 0.05, **p < 0.01 vs HQ group.
F. Song et al. / Resuscitation 82S (2011) S52–S55
compression with a FIO2 of 0.21. After 5 mins of LQ CPR with 0.21 of FIO2 or 13 mins of VF, animals in both groups were ventilated with 100% oxygen. At PR 240 mins, animals in the HQ group showed higher lactate and lower pH in blood than those in the LQ group. Therefore, survival time was longer in the LQ group compared with that of the HQ group. Postresuscitation myocardial dysfunction has been recognized as one of the leading causes of the high postresuscitation mortality rate. With the initiation of LQ CPR or with a delayed HQ CPR, the heart is not adequately perfused for a prolonged period. This accounts for increased severity of myocardial ischemia and leads to the condition of “stone heart”. In the present study, postresuscitation myocardial function was impaired in both groups. However, it was better in the LQ group than in the HQ group. Long-term survival was not improved, most probably due to the long intervals of cardiac arrest. We acknowledge several limitations of the present study. Although 3 of the animals in the LQ group survived more than 24 hours, the neurological outcomes were not compared between the two groups because all of the animals died within 24 hours following resuscitation in the HQ group. Additionally, we did not measure indicators of multi-organ dysfunction. In fact, with this setting, with a total of 21 mins of ischemia (including cardiac arrest and CPR), though all of the animals in the LQ group and 7 of 9 in the HQ group were resuscitated, survival was poor which might have been the result of multi-organ dysfunction. More studies need to be performed to answer these questions.
7.
8.
9.
10. 11. 12. 13.
14. 15.
16.
17.
18. 19.
5. Conclusion Performing immediate LQ CPR without delay for HQ CPR was preferable in this rat model of cardiac arrest and resuscitation.
20.
21.
Acknowledgement 22.
This study was supported by the Weil Institute of Critical Care Medicine, Rancho Mirage, CA. 23.
Conflict of interest 24.
The authors have no conflicts of interest to disclose in this study. 25.
References 26. 1. Eckstein M, Stratton SJ, Chan LS. Cardiac arrest resuscitation evaluation in Los Angeles: CARE-LA. Ann Emerg Med 2005;45:504–9. 2. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008;300:1423–31. 3. Kellum MJ, Kennedy KW, Barney R, et al. Cardiocerebral resuscitation improves neurologically intact survival of patients with out-of-hospital cardiac arrest. Ann Emerg Med 2008;52:244–52. 4. Bobrow BJ, Ewy GA, Clark L, et al. Passive oxygen insufflation is superior to bag-valve-mask ventilation for witnessed ventricular fibrillation out-ofhospital cardiac arrest. Ann Emerg Med 2009;54:656–662. 5. Wik L, Hansen TB, Fylling F, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial. JAMA 2003;289:1434–6. 6. Van Hoeyweghen RJ, Bossaert LL, Mullie A, et al. Quality and efficiency of
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bystander CPR. Belgian Cerebral Resuscitation Study Group. Resuscitation 1993;26:47–52. Gallagher EJ, Lombardi G, Gennis P. Effectiveness of bystander cardiopulmonary resuscitation and survival following out-of-hospital cardiac arrest. JAMA 1995;274:1922–5. Herlitz J, Svensson L, Holmberg S, Angquist KA, Young M. Efficacy of bystander CPR: intervention by lay people and by health care professionals. Resuscitation 2005;66:291–5. Assar D, Chamberlain D, Colquhoun M, et al. Randomised controlled trials of staged teaching for basic life support. 1. Skill acquisition at bronze stage. Resuscitation 2000;45:7–15. Wik L, Kramer-Johansen J, Myklebust H, et al. Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest. JAMA 2005;293:299–304. Hightower D, Thomas SH, Stone CK, Dunn K, March JA. Decay in quality of closed-chest compressions over time. Ann Emerg Med 1995;26:300–3. Ochoa FJ, Ramalle-Gomara E, Lisa V, Saralegui I. The effect of rescuer fatigue on the quality of chest compressions. Resuscitation 1998;37:149–52. Ashton A, McCluskey A, Gwinnutt CL, Keenan AM. Effect of rescuer fatigue on performance of continuous external chest compressions over 3 min. Resuscitation 2002;55:151–5. Stone CK, Thomas SH. Can correct closed-chest compressions be performed during prehospital transport? Prehosp Disaster Med 1995;10:121–3. Sunde K, Wik L, Steen PA. Quality of mechanical, manual standard and active compression–decompression CPR on the arrest site and during transport in a manikin model. Resuscitation 1997;34:235–42. Wang HC, ChiangWC, Chen SY, et al. Video-recording and time–motion analyses of manual versus mechanical cardiopulmonary resuscitation during ambulance transport. Resuscitation 2007;74:453–60. Olasveengen TM, Wik L, Steen PA. Quality of cardiopulmonary resuscitation before and during transport in out-of-hospital cardiac arrest. Resuscitation 2008;76:185–90. von Planta I, Weil MH, von Planta M, et al. Cardiopulmonary resuscitation in the rat. J Appl Physiol 1988;65:2641–7. Sun S, Weil MH, Tang W, Povoas H. Combined effects of buffer and adrenergic agents on postresuscitation myocardial function. J Pharmacol Exp Ther 1999;291:773–7. D’Cruz BJ, Fertig KC, Filiano AJ, Hicks SD, DeFranco DB, Callaway CW. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. J Cereb Blood Flow Metab 2002;22:843–51. Ristagno G, Tang W, Chang YT, et al. The quality of chest compressions during cardiopulmonary resuscitation overrides importance of timing of defibrillation. Chest 2007;132:70–5. Sun S, Weil MH, Tang W, Kamohara T, Klouche K. Delta-opioid receptor agonist reduces severity of postresuscitation myocardial dysfunction. Am J Physiol Heart Circ Physiol 2004;287:H969–74. Fang X, Tang W, Sun S, Huang L, Huang Z, Weil MH. Mechanism by which activation of delta-opioid receptor reduces the severity of postresuscitation myocardial dysfunction. Crit Care Med 2006;34:2607–12. Hendrickx HL, Rao GR, Safar P, Gisvold SE. Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery. Resuscitation 1984;12:97–116. Larsen MP, Eisenberg MS, Cummins RO, Hallstrom. Predicting survival from out-of-hospital cardiac arrest: a graphic model. Ann Emerg Med 1993;22:1652–8. Valenzuela TD, Roe DJ, Cretin S, Spaite DW, Larsen MP. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation 1997;96:3308–13. Holmberg M, Holmberg S, Herlitz J, Swedish Cardiac Arrest Registry. Factors modifying the effect of bystander cardiopulmonary resuscitation on survival in out-of-hospital cardiac arrest patients in Sweden. Eur Heart J 2001;22:511– 9. Wik L, Steen PA, Bircher NG. Quality of bystander cardiopulmonary resuscitation influences outcome after prehospital cardiac arrest. Resuscitation 1994;28:195–203. Abella BS, Alvarado JP, Myklebust H, et al. Quality of cardiopulmonary resuscitation during in-hospital cardiac arrest. JAMA 2005;293:305–10. Yannopoulos D, Matsuura T, McKnite S, et al. No assisted ventilation cardiopulmonary resuscitation and 24-hour neurological outcomes in a porcine model of cardiac arrest. Crit Care Med 2010; 38:254–60.
Delayed high-quality CPR does not improve outcomes Fengqing Song a , Shijie Sun a,b , Giuseppe Ristagno a , Tao Yu a , Yi Shan a , Sung Phil Chung a , Max Harry Weil a,b , Wanchun Tang a,b, * a b
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA The Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
A R T I C L E
I N F O
Keywords: Cardiac arrest Cardiopulmonary resuscitation Quality
A B S T R A C T Aim of Study: The quality of cardiopulmonary resuscitation (CPR) is an important factor in the outcome of cardiac arrest. Our objective was to compare outcomes following either immediate low-quality (LQ) CPR or delayed high-quality (HQ) CPR. We hypothesized that delayed HQ CPR will improve the outcomes of CPR in comparison to immediately performing LQ CPR. Methods: Eighteen Sprague-Dawley rats were randomized into two groups: (1) Delayed HQ CPR (HQ group, n = 9). (2) Immediate LQ CPR (LQ group, n = 9). Ventricular fibrillation (VF) was induced and untreated for 8 mins. CPR was immediately performed in LQ group for 5 mins. Compression depth was set at 70% of the “optimal compression depth”. VF was untreated for an additional 5 mins in HQ group. HQ CPR was started together with ventilation (100% oxygen) and external hypothermia for 8 mins in both groups. The “optimal compression depth” was approximately 30% of the anteroposterior chest diameter. Epinephrine was administrated 3 mins prior to defibrillation attempt. Restoration of spontaneous circulation, postresuscitation myocardial function and survival time were monitored. Results: All animals in the LQ group and 7 of 9 animals in the HQ group were resuscitated. Myocardial function, including ejection fraction and cardiac output was better in the LQ group than in the HQ group (p < 0.05) and survival time was longer in the LQ group (p < 0.05). Conclusion: The outcomes after immediate LQ CPR, were better than those after delayed HQ CPR in this rat model of cardiac arrest and resuscitation. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Cardiopulmonary resuscitation (CPR) to revive victims of sudden cardiac arrest, drowning and asphyxia, has been performed for decades. Despite major efforts to improve outcomes, survival rates are still poor. 1 –4 Early and high-quality (HQ) of CPR, especially chest compression, is an important determinant for survival of these victims. 5 –8 CPR by bystanders including chest compressions and mouthto-mouth ventilation prior to the arrival of emergency medical services (EMS) has been documented to save lives. 8 Nevertheless, several studies have shown that the quality of CPR performed by bystanders is sub-optimal. 9 –13 Either lay rescuers allow for long interruptions between chest compressions, 9 which significantly decrease the number of compressions provided per min, or chest compression depth is too shallow and continues to decline as the fatigue increases. 10 –13 The deteriorated quality of CPR during transport has been observed in both manikin investigations 14,15 and clinical studies. 16,17
* Address for correspondence: Wanchun Tang, MD, Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA, 92270, USA. Tel.: +1-760778-4911; fax: +1 760-778-3468. E-mail address: [email protected] (W. Tang). 0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
EMS professionals performing HQ CPR usually arrive after a delayed interval. Since low-quality (LQ) CPR results in poor outcome, it was suggested that waiting for EMS professionals to perform HQ CPR may be preferable rather than immediately performing LQ CPR. Accordingly, whether the low blood flow produced by LQ CPR was better than no flow with delayed HQ CPR remained unclear. We proposed to compare the outcome of immediate LQ CPR with delayed HQ CPR. We hypothesized that delayed HQ CPR would improve the outcomes of CPR in comparison to immediately performing LQ CPR. 2. Methods All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86-32, revised 1985). The protocol was approved by the Institutional Animal Care and Use Committee of the Weil Institute of Critical Care Medicine.
F. Song et al. / Resuscitation 82S (2011) S52–S55
2.1. Animal preparation Eighteen male Sprague-Dawley rats weighing 450–550 g were fasted overnight except for free access to water. The animals were anesthetized by an intraperitoneal injection of pentobarbital (45 mg/kg). Additional doses (10 mg/kg) were administrated at intervals of approximately one hour or when required to maintain anesthesia, except for the 30 mins before induction of cardiac arrest. The trachea was orally intubated with a 14G cannula mounted on a blunt needle with a 145° angled tip. 18 End-tidal CO2 (EtCO2 ) was continuously monitored with a side-stream infrared CO2 analyzer (model 200; Instrumentation Laboratories, Lexington, MA). A conventional lead II EKG was continuously monitored. Animals spontaneously breathed room air. A polyethylene catheter (PE-50; Becton-Dickinson, Franklin Lakes, NJ) was advanced into the descending aorta from the surgically exposed left femoral artery for measurement of arterial pressure and blood gases. Another polyethylene catheter (PE-50; Becton-Dickinson, Franklin Lakes, NJ) was advanced through the left external jugular vein and into the right atrium for measurement of right atrial pressures and the drug treatment. Aortic and right atrial pressures were measured with reference to the midchest with high-sensitivity transducers (model 42584-01, Abbott Critical Care Systems, North Chicago, IL). A thermocouple microprobe, 10 cm in length and 0.5 mm in diameter (9030-12-D-34, Columbus Instruments, Columbus, OH), was inserted into the thoracic aorta for measurement of blood temperature. A 3-French PE catheter (model C-PMS-301J, Cook Critical Care, Bloomington, IN) was advanced through the right external jugular vein into the right atrium. A pre-curved guide wire supplied with this catheter was then advanced through the catheter into the right ventricle for inducing ventricular fibrillation (VF) as confirmed by an endocardial electrocardiogram. All catheters were flushed intermittently with saline containing 2.5 IU/ml of crystalline bovine heparin. 2.2. Experimental procedures Mechanical ventilation was established at a tidal volume of 0.65 ml/100 g of body weight and a frequency of 100 breaths/min. The inspired O2 fraction (FIO2 ) was maintained at 0.21. A progressive increase in 60 Hz current to a maximum of 3 mA was delivered to the right ventricular endocardium and current flow was continued for 3 min such as to prevent spontaneous defibrillation. Mechanical ventilation was stopped after onset of VF. 19 Eighteen animals were randomized into two groups. In the “immediate LQ CPR” group (LQ group), precordial compression with a mechanical chest compressor was begun 8 min after onset of VF. LQ chest compression was performed at a rate of 200 compressions per min with 70% of “optimal compression depth”. Ventilation was started and FIO2 was maintained at 0.21. After 5 min of LQ CPR, HQ CPR with hypothermia, a rapid cooling performed externally with the aid of ice packs and an electrical fan, 20 was started for an additional 8 mins prior to defibrillation and FIO2 was switched to 1.0. In the “delayed HQ CPR” group (HQ group), after 13 mins of untreated VF, HQ CPR was initiated and animals were mechanically ventilated with a FIO2 of 1.0 and
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hypothermia was induced. For the “optimal compression depth”, the HQ precordial compression depth at maximal compression was approximately 30% of the anteroposterior chest diameter. 21 Epinephrine (20 μg/kg) was administered following 5 mins of HQ CPR. Resuscitation was attempted with up to 3 two (2) joule countershocks after 8 mins of HQ CPR. ROSC was defined as the return of supraventricular rhythm with a mean aortic pressure of 50 mm Hg for a minimum of 5 mins (Fig. 1). 22,23 For the hypothermic treatment, upon reaching the target cooling temperature of 32°C ± 0.2 at ROSC, temperature was maintained with the aid of Blanketrol II (CSZ, Cincinnati, OH) until 4 hours after ROSC. After a 4-hour observation, body temperature was gradually increased over 2 hours with a heating lamp to 37°C ± 0.2. Following ROSC, mechanical ventilation was continued with 100% inspired oxygen for 1 hour and then maintained at 21% inspired oxygen for the following 3 hours. Animals were then allowed to recover from anesthesia. All catheters, including the endotracheal tube were then removed. The animals were continuously observed by the investigators for an additional 2 hours. Butorphanol (0.4 mg/kg) was injected intramuscularly if discomfort was identified. The status of the animals was then evaluated at 4-hour intervals by the investigators for a total of 72 hours. Levels of consciousness, brain stem function and overall performance were observed and scored according to the method of Hendrickx et al. 24 (neurological deficit score (NDS) ranged from: normal = 0 to coma = 500). The animals were euthanized by intraperitoneal injection of pentobarbital (150 mg/kg) after 72 hours. At autopsy, organs were inspected for gross abnormalities, including evidence of traumatic injuries consequent to cannulation or precordial compression. 2.3. Measurements Aortic and right-atrial pressures, electrocardiographic tracings, and EtCO2 were continuously recorded on a PC-based dataacquisition system supported by WIND AQ software (DataQ, Akron, OH). Coronary perfusion pressure (CPP) was calculated as the difference between decompression diastolic aortic and time-coincident right-atrial pressure measured at the end of each min of precordial compression. Baseline and hourly interval measurements after ROSC of echocardiographic cardiac output (CO) and ejection fraction (EF) were obtained with a Philips ultrasound system, utilizing a 12.5-Hz transducer (HD 11 XE, Philips Ultrasound, Bothell, WA). EF served as an indicator of myocardial contractility. Blood gas measurements of arterial oxygen partial pressure (PO2 ), CO2 partial pressure (PCO2 ), pH, and lactate were made from 0.2 ml samples at each time point. 3. Results Baseline haemodynamics were not significantly different between the two groups (Table 1), nor was there any between the two groups regarding the duration of HQ CPR (Table 2). Seven of 9 animals were resuscitated in the HQ group and all animals were resuscitated in the LQ group. Animals survived longer in the LQ group than those in the HQ group (p < 0.05, Table 2). CPP and ETCO2 were significantly lower during LQ CPR than
Fig. 1. The experimental procedure. BL = baseline; CA = cardiac arrest; PR = postresuscitation.
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Table 1 Variables at baseline between two groups. Group
Weight (g)
Heart rate (beats/min)
MAP (mm Hg)
RAP (mm Hg)
ETCO2 (mm Hg)
HQ (n = 9) LQ (n = 9)
515 ± 10 516 ± 4
357 ± 24 354 ± 25
137 ± 6 139 ± 8
0.2 ± 0.4 0.4 ± 0.5
42 ± 7 43 ± 6
Table 2 Variables of resuscitation between groups.
Duration of high-quality CPR (s) Survival time (h) Resuscitated animals (n)
HQ
LQ
469 ± 23 5.5 (2.5, 18) 7/9
476 ± 43 18 (12, 51)* 9/9
*p < 0.05 vs HQ group.
during HQ CPR (6 ± 1 and 5 ± 2 mm Hg vs 23 ± 2 and 14 ± 6 mm Hg, p < 0.001). There were no differences at baseline in blood gas between two groups. pH was lower in the HQ group than LQ group at VF 12 min (7.36 ± 0.05 vs 7.49 ± 0.08, p <0.01) and PR 240 min (7.29 ± 0.08 vs 7.37 ± 0.04, p < 0.05). There were no differences in PO2 and PCO2 at PR 240 min. However, lactate was higher in the HQ group at PR 240 min than that of the LQ group (2.99 ± 2.51 vs 0.97 ± 0.32, p < 0.05, Table 3). Myocardial function was significantly impaired after resuscitation from cardiac arrest in both groups. However, at PR 240 mins, EF and CO were higher in the LQ group than those of HQ group (57 ± 10 and 103 ± 26 vs 45 ± 9 and 69 ± 21, p < 0.05, Fig. 2). 4. Discussion The present study demonstrated that with immediate LQ CPR followed by delayed HQ CPR, all animals were successfully resuscitated while only 7 of 9 animals were resuscitated in the delayed HQ CPR group. Cardiac function, including EF and CO was impaired more severely in the delayed HQ group than those in the early LQ group. Consequently survival time was shorter in the HQ group than in the LQ group. Successful treatment of VF becomes increasingly more difficult when the duration of VF exceeds 5 min. When performed immediately after prolonged VF of cardiac arrest, bystander CPR provides a small but critical amount of blood flow to the heart and brain so that it can double or triple the victim’s chance of survival. 25 –27 In the present study, we simulated bystander initiated LQ CPR for 5 mins followed by professional HQ CPR. The delayed HQ CPR did not show benefits in the outcome of cardiac arrest. Optimal chest compressions appear to be the most important factor accounting for the quality of CPR, both in human and animal
Fig. 2. Comparison of ejection fraction and cardiac output between the two groups. *p < 0.05 vs HQ group.
studies. 7,28 However, in the Wik et al. study on 176 victims of out-of-hospital cardiac arrest, 10 only 28% of rescuers performed competent chest compressions, in which the anteroposterior diameter was decreased by approximately 5 cm, according to the international guidelines. Abella et al. 29 also observed inadequate depth of chest compressions based on 67 instances of in-hospital cardiac arrest. In the present study, HQ precordial compression depth was approximately 30% of the anteroposterior chest diameter, 21 while LQ chest compression was defined as precordial compression depth of approximately 70% of the “optimal compression depth”. As expected, CPP generated by LQ compression was significantly lower than that achieved during HQ chest compression. Nevertheless, when LQ chest compression was performed at the onset of CPR followed by HQ CPR, all the animals were succesfully resuscitated and 3 of them survived for more than 24 hours. Seven of 9 animals were resuscitated in the group in which no CPR was performed prior to HQ CPR and none of them survived more than 24 hours. Both ventilations and compressions are important for victims of prolonged VF cardiac arrest. With oxygen deprivation for a long interval, tissue hypoxia will persist until restoration of effective spontaneous perfusion. Tissue hypoxia leads to anaerobic metabolism and metabolic acidosis. In an earlier pig study, CPR without assisted ventilation resulted in profound hypoxemia and respiratory acidosis. 30 In the present study, after 8 mins of untreated cardiac arrest, ventilation was started during LQ chest
Table 3 Comparison of blopd gases variables between the two groups. BL***
VF12
HQPC7
PR5
PR60
PR240
pH HQ LQ
7.46 ± 0.03 7.47 ± 0.01
7.36 ± 0.05 7.49 ± 0.08**
7.06 ± 0.13 7.11 ± 0.11
7.02 ± 0.08 7.07 ± 0.11
7.21 ± 0.08 7.28 ± 0.09
7.29 ± 0.08 7.37 ± 0.04
PO2 (mm Hg) HQ LQ
81 ± 9 83 ± 6
46 ± 5 50 ± 7
55 ± 14 81 ± 39
133 ± 93 143 ± 86
314 ± 73 328 ± 58
99 ± 14 103 ± 7
PCO2 (mm Hg) HQ LQ
35 ± 7 35 ± 4
44 ± 7 23 ± 8**
55 ± 24 53 ± 30
43 ± 7 50_23
33 ± 5 35 ± 4
24 ± 6 27 ± 5
LAC (mmol/l) HQ LQ
0.51 ± 0.17 0.48 ± 0.05
2.47 ± 0.71 3.42 ± 0.73*
7.64 ± 2.59 9.32 ± 1.29
10.65 ± 1.34 10.37 ± 1.31
5.29 ± 1.51 3.07 ± 1.41
2.99 ± 2.51 0.97 ± 0.32*
***Baseline ventilation with 21% oxygen. *p < 0.05, **p < 0.01 vs HQ group.
F. Song et al. / Resuscitation 82S (2011) S52–S55
compression with a FIO2 of 0.21. After 5 mins of LQ CPR with 0.21 of FIO2 or 13 mins of VF, animals in both groups were ventilated with 100% oxygen. At PR 240 mins, animals in the HQ group showed higher lactate and lower pH in blood than those in the LQ group. Therefore, survival time was longer in the LQ group compared with that of the HQ group. Postresuscitation myocardial dysfunction has been recognized as one of the leading causes of the high postresuscitation mortality rate. With the initiation of LQ CPR or with a delayed HQ CPR, the heart is not adequately perfused for a prolonged period. This accounts for increased severity of myocardial ischemia and leads to the condition of “stone heart”. In the present study, postresuscitation myocardial function was impaired in both groups. However, it was better in the LQ group than in the HQ group. Long-term survival was not improved, most probably due to the long intervals of cardiac arrest. We acknowledge several limitations of the present study. Although 3 of the animals in the LQ group survived more than 24 hours, the neurological outcomes were not compared between the two groups because all of the animals died within 24 hours following resuscitation in the HQ group. Additionally, we did not measure indicators of multi-organ dysfunction. In fact, with this setting, with a total of 21 mins of ischemia (including cardiac arrest and CPR), though all of the animals in the LQ group and 7 of 9 in the HQ group were resuscitated, survival was poor which might have been the result of multi-organ dysfunction. More studies need to be performed to answer these questions.
7.
8.
9.
10. 11. 12. 13.
14. 15.
16.
17.
18. 19.
5. Conclusion Performing immediate LQ CPR without delay for HQ CPR was preferable in this rat model of cardiac arrest and resuscitation.
20.
21.
Acknowledgement 22.
This study was supported by the Weil Institute of Critical Care Medicine, Rancho Mirage, CA. 23.
Conflict of interest 24.
The authors have no conflicts of interest to disclose in this study. 25.
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