Echocardiographic comparison of cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) versus chest compression

Resuscitation 66 (2005) 91–97

Echocardiographic comparison of cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) versus chest compression夽 Guillermo Nava, Jose A. Adams ∗ , Jorge Bassuk, Dongmei Wu, Paul Kurlansky, Gervasio A Lamas Divisions of Cardiology, Neonatology, Department of Research, Mount Sinai Medical Center, Miami Heart Research Institute, 4300 Alton Road, Miami Beach, FL 33140, USA Received 27 August 2004; received in revised form 29 November 2004; accepted 29 November 2004

Abstract Objective: This investigation compared the effects of conventional cardiopulmonary resuscitation (CPR) using an automated ThumperTM chest compression device to periodic acceleration CPR (pGz-CPR) on early post-resuscitation ventricular function assessed by echocardiography, in an adult pig model of CPR. Background: Whole body periodic acceleration along the spinal axis (pGz) is a new method of cardiopulmonary resuscitation (CPR). Biomechanical forces and biochemical release produced by pGz impart ventilation and increase blood flow. Our laboratory has reported normal neurological and cardiovascular function 48 h after return of spontaneous circulation in animals that have undergone 22 min of pGz-CPR. Methods: Ventricular fibrillation (VF) was induced in 16 animals (25–35 kg). After 3 min of non-interventional period, the animals were randomized to receive either pGz-CPR or Thumper-CPR for 15 min. After 18 min of VF, a single dose of vasopressin and bicarbonate were administered and defibrillation attempted. An echocardiogram was performed at baseline and serially for 6 h. Ejection fraction (EF), fractional shortening (FS) and wall motion were assessed by 2D and M-mode echocardiography. Results: Return of spontaneous circulation to 360 min occurred in 5/8 (62%) of the animals receiving Thumper-CPR and in 7/8 (88%) receiving pGz-CPR. FS and EF were impaired after CPR, but pGz-CPR animals had less impairment than Thumper-CPR animals. Further, wall motion score index (WMSI) was more impaired after Thumper-CPR and remained as such even 6 h post-CPR. Conclusion: pGz holds promise as a new method for CPR with better left ventricular (LV) function post-CPR than the more traditional chest compression method. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Cardiopulmonary resuscitation; Periodic acceleration; Post-resuscitation myocardial dysfunction; Echocardiography; Nitric oxide; Prostaglandins

1. Introduction Post-resuscitation myocardial stunning is a well-known phenomenon that occurs after cardiopulmonary resuscitation [13,18,20,21,27]. Short term, total or near total reduction of coronary blood flow with reestablishment of coronary blood flow and subsequent left ventricular dysfunction form the basis of transient myocardial depression, or my夽 A Spanish and Portuguese translated version of the Abstract and Key-

words of this article appears at 10.1016/j.resuscitation.2004.11.029. ∗ Corresponding author. Tel.: +1 305 674 2727; fax: +1 305 674 2306. E-mail address: [email protected] (J.A. Adams). 0300-9572/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2004.11.029

ocardial stunning. Thus, a method of CPR that can ameliorate or reduce post-CPR stunning could have clinical application. Periodic acceleration (pGz) is a new method of CPR which supports ventilation, and blood flow during cardiac arrest [2,4,7]. It is performed by a motion platform which moves the body head-ward to foot-ward, and back. The forces imparted by this movement are quantitated along the spinal axis (z-plane). These acceleration–deceleration forces generate changes in intrathoracic pressure and mechanical motion of the diaphragm producing a net forward movement of blood flow [3,5,6]. Additionally the imparted Gz forces also impose pulsatile shear stress on the vascular endothelium,

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stimulating release of endothelial derived nitric oxide and prostaglandins, among some of the known products [1,7]. We reported previously hemodynamic and survival data using periodic acceleration (pGz) cardiopulmonary resuscitation (pGz-CPR) in juvenile and adult pigs [2,4,7]. Additionally, we have compared this technique for resuscitation to chest compression using a standard automated chest compression device and showed that adult pigs undergoing pGzCPR have a significantly better rate of return of spontaneous circulation (ROSC) and less hemodynamic instability postresuscitation, compared to animals undergoing automated chest compressions [2]. The purpose of the present study was to measure short-term changes in myocardial function following resuscitation from VF cardiac arrest using Thumper chest compression compared with pGz-CPR.

Three sets of electrodes were placed on the animal’s chest. A bipolar fibrillating electrode was placed subcutaneously across the apex of the heart for the delivery of 30 V of ac current at 60 Hz to induce ventricular fibrillation, a standard 3 lead ECG 3 was placed on the chest to monitor ECG, and a pair of defibrillating electrodes (Fast Patch® Plus, PhysioControl, Corp., Redmond, WA) was placed across the chest for defibrillation by connecting the electrodes to a LifePak 8 Defibrillator (Physio-Control Corp., Redmond, WA). Periodic acceleration (pGz) was delivered by supporting the animal on the oscillating motion platform in the supine position. During pGz, platform acceleration was measured with an accelerometer. All animals were paralyzed with pancuronium bromide (0.1 mg/kg). During pGz, animals received a bias flow of 100% O2 , and CPAP of 5 cm H2 O to maintain oxygenation and functional residual capacity, respectively.

2. Methods

2.3. Experimental design

This study complies with the Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research [15].

The experimental design and time line in this series is depicted in Fig. 1. Sixteen adult pigs were used for this study. Ventricular fibrillation was induced and after a 3 min non-intervention period, the animals were randomized to the following groups prior to induction of VF: (a) periodic acceleration (pGz-CPR) (n = 8) and (b) closed chest massage (Thumper-CPR) (n = 8) was accomplished with a TM pneumatic piston device (Thumper , Michigan Instrument, Grand Rapids, MI). pGz was performed as previously described at a frequency of 2 cycles/sec and ± 0.6 Gz (5.9 m/s2 ) [4,7]. All animals received warm intravenous saline during the fibrillation period at a rate of 7 ml/min. Animals in the Thumper-CPR group received chest compression at a rate of 120 min−1 , with a compression ventilation ratio of 5:1. The force of the compression was adjusted to decrease the anterior–posterior diameter of the chest by 25–30% using between 60 and 70 lb/in.2 pressure. After 18 min of ventricular fibrillation, the animals underwent a 3-min period of manual chest wall compressions (about 1 s−1 ) to decompress the engorged ventricles in the pGz group while chest compression with the piston device was continued in the Thumper-CPR [4]. During the decompression phase of the protocol, the following drugs were administered, i.v. vasopressin 1.6 U/kg (Sigma, St. Louis, MO), and sodium bicarbonate 10 mEq. Defibrillation was then initiated by a series of monophasic dc current electroshocks, of 3–6 J/kg until ROSC or a maximum of 15 shocks had been delivered to the pre-placed defibrillating pads by the defibrillator. Inability to achieve ROSC after 15 defibrillating shocks resulted in termination of the experiment. ROSC was defined as an unassisted systolic blood pressure of >50 mmHg for at least 60 min. Animals that achieved ROSC were given additional sodium bicarbonate if required to correct the arterial blood gas data obtained after 15 min of spontaneous circulation. No further pharmacological intervention was given subsequently (Figs. 2 and 3). Echocardiographic studies were performed with HewlettPackard HP Sonos 2000 (Hewlett-Packard/Agilent, Ana-

2.1. Platform design The motion platform that imparts whole body periodic acceleration has been described previously in detail [3,4,6]. Briefly, this platform consists of a linear displacement motor powered by an amplifier (APS Dynamics Inc., Carlsbad, CA, model 400, 12 V) and controlled by a sine wave controller (NIMS, North Bay Village, FL). The table platform is directly driven by the underlying motor and articulates across the frame on stainless steel tracks and nylon wheels. Periodic acceleration is imparted in the spinal axis head-foot at a frequency of 2 cycles/sec, and pGz ± 0.6–0.7 (5.9–6.9 m/s2 ). Details and videos of pGz can be found on http://www.floridaheartresearch.org/pgzmotion. 2.2. Animal preparation All animal studies were approved by the Institutional Animal Care and Use Committee and were in compliance with the Animal Welfare Act. Sixteen adult pigs, weight range of 20–30 kg, were used in this study. The animals were anesthetized with ketamine (10 mg/kg, i.m.) and maintained in a surgical plane of anesthesia with intravenous propofol. An airway was established by direct laryngoscopy and intubation using a 6.0 mm tracheal tube. Intravascular catheters were placed into the femoral artery to measure systemic blood pressure by connecting the fluid filled catheter to a pressure transducer (Transpac® , Abbott Critical Care Systems, North Chicago, IL). A right atrial catheter was placed via the left external jugular vein for administration of fluids and drugs and the measurement of right atrial pressure. Arterial blood gases were measured using a blood gas analyzer (Rapid Lab TM348, Bayer Diagnostics, Tarrytown, NY).

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Fig. 1. Diagram of the experimental protocol involving CPR and ROSC.

heim, using a 2.5 mHz transthoracic transducer, at baseline and serially at 10, 30, 60, 120, 240 and 360 min postresuscitation. Images were obtained in long- and short-axis parasternal views with 2D and M-mode modalities. Analyses of the echocardiographic studies were performed unblinded. Ejection fraction (EF) was obtained by the modified Simpson’s method and fractional shortening (FS) measured from the short axis at the level of the papillary muscles. Mmode tracings, acquired from the parasternal long-axis plane, were used to measure systolic and diastolic left ventricular chamber diameter and posterior wall and interventricular septal thickness. Wall motion was assessed by the wall motion score index (WMSI) that was obtained by the sum of wall motion scores divided the number of visualized segments. In this scoring system, higher scores indicate more severe wall motion abnormalities (1 = normal, 2 = hypokinesis, 3 = akinesis, 4 = dyskinesis, 5 = aneurysm) [11,12,22,24]. All animals were monitored continuously for 6 h after ROSC, and were subjected to euthanasia at the end of this time period and an autopsy performed.

for repeated measures. Differences in sample means were considered statistically significant if p < 0.05. Non parametric data were analyzed using the Mann–Whitney U-test and Kruskal–Wallis ANOVA. Data are expressed as mean (S.D.). The data was analyzed using Statisca Software (Statsoft, Tulsa, OK).

3. Results Defibrillation and return of spontaneous circulation occurred in seven of the eight animals in the pGz-CPR group (88%), compared to five of the eight (63%) in the ThumperCPR group. There were significant decreases in PaO2 in all animals compared to baseline levels during CPR (Table 1). Total energy for used for successful defibrillation was 2250 ± 560 and 2100 ± 700 J for pGz-CPR and ThumperCPR, respectively. After ROSC, none of the animals received vasopressors or antiarrhythmics. Autopsy showed that three of the eight animals (38%) in the Thumper-CPR had a rib fractures whereas none of the pGz-CPR animals had rib fractures.

2.4. Data analysis 3.1. Echocardiographic results Comparison between the two groups on normally distributed data was performed using t-test for independent samples. Continuous, normally distributed data were analyzed using analysis of variance with Bonferroni’s post-test

FS and EF were significantly impaired after CPR, more so in Thumper-CPR group than pGz-CPR group. FS at baseline for Thumper-CPR 31.1% (2.7%) and pGz-CPR 30.5%

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Fig. 3. Representative echocardiographic images at of the left ventricular area, volume calculation and ejection fraction calculation at 120 min after ROSC in pGz-CPR (panel A) and Thumper-CPR (panel B). Fig. 2. Graphic representation of echocardiographic data. All data are significantly different from baseline (BL) values (p < 0.05). * pGz-CPR vs. Thumper-CPR (p < 0.05).

4. Discussion

(3.5%). Six hours after ROSC FS was most impaired in the Thumper-CPR compared to pGz-CPR [10% (1.5%) versus 16.8% (3.2%) (p < 0.05)]. EF was impaired 6 h after ROSC [26.5% (10.3%) versus 40% (5%) (p < 0.05)] in the Thumperand pGz-CPR group, respectively. Further, wall motion score index (WMSI) was also more impaired after Thumper-CPR compared to pGz-CPR and remained so even after 6 h postCPR [1.7 (0.18) versus 2.3 (0.47) (p < 0.05)] (Table 2). Mitral regurgitation was detected by color Doppler in five animals in each group after ROSC.

The present study demonstrates that pGz-CPR is associated with less early post-resuscitation myocardial dysfunction, as indicated by better ejection fraction, less wall motion abnormalities, and greater fractional shortening than does closed chest compression CPR achieved with a Thumper. Like other investigators, we found that Thumper-CPR produced a significant decrease in left ventricular ejection fraction post-CPR [8,20]. Further, in the current study, wall motion abnormalities and fractional shortening were also impaired after Thumper-CPR. The wall motion abnormalities persisted for at least 6 h post-resuscitation.

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Table 1 Arterial blood gases Condition

Blood pH

PaCO2 (mmHg)

PaO2 (mmHg)

Serum HCO3 (mequiv./dl)

pGz-CPR

Thumper-CPR

pGz-CPR

Thumper-CPR

PGz-CPR

Thumper-CPR

PGz-CPR

Thumper-CPR

BL

7.43 (0.05)

7.43 (0.05)

36.7 (3.7)

36.2 (5.1)

512 (82)

539 (57)

24 (2)

24 (4)

VF 5 min 15 min

7.48 (0.06) 7.47 (0.12)

7.54 (0.12) 7.42 (0.14)

30.4 (7.3) 29.4 (7.8)a

23.7 (7.7)a 25.5 (5.7)a

357 (167)a 375 (113)a

400 (72)a 315 (143)a

22 (3) 20 (2)

19 (3) 16 (3)

ROSC 15 min 30 min 60 min 90 min 120 min 150 min 180 min 300 min

7.34 (0.08) 7.27 (0.15)a 7.28 (0.11)a 7.26 (0.13)a 7.29 (0.05)a 7.37 (0.08) 7.38 (0.12) 7.45 (0.01)

7.35 (0.15) 7.37 (0.14) 7.21 (0.05)a 7.27 (0.08)a 7.31 (0.01) 7.28 (0.05)a 7.36 (0.01) 7.43 (0.01)

39.9 (6.4)a,b 49.8 (8.2)a,b 38.4 (7) 33.7 (7.2) 35.9 (3.4) 32.0 (7.1) 34.8 (1.5) 40.0 (0.7)

25.4 (4.3)a 31.3 (6.3) 33.2 (6.3) 30.7 (6.1) 27.3(3.6) 29.3 (1.0) 32.5 (6.4) 30.7 (1.0)

294 (152)a 338 (174) 399 (90) 335 (125) 358 (87) 485 (63) 445 (31) 598 (30)

276 (118)a 239 (111)a 361 (92) 437 (79) 436 (66) 392 (136) 410 (116) 416 (100)

21 (6) 20 (6) 17 (4)a 15 (5)a 17 (2)a 18 (2) 19 (2) 21 (2)

14 (3) 19 (9) 13 (3)a 14 (4)a 14 (1)a 17 (4) 15 (1) 20 (2)

BL: baseline values; ROSC: return of spontaneous circulation, at 15–300 min. VF 5 min and VF 15 min, 5 and 15 min of ventricular fibrillation and CPR. Values are given in mean (S.D.). a Significantly different from baseline (BL) (p < 0.05). b pGz-CPR vs. CONV-CPR (p < 0.05).

Post-resuscitation myocardial dysfunction is a wellknown phenomena occurring after successful CPR. The reduction in blood flow produced during VF and CPR produces a “stunned myocardium”. The echocardiographic features of stunned myocardium include reduced fractional shortening and ejection fraction, diffuse wall motion dysfunction, and decreased left ventricular systolic and diastolic function. Investigators have studied post-resuscitation myocardial dysfunction, and have documented both experimental and clinical evidence of its occurrence [19,20,29]. Indeed, while the principal mechanism responsible for post-CPR stunning has not been convincingly identified, various factors have been identified as contributory. Exper-

imental studies have shown that epinephrine, endothelin1 and the combination of buffer therapy and vasoconstrictors significantly worsens post-resuscitation myocardial dysfunction [14,25,28]. Additionally, both high energy defibrillation, monophasic waveform defibrillation, and prolonged resuscitative efforts have also been linked to worsen post-resuscitation myocardial function [26,29]. Thus, postresuscitation myocardial dysfunction is complex, and likely to be multifactorial. With regards to the present experiment, both pGz- and Thumper-CPR groups received a similar amount of sodium bicarbonate and vasopressin and a similar number of defibrillation attempts. Therefore, based on the controlled nature

Table 2 Hemodynamic data Condition

Hr (beats/m)

Mean BP (mmHg)

Mean RAP (mmHg)

Mean driving pressure

pGz-CPR

Thumper-CPR

pGz-CPR

Thumper-CPR

pGz-CPR

Thumper-CPR

pGz-CPR

Thumper-CPR

BL

135 (20)

134 (18)

124 (14)

114 (13)

11 (9)

11 (5)

95 (56)

96 (18)

27 (5)a 25 (5)a

40 (4)a 35 (7)a

16 (5) 14 (3)

28 (7)a 26 (7)a

11 (5)a 10 (5)a

12 (8)a 9 (7)a

74 (16)a 83 (17) 88 (19) 85 (12) 94 (20) 98 (20) 92 (29) 94 (37)

79 (18)a 85 (20) 72 (18) 70 (5) 83 (22) 89 (20) 78 (13) 76 (20)

11 (1) 10 (2) 9 (1) 9 (2) 9 (2) 7 (1) 6 (0.5) 7 (1)

20 (8)a 18 (7) 17 (7) 15 (7) 16 (7) 14 (7) 13 (8) 11 (5)

69 (20) 72 (20) 68 (20) 72 (19) 81 (23) 84 (38) 88 (38) 89 (48)

62 (13) 66 (17) 69 (21) 67 (17) 83 (26) 80 (18) 73 (19) 70 (17)

VF 5 min 15 min ROSC 15 min 30 min 60 min 90 min 120 min 150 min 180 min 300 min

176 (75) 185 (50) 167 (87) 161 (53) 182 (55) 151 (85) 188 (59)a,b 190 (51)a,b

180 (1) 175 (45) 152 (23) 151 (27) 164 (38) 202 (72)a 232 (49)a 267 (52)a

Values are given in mean (S.D.). Driving pressure = BP mean − RAP mean. All pressures and heart rate are expressed as mean (S.D.). BL: baseline values; ROSC: return of spontaneous circulation, at 15–300 min. VF 5 min and VF 15 min, 5 and 15 min of ventricular fibrillation and CPR. a Significantly different from baseline (BL) (p < 0.05). b pGz-CPR vs. Thumper-CPR (p < 0.05).

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of the experiments reported here, we believe that the striking differences observed in post-resuscitation myocardial function relate to the method of CPR. There are several mechanisms whereby pGz might lead to improved LV function. pGz produces pulsatile shear stress on the vascular endothelium with production of endothelial derived nitric oxide, prostaglandin, and prostacyclin [1,7]. Endothelial derived NO and prostaglandins, play a role in the process of preconditioning and hibernation of the myocardium [9,10,16,17,23]. Therefore, pGz-CPR while the heart is arrested might promote a conditioning effect on the myocardium, allowing for decrease metabolic demands. Additionally pGz may lessen the development of a stone heart through mechanical means. The current study is limited by the inability to study echocardiographic evidence of diastolic function due to technical difficulties in obtaining a consistently adequate imaging window using a transthoracic echocardiogram. Transesophageal echocardiography may allow better reproducible imaging for diastolic function assessment. Notwithstanding this technical limitation, data for our Thumper-CPR group is similar to those reported by other investigators using transthoracic and transesophageal echocardiography. Furthermore, we characterized only the early post-resuscitation effects and cannot extrapolate to late outcomes. The current results support our previous study where we showed that animals undergoing pGz-CPR had significantly fewer arrhythmias, less hypotension, and bradycardia compared to a group which had undergone Thumper-CPR [2] The present study expands these findings and examines myocardial function under two methods of CPR. Both left ventricular dysfunction and wall motion abnormalities occur with both methods of CPR but less so for pGz-CPR. These functional differences last for at least 6 h after return of spontaneous circulation. Thus, the method of CPR is important and determines post-arrest LV function. In conclusion, pGz-CPR produces less detrimental postresuscitation myocardial dysfunction than Thumper-CPR This finding requires further investigation to elucidate its mechanism.

Acknowledgements This work was supported by a grant from the Miami Heart Research Institute. We thank Dr. Marvin Sackner for his editorial comments

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