Original Contribution

External cardiac defibrillation during wet-Surface cooling in pigs^B

Alexandra Schratter MD^a, Wolfgang Weihs Mag Vet^a, Michael Holzer MD^a, Andreas Janata MD^a, Wilhelm Behringer MD^a, Udo M. Losert DVM, PhD^b, William J. Ohley PhD^c, Robert B. Schock PhD^d, Fritz Sterz MD^a,*

^aDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria

^bCore Unit for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria

^cDepartment of Electrical and Computer Engineering, University of Rhode Island, Kingston, RI 02881, USA

^dLife Recovery Systems, HD, LLC, Kinnelon, NJ 07405, USA

Received 25 February 2007; accepted 28 February 2007

Abstract

Objective: During surface cooling with ice-cold water, safety and effectiveness of Transthoracic defibrillation was assessed.

Methods: In a pig ventricular fibrillation cardiac arrest model, once (n = 6), defibrillation was done first in a dry and then in a wet condition using the ThermoSuit System (Life Recovery Systems, HD, LLC, Kinnelon, NJ), which circulates a thin layer of ice-cold water (648C) over the skin surface. Another time (n = 6), defibrillation was done first in a wet and then in a dry condition. Success of defibrillation was defined as restoration of spontaneous circulation, and the current and voltage of the defibrillation signal was measured.

Results: There was a tendency toward less number of shocks needed for achieving restoration of spontaneous circulation in the wet condition as compared with the number of shocks needed in the dry condition. The energy delivered in both dry and wet conditions was 144 F 3 J.

Discussion: Transthoracic defibrillation is safe and effective in a wet condition after cooling with ice- cold water.

D 2007

Introduction

Prior studies have shown that resuscitative Mild hypothermia (approximately 38C to 58C below normal

^B This work was supported by Life Recovery Systems, HD, LLC (Kinnelon, NJ).

* Corresponding author. Tel.: +43 1 40400 1964; fax: +43 1 40400 1965.

E-mail address: [email protected] (F. Sterz).

body temperature) can reduce the level of damage to vital organs, including the brain, after cardiac arrest [1-5]. Conventional noninvasive means that are currently available for cooling include water-filled cooling blankets and cool air-emitting coverings [5,6]. Some investigators have sought to increase the rate of cooling and have developed invasive methods, such as endovascular cool- ing catheters [7-9] and cold saline [8,10] or iced saline slurry injected into the circulatory system [11]. However,

0735-6757/$ - see front matter D 2007 doi:10.1016/j.ajem.2007.02.044

these would be challenging, if not impossible, to implement in the field.

Life Recovery Systems, HD, LLC (Kinnelon, NJ) has developed an advanced surface cooling system, the Thermo- Suit System (TSS), for rapid cooling of the patient. The fundamental approach of using ice water to cool the human body is already known to be rapid [12], and it has been shown to be safe when used in certain surgical applications requiring extended periods of cardiac arrest [12]. The TSS is being developed so that cooling could be efficiently delivered even while the patient is in a state of cardiac arrest or if a converted patient requires defibrillation again while being cooled. The ability to use defibrillation during the use of the TSS would avoid interruption in the cooling of the patient and eliminate the time delay in returning the patient to normal sinus rhythm because of the need to drain the water from the TSS [13].

Therefore, our objective was to prove the safety of performing transthoracic defibrillation in a wet condition during the use of the TSS. We compared the current leakage and defibrillation success in dry and wet conditions after 1 minute of ventricular fibrillation (VF) cardiac arrest.

Methods

Animals in which a sequence of induced VF was followed by defibrillation were prospectively studied. This study was conducted in compliance with the good labora- tory practice regulations set forth in part 58 of title 21 of the United States Code of Federal Regulation. The study was approved by our institutional animal investigation commit- tee. Animal care and use was performed by qualified personnel and supervised by veterinarians. All animal facilities and transportations complied with the current legal requirements and guidelines.

Animal preparation

Female pigs (Large White breed) weighing 28 to 35 kg were obtained from the licensed farm of the University for Veterinary medicine of Vienna, Vienna, Austria (Hochschulgut Medau) and brought to the testing facility

14 days before the experiment. They were given cefquinom sulfate (2 mL) intramuscularly for infection prophylaxis and fasted with free access to water 12 hours before the experiment.

After premedication with intramuscularly administered atropine sulfate (0.5 mg), ketamine hydrochloride (20 mg/ kg), acepromazine maleate (1.75 mg/kg), and piritramide (22.5 mg), sedation was induced with an IV propofol bolus (40 mg). Then, the pigs were intubated and mechanically ventilated (Servo 300, Maquet Critical Care, Solna, Swe- den) with tidal volumes of 10 mL/kg, positive end- expiratory pressure of 5 cm H₂O, Fio₂ of 0.3, and a ratio of inspiration to expiration of 1:2. The respiratory rate was adjusted to achieve a Paco₂ of 35 to 40 mm Hg (4.7 to 5.3 kPa). To maintain anesthesia during preparation, propofol

(20 mg/kg/h) and boluses of piritramide (15 mg IV) were given via a peripheral IV cannula (ear vein, 18 G). Rocuronium (20 mg) was given for Muscle relaxation. Saline (5 mL d kg ^-1 d h^-1) was administered to maintain central venous pressure N3 mm Hg.

Monitoring

Electrocardiogram (ECG) electrodes were attached to the extremities and connected to the ECG monitor. A gastric tube, featured with an esophageal temperature probe (Mon- a-therm General Purpose, 9 F, Mallinckrodt Medical, St Louis, MO) was inserted. The esophageal temperature probe was connected to a data acquisition system (DATAQ Instruments, Akron, Ohio). A Foley catheter with a temperature probe (Ruesch Sensor Ch 12; Ruesch, Kernen, Germany) (Tbl) was inserted for collecting urine.

A catheter was placed by Seldinger technique in the left Brachial artery to monitor mean arterial pressure (MAP) and for blood sampling. A pulmonary artery catheter (Thermo- dilution Paceport Catheter, 7.5 F, Edwards Lifesciences LLC, Irvine, CA) was inserted via the right jugular vein by Seldinger technique for monitoring of pulmonary artery blood temperature and administration of medications and infusions as well as for inserting a pacing wire to induce VF. After insertion of all catheters, heparin (50 IU/kg) was applied to avoid clotting.

The following parameters were monitored continuously: ECG, MAP, central venous pressure, pulmonary artery pressure, tidal volume, respiratory rate, ventilation pressures (peak, mean, and end-expiratory), and all temperatures described previously. Blood gases, electrolytes, hematocrit, lactate, and glucose were measured at selected time points. Baseline blood temperature was taken as a reference temperature and maintained within the reference range for pigs (38.58C F 0.28C) using heating blankets (Warm Air Hyperthermiasystem 134, CSZ Cincinnati Subzero Products, Cincinnati, OH) or fans.

To record voltage and current of the defibrillation signal,

2 Pearson current probes (Pearson Electronics Inc, Palo Alto, Calif) were interposed between defibrillator and automatic external defibrillator (AED) pads (for details, see Supplementary Material).

Test item

The TSS provides highly efficient cooling of the skin by circulating a thin layer of ice-cold water (648C) over most of the skin surface by means of a suit component that conforms to the body and an external water-circulating pump. The TSS was set up before the experiment. The equipment was specially designed for the 30-kg swine model used in this study (Fig. 1).

Experimental protocol

After cardiopulmonary parameters and temperatures were stabilized, 2 baseline measurements were made, and

Fig. 1 Life Recovery Systems (Life Recovery Systems, HD, LLC, Kinnelon, NJ) TSS, an advanced surface cooling system, for the rapid cooling used in the experiments (external water- circulating pump not shown).

a bolus of 40 mg of propofol was administered; VF was initiated electrically by the passage of a 60-Hz alternating current through a catheter to the right ventricular apex. Abrupt reduction of blood pressure and ECG readings confirmed the arrest. Heating devices, IV fluids, and anesthesia were discontinued, and the endotracheal tube was disconnected from the ventilator. Ventricular fibrilla- tion was allowed to persist for 1 minute. Defibrillating shocks were delivered from an AED (Heartstart 4000; Laerdal, Stavanger, Norway), which was determined to deliver biphasic truncated exponential waveform shocks of equal pulse duration and a selected energy of 150 J. The biphasic waveform shocks composed of equal-duration pulses included a negative pulse (4.5 ms/4 ms) and a positive pulse (4.5 ms/4 ms). Defibrillation shocks were

delivered via commercially available self-adhesive moni- tor-defibrillator electrode pads (model M3713A; Philips Medical Systems, Andover, Mass), placed on the shaved chest of the pig. The 2 pads were placed on either side of the chest, just below the upper extremities. After restora- tion of spontaneous circulation (ROSC), the procedure was repeated after 20 minutes.

In a Crossover design, 2 different conditions were chosen to represent conditions that may exist during the use of the TSS system. These were (1) subject dry (n = 6) and (2) subject wet (n = 6) with water contaminated with saline solution. Once, animals received VF in the dry condition first followed by the wet condition. Another time, the animals first had the wet condition and then were dried completely for the dry condition. During TSS application with cooling water, VF was initiated after the core temperature had fallen to 338C F 18C. The sequence of treatment was randomly selected by sealed envelopes after data recording had begun. Randomization of animals to a treatment sequence was performed using a computer- printed randomization schedule. The defibrillation for achieving ROSC in the wet setting was performed while the suit was pumping. The water was drained from the suit as soon as ROSC was achieved. Consequently, 6 experi- ments were performed in a wet condition and 6 in a dry condition. Pigs that underwent wet defibrillation first were carefully dried before the procedure was repeated in the dry condition. Afterwards, pigs were killed with a potassium chloride solution.

Outcome

Defibrillation success was defined as ROSC with a MAP of 50 mm Hg for at least 5 minutes. In addition, the number of defibrillation shocks needed to achieve ROSC was

Fig 2 Example of voltage and current curves of the defibrillation signal in dry and wet conditions (arbitrary values on the y-axis, voltage in volts, and current in amperes).

recorded. Voltage and current of the defibrillation signal were measured. Energy over time was calculated by multiplying the voltage by the current and then, integrated, dividing them by the delivery time of the shock. This resulted in total joules delivered. leakage current, defined as current that could flow from the surface of the human body to the ground and therefore reflects a shock hazard to the rescuer if there is a failure, was estimated by calculation of the area under the curve (AUC) of the energy-time curves during the first shock in both dry and wet conditions. At the end of the experiment, the skin areas under the defibrillation pads were carefully examined for skin lesions and burns. After the animals were killed, a necropsy was performed to exclude severe cardiac or lung diseases that could interfere with defibrillation success.

Table 2 Physiologic variables at baseline and 5 minutes after

ROSC in dry (n = 6) and wet (n = 6) conditions

Baseline 5 min after ROSC

Variables are given as median and the range from the first to the third

quartile.

* P = .03.

** P = .04.

Statistical analysis

Temperature and AUC values were normally distributed and thus reported as mean and SD. Continuous variables not normally distributed are given as median and the range from the first to the third quartile. Heart rate and MAP as well as physiologic parameters at baseline and 5 minutes after ROSC were compared between dry and wet conditions with the Wilcoxon Signed Rank Test using the exact version of the test. The energy AUC between dry and wet conditions was compared with the t test. All calculations were performed with SPSS for Windows, 10.0 (SPSS Inc, Chicago, Ill). P b .05 was considered statistically significant.

Results

Pigs weighed 30.7 F 1.0 kg, and ROSC was achieved in all animals. There was a tendency toward less number of shocks needed for achieving ROSC in the wet condition (1, 1, 1, 1, 1, 2) as compared with the number of shocks needed

in a the dry condition (1, 1, 2, 2, 2, 2). The energy AUC in both dry and wet conditions was 144 F 3 J ( P = .96). This concordance indicates that no appreciable leakage current existed in the wet condition (Fig. 2). The impedance was similar in both dry and wet conditions (Table 1).

Table 1 Transthoracic impedance

Wet condition (n = 6)

Leading-edge

impedance (V)

Trailing-edge impedance (V)

53.2 (46.8-58.8)

Dry condition

(n = 6)

48.6 (47.0-54.0)

53.7 (47.5-104.4)

51.4 (47.2-61.3)

Variables are given as median and the range from the first to the third

quartile. Leading-edge impedance is the value that corresponds to the left edge of the impedance plateau. Trailing-edge impedance is the value that corresponds to the right edge of the impedance plateau.

Heart rate	Wet	110 (97-120)	126 (111-135)
(beats/min)	Dry	116 (113-149)	150 (126-162)*
Mean arterial	Wet	70 (66-72)	65 (48-86)
pressure	Dry	70 (62-86)	63 (54-67)
(mm Hg)
pH	Wet	7.50 (7.46-7.53)	7.43 (7.41-7.45)
	Dry	7.47 (7.45-7.55)	7.38 (7.34-7.42)
Potassium	Wet	4.0 (3.8-4.2)	3.6 (3.2-4.0)
(mmol/L)	Dry	3.7 (3.4-4.3)	4.1 (3.3-4.4)*
Base excess	Wet	3.6 (2.6-4.1)	1.6 (0.6-3.5)
(mEq/L)	Dry	2.5 (1.2-4.4)	-0.3 (-2.0 to 1.3)**
Lactate	Wet	1.5 (1.1-2.3)	2.0 (1.8-2.3)
(mmol/L)	Dry	1.7 (0.9-2.3)	3.5 (2.3-4.4)**

Heart rate was lower in the wet vs dry condition at 5 minutes after ROSC (126 [111-135] vs 150 [126-162] beats per minute, P = .03]. There was no significant difference in the MAP between dry and wet conditions. Potassium and lactate were higher during the dry as compared with the wet condition at 5 minutes after ROSC (4.1 [3.3-4.4] vs 3.6 [3.2- 4.0] mmol/L, P = .03, and 3.5 [2.3-4.4] vs 2.0 [1.8-2.3] mmol/

L, P = .04). Base excess was -0.3 mEq/L (-2.0 to 1.3 mEq/ L) during the dry vs 1.6 mEq/L (0.6-3.5 mEq/L) during the wet condition at 5 minutes after ROSC ( P = .04) (Table 2). Furthermore, no skin lesions or burns were found on the skin areas located underneath the defibrillation pads in particular or elsewhere, and no frostbite was observed. Within the 20-minute postdefibrillation observation peri- od, ventricular tachycardia occurred in 3 pigs at hypo- thermia (53, 349, and 30 seconds) and in 2 pigs at normothermia (3 seconds each). However, these tachycar- dia periods did not affect the hemodynamic stability and did not have to be treated either pharmacologically or

electrically (Table 2).

Discussion

External cardiac defibrillation from VF with an AED is safe and effective in a wet-surface cooling setting. Defibril- lation success was defined as ROSC, which could be achieved in all included animals. In the dry condition, 2 pigs achieved ROSC after 1 shock and 4 pigs after 2 shocks. In the wet condition, 5 pigs achieved ROSC after 1 shock and 1 pig after 2 shocks. The approach performed seems to be safe for personnel using this device.

The safety of external cardiac defibrillation with an AED in a wet condition has already been assessed [14].

However, the study of Lyster et al [14] focused only on the safety for the bystanders and did not use large ani- mals in conditions after cardiac arrest. Similarly, we did not observe any appreciable leakage current in the wet condition because the energy AUC did not differ between dry and wet settings.

There appears to be a tendency that with a drop in core temperature, the defibrillation success increases. In fact, this assumption has already been investigated [15,16]. In these studies, the beneficial effect of hypothermia on defibrillation success could be shown.

Since the beneficial effects of therapeutic hypothermia after cardiac arrest have been shown in multiple studies [17], various cooling methods, including surface cooling devices, have become an important issue to emergency and intensive care units. Especially for the handling of surface cooling devices using freely Circulating water, such as the TSS, it is fundamental to guarantee the safety for the attending personnel and patient. Furthermore, the possibility of defibrillating effectively in a wet condition is very important in case a successfully resuscitated patient requires defibrillation again while being cooled. This study suggests that no risks result from the use of an AED during surface cooling with contaminated ice water.

The more frequent and prolonged durations of ventricular tachycardia, higher heart rates, lower Potassium levels, and less lactate acidosis within the 20-minute postdefibrillation observation period observed after wet conditions could be explained by the Physiologic effects of cooling. However, these tachycardia periods seemed not to have significantly affected the experiments during the observation period, such as in the alterations of the laboratory results, which were within clinical tolerable ranges (Table 2).

A limitation of our study could be the small sample size and its crossover design because of the possible interference of the first 1-minute cardiac and respiratory arrest event on outcome of the second arrest event in the same subject. Even so, we think that it is justified to draw the conclusions, especially with regard to the safety and efficacy of defibrillation in a wet condition, because this design equally allows both conditions to follow each other 6 times.

Transthoracic defibrillation via AED pads is safe and effective in a wet condition after cooling with ice-cold water in a pig VF cardiac arrest model because ROSC could be achieved in all animals. Thus, this new cooling device needs further exploration in cases of cardiac arrest in humans.

Appendix A. Supplementary material

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ajem.2007. 02.044.

Acknowledgments

The authors gratefully acknowledge the help of all the laboratory technicians and nurses of the Core Center of Biomedical Research, Vienna, Austria.

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