American Journal of Emergency Medicine (2011) 29, 1141-1146

Brief Report

A novel hands-free carotid ultrasound detects low-flow cardiac output in a swine model of pulseless electrical

activity arrest^?,??,?

Todd M. Larabee MD ^a,?, Charles M. Little DO ^a, Balasundar I. Raju PhD ^b, Eric Cohen-Solal PhD ^b, Ramon Erkamp PhD ^b, Scott Wuthrich MSE ^c,

John Petruzzello ^b, Michael Nakagawa MSE ^c, Shervin Ayati MSE ^c

^aDepartment of Emergency Medicine, University of Colorado Denver School of Medicine, Denver, CO 80045, USA

^bPhilips Research, Briarcliff Manor, NY 10510, USA

^cPhilips Medical Systems, Andover, MA 01810, USA

Received 13 November 2009; revised 6 May 2010; accepted 24 May 2010

Abstract

Objective: To determine if a hands-free, noninvasive Doppler Ultrasound device can reliably detect low- flow cardiac output by measuring carotid artery blood flow velocities. We compared the ability of observers to detect carotid artery flow velocity differences between pseudo-Pulseless electrical activity and true-PEA cardiac arrest.

Methods: Five swine were instrumented with aortic (Ao) and right atrial pressure-transducing catheters. The Doppler ultrasound device was adhered to the neck over the carotid artery. Continuous electrocardiogram, pressure readings, and Doppler signal were recorded. Each swine underwent multiple episodes of fibrillation and resuscitation. Episodes of true-PEA and pseudo-PEA were retrospectively identified from all resuscitation attempts by examination of electrocardiogram and Ao waveforms. The sensitivity and specificity of the device to detect pseudo-PEA was obtained using observers blinded to Ao waveform recordings.

Results: There was good interobserver reliability related to identification of pseudo- and true-PEA (? = 0.873). The observers blinded to Ao waveform recordings agreed on 8 of the 9 episodes of pseudo-PEA, whereas 4 false positives of 26 true-PEA events were reported (sensitivity, 0.89; specificity, 0.85). The Doppler device was able to detect carotid flow velocity over a wide range of Ao blood pressures.

Conclusions: This hands-free, noninvasive Doppler ultrasound device can reliably differentiate pseudo- PEA from true-PEA during resuscitation from cardiac arrest, detecting pressure gradient changes of less than 5 mm Hg through to normotension. This device distinguishes conditions of no cardiac output from

^? Financial support: This work was supported by Philips Medical Systems, Andover, Mass.

^?? Presented as an abstract at the American Heart Association Resuscitation Sciences Symposium, Chicago, Ill, November, 2006 [Circulation

(supplement) 2006. 114(18): II-1207].

^? Conflict of interest statement: This study was funded by Philips Medical Systems. Dr Larabee and Dr Little received financial support for the performance of this study and have no financial interest in the device. All other investigators are employed by Philips Medical Systems.

* Corresponding author. Tel.: +1 720 848 6777; fax: +1 720 848 7374.

E-mail address: [email protected] (T.M. Larabee).

0735-6757/$ – see front matter (C) 2011 doi:10.1016/j.ajem.2010.05.013

low cardiac output and may have applications for use during resuscitation from various etiologies of arrest and shock.

(C) 2011

Introduction

The ability of clinicians to easily detect conditions of low cardiac output during resuscitation from cardiac arrest, or severe hypotension in conditions such as sepsis, remains elusive. Bedside cardiac ultrasound is generally required to detect Cardiac activity for these conditions in the emergency department, but this technology is not readily available in the prehospital arena, in clinics, or even some intensive care units. Invasive monitoring may be needed to determine if cardiac wall motion seen on a bedside cardiac ultrasound corresponds to any measurable cardiac output [1,2]. The placement of central arterial and venous catheters to obtain central blood flow measurements requires time and skilled manpower, both of which may be limited during resuscita- tion efforts.

With these considerations, the development of a nonin- vasive, hands-free device that could easily detect blood flow was undertaken. Past work has documented the initial engineering and development of such a device using Doppler ultrasound technology that measures carotid blood flow velocity (Fig. 1) [3-5]. Once applied to the surface of the neck, the device is left in place, and continuous waveform data is displayed on a monitor. This allows the clinician to concentrate on other aspects of the resuscitation such as Advanced cardiac life support algorithms or central line placement while having an easily visualized waveform that represents carotid blood flow velocity.

Recent literature has documented the increasing preva- lence of PEA arrest presenting to Emergency Departments [6,7]. As a model to test the hands-free Doppler device, PEA arrest would work well as it is not a homogenous clinical

Fig. 1 Prototype carotid Doppler ultrasound device.

entity and it is reproducible in the laboratory. During PEA arrest, associated blood pressures may range from completely absent without cardiac wall motion (true-PEA) through states of extreme hypotension without clinically detectable pulses but with cardiac mechanical activity (pseudo-PEA) [8]. These diverse clinical states often remain undifferentiated during resuscitation efforts. Some studies have found that a large percentage of the patients who present in PEA are actually in pseudo-PEA, with blood pressures and pulses undetectable by routine clinical exam [1,2,8]. The ability to differentiate conditions of low flow cardiac output from no cardiac output would be increasingly important if recognition of this difference was associated with a Survival benefit. There are no studies to date that specifically address a survival difference in true- and pseudo-PEA.

The purpose of this study was to determine if the hands- free, noninvasive Doppler ultrasound device could reliably differentiate the heterogeneous clinical conditions of true- PEA and pseudo-PEA using a post-countershock swine model of PEA cardiac arrest. This PEA arrest model was chosen as it is well described in the literature and reliably generates conditions of PEA arrest [9-12]. It was unclear what percentage of the post-countershock PEA would actually be pseudo-PEA when examining the previously published papers. If successful, the use of the device could be extrapolated to a wide variety of clinical scenarios, including all forms of cardiac arrest, sepsis, and other causes of severe clinical shock.

Methods

The animal protocol was reviewed and approved by the Institutional Animal Care And Use Committee of the University of Colorado Denver School of Medicine. Five immature mixed-breed, mixed-sex swine weighing 35 to 50 kg were used. Animals were housed in accordance with Institutional Animal Care And Use Committee/Center for Laboratory Animal Care policy. Animals were sedated using ketamine (15 mg/kg) and acepromazine (0.2 mg/kg). The animals were induced with isoflurane 5%, oxygen 100%, endotracheally intubated and placed under general anesthesia using 2% to 3% isoflurane, 100% O₂ and a volume-controlled ventilator (Draeger Medical, Inc., Telford PA, Model EV-A). The animals were ventilated with a tidal volume of 10 mL/kg and a respiratory rate of 12 to 14 breaths per minute. End-tidal CO₂ (ET-CO₂) was continuously monitored and minute ventilation was adjusted to maintain eucapnia. Appropriate baseline ventilation was confirmed by arterial blood gas analysis. Isoflurane was adjusted to maintain an adequate

plane of surgical anesthesia as assessed by blood pressure and pulse rate.

The animals were instrumented with a microprocessor- tipped pressure-transducing catheter (Millar Instruments, Houston, Tex, Model SPC-450) placed into the descending aorta above the diaphragm via surgical cutdown of a femoral artery. A right atrial pressure-transducing catheter (Millar Instruments, Model SPC-450) was placed either through a surgical cutdown of the external jugular vein or the femoral vein. Correct placement was confirmed by linear measure- ment and appropriate pressure waveform. A rectal temper- ature probe was placed and the animals were kept euthermic with a warming blanket. unfractionated heparin (100 U/kg) was given to prevent catheter clotting. Pancuronium (0.1 mg/kg) was given just before defibrillation to prevent gasping during cardiopulmonary resuscitation (CPR) only after confirmation of adequate depth of anesthesia. Continuous 3-lead electrocardiogram (ECG), aortic pressures (AOP), right atrial pressures, calculated coronary perfusion pressure and temperature were recorded using a computerized software program (Chart 5, Powerlab, AD Instruments, Sydney, Australia) and saved to disc at 400 Hz. The Doppler device was adhered to the neck over the carotid artery and positioned to obtain maximal signal. Carotid Doppler signal was digitized at 20 kHz using Labview software (National Instruments, Model 6036E) and saved continuously to disc. Ventricular fibrillation (VF) was induced using a bipolar pacing catheter placed in the right ventricle via the Central venous line. Once VF was induced, the pacing catheter was removed. No-flow VF was maintained for 1 minute, after which standard ACLS protocols, including electrical defibrillation, were used to resuscitate the animal. After the animal was resuscitated, and after a 15-minute recovery period, VF was again induced in the same animal with progressively longer No-flow time periods of VF before resuscitation efforts. Each animal underwent several Resuscitative efforts before termination of the experiment

and euthanasia.

The ECG tracings were examined by a non-blinded researcher (TL) for episodes of post-countershock orga- nized electrical activity. These epochs were identified and the corresponding aortic wave forms with systolic blood pressures of less than 60 mmHg were further reviewed. Aortic wave forms were divided into true-PEA, defined as aortic systolic pressure waveforms of b5 mm Hg to accommodate potential error in the Millar catheter and Doppler device, or pseudo-PEA, with corresponding Ao waveforms of greater than 5mmHg or less than 60mmHg. The ECG and carotid Doppler signals from these time periods were then randomly analyzed for deflections by two investigators (BR, ECS). These observers were specifically blinded to the Ao blood pressure recordings. Both of the blinded investigators (BR, ECS) were involved in the design and engineering of the Doppler device and were familiar with the appearance of a positive Doppler waveform.

Fig. 2 Post-defibrillation pseudo-PEA with ECG, AOP, and Doppler Signals.

The sensitivity and specificity of the blinded investigators to detect pseudo-PEA and true-PEA using the carotid Doppler ultrasound device were calculated. SPSS statistical software (SPSS, Inc, Chicago, Ill) and Stata statistical software (StataCorp LP, College Station, Tex) was used in the data analysis.

Results

There were 9 episodes of post-resuscitation pseudo-PEA retrospectively identified among 3 of the 5 animals (Fig. 2). There were 26 episodes of post-resuscitation true-PEA identified that occurred among all 5 animals (Fig. 3). Pseudo-PEA accounted for 26% of the post-countershock PEA arrest rhythms. The aortic systolic blood pressures of the

Fig. 3 Post-defibrillation true-PEA with ECG signal but absent AOP and Doppler signals.

Fig. 4 Low-flow Doppler signal from isolated atrial activity.

animals with pseudo-PEA ranged from 16 to 27 mmHg. The blinded observers both recognized 8 of the 9 episodes of pseudo-PEA (89%) and 22 of 26 true-PEA episodes (85%). There was good interobserver reliability related to the findings of pseudo- and true-PEA (? = 0.873). For the one episode of pseudo-PEA that was not agreed upon, the event was scored as a false negative. There were 4 false positives of carotid blood flow velocity in the 26 true-PEA events identified by the observers. Review of these episodes demonstrated that the device recorded changes in Pulse pressure of 1.5 to 3 mmHg from baseline, thus creating a

positive Doppler deflection. These false-positive pressure values were below the limit for defining pseudo-PEA (b5 mm Hg) as identified by the non-blinded observer but did retrospectively appear to create a reliable Doppler signal. Two of the false positives corresponded to ECG rhythms that appeared to be isolated atrial activity without associated ventricular contractions (Fig. 4). The other 2 false positives had ECG rhythms corresponding to third degree heart block. The overall sensitivity of the device to detect carotid artery blood flow velocity was 89% (95% CI, 52%-100%), with a specificity of 0.85 (95% CI: 65%-96%) using these observers. During the experiments, there were several instances when return of spontaneous circulation (ROSC) was achieved after CPR was performed. Fig. 5 is a representative recording of ROSC after CPR, demonstrating the range of aortic pressures detectable during resuscitation using the Doppler ultrasound device and the Doppler signal achieved

by performing CPR alone.

Discussion

The ability to accurately quantitate conditions of blood flow during resuscitation from cardiac arrest without the use of invasive monitoring devices remains elusive. Past studies have demonstrated that the ability to successfully resuscitate an individual from cardiac arrest decreases with time and with increasing periods of no-flow [13-16]. It would be useful to have a noninvasive means to measure blood flow that provides immediate blood flow feedback during resuscitation efforts in order to guide therapy.

Fig. 5 Doppler signal detection range during CPR and after ROSC.

In the laboratory and in humans, one comparative measurement that can predict successful resuscitation from cardiac arrest has been CPP [17]. In humans, this is a difficult value to obtain as it requires time-consuming invasive procedures and personnel trained to perform the procedures. Another surrogate for blood flow (and CPP) is ET-CO₂ measurement. Studies by Sanders et al demonstrated that ET- CO₂ correlated with CPP measurements and survival in dogs and later humans [18-20]. Unfortunately the administration of vasopressors, which is a frequent practice during cardiac arrest, interferes with pulmonary blood flow and hence the accuracy of ET-CO₂ [21]. A more accurate and reliable noninvasive means to detect blood flow during resuscitation efforts, if correlated with survival, would be beneficial.

The Doppler ultrasound device being studied was both sensitive and specific in detecting carotid artery blood flow velocities corresponding to changes in aortic blood pressure in low flow states as represented by the comparison of flow velocities seen in conditions of true- and pseudo-PEA. The device was able to detect aortic pressure changes as low as

1.5 mmHg. Furthermore, the device was able to detect carotid artery blood flow velocities throughout the spectrum of blood pressures after ROSC from CPR.

There are several applications where this technology may be useful. For example, there have been discrepancies noted in outcomes when comparing laboratory animal and human resuscitation studies [22,23]. The effectiveness of standard resuscitation medications has been noted to vary among clinical trials, and these same medications have been noted to have variable success within our own clinical practices. It would be useful during resuscitation attempts from any cause of shock to have a tool that qualitatively or quantitatively measures the effectiveness of a given therapy while the therapy is actually being performed.

The focus of the current research is to create a device that can measure blood flow in a simple, noninvasive fashion that would be applicable in most critical care settings. Limitations of this study for this particular application of the device include a small number of recorded pseudo-PEA and true- PEA events from which to gather sensitivity and specificity data. The device is in an early prototype stage, and issues related to carotid velocity flow detection and ease of placement of the final device will need to be addressed. Furthermore, the Doppler ultrasound measures carotid artery blood flow velocity, which is a semiquantitative measure of carotid blood flow but not an exact corollary. It would be helpful in future work to create an algorithm that directly quantifies the Doppler signal as carotid blood flow.

In this study, direct measurement of carotid blood flow velocity during resuscitation is investigated using a proto- type Doppler Ultrasound device as a real-time measure of carotid artery blood flow velocity during the extreme low- and no-flow conditions of pseudo-PEA and true-PEA cardiac arrest. Future studies should include direct observation of changes in carotid blood flow velocity during resuscitation efforts from various etiologies of cardiac arrest and shock

with the use of standard resuscitative techniques, routine ACLS medications, and adjunct devices to help gauge the effectiveness of these interventions.

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