FACULTEIT GENEESKUNDE EN

GEZONDHEIDSWETENSCHAPPEN

Academiejaar 2010 - 2011

The effect of chest compressions and intrathoracic pressure differences on end-tidal

CO2 tension in cardiac arrest patients

Jan FIERENS

Promotor: Prof. Dr. K. Monsieurs

Onderzoeksapport 4de master geneeskunde Voor “STAGE Wetenschappelijk onderzoek voor de ziekenhuisarts”

in het kader van de opleiding tot

ARTS

FACULTEIT GENEESKUNDE EN

GEZONDHEIDSWETENSCHAPPEN

Academiejaar 2010 - 2011

The effect of chest compressions and intrathoracic pressure differences on end-tidal

CO2 tension in cardiac arrest patients

Jan FIERENS

Promotor: Prof. Dr. K. Monsieurs

Onderzoeksapport 4de master geneeskunde Voor “STAGE Wetenschappelijk onderzoek voor de ziekenhuisarts”

in het kader van de opleiding tot

ARTS

Index

Abstract ...................................................................................................................................... 1

Background ................................................................................................................................ 3

Aim of the study ......................................................................................................................... 6

Materials and methods ............................................................................................................... 8

1. Study design .................................................................................................................... 8

2. Patient selection ............................................................................................................... 8

3. Materials .......................................................................................................................... 8

4. Data processing ............................................................................................................. 11

5. Statistical analysis ......................................................................................................... 14

Results ...................................................................................................................................... 15

1. Patient population .......................................................................................................... 15

2. Univariate analysis ........................................................................................................ 15

Discussion ................................................................................................................................ 21

Perspectives for further research .............................................................................................. 26

Conclusion ................................................................................................................................ 28

References ................................................................................................................................ 29

List of abbreviations A(C)LS advanced (cardiac) life support

AUCc area under the curve of compression peaks in the pressure waveform

BLS basic life support

#C number of compressions

CD median compression depth (in centimetre)

CPR cardiopulmonary resuscitation

CI confidence interval

CO cardiac output

CO2 carbon dioxide

CPP coronary perfusion pressure

ΔCP delta compression pressure/intrathoracic pressure difference

PetCO2 end-tidal carbon dioxide tension

EMT-D emergency medical technician with automated external defibrillator training

ERC European Resuscitation Council

ETT endotracheal tube

Hz Hertz

MICU mobile intensive care unit

Mm Hg millimeters of mercury

Mm H2O millimeters of water

OHCA out-of-hospital cardiopulmonary arrest

Pη² partial eta-squared

PEA pulseless electrical activity

PEEP positive end-expiratory pressure

PIP average intrathoracic pressure

Ppeak peak pressure

Pvent ventilation pressure

ROSC return of spontaneous circulation

SD standard deviation

GUH Ghent University Hospital

VF ventricular fibrillation

VT ventricular tachycardia

1

Abstract

Introduction. This study tested the hypothesis that cardiac arrest patients use a “cardiac

pump” and a “thoracic pump” to generate blood flow during resuscitation. We aimed to

quantify the effect of both mechanisms on PetCO2 (end-tidal carbon dioxide tension) in

individual out-of-hospital cardiac arrest (OHCA) patients.

Material and methods. Twenty-seven patients were studied in this observational prospective

study. Compression depth, rate and PetCO2 were assessed using an accelerometer and a

mainstream PetCO2 monitor (Zoll E series defibrillator). An experimental apparatus was

connected to the endotracheal tube, measuring intratracheal pressures. In 20 s interval before

each ventilation, we measured compression depth (CD), ventilation pressure (Pvent), number

of compressions (#C), intrathoracic pressure difference (ΔCP) and total intrathoracic pressure

(PIP). Individual patient models were created using UNIANOVA. Patients were categorised

according to the variables best predicting PetCO2 changes. A “cardiac pump” was considered

to be present when CD and/or # predicted PetCO2 changes and a “thoracic pump” when ΔCP

predicted PetCO2.

Results. In 13/27 (48%) patients a “cardiac pump mechanism” was identified.. In 1/27 (4%) a

“thoracic pump mechanism” and 10/27 (37%) a combination of both mechanisms was found.

An increase of depth with one centimetre increased PetCO2 from 1 to 12 mm Hg in 18/27

(67%) patients. An increase in rate with 10/min raised PetCO2 from 3 to 12 mm Hg in 6/27

(22%) patients. An increase of 10 mm H2O in ΔCP would increase PetCO2 from 1 to 19 mm

Hg in 10/27 (37%) in patients. Ten patients (37%) showed a negative influence of either PIP or

Pvent on PetCO2.

Conclusion. We developed a method to quantify the relative effect of the “cardiac” and of the

“thoracic pump mechanism” in OHCA patients, showing that a “thoracic pump mechanism”

is currently not accessed in all patients. While excessive PIP negatively influenced PetCO2, a

higher ΔCP can increase PetCO2.

2

Abstract

Introductie. Deze studie test de hypothese dat patiënten met een hartstilstand gebruik maken

van een “cardiale pomp” en een “thoracale pomp” om bloed flow te genereren tijdens

reanimtie. Het doel van deze studie is om het effect van beide mechanismen te kwantificeren

op de end-tidal CO2 spanning (PetCO2) bij patiënten die lijden aan een uit-hospitaal

hartstilstand (OHCA).

Materialen en methoden. Zevenentwintig patiënten zijn bestudeerd in deze observationele

prosepctieve studie. Compressiediepte, -snelheid en PetCO2 werden bekomen door

respectievelijk een accelerometer en een mainstream PetCO2 monitor (Zoll E Series

defibrillator). Een experimenteel toestel werd verbonden aan de endotracheale tube en maakte

intratracheale drukmeting mogelijk. Over een tijdsinterval van 20 seconden voor elke

ventilatie, werden mediane compressiediepte (CD), mediane ventilatiedruk (Pvent),

intrathoracaal drukverschil (ΔCP) en gemiddelde intrathoracale druk (PIP) gemeten.

Individuele patiëntmodellen werden gemaakt met UNIANOVA. De patiënten werden

gecategoriseerd volgens de variabelen die het beste de veranderingen in PetCO2 voorspellen.

Een “cardiale pomp” werd weerhouden als CD en/of #C PetCO2 veranderingen voorspelde en

een “thoracale pomp” als ΔCP PetCO2 veranderingen voorspelde.

Resultaten.. In 13/27 (48%) patiënten werd een “cardiale pompmechanisme” weerhouden, in

één (4%) een “thoracaal pompmechanisme” en in 10/27 (37%) patiënten een combinatie van

beide mechanismen. Een toename van diepte met één centimeter deed PetCO2 toenemen van 1

tot 12 mm Hg in 18/27 (67%) patiënten. Een toename in frequentie van 10/min deed PetCO2

toenemen van 3 tot 12 mm Hg. Een toename van 10 mm H2O zou een toename in PetCO2 van

1 tot 19 mm Hg bewerkstelligen in 10/27 (37%) patiënten. Tien (37%) patiënten toonden een

negatieve invloed van ofwel PIP ofwel Pvent op PetCO2.

Conclusie. We hebben een methode ontwikkeld om het relatieve effect van een “cardiaal” en

“thoracaal pomp mechanisme” in OHCA patiënten te kwantificeren en hebben aangetoond dat

het “thoracaal pompmechanisme” niet gebruikt word in alle patiënten. Hoewel een

overdreven PIP de PetCO2 negatief beïnvloedde, deed een hogere ΔCP PetCO2 toenemen.

3

Background

During the course of history, attempts to restore vital functions are not uncommon. Depictions

of air insufflations were first described in Egyptian and biblical mythology. The research of

Kouwenhower, Jude and Knickerbocker during the late fifties demonstrated that closed chest

compressions raised arterial blood pressure, facilitated defibrillation and consequently rapid

resuscitation in a canine model (Kouwenhouwer et al., 1960). This research made the

combination of closed chest compressions and periodical air insufflation the cornerstone of

modern cardiopulmonary resuscitation (CPR) (Koster et al., 2010).

Approximately 80 to 90% of all cardiopulmonary arrests are cardiac in origin and are

associated with a higher chance of resuscitation and survival compared with their non-cardiac

counterparts (Pell et al., 2003). The most common cardiac aetiology of out-of-hospital

cardiopulmonary arrest (OHCA) is myocardial ischemia due to atherosclerotic multivessel

disease of the coronary arteries. If an initial electrocardiogram is obtained shortly after the

occurrence of OHCA, most patients will present with ventricular fibrillation (VF), reflecting

electrical instability inherent to the chronic cardiac ischemia (Kremers et al., 1989; Engdahl et

al., 2003). Non-cardiac causes of OHCA include trauma, postoperative complications, drug

abuse, pulmonary embolism, aortic dissection/aneurysm, obstructive pulmonary disease and

pneumonia. These conditions present mostly with asystole and pulseless electrical activity

(PEA). These cardiac rhythms are associated with a lower chance of successful resuscitation

and survival (Engdahl et al., 2003).

The major role of CPR is to provide sufficient blood flow to vital organs (like the

myocardium and central nervous tissue) in order to provide both successful defibrillation and

return of spontaneous circulation (ROSC) and maintaining the function of these vital organs.

Despite 30 years of research, the mechanisms by which blood flows through the body during

CPR is not fully understood. Two theories have been proposed to explain the mechanisms of

blood flow. The first is the direct cardiac compression model. External compressions squeeze

the heart between sternum and spine, causing elevated pressure in both ventricles, opening

both semilunar valves and pumping blood in the pulmonary artery and in the aorta

(Kouwenhouwer et al., 1960; June et al., 1961). Several observations indicate that this

mechanism may not always be operative. Coughing can prolong consciousness up to 40

seconds in patients with VF during cardiac catheterization. This demonstrates that blood flow

4

can be generated by changes in extra- to intrathoracic pressure gradient (Criley et al., 1976).

In addition, echocardiography has shown that late in the course of CPR the mitral and

tricuspid valves do not close (Werner et al., 1981) and that the dimensions of the left ventricle

do not change (Rich et al., 1981). These data led to the “thoracic pump mechanism” as a

model for blood flow during CPR. It theorizes that the heart serves as a passive conduit

between the pulmonary artery and aorta with selective flow to the aorta and the

brachiocephalic veins who are protected by the closing of intrathoracic inlet venous valves.

The negative pressure generated during decompression in experimental resuscitation settings

supports this assumption. The use of an intrathoracic pressure regulator to create a superior

intrathoracic pressure gradient improved the venous return, perfusion of and flow to vital

organs, cardiac output and cerebral flow in pigs (Yannopoulos et al., 2005; Yannopoulos et

al., 2006). Other studies demonstrated that excessive positive intrathoracic pressure caused by

overzealous ventilation (Aufderheide et al., 2004) or incomplete chest wall recoil

(Aufderheide et al., 2005) may have a detrimental effect on survival from cardiac arrest.

Positive end-expiratory pressure (PEEP) increased intrathoracic pressure, preventing venous

return and thus lowering cardiac output (Hodgkin et al., 1980). An observational study in a

porcine model however, demonstrated that PEEP created an increase in carotid blood flow

(Chandra et al., 1981). A canine model confirmed this increase in carotid blood flow to a

maximum threshold of 5 cm PEEP, suggesting a similar PEEP threshold may exist in humans

(Ido et al., 1982). These various results show that neither theory fully explains all

hemodynamic processes during CPR, suggesting that in reality a combination of both

mechanism may be present.

Capnography and end-tidal carbon dioxide tension (PetCO2), i.e. the measurement of CO2 at

the end of expiration, has found its way into pre-hospital medicine and the emergency

department. Though initially its main use was verification of correct placement of the

endotracheal tube (ETT) (Timmerman et al., 2007), it can be employed for hemodynamic

monitoring of intubated and non-intubated patients and monitoring of CPR efforts

(Ward and Yearly, 1998). While cardiac output (CO) in humans is not routinely measured

because insertion of a pulmonary artery catheter is not possible or indicated, several animal

studies indicated a relationship between CO and PetCO2 in situations of low flow such as

resuscitation and shock (Blumenthal and Voorhees, 1997; Jin et al., 2000). Several other

researchers showed a similar relationship between PetCO2 and coronary perfusion pressure

(CPP) (Sanders et al., 1985; Kern et al., 1989; Von Planta et al., 1989). This association of

5

PetCO2 and physiological parameters makes it a valuable parameter during CPR. Several

investigators reported that PetCO2 may offer prognostic information concerning the likelihood

of obtaining ROSC. These included averaging PetCO2 over 20 minutes of resuscitation, taking

initial and maximal PetCO2, PetCO2 changes after ROSC and PetCO2 during resuscitation of

various presenting rhythms such as asystole and PEA. Numerous studies illustrated that

ROSC is associated with a sudden increase in PetCO2, sometimes even before a pulse is felt

(Kalenda, 1987; Garnett et al., 1987; Sanders et al., 1989; Grmec et al., 2003). Several groups

have also demonstrated that an initial PetCO2 of 10 to 15 mmHg has a high predictive value

for non-ROSC (Grmec and Klemen, 2001: Gmrec et al., 2003; Grmec et al., 2007; Grmec et

al., 2011). Other research groups have associated a PetCO2 value of less than 10 mmHg after

20 minutes of resuscitation with a low chance of obtaining ROSC (Wayne et al., 1995;

Cantineau et al., 1996; Levine et al., 1997; Kolar et al., 2008). This prognostic value of

PetCO2 was also applicable in cardiac arrest due to asphyxia after 1 to 5 minutes of ventilation

during the CPR algorithm (Grmec et al., 2003; Grmec et al., 2011). During a respiratory

arrest, cardiac output and pulmonary blood flow continues for a period of time prior to cardiac

standstill. During this stage cellular metabolism continues so CO2 is still being delivered to

the lungs, thereby increasing the alveolar CO2 tension (Berg et al., 1996). Research has found

that several factors may alter the PetCO2 during CPR. A theoretical animal model showed an

augmentation of CO following an increase in compression rate from 60/‟ to 120/‟ (Maier et

al., 1984). This is confirmed by an increase in CPP, PetCO2, higher chance for successful

defibrillation and a higher chance for ROSC in animals (Feneley et al., 1988; Swenson et al.,

1988). Not all animal models, however, reached the same conclusion, as some showed no

difference in CPP and survival (Kern et al., 1986; Milander et al., 1995). Human studies have

not demonstrated a conclusive correlation between compression rate or depths and PetCO2

(Ornato et al., 1988; Kern et al., 1991). No randomized studies exist comparing different

compression rates in humans and their effect on PetCO2 and/or survival. A porcine model

demonstrated a linear relationship between depth and PetCO2 (Babbs et al., 1983). Increasing

compression depth in humans is associated with a higher chance of successful defibrillation,

ROSC and hospital discharge (Edelson et al., 2006; Kramer-Johansen et al., 2006; Babbs et

al., 2008; Edelson et al., 2008). However resuscitation in these studies was performed

according to the 2005 resuscitation guidelines (Handley et al., 2005), limiting the number of

patients with compression depths higher than 5,1 cm. There are no studies prospectively

linking different compression depths to PetCO2 in cardiac arrest patients.

6

Aim of the study

This study tested the hypothesis that cardiac arrest patients use a “cardiac pump mechanism”

and a “thoracic pump mechanism” to generate blood flow during resuscitation efforts. We

aimed to quantify the effect of both pump mechanisms on PetCO2 in individual OHCA

patients.

Previous research of intrathoracic pressure showed that during a ventilation cycle, a

ventilation pressure (Pvent ) is built up, amplifying the compression waveforms (Aufderheide

et al., 2004). To describe the pressure difference between Pvent and the amplified compression

wave, we introduced a new parameter, the intrathoracic pressure difference (Delta

compression pressure (ΔCP)). A self-made apparatus connected to the ETT allowed us to

measure pressures in the trachea, which represent the overall intrathoracic pressures, and to

calculate pressure differences in the thoracic cavity. We hypothesized that by altering

compression and ventilation parameters, ΔCP will change accordingly. This change could

lead to a change in PetCO2.

Another possible way to influence PetCO2 is by enhancing the cardiac pump. Current CPR

guidelines recommend a compression depth of “at least 5 cm” (Koster et al., 2010). We

hypothesized that increasing compression depth beyond the current guidelines will lead to an

increase in cardiac output. The current CPR guidelines advise a minimal compression rate of

“at least 100 per minute” (Koster et al., 2010). We hypothesized that an increase in

compression rate will affect the PetCO2.

Moreover the intrathoracic pressure measuring device allowed the calculation of average

intrathoracic pressure (PIT). Elevated intrathoracic pressures may cause inhibition of venous

return and consequently a reduction in CO. Examining the PIT in patients undergoing CPR,

allowed us to correlate changes in PIT to CO, expressed by changes in the PetCO2. This study

also focused on describing the effect of PIT on PetCO2.

Finally both the “cardiac” and “thoracic pump model” were combined to quantify and predict

the PetCO2 changes present in single patients suffering from cardiac arrest. Optimizing both

“the thoracic pump”, by augmentation of ΔCP, and “the cardiac pump”, by altering

compression rate and depth, may lead to an increase in PetCO2 in certain patients suffering

7

from cardiac arrest. In this study we tried to ascertain the influence of both mechanisms on

PetCO2.

8

Materials and methods

1. Study design

A single centre observational study was conducted in patients suffering from OHCA between

October 2010 and April 2011. The study population was the municipality of Ghent including

its eastern suburbs, with a population of approximately 150 000 inhabitants. Initial basic life

support (BLS) for OHCA was provided by Emergency Medical Technicians with defibrillator

training (EMT-D). Advanced (cardiac) life support (ACLS) was provided by the Mobile

Intensive Care Unit (MICU) of Ghent University Hospital (GUH). This MICU was manned

by an EMT-D, a nurse specialized in emergency medicine and a physician, training for or

certified in the specialty of emergency medicine, anaesthesiology or internal medicine.

Physicians, paramedics and nurses staffing the MICU were informed about the study protocol.

Patients resuscitated before December 2010 received ALS according to the European

Resuscitation Council (ERC) 2005 guidelines (Nolan et al., 2005), afterwards the ERC 2010

guidelines were used (Deakin et al., 2010).

2. Patient selection

All patients suffering from OHCA resuscitated by the MICU of the GUH older than 18 years

between 22nd

October and 15th

April were eligible. Approval of this study was given by the

Ethics Committee of the Ghent University Hospital, under conditions for deferred informed

consent. In case of ROSC and transfer to a hospital, a family member was asked to give

informed consent. ROSC was defined as the return of a palpable pulse at any given time. The

decision to stop resuscitation efforts was solely the responsibility of the treating physician.

3. Materials

On arrival of the MICU patients were monitored and, when indicated, defibrillated with a

manual Zoll E Series defibrillator (Zoll Medical Company, Chelmsford, USA) (Figure 1 -

left). ECG data were obtained in all patients. CPR D-padz (Zoll Medical Company,

Chelmsford, USA) were applied on the patient‟s chest according to the manufacturer‟s

instructions. These pads included an accelerometer, which was placed between the rescuer‟s

hand and the patient‟s sternum (Figure 1 - right). This device measured compression depth

and rate. Using these data, the defibrillator provided the rescuers with real-time visual and

9

audible feedback of compression quality. All defibrillator data were stored on an external

memory card (Linear flash 32 Mb memory card, Zoll Medical Company, Chelmsford, USA).

Figure 1: Left: The Zoll E Series defibrillator. Right: CPR D-Padz, consisting out of two defibrillator pads, an

accelerometer and the connector to the defibrillator

After endotracheal intubation (Hi-Contour Tracheal Tube, Mallinckrodt Medical, Athlone,

Ireland), patients were manually ventilated using an adult size, self-refilling ventilation bag

(Laerdal Silicone Resuscitation Adult, Laerdal Medical, Stavanger, Norway). After

confirmation of correct tube placement, mechanical or manual ventilation was performed at

the discretion of the physician. On March 4th

, a change was made in hospital guidelines,

urging physicians to switch to mechanical ventilation as soon as possible. Patients were

mechanically ventilated using an Oxylog 3000 ventilator (Dräger Medical GmbH, Lübeck,

Germany). Based on the ERC 2010 guidelines (Koster et al., 2010), the ventilator was set as

follows: tidal volume of 6 to 7 ml per kilo, PEEP of 0 millimeters of water (mm H2O) (1 mm

H2O = 10 Pa), ventilatory rate of 10 per minute and inspiratory oxygen fraction of 100 %. An

oxygen saturation of 94 to 98 % was aimed at after obtaining ROSC. By making its value

independent of ventilatory parameters, the PetCO2 better reflected the efficiency of

resuscitation efforts.

A swivel and pediatric filter (Hygrobac, Mallinckrodt Medical, Athlone, Ireland) were

attached to the endotracheal tube. A portable infrared mainstream PetCO2 sensor (Capnostat 5,

Zoll Medical Company, Chelmsford, USA) was attached to this filter, i.e. between the

ventilation bag or the ventilation tubes of the Oxylog 3000 ventilator and the filter (Figure 2 -

left). This capnograph worked on the principle of non-dispersed infrared absorption with

dual-wavelength single-beam optics. It was calibrated and zeroed daily according to the

manufacturer‟s instructions. After connection to the defibrillator, it allowed real-time

quantitative measurements of the PetCO2. PetCO2 was expressed in millimeters mercury (mm

Hg) (1 mm Hg = 133 Pa). Digital PetCO2 reading, ventilatory rate and capnograph waveforms

10

were visualized real-time on the defibrillator‟s screen and stored on the external memory card

(Figure 2 - right). During the resuscitation this information was always available to the

treating resuscitation team.

Figure 2: Left: PetCO2 sensor Right: The screen of the Zoll E Series defibrillator showing the PetCO2,

capnograph waveform and respiratory rate

A self-developed pressure measurement system was used to ascertain intrathoracic pressures,

making use of a disposable extension piece connected to pressure sensors. This extension

piece consisted of a coupling piece which was directly attached to the endotracheal tube,

positioned before the filter, the PetCO2 sensor and the tubes of the mechanical ventilator.

Furthermore it consisted of two small tubes (length : 150 cm, diameter : 1,5 mm) (Extension

Line, Ciam Laboratories, Sallanches, France). One small tube was connected by a luer-lock

mechanism to the coupling piece on one end and an external device on the other end. The

second small tube was passed through the ETT on one end and connected to the same external

device on the other end. Consequently the first small tube was positioned at the proximal end

of the ETT, providing superficial pressure measurements, and the second small tube was

positioned at the distal end of the ETT, providing deep pressure measurements (Figure 3 -

left). For the purpose of this study, only the deep pressure measurements were used. The

external device contained two pressure sensors, two Wheatstone bridge amplifiers (Type

132B Sensor Amplifier, Datum Electronics, Isle of Wight, UK) and a pressure logger

(MSR145, MSR Electronics GmbH, Henggart, Switzerland) to digitize and record the

enhanced pressure data. A sturdy case enfolded the pressure sensors, amplifiers and the

logger. This device had an on/off switch, two luer-lock connection ports for the small tubes

and a USB2 port, to download the data on a personal computer (Figure 3 - right). During

resuscitation, pressure data were not visible to the treating physician. Disposables were not

reused. They were examined by an independent observer for potential clogging of the small

tubes with secretions or blood, prohibiting an adequate pressure measurement. Two pressure

11

loggers were present, one being used by the resuscitation team. The other was stored at the

emergency department, for use in case of technical malfunctioning. The logger was reset after

downloading the data.

Applying the disposable and PetCO2 sensor did not delay the resuscitation efforts and had no

adverse effect on the outcome of the patient. Resuscitated patients without either pressure

measurements or PetCO2 were excluded from the study. Other exclusion criteria are listed in

Table 1.

Figure 3: Left: The self-developed system to measure intratracheal pressures. It consists of a small tube

positioned in the endotracheal tube, another small tube connected to the connecting piece, swivel and filter. This

figure also shows the position of the PetCO2 sensor. Right: The external device, containing the pressure sensors,

amplifier and pressure logger, enfolded by a sturdy case.

4. Data processing

After each resuscitation, the data on the memory card of the defibrillator was downloaded and

reviewed in RescueNet Code Review (Zoll Medical Company, Chelmsford, USA) (Figure 4 -

left). Patients without PetCO2 were excluded from the study (Table 1). The initial rhythm and

post-resuscitation rhythm in case of ROSC were assessed. The defibrillator data were sampled

at 250 Hz (250 samples per second) and converted to an exportable text format (.txt).

The data on the pressure logger was transferred to a portable computer by USB connection

and reviewed in MSR Viewer 5.12 (MSR Electronics GmbH, Henggart, Switzerland) (figure

4 - right). Patients without deep pressure measurement or damped pressure waveforms during

resuscitation due to clogging of the small tubes were excluded. Additionally, patients who did

not have a minimum of one minute of resuscitation with both pressure data and PetCO2

available were excluded from the study (Table 1). The pressure data were sampled at 50 Hz

(50 samples per second) and converted to comma separated value format (.csv).

12

Figure 4: Left: A screenshot from the RescueNet Code review software showing a resuscitation trace with the

capnograph waveform, PetCO2, the respiratory rate, compression depth and rate. Right: A screenshot showing

the MSR Viewer software visualizing the pressure waveforms. The green waveforms correspond with the

superficial pressure measurements and the black waveforms with the deep pressure measurements.

Both text formats were imported in a Microsoft Excel (Microsoft Corporation, Redmond,

USA) spreadsheet using a self-developed macro, written in Microsoft Visual Basic for

Applications. To find an exact time match of pressure data and compression data, a “three

point approach” was used. These points were “transition points”, signalling the transition

from a period of chest compressions to a period of rest or vice versa. The pressure waveforms

between two of these transit points formed a “pressure profile”. A similar “compression

profile” could be found in the Zoll data. The time difference between these two profiles was

noted and an adjustment was made, matching both profiles. This process was repeated for two

other transition points. The course of the resuscitation was then reviewed per thirty seconds

perfectly matching the compression data and the corresponding pressure waveforms.

Each patient had a separate spreadsheet and was analysed individually. Utilizing the

technology of Visual Basic for Applications, several parameters were calculated per patient.

For each compression, the following parameters were obtained: compression depth (CD),

isolated distal and proximal peak pressure and the isolated ventilation pressure. Furthermore a

subtraction was made between the distal peak pressure (Ppeak) and ventilation pressure (Pvent).

We called this value the “delta compression pressure” or DeltaCP (ΔCP). We also calculated

the area under the curve (AUC) of the compressions in the pressure waveforms (AUCc) and

the AUC of the total pressure waveform. This variable corresponded with the average

intrathoracic pressure (PIP). For each variable, a mean, median and summation for a time

interval of 5, 10, 15 and 20 seconds were derived for every PetCO2. Additionally the number

of compressions given during these time intervals was calculated.

13

Figure 5: Imported pressure and compression data in MS Excel document. The capnograph waveform are blue

with the PetCO2 of a ventilation marked with a thick dark blue line. Compression depths are marked with small

black lines. The deep pressure waveform is coloured red with the grey areas defined as the area under the curve

of the compression peaks. The yellow arrow illustrates intrathoracic pressure difference or ΔCP.

0

10

20

30

40

50

60

10:24:08 10:24:13 10:24:18

0

5

10

15

20

25

30

35

Table 1: Exclusion criteria

Patients manually ventilated

Patients who did not have any PetCO2, due to sensor malfunctioning or non-

application of the PetCO2 sensor

Patients who did not have any pressure measurement (either deep pressure

measurements of no pressure measurements at all) due to non-application of the

disposable, sensor malfunctioning, clogging of the small tubes or not activating the

logger

Patients with less than one minute of both PetCO2 and pressure measurements

available before obtaining ROSC

Figure 6: Imported pressure data in MS Excel document, illustrating total intrathoracic pressure (PIP).

14

5. Statistical analysis

Statistical analysis was performed using PASW Statistics 18.0 (IBM, New York, USA). The

null hypothesis was considered to be rejected at a two-tailed alpha rate of 0.05 or less.

Population statistics were expressed as mean ± standard deviation (SD). Comparison between

the included and excluded patient groups was performed using the Mann-Whitney test for

continuous variables and Chi square test for categorical variables.

Patients were analysed individually. A simple linear regression was used to study the

relationship between each parameter and the corresponding PetCO2 during a time interval of 5,

10, 15 and 20 seconds. An individual patient model was made using a univariate analysis with

PetCO2 as the dependent variable. The proportion of variance in PetCO2 by a variable was

expressed as the partial eta-squared coefficient (partial η² or Pη²). A variable with a partial

eta-squared less than 0.01 and/or not statistically significant P-value was not further included

in the patient model. This resulted in a statistical model per patient, which optimally described

the individual set of parameters that could quantitatively predict changes in PetCO2.

15

Results

1. Patient population

From 22nd

of October to 15th

of April 51 patients suffering from OHCA were resuscitated by

the MICU of the GUH. 23/51 patients (47%) were excluded from the study. 27/51 (53%)

patients were included for further analysis. Patients‟ characteristics of both groups are

summarised in Table 2.

Table 2 : Patients’ characteristics

Included patients Excluded patients P

Number of patients 27 (53%) 24 (47%)

Age (years) 60 (18) 62 (17) 0.75

Sex (n)

Male 22 (82%) 21 (88%)

Female 5 (18%) 5 (12%) 0.56

ROSC (n)

Yes 10 (37%) 12 (50%)

No 17 (63%) 15 (50%) 0.35

Initial rhythm (n)

Asystole 21 (78%) 17 (71%)

VF/VT 3 (11%) 2 (8%)

PEA 3 (11%) 5 (21%) 0.62

Rhythm if ROSC (n)

Sinus rhythm 7 (70%) 5 (42%)

Paced rhythm 0 (0%) 2 (17%)

AF 3 (30%) 2 (17%)

VT 0 (0%) 3 (25%) 0.15

SD = standard deviation; ROSC = return of spontaneous circulation; VF = ventricular fibrillation;

VT = ventricular tachycardia; PEA/EMD = pulseless electrical activity; AF = atrial fibrillation

There were no significant differences between both groups regarding demographic data.

2. Univariate analysis

A simple linear regression analysis was made for each set of parameters of each individual

patient. This demonstrated that both the median and summation of all parameters, made

16

during a time interval of 20 seconds before each ventilation, had superior R² values, with a

corresponding statistically significant P-value, when compared with a time interval of either

5, 10 or 15 seconds.

Table 3 shows the descriptive statistics for all variables in the entire included patient

population.

Table 3: Descriptive statistics of measured variables of included patients (n = 27)

PetCO2 CD ΔCP PIP Ppeak Pvent #C AUCc Dur

Mean 23 5.3 23 8 35 13 23 507 393

Median 21 5.1 22 9 34 16 23 502 302

SD 12 1.0 7 6 8 5 9 142 335

Min 4 3.0 3 0.02 16 -8 1 103 51

Max 71 8.9 46 21 68 29 54 1198 1634

All variables were measured 20 seconds before each ventilation; for CD, ΔCP, Ppeak, Pvent and AUCc median

values were calculated during this time interval

PetCO2= end-tidal CO2 tension (in mm Hg); CD = compression depth (in cm); ΔCP = intrathoracic pressure

difference (in mm H2O); PIP = average intrathoracic pressure (in mm H2O); Ppeak = peak pressure (in mm H2O);

Pvent = ventilatory pressure (in mm H2O); #C = number of compressions given; AUCc = area under the curve of

the compression peaks; Dur = duration of the resuscitation (in seconds); SD = standard deviation; Min =

minimum; Max = maximum

In total there were 3457 CO2 measurements. The mean PetCO2 was 23 mmHg (± 12mmHg).

The mean duration of CPR was 393 seconds (± 335 seconds).

A univariate model per patient was developed to explain changes in PetCO2 quantitatively. We

aimed at a “tolerance level” lower than one and a “variation inflation factor” less than three

for all used variables, thus avoiding multicollinearity between the used variables. The

variables used in each patient model were measured in a time interval of 20 seconds before

each ventilation. Table 4 shows these individual univariate models.

17

Table 4: Patients’ individual model using univariate analysis

Patient ID Pη² model° ΔCP CD PIP ΣPvent AUCc #C Category

B Pη² B Pη² B Pη² B Pη² B Pη² B Pη²

1 22102010 <0.001 N

2 24102010 0.475 0.29 0.10 1.35 0.12 0.013 0.10 C,T

3 30102010 0.203 0.004 0.21 -0.39 0.13 C

4 28112010 0.129 -1.75 0.10 -0.004 0.05 N

5 06122010 0.383 0.16 0.02 11.81 0.24 -0.002 0.29 0.47 0.11 C

6 08122010a 0.513 -0.023 <0.01 5.11 0.45 C

7 08122010b 0.451 -0.096 0.06 1.33 0.25 0.029 0.07 C

8 08122010c 0.304 -0.26 0.05 0.001 0.18 -0.035 0.27 N

9 25122010 0.289 0.041 0.29 C,T

10 31122010 0.692 2.79 0.28 -0.001 0.16 -0.001 0.23 C,T

11 25012011 0.205 0.29 0.07 -2.78 0.12 -0.10 0.03 C

12 04022011 0.364 0.74 <0.01 0.91 0.33 0.41 0.09 0.38 0.06 C

13 10202011 0.523 2.23 0.15 -0.001 0.20 0.014 0.062 0.018 0.29 C,T

14 19022011 0.122 0.81 0.12 C

15 24022011 0.315 0.14 0.02 -0.22 0.05 0.297 0.10 0.45 0.14 C,T

16 25022011 0.648 0.067 0.04 1.34 0.56 0.00033 0.19 C

17 27022011 0.324 0.44 0.03 6.21 0.30 -0.010 0.03 C

18

Patient ID Pη² model° ΔCP CD PIP ΣPvent AUCc #C Category

B Pη² B Pη² B Pη² B Pη² B Pη² B Pη²

18 28022011 0.514 3.18 0.35 0.049 0.37 0.008 0.02 C

19 11032011 0.237 0.29 0,14 -0.004 <0.01 -0.019 0.21 C,T

20 18032011 0.140 0.25 0,15 5.95 0.15 C,T

21 21032011 0.239 1.9 0,28 T

22 28032011 0.597 3.53 0.12 -0.002 0.26 -0.046 0.36 0.74 0.52 C

23 29032011 <0.001 N

24 02042011 0.562 -14.21 0.32 -0.24 0.21 C

25 05042011a 0.366 -0.072 0,05 -0.072 0.02 0.038 0.13 1.16 0.16 C,T

26 05042011b 0.584 -0.94 0,34 -7.79 0.34 -0.002 0.18 -0.025 0.18 C,T

27 14042011 0.351 1.88 0.29 0.001 0.16 C

All variables were measured in a time interval of 20 seconds before each ventilation; for CD, ΔCP, Ppeak, Pvent and AUCc median values were calculated during this time interval

PetCO2 was the dependent variable in all patients

° All patients models, with the exception of patients 1 and 23, had an P < 0,001

Pη² = partial eta-squared coefficient; B = estimate of the parameter; ΔCP = median intrathoracic pressure difference (in mmH2O); CD = median compression depth (in cm); PIP = average

intrathoracic pressure (in mm H2O); ΣPvent = sum of ventilation pressures (in mm H2O); AUCc = median area under the curve of compression peaks; #C = the number of compression

given

Category = categorisation of the pump mechanism; N = no discernable pump mechanism; C = cardiac pump mechanism; T = thoracic pump mechanism; C,T = both a cardiac and thoracic

pump mechanism

19

In two (7%) out of 27 included patients, we were not able to fit a model to explain changes in

PetCO2. The partial eta-squared for all other patients ranged from 0.122 to 0.692 with

corresponding P-values lower than 0.001. A categorisation was made of the patients

according to the parameters used in each patient‟s model to describe changes in PetCO2:

Average intrathoracic pressure and sum of ventilation pressures were considered as

neutral variables. According to our hypothesis, we stated that excessive intrathoracic

pressure (either by increased PIP directly or indirectly by increasing the Pvent)

correlated with a decreased CO, due to inhibition of venous return. When venous

return is inhibited, neither pump mechanism will function properly.

A patient wherein compression depth and/or number of compression explained the

greatest fraction of PetCO2 variation, was considered using a “„cardiac pump

mechanism” to generate flow during resuscitation

A patient wherein intrathoracic pressure difference explained the greatest fraction of

PetCO2variation, was considered using a “thoracic pump mechanism” to generate flow

during resuscitation

A patient that used a combination of both categories mentioned above, or wherein area

under the curve of the compression peaks explained the greatest fraction of PetCO2

variation, was considered to use a combined “cardiac and thoracic pump mechanism”.

In 9/27 (33%) patients compression depth and/or rate were the discriminating factors

determining increase in PetCO2. In 4/27 (15%) patients there existed a negative relationship

between these parameters and PetCO2. Only in one (4%) patient ΔCP was the only parameter

explaining changes in PetCO2. For the other nine (33%) patients, a combination of

compression parameters and of the intrathoracic pressure difference and/or the area under the

curve of the compression peaks were the discriminating factors responsible for changes in

PetCO2. Although all patients received precordial compressions and intermittent ventilations,

the first group was categorized as using a “cardiac pump mechanism”, the second as a

“thoracic pump mechanism” and the third group as a combined “cardiac and thoracic pump

mechanism”.

In 18/27 (67%) patients compression depth was the most important factor to explain changes

in PetCO2. Four of these 18 patients showed a negative correlation between compression depth

and PetCO2, leading to a decrease of this value from 2 to 14 mm Hg when compression depth

was increased with one centimetre. These four patients also showed a negative association

20

between Pvent and/or PIP and PetCO2, indicating that in increased depth may be associated with

an increased intrathoracic pressure, inhibiting venous return. An increase of one centimetre

depth in the remaining 14 patients would increase PetCO2 from 1 to 12 mmHg. While only one

quarter of all patients incorporated the number of compression in a 20 seconds time interval

before each ventilation into their unique patient model, this parameter showed great influence

when predicting PetCO2. In six of these patients, an increase of ten compressions in a twenty

second time interval increased PetCO2 from 1 to 12 mmHg. Only one of these patient showed

a negative association between the number of compressions and PetCO2.

In fifteen (56%) patients, a relationship existed between PetCO2 and ΔCP. In only 1/15

patients the intrathoracic pressure difference was the parameter solely explaining changes in

PetCO2. ΔCP together with other pressure and compression related parameters explained

changes in PetCO2 in the remaining 14/15 patients. These patients were therefore classified

using a combined “cardiac and thoracic pump mechanism” to explain changes in PetCO2. In

10/15 patients the intrathoracic pressure difference was positively correlated with PetCO2,

meaning that an increase in ΔCP of 10 mmH2O in this patient group would lead to an increase

of PetCO2 of 1 to 19 mmHg. The 5/15 remaining patients demonstrated a negative association

between ΔCP and PetCO2. An increase of ΔCP of 10 mmH2O would decrease PetCO2 from 0

to 9 mmHg.

These same five patients also exhibited a negative association between average intrathoracic

pressure and/or sum of ventilation pressure, meaning that an increased intrathoracic pressure

resulted in a decrease in PetCO2. In eight other patients, showing a correlation between ΔCP

and PetCO2, a similar relationship between these neutral pressure variables and PetCO2 was

found. This resulted in a total of 13/27 (48%) patients who had a negative association between

PIP or Pvent and PetCO2. An increased Pvent was associated with lower PetCO2 in the majority of

patients who integrated this variable in their respective models. On the contrary an increased

PIP was only associated with lower PetCO2 in 6 out of 11 patients who had this variable built

into their model.

21

Discussion

To our knowledge, this is the first study that combined information from both cardiac

compressions and intrathoracic pressures to study their relationship with PetCO2 in patients

suffering from out-of-hospital cardiac arrest. Several other studies (Schultz et al., 1994;

Aufderheide et al., 2004; Yannopoulos et al., 2005) have measured intrathoracic pressures in

an experimental resuscitation setting, but this is the first attempt to combine these data in a

pre-hospital resuscitation setting.

In our study all resuscitated patients received precordial chest compressions and ventilations

according to standard resuscitation guidelines (Deakin et al., 2010). It has been demonstrated

both in animals (Marn-Pernat et al, 2001; Berg et al., 2001) and human studies (Kramer-

Johansen, 2006) that cardiac compression are the determining factor for high-quality CPR.

Even small pauses in compressions can significantly decrease coronary perfusion pressure

(Berg et al., 2001). Our analysis demonstrated that in most patients the primary mechanism

for generating blood flow during CPR are these chest compressions. Though current CPR

guidelines advise a compression depth of at least 5 cm, our analysis demonstrated that a

compression depth of even 7 and 8 cm can significantly raise PetCO2 in some cardiac arrest

patients. This increased PetCO2 associated with a higher cardiac output (Jin et al., 2000) and

coronary perfusion pressure (Von Planta et al., 1989), which are both associated with a higher

likelihood of gaining ROSC (Grmec et al., 2011; Reynolds et al., 2010). We also showed that

the number of compressions in a time interval of twenty seconds before each CO2

measurement is an important factor in explaining changes in PetCO2. Seven patients have

incorporated this parameter in their respective models. A increase of rate with 10/minute can

lead to an increase of up to 10 mmHg in PetCO2, emphasizing the importance of a

compression rate of at least 100/minute as recommended by the current CPR guidelines

(Koster et al., 2010). Similar observations have been found in animal models where a higher

mean compression rate is associated with a higher cardiac output (Maier et al., 1984) and

coronary perfusion pressure (Feneley et al., 1988), both characterised by an increased PetCO2.

This could explain the increased PetCO2 in several patients in our research population when

compression rate would be augmented.

In numerous studies evidence has been provided proving the existence of “a thoracic pump

mechanism” (Criley et al., 1976; Werner et al., 1981; Rich et al., 1981). Besides the direct

22

cardiac compression, intrathoracic pressure differences could also be responsible for the

promulgation of blood during CPR. We introduced a new parameter to describe these

intrathoracic pressure differences. During a ventilatory cycle a ventilatory pressure is

generated. The compressions given during this cycle, are superimposed on this ventilatory

pressure waveform, creating discrete peak pressures. The difference between the peak

pressure and ventilatory pressure was defined as the intrathoracic pressure difference, ΔCP or

Delta compression pressure. It is the first time such a parameter has been used to directly

quantify the intrathoracic pressure differences. While we believe that blood flow during

resuscitation is probably generated by a combination of both cardiac compressions and

intrathoracic pressure differences, only nine patients in our study group demonstrated such a

combination. A probable explanation is the way out-of-hospital cardiac arrest patients are

currently ventilated. Patients are intubated and ventilated using a semi-closed airway circuit.

Other airway circuits should be explored to fully access the potential of this “thoracic pump

mechanism”. For example the endotracheal tube could be clamped during precordial

compressions and declamped during the intermittent ventilations. Another possibility to fully

access the “thoracic pump mechanism” is the titration of PEEP. Lastly the build-up of

ventilatory pressure could be altered, by not only changing ventilator setting but also by

exploring high-frequency jet ventilation and continuous positive airway pressure ventilation

during resuscitation. This will lead to a different ventilatory pressure waveform.

The intratracheal pressure sensors also made it possible to ascertain the average intrathoracic

pressure during the resuscitation. In several of our patients excessive intrathoracic pressure

was associated with significantly lower PetCO2. During the decompression phase, each time

the chest returns back to its neutral state, a small relative negative pressure is generated in the

thoracic cavity. This draws venous blood back to the right atrium. This negative pressure is

relative to the rest of the body. An excessive intrathoracic pressure inhibits the creation of this

negative pressure and thus inhibits the return of venous blood to the right atrium. It

subsequently decreases pulmonary circulation and PetCO2. It has been previously

demonstrated by other research groups in animal models that overzealous ventilation and

incomplete chest wall recoil can lead to increased intrathoracic pressures (Aufderheide et al.,

2004; Aufderheide et al. 2005), both resulting in a significantly lower PetCO2, coronary

perfusion pressure and cardiac output. Other studies showed a beneficial effect of an

intrathoracic pressure regulator, augmenting the negative pressure vacuum during the

decompression phase, during resuscitation of OHCA patients. It increased chances for

23

obtaining ROSC and admittance to the Intensive Care Unit (Aufderheide et al., 2005).

Increased negative intrathoracic pressures during resuscitation could also augment the

intrathoracic pressure difference, not only creating more venous return, but also driving more

blood forward. Though their study could not demonstrate causes of increased intrathoracic

pressures, it did show its negative effect on PetCO2, correlating with decreased cardiac output,

pulmonary circulation and coronary perfusion pressure.

Our study had several limitations. First and foremost its study design. We used simple and

multiple linear regression, thus making the assumption that all used parameters had an

adequate range to analyse. In several patients the range of ΔCP and compression depth was

limited, mostly due to a short resuscitation time before obtaining ROSC. Compression depth

was also limited due to the use of ERC 2010 guidelines, advising a compression depth of at

least 5 cm in the new 2010 guidelines (Deakin et al., 2010) and a compression depth ranging

from 4 to 5 cm in the ERC 2005 guidelines (Nolan et al., 2005). This study encompasses

patients resuscitated according to both guidelines. The use of these guidelines limits the range

of available compression depths, making it sometimes difficult to relate depth to PetCO2.

Though neither patients groups were excluded, it was not always possible to fully ascertain

the pump mechanism(s) responsible for generating cardiac output in these patients. Our

current patient group showed great heterogeneity both in compression data, pressure variables

and PetCO2. The impossibility to create a generalised model to describe PetCO2 changes in the

entire patient population illustrates this heterogeneity and highlights the individual aspects of

each patient.

Another limitation is found in the methodology used to analyse the patients. All used

variables were considered to be independent, while in fact they are not. ΔCP was defined in

this study as the difference between Ppeak and Pvent, rendering this variable automatically

dependent of the other two. The peak pressure and area under the curve of the compression

peaks are dependent of depth and rate of compressions. Lastly the average intrathoracic

pressure is in fact a summation of all possible factors capable of changing the total pressure in

the thoracic cavity: compression depth and rate, ventilation pressure and peak pressure.

Neither of these intervariable dependencies are taken into account when the individual patient

models were created.

The majority of included patients presented with asystole or pulseless electrical activity. Only

five patients (10%) presented with VT/VF in the total patient population. In the included

24

group three patients (11%) presented with VF/VT. Though the incidence of patients

presenting with VF during OHCA is declining, current literature states that 20 to 40 % of

patients with OHCA will present with ventricular fibrillation (Cobb et al., 2002; Herlitz et al.,

2004). These numbers prompt the possibility that the patient models presented is this study

may primarily apply to patients presenting with asystole or PEA.

This study was set up as a pilot project, testing for the first the time the combination of

intratracheal pressure sensors and PetCO2 monitoring in a out-of-hospital resuscitation setting.

Especially during the initial phase of the study, we encountered several technical difficulties

with the PetCO2 sensor, pressure transducers and/or the Oxylog 3000 ventilator. Consequently

only 53% of patients suffering from OHCA were included in this study. We had no previous

experience with the PetCO2 sensor in our emergency department prior to the start of this study.

Several episodes of technical malfunctioning of the PetCO2 sensor led to the exclusion of five

patients during the months of February and April (5/51, 10%). The pressure transducers were

omitted or applied only after obtaining ROSC in several resuscitations (10/51, 20%). Another

recurring problem is the clogging of the small tube of the pressure sensors, placed in the

endotracheal tube, due to bloody or mucous secretions (3/51, 6%). During the development of

the pressure measurement apparatus, both a different internal diameter and different method

for cutting off the ends of the small tube were tried. Unfortunately a solution has yet to be

found. Difficult ventilation in patients was another problem. During this study an Oxylog

3000 ventilator with intermittent positive pressure ventilation was used. When encountering a

patients with severe airway disease or airway obstruction, the airway pressure spiked and the

ventilator automatically provided an oscillatory airflow pattern, producing rapid changes of

airway pressures. This airflow pattern generated a jerky inspiratory pattern with very high

airway pressures. A bench study confirmed these observations (Frank et al., 2005). It made

the analysis of the corresponding pressure waveform practically impossible, leading to patient

exclusion (2/51, 4%).

Patients who were exclusively manually ventilated were excluded from the study. The minute

volume and ventilator frequency during manual ventilation changes constantly, generating a

different and unpredictable pressure waveform compared to mechanical ventilation. It has

been demonstrated that PetCO2 in situations of low flow is limited by the cardiac output and

not by ventilatory changes (Blumenthal and Voorhees, 1997; Jin et al., 2000). A porcine

model also showed that diminishing the minute volume with 50% will not alter the PetCO2 nor

the PaCO2 in resuscitated pigs (Winkler et al., 1998). Despite these two observations, we

25

opted to omit these patients for further analysis to avoid any possible alterations in PetCO2 due

to changes in ventilatory pattern.

26

Perspectives for further research

This study demonstrated that most patients used “a cardiac pump mechanism” to generate

flow during resuscitation. We demonstrated a relationship between an increase in

compression depth and PetCO2. The next phase to unravel the exact influence of cardiac

compression on cardiac output should be approached in a prospective manner. Using a

mechanical thumper or the voice feedback provided by the accelerometer, a series of fixed

compressions depths (e.g. 5 cm, 6 cm and 7 cm) should be sustained during a fixed period of

time in patients suffering from OHCA, who are intubated after application of the PetCO2

sensor and pressure sensors. This way the correct impact of deeper compressions on PetCO2

and intrathoracic pressure differences can be ascertained. It will be possible to look for the

impact of patient‟s characteristics on the optimal compression depth. This could be a first step

in creating a „patient individual‟ resuscitation.

This study also demonstrated that, although “a thoracic pump” is probably present in all

patients, only a minority of patients accessed this mechanism to amplify the cardiac output

during their resuscitation. The pressure differences in the chest were currently obtained using

different ventilatory settings. PEEP, tidal volume and respiratory frequency were different for

every patient and sometimes even during the resuscitation of a single patient. To further

ascertain the effect of intrathoracic pressure changes on circulation, these parameters should

be investigated in a prospective study. While holding all other ventilatory parameters

constant, changes in minute volume, inspiratory/expiratory time, ventilatory frequency, PEEP

or a combination of these parameters could be made. These changes will reflect themselves in

changes in the pressure waveform, altering intrathoracic pressure differences. By using

PetCO2, it would be possible to link these pressure differences to changes in cardiac output.

By changing the ventilatory parameters and coupling them to patients‟ characteristics, it will

be possible to ascertain „patient-individual‟ ventilatory parameters which are necessary to

obtain a maximised cardiac output in a specific patient.

While both superficial and deep pressure measurements were made, at present only deep

measurements are used in the analysis. The pressure difference between both measurements

makes it possible to calculate and visualize the direction of air flow and calculate the tidal

volume given during each ventilation without the need to use other equipment. This could

give the treating physician a real-life image of air movement during the resuscitation.

27

Currently the PetCO2 probe and the accelerometer are coupled to the defibrillator. The

pressure sensors, amplifiers and logger are connected to a separate external device without a

display. The treating physician had no visible access to the pressure data during the

resuscitation. Research should focus on making this pressure device more portable and usable

by means of a monitor and an application to make prospective research possible. Ideally, both

the accelerometer, PetCO2 sensor and the pressure sensors should be integrated in one device,

integrating the information of both separate devices. This device could include a monitor

visualizing both compression and pressure data and to be used at the treating physician‟s

discretion.

Eventually the compression data, the pressure data, corresponding PetCO2 and patient

characteristics can be integrated in „a smart resuscitation system‟. This automated system

could be programmed to perform resuscitation according to current guidelines or to fully

optimize both pump mechanisms in order to obtain a maximum cardiac output, reflected by a

maximized PetCO2. It could be programmed to use a „trial and error‟ method, trying different

compression and ventilator setting, to optimize cardiac output. The responsibility for the

entire resuscitation process lies of course with the treating physician, whereas the „smart

resuscitation system‟ is used to support the resuscitation process.

28

Conclusion

We developed a method to differentiate the effect of both the “cardiac” and “thoracic pump

mechanism”. Most patient made use of a “cardiac pump mechanism” to generate flow during

resuscitation. Only a minority of patients accessed a “thoracic pump mechanism” to further

optimize PetCO2. We believe nonetheless that both mechanisms can be used in all patients,

under appropriate circumstances. We also demonstrated that while negative intrathoracic

pressure negatively affects PetCO2, a moderately increased intrathoracic pressure showed a

beneficial effect on PetCO2.

29

References

AUFDERHEIDE T.P., PIRRALLO R.G., PROVO T.A. ET AL.: Clinical evaluation of an

inspiratory impedance threshold device during standard cardiopulmonary resuscitation in

patients with out-of-hospital cardiac arrest. Crit Care Med, 2005, 734-740.

AUFDERHEIDE T.P., PIRRALLO R.G., YANNOPOULOS D. ET AL.: Incomplete chest

wall decompression: a clinical evaluation of CPR performance by EMS personnel and

assessment of alternative manual chest compression-decompression techniques.

Resuscitation, 2005, 353-362.

AUFDERHEIDE T.P., SIGURDSSON G., PIRRALLO R.G. ET AL.: Hyperventilation-

induced hypotension during cardiopulmonary resuscitation. Circulation, 2004, 1960-1965.

BABBS C.F., KEMENY A.E., QUAN W. ET AL.: A new paradigm for human resuscitation

research using intelligent devices. Resuscitation, 2008, 306-315.

BABBS C.F., VOORHEES W.D., FITZGERALD K.R. ET AL.: Relationship of blood

pressure and flow during CPR to chest compression amplitude: evidence for an effective

compression threshold. Ann Emerg Med, 1983, 527-532.

BERG R.A., HENRY C., OTTO C.W. ET AL.: Initial end-tidal CO2 is markedly elevated

during cardiopulmonary resuscitation after asphyxia cardiac arrest. Ped Emerg Care, 1996,

245-248.

BERG R.A., SANDERS A.G., KERN K.B. ET AL.: Adverse hemodynamic effects of

interrupting chest compressions for rescue breathing during cardiopulmonary resuscitation for

ventricular fibrillation cardiac arrest. Circulation, 2001, 2465-2470.

BLUMENTHAL S.R., VOORHEES W.: The relationship between carbon dioxide excretion

during cardiopulmonary resuscitation to regional blood flow and survival. Resuscitation,

1997, 135-143.

CANTINEAU J.P., LAMBERT Y., MERCKX P. ET AL.: End-tidal carbon dioxide during

cardiopulmonary resuscitation in humans presenting mostly with asystole: a predictor of

outcome. Crit Care Med, 1996, 791-796.

CHANDRA N., WEISFELDT M.L., TSITLIK J. ET AL.: Augmentation of carotid flow

during cardiopulmonary resuscitation by ventilation at high airway pressure simultaneous

with chest compression. Am J Cardiol, 1981, 1053-1063.

CRILEY J.M., BLAUFUSS A.H., KISSEL G.L.: Cough induced cardiac compression.

JAMA, 1976, 1246-1250.

30

COBB L.A., FAHRENBRUCH C.E., OLSUFKA M. ET AL.: Changing incidence of out-of-

hospital ventricular fibrillation, 1980-2000. JAMA, 2002, 3008-3013.

DEAKON C.D., NOLAN J.P., SOAR J. ET AL.: European Resuscitation Council Guidelines

for resuscitation 2010 section 4. Adult advanced life support. Resuscitation, 2010, 1305-1352.

EDELSON D.P., ABELLA B.S., KRAMER-JOHANSEN J. ET AL.: Effects of compression

depth and pre-shock pauses predict defibrillation failure during cardiac arrest. Resuscitation,

2006, 137-145.

EDELSON D.P., LITZINGER B., ARORA V. ET AL.: Improving in-hospital cardiac arrest

process and outcomes with performance debriefing. Arch Intern Med, 2008, 1063-1069.

ENGDAHL J., BÅNG A., KARLSON B.W. ET AL.: Characteristics and outcome among

patients suffering from out of hospital cardiac arrest of non-cardiac aetiology. Resuscitation,

2003, 33-41.

FENELEY M.P., MAIER G.W., KERN W.B. ET AL.: Influence of compression rate on

initial success of resuscitation and 24 hour survival after prolonged manual cardiopulmonary

resuscitation in dogs. Circulation, 1988, 240-250.

FRANK G.E., TRIMMEL H., FITZGERALD R.D.: Inspiratory oscillatory flow with a

portable ventilator: a bench study. Crit Care Med, 2005, 315-322.

GARNETT A.R., ORNATO J.P., GONZALEZ E.R. ET AL.: End-tidal carbon dioxide

monitoring during cardiopulmonary resuscitation. JAMA, 1987, 512-515.

GRMEC S., KLEMEN P.: Does the end-tidal carbon dioxide (EtCO2) concentration have a

prognostic value during out-of-hospital cardiac arrest? Eur J Emerg Med, 2001, 236-269.

GRMEC S., KRIZMARIC M., MALLY S. ET AL.: Utstein analysis of out-of-hospital

cardiac arrest – Bystander CPR and end expired carbon dioxide. Resuscitation, 2007, 404-

414.

GRMEC S., LAH K., TUSEK-BUNC K.: Difference in end-tidal CO2 between asphyxia

cardiac arrest and ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest in the

prehospital setting. Crit Care, 2003, 139-144.

HANDLEY A.J., KOSTER R., MONSIEURS K. ET AL.: European Resuscitation Council

guidelines for resuscitation 2005 section 2. Adult basic life support and use of automated

external defibrillators. Resuscitation, 2005, 7-23.

HERLITZ J., ENGDAHL J., SVENSSON L. ET AL.: Decrease in the occurrence of

ventricular fibrillation as the initially observed arrhythmia after out-of-hospital cardiac arrest

during 11 years in Sweden. Resuscitation, 2004, 283-290.

31

HODGKIN B.C., LAMBREW C.T., LAWRENCE F.H. ET AL.: Effects of PEEP and of

increased frequency of ventilation during CPR, Crit Care Med, 1980, 123-126.

IDO Y., GOTO H., LAVIN M.J. ET AL.: Effects of positive end-expiratory pressure on

carotid blood flow during closed-chest cardiopulmonary resuscitation in dogs. Anesth Analg,

1982, 557-560.

JIN X., WEIL M.H., TANG W. ET AL.: End-tidal carbon dioxide as a noninvasive indicator

of cardiac index during circulatory shock. Crit Care Med, 2000, 2415-2419.

JUDE J.R., KOUWENHOUWER W.B., KNICKERBOCKER G.G.: Cardiac arrest: report of

application of external cardiac massage in 118 patients. JAMA, 1961, 1063-1070.

KALENDA Z.: The capnogram as a guide to the efficacy of cardiac massage. Resuscitation,

1987, 259-263.

KERN K.B., SANDERS A.B., RAIFE J. ET AL.: A study of chest compression rates during

cardiopulmonary resuscitation in humans. The importance of rate-directed chest

compressions. Arch Intern Med, 1992, 145-149.

KERN K.B., SANDERS A.B., VOORHEES W.D. ET AL.: Changes in expired end-tidal

carbon dioxide during cardiopulmonary resuscitation in dogs: a prognostic guide for

resuscitation efforts. J Am Coll Cardiol, 1989, 1184-1189.

KOLAR M., KRIZMARIC M., KLEMEN P. ET AL.: Partial pressure of end-tidal carbon

dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective

observational study. Crit Care, 2008, 115-127.

KOUWENHOUWER W.B., JUDE J.R., KNICKERBOCKER G.G.: Closed-chest cardiac

massage. JAMA, 1960, 1064-1067.

KOSTER R.W., BAUBIN M.A., BOSSAERT L.L. ET AL.: European Resuscitation Council

guidelines for resuscitation 2010 section 2. Adult basic life support and use of automated

external defibrillators. Resuscitation, 2010, 1277-1292.

KRAMER-JOHANSEN J., MYKLEBUST H., WIK L. ET AL.: Quality of out-of-hospital

resuscitation with real time automated feedback: a prospective interventional study.

Resuscitation, 2006, 283-292.

KREMERS M.S., BLACK W.H., WELLS P.J.: Sudden cardiac death: etiologies,

pathogenesis, and management. Dis Mon, 1989, 381-445.

LAH K., KRIZMARIC M., GRMEC S.: The dynamic pattern of end-tidal carbon dioxide

during cardiopulmonary resuscitation – difference between asphyxia cardiac arrest and

ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. Crit Care, 2011, Epub.

32

LEVINE R.L., WAYNE M.A., MILLER C.C.: End-tidal carbon dioxide and outcome of out-

of-hospital cardiac arrest. N Eng J Med, 1997, 301-306.

MAIER G.W., TYSON G.S., OLSEN C.O. ET AL.: The physiology of external cardiac

massage: high-impulse cardiopulmonary resuscitation. Circulation, 1984, 86-101.

MERN-PERNAT A., WEIL M.H., WANCHUN T. ET AL.: Optimizing timing of ventricular

defibrillation. Crit Care Med, 2001, 2360-2365.

MILANDER M.M., HISCOK P.S., SANDERS A.B. ET AL.: Chest compression and

ventilation rates during cardiopulmonary resuscitation: the effects of audible tone guidance.

Acad Emerg Med, 1995, 708-713.

NOLAN J.P., DEAKIN C.D., SOAR J. ET AL.: European Resuscitation Council guidelines

for resuscitation 2005 section 4. Adult advanced life support. Resuscitation, 2005, 539-586.

ORNATO J.P., GONZALEZ E.R., GARNETT A.R. ET AL.: Effect of cardiopulmonary

resuscitation compression rate on end-tidal carbon dioxide concentration and arterial pressure

in man. Crit Care Med, 1988, 241-245.

PARADIS N.A., MARTIN G.B., RIVERS E.P. ET AL.: Coronary perfusion pressure and the

return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA, 1990,

1106-1113.

PELL J.P., SIREL J.M., MARSDEN A.K. ET AL.: Presentation, management and outcome

of out of hospital cardiopulmonary arrest: comparison by underlying aetiology. Chest, 2003,

839-842.

REYNOLDS J.C., SALCIDO D.D., MENEGAZZI J.J.: Coronary perfusion pressure and

return of spontaneous circulation after prolonged cardiac arrest. Prehosp Emerg Care, 2010,

78-84.

RICH S., WIX H.L., SHAPIRO E.P.: Clinical assessment of heart chamber size and valve

motion during cardiopulmonary resuscitation by two-dimensional echocardiography. Am

Heart J, 1981, 368-373.

SANDERS A.B., KERN K.B., OTTO C.W. ET AL.: End-tidal carbon dioxide monitoring

during cardiopulmonary resuscitation. A prognostic indicator for survival. JAMA, 1989,

1347-1351.

SCHULTZ J.J., COFFEEN P., SWEENEY M. ET AL.: Evaluation of standard and active

compression-decompression CPR in an acute human model of ventricular fibrillation.

Circulation, 1994, 684-693.

33

SWENSON R.D., WEAVER W.D., NISKANEN R.A. ET AL.: Hemodynamics in humans

during conventional and experimental methods of cardiopulmonary resuscitation. Circulation,

1988, 630-639.

TIMMERMAN A., RUSSO S.G., EICH C. ET AL.: The out-of-hospital esophageal and

endobronchial intubations performed by emergency physicians. Anesth Analg, 2007, 619-

623.

VON PLANTA M., VON PLANTA I., WEIL M.H. ET AL.: End tidal carbon dioxide as an

haemodynamic determinant of cardiopulmonary resuscitation in the rat. Cardiovasc Res,

1989, 364-368.

WARD K.R., YEALY D.M.: End-tidal carbon dioxide monitoring in emergency medicine,

part 2: clinical applications. Acad Emerg Med, 1998, 637-646.

WAYNE M.A., LEVINE R.L., MILLER C.C.: Use of end-tidal carbon dioxide to predict

outcome in prehospital cardiac arrest. Ann Emerg Med, 1995, 762-767.

WERNER J.A., GREENE H.L., JANKO C. L. ET AL.: Visualization of cardiac valve motion

in man during external compression using two-dimensional echocardiography: implications

regarding the mechanism of blood flow. Circulation, 1981, 1417-1421.

WINKLER M., MAURITZ W., HACKL W. ET AL.: Effects of half the tidal volume during

cardiopulmonary resuscitation on acid-base balance and haemodynamics in pigs. Eur J Emerg

Med ,1998, 201-206.

YANNOPOULOS D., AUFDERHEIDE T.P., MCKNITE S.H. ET AL.: Hemodynamic and

respiratory effects of negative tracheal pressure during CPR in pigs. Resuscitation, 2006, 487-

494.

YANNOPOULOS D., NADKARNI V.M., MCKITE S.H. ET AL.: Intrathoracic pressure

regulator during continuous-chest-compression advanced cardiac resuscitation improves vital

organ perfusion pressures in a porcine model of cardiac arrest. Circulation, 2005, 803-811.

YU T., WEIL M.H., TANG W. ET AL.: Adverse outcomes of interrupted precordial

compressions during automated defibrillation. Circulation, 2002, 368-372.

34

Acknowledgements

We are grateful to Prof Dr K Monsieurs for the guidance, support and helpful tips writing this

paper, to Charlotte Vankeirsbilck for the administrative support and the introduction in the

miraculous world of MSR, Zoll and Lazarus, to Dr S Lemoyne for the help with the

interpretation of the results and hints for further data processing and to Alain Kalmar for

writing the Visual Basic macro and helping with the interpretation of the results. Also to Lien

Yde for the mental support and the numerous days spent in a small windowless office. Last

but not least a big thank you for all the physicians, EMTs, nurses and administrative

personnel of the Emergency Department of the Ghent University Hospital for the data

collecting during every resuscitation.