Petco2 Of 8 Mmhg Means

Braz J Cardiovasc Surg. 2016 November-Dec; 31(6): 468–473.

PetCO₂, VCO₂ and CorPP Values in the Successful Prediction of the Return of Spontaneous Circulation: An Experimental Written report on Unassisted Induced Cardiopulmonary Abort

Ana Carolina Longui Macedo, MSc,¹ Luiz Claudio Martins, MD, PhD,ⁱ Ilma Aparecida Paschoal, MD, PhD,^ane Carlos Cesar Ivo Sant'Ana Ovalle, PhD,² Sebastião Araújo, MD, PhD,¹ and Marcos Mello Moreira, PhD^one

Ana Carolina Longui Macedo

¹ Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Luiz Claudio Martins

^one Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Ilma Aparecida Paschoal

¹ Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Carlos Cesar Ivo Sant'Ana Ovalle

² Universidade Paulista, São Paulo, SP, Brazil.

Sebastião Araújo

^ane Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Marcos Mello Moreira

¹ Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Received 2016 Jun 24; Accepted 2016 Sep 19.

Abstract

Introduction

During cardiac arrest, stop-tidal CO₂ (PetCO₂), VCO₂ and coronary perfusion pressure fall abruptly and tend to return to normal levels after an effective return of spontaneous circulation. Therefore, the monitoring of PetCO_ii and VCO₂ past capnography is a useful tool during clinical direction of cardiac arrest patients.

Objective

To appraise if PetCO_two, VCO₂ and coronary perfusion force per unit area are useful for the prediction of return of spontaneous apportionment in an animal model of cardiac arrest/cardiopulmonary resuscitation treated with vasopressor agents.

Methods

42 swine were mechanically ventilated (FiO₂=0.21). Ventricular fibrillation was induced and, subsequently 10 min, unassisted cardiac arrest was initiated, followed by compressions. After 2 min of basic cardiopulmonary resuscitation, each group received: Adrenaline, Saline-Placebo, Terlipressin or Terlipressin + Adrenaline. Two minutes later (4^thursday min of cardiopulmonary resuscitation), the animals were defibrillated and the ones that survived were observed for an boosted 30 min period. The variables of interest were recorded at the baseline period, ten min of ventricular fibrillation, 2^nd min of cardiopulmonary resuscitation, 4^th min of cardiopulmonary resuscitation, and 30 min after return of spontaneous circulation.

Results

PetCO₂ and VCO₂ values, both recorded at 2 min and 4 min of cardiopulmonary resuscitation, have no correlation with the return of spontaneous apportionment rates in any group. On the other hand, higher values of coronary perfusion pressure at the 4th min of cardiopulmonary resuscitation have been associated with increased return of spontaneous circulation rates in the adrenaline and adrenaline + terlipressin groups.

Conclusion

Although higher values of coronary perfusion pressure level at the 4th min of cardiopulmonary resuscitation take been associated with increased return of spontaneous circulation rates in the animals that received adrenaline or adrenaline + terlipressin, PetCO_ii and VCO₂ have not been shown to exist useful for predicting render of spontaneous circulation rates in this porcine model.

Keywords: Center Arrest, Induced, Cardiopulmonary Resuscitation, Capnography, Epinephrine

Abbreviations, acronyms & symbols
ADR	=Adrenaline
AHA	=American Heart Association
CA	=Cardiac arrest
CorPP	=Coronary perfusion pressure level
CPR	=Cardiopulmonary resuscitation
DC	=Decreased cardiac output
IMV	=Invasive mechanical ventilation
PetCO²	=End-tidal CO_two
ROSC	=Return of spontaneous apportionment
TP	=Terlipressin
VF	=Ventricular fibrillation
Five/Q	=Ventilation/perfusion ratio

INTRODUCTION

Cardiac arrests occur daily in big numbers in several countries of the globe and, for the nigh part, issue in decease. Cardiopulmonary resuscitation (CPR) is proposed by the American Heart Clan (AHA) as an easy intervention, with the goal of reducing the number of deaths, despite discouraging statistics showing that simply a pocket-sized number of patients survive later on this event. The apply of methods that assess the effectiveness of CPR and that are preferably non-invasive, indicating the metabolic country and the dynamics of the cardiovascular organization, would be of not bad value. Substantially, CPR consists of transmission compressions of the patient'due south thorax, in an endeavour to help create an bogus anterograde blood flow, combined with either a noninvasive ventilation technique (e.grand., mouth-to-mouth) or invasive mechanical ventilation in order to oxygenate the claret that reaches the lungs^[ ⁱ ^].

Capnography presents itself as a non-invasive method, applicable at the bedside, that allows for the cess of cardiorespiratory status both in experimental² ^- ⁶ ^] and clinical studies^[ ⁷ ^- ¹² ^]. In addition, it is considered an indicator and/or guide for decisions that enables the assessment of the quality of the CPR maneuvers^[ ^xiii ^]. Capnography evaluates and monitors physiological conditions by measuring exhaled CO_ii through an infrared lite sensor. CO₂ excretion (VCO_ii) and partial pressure of CO₂ at the end of the exhalation (PetCO₂) are indicative of O_two consumption by the oxidative metabolism in the tissues and those values are closely related to the pulmonary ventilation/perfusion ratio (V/Q); hence, it is expected that both volition increase in an effective CPR. Therefore, the monitoring of exhaled CO₂ has been proposed and used every bit a non-invasive method to assess cardiorespiratory role, especially in situations of decreased cardiac output (DC), such as during shock and CPR, and its use is compulsory in Surgical Centers^[ ¹⁴ ^].

Capnography has been regarded as a potentially useful monitoring method in evaluating the effectiveness of CPR maneuvers, despite limitations and controversies surrounding the subject^[ ^xv ^]. Brute and human studies have shown a good correlation between PetCO₂ and DC during stages of decreased blood flow and during CPR^[ ^sixteen ^]. PetCO₂ can reflect the pulmonary blood flow generated in CPR if CO₂ product and alveolar ventilation are relatively constant during resuscitation maneuvers; however, information technology is difficult to be measured when CPR is stopped because of changes in the alveolar dead infinite and minute volume ratio, which affects the correlation betwixt PetCO₂ and DC^[ ¹⁷ ^].

Some studies suggest that the increase in PetCO₂ during CA is a predictor of the success of the CPR. Considering the consequence of cardiac arrest, CPR and the post-result, we can find several changes in PetCO₂ levels. Information technology is known that the values of PetCO₂ at the starting time of ventricular fibrillation (VF) autumn significantly, and this reduction is attributed to decreased pulmonary claret flow, which is insufficient to behave and eliminate the CO₂ produced in the tissues. Plainly, in extreme cases of low DC, there would besides be a lower CO₂ production considering of the anaerobic metabolism, given the low O_ii supply to the tissues. Once CPR is started, and it is effective in oxygenating the claret and increasing the tissue menstruation, PetCO₂ values as well increase, equally an increase in claret flow must occur in the pulmonary capillaries, which in turn results in the exhalation of CO₂. When the return of spontaneous circulation (ROSC) occurs, those values increase significantly, reaching levels comparable to those before CA. These changes are useful to quantify the effectiveness and success of the CPR maneuvers as well as to assess the cardiorespiratory status of the patient later ROSC. It has been observed that there is no survival for a PetCO_ii < 5 mmHg^[ ¹⁸ ^].

Some studies have mentioned a few factors that can affect the levels of CO₂ eliminated by expiration. Among them, we can mention alveolar ventilation, DC, the area of distribution of blood menstruum in the body, and the production of CO₂ by tissues. Some authors also reported that the measurement of CO_ii is not able to reflect the certain success of CPR, since the results do not ostend those reported in studies that accept measured other parameters^[ ¹⁹ ^]. However, capnography is still used and regarded as the all-time and about effective non-invasive method of measuring the elimination of CO₂ in Emergency Rooms, Surgery Centers, and ICU in cases of CA, being considered essential when performing CPR, for conclusion-making, assessment of its initial success (ROSC), and subsequent clinical development (cardiorespiratory stabilization).

The objective of this study was to appraise if PetCO_ii, VCO₂, and coronary perfusion pressure level (CorPP) values are useful in predicting the success of ROSC in an animal model of CA/CPR using vasopressor agents.

METHODS

This study was approved by the Institutional Review Committee for Experiments with Animals (EAEC-IB-Unicamp-1276-1/2007) and information technology was conducted in the laboratory of Experimental Surgery and Medicine, School of Medical Sciences - Universidade Estadual de Campinas (UNICAMP), São Paulo, Brazil.

The methods used were the same as the ones described in the novel commodity of Ovalle et al.^[ ²⁰ ^], using 40-2 Large-White, immature swine, weighing approximately 20 kg, which presented ROSC. Under anesthesia with ketamine (x mg.kg^-1 intramuscularly) and thiopental (25 mg.kg^-1 intravenously), the animals were intubated endotracheally and ventilated with FiO_two=0.21 (and positive pressure at the end of exhalation of 0 cmH2O), a fixed respiratory rate (10 cpm), and a tidal volume ranging from 15 to 20 mL/kg (Ventilator DX-3010^®, Dixtal, Brazil), in gild to maintain a PetCO_ii between 36-44 mmHg (Respiratory Profile Monitor CO_twoSMO Plus 8100^®, Dixtal/Novametrix, Respironics, Murrisville, PA, USA). Surgical vascular catheterizations were performed to mensurate pressure in the thoracic aorta and the right atrium (DX-2020^®, Dixtal, Brazil).

Using a bipolar pacemaker placed on the correct ventricular cavity, nosotros induced VF, which remained without aid for 10 minutes. Then, the animals were kept in the supine position and reattached to the mechanical ventilator, and we started CPR (100 compressions/10 ventilations/min, continuously, without alternating with chest compressions).

After two minutes, the animals were allocated into four groups (randomized and blind), receiving via central IV: Group i - Adrenaline (ADR - 45 µg.kg^-one); Group ii - saline-placebo (10 ml); Group iii - Terlipressin (TP* - *Glypressin^®, Laboratórios Ferring Ltda., Brazil - 20 µg.kg^-1); and Group 4 - TP (twenty µg.kg^-1) + ADR (45 µg.kg^-1). All drugs were diluted in saline solution (ten ml), in equal syringes, thus the primary resuscitator did not know what drug was existence administered.

Two minutes after injecting the drugs, defibrillation was performed with sequential shocks (every 15 seconds) of 200 J (Biphasic Defibrillator, Cardiomax, Instramed, Brazil), until ROSC, a pace other than VF was obtained or ii minutes of attempts had elapsed. We gear up the return of spontaneous apportionment every bit the recovery of spontaneous eye charge per unit with a systolic blood pressure level ≥ sixty mmHg for ≥ 5 minutes. The animals were considered as survivors when they remained alive, with a systolic blood pressure ≥ sixty mmHg, without the use of additional vasopressor agents for 30 minutes subsequently ROSC.

During spontaneous circulation, CorPP was calculated as the difference between mean arterial pressure level and mean cardinal venous pressure level. During CPR maneuvers, CorPP was calculated as diastolic arterial force per unit area (decompression) minus central venous pressure level (decompression)^[ ²¹ ^]. At the completion of the experiment, all animals resurrected were killed with an overdose of thiopental and nineteen.1% potassium chloride.

Statistical Analysis

Initially, we performed a descriptive analysis, presented in the form of tables with frequency and measures of the location and dispersion of values. For comparison of the parameters assessed in just one moment betwixt the groups, we used the Kruskal-Wallis examination. For comparison of the parameters measured among the groups and times, we used the analysis of variance (ANOVA) for repeated measures, with transformation by posts, followed by multiple comparisons through the Tukey exam for the location of differences between groups and the contour test for contrasts for the location of the differences between times. To verify the difference between proportions, we used Fisher's exact test. Statistical tests were bilateral and the significance level adopted was five% (P<0.05).

RESULTS

In Table 1, nosotros describe the values of the following variables:

Table 1

Descriptive analysis and comparisons of the variables assessed at baseline (0), 2 min of CPR (2), and 4 min of CPR (4) within and among groups.

	ADR + TP (northward=11)	ADR (n=x)	Placebo (northward=10)	TP (n=xi)	P
PetCO₂ 0^*	42.v±5.2	39.iv+three.5	43.iv+3.5	twoscore.iv+half dozen	^*
VCO₂ 0^¥	121.ii+20.5	133.4+53.seven	110.2+21.two	119.three+twoscore.8	¥
CorPP 0^§	88.9±21	89.seven+19.5	91.0+eighteen.three	85.five+23.2	^§
PetCO_ii 2^*	50.seven+13.1	37.4+14	43.four+sixteen.3	44.two+17.7	^*
VCO₂ 2^¥	48.7±27.5	57.5+xxx.two	47.5+21.2	45.3+24.5	¥
CorPP 2^§	21.3+10.4	12.vi+12.i	22.seven+13.five	20.2+15.5	^§
PetCO_two 4^*	44.three+15	43.half dozen+19.3	46.3+12.iv	51.0+19.4	^*
VCO₂ 4^¥	46.4+31.ane	49.half dozen+32.9	49.2+21.3	35.5+25.5	¥
CorPP 4^§	44.6+13.1	53.1+15.2	13.vii+12	7.0+10.5	^§

PetCO_ii (mmHg) measured at baseline (earlier induction of CA), two minutes of CPR (before the injection of drugs), and 4 min of CPR (2 min after the injection of drugs and immediately before ventricular defibrillation); there were no statistically significant differences betwixt the groups;
VCO₂ (mL/min) measured at baseline (before consecration of CA), two minutes of CPR (before the injection of drugs), and 4 min of CPR (2 min afterward the injection of drugs and immediately before ventricular defibrillation); although there was a statistically significant decrease in VCO₂ at 2 min and 4 min of CPR in relation to baseline, in that location were no statistically significant differences between the groups at whatever moment;
CorPP (mmHg) measured at baseline (before induction of CA), two minutes of CPR (before the injection of drugs), and 4 min of CPR (ii min after the injection of drugs and immediately earlier ventricular defibrillation). A statistically pregnant increase in CorPP between the ii min of CPR (before the injection of drugs) and 4 min of CPR (two min after the injection of drugs) was observed in the ADR and ADR+TP groups compared to the placebo and isolated TP groups (which was equal to placebo);
Baseline rectal temperature (ºC): ADR: 39.0±0.7; Placebo: 39±0.5; TP: 39.iii±0.6; and ADR+TP: 39.six±0.4 (P=0.2085).

Those aforementioned variables are shown in Figures 1, 2 and three.

An external file that holds a picture, illustration, etc. Object name is rbccv-31-06-0468-g01.jpg

Comparative evolution of the variables assessed at baseline (0), 2 min of CPR (2) and 4 min of CPR in the groups studied. Average value and standard departure of PetCO₂ in each moment and group.

An external file that holds a picture, illustration, etc. Object name is rbccv-31-06-0468-g02.jpg

Comparative evolution of the variables assessed at baseline (0), 2 min of CPR (2) and iv min of CPR in the groups studied. Average value and standard deviation of VCO₂ in each moment and group.

An external file that holds a picture, illustration, etc. Object name is rbccv-31-06-0468-g03.jpg

Comparative evolution of the variables assessed at baseline (0), two min of CPR (2) and four min of CPR in the groups studied. Average value and standard difference of CorPP in each moment and group.

Discussion

Several studies, both clinical and trial, accept investigated the prognostic value of capnography in CA/CPR. The PetCO₂ measured by capnography in intubated patients has been correlated with the quality of CPR maneuvers and with ROSC, considering that it is directly related to DC, which in turn is directly related to pulmonary claret flow, PetCO₂ being its reflection^[ ²² ^]. However, no experimental model under invasive mechanical ventilation (IMV), with PEEP=0 cmH₂O and FiO_ii=0.21, has assessed PetCO₂, VCO₂, and CorPP in the prediction of success of ROSC on unassisted CPR for 10 min using terlipressin (a pro-drug, a vasopressin synthetic analogue, with a longer half-life than vasopressin), adrenaline and their combination as vasopressor agents, in addition to placebo.

Tabular array two

Descriptive analysis and comparison of the percentage of survivors amidst the groups.

Surviving groups	ADR+TP (due north=xi)	ADR (n=10)	Placebo (north=10)	TP (n=11)	Full (north=42)
No n (%)	two (18)	2 (xx)	8 (80)	x (91)	22 (52)
Yeah due north (%)	9 (82)	8 (80)	two (20)	one (9)	20 (48)

In several published studies, PetCO₂ has proved to be a useful variable in assessing the effectiveness of CPR maneuvers and results in unlike models of CA.

In the 1980s, Sanders et al.^[ ²³ ^] monitored the emptying of CO_two (VCO₂) in experimental studies of CA/CPR. The elimination of CO₂ was assessed in different types of breast pinch, and the study reported that all types of maneuvers increased PetCO₂. Piffling more than a decade later, Blumenthal et al.^[ ²⁴ ^], also in an experimental written report, measured PetCO_two and VCO_ii and concluded that college values of PetCO_ii during and subsequently CPR were associated with a better prognosis.

In our written report, at that place was no statistically significant association between the times and the registered values for PetCO₂ with ROSC, although a sudden and immediate increase in PetCO₂ at the beginning of the CPR was observed, which expresses the pulmonary blood flow, and thus, DC. The data indicates that PetCO_two, both at 2 min and 4 min of CPR (more importantly, because it was after the administration of the drugs), is non correlated with ROSC rates, i.east., information technology was not different among the four groups. Nevertheless, we have to consider that in our written report the CA/CPR model was performed on very young (young) animals, being an farthermost CA model, for ten min without whatever aid, and, later this period, the animals were ventilated with an initial FiO₂ (0.21). We should also highlight the fact that we did not alternate between ventilation and compression, which may have compromised the effectiveness of the alveolar ventilation.

In relation to VCO_ii at 2 and iv min of CPR, it did not differ statistically between the four groups and, therefore, it was non indicative of ROSC. On the other manus, CorPP proved to exist significantly higher in the ADR and ADR+TP groups compared to the Placebo and Terlipressin groups at four minutes of CPR, which indicates that CorPP was a predictive factor for ROSC.

Human studies use other variables to assess the successful prediction of ROSC. Different criteria are used, but capnography is also the main focus of the prognostic cess later on CA. I of the kickoff studies in the 1980s by Garnett et al.^[ ²⁵ ^] assessed patients under IMV who presented CA, and they concluded that the monitoring of PetCO₂ during CPR can be useful and serve every bit a guide during resuscitation maneuvers.

Another clinical study, conducted by Sanders et al.^[ ²⁶ ^], assessed PetCO₂ in patients subjected to CPR. The authors reported that all patients listed and those who presented ROSC showed an average PetCO₂ ≥ 10 mmHg. None of the patients with an average PetCO₂ ≤ 10 mmHg presented ROSC. The data in this prospective clinical test indicate that the monitoring of PetCO₂ during CPR tin can be useful in the prediction of ROSC in CPR in humans.

PetCO_two values have been correlated with CorPP and ROSC rate. Thus, in an creature model (dogs) of CA/CPR, Sanders et al.^[ ²⁷ ^], in another report, plant a significant correlation (P<0.01) betwixt PetCO_two and CorPP. The information in this study were confirmed past the aforementioned group, in the same year, with small variations in the method. All the same, the actual physiological relationship between CorPP and PetCO₂ during CPR remains uncertain^[ ²³ ^].

In our study, nosotros accept observed a significant increment in CorPP (P<0.0001) in the 4^th minute of CPR (after drugs) in relation to the two^nd min (before drugs) of CPR in the ADR and ADR+TP groups. Nonetheless, the same beliefs was no observed in PetCO₂ and VCO_two.

The utilize of vasopressor agents is suggested in the first cycles of CPR^[ ²⁵ ^]. For different types of CA, vasopressor, adrenaline or vasopressin can be administered in social club to increment myocardial and cognitive blood flow. In the report of Ovalle et al.^[ ²⁰ ^], the apply of some vasopressor agents during CPR was assessed. It was observed that ADR and its combination with terlipressin, but not isolated terlipressin, were effective in increasing CorPP and ROSC. Furthermore, the ADR+TP combination provided greater hemodynamic stability after ROSC in the surviving animals, suggesting that TP can be a useful drug in handling hypotension after CPR^[ ²⁸ ^].

In most published studies, both clinical and experimental ones, the initial, final, maximum and minimum readings show higher values of PetCO₂ in patients who presented ROSC. These authors highlight that clinical studies receive influences from diseases already present in patients, and this factor should be considered^[ ¹⁸ ^].

The PetCO₂ values assessed in many (clinical and experimental) studies can assist in verifying the effectiveness of CPR maneuvers in order to guide, with due caution, the actual results of resuscitation, since very low PetCO_two values may point that there is no more reason to continue the efforts of CPR^[ ²⁹ ^].

In brusk, PetCO_two and VCO_two values obtained past volumetric capnography accept differed from the findings in some published studies. In add-on, those values are not correlated with hemodynamic variables (CorPP) or with ROSC rates in our experimental model with immature swine, in which CA was induced past ventricular fibrillation and the animals remained without assist for 10 min with subsequent CPR. Information technology should exist noted that the animals were under IMV, with FiO_ii=0.21 and PEEP=0 cmH₂O, and we used vasopressor agents (ADR and TP; isolated or in association).

Decision

From the results obtained in the report, both PetCO₂ and VCO₂ showed no correlation with ROSC, although VCO₂ was 50% lower during the CPR maneuvers (would it be more sensitive in the detection of a decrease in pulmonary blood flow?). Although we cannot assert with certainty, some hypotheses were made to explain this fact, namely: FiO_two=0.21 during the entire experiment, immaturity of the animals, fourth dimension of non-help after CA (10 minutes), and positive pressure (IMV) in the CPR, which may accept led to an even sharper decrease in the right preload. Thus, further studies are needed to verify the value of volumetric capnography (PetCO₂ and VCO₂) to guide the effectiveness of CPR maneuvers, especially with the apply of adjuvant vasopressor agents.

Authors' roles & responsibilities
ACLM	Analysis and/or data interpretation; manuscript writing or disquisitional review of its content; final manuscript blessing
LCM	Analysis and/or data interpretation; manuscript writing or disquisitional review of its content; terminal manuscript approval
IAP	Analysis and/or data interpretation; manuscript writing or critical review of its content; final manuscript approval;
CCISO	Formulation and blueprint written report; realization of operations and/ or trials; analysis and/or data interpretation; manuscript writing or critical review of its content
SA	Conception and study blueprint; execution of operations and/ or trials; assay and/or data interpretation; manuscript writing or disquisitional review of its content; terminal manuscript approval;
MMM	Execution of operations and/or trials; assay and/or data interpretation; manuscript writing or critical review of its content; final manuscript approval

ACKNOWLEDGMENTS

We are grateful to Fundação de Amparo à Pesquisa practise Estado de São Paulo (Fapesp) (process Nº. 07/08315-0) and to Fundo de Apoio ao Ensino, Pesquisa e Extensão (Faepex)-Unicamp (process Nº 17809) for their financial support; to Ferring Laboratories-Brazil-Ltda, for their kind donation of two one mg terlipressin vials for the pilot studies; to the biologists Ana C. Moraes and William A. Silva, from Núcleo de Medicina e Cirurgia Experimental-FCM-Unicamp, for their technical assistance during experimental procedures; and to the statisticians from the Inquiry Commission-FCM-Unicamp, for their technical assist during data assay.

The authors besides give thanks Espaço da Escrita - General Coordination of the University - UNICAMP - for the language services provided.

Footnotes

This study was carried out at Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

This study was funded past the São Paulo Research Foundation (FAPESP), process Nº 07/08315-0, and the Instruction, Research and Extension Support Fund (FAEPEX), UNICAMP, procedure Nº 17809.

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