Evaluation of the cardiopulmonary status using a noninvasive respiratory profi le monitor in chronic obstructive lung disease patients during low-ventilation strategy

Introduction Invasive mechanical ventilatory support has two important considerations in respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (COPD): they are minimizing regional overdistention and managing positive endexpiratory pressure (PEEP). Overdistention injury occurs when an excessive end-inspiratory alveolar ‘stretch’ physically damages alveolar structures and produces local and systemic infl ammation (ventilatorinduced lung injury). Th is stretch injury may be a consequence of excessive tidal volumes. Th is has led to recommendation to reduce tidal volumes (e.g. 5–7 ml/kg) to protect the lung in acute exacerbation of COPD [1]. Monitoring of the ventilated patient should focus on the assessment of patient response to and titration of mechanical ventilation, while avoiding complications [2]. Th e use of volumetric capnography in mechanically ventilated patients has the capability to monitor not only lung mechanics but also cardiac and respiratory interaction noninvasively [3].


Introduction
Invasive mechanical ventilatory support has two important considerations in respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (COPD): they are minimizing regional overdistention and managing positive endexpiratory pressure (PEEP). Overdistention injury occurs when an excessive end-inspiratory alveolar 'stretch' physically damages alveolar structures and produces local and systemic infl ammation (ventilatorinduced lung injury). Th is stretch injury may be a consequence of excessive tidal volumes. Th is has led to recommendation to reduce tidal volumes (e.g. 5-7 ml/kg) to protect the lung in acute exacerbation of COPD [1]. Monitoring of the ventilated patient should focus on the assessment of patient response to and titration of mechanical ventilation, while avoiding complications [2]. Th e use of volumetric capnography in mechanically ventilated patients has the capability to monitor not only lung mechanics but also cardiac and respiratory interaction noninvasively [3].

Study design
Forty patients, who presented with clinical and radiological evidence of COPD with respiratory failure due to exacerbation and were in need of mechanical ventilation, were recruited in the respiratory ICU of Abbassia Chest Hospital in the period between 2011 and 2013. Th ese patients were divided into two groups: 20 COPD patients with the predominant pathology of chronic bronchitis (CB) and 20 patients with the predominant pathology of emphysema disease; we used clinical criteria, clinical history with compatible physical fi ndings, and evidence of hyperinfl ation on chest radiograph, in support of the diagnosis of COPD and for diff erentiation between Evaluation of the cardiopulmonary status using a noninvasive respiratory profi le monitor in chronic obstructive lung disease patients during low-ventilation strategy Adel M. Saeed a , Gehan M. El Asaal a , Hesham A. Abd El Halim a , Shaymaa A. Ahmad b Background Patients with chronic obstructive pulmonary disease (COPD) patients are susceptible to complications, especially volutrauma, during the period of mechanical ventilation; low ventilation is a safe strategy to avoid these complications. Noninvasive capnography is a suitable technique for monitoring and assessing the cardiac and the pulmonary status of these patients during the period of mechanical ventilation.
Objectives Assessment of the cardiac and the pulmonary status of two COPD patient groups receiving mechanical ventilation with a low tidal volume strategy using a noninvasive CO 2 respiratory profi le monitor (volumetric capnography).

Patients and methods
Forty patients were recruited in the respiratory ICU of Abbassia Chest Hospital; these patients were divided into two groups: 20 COPD patients with the predominant pathology of chronic bronchitis (CB) and 20 patients with the predominant pathology of emphysema disease, who presented with clinical and radiological evidence of chronic obstructive lung disease and were in need of mechanical ventilation. All the patients in the study were followed up three times per day until weaning; data were recorded on admission, after 24 h and before weaning using volumetric capnography.

Results
There was signifi cant correlation between EtCO 2 and arterial PCO 2 during the whole period of mechanical ventilation in CB and emphysematous patients; the mean dead-space fraction was signifi cantly higher in the emphysema group than in the CB group. There was a signifi cant negative correlation between the mean values of V d /V t and the pulmonary capillary blood fl ow on admission and after 24 h in the emphysema group. The mean cardiac output, the mean stroke volume, and the pulmonary capillary blood fl ow increased signifi cantly before extubation in the CB group, in contrast to the emphysema group in which there was an insignifi cant difference. the two groups [4]. All patients were subjected to full history taking from a relative of the patient, clinical examination, chest radiography, computed tomography, ECG, echocardiography, and arterial blood gas measurement. Continuous infusion of midazolam and elective invasive mechanical ventilation and volumetric capnography monitoring were performed. All the patients in the study were followed up three times per day until weaning, and the data were recorded on admission, after 24 h and before weaning.

Monitoring
Variables measured included the cardiac output, the stroke volume, the pulmonary capillary blood fl ow (PCBF), EtCO 2 , VCO 2 , V t /V d , V t alv, MV alv, Raw, PEEP, and compliance.

Data analysis
Analysis of data was performed using the Statistical Package for Social Sciences ( SPSS version 15.0.1 for Windows; SPSS Inc., Chicago, Illinois, USA).
(1) Descriptive statistics: (a) Parametric data were expressed as range and mean ± SD. (b) Nonparametric data were expressed as frequency and percentage.

Results
Forty participants were chosen randomly. Twenty of them had CB: this group consisted of 85% men, with a mean age of 63.75 years; and 20 participants had emphysema: all of them in this group were men with a mean age of 59 years. CB patients in this study were successfully weaned from mechanical ventilation within 3-9 days, whereas emphysematous patients took longer (3-15 days). Tracheostomy operation was performed in 12.5% patients in the emphysematous group at a median time of 15 days from the beginning of mechanical ventilation; the main demographic data are illustrated in Table 1.
On admission, PO 2 in the CB group was signifi cantly less than in the emphysema group with P value of 0.013 as shown in Fig. 1. Signifi cantly better values of PH and PCO 2 were observed in the CB group than in the emphysema group after 24 h of mechanical ventilation, with P values of 0.014 and 0.009, respectively, as shown in Figs. 2 and 3.
In the CB group, there was signifi cant improvement in the hemodynamic parameters during the whole period of mechanical ventilation with regard to blood pressure, pulse, and temperature. In the emphysema group, there were no signifi cant diff erences in the hemodynamic parameters except for pulse, which showed signifi cant improvement until trial of weaning. On comparison, there was no signifi cant diff erence between the two groups. Comparison between chronic bronchitis (CB) and emphysema groups regarding PO 2 : a significant decrease was observed in PO 2 in the CB group compared with the emphysema group (t = 2.57, P = 0.013).

Fig. 1
Comparison between the two groups regarding PH after 24 h: a signifi cant decrease in PH was observed in the emphysema group compared with the chronic bronchitis (CB) group (t = 2.86, P = 0.014).

Fig. 2
Regarding the cardiac parameters, pulmonary blood fl ow, cardiac output, and stroke volume, there was no signifi cant diff erence between the two groups during the whole period of mechanical ventilation. At baseline in CB, the mean stroke volume and the cardiac index were 49.5 ml/beat and 2.43 l/min/m 2 , respectively, and increased to 69.1 ml/beat (P < 0.01) and 3.1 l/min/m 2 (P < 0.01), respectively, before extubation; also, the mean PCBF level and the cardiac output were 3.6 and 5.2 l/min, respectively, at baseline compared with 4.2 l/min (P < 0.05) and 6.1 l/min (P = 0.05), respectively, before extubation.
In emphysematous patients, only the stroke volume at baseline of 47.2 ml/beat increased signifi cantly to 61.3 ml/beat (P < 0.05) before extubation as shown in Table 2.
On admission, the mean values of the dead-space fraction, the peak expiratory fl ow (PEF), and the PEEP measured among emphysema patients group were signifi cantly higher than the values among patients in the CB group, with P values of 0.000, 0.004, and 0.004, respectively, as shown in Fig. 4a, whereas the mean values of EtCO 2 and V t in the CB group were signifi cantly higher than the values in the emphysema group, with P values of 0.025 and 0.044, respectively, as shown in Fig. 4b.
After 24 h, the mean dead-space fraction, the PEF and the PEEP were signifi cantly increased in the emphysema group compared with the CB group, with P values of 0.000, 0.021, and 0.002, respectively, as shown in Fig. 5.
Before extubation, the mean dead-space fraction, the PEF, and the PEEP were signifi cantly higher in the emphysema group than in the CB group, with P values of 0.048, 0.015, and 0.002, respectively (Fig. 6).
With regard to the two groups studied, the end-tidal carbon dioxide was signifi cantly correlated to the arterial partial pressure of carbon dioxide on admission, after 24 h and before extubation. Comparison between the two groups regarding PCO 2 after 24 h: a signifi cant increase in PCO 2 was observed in the emphysema group compared with the chronic bronchitis (CB) group (t = 2.79, P = 0.009).

Fig. 3
The difference between chronic bronchitis (CB) and emphysema groups with regard to their (a) EtCO 2 , peak expiratory fl ow (PEF), and tidal volume (VT) and (b) V t /V d and positive end-expiratory pressure (PEEP) on admission.

Fig. 4
In the CB group, there was a highly signifi cant negative correlation between the dead-space fraction and the cardiac output during all periods of mechanical ventilation. Th ere was also a signifi cant negative correlation between the two variables in the emphysema group on admission and after 24 h.
In the emphysema group, there was a highly signifi cant negative correlation between dead-space fractions and PCBF on admission and it also had a signifi cant negative correlation after 24 h (Tables 3-6).

Discussion
Th is study enrolled 40 COPD patients and diff erentiated them into two groups, according to the history, clinical fi ndings, and radiological fi ndings of each group: there were 20 COPD patients, with the predominant pathology of CB, and 20 patients with the predominant pathology of emphysema diseases. Th is selective methodology was partially in agreement with the methodology used by Farah and Makhoul [5], who enrolled COPD patients and dealt with them as one group without diff erentiated them into the CB and the emphysematous groups, but their study depended on history and clinical fi ndings to diagnose the disease. Frazier et al. [6] measured the mean cardiac output by volumetric capnography, which was 5.3 l/min at baseline during mechanical ventilation and increased signifi cantly to 6.5 l/min during the weaning trial by continues positive airway pressure (CPAP) trial (P = 0.036). Th ese were in agreement with the results in the present study as there was a signifi cant increase in the mean cardiac output measured by volumetric capnography of the CB group at baseline (5.25 ± 1.4 l/ min), which reached 6.1 ± 1.3 l/min before extubation, whereas in the emphysematous group, there was no signifi cant diff erence between the two stages. In our study, the cardiac output of the two groups was recorded using the partial CO 2 rebreathing technique, which yielded a mean cardiac output at baseline of 5.25 ± 1.4 and 5.3 ± 1.5 l/min in the CB and the emphysematous groups, respectively. Th is coincides with the study of Jérôme et al.
[7] which enrolled 20 consecutive mechanically ventilated patients who h ad acute respiratory distress syndrome (ARDS). Th ey measured the cardiac output after a 2-h period of hemodynamic stability. Th e mean cardiac output value was 5.8 ± 1.7 l/ min with the partial carbon dioxide rebreathing technique. Th eir study compared this method with thermodilution in which the mean cardiac output was 6.7 ± 1.9 l/min and there was signifi cant correlation between the two methods. Th e mean stoke volume at baseline was 49.5 ± 14.8 and 47.2 ± 17.8 ml/beat, respectively, and increased signifi cantly to 69.1 ± 16.5 and 61.3 ± 16.9 ml/beat in the CB and the emphysema groups, respectively, during weaning. Th ese results were in agreement with Frazier et al. [6] who studied the hemodynamic function during baseline mechanical ventilation and during a trial of CPAP by the carbon dioxide rebreathing technique: the mean stroke volume was 52 ± 36 ml/beat at baseline during mechanical ventilation and increased signifi cantly to 78 ± 38 ml/ beat (P < 0.001) during the CPAP trial. Th e pulmonary blood fl ow was measured noninvasively by the partial The difference between chronic bronchitis (CB) and emphysema groups with regard to their (a) peak expiratory fl ow (PEF) and positive end-expiratory pressure (PEEP) and (b) V t /V d after 24 h.

Fig. 5
The difference between chronic bronchitis (CB) and emphysema groups with regard to their (a) peak expiratory fl ow (PEF) and positive end-expiratory pressure (PEEP) and (b) V t /V d before extubation. CO 2 rebreathing technique: the mean pulmonary blood fl ow was 3.6 ± 0.7 l/min in CB at baseline and it signifi cantly increased before extubation to reach 4.2 ± 0.9 l/min, in contrast to the emphysema group, in which there was an insignifi cant diff erence, with a mean PBF of 3.7 ± 1.03 l/min at baseline and 3.5 ± 1.03 l/min before extubation. Th ese results are in agreement with the study of Jérôme et al. [7], in which the mean value of PCBF was 4.6 ± 1.3 l/min by the carbon dioxide rebreathing technique. In this study, before extubation, the mean dead-space fraction measured by volumetric capnography in the emphysema group was 0.15 ± 0.1, which was signifi cantly higher than that of the CB group (0.09 ± 0.06); this was in agreement with González-Castroa et al. [8] who enrolled 76 patients for mechanical ventilation, out of whom 14 patients were diagnosed to have COPD with exacerbation, nine patients were diagnosed to have pneumonia, and the remaining had other causes: the mean value of V d /V t in the 59 extubated patients was 0.48 ± 0.09, whereas in the 17 patients with failed extubation, the mean value of V d /V t was 0.65 ± 0.08. Our result demonstrated that the mean dead-space fraction measured by volumetric capnography on admission and before extubation reduced from 0.345 to 0.15, respectively, in the emphysema group, which was signifi cantly higher than that of CB group, which was 0.14 and reduced to 0.09, respectively. Th ese results were in agreement with Kallet et al. [9], who measured the ratio of the physiologic dead-space to tidal volume V d /V t with volumetric capnography before therapy with human recombinant activated protein C, and found a reduction in V d /V t from 0.55 to 0.27. In the present study, before extubation, there were two modes of weaning used: pressure support and T piece. Th ere was no signifi cant diff erence between the two modes between the two groups. Th e mean values of dynamic compliance were 41.05 and 43.00 ml/cmH 2 O, the static compliance were 25.8 and 26.90 ml/cmH 2 O, airway resistance was 24.30 and 26.75 cmH 2 O/l/s, and the mean dead-space fraction values were 0.15 and 0.09 in the emphysema group and the CB group, respectively. Th ese results were comparable to those of El Ghamrawy et al. [10 ] who used BIPAP compared with pressure support for the weaning of 32 COPD patients with acute respiratory failure. Th e respiratory system static, dynamic compliance, and the resistance were calculated by equations, but the ratio of deadspace to tidal volume was calculated automatically from capnography and displayed on the ventilator screen. Th ey did not use the non-rebreathing CO 2 monitor as in our study. Th e mean level of respiratory dynamic compliance with BIPAP was 21.8 ml/cmH 2 O, which was signifi cantly lower than its level with PS (25.0 ml/cmH 2 O); the static compliance was 38.9 ± 11.3 ml/cmH 2 O with BIPAP, which was insignifi cantly higher than its level with PS (39.3 ± 12.1 ml/cmH 2 O); these values were less than our values, and this may be explained by the fact that they used the method of calculation. Th e mean level of resistance with bi-level positive air pressure (BIPAP) was 28.3 cmH 2 O/l/s, which was signifi cantly higher than the corresponding level with PS (22.8 cmH 2 O); these values coincided with our result. Th e mean dead-space ventilation was 0.57 and 0.54 with BIPAP and PS, respectively, with no signifi cant diff erence, but these results were slightly higher than our result. In the present study, the P (a-et) CO 2 gradient decreased from 25.15 ± 13.6 on admission to 8.15 ± 6.2 before extubation in the emphysema There was a signifi cant negative correlation between the external PEEP and airway resistance before extubation among the chronic bronchitis group. PEEP, positive end-expiratory pressure.  Defi lippis et al. [11] studied the P (a-et) CO 2 gradient in 20 patie nts with severe dyspnea and hypercapnia undergoing noninvasive ventilation. Th e P (a-et) CO 2 gradient was measured at subsequent times: T0 (admission) was 60.7 ± 17.7 mmHg; it decreased progressively, reaching 8.4 ± 8 mmHg at T6 h and 4.7 ± 6.7 mmHg at T12 h, which was lower than the baseline value. A positive correlation was found between EtCO 2 and PaCO 2 values (r = 0.89, P = 0.001).
In the present study, with regard to the CB group, EtCO 2 was signifi cantly correlated to PaCO 2 on admission (r = 0.7, P = 0.00), after 24 h (r = 0.9, P = 0.00), and before extubation (r = 0.8, P = 0.00); however, in the emphysema group, the EtCO 2 was signifi cantly correlated to the PaCO 2 only before extubation (r = 0.7, P = 0.00). Th ese results were in agreement with Yosefy et al. [12], who enrolled 73 patients in their study. Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml/kg of body weight, which result in volutrauma [15]. A prospective cohort of 361 ICUs from 20 countries with a total of 5183 mechanically ventilated patients with limited tidal volumes 6-8 ml/kg were included in the study. Th is study found that barotrauma was present in 2.9% of the patients with COPD, 6.3% of the patients with asthma, 10.0% of the patients with chronic interstitial lung disease, 6.5% of the patients with acute respiratory distress syndrome, and 4.2% of the patients with pneumonia [16]. In the present study, barotrauma was not recorded in 40 patients in whom the low-ventilation strategy was used.

Conclusion
Low ventilation is a safe strategy to avoid complications such as volutrauma and barotrauma. Noninvasive capnography is a simple and safe bedside method for noninvasive estimation of pulmonary and cardiac parameters for monitoring COPD patients during the period of mechanical ventilation. Th ere was signifi cant correlation between EtCO 2 and arterial PCO 2 throughout the period of mechanical ventilation in CB and emphysematous patients; hence, monitoring PetCO 2 provided a good noninvasive assessment of hypercapnic episodes during weaning from mechanical ventilation. Th e P (a−et) CO 2 gradient decreased before extubation in emphysematous and CB patients, and this indicates a change in perfusion to help with weaning. Th e mean dead-space fraction was signifi cantly higher in the emphysema group than in the CB group throughout the period of mechanical ventilation. Also, there was a signifi cant negative correlation between the mean values of dead-space fractions V t /V d and the PCBF in the emphysematous patients. Hence, early and repeated measurements of the pulmonary and the cardiac function by this monitor could provide clinicians with valuable information for prognosis and disease monitoring.