The Predictive Value of Integrated Pulmonary Index after Off-Pump Coronary Artery Bypass Grafting: A Prospective Observational Study

Background The early warning scores may increase the safety of perioperative period. The objective of this study was to assess the diagnostic and predictive role of Integrated Pulmonary Index (IPI) after off-pump coronary artery bypass grafting (OPCAB). Materials and Methods Forty adult patients undergoing elective OPCAB were enrolled into a single-center prospective observational study. We assessed respiratory function using IPI that includes oxygen saturation, end-tidal CO2, respiratory rate, and pulse rate. In addition, we evaluated blood gas analyses and hemodynamics, including ECG, invasive arterial pressure, and cardiac index. The measurements were performed after transfer to the intensive care unit, after spontaneous breathing trial and at 2, 6, 12, and 18 h after extubation. Results and Discussion The value of IPI registered during respiratory support correlated weakly with cardiac index (rho = 0.4; p = 0.04) and ScvO2 (rho = 0.4, p = 0.02). After extubation, IPI values decreased significantly, achieving a minimum by 18 h. The IPI value ≤9 at 6 h after extubation was a predictor of complicated early postoperative period (AUC = 0.71; p = 0.04) observed in 13 patients. Conclusion In off-pump coronary surgery, the IPI decreases significantly after tracheal extubation and may predict postoperative complications.

inTrODUcTiOn Cardiac surgery can be complicated by respiratory failure that may contribute to increased morbidity and additional health-care costs (1,2). The outcome of coronary artery bypass grafting can be significantly influenced by decompensation caused by chronic pulmonary diseases and other complications (atelectases, pleuritis, etc.) (3)(4)(5). Therefore, the thorough postoperative monitoring of pulmonary function during both mechanical ventilation and spontaneous breathing may be of a great value. Notably, the modern monitoring devices should be accurate and non-or minimally invasive with measurements that are continuous and results easily interpreted (6).
To maintain respiratory function, the cardiosurgical patients are monitored using pulse oximetry, capnography, respiratory rate, and discrete blood gas analysis (7)(8)(9). Although blood gas analyses are the gold standard for early detection of different types of respiratory failure, they are invasive, cannot be measured continuously, and frequently impose a delay between sampling and availability of results (10). Thus, the early warning systems allowing early recognition of critical respiratory events might be of value when patient is monitored both in the intensive care unit (ICU), postoperative ward, and high dependency unit. This approach can be particularly useful with a limited number of medical staff. Several observational studies indicate that early warning systems improve detection of complications (11), and their use is recommended by the World Federation of Societies of Anesthesiologists to facilitate the work of nurses and physicians in the ICU (12,13).
The Integrated Pulmonary Index (IPI) is an automated value calculated by one monitor (Capnostream-20, Medtronic, Israel) and can be considered as an automated early warning system. The IPI algorithm utilizes the real time measures and interactions of four parameters-end-tidal CO2 (PetCO2), respiration rate, pulse rate, and oxygen saturation (SpO2) to provide an assessment of the patient's respiratory status. The calculation of the IPI is based on the fuzzy logic principle, a mathematical model, which mimics human logic thinking; detailed description of the algorithm was provided by Ronen et al. (14) The values of IPI below 7 have been suggested to be an indicator for respiratory deterioration (14).
Currently, only few investigations of IPI were performed during non-cardiosurgical procedures (14)(15)(16)(17)(18) In these studies, IPI algorithm correlated with the respiratory status and has demonstrated the ability for promoting early awareness to changes in a patient's respiratory system.
The aim of our study was to assess the diagnostic and predictive role of IPI during the discontinuation from mechanical ventilation and in the early postextubation period after off-pump coronary artery bypass grafting (OPCAB).

MaTerials anD MeThODs
The study was performed in a 900-bed university hospital (City Hospital #1 of Arkhangelsk, Russia). During 2015, 40 adult patients undergoing elective OPCAB were enrolled into an observational prospective study. The study design and the informed consent form were approved by the Ethical Committee of Northern State Medical University (Arkhangelsk, Russian Federation) and registered with http://ClinicalTrials.gov (ref: NCT02524522). Written informed consent was obtained from every patient. Exclusion criteria were age <18 and >80 years, morbid obesity with body mass index >40 kg/m 2 , and constant atrial fibrillation.
In all cases, preoxygenation with 80% O2 was provided during 3-5 min before anesthesia. After tracheal intubation, patients were ventilated using a protective volume-controlled mode (Dräger Primus, Germany) with tidal volume of 6-8 mL/kg of predicted body weight, flow of 1 L/min and positive end-expiratory pressure (PEEP) of 5 cm H2O. FiO2 was set to at least 50% or higher to achieve intraoperative SpO2 above 95%. The respiratory rate was adjusted to maintain PetCO2 value within 30-35 mmHg.
After surgery, all patients were transferred to the postoperative cardiac ICU and shortly sedated with continuous infusion of propofol (2-4 μg/kg/h) to maintain BIS values within 60-70. Respiratory support in ICU was provided by a G5 ventilator (Hamilton Medical, Switzerland) using pressure controlled ventilation mode with parameters of intraoperative ventilation. Additionally, all patients received recruitment maneuver by raising the PEEP to 20 cm H2O for 5 min.
After the initial measurements, sedation was stopped, and the weaning from respiratory support was initiated. The weaning protocol included gradual reduction of inspiratory pressure and mandatory respiratory rate, as well as spontaneous breathing trial. After passing the 30-min spontaneous breathing trial, all the patients were immediately extubated. After extubation, the patients received a supplementary oxygen flow of 4 L/min via a nasal catheter. During the weaning process and in the early postextubation period, all the patients received continuous infusion of fentanyl and discrete administration of paracetamol for multimodal analgesia. In addition, the postoperative therapy included aspirin, low-molecular weight heparins, and bisoprolol.
The measurements included ventilator parameters, blood gas analyses (ABL800Flex, Radiometer, Denmark), PetCO2, SpO2, respiratory rate, pulse rate, and IPI (Capnostream-20, Medtronic). The IPI measurement is based on continuous transformation of SpO2, PetCO2, pulse rate, and respiratory rate values into a single index from 1 to 10, where "10" indicates a normal respiratory status, and "1" indicates that patient requires immediate intervention. We distributed patients into two subgroups: with optimal (IPI 9-10) and suboptimal (IPI ≤ 8) IPI values ( Table 1). After tracheal extubation, for a more accurate assessment of the IPI, all the values were measured following breathing during 5 min without supplemental oxygen (FiO2 0.21), avoiding the reduction of SpO2 less than 88%. Continuous hemodynamic measurements included ECG monitoring, invasive arterial pressure and cardiac output measured with pulse wave transit time (esCCO, Nihon Kohden, Japan).
All these parameters were registered after transfer to the ICU, as well as after spontaneous breathing trial and at 2, 6, 12, and 18 h after extubation. In addition, we recorded the preoperative EuroScore II, perioperative fluid balance, left ventricle ejection fraction assessed by transthoracic echocardiography before and 24 h after surgery, duration of postoperative mechanical ventilation and ICU stay, as well as early postoperative complications and hospitalization time. Postoperative complications were assessed according to the categories as predefined the study protocol: arrhythmias, hemorrhage, respiratory complications,

resUlTs
We enrolled 30 males and 10 females. Demographic and baseline characteristics of the patients, as well as postoperative complications are shown in Table 2.
All patients were successfully weaned from mechanical ventilation. PaO2/FiO2 ratio was stable both during the spontaneous breathing trial and after tracheal extubation. In contrast, IPI decreased significantly after OPCAB with a minimal value at 18 h after extubation (Figure 2). As shown in Figure 3, in patients with PaO2/FiO2 < 200 mmHg on ICU admission, the IPI values at 2, 6, 12, and 18 h after extubation did not exceed suboptimal range (≤8) (p < 0.05 as compared to IPI values of the subgroup with PaO2/FiO2 > 200 mmHg). In addition, the suboptimal IPI values at 2 h after tracheal extubation were associated with higher preoperative EuroScore and decreased left ventricular ejection fraction before and after OPCAB ( Table 3). In the subgroup with IPI ≤ 8, we observed decreased SpO2 and etCO2, as well as increased pulse rate. Higher IPI values were associated with positive fluid balance and decreased rate of diuretic administration at the first day of ICU stay.
The length of ICU and hospital stay did not differ between the patients with optimal and suboptimal IPI values. We did not find any associations between PaO2/FiO2 ratio and the length of ICU stay either. However, IPI value ≤9 at 6 h after extubation demonstrated moderate predictive ability for early postoperative complications (AUC = 0.707; p = 0.04, with sensitivity 92% and specificity 48%, positive predictive value 57%, negative predictive value 89%, Figure 4). PaO2/FiO2 ratio at 6 h after extubation did not demonstrate any predictive ability for postoperative complications (AUC = 0.543; p = 0.67).

DiscUssiOn
Our study has shown that IPI can provide important information about respiratory and hemodynamic status of the cardiosurgical patient, especially during the postextubation period.
In our study, we observed difficulties in registration of the IPI value after admission to the ICU in one patient from 40 enrolled into the study; this problem can be explained by decreased perfusion, leading to low SpO2 signal. Low perfusion as well as motion artifacts are the well-known limitations of pulse oximetry observed in the early postoperative period after cardiac surgery (19).
After admission to the ICU, the number of patients with compromised respiratory function according to their PaO2/FiO2 values (63%) was higher than the number of patients requiring attention according to the IPI values (5%). During controlled mechanical ventilation, several components of IPI like respiratory rate, SpO2, and PetCO2, are determined mainly by the operator-depending settings of the ventilator that may not reflect the complex respiratory status. The association of IPI, measured after admission to the ICU, with cardiac index and ScvO2, observed in our study can be explained by the relationship between cardiac output, PetCO2, and oxygen transport (20). Although the described correlations were weak that can be caused by dependence of end-tidal CO2 not only from cardiac output but also from ventilation, metabolism, and other factors, our findings are consistent with other investigations in this field. In several studies, authors demonstrated that PetCO2 and cardiac output had a positive association in different categories of patients (21)(22)(23). Thus, Baraka and colleagues have shown that cardiac output correlated with PetCO2 during partial cardiopulmonary bypass and following weaning from bypass (22). In this study, PetCO2 > 30 mmHg during partial bypass predicted an adequate cardiac output after perfusion. At the same time, PetCO2 < 30 mmHg may correctly denote a low cardiac output only in combination with low ScvO2 (22). This relationship between PetCO2 and cardiac function can be relevant not only for cardiac surgery; thus, Dunham and colleagues have found that a decline in PetCO2 correlates with decrease in noninvasive cardiac output in emergently intubated trauma patients (23). Notably, the addition of pulse rate into the algorithm for calculation of IPI could improve the ability of this parameter to predict decreased cardiac output compared with PetCO2 alone. However, our ROC analysis has shown equal AUC to predict CI < 2.5 L/min/m 2 both for IPI < 8 and for PetCO2 < 30 mmHg. The possible explanation for this finding could be that the heart rate is just one of the determinants of cardiac output, thus PetCO2 alone may have similar accuracy with IPI in predicting cardiac output after OPCAB.
Notably, reduced IPI values during controlled mechanical ventilation observed in our study can be explained by decreased PetCO2 levels. During spontaneous breathing with ambient air (FiO2 21%), suboptimal IPI was also associated with decreased SpO2 values and increased pulse rate, aiming to maintain adequate cardiac output and oxygen delivery. We suppose that, summarizing the key cardiovascular and respiratory parameters, IPI can be a useful tool for postoperative assessment of patient in addition to PaO2/FiO2 ratio, which has a limited value due to dependence on FiO2 (24) This can explain the stable values of PaO2/FiO2 with simultaneous reduction of SpO2 and IPI after extubation while breathing with ambient air. It is important to mention that the measurement of IPI does not replace postoperative blood gases but it can potentially reduce the number of blood gas samples, is continuous as compared to discrete blood gases and can serve as a "monitoring bridge" after discontinuation of mechanical ventilation and invasive monitoring.
The association of suboptimal IPI values with preoperative EuroScore and ejection fraction before and after intervention demonstrates the relationship of IPI and severity of cardiac comorbidities. Several studies have shown that decreased ejection fraction after cardiac surgery may be associated with risk of sepsis, postoperative respiratory failure and prolonged mechanical ventilation (25,26). Thus, the reduction of IPI after cardiac surgery can detect patients who require more complex hemodynamic monitoring and optimization including fluids, diuretics, inotrope/vasopressor support, and other therapies.
Association between IPI value ≤9, recorded at 6 h after extubation and the incidence of early complications after OPCAB seems to be relevant for prediction of the course of postoperative period. We did not find in other studies the data about the opportunity of IPI to predict the course of postoperative period, although IPI was effective in detection of clinically significant events, such as hypoxia or bradypnea, during the intraoperative period (16,17). The complications observed during our study (predominantly, atrial fibrillation and respiratory failure) are accompanied by changes in respiratory and hemodynamic status of the patient. The patients after cardiac surgery can have a higher alert threshold of IPI as compared to other settings where the attention is required when IPI is ≤7. The diagnostic capabilities of IPI need further validation and studies including the assessment of IPI as a marker for the safe transfer from ICU.

study limitations
Our findings have a limitation due to relatively small sample size. In addition, all the patients from our study received bisoprolol postoperatively that may influence the heart rate, as well as the IPI value.