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Prevalence and Implications of Abnormal Respiratory Patterns in Cardiac Surgery: A Prospective Cohort Study
Author’s Accepted Manuscript Prevalence and implications of abnormal respiratory patterns in cardiac surgery: A prospective cohort study Dmitry Ponomarev, Oksana Kamenskaya, Asya Klinkova, Irina Loginova, Vladimir Lomivorotov, Igor Kornilov, Vladimir Shmyrev, Aleksander Chernavskiy, Giovanni Landoni, Aleksander Karaskov
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S1053-0770(16)30657-7 http://dx.doi.org/10.1053/j.jvca.2016.12.005 YJCAN3935
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Dmitry Ponomarev, Oksana Kamenskaya, Asya Klinkova, Irina Loginova, Vladimir Lomivorotov, Igor Kornilov, Vladimir Shmyrev, Aleksander Chernavskiy, Giovanni Landoni and Aleksander Karaskov, Prevalence and implications of abnormal respiratory patterns in cardiac surgery: A prospective cohort study, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2016.12.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Prevalence and implications of abnormal respiratory patterns in cardiac surgery: a prospective cohort study Dmitry Ponomareva1, MD, PhD, Oksana Kamenskayab, MD, PhD, Asya Klinkovab, PhD, Irina Loginovab, Vladimir Lomivorotova, MD, PhD, Igor Kornilova, MD, PhD, Vladimir Shmyreva, MD, PhD, Aleksander Chernavskiyc, MD, PhD, Giovanni Landonid, MD and Aleksander Karaskovc, MD, PhD 1
Corresponding author, email: [email protected], phone: +79232339205
a
Department of Anesthesia and Intensive Care, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
b
Department of Physiology, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
c
Department of Cardiac Surgery, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
d
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy, and Vita-Salute San Raffaele University, Milan, Italy
Conflict of interest: none This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
1
Objective To investigate prevalence and impact of abnormal respiratory patterns in cardiac surgery patients. Design Prospective cohort study. Setting Tertiary hospital. Participants Patients scheduled for elective coronary artery bypass graft surgery. Interventions None. Measurements and Main Results Pulmonary function tests were performed in 454 patients before surgery. Abnormal respiratory patterns were defined as follows: obstructive (forced expiratory volume in 1 second/forced vital capacity < 0.70), restrictive (forced expiratory volume in 1 second/forced vital capacity ≥ 0.70 and forced vital capacity < 80% of predicted), mixed (forced expiratory volume in 1 second/forced vital capacity < 0.70 and both forced expiratory volume in 1 second and forced vital capacity < 80% of predicted). Of 31 patients with history of chronic obstructive pulmonary disease, no abnormal respiratory pattern was confirmed in 5. Of 423 patients without a history of lung disease, we newly identified 57 obstructive, 46 restrictive and 4 mixed patterns. Therefore, lung disease was reclassified in 24.7% cases. Independent
2
predictors of obstructive pattern were age, male gender, history of smoking and chronic obstructive pulmonary disease. Obstructive lung disease was associated with 16 hours longer ventilation. A reduced forced expiratory volume in 1 second was associated with likelihood of atrial fibrillation (1 liter decrement, odds ratio: 1.38, 95% CI: 1.01 to 1.90, p=0.04) and hospitalisation time (regression coefficient: 1.23, 95% CI: 0.54 to 1.91, p<0.001). Conclusions Abnormal respiratory patterns are common and often underdiagnosed in the cardiac surgery setting. Pulmonary function tests help reveal patients at risk of complications and may provide an opportunity for intervention.
Key Words: pulmonary function tests, obstructive respiratory pattern, restrictive respiratory pattern, chronic obstructive pulmonary disease, cardiac surgery.
Introduction Heart and respiratory diseases often coexist whether due to common lifestyle-related risk factors1,2, organ cross-talks3–5 or shared pathophysiology6. Obstructive, restrictive and mixed respiratory disorders are associated with increased cardiovascular morbidity and mortality2,7–9. Furthermore, patients with airflow limitation die more from cardiovascular causes than from the respiratory sequelae of chronic obstructive pulmonary disease (COPD)10. The latter, characterised by airflow limitation that is not fully reversible11, is present in up to 21% of cardiac surgical patients12. In cardiac surgery, airflow limitation as measured by forced expiratory volume in 1 second (FEV1), is associated with increased complication rates, such as postoperative arrhythmia13, and short- and long-term mortality12,14–16. Pulmonary
3
functional tests (PFTs) help reclassify chronic lung disease in 31%15 to 39%17 cases, with an overwhelming underestimation of the severity of the condition in those misclassified17, thus suggesting considerable underutilisation of PFTs in the cardiac surgery setting. However, methodological issues, such as retrospective design12,14,16 and high chances for selection bias15 call into question both internal and external validity of the above results. Additionally, majority of the studies focus on obstructive respiratory pattern, whereas restrictive and mixed disorders, prevalent in patients with heart diseases18, remain largely beyond the scope of research, with potential impact of this neglect on clinical outcome. Therefore, the aim of the present study was to investigate prevalence and patterns of respiratory disorders and their impact on clinical course after elective coronary artery bypass graft (CABG) surgery with or without concomitant procedures.
Methods Subject population Between March 2015 and August 2016, 454 consecutive patients scheduled for elective CABG surgery were recruited at Novosibirsk Research Institute of Circulation Pathology, Novosibirsk, Russian Federation. This prospective cohort study was approved by the local Ethics Committee and was conducted in compliance with the principles of the Declaration of Helsinki. The only inclusion criterion was planned CABG surgery (including concomitant surgeries). Exclusion criteria were: patient’s refusal to participate, contraindications for PFTs19,20, emergency surgery, recent or ongoing myocardial infarction, angina. After providing an informed written consent, all eligible patients underwent PFTs, completed both the modified Medical Research Council (mMRC) breathlessness scale21 and the COPD assessment test (CAT)22 before surgery. 4
Measurement of lung function Pulmonary functional tests were performed by an experienced physiologist using fullbody plethysmograph (Master Screen, Erich Jaeger, Germany) and in accordance with international standards, including the acceptability and reproducibility criteria23,24. Pulse oximetry was used to measure baseline oxygen saturation during air breathing. All subjects were seated during measurements. Airway reversibility test with 400 micrograms of salbutamol using a spacer inhaler was applied when indicated. Absolute and percent-ofpredicted (for height, weight, and age) FEV1 and Forced Vital Capacity (FVC) as well as FEV1/FVC ratio were estimated and used to define abnormal respiratory patterns. Obstructive pattern was defined as FEV1/FVC < 0.70; restrictive respiratory pattern was defined as a combination of FEV1/FVC ≥ 0.70 and FVC < 80% of predicted; and mixed pattern was defined as a combination of FEV1/FVC < 0.70, FEV1 < 80% of predicted, and FVC < 80% of predicted25; normal pattern was none of the above. Following determination of abnormal respiratory pattern, its severity was classified based on FEV125. Mild abnormality was defined as FEV1 > 70% of predicted, moderate 60 - 69% of predicted, moderately severe 50 - 59% of predicted, severe 35 - 49% of predicted, very severe was defined as FEV1 < 35% of predicted. Variables The following data were collected: demographics (date of birth, gender and race), body mass index, self-reported smoking status (never, former or current smoker), documented New York Heart Association (NYHA) functional class, Canadian Cardiovascular Society (CCS) grade of angina, arterial hypertension, diabetes, peripheral vascular disease, stroke, documented COPD, asthma, atrial fibrillation (AF), chronic kidney disease26, previous percutaneous coronary angioplasty (PCI), history of myocardial infarction (MI). Logistic EUROscore II27 and creatinine clearance28 were calculated, and left ventricular ejection
5
fraction was obtained for all patients. Intraoperative data included: type of surgery (isolated CABG or not, type of concomitant intervention if not), whether or not cardiopulmonary bypass (CPB) was used, number of grafts (distal anastomoses) performed, number of internal mammary arteries used, duration of cardiopulmonary bypass (if used), aortic cross-clamp time (if used), use of intra-aortic balloon pump (IABP) or other assist device. The definitions of adverse events are presented below. Heart failure was defined as need for intra-aortic balloon pump (IABP) or ≥ 2 inotropes at 48 hours. An episode of AF was defined as the loss of P-waves in the presence of irregular ventricular beats on electrocardiogram (ECG) throughout the monitoring ECG tracing29,30 (when examining associations between PFTs results and postoperative AF, no distinction was made between recurrence of AF and new-onset AF). Myocardial infarction was defined according to the Third Universal Definition of MI31. Pleuritis was defined as pleural effusion requiring surgical intervention. Renal failure was defined as need for renal replacement therapy. Postoperative characteristics were recorded, such as: duration of mechanical ventilation, intensive care unit (ICU) stay, left ventricular ejection fraction at discharge, length of hospital stay. Hospitalisation was time period (in days) between day of surgery (inclusive) and day of hospital discharge (exclusive). Thirty day mortality was defined as death from any cause within 30 days after surgery (including day of surgery); patient’s status after hospital discharge was established via telephone call to either the patient or patient’s next of kin, as indicated in informed consent form. All patients were treated according to the institutional standards, including recording of ECG daily after surgery. Patients with history of COPD continued disease-specific treatment throughout hospital stay; their perioperative care was left to the discretion of attending physician. General anesthesia was induced with fentanyl (3-8 µg/kg), propofol (1–3 mg/kg) and pipecuronium bromide (0.1 mg/kg) and maintained with sevoflurane (1-2 vol%), further 6
fentanyl, propofol and pipecuronium bromide were given as needed. When used, cardiopulmonary bypass was performed with normothermia (nasopharyngeal temperature above 35.5°C), with non-pulsatile flow of 2.4-2.8 L/min/m2. Off-pump surgeries were performed using various myocardial stabilisers. Standard extubational protocol was applied to all the patients. It comprised assessment of the patient’s neurological status (ability to follow verbal command, intact cough reflex), full reversal of muscle relaxation (sustained head or leg lift or hand grasp for 4-5 seconds), rewarming to 35.5°C, correction of coagulopathies, metabolic and electrolyte abnormalities, presence of stable hemodynamics in the absence of high dose vasopressors, adequate urine output (0.5-1.0 ml/kg/hr in patients younger than 65 years, 0.25-0.50 ml/kg/hr in older patients), pO2/FiO2 ≥ 200, absence of bleeding requiring surgical intervention, successful weaning trial with minimal support (5 cm H2O pressure support, 5 cm H2O positive end expiratory pressure, FiO2 40%) for 30 minutes. Statistical analysis Continuous variables are presented as mean ± standard deviation or as mean (95% confidence interval, CI), ordinal data are presented as median (interquartile range). Categorical variables are expressed as frequencies (percent) or as frequencies (percent, 95% CI). Associations between continuous variables were assessed with linear regression, results are presented as regression coefficient (95% CI). Binary logistic regression was used to examine binary outcomes. Ordinal logistic regression was used to assess an association between the severity of respiratory abnormality and candidate predictors. Results of all logistic regression models are presented as odds ratio (OR) and associated 95% CI. For the multivariable logistic regression analyses, a manual forward step-wise procedure with a cutoff p-value of 0.20 was used for formulating a final regression model. Otherwise, a two-tailed
7
p value below 0.05 was considered statistically significant. Unpaired t-test was used to compare two continuous variables, Mann-Witney test was used for ordinal data. For comparison of two categorical variables, Fisher’s exact test was utilised. All analyses were performed using R statistical software (R Core Team (2015). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.).
Results The patients’ flow is presented in Figure 1. Of 501 eligible patients, 41 were not enrolled mainly due to logistical or administrative reasons (conflicting procedures, late admission to the ward), 5 patients underwent PCI, and 1 patient was listed for heart transplantation. The baseline characteristics of the 454 patients included in the study are outlined in Table 1. Mean age was 63 years, 82% of patients were males. Documented AF (any type) was present in 11.5% of the patients. Most of the patients (96.2%) had sinus rhythm at the morning of surgery. Out of the 31 patients with history of COPD, 15 (48.4%) had obstructive respiratory pattern, 4 (12.9%) - restrictive, and 7 (22.6%) patients exhibited mixed features (Figure 1). In 5 (16.1%) patients with history of COPD, no abnormal respiratory pattern was confirmed with PFTs. Table 2 shows that the most prevalent abnormal respiratory pattern was obstructive lung disease. In total, obstructive, restrictive and mixed patterns were revealed in 15.8%, 11.0% and 2.4% of patients, respectively (Table 2). These data indicate that PFTs helped reclassify lung disease in 24.7% of patients. Most of the patients had mild (18.9%) or moderate (5.7%) abnormalities. As follows from Table 3, independent predictors of obstructive respiratory pattern were age, male gender, history of smoking, and preoperative 8
diagnosis of COPD. It was not feasible to assess association of obstructive pattern with asthma due to separation of the data (none of the patients with asthma had obstructive lung disease). Predictors of restrictive pattern were history of asthma, BMI and p eripheral vascular disease. Logistic EUROscore II was not significantly associated with either of the abnormal patterns. Further ordinal logistic regression analysis of severity of any respiratory disorder indicated increased chances of more severe abnormality (as compared to all less severe grades combined) associated with age (for a 1 year increment, OR: 1.05, 95% CI: 1.02 - 1.08, p<0.01), male gender (OR: 2.74, 95% CI: 1.36 - 5.94, p<0.01), history of smoking (OR: 1.84, 95% CI: 1.16 - 2.95, p=0.01) and asthma (OR: 4.47, 95% CI: 1.06 - 16.76, p=0.03). No significant association between questionnaires results and abnormal respiratory patterns or their severity was observed. Baseline oxygen saturation was not
significantly different between the patients’ categories based on respiratory pattern. Perioperative characteristics are presented in Table 4. Isolated CABG surgery was performed in 85.9% cases with the most frequent concomitant procedures being left ventricular aneurism repair (4.2%) and radiofrequency ablation (3.7%). Cardiopulmonary bypass was used in 83.7% cases, with a mean duration of 61 minutes. Obstructive lung disease was associated with 16
hours (95% CI: 2 to 31 hours, p=0.02) longer ventilation as compared to normal pattern. Perioperative course was complicated by heart failure in 13% cases; in 1 case it required emergency veno-arterial extracorporeal membrane oxygenation use. During postoperative period, at least one episode of AF was detected in 20.7% patients, with significantly higher rate of new-onset AF in patients with respiratory disorder as compared to patients without abnormal pattern (15.7% vs 8.0%, p=0.02). Mortality rate in ICU was 5 (1.1%), with total 30 days mortality of 6 (1.3%). Four fatal outcomes were due to intraoperative MI, where all available treatments, including use of assist devices, proved ineffective. In one case, intraoperative acute aortic dissection required aortic hemiarch replacement under deep hypothermic circulatory arrest, however, the patient died from massive bleeding the same day. One more patient died of stroke after hospital discharge. Two patients were lost to follow-up. Median length of hospital stay was 12 days.
9
Pre-planned univariable analyses indicated that FEV1 was associated with likelihood of AF in postoperative period (1 liter decrement, OR: 1.38, 95% CI: 1.01 to 1.90, p=0.04) and length of hospital stay (1 liter decrement, regression coefficient: 1.23, 95% CI: 0.54 to 1.91, p<0.001). Further exploratory analysis suggested on average 2 days (95% CI: 1 to 3 days, p<0.001) longer hospital stay in patients having developed AF in postoperative period as compared to those who had not (respective mean FEV1 values: 2.65±0.68 and 2.82±0.72 liters, p=0.04). Discussion In the present study, aimed at investigating prevalence and patterns of respiratory disorders and their impact on clinical course after CABG surgery, we found out that, in spite of low prevalence of clinically diagnosed COPD (6.8%), abnormal respiratory patterns are present in 29.3% of patients. PFTs helped reclassify (mostly revealing new cases) lung disease in 24.7% of patients. Independent predictors of obstructive pattern were age, male gender, history of smoking and history of COPD. Importantly, obstructive lung disease was associated with increased duration of mechanical ventilation, whereas FEV1, commonly used as a measure of airflow limitation, was linked to increased likelihood of AF in postoperative period and length of hospital stay. Restrictive lung disease was associated with history of asthma, BMI and peripheral vascular disease. Independent predictors of severity of any respiratory disorder were age, male gender, history of smoking and asthma.
Pulmonary diseases, such as COPD, are important risk factors of ischemic heart disease, heart failure and sudden cardiac death7,18,32,33. Suggested mechanisms include (but are not confined to) systemic inflammation, oxidative stress, hypoxia, vascular wall abnormalities, accelerated aging, protease/antiprotease imbalance34. In a recent study with mean follow-up of 13 years by Wannamethee at al., reduced FEV1 and FVC were associated with biomarkers of
10
heart failure and myocardial damage in 3,242 older (60-79 years) men not undergoing cardiac surgery; furthermore, reduced FEV1 was also linked to incidence of heart failure35. This notion is further supported by evidence indicating that in patients with COPD cardiovascular mortality prevails over deaths due respiratory causes10,36. In the cardiac surgery setting, coexisting COPD is associated with complicated postoperative course, longer hospital stay and increased mid- and long-term morbidity and mortality12,14–16. In some studies, however, these associations were not confirmed37,38. Interestingly, in a study by Gao et al., a timevarying effect of COPD on mortality after cardiac surgery was demonstrated, with little or no associated risk immediately after surgery, significant risk at 1 month and almost doubled chances of death associated with COPD at 3-4 months39. In clinical practice, PFTs are not routinely utilised in patients without COPD, which is commonly diagnosed based on clinical signs (mainly dyspnea) and presence of predisposing factors (occupational exposure, smoking)40,41. In the cardiac surgery setting, using these criteria without PFTs leads to misdiagnosis of COPD in 31%15 to 39%17 cases, thereby an established risk factor for postoperative complications and mortality after cardiac surgery is undeservedly neglected by many. In the present study, lung disease was reclassified in every fourth patient (24.7%). An important observation was the association between lung function and postoperative AF occurrence. This relationship has been suggested by several studies, implicating
hypoxia,
pulmonary
hypertension
and
chronic
inflammation
within
cardiorespiratory system42–44, although the exact mechanisms remain to be determined. In our study, higher incidence of new-onset AF in patients with reduced lung function could add to the explanation of an observed association between FEV1 and length of hospital stay as postoperative AF was associated with on average 2 days longer hospitalisation. Relatively long hospitalisation (median 12 days) is attributed to the fact that at our centre patients are discharged home for self-care rather than to a post-surgery care facility. 11
Apart from helping patients and clinicians make informed decisions about risks associated with cardiac surgery, performing PFTs may actually contribute to improved clinical outcomes through optimised disease management (smoking cessation, pulmonary hygiene)45,46, appropriate respiratory medicines, wider use of non-invasive ventilation techniques47, prevention and timely treatment of arrhythmias. The fact that no specific measures based on PFTs results had been imposed in the present study (treatment was always at the discretion of attending physician) was reflected in longer ventilation time, higher incidence of AF and prolonged hospital stay of patients with respiratory abnormalities, thus underscoring the necessity for wider adoption of PFTs in routine practice. Interestingly, predictors of obstructive and restrictive patterns did not overlap, suggesting diverging pathophysiology and clinical implications, which merits further research. The strengths of our study include rigorous prospective design with high recruitment rate and use of full body plethysmography, that is believed to allow for more robust assessment of pulmonary function as compared to commonly used spirometry48. Several limitations must be acknowledged as well. Relatively small sample size may affect precision of the estimates. Attending physicians were not blinded to PFTs results that may have introduced information bias to the study. Finally, the follow-up is limited to 30 days, forcing mid- and long-term clinical outcomes beyond the scope of the present paper. In conclusion, in the cohort of 454 consecutive patients undergoing CABG surgery, use of PFTs provided important insights into the preoperative state of the patients, with implications for their postoperative clinical course. PFTs helped reclassify respiratory abnormality in every fourth patient, suggesting considerable underutilization thereof. Therefore, an opportunity exists for improvement of perioperative care and clinical outcome. Additionally, to the best of our knowledge, this is the first study that identified predictors of abnormal respiratory patterns in the cardiac surgery setting. Prevention of arrhythmias, 12
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Figure legend Figure 1. Patients’ flow chart.
17
Table 1. Baseline characteristics of the study cohort (n=454). Continuous data are mean ± standard deviation or median (interquartile range). Categorical variables are frequencies (percentage) Age, years
63 ± 8
Females
81 (17.8%)
Body mass index, kg/m2 NYHA functional class
CCS functional class
30 ± 5 I
13 (2.9%)
II
165 (36.3%)
III
276 (60.8%)
IV
none
I
3 (0.6%)
II
87 (19.2%)
III
364 (80.2%)
IV
none
Left ventricular ejection fraction, %
58 ± 10
Hypertension
418 (92.1%)
Previous myocardial infarction
288 (63.4%)
Peripheral vascular disease
103 (22.7%)
History of smoking
Never
233 (51.3%)
Former
98 (21.6%)
Current
123 (27.1%)
Chronic obstructive pulmonary disease
31 (6.8%)
Asthma
11 (2.4%)
Type 1 diabetes
14 (3.1%)
Type 2 diabetes
96 (21.1%)
History of atrial fibrillation
52 (11.5%)
Sinus rhythm at the morning of surgery
437 (96.2%)
History of cerebrovascular accident
24 (5.3%)
Previous percutaneous coronary intervention
84 (18.5%)
Chronic kidney disease
73 (16.1%)
Creatinine clearance, ml/min† Logistic EuroSCORE II
72 ± 16 1.3 (0.9; 1.9) 18
NYHA: New York Heart Association; CCS: Canadian Cardiovascular Society; †Levey AS, Stevens LA, Schmid CH, et al: A new equation to estimate glomerular filtration rate. Ann. Intern. Med. United States, 150:604–12, 2009.
Table 2. Baseline pulmonary functional data and questionnaires responses at baseline. Continuous variables are means (95% confidence interval, CI), ordinal data are medians (interquartile range). Categorical variables are frequencies (percentage, 95% CI). Normal pattern
Obstructive
Restrictive
Mixed
3.0 (2.9 - 3.0) (321 patients) 102.9 (101.3 - 104.6) 3.7 (3.6 - 3.8)
(72 patients, 2.5 (2.3 - 2.6) 15.8%) 84.6 (80.6 88.5) 3.9 (3.7 - 4.1)
(50 patients, 2.2 (2.1 - 2.4) 11.0%) 75.9 (72.2 79.6) 2.7 (2.5 - 2.8)
(11 patients, 1.7 (1.5 - 1.9) 2.4%) 58.4 (51.7 65.1) 2.7 (2.4 - 3.0)
FEV1/ FVC
101.5 (99.9 103.0) 0.8 (0.8 - 0.8)
103.1 (99.0 107.1) 0.6 (0.6 - 0.7)
71.7 (69.1 74.2) 0.9 (0.8 - 0.9)
71.8 (66.0 77.6) 0.6 (0.6 - 0.7)
TLC, L
7.4 (6.8 - 8.0)
7.9 (7.4 - 8.4)
6.2 (5.9 - 6.5)
7.5 (6.8 - 8.1)
TLC % predicted
114.9 (112.0 - 117.8) --
121.1 (115.7 - 128.6) 50 (11.0, 8.3 - 14.3) 14 (3.1, 1.7 5.2) 3 (0.6, 0.1 2.1) 5 (1.1, 0.4 2.7) 95.1 (94.6 95.5) 13.0 (11.0; 15.2) 2.0 (1.0; 2.0)
97.2 (92.4 101.9) 35 (7.7, 5.4 10.5) 8 (1.7, 0.7 3.4) 4 (0.9, 0.2 2.2) 3 (0.7, 0.1 1.9) 94.9 (94.4 95.4) 10.0 (9.2; 16.7) 1.5 (1.0; 2.7)
114.3 (105.7 - 123) 1 (0.2, 0.0 1.2) 4 (0.9, 0.2 2.2) 2 (0.4, 0.1 1.5) 4 (0.9, 0.2 2.2) 95.0 (93.4 96.6) 14.5 (12.7; 16.2) 2.0 (1.5; 2.5)
FEV1, L FEV1 % predicted FVC, L FVC % predicted
Severity of any spirometric
Mild Moderate
--
abnormality based on FEV1†
Moderately severe Severe
--
Oxygen saturation, %
COPD assessment test Medical Research Council breathlessness scale
-95.3 (95.2 95.5) 12.0 (7.0; 15.0) 1.0 (1.0; 2.0)
FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity, TLC: total lung capacity; †Pellegrino R, Viegi G, Brusasco V, et al: Interpretative strategies for lung function tests. Eur. Respir. J. 26:948–68, 2005; COPD: chronic obstructive pulmonary disease.
19
Table 3. Univariable and multivariable analyses of obstructive and restrictive respiratory patterns. Data are odds ratios (95% confidence intervals) Obstructive pattern
Age (1 year incr.) Male gender Smoking (current or former) History of COPD History of asthma BMI (1 kg/m2 incr.) Peripheral vascular disease History of atrial fibrillation LV ejection fraction (1% incr.) Diabetes Creatinine clearance (1 ml/min incr.) History of myocardial infarction EUROscore II
Restrictive pattern
Univariable
Multivariable
Univariable
Multivariable
1.03 (0.99 1.06) 2.69 (1.21 7.15)* 2.25 (1.34 3.85)** 6.02 (2.80 12.9)** NA
1.05 (1.01 1.09)* 2.27 (1.01 6.41)* 2.21 (1.23 4.09)** 4.70 (2.12 10.36)** --
--
0.95 (0.90 1.01) 1.13 (0.59 2.08) 1.00 (0.40 2.21) 0.99 (0.96 1.02) 0.74 (0.36 1.40) 1.00 (0.98 1.01) 0.64 (0.37 1.10) 1.01 (0.79 1.23)
--
1.01 (0.97 1.05) 1.67 (0.74 4.50) 0.97 (0.54 1.75) 1.21 (0.35 3.28) 4.93 (1.25 16.98)* 1.06 (1.01 1.13)* 1.90 (1.02 3.54)* 0.84 (0.28 2.05) 0.98 (0.95 1.01) 1.72 (0.90 3.19) 1.00 (0.98 1.02) 1.13 (0.62 2.15) 1.12 (0.89 1.36)
--------
---4.76 (1.18 16.88)* 1.06 (1.01 1.13)* 2.13 (1.10 4.04)* -------
COPD: chronic obstructive pulmonary disease; BMI: body mass index; LV: left ventricle; *p<0.05; **p<0.01
20
Table 4. Perioperative characteristics of patients with and without abnormal respiratory pattern. Continuous variables are mean ± standard deviation or medians (interquartile range). Categorical variables are frequencies (percentage within relevant category). With pattern,
Without pattern,
133 patients, 29.3%
321 patients, 70.7%
109 (81.9%)
281 (87.5%)
0.13
CABG + left ventricular aneurism repair
7 (5.3%)
12 (3.6%)
0.30
CABG + radiofrequency ablation
6 (4.5%)
11 (3.4%)
0.41
CABG + intervention on mitral valve
1 (0.8%)
6 (1.9%)
0.68
Other interventions
10 (7.5%)
11 (3.4%)
0.08
100 (75.2%)
280 (87.2%)
0.66
Duration of cardiopulmonary bypass, min
51 ± 32
53 ± 44
0.55
Duration of aortic cross-clamping, min
30 ± 21
32 ± 23
0.43
Intra aortic balloon pump use
2 (1.5%)
7 (2.2%)
>0.99
Number of grafts (distal anastomoses)
3 (2; 3)
2 (2; 3)
0.29
Number of internal mammary arteries used
1 (1; 1)
1 (1; 1)
0.68
Ventilation time, h
6 (4; 10)
4 (4; 6)
0.04
Prolonged ventilation (>24 h)
2 (1.5%)
8 (2.5%)
>0.99
Atrial fibrillation postoperatively
26 (19.5%)
68 (21.2%)
0.79
New –onset atrial fibrillation
20 (15.7%)
22 (8.0%)
0.02
Heart failure
17 (12.8%)
42 (13.1%)
0.75
9 (6.8%)
29 (9.0%)
0.71
Bleeding (requiring re-exploration)
2 (1.5%)
7 (2.2%)
>0.99
Myocardial infarction
1 (0.8%)
5 (1.6%)
>0.99
Renal replacement therapy
0 (0.0%)
3 (0.9%)
0.56
Extracorporeal membrane oxygenation use
0 (0.0%)
1 (0.3%)
>0.99
ICU stay, days
1 (1; 2)
1 (1; 2)
0.91
13 (10; 15)
11 (10; 14)
0.05
1 (0.8%)
4 (1.2%)
>0.99
p
Isolated CABG surgery
Cardiopulmonary bypass use
Pleural effusion (requiring surgical intervention)
Length of hospital stay, days ICU mortality
21
All-cause mortality at 30 days†
1 (0.8%)
5 (1.6%)
>0.99
CABG: coronary artery bypass graft; ICU: intensive care unit; †based on 99.6% complete follow-up.
501 eligible patients
Not included: 41 for logistical reasons 5 underwent PCI 1 listed for heart transplantation 454 patients recruited
31 patients with history of COPD
423 patients without history of COPD
Respiratory patterns:
Respiratory patterns:
5 normal 15 obstructive 4 restrictive 7 mixed
Lost to follow-up none
316 normal 57 obstructive 46 restrictive 4 mixed
Lost to follow-up 2 patients
22
PII: DOI: Reference:
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S1053-0770(16)30657-7 http://dx.doi.org/10.1053/j.jvca.2016.12.005 YJCAN3935
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Dmitry Ponomarev, Oksana Kamenskaya, Asya Klinkova, Irina Loginova, Vladimir Lomivorotov, Igor Kornilov, Vladimir Shmyrev, Aleksander Chernavskiy, Giovanni Landoni and Aleksander Karaskov, Prevalence and implications of abnormal respiratory patterns in cardiac surgery: A prospective cohort study, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2016.12.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Prevalence and implications of abnormal respiratory patterns in cardiac surgery: a prospective cohort study Dmitry Ponomareva1, MD, PhD, Oksana Kamenskayab, MD, PhD, Asya Klinkovab, PhD, Irina Loginovab, Vladimir Lomivorotova, MD, PhD, Igor Kornilova, MD, PhD, Vladimir Shmyreva, MD, PhD, Aleksander Chernavskiyc, MD, PhD, Giovanni Landonid, MD and Aleksander Karaskovc, MD, PhD 1
Corresponding author, email: [email protected], phone: +79232339205
a
Department of Anesthesia and Intensive Care, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
b
Department of Physiology, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
c
Department of Cardiac Surgery, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, 15 Rechkunovskaya street, Novosibirsk 630055, Russia
d
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy, and Vita-Salute San Raffaele University, Milan, Italy
Conflict of interest: none This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
1
Objective To investigate prevalence and impact of abnormal respiratory patterns in cardiac surgery patients. Design Prospective cohort study. Setting Tertiary hospital. Participants Patients scheduled for elective coronary artery bypass graft surgery. Interventions None. Measurements and Main Results Pulmonary function tests were performed in 454 patients before surgery. Abnormal respiratory patterns were defined as follows: obstructive (forced expiratory volume in 1 second/forced vital capacity < 0.70), restrictive (forced expiratory volume in 1 second/forced vital capacity ≥ 0.70 and forced vital capacity < 80% of predicted), mixed (forced expiratory volume in 1 second/forced vital capacity < 0.70 and both forced expiratory volume in 1 second and forced vital capacity < 80% of predicted). Of 31 patients with history of chronic obstructive pulmonary disease, no abnormal respiratory pattern was confirmed in 5. Of 423 patients without a history of lung disease, we newly identified 57 obstructive, 46 restrictive and 4 mixed patterns. Therefore, lung disease was reclassified in 24.7% cases. Independent
2
predictors of obstructive pattern were age, male gender, history of smoking and chronic obstructive pulmonary disease. Obstructive lung disease was associated with 16 hours longer ventilation. A reduced forced expiratory volume in 1 second was associated with likelihood of atrial fibrillation (1 liter decrement, odds ratio: 1.38, 95% CI: 1.01 to 1.90, p=0.04) and hospitalisation time (regression coefficient: 1.23, 95% CI: 0.54 to 1.91, p<0.001). Conclusions Abnormal respiratory patterns are common and often underdiagnosed in the cardiac surgery setting. Pulmonary function tests help reveal patients at risk of complications and may provide an opportunity for intervention.
Key Words: pulmonary function tests, obstructive respiratory pattern, restrictive respiratory pattern, chronic obstructive pulmonary disease, cardiac surgery.
Introduction Heart and respiratory diseases often coexist whether due to common lifestyle-related risk factors1,2, organ cross-talks3–5 or shared pathophysiology6. Obstructive, restrictive and mixed respiratory disorders are associated with increased cardiovascular morbidity and mortality2,7–9. Furthermore, patients with airflow limitation die more from cardiovascular causes than from the respiratory sequelae of chronic obstructive pulmonary disease (COPD)10. The latter, characterised by airflow limitation that is not fully reversible11, is present in up to 21% of cardiac surgical patients12. In cardiac surgery, airflow limitation as measured by forced expiratory volume in 1 second (FEV1), is associated with increased complication rates, such as postoperative arrhythmia13, and short- and long-term mortality12,14–16. Pulmonary
3
functional tests (PFTs) help reclassify chronic lung disease in 31%15 to 39%17 cases, with an overwhelming underestimation of the severity of the condition in those misclassified17, thus suggesting considerable underutilisation of PFTs in the cardiac surgery setting. However, methodological issues, such as retrospective design12,14,16 and high chances for selection bias15 call into question both internal and external validity of the above results. Additionally, majority of the studies focus on obstructive respiratory pattern, whereas restrictive and mixed disorders, prevalent in patients with heart diseases18, remain largely beyond the scope of research, with potential impact of this neglect on clinical outcome. Therefore, the aim of the present study was to investigate prevalence and patterns of respiratory disorders and their impact on clinical course after elective coronary artery bypass graft (CABG) surgery with or without concomitant procedures.
Methods Subject population Between March 2015 and August 2016, 454 consecutive patients scheduled for elective CABG surgery were recruited at Novosibirsk Research Institute of Circulation Pathology, Novosibirsk, Russian Federation. This prospective cohort study was approved by the local Ethics Committee and was conducted in compliance with the principles of the Declaration of Helsinki. The only inclusion criterion was planned CABG surgery (including concomitant surgeries). Exclusion criteria were: patient’s refusal to participate, contraindications for PFTs19,20, emergency surgery, recent or ongoing myocardial infarction, angina. After providing an informed written consent, all eligible patients underwent PFTs, completed both the modified Medical Research Council (mMRC) breathlessness scale21 and the COPD assessment test (CAT)22 before surgery. 4
Measurement of lung function Pulmonary functional tests were performed by an experienced physiologist using fullbody plethysmograph (Master Screen, Erich Jaeger, Germany) and in accordance with international standards, including the acceptability and reproducibility criteria23,24. Pulse oximetry was used to measure baseline oxygen saturation during air breathing. All subjects were seated during measurements. Airway reversibility test with 400 micrograms of salbutamol using a spacer inhaler was applied when indicated. Absolute and percent-ofpredicted (for height, weight, and age) FEV1 and Forced Vital Capacity (FVC) as well as FEV1/FVC ratio were estimated and used to define abnormal respiratory patterns. Obstructive pattern was defined as FEV1/FVC < 0.70; restrictive respiratory pattern was defined as a combination of FEV1/FVC ≥ 0.70 and FVC < 80% of predicted; and mixed pattern was defined as a combination of FEV1/FVC < 0.70, FEV1 < 80% of predicted, and FVC < 80% of predicted25; normal pattern was none of the above. Following determination of abnormal respiratory pattern, its severity was classified based on FEV125. Mild abnormality was defined as FEV1 > 70% of predicted, moderate 60 - 69% of predicted, moderately severe 50 - 59% of predicted, severe 35 - 49% of predicted, very severe was defined as FEV1 < 35% of predicted. Variables The following data were collected: demographics (date of birth, gender and race), body mass index, self-reported smoking status (never, former or current smoker), documented New York Heart Association (NYHA) functional class, Canadian Cardiovascular Society (CCS) grade of angina, arterial hypertension, diabetes, peripheral vascular disease, stroke, documented COPD, asthma, atrial fibrillation (AF), chronic kidney disease26, previous percutaneous coronary angioplasty (PCI), history of myocardial infarction (MI). Logistic EUROscore II27 and creatinine clearance28 were calculated, and left ventricular ejection
5
fraction was obtained for all patients. Intraoperative data included: type of surgery (isolated CABG or not, type of concomitant intervention if not), whether or not cardiopulmonary bypass (CPB) was used, number of grafts (distal anastomoses) performed, number of internal mammary arteries used, duration of cardiopulmonary bypass (if used), aortic cross-clamp time (if used), use of intra-aortic balloon pump (IABP) or other assist device. The definitions of adverse events are presented below. Heart failure was defined as need for intra-aortic balloon pump (IABP) or ≥ 2 inotropes at 48 hours. An episode of AF was defined as the loss of P-waves in the presence of irregular ventricular beats on electrocardiogram (ECG) throughout the monitoring ECG tracing29,30 (when examining associations between PFTs results and postoperative AF, no distinction was made between recurrence of AF and new-onset AF). Myocardial infarction was defined according to the Third Universal Definition of MI31. Pleuritis was defined as pleural effusion requiring surgical intervention. Renal failure was defined as need for renal replacement therapy. Postoperative characteristics were recorded, such as: duration of mechanical ventilation, intensive care unit (ICU) stay, left ventricular ejection fraction at discharge, length of hospital stay. Hospitalisation was time period (in days) between day of surgery (inclusive) and day of hospital discharge (exclusive). Thirty day mortality was defined as death from any cause within 30 days after surgery (including day of surgery); patient’s status after hospital discharge was established via telephone call to either the patient or patient’s next of kin, as indicated in informed consent form. All patients were treated according to the institutional standards, including recording of ECG daily after surgery. Patients with history of COPD continued disease-specific treatment throughout hospital stay; their perioperative care was left to the discretion of attending physician. General anesthesia was induced with fentanyl (3-8 µg/kg), propofol (1–3 mg/kg) and pipecuronium bromide (0.1 mg/kg) and maintained with sevoflurane (1-2 vol%), further 6
fentanyl, propofol and pipecuronium bromide were given as needed. When used, cardiopulmonary bypass was performed with normothermia (nasopharyngeal temperature above 35.5°C), with non-pulsatile flow of 2.4-2.8 L/min/m2. Off-pump surgeries were performed using various myocardial stabilisers. Standard extubational protocol was applied to all the patients. It comprised assessment of the patient’s neurological status (ability to follow verbal command, intact cough reflex), full reversal of muscle relaxation (sustained head or leg lift or hand grasp for 4-5 seconds), rewarming to 35.5°C, correction of coagulopathies, metabolic and electrolyte abnormalities, presence of stable hemodynamics in the absence of high dose vasopressors, adequate urine output (0.5-1.0 ml/kg/hr in patients younger than 65 years, 0.25-0.50 ml/kg/hr in older patients), pO2/FiO2 ≥ 200, absence of bleeding requiring surgical intervention, successful weaning trial with minimal support (5 cm H2O pressure support, 5 cm H2O positive end expiratory pressure, FiO2 40%) for 30 minutes. Statistical analysis Continuous variables are presented as mean ± standard deviation or as mean (95% confidence interval, CI), ordinal data are presented as median (interquartile range). Categorical variables are expressed as frequencies (percent) or as frequencies (percent, 95% CI). Associations between continuous variables were assessed with linear regression, results are presented as regression coefficient (95% CI). Binary logistic regression was used to examine binary outcomes. Ordinal logistic regression was used to assess an association between the severity of respiratory abnormality and candidate predictors. Results of all logistic regression models are presented as odds ratio (OR) and associated 95% CI. For the multivariable logistic regression analyses, a manual forward step-wise procedure with a cutoff p-value of 0.20 was used for formulating a final regression model. Otherwise, a two-tailed
7
p value below 0.05 was considered statistically significant. Unpaired t-test was used to compare two continuous variables, Mann-Witney test was used for ordinal data. For comparison of two categorical variables, Fisher’s exact test was utilised. All analyses were performed using R statistical software (R Core Team (2015). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.).
Results The patients’ flow is presented in Figure 1. Of 501 eligible patients, 41 were not enrolled mainly due to logistical or administrative reasons (conflicting procedures, late admission to the ward), 5 patients underwent PCI, and 1 patient was listed for heart transplantation. The baseline characteristics of the 454 patients included in the study are outlined in Table 1. Mean age was 63 years, 82% of patients were males. Documented AF (any type) was present in 11.5% of the patients. Most of the patients (96.2%) had sinus rhythm at the morning of surgery. Out of the 31 patients with history of COPD, 15 (48.4%) had obstructive respiratory pattern, 4 (12.9%) - restrictive, and 7 (22.6%) patients exhibited mixed features (Figure 1). In 5 (16.1%) patients with history of COPD, no abnormal respiratory pattern was confirmed with PFTs. Table 2 shows that the most prevalent abnormal respiratory pattern was obstructive lung disease. In total, obstructive, restrictive and mixed patterns were revealed in 15.8%, 11.0% and 2.4% of patients, respectively (Table 2). These data indicate that PFTs helped reclassify lung disease in 24.7% of patients. Most of the patients had mild (18.9%) or moderate (5.7%) abnormalities. As follows from Table 3, independent predictors of obstructive respiratory pattern were age, male gender, history of smoking, and preoperative 8
diagnosis of COPD. It was not feasible to assess association of obstructive pattern with asthma due to separation of the data (none of the patients with asthma had obstructive lung disease). Predictors of restrictive pattern were history of asthma, BMI and p eripheral vascular disease. Logistic EUROscore II was not significantly associated with either of the abnormal patterns. Further ordinal logistic regression analysis of severity of any respiratory disorder indicated increased chances of more severe abnormality (as compared to all less severe grades combined) associated with age (for a 1 year increment, OR: 1.05, 95% CI: 1.02 - 1.08, p<0.01), male gender (OR: 2.74, 95% CI: 1.36 - 5.94, p<0.01), history of smoking (OR: 1.84, 95% CI: 1.16 - 2.95, p=0.01) and asthma (OR: 4.47, 95% CI: 1.06 - 16.76, p=0.03). No significant association between questionnaires results and abnormal respiratory patterns or their severity was observed. Baseline oxygen saturation was not
significantly different between the patients’ categories based on respiratory pattern. Perioperative characteristics are presented in Table 4. Isolated CABG surgery was performed in 85.9% cases with the most frequent concomitant procedures being left ventricular aneurism repair (4.2%) and radiofrequency ablation (3.7%). Cardiopulmonary bypass was used in 83.7% cases, with a mean duration of 61 minutes. Obstructive lung disease was associated with 16
hours (95% CI: 2 to 31 hours, p=0.02) longer ventilation as compared to normal pattern. Perioperative course was complicated by heart failure in 13% cases; in 1 case it required emergency veno-arterial extracorporeal membrane oxygenation use. During postoperative period, at least one episode of AF was detected in 20.7% patients, with significantly higher rate of new-onset AF in patients with respiratory disorder as compared to patients without abnormal pattern (15.7% vs 8.0%, p=0.02). Mortality rate in ICU was 5 (1.1%), with total 30 days mortality of 6 (1.3%). Four fatal outcomes were due to intraoperative MI, where all available treatments, including use of assist devices, proved ineffective. In one case, intraoperative acute aortic dissection required aortic hemiarch replacement under deep hypothermic circulatory arrest, however, the patient died from massive bleeding the same day. One more patient died of stroke after hospital discharge. Two patients were lost to follow-up. Median length of hospital stay was 12 days.
9
Pre-planned univariable analyses indicated that FEV1 was associated with likelihood of AF in postoperative period (1 liter decrement, OR: 1.38, 95% CI: 1.01 to 1.90, p=0.04) and length of hospital stay (1 liter decrement, regression coefficient: 1.23, 95% CI: 0.54 to 1.91, p<0.001). Further exploratory analysis suggested on average 2 days (95% CI: 1 to 3 days, p<0.001) longer hospital stay in patients having developed AF in postoperative period as compared to those who had not (respective mean FEV1 values: 2.65±0.68 and 2.82±0.72 liters, p=0.04). Discussion In the present study, aimed at investigating prevalence and patterns of respiratory disorders and their impact on clinical course after CABG surgery, we found out that, in spite of low prevalence of clinically diagnosed COPD (6.8%), abnormal respiratory patterns are present in 29.3% of patients. PFTs helped reclassify (mostly revealing new cases) lung disease in 24.7% of patients. Independent predictors of obstructive pattern were age, male gender, history of smoking and history of COPD. Importantly, obstructive lung disease was associated with increased duration of mechanical ventilation, whereas FEV1, commonly used as a measure of airflow limitation, was linked to increased likelihood of AF in postoperative period and length of hospital stay. Restrictive lung disease was associated with history of asthma, BMI and peripheral vascular disease. Independent predictors of severity of any respiratory disorder were age, male gender, history of smoking and asthma.
Pulmonary diseases, such as COPD, are important risk factors of ischemic heart disease, heart failure and sudden cardiac death7,18,32,33. Suggested mechanisms include (but are not confined to) systemic inflammation, oxidative stress, hypoxia, vascular wall abnormalities, accelerated aging, protease/antiprotease imbalance34. In a recent study with mean follow-up of 13 years by Wannamethee at al., reduced FEV1 and FVC were associated with biomarkers of
10
heart failure and myocardial damage in 3,242 older (60-79 years) men not undergoing cardiac surgery; furthermore, reduced FEV1 was also linked to incidence of heart failure35. This notion is further supported by evidence indicating that in patients with COPD cardiovascular mortality prevails over deaths due respiratory causes10,36. In the cardiac surgery setting, coexisting COPD is associated with complicated postoperative course, longer hospital stay and increased mid- and long-term morbidity and mortality12,14–16. In some studies, however, these associations were not confirmed37,38. Interestingly, in a study by Gao et al., a timevarying effect of COPD on mortality after cardiac surgery was demonstrated, with little or no associated risk immediately after surgery, significant risk at 1 month and almost doubled chances of death associated with COPD at 3-4 months39. In clinical practice, PFTs are not routinely utilised in patients without COPD, which is commonly diagnosed based on clinical signs (mainly dyspnea) and presence of predisposing factors (occupational exposure, smoking)40,41. In the cardiac surgery setting, using these criteria without PFTs leads to misdiagnosis of COPD in 31%15 to 39%17 cases, thereby an established risk factor for postoperative complications and mortality after cardiac surgery is undeservedly neglected by many. In the present study, lung disease was reclassified in every fourth patient (24.7%). An important observation was the association between lung function and postoperative AF occurrence. This relationship has been suggested by several studies, implicating
hypoxia,
pulmonary
hypertension
and
chronic
inflammation
within
cardiorespiratory system42–44, although the exact mechanisms remain to be determined. In our study, higher incidence of new-onset AF in patients with reduced lung function could add to the explanation of an observed association between FEV1 and length of hospital stay as postoperative AF was associated with on average 2 days longer hospitalisation. Relatively long hospitalisation (median 12 days) is attributed to the fact that at our centre patients are discharged home for self-care rather than to a post-surgery care facility. 11
Apart from helping patients and clinicians make informed decisions about risks associated with cardiac surgery, performing PFTs may actually contribute to improved clinical outcomes through optimised disease management (smoking cessation, pulmonary hygiene)45,46, appropriate respiratory medicines, wider use of non-invasive ventilation techniques47, prevention and timely treatment of arrhythmias. The fact that no specific measures based on PFTs results had been imposed in the present study (treatment was always at the discretion of attending physician) was reflected in longer ventilation time, higher incidence of AF and prolonged hospital stay of patients with respiratory abnormalities, thus underscoring the necessity for wider adoption of PFTs in routine practice. Interestingly, predictors of obstructive and restrictive patterns did not overlap, suggesting diverging pathophysiology and clinical implications, which merits further research. The strengths of our study include rigorous prospective design with high recruitment rate and use of full body plethysmography, that is believed to allow for more robust assessment of pulmonary function as compared to commonly used spirometry48. Several limitations must be acknowledged as well. Relatively small sample size may affect precision of the estimates. Attending physicians were not blinded to PFTs results that may have introduced information bias to the study. Finally, the follow-up is limited to 30 days, forcing mid- and long-term clinical outcomes beyond the scope of the present paper. In conclusion, in the cohort of 454 consecutive patients undergoing CABG surgery, use of PFTs provided important insights into the preoperative state of the patients, with implications for their postoperative clinical course. PFTs helped reclassify respiratory abnormality in every fourth patient, suggesting considerable underutilization thereof. Therefore, an opportunity exists for improvement of perioperative care and clinical outcome. Additionally, to the best of our knowledge, this is the first study that identified predictors of abnormal respiratory patterns in the cardiac surgery setting. Prevention of arrhythmias, 12
optimisation of care in those at risk and improving risk stratification with PFTs merits further research. References 1.
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Figure legend Figure 1. Patients’ flow chart.
17
Table 1. Baseline characteristics of the study cohort (n=454). Continuous data are mean ± standard deviation or median (interquartile range). Categorical variables are frequencies (percentage) Age, years
63 ± 8
Females
81 (17.8%)
Body mass index, kg/m2 NYHA functional class
CCS functional class
30 ± 5 I
13 (2.9%)
II
165 (36.3%)
III
276 (60.8%)
IV
none
I
3 (0.6%)
II
87 (19.2%)
III
364 (80.2%)
IV
none
Left ventricular ejection fraction, %
58 ± 10
Hypertension
418 (92.1%)
Previous myocardial infarction
288 (63.4%)
Peripheral vascular disease
103 (22.7%)
History of smoking
Never
233 (51.3%)
Former
98 (21.6%)
Current
123 (27.1%)
Chronic obstructive pulmonary disease
31 (6.8%)
Asthma
11 (2.4%)
Type 1 diabetes
14 (3.1%)
Type 2 diabetes
96 (21.1%)
History of atrial fibrillation
52 (11.5%)
Sinus rhythm at the morning of surgery
437 (96.2%)
History of cerebrovascular accident
24 (5.3%)
Previous percutaneous coronary intervention
84 (18.5%)
Chronic kidney disease
73 (16.1%)
Creatinine clearance, ml/min† Logistic EuroSCORE II
72 ± 16 1.3 (0.9; 1.9) 18
NYHA: New York Heart Association; CCS: Canadian Cardiovascular Society; †Levey AS, Stevens LA, Schmid CH, et al: A new equation to estimate glomerular filtration rate. Ann. Intern. Med. United States, 150:604–12, 2009.
Table 2. Baseline pulmonary functional data and questionnaires responses at baseline. Continuous variables are means (95% confidence interval, CI), ordinal data are medians (interquartile range). Categorical variables are frequencies (percentage, 95% CI). Normal pattern
Obstructive
Restrictive
Mixed
3.0 (2.9 - 3.0) (321 patients) 102.9 (101.3 - 104.6) 3.7 (3.6 - 3.8)
(72 patients, 2.5 (2.3 - 2.6) 15.8%) 84.6 (80.6 88.5) 3.9 (3.7 - 4.1)
(50 patients, 2.2 (2.1 - 2.4) 11.0%) 75.9 (72.2 79.6) 2.7 (2.5 - 2.8)
(11 patients, 1.7 (1.5 - 1.9) 2.4%) 58.4 (51.7 65.1) 2.7 (2.4 - 3.0)
FEV1/ FVC
101.5 (99.9 103.0) 0.8 (0.8 - 0.8)
103.1 (99.0 107.1) 0.6 (0.6 - 0.7)
71.7 (69.1 74.2) 0.9 (0.8 - 0.9)
71.8 (66.0 77.6) 0.6 (0.6 - 0.7)
TLC, L
7.4 (6.8 - 8.0)
7.9 (7.4 - 8.4)
6.2 (5.9 - 6.5)
7.5 (6.8 - 8.1)
TLC % predicted
114.9 (112.0 - 117.8) --
121.1 (115.7 - 128.6) 50 (11.0, 8.3 - 14.3) 14 (3.1, 1.7 5.2) 3 (0.6, 0.1 2.1) 5 (1.1, 0.4 2.7) 95.1 (94.6 95.5) 13.0 (11.0; 15.2) 2.0 (1.0; 2.0)
97.2 (92.4 101.9) 35 (7.7, 5.4 10.5) 8 (1.7, 0.7 3.4) 4 (0.9, 0.2 2.2) 3 (0.7, 0.1 1.9) 94.9 (94.4 95.4) 10.0 (9.2; 16.7) 1.5 (1.0; 2.7)
114.3 (105.7 - 123) 1 (0.2, 0.0 1.2) 4 (0.9, 0.2 2.2) 2 (0.4, 0.1 1.5) 4 (0.9, 0.2 2.2) 95.0 (93.4 96.6) 14.5 (12.7; 16.2) 2.0 (1.5; 2.5)
FEV1, L FEV1 % predicted FVC, L FVC % predicted
Severity of any spirometric
Mild Moderate
--
abnormality based on FEV1†
Moderately severe Severe
--
Oxygen saturation, %
COPD assessment test Medical Research Council breathlessness scale
-95.3 (95.2 95.5) 12.0 (7.0; 15.0) 1.0 (1.0; 2.0)
FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity, TLC: total lung capacity; †Pellegrino R, Viegi G, Brusasco V, et al: Interpretative strategies for lung function tests. Eur. Respir. J. 26:948–68, 2005; COPD: chronic obstructive pulmonary disease.
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Table 3. Univariable and multivariable analyses of obstructive and restrictive respiratory patterns. Data are odds ratios (95% confidence intervals) Obstructive pattern
Age (1 year incr.) Male gender Smoking (current or former) History of COPD History of asthma BMI (1 kg/m2 incr.) Peripheral vascular disease History of atrial fibrillation LV ejection fraction (1% incr.) Diabetes Creatinine clearance (1 ml/min incr.) History of myocardial infarction EUROscore II
Restrictive pattern
Univariable
Multivariable
Univariable
Multivariable
1.03 (0.99 1.06) 2.69 (1.21 7.15)* 2.25 (1.34 3.85)** 6.02 (2.80 12.9)** NA
1.05 (1.01 1.09)* 2.27 (1.01 6.41)* 2.21 (1.23 4.09)** 4.70 (2.12 10.36)** --
--
0.95 (0.90 1.01) 1.13 (0.59 2.08) 1.00 (0.40 2.21) 0.99 (0.96 1.02) 0.74 (0.36 1.40) 1.00 (0.98 1.01) 0.64 (0.37 1.10) 1.01 (0.79 1.23)
--
1.01 (0.97 1.05) 1.67 (0.74 4.50) 0.97 (0.54 1.75) 1.21 (0.35 3.28) 4.93 (1.25 16.98)* 1.06 (1.01 1.13)* 1.90 (1.02 3.54)* 0.84 (0.28 2.05) 0.98 (0.95 1.01) 1.72 (0.90 3.19) 1.00 (0.98 1.02) 1.13 (0.62 2.15) 1.12 (0.89 1.36)
--------
---4.76 (1.18 16.88)* 1.06 (1.01 1.13)* 2.13 (1.10 4.04)* -------
COPD: chronic obstructive pulmonary disease; BMI: body mass index; LV: left ventricle; *p<0.05; **p<0.01
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Table 4. Perioperative characteristics of patients with and without abnormal respiratory pattern. Continuous variables are mean ± standard deviation or medians (interquartile range). Categorical variables are frequencies (percentage within relevant category). With pattern,
Without pattern,
133 patients, 29.3%
321 patients, 70.7%
109 (81.9%)
281 (87.5%)
0.13
CABG + left ventricular aneurism repair
7 (5.3%)
12 (3.6%)
0.30
CABG + radiofrequency ablation
6 (4.5%)
11 (3.4%)
0.41
CABG + intervention on mitral valve
1 (0.8%)
6 (1.9%)
0.68
Other interventions
10 (7.5%)
11 (3.4%)
0.08
100 (75.2%)
280 (87.2%)
0.66
Duration of cardiopulmonary bypass, min
51 ± 32
53 ± 44
0.55
Duration of aortic cross-clamping, min
30 ± 21
32 ± 23
0.43
Intra aortic balloon pump use
2 (1.5%)
7 (2.2%)
>0.99
Number of grafts (distal anastomoses)
3 (2; 3)
2 (2; 3)
0.29
Number of internal mammary arteries used
1 (1; 1)
1 (1; 1)
0.68
Ventilation time, h
6 (4; 10)
4 (4; 6)
0.04
Prolonged ventilation (>24 h)
2 (1.5%)
8 (2.5%)
>0.99
Atrial fibrillation postoperatively
26 (19.5%)
68 (21.2%)
0.79
New –onset atrial fibrillation
20 (15.7%)
22 (8.0%)
0.02
Heart failure
17 (12.8%)
42 (13.1%)
0.75
9 (6.8%)
29 (9.0%)
0.71
Bleeding (requiring re-exploration)
2 (1.5%)
7 (2.2%)
>0.99
Myocardial infarction
1 (0.8%)
5 (1.6%)
>0.99
Renal replacement therapy
0 (0.0%)
3 (0.9%)
0.56
Extracorporeal membrane oxygenation use
0 (0.0%)
1 (0.3%)
>0.99
ICU stay, days
1 (1; 2)
1 (1; 2)
0.91
13 (10; 15)
11 (10; 14)
0.05
1 (0.8%)
4 (1.2%)
>0.99
p
Isolated CABG surgery
Cardiopulmonary bypass use
Pleural effusion (requiring surgical intervention)
Length of hospital stay, days ICU mortality
21
All-cause mortality at 30 days†
1 (0.8%)
5 (1.6%)
>0.99
CABG: coronary artery bypass graft; ICU: intensive care unit; †based on 99.6% complete follow-up.
501 eligible patients
Not included: 41 for logistical reasons 5 underwent PCI 1 listed for heart transplantation 454 patients recruited
31 patients with history of COPD
423 patients without history of COPD
Respiratory patterns:
Respiratory patterns:
5 normal 15 obstructive 4 restrictive 7 mixed
Lost to follow-up none
316 normal 57 obstructive 46 restrictive 4 mixed
Lost to follow-up 2 patients
22