Establishing failure predictors for the planned extubation of overweight and obese patients

We investigated failure predictors for the planned extubation of overweight (body mass index [BMI] = 25.0–29.9) and obese (BMI ≥ 30) patients. All patients admitted to the adult intensive care unit (ICU) of a tertiary hospital in Taiwan were identified. They had all undergone endotracheal intubation for > 48 h and were candidates for extubation. During the study, 595 patients (overweight = 458 [77%]); obese = 137 [23%]) with planned extubation after weaning were included in the analysis; extubation failed in 34 patients (5.7%). Their mean BMI was 28.5 ± 3.8. Only BMI and age were significantly different between overweight and obese patients. The mortality rate for ICU patients was 0.8%, and 2.9% for inpatients during days 1–28; the overall in-hospital mortality rate was 8.4%. Failed Extubation group patients were significantly older, had more end-stage renal disease (ESRD), more cardiovascular system-related respiratory failure, higher maximal inspiratory pressure (MIP), lower maximal expiratory pressure (MEP), higher blood urea nitrogen, and higher ICU- and 28-day mortality rates than did the Successful Extubation group. Multivariate logistic regression showed that cardiovascular-related respiratory failure (odds ratio [OR]: 2.60; 95% [confidence interval] CI: 1.16–5.80), ESRD (OR: 14.00; 95% CI: 6.25–31.35), and MIP levels (OR: 0.94; 95% CI: 0.90–0.97) were associated with extubation failure. We conclude that the extubation failure risk in overweight and obese patients was associated with cardiovascular system-related respiratory failure, ESRD, and low MIP levels.


Introduction
The prevalence of obesity is increasing worldwide and it has become a global public health threat. Obesity increases the risks of diabetes mellitus (DM), coronary artery disease (CAD), stroke, renal function impairment, respiratory dysfunction, and malignancy [1][2][3][4]. Because obesity has so many pathophysiologic effects upon all major organ systems and increases the prevalence of comorbidities, it is also significantly associated with higher risks of morbidity and mortality [5][6][7]. Therefore, an increasing number of obese patients need to be admitted to the intensive care unit (ICU) for critical care, and ICUs will inevitably have to treat a greater number of critically ill obese patients [8,9].
Acute respiratory failure is one of the most frequent reasons that patients are transferred to the ICU. This condition is usually treated using endotracheal intubation with invasive mechanical ventilation, regardless of whether the patient is obese or normal weight [10][11][12]. A patient who has survived an acute condition that requires intubation must first be weaned from invasive ventilation. The critical care physician must then do a weaning test and decide the appropriate timing for extubation. However, even after a comprehensive evaluation, extubation fails for a significant percentage of patients, who then require reintubation. Several studies [13][14][15][16][17] have identified useful factors to accurately predict successful extubation. Several physiological parameters of pulmonary mechanisms [13,16,17], such as respiratory frequency-to-tidal volume (the rapid shallow breathing index [RSBI]), thoracic compliance, oxygenation, maximum occlusion pressure, and dynamic changes through the course of a spontaneous breathing trial (SBT), and airway protection capabilities, including mental status, cough strength, and secretion loads have been identified as possible predictors of successful extubation. However, the lung function of overweight patients is different from that of normal weight and underweight patients [18][19][20][21]. Thus, we aimed to determine what would predict the successful extubation of overweight and obese patients.

Patients and hospital setting
This study was done at the Chi Mei Medical Center, a 1288-bed tertiary medical center with 96 ICU beds for adults. The ICU is staffed by critical care attending physicians, senior residents, nurses, respiratory therapists, dietitians, physical therapists, and clinical pharmacists. Each team makes rounds at least once daily, and respiratory therapists manage all mechanical ventilation (MV) patients, including SBTs: T-piece or pressure support ventilation (PSV) for 30-120 minutes and weaning them from MV processes. All patients who required an invasive MV using an endotracheal tube for 48 hours and who were prepared for a scheduled extubation according to a weaning protocol and physicians' judgment between January 2010 and December 2011 were eligible for inclusion. Each patient's ICU admission weight and height were used to calculate their body mass index (BMI = weight in kg/height in m 2 ). We measured weight in ICU patients with electronic weighing beds (Chang Gung Medical Technology Co., Ltd). Only adult (> 18 years old) patients with a BMI ! 25 kg/m 2 were included in this study. For patients who required repeated intubation, only the first episode was included in the analysis.

Variables measured
The medical records of all included patients were retrospectively reviewed and information was collected about age, gender, type of ICU, level of consciousness, intubation pathway (nose or mouth), why intubation was required, underlying diseases, and comorbidities, laboratory examination results, organ failure, intubation details, disease severity, length of ICU and hospital stays, reintubation rate, and mortality rate. After a patient had completed a successful SBT, the weaning parameters-respiratory rate, tidal volume, minute ventilation, RSBI, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and cuff leak test (CLT) -were measured when the patients were presumed ready for extubation. To accurately measure MIP, we measured 3 times with an interval of 5-6 seconds (2-3 breaths), and the value was recorded as the maximal data within these 3 checks. Additionally, we held the breath of unconscious and of uncooperative patients for 20 seconds from the end of inspiration to obtain the level of MIP. Thus, we improved the accuracy of MIP measurements. All data were routinely retrospectively collected and then analyzed. The Chi Mei Medical Center Institutional Review Board approved the study and specifically waived informed consent (IRB NO: 10206-005).

Definitions
CLT scores were 2+ (audible flow without a stethoscope), 1+ (audible flow with a stethoscope), and N (negative; no audible flow with a stethoscope). Extubation failure was defined as reintubation within 48 hours of extubation. Overweight was defined as a BMI of 25.0-29.9 kg/m 2 and obesity as a BMI of ! 30 kg/m 2 . Causes of respiratory failure were classified as the pulmonary system (upper airway obstruction, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, pneumonia, malignant effusion, lobar collapse, asthma attack), cardiovascular system (congestive heart failure, pericarditis, cardiomyopathy, acute myocardial infarction, endocarditis), neurological system (status epilepticus, stroke), renal system (acute renal failure), gastrointestinal system, and others, as previously described [22,23].

Statistical analysis
Continuous variables are reported as mean ± standard deviation (SD). Categorical variables are presented as n (%). In addition, the differences in baseline characteristics and clinical variables between the Successful and Failed Extubation groups were evaluated using a Student's t test for continuous variables and a Pearson χ 2 test for categorical variables. Those significantly associated with failed extubation in a univariate analysis (P < 0.05) were tested for interaction using a multivariate logistic regression analysis. Univariate and multivariate logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of significant variables to determine the association between predictive variables and successful extubation. SAS 9.4 for Windows (SAS Institute, Cary, NC, USA) was used for all analyses. Significance was set at P < 0.05 (two-tailed).

Demographic characteristics
We enrolled 1934 patients who had been scheduled for a first-time extubation after more than 48 h of invasive MV (an endotracheal tube) after we had excluded eight patients without available BMI data (S1 File). More than half (55.9%; n = 1082) of the patients had a normal body weight (BMI = 18.5 to < 25), 257 (13.3%) were underweight (BMI < 18.5), and 595 (30.8%) were overweight or obese (BMI = ! 25). All patients were followed up until the primary outcome: in-hospital death or survival to discharge.

Comparison of patients in the Failed and Successful Extubation groups
There were many significant differences between the Failed and the Successful Extubation group patients. Those in the Failed Extubation group were older, had more end-stage renal disease (ESRD), and had a higher blood urea nitrogen (BUN) level (Table 2). They also had more respiratory failure because of cardiovascular system failure, had a less-negative MIP, and a less-positive MEP ( Table 2). Failed Extubation group patients had higher mortality rates than did Successful Extubation group patients (Table 3). They were also transferred to the Respiratory Care Center and Respiratory Care ward because it was difficult to wean them from MV Consequently, they had longer ICU and hospital stays, and higher hospital costs than did patients in the Successful Extubation group (Table 3).

Discussion
Our most important finding was that the MIP level was significantly associated with the outcome of extubation. Although impaired respiratory muscle loading might be induced by dysfunctional respiratory system mechanics and high ventilation demands, our finding indicated that extubation failure might be closely related to the power of respiratory muscle to overcome the burden of a large body size. In contrast, the RSBI, which is most commonly used to evaluate the ability of patients to breathe spontaneously and to be successfully weaned from MV, was not significantly different between the Failed and Successful Extubation groups. Studies [24,25] on neurology patients report that the RSBI does not predict extubation failure. Although others [26][27][28] have identified many variables, e.g., age, mental status, oxygenation impairment, and the severity of acute illnesses, as risk factors for extubation failure and reintubation, we did not find that these variables were independent predictors of reintubation. This might be partly because of our unique study population: overweight and obese patients. It indicates that more studies are needed to investigate and establish prediction models of failed and successful extubation in specific populations.
We also found that ESRD was independently associated with extubation failure. A recent study [29] on surgical ICUs reported that an elevated BUN level (> 8.2 mmol/L) was an independent risk factor for reintubation (OR: 3.66; 95% CI: 1.97-6.80) in patients with a median BMI of 26.9 (no reintubation group; n = 699) and with a median BMI of 26.2 (reintubation group; n = 65). Another study [30] reported that acute kidney injury (OR: 2.98; 95% CI: 2.13-4.02) was associated with reintubation after coronary artery bypass grafting surgery. Overall, renal failure can be a risk factor of extubation failure in overweight patients and other populations.
A third important finding is that the risk of extubation failure was higher when the cause of respiratory failure was a cardiovascular system failure. In the present study, more than 40% of our patients with extubation failure had cardiovascular system failure that had required the patients to be intubated. Obesity itself is an important risk factor for the development of cardiovascular diseases [31]; therefore, physicians should more carefully assess the timing of extubation, especially for obese patients with cardiac failure. However, additional studies are required to confirm this finding. Finally, our patients with a failed extubation, like those in other studies [22,26,32], had worse outcomes, including higher mortality and longer hospital stays. However, the extubation failure rate in the present study was only 5.7%, significantly lower than those in two of those studies [26,32]. The difference might be attributable to different study designs and weaning protocols. Our finding suggests, however, that it is possible to select patients who can be successfully extubated after a comprehensive assessment, including a conventional weaning profile, underlying disease, and the cause of acute respiratory failure. It is also possible that the low failure rate in our study was caused by delayed extubation (the average duration of MV was 7-8 days in the present study). However, delayed extubation is also reported to be associated with worse outcomes, such as pneumonia, length of stay in the ICU and in the hospital, and mortality [33]. Therefore, it is important for physicians to weigh risks versus benefits between delayed and early extubation. We recommend that for overweight and obese patients, physicians should carefully evaluate MIP level, the cause of respiratory failure, and comorbid ESRD before scheduling an extubation.
This study has some limitations. It was done in a single tertiary medical center, the final decision to extubate was made by ICU physicians. Extubation can be delayed until patients show improvement in all variables. Therefore, our findings might not be generalizable to other populations. Because this is the first report that focuses on the risk factors of extubation failure in overweight and obese patients, it offers some useful insights. Although we tried to adjust for all possible confounding factors in this retrospective study, we might have missed some other cofactors, such as previously prescribed and taken sedatives. Further investigations are warranted. Categorical variables are expressed as n (%) and continuous variables as means ± standard deviation (SD).