Abstract

Methods: This retrospective observational cohort study included 57 lung cancer patients admitted to ICU who developed acute respiratory failure after pneumonectomy or lobectomy. Patients were divided as pneumonectomy (group 1; 19 males, 1 females; median age 65 years) and lobectomy (group 2; 36 males, 1 females; median age 62 years) groups. Pulmonary function test, invasive or noninvasive mechanical ventilation results, duration of ICU stay, and ICU mortality and long-term mortality were recorded. The groups were compared according to the recorded data.

Results: In group 1 and group 2, median preoperative forced expiratory volume in one second values were 1.58 L (predicted 61%) and 1.82 L (predicted 63%), respectively (p=0.82). Rates of patients with acute respiratory failure due to postoperative sepsis were similar in group 1 (65%) and group 2 (52.6%) (p=0.37). Group 1 and group 2 had similar median duration of ICU stay (9 and 8 days, respectively; p=0.76), ICU mortality (30.0% and 18.6%, respectively; p=0.34), and long term survival (n=6, 11 months; n=21, 5 months, respectively; p=0.79).

Conclusion: Lung cancer patients who were performed pneumonectomy or lobectomy might require ICU stay due to postoperative sepsis. Our study suggests that ICU mortality and long-term survival are not affected by the type of lung resection in these patients.

To best of our knowledge, there has been no definitive study in the English literature that has evaluated the outcomes of pneumonectomies or lobectomies in the ICU, and only limited data exists concerning those patients’ pulmonary functions, length of ICU stays, and long-term outcomes. In this study, we compared the ICU data and outcomes for acute respiratory failure (ARF) patients who underwent pneumonectomies and lobectomies along with their long-term survival rates.

Methods

Fifty-seven consecutive lung cancer patients (55 males and 2 females) who had resections via either a pneumonectomy or lobectomy and who had been admitted to the ICU with ARF were included in this study. Group 1 consisted of patients who had a pneumonectomy while group 2 was composed of those who had a lobectomy. Additionally, the study was open only to patients with a histopathological diagnosis of NSCLC.

The preoperative evaluation included obtaining the patients’ medical history, giving a physical examination, and performing routine blood tests, electrocardiography (ECG), a pulmonary function test (PFT), and a perfusion lung scan. In addition, spirometry (Zan GPI 3.00, nSpire Health, Longmont, Colorado, USA) was performed according to the European Respiratory Society (ERS) guidelines[6] to obtain the forced expiratory volume in one second (FEV₁), percentage of the predicted FEV₁ (%), forced vital capacity (FVC), percentage of predicted FVC (%), and FEV₁/FVC ratio. If the FEV₁ was more than 80% of the predicted norm or more than two liters, the patient was considered to be suitable for a pneumonectomy without any further evaluation,[7] and if the FEV₁ was m ore t han 1.5 l iters, t he p atient was considered suitable for a lobectomy without any further evaluation. Those patients with FEV1 values of less than 80% of the predicted norm underwent additional tests such as a ventilation-perfusion scan with technetium-99m, after which calculations were made to understand the postoperative lung reserve of the patients. The predicted postoperative FEV1 (ppoFEV₁) for the pneumonectomy candidates was calculated using the following formula: preoperative FEV₁ x rate of perfusion of remaining lung/perfusion of total ipsilateral lung. Furthermore, a quantitative radionuclide perfusion scan was performed to measure the relative function of each lung. The ppoFEV₁ for the lobectomy was calculated with a similar to the perfusion scan using the number of segments removed via the following formula: the preoperative FEV₁ x the number of segments which is remaining/the number of total segments.

The patients who underwent a lung resection were followed up in the recovery room for a period ranging from a few hours to 24 hours by an anesthesiologist after surgery. Those who were spontaneously breathing were either extubated in the operating room or in the recovery room after a few hours had passed. The stable patients were admitted to the surgical ward after being extubated in the recovery room. The patients who needed respiratory support via mechanical ventilation or who were clinically unstable (hemodynamically unstable, hypotensive, or hypoxemic [partial arterial oxygen pressure over fractionated inspired oxygen (PaO₂/FiO₂) of <200] or those with a systolic pressure <90 mmHg were admitted to the respiratory ICU. The ICU patients were cared for with both invasive and noninvasive mechanical ventilation (IMV and NIMV). The NIMV was applied when it was not contraindicated,[8] whereas the IMV was applied when the NIMV was not suitable or when it was contraindicated.[8]

The pressure assist-control mode was initially chosen for the IMV, and the inspiratory positive airway pressure (IPAP) was set to have a tidal volume of 250-300 mL for the pneumonectomies and 300-350 mL for the lobectomies. We also paid special attention to make sure that the plateau pressure was less than 35 cm H₂O and that the positive end-expiratory pressure (PEEP) was cautiously applied with less than 5 cm H₂O. In addition, the respiratory rate was set at 12-20 breaths/minute. All of the patients were weaned using our normal ICU protocol, which we adapted from the ERS protocol.[9] The patients’ IPAP settings were then slowly raised from 5 cm H₂O to 25 cm H₂O using the ventilators in the NIMV mode. Furthermore, the sedation and agitation levels of the patients were determined according to the Richmond Agitation- Sedation Scale (RASS).[10]

All of the patients’ data was recorded retrospectively from an electronic database and written medical records, and information regarding age, gender, body mass index (BMI), comorbid diseases such as chronic obstructive pulmonary diseases (COPD)[11] diabetes mellitus (DM), arrhythmia [atrial fibrillation (AF) and supraventricular tachycardia), hypertension (HT), type of surgery (pneumonectomy or lobectomy), and the preoperative PFT results of both groups was obtained. Those patients who were 70 years old or older were deemed to be elderly.[12] Moreover, the C-reactive protein (CRP) levels, leukocyte counts, serum albumin levels, and blood biochemistry results (blood glucose and creatinine) were recorded when the patients were admitted to the hospital for the surgery and when they were admitted to the ICU. The IMV/NIMV demand and duration and arterial blood gas (ABG) values were also recorded. In addition, the ICU severity score was evaluated using the Acute Physiology and Chronic Health Evaluation II (APACHE II) after admission to the ICU.[13] Postoperative respiratory failure and ICU demand were defined as having hypoxemia (paO₂/FiO₂ <300) as well as either sepsis, severe sepsis, or septic shock.[14]

Statistical analysis
The two groups were compared using the Mann- Whitney U test for nonparametric continuous variables, Student’s t-test for parametric continuous variables, and a chi-square test for dichotomous variables. The median and interquartile range (IQR) were used to describe the nonparametric continuous variables, and mean ± standard deviation (SD) was used for the parametric continuous variables. Furthermore, numerical values and percentages were used when applicable, and the Kaplan-Meier survival analysis was used to determine long-term survival. A p value of <0.05 was considered to be statistically significant.

Results

Table 1: Patient demographics and pre- and postoperative surgical intensive care unit outcomes of groups 1 and 2

Groups 1 and 2 had similar basic blood chemistry results (Table 2), but the serum albumin levels were significantly lower in group 1 (p=0.034). Moreover, the ABG analysis upon admission to the respiratory ICU were similar in both groups (Table 2). We also determined that approximately 90% of the patients in the two groups were initially ventilated with IMV but that after extubation, half of the patients underwent NIMV (Table 2). Furthermore, the patients in group 2 (41.4%) needed a higher rate of IMV (more than 14 days) than those in group 1 (22.2%) (Table 2). Although not statistically significant, the number of patients who required a blood transfusion during their stay in the ICU was four times higher in group 2 than in group 1 (21% vs. 5%, respectively). Furthermore, the length of time spent in the respiratory ICU was similar in both groups as was the mortality and long-term survival rate in months (Table 2).

Table 2: Respiratory intensive care unit outcomes of groups 1 and 2

Figure 1 shows the similar long-term survival rates of groups 1 and 2 (p=0.79). Twenty-seven patients were discharged from the respiratory ICU; the patients with pneumonectomies (n=6) median survival was 11 months (IQR, 3-25) and the patients with lobectomies (n=21) median survey was five months (IQR, 1-17). However, this difference was not statistically significant (Figure 1).

Figure 1: Comparison of the long-term survival after ICU discharge of the pneumonectomy (group 1) and lobectomy (group 2) patients.

Discussion

Two past studies with very large sample sizes found mortality rates of between 1.2 and 4.2% for lobectomies and 3.2 and 11.6% for pneumonectomies.[15,16] In this study, although the overall lung resection mortality rate in our hospital was not included in the data, the mortality rates for lobectomies and pneumonectomies in the ICU were 18.9% and 30.0%, respectively. We previously found that postoperative respiratory failure was affected independently by the type of surgery and that the demand for mechanical ventilation was correlated with advanced disease and lower PFT scores.[17]

Several studies have shown that the postoperative complications associated with these procedures are primarily cardiac in nature and include myocardial infarction (MI), stroke, and severe arrhythmias.[18-20] In this study, we determined that a third of the patients had arrhythmias, despite having similar heart rates and HT, and that the arrhythmia rates were higher in group 2 than in group 1 (35% vs. 15%). This might be explained by the fact that the long-term survival of the majority of patients in group 2 (11 months) was twice as high as those in group 1 (5 months).

Perioperatively, age and comorbid diseases were important factors related to the morbidity and mortality of our patients with lung cancer. Recently Takamochi et al.[12] compared 409 elderly l ung cancer patients (≥70 years) and 664 younger patients (<70 years) with regard to morbidity and mortality and found that the mortality and morbidity rates were higher for the elder patients.[12] In addition, Sekine et al.[21] determined that for postoperative patients diagnosed with NSCLC who underwent thoracic surgical procedures, pulmonary complications occurred more frequently in COPD patients than in non-COPD patients and that the major cause of noncancer- related deaths in their COPD patient group was respiratory failure. In our study, approximately 50% of the patients in both groups had COPD.

Karakurt et al.[22] found t hat p atients w ho u ndergo extended surgical procedures require prolonged mechanical ventilation, and they believed that this might have been the reason for the profound alterations in diaphragm functions and respiratory mechanics in their patients. They also determined that their patients who experienced weaning failure had higher blood glucose levels, lower PaO2/FiO2, and increased mortality. We did not measure diaphragm functions in our study, but the number of patients who had a prolonged weaning period of longer than 14 days was higher in group 2 (41%) than in group 1 (22%). After lung resection, the rate of ICU demand due to acute respiratory distress is 2.5% for lobectomies and 3.9% for pneumonectomies,[23,24] and Dulu et al.[23] indicated that earlier ICU admission may lead to favorable patient outcomes for those who undergo these procedures. In our study, the majority of patients had hypoxemia along with elevated inflammatory and infectious markers, and half were diagnosed with septic shock. The mortality rate was higher in those patients who had septic shock. In contrast, Dulu et al.[23] reported that ICU mortality occurred in the majority of their patients who were admitted early to the ICU.

The main limitation of our study was that it was a retrospective, single-center cohort. In addition, because of the specific patient population, our results may not apply to all lung resection patients. Therefore, further randomized controlled studies must be conducted with a larger patient population. Furthermore, the inflammatory markers in this study were recorded upon admission to the ICU, and even though the majority of the patients in both groups were admitted to the ICU a couple of days after the surgery, we accepted that these values were still remarkable. Moreover, we did not record the pathogen of the sepsis/severe sepsis; however, the presence of sepsis and the mortality rates were statistically similar in both groups of patients in the ICU. Hence, a further detailed clarification of the pathogens may not have aided our results. Finally, the overall mortality rate in our hospital for lobectomies and pneumonectomies was not taken into account because our aim was to evaluate the ICU outcomes of the patients who had ARF.

The strength of our study was that all the patients in the ICU are followed around the clock during their hospital stays by pulmonary intensivists who were very familiar with the management of pulmonary complications, ventilator settings, and weaning procedures.

Conclusion

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

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