Cheng-Huei Lee

Elastance of the Pleural Space: A Predictor for the Outcome of Pleurodesis in Patients with Malignant Pleural Effusion

Pleural effusion is a frequent complication in patients with advanced stages of cancer [1-8], and malignant pleural effusion that is resistant to chemotherapy carries a grave prognosis [1-7]. Respiratory symptoms in patients with this disorder usually require palliative management of the effusion. Drainage of the effusion using a chest tube or during thoracoscopy with the introduction of sclerosing agents into the pleural space for pleurodesis is the most cost-effective approach [2-8]. Pleurodesis is unsuccessful in patients with symptomatic malignant pleural effusion and trapped lung (defined as poor approximation of the pleurae after drainage of the effusion); insertion of a thoracostomy tube or performance of thoracoscopy in such patients provides little benefit [2-57, 9, 10]. Thus, the diagnosis of trapped lung before such invasive procedures is important but difficult [5, 6]. The outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung, however, is difficult to predict. Therefore, we studied pleural elastance as a predictor of successful pleurodesis and compared its predictive ability with that of the biochemical characteristics of pleural fluid. Methods Patients Patients who were admitted to our institution because of symptomatic malignant pleural effusion and who required therapeutic thoracentesis were candidates for this 3-year prospective study. Malignant effusion was diagnosed only if malignant cells were found in a pleural biopsy specimen or effusion fluid. Exclusion criteria were 1) previous effusion of chemotherapy-sensitive cell types [for breast cancer, ovarian cancer, small-cell cancer of the lung, or lymphoma, for example], except when the patients had undergone a course of chemotherapy that had not eliminated the effusion; 2) chemotherapy or radiotherapy previously administered or planned within 2 months; 3) life expectancy of 1 month or less; and 4) loculated pleural effusion. Measurements and Interventions Figure 1 is a diagram of the device that was used to measure the elastance of the pleural space. Measurements were done while patients were in a sitting position. Under ultrasonographic guidance, an appropriate intercostal space was selected. After a local anesthetic was administered, 20 mL of pleural effusion was drawn into a heparin-rinsed plastic syringe for the measurement of glucose level and pH and for cytologic examination. Then, a 16-gauge intracatheter needle was inserted into the pleural space. The needle was attached to a three-way stopcock with two extension tubes that led to a central venous pressure monitor and a 50-mL syringe. The whole system was filled with normal, heparinized saline. Using a leveling rod, we marked a zero point on the central venous pressure monitor at the level of the puncture site. The pleural pressure, defined as the mean of the pleural fluid pressures during inspiration and expiration, was measured immediately and after each 100 mL of effusion was withdrawn. Thoracentesis was terminated when the pressure was lower than 10 cm H2O, when the patient developed symptoms potentially related to reexpansion pulmonary edema, or when a total of 500 mL of effusion had been drained. The elastance of the pleural space was calculated as the change in pressure of the pleural effusion (in cm H2O) divided by the amount of fluid removed [11]; the standard measure was expressed as being equivalent to the decline in pressure of the pleural effusion after 500 mL of fluid had been removed. In five patients who had a decrease in pressure of at least 19 cm H2O and trapped lung, thoracentesis was stopped before 500 mL of effusion had been drained; the elastance value in these patients was adjusted by linear extrapolation on the basis of the change in pressure that would have occurred if 500 mL had actually been removed [11]. Figure 1. Device used to measure the elastance of the pleural space. After these measurements had been done, a 9.3-mm thoracostomy tube connected to a watersealed bottle was placed in the pleural space for further drainage of the effusion by gravity. Suction was applied to the chest tube only if the patient had radiographic evidence of trapped lung. Radiography was done to ensure proper positioning of the thoracostomy tube. Drainage was discontinued when less than 150 mL of effusion was drained per day [3, 7, 12] for 2 consecutive days and the lung had reexpanded, when less than 250 mL of effusion was drained per day for 4 consecutive days and the lung had reexpanded, or when drainage had continued for 10 days. When one of the three criteria was met, radiography was done to evaluate the reexpansion of the affected lung and the approximation of the pleurae. Figure 2 shows the degrees of reexpansion of the affected lung and the approximation of the pleurae. In category 1, the lung had completely reexpanded and the pleurae had approximated well. In category 2, the affected lung had reexpanded and the pleurae had approximated in most areas, but a small amount of residual pneumothorax, pleural effusion, or some heterogeneous white patches were evident on radiographs. In category 3, the lung did not reexpand and the visceral and parietal pleurae were separated by pneumothorax in most places. The radiographs were evaluated by at least two of the authors. If reexpansion of the lung and approximation of the pleurae were difficult to interpret, the patients were placed in category 2. Patients in category 1 or 2 were classified as having a nontrapped lung. Figure 2. Categories of reexpansion of the affected lung and approximation of the pleurae. The chest tube was then clamped, and we injected 60 mg of bleomycin diluted in 100 mL of normal saline (usual-dose group) [4, 5, 7, 8, 13-15] or, in the latter half of the study, 30 mg diluted in 50 mL of normal saline (low-dose group) [13, 14] into the pleural space for pleurodesis in all patients except two who had trapped lung. The body position of the patient was changed if the patient was not too ill [16-18]. The chest tube was reopened 2 hours later and removed the next day [5]. Chest radiography was done to ensure that the chest tube had been removed properly. Patients were then followed closely in the outpatient clinic, and chest radiography was done to evaluate the outcome of pleurodesis. If the results were equivocal, we did either chest ultrasonography with or without diagnostic thoracentesis or computed tomography of the chest. The results of pleurodesis were evaluated 30 days after the chest tube was removed and then until the patient died or was lost to follow-up [3, 4, 12-15, 19]. Successful pleurodesis was defined as no recurrence of effusion, recurrence of only a small amount of effusion, or loculated effusion and elimination of the requirement for further therapeutic thoracentesis to alleviate symptoms [10, 12-15, 19]. Unsuccessful pleurodesis was defined as recurrence of the effusion in an amount similar to that seen before treatment or the requirement for further therapeutic thoracentesis to alleviate symptoms. Statistical Analysis The two-sample t-test was used to compare the mean elastance, pH, glucose level, and duration of follow-up for patients with trapped and nontrapped lungs. The Fisher exact test was used to evaluate the association between categorized variables. Confidence intervals for means and proportions were determined when appropriate. Results Sixty-five patients (38 men and 27 women) between 39 and 83 years of age (mean age, 62.7 years) were included in the study. Two patients had gastric cancer, 2 had breast cancer, 1 had renal cancer, 1 had rectal cancer, 45 had bronchogenic adenocarcinoma, and 14 had adenocarcinoma of uncertain origin. All patients had pleural effusion on chest radiography that reached the hilar level or higher in the sitting or standing position. Fourteen patients had trapped lung, and 51 did not have trapped lung. As Table 1 and Figure 3 show, 11 of 14 patients with trapped lung (groups 1 and 4) had an elastance of 19 cm H2O or more, although only 3 of the 51 patients without trapped lung (groups 2, 3, and 5) had such an elastance (P < 0.001). Mean elastance was 30.59 cm H2O in the 14 patients with trapped lung and 8.31 cm H2O in the 51 patients without trapped lung (difference, 22.3 cm H2O [95% CI, 11.1 to 33.5]; P = 0.001). Table 1. Results of Chest-Tube Drainage and Pleurodesis at 1 Month Figure 3. Relation of pleural elastance, effusion pH, effusion glucose level, trapped lung, and outcome of pleurodesis. Five patients who had trapped lung were lost to follow-up at 1 month (Figure 3; group 1); pleurodesis was noted to have been unsuccessful in two of these five patients before they were lost to follow-up. Another five patients with elastance less than 19 cm H2O who did not have trapped lung (Figure 3; group 2) were also not evaluated at 1 month because of loss to follow-up (n = 3), death (n = 1), or postoperative cardiac tamponade (n = 1). Tight pleural approximation was noted during surgery in the patient with postoperative cardiac tamponade. Fifty-five patients were evaluated 1 month after the thoracostomy tube was removed (Figure 3; groups 3, 4, and 5). Pleurodesis was unsuccessful in all 9 patients who had trapped lung (Figure 3; group 4) and in the 3 patients who had an elastance of 19 cm H2O or more without trapped lung (Figure 3; group 5). In contrast, 42 of the 43 patients (98%) with an elastance less than 19 cm H2O without trapped lung had successful pleurodesis (Figure 3; groups 3 and 5). The 14 patients with trapped lung had a higher elastance (30.59 cm H2O) than did the 51 patients without trapped lung (8.31 cm H2O) (P = 0.001); the effusion from the former group also had a lower pH (7.133 compared with 7.308; P = 0.001) and a lower glucose level (3.16 mmol/L compared with 5.27 mmol/L; P = 0.011) than the effusion from the latter group. Duration of follow-up in the group with trapped lung (2.7 months) was similar t

Spontaneous variability of cardiac output in ventilated critically ill patients.

Objective: To define the magnitude of spontaneous cardiac output variability over time in sedated medical intensive care unit patients attached to a continuous cardiac output monitor, and to determine whether high level positive end‐expiratory pressure or inverse inspiratory‐to‐expiratory (I:E) ratio ventilation resulted in greater variability over time than low positive end‐expiratory pressure with conventional I:E ratio ventilation. Design: Prospective study. Setting: Medical intensive care unit in a tertiary medical center. Patients: A total of 22 hemodynamically stable acute respiratory failure patients with a pulmonary artery catheter inserted for hemodynamic monitoring Interventions: After being sedated, patients were randomized alternately to receive pressure control ventilation first at setting A (high positive end‐expiratory pressure [15 cm H2O] with conventional I:E ratio [1:2]) and then at setting B (low positive end‐expiratory pressure [5 cm H2O] with inverse I:E ratio [2:1]), or vice versa, and then at setting C (low positive end‐expiratory pressure [5 cm H2O] with conventional I:E ratio [1:2]). Each ventilation setting period lasted 1 hr. Measurements and Main Results: Cardiac output (CO) was measured continuously. The continuous CO value displayed was updated every 30‐60 secs. The updated value reflected an average of the previous 3‐6 mins. The coefficient of variation (CV) of CO for each setting in each patient was calculated to represent the spontaneous variability. The mean CO ± SD and CV of each setting was 5.7 ± 1.8 L/min and 4.4% for setting A, 5.6 ± 1.5 L/min and 4.6% for setting B, and 5.9 ± 1.7 L/min and 4.8% for setting C. Analysis of variance revealed no significant differences between the CVs of the three settings. The 95% confidence interval for the COs for each setting was approximately the mean CO ± 0.1 × mean CO measured. Conclusions: In critically ill sedated medical intensive care unit patients with stable hemodynamics, the spontaneous variability of cardiac output over time was not significant. High positive end‐expiratory pressure (15 cm H2O) and inverse ratio ventilation (2:1) did not contribute to increased spontaneous variability of cardiac output.

Dose-finding and phase 2 study of weekly paclitaxel (taxol) and cisplatin combination in treating Chinese patients with advanced nonsmall cell lung cancer.

Objectives:The aim of the present study is to evaluate the efficacy and toxicity of weekly paclitaxel combined with cisplatin as first-line chemotherapy in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and to identify the optimal dose of weekly paclitaxel to be administered safely and effectively. Methods:Chemonaive patients with NSCLC, stage 3B with malignant pleural effusion, or stage 4 were enrolled in this study. In the dose-finding study, patients took paclitaxel once weekly at an initial dose of 50 mg/m2 and 3 weeks followed by cisplatin on day 15 at a fixed dose of 80 mg/m2. The escalating dose for paclitaxel was 10mg/m2 for each level. In the phase 2 study, patients received paclitaxel at maximum tolerated dose (MTD). Results:The MTD for paclitaxel was 60 mg/m2. Of the 47 eligible patients, 7 patients had a complete response and 15 achieved a partial response. The overall response was 46.8% (95% CI, 32.0% to 61.6%). The median survival was 16 months (95% CI, 13.4 to 18.6 months). Twenty-four patients (51.1%) completed 6 cycles of treatment. With regard to hematological toxicity, although grade 3/4 neutropenia was observed in 5 patients (10.6%), there was no febrile neutropenia. The major nonhematological toxicity was asthenia, which was observed in all patients (17 patients grade 1/2 and 30 patients with grade 3/4). Conclusions:Weekly paclitaxel combined with cisplatin on day 15 is a safe and effective regimen as a first-line chemotherapy in NSCLC. The MTD for this regimen was 60 mg/m2.

Spontaneous variability of arterial oxygenation in critically ill mechanically ventilated patients.

Objective: To assess the magnitude of spontaneous variability of arterial oxygenation and oxygen tension-based indices over time in medical intensive care unit (ICU) patients and to study whether high positive end-expiratory pressure (PEEP) or inverse inspiratory-to-expiratory (I:E) ratio ventilation (IRV) results in a greater variability than low PEEP with conventiona l I:E ratio ventilation. Design: Prospective study. Setting: Medical ICU in a tertiary medical center. Participants: 23 patients requiring a pulmonary artery floating catheter for hemodynamic monitoring. Intervention: After being completely sedated, patients were randomized to receive pressure-control ventilation at setting A: high PEEP (15 cmH2O) with conventional I:E ratio (1:2) and setting B: inverse I:E ratio (2:1) with low PEEP (5 cmH2O) alternately, and then at setting C: low PEEP (5 cmH2O) with conventional I:E ratio (1:2). Each ventilation setting lasted 1 h. Measurements and results: The arterial and mixed venous blood samples were measured simultaneously at baseline (time 0), and at 15, 30, 45, and 60 min thereafter. The coefficient of variation (CV) of arterial oxygen tension (PaO2) over time was 5.9 % for setting A, 7.2 % for setting B, and 6.9 % for setting C. ANOVA showed no significant differences in CVs of PaO2 between the three settings. Oxygen tension-based indices, alveolar-arterial oxygen difference (A-aDO2) and PaO2/PAO2 (alveolar oxygen tension), displayed CV s equal to that of PaO2; the CV of A-aDO2/PaO2 was significantly greater than that of PaO2. Conclusions: In critically ill medical ICU patients, despite sedation, the spontaneous variability in PaO2 over time is substantial. A high PEEP or IRV does not contribute to the increased variation in PaO2.