Clinical Outcome and Risk Factors for Emergency Department Adult Patients with Thoracic Empyema after Video-Assisted Thoracic Surgical Procedure

Abstract

Background:

Empyema is a purulent infection of the pleural cavity that is most relevant to parapneumonia effusion. Video-assisted thoracoscopic surgery (VATS) is an option for stage 2 (fibrinopurulent) and stage 3 (organizational). Surgeons may see critically ill patients with pleural empyema who present to the emergency department (ED). The purpose of this work is to investigate the outcomes of ED adult patients with thoracic empyema undergoing a thoracoscopic surgical procedure and to identify possible risk factors for death.

Methods:

We reviewed retrospectively the clinical characteristics and treatment outcomes of patients with thoracic empyema who received this diagnosis at our center from January 2012 to June 2014. Patients <20 years old were excluded from this study. The prognostic values of age, sex, comorbidities, clinical presentations, location, stage, and laboratory examinations were evaluated. Uni-variable analysis and multi-variable modeling were performed to determine significant risk factors for post-operative death.

Results:

Seventeen of 160 patients died post-operatively. Two groups (survivors and non-survivors) significantly differed in age (p = 0.013), sex (p = 0.026), comorbidity (p = 0.017), cough (p = 0.024), chest pain (p = 0.016), serum hemoglobin (p = 0.001), and potassium (p = 0.004) levels. Further logistic regression analysis showed statistically significant differences in age, hemoglobin levels, and potassium levels.

Conclusion:

Among the ED patients with thoracic empyema, older age, lower hemoglobin levels, and higher potassium levels are associated with post-operative death after VATS. These findings underline the importance of careful peri-operative treatment in older patients with signs of empyema when they present to the ED.

Empyema is an infection accompanied by a collection of pus in the pleural space. It can be a potential fatal complication of malignancy, chest trauma, and ineffective antibiotic management of pneumonia followed by pleural effusion [1,2]. There are three stages of empyema (I: exudative; II: fibropurulent; III: organization) [3], and treatment with surgical intervention has been suggested for advanced stage and inadequate thoracostomy drainage [4,5]. The life threatening and complicated condition remains a big challenge for the thoracic surgeon, and death from empyema is reported as approximately 10%–20% [6,7]. The recent trend of performing video-assisted thoracoscopic surgery (VATS) to manage thoracic empyema has a higher success rate, fewer post-operative complications, and shorter hospital stay [8 –10].

The timing of VATS is difficult for the surgeon to determine, however, particularly in the growing population of aging individuals with a variety of comorbidities. In this study, we analyzed retrospectively the prognosis and independent risk factors for emergency department (ED) patients with a diagnosis of thoracic empyema who underwent VATS at our institution.

Patients and Methods

From January 2012 to June 2014, 160 patients who presented to the ED and received a diagnosis of thoracic empyema underwent VATS at the department of thoracic surgery in the medical center. Patients who presented with symptoms and signs of pneumonia and pleural effusion, such as fever, cough, dyspnea, and chest pain, were prescribed empirically broad-spectrum intravenous antibiotic agents when empyema thoracis was suspected before the causative pathogen was identified in the ED.

The diagnosis of empyema thoracis was made if a patient had at least one of the following conditions: (1) Grossly purulent loculated pleural effusion; (2) positive Gram stain or culture of pleural effusion; and (3) pleural fluid analysis with the following results: pH ≤7.2, lactate dehydrogenase levels ≥1000 U/L, and glucose levels ≤40 mg/dL [11]. Surgical intervention was recommended if the patients had any of the following conditions: (1) Thoracostomy drainage was inadequate; (2) thoracic computed tomography scan showed fiberboard, extensive adhesion, and incomplete re-expansion of the lung (trapped lung); (3) multi-loculated empyema; and (4) unidentified etiology of pleural effusion.

Patients older than 20 years with thoracic empyema who underwent VATS were included in this study. For the operation, patients were sedated by general anesthesia with the use of double-lumen endotracheal tubes for selective ventilation, and then placed in the lateral position. The procedure was performed with thoracoscopic visualization under the observational hole, which was shaped in the empyema cavity; two other operation holes were used to allow surgical instruments access to deal with the empyema. We excluded the patients with long-term ventilator dependence and septic shock. Those with empyema caused by mediastinitis, esophageal rupture, hemothorax, pneumothorax, post-operative empyema, fungal infection, and chronic drainage of malignant pleural effusion were also excluded.

Variables recorded included age, sex, smoking, location and stages of empyema (Stage I: exudative; Stage II: fibropurulent; and Stage III: organizational)[3], clinical symptoms, and comorbidities to evaluate the risk factors for post-operative death. Clinical symptoms included fever, cough, dyspnea, and chest pain; comorbidities included chronic obstructive pulmonary disease (COPD), hypertension, diabetes mellitus (DM), renal failure, cardiovascular disease, and malignancy. This study was approved by the Institutional Review Board; the requirement of informed consent was waived because of its retrospective nature.

Statistical analysis

All data were analyzed using Statistical Package for Social Sciences (version 18). Categoric variables were described as percentages, and the Fisher exact test was used to compare the results between the two groups (survivors and non-survivors). The association between various risk factor parameters and death was evaluated using uni-variable analysis. The factors showing significant difference between survivors and non-survivors in uni-variable analysis were included in multi-variable logistic regression; p < 0.05 was considered statistically significant.

Results

During the three-year study period, 160 patients (124 male; 36 female) received a diagnosis of thoracic empyema in the ED and underwent VATS treatment in he department; median age was 58.2 years (range, 20–95 years). Of these, 17 patients (nine male; eight female) died post-operatively and were assigned to the non-survivors group. The mortality rate was 10.6% for all patients. Demographic data and clinical characteristics are shown in Table 1. Fifty-five (34.4%) patients were ≥65 years, and 11 (20.0%) of these died post-operation. Sixty-eight (42.5%) patients had a smoking habit.

Table 1.

Clinical Characteristics of Patients

Variables	Survivors (n = 143)	Non-survivors (n = 17)	p^*
Age, y			0.013
<65	99 (94.3%)	6 (5.7%)
≥65	44 (80.0%)	11 (20.0%)
Sex			0.026
Male	115 (92.7%)	9 (7.3%)
Female	28 (77.8%)	8 (22.2%)
Smoking	63 (92.6%)	5 (7.4%)	0.306
Comorbidity			0.017
COPD	2 (66.7%)	1 (33.3%)	0.288
Hypertension	44 (93.6%)	3 (6.4%)	0.399
Diabetes mellitus	24 (82.8%)	5 (17.2%)	0.197
Renal failure	2 (50.0%)	2 (50.0%)	0.056
Cerebrovascular disease	15 (71.4%)	6 (28.6%)	0.012
Malignancy	19 (73.1%)	7 (26.9%)	0.009
Clinical presentation
Fever	68 (94.4%)	4 (5.6%)	0.073
Cough	49 (98.0%)	1 (2.0%)	0.024
Dyspnea	70 (85.4%)	12 (14.6%)	0.124
Chest pain	62 (96.9%)	2 (3.1%)	0.016
Location			0.790
Left	52 (91.2%)	5 (8.8%)
Right	91 (88.3%)	12 (11.7%)
Stage			0.552
I–II	137 (89.5%)	16 (10.5%)
III	6 (85.7%)	1 (14.3%)

COPD = chronic obstructive pulmonary disease.

Significance level: p < 0.05 (Fisher test).

Hypertension (47/161, 29.4%) and DM (29/160, 18.1%) were frequent comorbidities followed by malignancy (26/160, 16.3%), cerebrovascular disease (21/160, 13.1%), renal failure (4/160, 2.5%), and COPD (3/160, 1.9%). The most common symptoms in patients were dyspnea (82/160, 51.3%) followed by fever (72/160, 45.0%), chest pain (64/160, 40.0%), and cough (50/160, 31.3%). Stage III empyema was found in seven patients. While 103 patients had right lung empyema, 57 individuals were affected in the left lung. Risk factors that might lead to death are age (p = 0.013), sex distribution (p = 0.026), comorbidity (p = 0.017), cerebrovascular disease (p = 0.012), malignancy (p = 0.009), cough (p = 0.024), and chest pain (p = 0.016). Renal failure was marginally significant (p = 0.056). There was no statistically significant difference between the two groups in terms of smoking and empyema location and stage.

Laboratory data showed no significant inter-group differences in white blood cell count, platelet count, and blood urea nitrogen, creatinine, or sodium levels. There were significant differences in the serum hemoglobin and potassium levels, however. The serum hemoglobin level was significantly lower in the non-survivors group than that in the survivors group (p = 0.001), and the serum potassium level was significantly higher in non-survivors than that in the survivors group (p = 0.004; Table 2).

Table 2.

Laboratory Examinations of Patients

Variables	Survivors (n = 143)	Non-survivors (n = 17)	p^*
White blood cell count	3,082 ± 2,572	3,623 ± 2,684	0.440
Hemoglobin	11.51 ± 2.23	9.54 ± 1.83	0.001
Platelet counts	319.87 ± 163.71	279.82 ± 163.72	0.352
Blood urea nitrogen	20.36 ± 1.79	31.24 ± 6.11	0.104
Creatinine	1.20 ± 0.10	1.68 ± 0.37	0.227
Serum sodium levels	134.45 ± 4.11	135.12 ± 6.44	0.680
Serum potassium levels	3.80 ± 0.56	4.02 ± 0.82	0.004

Significance level: p < 0.05 (Fisher test).

The univariable logistic regression analysis was performed to evaluate significant relationships between clinical features and patient death. Among the 11 clinical and laboratory variables analyzed, age (odds ratio [OR] = 3.017; 95% confidence interval [CI] = 0.019–0.448; p = 0.003) and serum hemoglobin levels (OR = 0.649; 95% CI = 0.430–0.981; p = 0.040) were significant predictors of death. The serum potassium level (OR = 3.230; 95% CI = 0.935–11.160; p = 0.064; Table 3) was marginally significant.

Table 3.

Univariable Logistic Regression Analysis of Risk Factors Affecting Death

Variable	Odds ratio	95% confidence interval	p^*
Age (≥65)	3.017	0.019–0.448	0.003
Sex	0.251	0.605–15.039	0.178
Smoking	1.537	0.322–7.348	0.590
Comorbidity	0.423	0.056–3.213	0.405
Renal failure	0.069	0.002–2.029	0.121
Cerebrovascular disease	0.301	0.052–1.737	0.301
Malignancy	0.535	0.098–2.922	0.470
Cough	7.088	0.651–77.174	0.108
Chest pain	2.545	0.426–15.207	0.306
Hemoglobin	0.649	0.430–0.981	0.040
Serum potassium levels	3.230	0.935–11.160	0.064

Significance level: p < 0.05 (Fisher test).

The multi-variable logistic regression analysis confirmed that an age ≥65 years (OR = 25.427; 95% CI = 2.587–249.900; p = 0.006), lower serum hemoglobin levels (OR = 0.516; 95% CI = 0.274–0.972; p = 0.041), and higher serum potassium levels (OR = 13.571, 95% CI 1.575116.950, p = 0.018; Table 4) were all independently related to risk of post-operative death.

Table 4.

Multivariable Logistic Regression Analysis of Risk Factors Affecting Death

Variable	Odds ratio	95% confidence interval	p^*
Age (≥65)	25.427	2.587–249.900	0.006
Sex	0.205	0.019–2.228	0.193
Smoking	1.215	0.113–13.046	0.872
Cough	0.036	0.001–1.136	0.059
Hemoglobin	0.516	0.274–0.972	0.041
Serum potassium levels	13.571	1.575–116.950	0.018

Significance level: p < 0.05 (Fisher test).

Discussion

In this study, we demonstrated that the following clinical and laboratory factors were correlated with a prognosis of patients with empyema thoracis undergoing VATS: (1) older age, (2) sex distribution, (3) comorbidity, (4) cerebrovascular disease, (5) malignancy, (6) cough, (7) chest pain, (8) serum hemoglobin levels, and (9) serum potassium levels. The logistic regression analysis revealed that older age, lower serum hemoglobin levels, and higher potassium levels were independent risk factors for the prognosis of patients with thoracic empyema undergoing VATS.

The overall mortality rate was 10.6% (17/160), which is higher than the reported mortality rates of 6.7% and 8%–9% [2,12]. Eleven (64.7%) of the 17 patients who died were ≥65 years of age. This may reflect the importance of careful peri-operative treatment and the timing of VATS in older patients. One reason for difficulty in an earlier diagnose in older patients is the atypical presentation of symptoms and signs, such as chest pain and fever [13]. Another reason is the decline of age-related physiologic function and comorbidities. Hence, older patients with thoracic empyema often have a higher mortality rate of up to 50% [14]. Our study showed that chest pain (p = 0.016) and cough (p = 0.024) may be risk factors for post-operative death. The results were not statistically significant after logistic regression analysis, however.

Although a population-based cohort study in Taiwan revealed that patients with DM had a higher risk (1.71-fold increased hazard) of pleural empyema developing [15], DM (p = 0.197) was not a risk factor of post-operative death for patients with empyema thoracis undergoing VATS in our study. Cerebrovascular disease and renal failure, however, which are chronic complications of DM that can affect vital organs through microangiopathy, may be prognostic risk factors. Although malignancy may also be a risk factor, it is uncertain that the death rate is higher when there is an underlying illness compared with the absence of any comorbid diseases [14].

To investigate additional risk factors that can affect patients with empyema undergoing VATS, we collected and analyzed pre-operative laboratory results. The results of the present study are consistent with previous observations. A 12-year study conducted in the United Kingdom demonstrated that low pre-operative hemoglobin levels, high red blood cell distribution width, low albumin levels, and high alkaline phosphatase levels were associated with early post-operative death. Age and serum hemoglobin levels have been shown to be related to the prognosis of thoracic empyema patients.

There is no result of serum potassium levels [16], however. In our study, we found that serum potassium levels is an independent predictor variable for post-operative death. The higher serum potassium concentration found in non-survivors could have been induced by sepsis and multiple organ failure as a result of the retained pus and compromised immunity.

With an increase in life expectancy, improved survival of patients with malignant diseases, and increased number of antibiotic-resistant cases, the number of potential thoracic empyema cases is expanding [17]. Although the death of older patients with empyema seems to have improved with the progress of diagnostic tools, surgical techniques, and critical care, thoracic empyema is still a complex clinical diagnosis with a dynamic process regardless of the laboratory or radiology findings. Some patients may experience delays in diagnosis and referral for operation, which can lead to difficulty in stripping the fiberboard and ease to damage peripheral tissue [18]. Some patients with borderline conditions may undergo a thoracoscopic surgical procedure depending on the decision of the surgeons.

The benefits of VATS to treat those with empyema have been reported [10,17,19], but only a few studies have demonstrated the risk factors for surgical outcome [16]. Our results demonstrate that older age, low serum hemoglobin levels, and high serum potassium levels are associated with the prognosis of patients with empyema thoracis undergoing VATS treatment. These findings should be investigated further because they may be helpful for the development of guidelines for surgical intervention of empyema, which in turn could improve overall survival.

Limitations

There were some limitations in our study. First, this was a retrospective design and a single-institution study with a small sample size. Second, we did not analyze all of the laboratory results, including analysis of pleural effusion. Last, we did not analyze the cause of death. Additional studies are warranted to confirm our findings.

Conclusion

We were able to identify a number of prognostic factors predictive of post-operative death, including older age, lower serum hemoglobin levels, and higher serum potassium levels. Recognizing these factors and initiating immediate treatment may help to improve the outcomes and reduce post-operative death.

Footnotes

Acknowledgment

We thank Miss Ya-Ling Lin for the collection of the patients' follow-up data.

Author Disclosure Statement

No competing financial interests exist.

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