Scott A. Helgeson, MD

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Hospitalized patients with pneumonia who develop a complicated parapneumonic effusion or empyema need to undergo chest tube placement.

WHAT IS PARAPNEUMONIC EFFUSION?

Parapneumonic effusion is a pleural effusion that forms concurrently with bacterial or viral pneumonia. Up to 40% of patients hospitalized with pneumonia develop a parapneumonic effusion.¹ The effusion progresses through a continuum of 3 stages: uncomplicated, complicated, and empyema.

Uncomplicated parapneumonic effusion is an exudative effusion without bacteria or pus that is caused by movement of fluid and neutrophils into the pleural space. Pneumonia itself causes an increase in interstitial fluid and capillary leakage. The effusion becomes complicated as a result of bacteria invading the pleural space, causing a further increase in neutrophils in the pleural fluid. Empyema is defined as the presence of frank pus in the pleural space.

CLINICAL SIGNIFICANCE

According to the US Centers for Disease Control and Prevention, pneumonia accounts for 674,000 emergency department visits each year; of the patients hospitalized, up to 40% develop a parapneumonic effusion.² The only study done on rates of death associated with parapneumonic effusion showed that, compared with patients with no effusion, the risk of death was 3.7 times higher with a unilateral effusion and 6.5 times higher with bilateral effusions.³

INITIAL EVALUATION

The initial evaluation of suspected parapneumonic effusion should include chest radiography with lateral or decubitus views, followed by thoracentesis if indicated. If thoracentesis is performed, the fluid should be tested as follows:

• Gram stain
• Appropriate cultures based on clinical scenario (eg, aerobic, anaerobic, fungal)
• Total protein in pleural fluid and serum
• Lactate dehydrogenase (LDH) in pleural fluid and serum
• Glucose
• pH.

CLASSIFICATION OF EFFUSIONS

When pleural fluid is obtained, the total protein and LDH levels are used to categorize the effusion as either transudative or exudative based on the Light criteria.⁴ An effusion is confirmed as exudative when 1 of the following 3 criteria is met:

• The ratio of pleural fluid protein to serum protein is greater than 0.5
• The ratio of pleural fluid LDH to serum LDH is greater than 0.6
• The pleural fluid LDH is greater than two-thirds the upper limit of normal for the serum LDH.

Category 1 effusions are defined as free- flowing fluid with a thickness of less than 10 mm on any imaging modality. Thoracentesis for pleural fluid analysis is not required. The prognosis is very good.

Category 2 effusions are defined as free- flowing fluid with a thickness greater than 10 mm and less than 50% of the hemithorax. Thoracentesis is typically done because of the size of the effusion, but Gram stain and culture of the pleural fluid are usually negative, and the pH is at least 7.2. The prognosis is good.

Category 3 effusions are considered complicated because the anatomy of the pleural space becomes altered or because bacteria have invaded the pleural space. The effusion is larger than 50% of the hemithorax or is loculated, or the parietal pleura is thickened. Since the bacteria have invaded the pleural space, Gram stain or culture of pleural fluid may be positive, the pleural fluid pH may be less than 7.2, or the glucose level of the fluid may be less than 60 mg/dL. The prognosis for category 3 is poor.

Category 4 effusions are defined as empyema. The only characteristic that separates this from category 3 is frank pus in the pleural space. The prognosis is very poor.

For category 1 or 2 effusions, treatment with antibiotics alone is typically enough. Category 3 effusions usually do not respond to antibiotics alone and may require complete drainage of the fluid with or without a chest tube depending on whether loculations are present, as loculations are difficult to drain with a chest tube. Category 4 effusions require both antibiotics and chest tube placement.

WHAT TYPE OF CHEST TUBE?

Studies have shown that small-bore chest tubes (< 20 F) are as efficacious as larger tubes (≥ 20 F) for the treatment of complicated parapneumonic effusion and empyema.^6,7 Studies have also shown that the size of the tube makes no difference in the time needed to drain the effusion, the length of hospital stay, or the complication rate.^8,9 Based on these studies, a small-bore chest tube should be placed first when clinically appropriate. When a chest tube is placed for empyema, computed tomography should be performed within 24 hours to confirm proper tube placement.

ADVANCED THERAPIES FOR EMPYEMA

Empyema treatment fails when antibiotic coverage is inadequate or when a loculation is not drained appropriately. Options if treatment fails include instillation of fibrinolytics into the pleural space, video-assisted thora­scopic surgery, and decortication.

The role of fibrinolytics has not been well-established, but fibrinolytics should be considered in loculated effusions or empyema, or if drainage of the effusion slows.¹⁰ Video-assisted thora­scopic surgery is reserved for effusions that are incompletely drained with a chest tube with or without fibrinolytics; studies have shown shorter hospital length of stay and higher treatment efficacy when this is performed earlier for loculated effusions.¹¹ Decortication is reserved for symptomatic patients who have a thickened pleura more than 6 months after the initial infection.¹² Timing for each of these procedures is not clearly defined and so must be individualized.

TAKE-AWAY POINTS

• Parapneumonic effusion occurs concurrently with pneumonia and with a high frequency.¹
• Effusions are associated with an increased risk of death.³
• Categorizing the effusion helps guide treatment.
• Chest tubes should be placed for some cases of complicated effusion and for all cases of empyema.
• A small-bore chest tube (< 20 F) should be tried first.

Hospitalized patients with pneumonia who develop a complicated parapneumonic effusion or empyema need to undergo chest tube placement.

WHAT IS PARAPNEUMONIC EFFUSION?

Parapneumonic effusion is a pleural effusion that forms concurrently with bacterial or viral pneumonia. Up to 40% of patients hospitalized with pneumonia develop a parapneumonic effusion.¹ The effusion progresses through a continuum of 3 stages: uncomplicated, complicated, and empyema.

Uncomplicated parapneumonic effusion is an exudative effusion without bacteria or pus that is caused by movement of fluid and neutrophils into the pleural space. Pneumonia itself causes an increase in interstitial fluid and capillary leakage. The effusion becomes complicated as a result of bacteria invading the pleural space, causing a further increase in neutrophils in the pleural fluid. Empyema is defined as the presence of frank pus in the pleural space.

CLINICAL SIGNIFICANCE

According to the US Centers for Disease Control and Prevention, pneumonia accounts for 674,000 emergency department visits each year; of the patients hospitalized, up to 40% develop a parapneumonic effusion.² The only study done on rates of death associated with parapneumonic effusion showed that, compared with patients with no effusion, the risk of death was 3.7 times higher with a unilateral effusion and 6.5 times higher with bilateral effusions.³

INITIAL EVALUATION

The initial evaluation of suspected parapneumonic effusion should include chest radiography with lateral or decubitus views, followed by thoracentesis if indicated. If thoracentesis is performed, the fluid should be tested as follows:

• Gram stain
• Appropriate cultures based on clinical scenario (eg, aerobic, anaerobic, fungal)
• Total protein in pleural fluid and serum
• Lactate dehydrogenase (LDH) in pleural fluid and serum
• Glucose
• pH.

CLASSIFICATION OF EFFUSIONS

When pleural fluid is obtained, the total protein and LDH levels are used to categorize the effusion as either transudative or exudative based on the Light criteria.⁴ An effusion is confirmed as exudative when 1 of the following 3 criteria is met:

• The ratio of pleural fluid protein to serum protein is greater than 0.5
• The ratio of pleural fluid LDH to serum LDH is greater than 0.6
• The pleural fluid LDH is greater than two-thirds the upper limit of normal for the serum LDH.

Category 1 effusions are defined as free- flowing fluid with a thickness of less than 10 mm on any imaging modality. Thoracentesis for pleural fluid analysis is not required. The prognosis is very good.

Category 2 effusions are defined as free- flowing fluid with a thickness greater than 10 mm and less than 50% of the hemithorax. Thoracentesis is typically done because of the size of the effusion, but Gram stain and culture of the pleural fluid are usually negative, and the pH is at least 7.2. The prognosis is good.

Category 3 effusions are considered complicated because the anatomy of the pleural space becomes altered or because bacteria have invaded the pleural space. The effusion is larger than 50% of the hemithorax or is loculated, or the parietal pleura is thickened. Since the bacteria have invaded the pleural space, Gram stain or culture of pleural fluid may be positive, the pleural fluid pH may be less than 7.2, or the glucose level of the fluid may be less than 60 mg/dL. The prognosis for category 3 is poor.

Category 4 effusions are defined as empyema. The only characteristic that separates this from category 3 is frank pus in the pleural space. The prognosis is very poor.

For category 1 or 2 effusions, treatment with antibiotics alone is typically enough. Category 3 effusions usually do not respond to antibiotics alone and may require complete drainage of the fluid with or without a chest tube depending on whether loculations are present, as loculations are difficult to drain with a chest tube. Category 4 effusions require both antibiotics and chest tube placement.

WHAT TYPE OF CHEST TUBE?

Studies have shown that small-bore chest tubes (< 20 F) are as efficacious as larger tubes (≥ 20 F) for the treatment of complicated parapneumonic effusion and empyema.^6,7 Studies have also shown that the size of the tube makes no difference in the time needed to drain the effusion, the length of hospital stay, or the complication rate.^8,9 Based on these studies, a small-bore chest tube should be placed first when clinically appropriate. When a chest tube is placed for empyema, computed tomography should be performed within 24 hours to confirm proper tube placement.

ADVANCED THERAPIES FOR EMPYEMA

Empyema treatment fails when antibiotic coverage is inadequate or when a loculation is not drained appropriately. Options if treatment fails include instillation of fibrinolytics into the pleural space, video-assisted thora­scopic surgery, and decortication.

The role of fibrinolytics has not been well-established, but fibrinolytics should be considered in loculated effusions or empyema, or if drainage of the effusion slows.¹⁰ Video-assisted thora­scopic surgery is reserved for effusions that are incompletely drained with a chest tube with or without fibrinolytics; studies have shown shorter hospital length of stay and higher treatment efficacy when this is performed earlier for loculated effusions.¹¹ Decortication is reserved for symptomatic patients who have a thickened pleura more than 6 months after the initial infection.¹² Timing for each of these procedures is not clearly defined and so must be individualized.

TAKE-AWAY POINTS

• Parapneumonic effusion occurs concurrently with pneumonia and with a high frequency.¹
• Effusions are associated with an increased risk of death.³
• Categorizing the effusion helps guide treatment.
• Chest tubes should be placed for some cases of complicated effusion and for all cases of empyema.
• A small-bore chest tube (< 20 F) should be tried first.

Hospitalized patients with pneumonia who develop a complicated parapneumonic effusion or empyema need to undergo chest tube placement.

WHAT IS PARAPNEUMONIC EFFUSION?

Parapneumonic effusion is a pleural effusion that forms concurrently with bacterial or viral pneumonia. Up to 40% of patients hospitalized with pneumonia develop a parapneumonic effusion.¹ The effusion progresses through a continuum of 3 stages: uncomplicated, complicated, and empyema.

Uncomplicated parapneumonic effusion is an exudative effusion without bacteria or pus that is caused by movement of fluid and neutrophils into the pleural space. Pneumonia itself causes an increase in interstitial fluid and capillary leakage. The effusion becomes complicated as a result of bacteria invading the pleural space, causing a further increase in neutrophils in the pleural fluid. Empyema is defined as the presence of frank pus in the pleural space.

CLINICAL SIGNIFICANCE

According to the US Centers for Disease Control and Prevention, pneumonia accounts for 674,000 emergency department visits each year; of the patients hospitalized, up to 40% develop a parapneumonic effusion.² The only study done on rates of death associated with parapneumonic effusion showed that, compared with patients with no effusion, the risk of death was 3.7 times higher with a unilateral effusion and 6.5 times higher with bilateral effusions.³

INITIAL EVALUATION

The initial evaluation of suspected parapneumonic effusion should include chest radiography with lateral or decubitus views, followed by thoracentesis if indicated. If thoracentesis is performed, the fluid should be tested as follows:

• Gram stain
• Appropriate cultures based on clinical scenario (eg, aerobic, anaerobic, fungal)
• Total protein in pleural fluid and serum
• Lactate dehydrogenase (LDH) in pleural fluid and serum
• Glucose
• pH.

CLASSIFICATION OF EFFUSIONS

When pleural fluid is obtained, the total protein and LDH levels are used to categorize the effusion as either transudative or exudative based on the Light criteria.⁴ An effusion is confirmed as exudative when 1 of the following 3 criteria is met:

• The ratio of pleural fluid protein to serum protein is greater than 0.5
• The ratio of pleural fluid LDH to serum LDH is greater than 0.6
• The pleural fluid LDH is greater than two-thirds the upper limit of normal for the serum LDH.

Category 1 effusions are defined as free- flowing fluid with a thickness of less than 10 mm on any imaging modality. Thoracentesis for pleural fluid analysis is not required. The prognosis is very good.

Category 2 effusions are defined as free- flowing fluid with a thickness greater than 10 mm and less than 50% of the hemithorax. Thoracentesis is typically done because of the size of the effusion, but Gram stain and culture of the pleural fluid are usually negative, and the pH is at least 7.2. The prognosis is good.

Category 3 effusions are considered complicated because the anatomy of the pleural space becomes altered or because bacteria have invaded the pleural space. The effusion is larger than 50% of the hemithorax or is loculated, or the parietal pleura is thickened. Since the bacteria have invaded the pleural space, Gram stain or culture of pleural fluid may be positive, the pleural fluid pH may be less than 7.2, or the glucose level of the fluid may be less than 60 mg/dL. The prognosis for category 3 is poor.

Category 4 effusions are defined as empyema. The only characteristic that separates this from category 3 is frank pus in the pleural space. The prognosis is very poor.

For category 1 or 2 effusions, treatment with antibiotics alone is typically enough. Category 3 effusions usually do not respond to antibiotics alone and may require complete drainage of the fluid with or without a chest tube depending on whether loculations are present, as loculations are difficult to drain with a chest tube. Category 4 effusions require both antibiotics and chest tube placement.

WHAT TYPE OF CHEST TUBE?

Studies have shown that small-bore chest tubes (< 20 F) are as efficacious as larger tubes (≥ 20 F) for the treatment of complicated parapneumonic effusion and empyema.^6,7 Studies have also shown that the size of the tube makes no difference in the time needed to drain the effusion, the length of hospital stay, or the complication rate.^8,9 Based on these studies, a small-bore chest tube should be placed first when clinically appropriate. When a chest tube is placed for empyema, computed tomography should be performed within 24 hours to confirm proper tube placement.

ADVANCED THERAPIES FOR EMPYEMA

Empyema treatment fails when antibiotic coverage is inadequate or when a loculation is not drained appropriately. Options if treatment fails include instillation of fibrinolytics into the pleural space, video-assisted thora­scopic surgery, and decortication.

The role of fibrinolytics has not been well-established, but fibrinolytics should be considered in loculated effusions or empyema, or if drainage of the effusion slows.¹⁰ Video-assisted thora­scopic surgery is reserved for effusions that are incompletely drained with a chest tube with or without fibrinolytics; studies have shown shorter hospital length of stay and higher treatment efficacy when this is performed earlier for loculated effusions.¹¹ Decortication is reserved for symptomatic patients who have a thickened pleura more than 6 months after the initial infection.¹² Timing for each of these procedures is not clearly defined and so must be individualized.

TAKE-AWAY POINTS

• Parapneumonic effusion occurs concurrently with pneumonia and with a high frequency.¹
• Effusions are associated with an increased risk of death.³
• Categorizing the effusion helps guide treatment.
• Chest tubes should be placed for some cases of complicated effusion and for all cases of empyema.
• A small-bore chest tube (< 20 F) should be tried first.