Jeffrey H. Barsuk, MD, MS

Ascites is the most common complication of cirrhosis and often leads to hospitalization. ¹ Paracentesis is recommended for all patients admitted with ascites and cirrhosis. ¹ Additionally, the Society of Hospital Medicine considers the ability to perform paracenteses a core competency for hospitalists. ² Although considered a safe procedure, major bleeding complications occur in 0.2% to 1.7% of paracenteses. ^3-7 Patients with cirrhosis form new abdominal wall vessels because of portal hypertension, and hemoperitoneum from the laceration of these vessels during paracentesis carries a high morbidity and mortality. ^6,8 Ultrasound guidance using a low-frequency ultrasound probe is currently standard practice for paracentesis and has been shown to reduce bleeding complications. ^9-11 However, the use of vascular ultrasound (high-frequency probe) is also recommended to identify blood vessels within the intended needle pathway to reduce bleeding, but no studies have been performed to demonstrate a benefit. ^3,11 This study aimed to evaluate whether this “2-probe technique” reduces paracentesis-related bleeding complications.

The procedure service at Cedars Sinai Medical Center (CSMC) in Los Angeles performs paracentesis regularly with ultrasound guidance. CSMC is a tertiary care, academic medical center with 861 licensed beds. We performed a pre- to postintervention study of consecutive patients (admitted and ambulatory) who underwent paracentesis done by 1 proceduralist (MJA) from the procedure service at CSMC from February 2010 through February 2016. From February 1, 2010, through August 2011, paracenteses were performed using only low-frequency, phased array ultrasound probes (preintervention group). From September 1, 2011, through February 2016, a 2-probe technique was used, whereby ultrasound interrogation of the abdomen using a low-frequency, phased array probe (to identify ascites) was supplemented with a second scan using a high-frequency, linear probe to identify vasculature within the planned needle path (postintervention group). As a standard part of quality assurance, CSMC documented all paracentesis-related complications from procedures performed by their center. Northwestern University investigators (JHB, EC, JF) independently evaluated these data to look at bleeding complications before and after the implementation of the 2-probe technique. The CSMC and Northwestern University institutional review boards approved this study.

Procedure Protocol

Each patient’s primary team or outpatient physician requested a consultation for paracentesis from the CSMC procedure service. All patient evaluations began with an abdominal ultrasound using the low-frequency probe to determine the presence of ascites and a potential window of access to the fluid. After September 1, 2011, the CSMC procedure service implemented the 2-probe technique to also evaluate the abdominal wall for the presence of vessels. Color flow Doppler ultrasound further helped to differentiate blood vessels as necessary. The optimal window was then marked on the abdominal wall, and the paracentesis was performed. Per the routine of the CSMC procedure service, antiplatelet or anticoagulant medications were not held for paracenteses.

Measurement

All data were collected prospectively at the time of the procedure, including the volume of fluid removed, the number of needle passes required, and whether the patient was on antiplatelet or anticoagulant medications (including warfarin, direct oral anticoagulants, thrombin inhibitors, heparin, or low molecular weight heparins). Patients were followed for complications for up to 24 hours after the procedure or until a clinical question of a complication was reconciled. Minor bleeding was defined as new serosanguinous fluid on repeat paracentesis not associated with hemodynamic changes, local bruising or bleeding at the site, or abdominal wall hematoma. Major bleeding was defined by the development of hemodynamic instability or by reaccumulation of fluid on ultrasound within 24 hours postparacentesis and one of the following: an associated hemoglobin drop of greater than 2 g/dl, blood seen on repeat paracentesis, blood density fluid on a computed tomography scan, or the lack of an alternative explanation. All data were recorded in a handheld database (HanDbase; DDH Software, Wellington, FL).

A query of the electronic medical record was performed to obtain patient demographics and relevant clinical information, including age, sex, body mass index, International Normalized Ratio (INR), partial thromboplastin time (PTT), platelet counts (10³/uL, hematocrit (%) and creatinine (mg/dl). Our query for laboratory data retrieved the closest laboratory entry up to 48 hours before the procedure.

Statistical Analysis

We used a χ² test, Student t test, or Kruskal-Wallis test to compare demographic and clinical characteristics of procedure patients between the 2 study groups (pre- and postintervention). Major and minor bleeding were compared between the 2 groups using the χ² test.¹² We used the χ² test instead of the Fisher’s exact test for several reasons. The usual rule is that the Fisher’s exact test is necessary when 1 or more expected outcome values are less than 5. However, McDonald argues that the χ² test should be used with large sample sizes (more than 1000) in lieu of the outcome-value-of-5 rule.¹² The Fisher’s exact test also assumes that the row and column totals are fixed. However, the outcomes in our study were not fixed because any patient could have a bleeding complication during each procedure. When row and column totals are not fixed, only 5% of the time will a P value be less than 0.05, and the Fisher’s exact test is too conservative.¹² We performed all statistical analyses using IBM SPSS Statistics Version 22 (IBM Corp, Armonk, NY).

Patient demographic and clinical information can be found in the Table. The proceduralist (MJA) performed a total of 5777 paracenteses (1000 preintervention, 4777 postintervention) on 1639 patients. Four hundred eighty-nine (10.2%) vascular anomalies were identified within the intended needle path in the postintervention group (Figure). More patients in the preintervention group were on aspirin (93 [9.3%] vs 230 [4.8%]; P < 0.001) and therapeutic intravenous anticoagulants (33 [3.3%] vs 89 [1.9%]; P = 0.004), while more patients in the postintervention group were on both an antiplatelet and oral anticoagulant (1 [0.1%] vs 38 [0.8%]; P = 0.015) and subcutaneous prophylactic anticoagulants (184 [18.4%] vs 1120 [23.4%]; P = 0.001) at the time of the procedure. There were no other differences between groups with antiplatelet or anticoagulant drugs. We found no difference in minor bleeding between pre- and postintervention groups. Major bleeding was lower after the 2-probe technique was implemented (3 [0.3%] vs 4 [0.08%]; P = 0.07). There were no between-group differences in INR, PTT, or platelet counts among major bleeders. One patient in the postintervention group had hemodynamic instability and dropped his hemoglobin by 3.8 g/dl at 7 hours after the procedure. This was unexplained, as the patient had no abdominal symptoms or findings on examination. The patient received several liters of fluid before ultimately dying, and the primary team considered sepsis as a possible cause, but no postmortem examination was performed. This was the only death attributed to a major bleeding complication. We included this patient in our analysis because the cause of his demise was not completely clear. However, excluding this patient would change the results from a trend to a statistically significant difference between groups (3 [0.3%] vs 3 [0.06%]; P = 0.03).

To our knowledge, we report the largest series of paracentesis prospectively evaluated for bleeding complications, and this is the first study to evaluate whether adding a vascular ultrasound (high-frequency probe) avoids major bleeding. In our series, up to 10% of patients had abnormal vessels seen with a vascular ultrasound that were within the original intended trajectory path of the needle. These vessels were also likely present yet invisible when ultrasound-guided paracentesis using only the standard, low-frequency probe was being performed. It is unknown whether these vessels are routinely traversed with the needle, nicked, or narrowly avoided during paracenteses performed using only a low-frequency probe.

Procedure-related bleeding may not be completely avoidable, despite using the vascular probe. Some authors have suggested that the mechanism of bleeding is more related to the rapid reduction in intraperitoneal pressure, which increases the gradient across vessel walls, resulting in rupture and bleeding.⁶ However, in our series, using vascular ultrasound also reduced major bleeding to numbers lower than those historically reported in the literature (0.2%).^3-4 Our preintervention number needed to harm was 333 procedures to cause 1 major bleed, compared to 1250 (or 1666 using the 3-patient bleeding analysis) in the postintervention group. In 2008, 150,000 Medicare beneficiaries underwent paracentesis.¹³ Using our study analysis, if vascular ultrasound was used on these patients, up to 360 major bleeds may have been prevented, along with a corresponding reduction in unnecessary morbidity and mortality.

Our study has several limitations. First, it was limited to 1 center with 1 very experienced proceduralist. Although it is possible that the reduction in major bleeding may have been due to the increasing experience of the proceduralist over time, we do not think that this is likely because he had already performed thousands of paracenteses over 9 years before the start of our study. Second, major bleeding was rare and therefore precluded a multivariate analysis to control for temporal trends that might have occurred in our pre- to poststudy design. Statistically significant demographic and clinical variable differences between groups were likely not clinically meaningful. Although more patients were on intravenous anticoagulants in the preintervention group, coagulopathy or low platelets do not increase the bleeding risk during paracenteses,^1,8 and there was no clinical difference in INR, PTT, or platelets between groups (Table). Third, it is possible that unmeasured characteristics contributed to more patient complications in the preintervention group. Finally, we were unable to evaluate length of stay and mortality differences between groups that might have been attributable to the procedure because of the low number of major bleeding complications and the inability to perform a multivariate analysis.

Our results suggest that using the 2-probe technique to predetermine the needle path before performing paracentesis might prevent major bleeding. Based on our findings, we believe that the addition of a vascular ultrasound during paracentesis should be considered by all hospitalists.

Acknowledgments

The authors acknowledge Drs. Douglas Vaughan and Kevin O’Leary for their support and encouragement of this work. They would also like to thank the Cedars-Sinai Enterprise Information Systems Department for assistance with their data query.

Disclosure

The authors have no relevant financial disclosures or conflicts of interest to report.

Ascites is the most common complication of cirrhosis and often leads to hospitalization. ¹ Paracentesis is recommended for all patients admitted with ascites and cirrhosis. ¹ Additionally, the Society of Hospital Medicine considers the ability to perform paracenteses a core competency for hospitalists. ² Although considered a safe procedure, major bleeding complications occur in 0.2% to 1.7% of paracenteses. ^3-7 Patients with cirrhosis form new abdominal wall vessels because of portal hypertension, and hemoperitoneum from the laceration of these vessels during paracentesis carries a high morbidity and mortality. ^6,8 Ultrasound guidance using a low-frequency ultrasound probe is currently standard practice for paracentesis and has been shown to reduce bleeding complications. ^9-11 However, the use of vascular ultrasound (high-frequency probe) is also recommended to identify blood vessels within the intended needle pathway to reduce bleeding, but no studies have been performed to demonstrate a benefit. ^3,11 This study aimed to evaluate whether this “2-probe technique” reduces paracentesis-related bleeding complications.

The procedure service at Cedars Sinai Medical Center (CSMC) in Los Angeles performs paracentesis regularly with ultrasound guidance. CSMC is a tertiary care, academic medical center with 861 licensed beds. We performed a pre- to postintervention study of consecutive patients (admitted and ambulatory) who underwent paracentesis done by 1 proceduralist (MJA) from the procedure service at CSMC from February 2010 through February 2016. From February 1, 2010, through August 2011, paracenteses were performed using only low-frequency, phased array ultrasound probes (preintervention group). From September 1, 2011, through February 2016, a 2-probe technique was used, whereby ultrasound interrogation of the abdomen using a low-frequency, phased array probe (to identify ascites) was supplemented with a second scan using a high-frequency, linear probe to identify vasculature within the planned needle path (postintervention group). As a standard part of quality assurance, CSMC documented all paracentesis-related complications from procedures performed by their center. Northwestern University investigators (JHB, EC, JF) independently evaluated these data to look at bleeding complications before and after the implementation of the 2-probe technique. The CSMC and Northwestern University institutional review boards approved this study.

Procedure Protocol

Each patient’s primary team or outpatient physician requested a consultation for paracentesis from the CSMC procedure service. All patient evaluations began with an abdominal ultrasound using the low-frequency probe to determine the presence of ascites and a potential window of access to the fluid. After September 1, 2011, the CSMC procedure service implemented the 2-probe technique to also evaluate the abdominal wall for the presence of vessels. Color flow Doppler ultrasound further helped to differentiate blood vessels as necessary. The optimal window was then marked on the abdominal wall, and the paracentesis was performed. Per the routine of the CSMC procedure service, antiplatelet or anticoagulant medications were not held for paracenteses.

Measurement

All data were collected prospectively at the time of the procedure, including the volume of fluid removed, the number of needle passes required, and whether the patient was on antiplatelet or anticoagulant medications (including warfarin, direct oral anticoagulants, thrombin inhibitors, heparin, or low molecular weight heparins). Patients were followed for complications for up to 24 hours after the procedure or until a clinical question of a complication was reconciled. Minor bleeding was defined as new serosanguinous fluid on repeat paracentesis not associated with hemodynamic changes, local bruising or bleeding at the site, or abdominal wall hematoma. Major bleeding was defined by the development of hemodynamic instability or by reaccumulation of fluid on ultrasound within 24 hours postparacentesis and one of the following: an associated hemoglobin drop of greater than 2 g/dl, blood seen on repeat paracentesis, blood density fluid on a computed tomography scan, or the lack of an alternative explanation. All data were recorded in a handheld database (HanDbase; DDH Software, Wellington, FL).

A query of the electronic medical record was performed to obtain patient demographics and relevant clinical information, including age, sex, body mass index, International Normalized Ratio (INR), partial thromboplastin time (PTT), platelet counts (10³/uL, hematocrit (%) and creatinine (mg/dl). Our query for laboratory data retrieved the closest laboratory entry up to 48 hours before the procedure.

Statistical Analysis

We used a χ² test, Student t test, or Kruskal-Wallis test to compare demographic and clinical characteristics of procedure patients between the 2 study groups (pre- and postintervention). Major and minor bleeding were compared between the 2 groups using the χ² test.¹² We used the χ² test instead of the Fisher’s exact test for several reasons. The usual rule is that the Fisher’s exact test is necessary when 1 or more expected outcome values are less than 5. However, McDonald argues that the χ² test should be used with large sample sizes (more than 1000) in lieu of the outcome-value-of-5 rule.¹² The Fisher’s exact test also assumes that the row and column totals are fixed. However, the outcomes in our study were not fixed because any patient could have a bleeding complication during each procedure. When row and column totals are not fixed, only 5% of the time will a P value be less than 0.05, and the Fisher’s exact test is too conservative.¹² We performed all statistical analyses using IBM SPSS Statistics Version 22 (IBM Corp, Armonk, NY).

Patient demographic and clinical information can be found in the Table. The proceduralist (MJA) performed a total of 5777 paracenteses (1000 preintervention, 4777 postintervention) on 1639 patients. Four hundred eighty-nine (10.2%) vascular anomalies were identified within the intended needle path in the postintervention group (Figure). More patients in the preintervention group were on aspirin (93 [9.3%] vs 230 [4.8%]; P < 0.001) and therapeutic intravenous anticoagulants (33 [3.3%] vs 89 [1.9%]; P = 0.004), while more patients in the postintervention group were on both an antiplatelet and oral anticoagulant (1 [0.1%] vs 38 [0.8%]; P = 0.015) and subcutaneous prophylactic anticoagulants (184 [18.4%] vs 1120 [23.4%]; P = 0.001) at the time of the procedure. There were no other differences between groups with antiplatelet or anticoagulant drugs. We found no difference in minor bleeding between pre- and postintervention groups. Major bleeding was lower after the 2-probe technique was implemented (3 [0.3%] vs 4 [0.08%]; P = 0.07). There were no between-group differences in INR, PTT, or platelet counts among major bleeders. One patient in the postintervention group had hemodynamic instability and dropped his hemoglobin by 3.8 g/dl at 7 hours after the procedure. This was unexplained, as the patient had no abdominal symptoms or findings on examination. The patient received several liters of fluid before ultimately dying, and the primary team considered sepsis as a possible cause, but no postmortem examination was performed. This was the only death attributed to a major bleeding complication. We included this patient in our analysis because the cause of his demise was not completely clear. However, excluding this patient would change the results from a trend to a statistically significant difference between groups (3 [0.3%] vs 3 [0.06%]; P = 0.03).

To our knowledge, we report the largest series of paracentesis prospectively evaluated for bleeding complications, and this is the first study to evaluate whether adding a vascular ultrasound (high-frequency probe) avoids major bleeding. In our series, up to 10% of patients had abnormal vessels seen with a vascular ultrasound that were within the original intended trajectory path of the needle. These vessels were also likely present yet invisible when ultrasound-guided paracentesis using only the standard, low-frequency probe was being performed. It is unknown whether these vessels are routinely traversed with the needle, nicked, or narrowly avoided during paracenteses performed using only a low-frequency probe.

Procedure-related bleeding may not be completely avoidable, despite using the vascular probe. Some authors have suggested that the mechanism of bleeding is more related to the rapid reduction in intraperitoneal pressure, which increases the gradient across vessel walls, resulting in rupture and bleeding.⁶ However, in our series, using vascular ultrasound also reduced major bleeding to numbers lower than those historically reported in the literature (0.2%).^3-4 Our preintervention number needed to harm was 333 procedures to cause 1 major bleed, compared to 1250 (or 1666 using the 3-patient bleeding analysis) in the postintervention group. In 2008, 150,000 Medicare beneficiaries underwent paracentesis.¹³ Using our study analysis, if vascular ultrasound was used on these patients, up to 360 major bleeds may have been prevented, along with a corresponding reduction in unnecessary morbidity and mortality.

Our study has several limitations. First, it was limited to 1 center with 1 very experienced proceduralist. Although it is possible that the reduction in major bleeding may have been due to the increasing experience of the proceduralist over time, we do not think that this is likely because he had already performed thousands of paracenteses over 9 years before the start of our study. Second, major bleeding was rare and therefore precluded a multivariate analysis to control for temporal trends that might have occurred in our pre- to poststudy design. Statistically significant demographic and clinical variable differences between groups were likely not clinically meaningful. Although more patients were on intravenous anticoagulants in the preintervention group, coagulopathy or low platelets do not increase the bleeding risk during paracenteses,^1,8 and there was no clinical difference in INR, PTT, or platelets between groups (Table). Third, it is possible that unmeasured characteristics contributed to more patient complications in the preintervention group. Finally, we were unable to evaluate length of stay and mortality differences between groups that might have been attributable to the procedure because of the low number of major bleeding complications and the inability to perform a multivariate analysis.

Our results suggest that using the 2-probe technique to predetermine the needle path before performing paracentesis might prevent major bleeding. Based on our findings, we believe that the addition of a vascular ultrasound during paracentesis should be considered by all hospitalists.

Acknowledgments

The authors acknowledge Drs. Douglas Vaughan and Kevin O’Leary for their support and encouragement of this work. They would also like to thank the Cedars-Sinai Enterprise Information Systems Department for assistance with their data query.

Disclosure

The authors have no relevant financial disclosures or conflicts of interest to report.

Ascites is the most common complication of cirrhosis and often leads to hospitalization. ¹ Paracentesis is recommended for all patients admitted with ascites and cirrhosis. ¹ Additionally, the Society of Hospital Medicine considers the ability to perform paracenteses a core competency for hospitalists. ² Although considered a safe procedure, major bleeding complications occur in 0.2% to 1.7% of paracenteses. ^3-7 Patients with cirrhosis form new abdominal wall vessels because of portal hypertension, and hemoperitoneum from the laceration of these vessels during paracentesis carries a high morbidity and mortality. ^6,8 Ultrasound guidance using a low-frequency ultrasound probe is currently standard practice for paracentesis and has been shown to reduce bleeding complications. ^9-11 However, the use of vascular ultrasound (high-frequency probe) is also recommended to identify blood vessels within the intended needle pathway to reduce bleeding, but no studies have been performed to demonstrate a benefit. ^3,11 This study aimed to evaluate whether this “2-probe technique” reduces paracentesis-related bleeding complications.

The procedure service at Cedars Sinai Medical Center (CSMC) in Los Angeles performs paracentesis regularly with ultrasound guidance. CSMC is a tertiary care, academic medical center with 861 licensed beds. We performed a pre- to postintervention study of consecutive patients (admitted and ambulatory) who underwent paracentesis done by 1 proceduralist (MJA) from the procedure service at CSMC from February 2010 through February 2016. From February 1, 2010, through August 2011, paracenteses were performed using only low-frequency, phased array ultrasound probes (preintervention group). From September 1, 2011, through February 2016, a 2-probe technique was used, whereby ultrasound interrogation of the abdomen using a low-frequency, phased array probe (to identify ascites) was supplemented with a second scan using a high-frequency, linear probe to identify vasculature within the planned needle path (postintervention group). As a standard part of quality assurance, CSMC documented all paracentesis-related complications from procedures performed by their center. Northwestern University investigators (JHB, EC, JF) independently evaluated these data to look at bleeding complications before and after the implementation of the 2-probe technique. The CSMC and Northwestern University institutional review boards approved this study.

Procedure Protocol

Each patient’s primary team or outpatient physician requested a consultation for paracentesis from the CSMC procedure service. All patient evaluations began with an abdominal ultrasound using the low-frequency probe to determine the presence of ascites and a potential window of access to the fluid. After September 1, 2011, the CSMC procedure service implemented the 2-probe technique to also evaluate the abdominal wall for the presence of vessels. Color flow Doppler ultrasound further helped to differentiate blood vessels as necessary. The optimal window was then marked on the abdominal wall, and the paracentesis was performed. Per the routine of the CSMC procedure service, antiplatelet or anticoagulant medications were not held for paracenteses.

Measurement

All data were collected prospectively at the time of the procedure, including the volume of fluid removed, the number of needle passes required, and whether the patient was on antiplatelet or anticoagulant medications (including warfarin, direct oral anticoagulants, thrombin inhibitors, heparin, or low molecular weight heparins). Patients were followed for complications for up to 24 hours after the procedure or until a clinical question of a complication was reconciled. Minor bleeding was defined as new serosanguinous fluid on repeat paracentesis not associated with hemodynamic changes, local bruising or bleeding at the site, or abdominal wall hematoma. Major bleeding was defined by the development of hemodynamic instability or by reaccumulation of fluid on ultrasound within 24 hours postparacentesis and one of the following: an associated hemoglobin drop of greater than 2 g/dl, blood seen on repeat paracentesis, blood density fluid on a computed tomography scan, or the lack of an alternative explanation. All data were recorded in a handheld database (HanDbase; DDH Software, Wellington, FL).

A query of the electronic medical record was performed to obtain patient demographics and relevant clinical information, including age, sex, body mass index, International Normalized Ratio (INR), partial thromboplastin time (PTT), platelet counts (10³/uL, hematocrit (%) and creatinine (mg/dl). Our query for laboratory data retrieved the closest laboratory entry up to 48 hours before the procedure.

Statistical Analysis

We used a χ² test, Student t test, or Kruskal-Wallis test to compare demographic and clinical characteristics of procedure patients between the 2 study groups (pre- and postintervention). Major and minor bleeding were compared between the 2 groups using the χ² test.¹² We used the χ² test instead of the Fisher’s exact test for several reasons. The usual rule is that the Fisher’s exact test is necessary when 1 or more expected outcome values are less than 5. However, McDonald argues that the χ² test should be used with large sample sizes (more than 1000) in lieu of the outcome-value-of-5 rule.¹² The Fisher’s exact test also assumes that the row and column totals are fixed. However, the outcomes in our study were not fixed because any patient could have a bleeding complication during each procedure. When row and column totals are not fixed, only 5% of the time will a P value be less than 0.05, and the Fisher’s exact test is too conservative.¹² We performed all statistical analyses using IBM SPSS Statistics Version 22 (IBM Corp, Armonk, NY).

Patient demographic and clinical information can be found in the Table. The proceduralist (MJA) performed a total of 5777 paracenteses (1000 preintervention, 4777 postintervention) on 1639 patients. Four hundred eighty-nine (10.2%) vascular anomalies were identified within the intended needle path in the postintervention group (Figure). More patients in the preintervention group were on aspirin (93 [9.3%] vs 230 [4.8%]; P < 0.001) and therapeutic intravenous anticoagulants (33 [3.3%] vs 89 [1.9%]; P = 0.004), while more patients in the postintervention group were on both an antiplatelet and oral anticoagulant (1 [0.1%] vs 38 [0.8%]; P = 0.015) and subcutaneous prophylactic anticoagulants (184 [18.4%] vs 1120 [23.4%]; P = 0.001) at the time of the procedure. There were no other differences between groups with antiplatelet or anticoagulant drugs. We found no difference in minor bleeding between pre- and postintervention groups. Major bleeding was lower after the 2-probe technique was implemented (3 [0.3%] vs 4 [0.08%]; P = 0.07). There were no between-group differences in INR, PTT, or platelet counts among major bleeders. One patient in the postintervention group had hemodynamic instability and dropped his hemoglobin by 3.8 g/dl at 7 hours after the procedure. This was unexplained, as the patient had no abdominal symptoms or findings on examination. The patient received several liters of fluid before ultimately dying, and the primary team considered sepsis as a possible cause, but no postmortem examination was performed. This was the only death attributed to a major bleeding complication. We included this patient in our analysis because the cause of his demise was not completely clear. However, excluding this patient would change the results from a trend to a statistically significant difference between groups (3 [0.3%] vs 3 [0.06%]; P = 0.03).

To our knowledge, we report the largest series of paracentesis prospectively evaluated for bleeding complications, and this is the first study to evaluate whether adding a vascular ultrasound (high-frequency probe) avoids major bleeding. In our series, up to 10% of patients had abnormal vessels seen with a vascular ultrasound that were within the original intended trajectory path of the needle. These vessels were also likely present yet invisible when ultrasound-guided paracentesis using only the standard, low-frequency probe was being performed. It is unknown whether these vessels are routinely traversed with the needle, nicked, or narrowly avoided during paracenteses performed using only a low-frequency probe.

Procedure-related bleeding may not be completely avoidable, despite using the vascular probe. Some authors have suggested that the mechanism of bleeding is more related to the rapid reduction in intraperitoneal pressure, which increases the gradient across vessel walls, resulting in rupture and bleeding.⁶ However, in our series, using vascular ultrasound also reduced major bleeding to numbers lower than those historically reported in the literature (0.2%).^3-4 Our preintervention number needed to harm was 333 procedures to cause 1 major bleed, compared to 1250 (or 1666 using the 3-patient bleeding analysis) in the postintervention group. In 2008, 150,000 Medicare beneficiaries underwent paracentesis.¹³ Using our study analysis, if vascular ultrasound was used on these patients, up to 360 major bleeds may have been prevented, along with a corresponding reduction in unnecessary morbidity and mortality.

Our study has several limitations. First, it was limited to 1 center with 1 very experienced proceduralist. Although it is possible that the reduction in major bleeding may have been due to the increasing experience of the proceduralist over time, we do not think that this is likely because he had already performed thousands of paracenteses over 9 years before the start of our study. Second, major bleeding was rare and therefore precluded a multivariate analysis to control for temporal trends that might have occurred in our pre- to poststudy design. Statistically significant demographic and clinical variable differences between groups were likely not clinically meaningful. Although more patients were on intravenous anticoagulants in the preintervention group, coagulopathy or low platelets do not increase the bleeding risk during paracenteses,^1,8 and there was no clinical difference in INR, PTT, or platelets between groups (Table). Third, it is possible that unmeasured characteristics contributed to more patient complications in the preintervention group. Finally, we were unable to evaluate length of stay and mortality differences between groups that might have been attributable to the procedure because of the low number of major bleeding complications and the inability to perform a multivariate analysis.

Our results suggest that using the 2-probe technique to predetermine the needle path before performing paracentesis might prevent major bleeding. Based on our findings, we believe that the addition of a vascular ultrasound during paracentesis should be considered by all hospitalists.

Acknowledgments

The authors acknowledge Drs. Douglas Vaughan and Kevin O’Leary for their support and encouragement of this work. They would also like to thank the Cedars-Sinai Enterprise Information Systems Department for assistance with their data query.

Disclosure

The authors have no relevant financial disclosures or conflicts of interest to report.

Pleural effusion can occur in myriad conditions including infection, heart failure, liver disease, and cancer.¹ Consequently, physicians from many disciplines routinely encounter both inpatients and outpatients with this diagnosis. Often, evaluation and treatment require thoracentesis to obtain fluid for analysis or symptom relief.

Although historically performed at the bedside without imaging guidance or intraprocedural monitoring, thoracentesis performed in this fashion carries considerable risk of complications. In fact, it has 1 of the highest rates of iatrogenic pneumothorax among bedside procedures.² However, recent advances in practice and adoption of newer technologies have helped to mitigate risks associated with this procedure. These advances are relevant because approximately 50% of thoracenteses are still performed at the bedside.³ In this review, we aim to identify the most recent key practices that enhance the safety and the effectiveness of thoracentesis for practicing clinicians.

Information Sources and Search Strategy

With the assistance of a research librarian, we performed a systematic search of PubMed-indexed articles from January 1, 2000 to September 30, 2015. Articles were identified using search terms such as thoracentesis, pleural effusion, safety, medical error, adverse event, and ultrasound in combination with Boolean operators. Of note, as thoracentesis is indexed as a subgroup of paracentesis in PubMed, this term was also included to increase the sensitivity of the search. The full search strategy is available in the Appendix. Any references cited in this review outside of the date range of our search are provided only to give relevant background information or establish the origin of commonly performed practices.

Study Eligibility and Selection Criteria

Studies were included if they reported clinical aspects related to thoracentesis. We defined clinical aspects as those strategies that focused on operator training, procedural techniques, technology, management, or prevention of complications. Non-English language articles, animal studies, case reports, conference proceedings, and abstracts were excluded. As our intention was to focus on the contemporary advances related to thoracentesis performance, (eg, ultrasound [US]), our search was limited to studies published after the year 2000. Two authors, Drs. Schildhouse and Lai independently screened studies to determine inclusion, excluding studies with weak methodology, very small sample sizes, and those only tangentially related to our aim. Disagreements regarding study inclusion were resolved by consensus. Drs. Lai, Barsuk, and Mourad identified additional studies by hand review of reference lists and content experts (Figure 1).

Conceptual Framework

All selected articles were categorized by temporal relationship to thoracentesis as pre-, intra-, or postprocedure. Pre-procedural topics were those outcomes that had been identified and addressed before attempting thoracentesis, such as physician training or perceived risks of harm. Intraprocedural considerations included aspects such as use of bedside US, pleural manometry, and large-volume drainage. Finally, postprocedural factors were those related to evaluation after thoracentesis, such as follow-up imaging. This conceptual framework is outlined in Figure 2.

The PubMed search returned a total of 1170 manuscripts, of which 56 articles met inclusion criteria. Four additional articles were identified by experts and included in the study.^4-7 Therefore, 60 articles were identified and included in this review. Study designs included cohort studies, case control studies, systematic reviews, meta-analyses, narrative reviews, consensus guidelines, and randomized controlled trials. A summary of all included articles by topic can be found in the Table.
 

PRE-PROCEDURAL CONSIDERATIONS

Physician Training

Studies indicate that graduate medical education may not adequately prepare clinicians to perform thoracentesis.⁸ In fact, residents have the least exposure and confidence in performing thoracentesis when compared to other bedside procedures.^9,10 In 1 survey, 69% of medical trainees desired more exposure to procedures, and 98% felt that procedural skills were important to master.¹¹ Not surprisingly, then, graduating internal medicine residents perform poorly when assessed on a thoracentesis simulator.¹²

Supplemental training outside of residency is useful to develop and maintain skills for thoracentesis, such as simulation with direct observation in a zero-risk environment. In 1 study, “simulation-based mastery learning” combined an educational video presentation with repeated, deliberate practice on a simulator until procedural competence was acquired, over two 2-hour sessions. In this study, 40 third-year medicine residents demonstrated a 71% improvement in clinical skills performance after course completion, with 93% achieving a passing score. The remaining 7% also achieved passing scores with extra practice time.¹² Others have built upon the concept of simulation-based training. For instance, 2 studies suggest that use of a simulation-based curriculum improved both thoracentesis knowledge and performance skills in a 3-hour session.^13,14 Similarly, 1 prospective study reported that a half-day thoracentesis workshop using simulation and 1:1 direct observation successfully lowered pneumothorax rates from 8.6% to 1.8% in a group of practicing clinicians. Notably, additional interventions including use of bedside US, limiting operators to a focused group, and standardization of equipment were also a part of this quality improvement initiative.⁷ Although repetition is required to gain proficiency when using a simulator, performance and confidence appear to plateau with only 4 simulator trials. In medical students, improvements derived through simulator-based teaching were sustained when retested 6 months following training.¹⁵

An instrument to ensure competency is necessary, given variability in procedural experience among both new graduates and practicing physicians,. Our search did not identify any clinically validated tools that adequately assessed thoracentesis performance. However, some have been proposed¹⁶ and 1 validated in a simulation environment.¹² Regarding the incorporation of US for effusion markup, 1 validated tool used an 11-domain assessment covering knowledge of US machine manipulation, recognition of images with common pleural effusion characteristics, and performance of thoracic US with puncture-site marking on a simulator. When used on 22 participants, scores with the tool could reliably differentiate between novice, intermediate, and advanced groups (P < 0.0001).¹⁷

Patient Selection

Coagulopathies and Anticoagulation. Historically, the accepted cutoff for performing thoracentesis is an international normalized ratio (INR) less than 1.5 and a platelet count greater than 50,000/µL. McVay et al.¹⁸ first showed in 1991 that use of these cutoffs was associated with low rates of periprocedural bleeding, leading to endorsement in the British Thoracic Society (BTS) Pleural Disease Guideline 2010.¹⁹ Other recommendations include the 2012 Society for Interventional Radiology guidelines that endorse correction of an INR greater than 2, or platelets less than 50,000/µL, based almost exclusively on expert opinion.⁵

However, data suggest that thoracentesis may be safely performed outside these parameters. For instance, a prospective study of approximately 9000 thoracenteses over 12 years found that patients with an INR of 1.5-2.9 or platelets of 20,000 - 49,000/µL experienced rates of bleeding complications similar to those with normal values.²⁰ Similarly, a 2014 review²¹ found that the overall risk of hemorrhage during thoracentesis in the setting of moderate coagulopathy (defined as an INR of 1.5 - 3 or platelets of 25,000-50,000/µL), was not increased. In 1 retrospective study of more than 1000 procedures, no differences in hemorrhagic events were noted in patients with bleeding diatheses that received prophylactic fresh frozen plasma or platelets vs. those who did not.²² Of note, included studies used a variety of criteria to define a hemorrhagic complication, which included: an isolated 2 g/dL or more decrement in hemoglobin, presence of bloody fluid on repeat tap with associated hemoglobin decrement, rapid re-accumulation of fluid with a hemoglobin decrement, or transfusion of 2 units or more of whole blood.

Whether it is safe to perform thoracentesis on patients taking antiplatelet therapy is less well understood. Although data are limited, a few small-scale studies^23,24 suggest that hemorrhagic complications following thoracentesis in patients receiving clopidogrel are comparable to the general population. We found no compelling data regarding the safety of thoracentesis in the setting of direct oral anticoagulants, heparin, low-molecular weight heparin, or intravenous direct thrombin inhibitors. Current practice is to generally avoid thoracentesis while these therapeutic anticoagulants are used.

Invasive mechanical ventilation. Pleural effusion is common in patients in the intensive care unit, including those requiring mechanical ventilation.²⁵ Thoracentesis in this population is clinically important: fluid analysis in 1 study was shown to aid the diagnosis in 45% of cases and changes in treatment in 33%.²⁶ However, clinicians may be reluctant to perform thoracentesis on patients who require mechanical ventilation, given the perception of a greater risk of pneumothorax from positive pressure ventilation.

Despite this concern, a 2011 meta-analysis including 19 studies and more than 1100 patients revealed rates of pneumothorax and hemothorax comparable to nonventilated patients.²⁵ Furthermore, a 2015 prospective study that examined thoracentesis in 1377 mechanically ventilated patients revealed no difference in complication rates as well.²⁰ Therefore, evidence suggests that performance of thoracentesis in mechanically ventilated patients is not contraindicated.

Skin Disinfection and Antisepsis Precautions

The 2010 BTS guidelines list empyema and wound infection as possible complications of thoracentesis.¹⁹ However, no data regarding incidence are provided. Additionally, an alcohol-based skin cleanser (such as 2% chlorhexidine gluconate/70% isopropyl alcohol), along with sterile gloves, field, and dressing are suggested as precautionary measures.¹⁹ In 1 single-center registry of 2489 thoracenteses performed using alcohol or iodine-based antiseptic and sterile drapes, no postprocedure infections were identified.²⁷ Of note, we did not find other studies (including case reports) that reported either incidence or rate of infectious complications such as wound infection and empyema. In an era of modern skin antiseptics that have effectively reduced complications such as catheter-related bloodstream infection,²⁸ the incidence of this event is thus likely to be low.

INTRAPROCEDURAL CONSIDERATIONS

Use of Bedside Ultrasound

Portable US has particular advantages for evaluation of pleural effusion vs other imaging modalities. Compared with computerized tomography (CT), bedside US offers similar performance but is less costly, avoids both radiation exposure and need for patient transportation, and provides results instantaneously.^29,30 Compared to chest x-ray (CXR), US is more sensitive at detecting the presence, volume, and characteristics of pleural fluid^30,31 and can be up to 100% sensitive for effusions greater than 100 mL.²⁹ Furthermore, whereas CXR typically requires 200 mL of fluid to be present for detection of an effusion, US can reliably detect as little as 20 mL of fluid.²⁹ When US was used to confirm thoracentesis puncture sites in a study involving 30 physicians of varying experience and 67 consecutive patients, 15% of sites found by clinical exam were inaccurate (less than 10 mm fluid present), 10% were at high risk for organ puncture, and a suitable fluid pocket was found 54% of times when exam could not.⁴

A 2010 meta-analysis of 24 studies and 6605 thoracenteses estimated the overall rate of pneumothorax at 6%; however, procedures performed with US guidance were associated with a 70% reduced risk of this event (odds ratio, 0.30; 95% confidence interval, 0.20 - 0.70).³² In a 2014 randomized control trial of 160 patients that compared thoracentesis with US guidance for site marking vs no US use, 10 pneumothoraces occurred in the control group vs 1 in the US group (12.5% vs 1.25%, P = 0.009).³³ Similarly, another retrospective review of 445 consecutive patients with malignant effusions revealed a pneumothorax rate of 0.97% using US in real time during needle insertion compared to 8.89% for unguided thoracenteses (P < 0.0001).³⁴ Several other studies using US guidance for either site markup or in real time reported similar pneumothorax rates, ranging from 1.1% - 4.8%.^35-37 However, it is unclear if real-time US specifically provides an additive effect vs site marking alone, as no studies directly comparing the 2 methods were found.

Benefits of US also include a higher rate of procedural success, with 1 study demonstrating a 99% success rate when using US vs. 90% without (P = 0.030).³³ A larger volume of fluid removed has been observed with US use as well, and methods have been described using fluid-pocket depth to guide puncture site localization and maximize drainage.³⁸ Finally, US use for thoracentesis has been associated with lower costs and length of stay.^39,40

Intercostal Artery Localization

Although rare (incidence, 0.18%-2%^20,21,39), the occurrence of hemothorax following thoracentesis is potentially catastrophic. This serious complication is often caused by laceration of the intercostal artery (ICA) or 1 of its branches during needle insertion.⁴¹

While risk of injury is theoretically reduced by needle insertion superior to the rib, studies using cadaver dissection and 3D angiography show significant tortuosity of the ICA.^6,41-43 The degree of tortuosity is increased within 6 cm of the midline, in more cephalad rib spaces, and in the elderly (older than 60 years).^41-43 Furthermore, 1 cadaveric study also demonstrated the presence of arterial collaterals branching off the ICA at multiple intercostal spaces, ranging between 8 cm and 11 cm from the midline.⁴¹ This anatomic variability may explain why some have observed low complication and hemothorax rates with an extreme lateral approach.³⁵ Bedside US with color flow Doppler imaging has been used to identify the ICA, with 88% sensitivity compared to CT imaging while adding little to exam time.^44,45 Of note, a 37% drop in the rate of hemothorax was observed in 1 study with routine US guidance alone.³⁹

Pleural Pressure Monitoring and Large-Volume Thoracentesis

While normal intrapleural pressures are approximately -5 to -10 cm H₂O,⁴⁶ the presence of a pleural effusion creates a complex interaction between fluid, compressed lung, and chest wall that can increase these pressures.⁴⁷ During drainage of an effusion, pleural pressures may rapidly drop, provoking re-expansion pulmonary edema (REPE). While rare (0 -1%), clinically-diagnosed REPE is a serious complication that can lead to rapid respiratory failure and death.^20,48 REPE is postulated to be caused by increased capillary permeability resulting from inflammation, driven by rapid re-inflation of the lung when exposed to highly negative intrapleural pressures.^47,49

Measurement of intrapleural pressure using a water manometer during thoracentesis may minimize REPE by terminating fluid drainage when intrapleural pressure begins to drop rapidly.^50,51 A cutoff of -20 cm H₂O has been cited repeatedly as safe since being suggested by Light in 1980, but this is based on animal models.^50,52 In 1 prospective study of 185 thoracenteses in which manometry was performed, 15% of patients had intrapleural pressure drop to less than -20 cm H₂O (at which point the procedure was terminated) but suffered no REPE.⁵⁰

Manometry is valuable in the identification of an unexpandable or trapped lung when pleural pressures drop rapidly with only minimal fluid volume removal.^47,53 Other findings correlated with an unexpandable lung include a negative opening pressure⁴⁷ and large fluctuations in pressure during the respiratory cycle.⁵⁴

While development of symptoms (eg, chest pain, cough, or dyspnea) is often used as a surrogate, the correlation between intrapleural pressure and patient symptoms is inconsistent and not a reliable proxy.⁵⁵ One study found that 22% of patients with chest pain during thoracentesis had intrapleural pressures lower than -20 cm H₂O compared with 8.6% of asymptomatic patients,⁵⁶ but it is unclear if the association is causal.

Thoracentesis is often performed for symptomatic relief and removal of large fluid volume. However, it remains common to halt fluid removal after 1.5 L, a threshold endorsed by BTS.¹⁹ While some investigators have suggested that removal of 2 L or more of pleural fluid does not compromise safety,^57,58 a 4- to 5-fold rise in the risk of pneumothorax was noted in 2 studies.^20,59 when more than 1.5 L of fluid was removed. The majority of these may be related to pneumothorax ex vacuo, a condition in which fluid is drained from the chest, but the lung is unable to expand and fill the space (eg, “trapped lung”), resulting in a persistent pneumothorax. This condition generally does not require treatment.⁶⁰ When manometry is employed at 200-mL intervals with termination at an intrapleural pressure of less than 20 mm H₂O, drainage of 3 L or more has been reported with low rates of pneumothorax and very low rates of REPE.^50,51 However, whether this is cause and effect is unknown because REPE is rare, and more work is needed to determine the role of manometry for its prevention.

POSTPROCEDURAL CONSIDERATIONS

Postprocedure Imaging

Performing an upright CXR following thoracentesis is a practice that remains routinely done by many practitioners to monitor for complications. Such imaging was also endorsed by the American Thoracic Society guidelines.⁶¹ However, more recent data question the utility of this practice. Multiple studies have confirmed that post-thoracentesis CXR is unnecessary unless clinical suspicion for pneumothorax or REPE is present.^36,58,62,63 The BTS guidelines also advocate this approach.¹⁹ Interestingly, a potentially more effective way to screen for postprocedure complications is through bedside US, which has been shown to be more sensitive than CXR in detecting pneumothorax.⁶⁴ In 1 study of 185 patients, bedside US demonstrated a sensitivity of 88% and a specificity of 97% for diagnosing pneumothorax in patients with adequate quality scans, with positive and negative likelihood ratios of 55 and 0.17, respectively.⁶⁵

Thoracentesis remains a core procedural skill for hospitalists, critical care physicians, and emergency physicians. It is the foundational component when investigating and treating pleural effusions. When the most current training, techniques, and technology are used, data suggest this procedure is safe to perform at the bedside. Our review highlights these strategies and evaluates which aspects might be most applicable to clinical practice.

Our findings have several implications for those who perform this procedure. First, appropriate training is central to procedural safety, and both simulation and direct observation by procedural experts have been shown by multiple investigators to improve knowledge and skill. This training should integrate the use of US in performing a focused thoracic exam.

Second, recommendations regarding coagulopathy and a “safe cutoff” of an INR less than 1.5 or platelets greater than 50,000/µL had limited evidentiary support. Rather, multiple studies suggest no difference in bleeding risk following thoracentesis with an INR as high as 3.0 and platelets greater than 25,000/µL. Furthermore, prophylactic transfusion with fresh frozen plasma or platelets before thoracentesis did not alter bleeding risk and exposes patients to transfusion complications. Thus, routine use of this practice can no longer be recommended. Third, further research is needed to understand the bleeding risk for patients on antiplatelet medications, heparin products, and also direct oral anticoagulants, given the growing popularity in their use and the potential consequences of even temporary cessation. Regarding patients on mechanical ventilation, thoracentesis demonstrated no difference in complication rates vs. the general population, and its performance in this population is encouraged when clinically indicated.

Intraprocedural considerations include the use of bedside US. Due to multiple benefits including effusion characterization, puncture site localization, and significantly lower rates of pneumothorax, the standard of care should be to perform thoracentesis with US guidance. Both use of US to mark an effusion immediately prior to puncture or in real time during needle insertion demonstrated benefit; however, it is unclear if 1 method is superior because no direct comparison studies were found. Further work is needed to investigate this potential.

Our review suggests that the location and course of the ICA is variable, especially near the midline, in the elderly, and in higher intercostal spaces, leaving it vulnerable to laceration. We recommend physicians only attempt thoracentesis at least 6 cm lateral to the midline due to ICA tortuosity and, ideally, 12 cm lateral, to avoid the presence of collaterals. Although only 2 small-scale studies were found pertaining to the use of US in identifying the ICA, we encourage physicians to consider learning how to screen for its presence as a part of their routine thoracic US exam in the area underlying the planned puncture site.

Manometry is beneficial because it can diagnose a nonexpandable lung and allows for pleural pressure monitoring.^52,53 A simple U-shaped manometer can be constructed from intravenous tubing included in most thoracentesis kits, which adds little to overall procedure time. While low rates of REPE have been observed when terminating thoracentesis if pressures drop below -20 cm H₂O or chest pain develops, neither measure appears to have reliable predictive value, limiting clinical utility. Further work is required to determine if a “safe pressure cutoff” exists. In general, we recommend the use of manometry when a nonexpandable (trapped) lung is suspected, because large drops in intrapleural pressure, a negative opening pressure, and respiratory variation can help confirm the diagnosis and avoid pneumothorax ex vacuo or unnecessary procedures in the future. As this condition appears to be more common in the setting of larger effusions, use of manometry when large-volume thoracenteses are planned is also reasonable.

Postprocedurally, routine imaging after thoracentesis is not recommended unless there is objective concern for complication. When indicated, bedside US is better positioned for this role compared with CXR, because it is more sensitive in detecting pneumothorax, provides instantaneous results, and avoids radiation exposure.

Our review has limitations. First, we searched only for articles between defined time periods, restricted our search to a single database, and excluded non-English articles. This has the potential to introduce selection bias, as nonprimary articles that fall within our time restrictions may cite older studies that are outside our search range. To minimize this effect, we performed a critical review of all included studies, especially nonprimary articles. Second, despite the focus of our search strategy to identify any articles related to patient safety and adverse events, we cannot guarantee that all relevant articles for any particular complication or risk factor were captured given the lack of more specific search terms. Third, although we performed a systematic search of the literature, we did not perform a formal systematic review or formally grade included studies. As the goal of our review was to categorize and operationalize clinical aspects, this approach was necessary, and we acknowledge that the quality of studies is variable. Lastly, we aimed to generate clinical recommendations for physicians performing thoracentesis at the bedside; others reviewing this literature may find or emphasize different aspects relevant to practice outside this setting.

In conclusion, evaluation and treatment of pleural effusions with bedside thoracentesis is an important skill for physicians of many disciplines. The evidence presented in this review will help inform the process and ensure patient safety. Physicians should consider incorporating these recommendations into their practice.

Acknowledgments

The authors thank Whitney Townsend, MLIS, health sciences informationist, for assistance with serial literature searches.

Disclosure

Nothing to report.

Pleural effusion can occur in myriad conditions including infection, heart failure, liver disease, and cancer.¹ Consequently, physicians from many disciplines routinely encounter both inpatients and outpatients with this diagnosis. Often, evaluation and treatment require thoracentesis to obtain fluid for analysis or symptom relief.

Although historically performed at the bedside without imaging guidance or intraprocedural monitoring, thoracentesis performed in this fashion carries considerable risk of complications. In fact, it has 1 of the highest rates of iatrogenic pneumothorax among bedside procedures.² However, recent advances in practice and adoption of newer technologies have helped to mitigate risks associated with this procedure. These advances are relevant because approximately 50% of thoracenteses are still performed at the bedside.³ In this review, we aim to identify the most recent key practices that enhance the safety and the effectiveness of thoracentesis for practicing clinicians.

Information Sources and Search Strategy

With the assistance of a research librarian, we performed a systematic search of PubMed-indexed articles from January 1, 2000 to September 30, 2015. Articles were identified using search terms such as thoracentesis, pleural effusion, safety, medical error, adverse event, and ultrasound in combination with Boolean operators. Of note, as thoracentesis is indexed as a subgroup of paracentesis in PubMed, this term was also included to increase the sensitivity of the search. The full search strategy is available in the Appendix. Any references cited in this review outside of the date range of our search are provided only to give relevant background information or establish the origin of commonly performed practices.

Study Eligibility and Selection Criteria

Studies were included if they reported clinical aspects related to thoracentesis. We defined clinical aspects as those strategies that focused on operator training, procedural techniques, technology, management, or prevention of complications. Non-English language articles, animal studies, case reports, conference proceedings, and abstracts were excluded. As our intention was to focus on the contemporary advances related to thoracentesis performance, (eg, ultrasound [US]), our search was limited to studies published after the year 2000. Two authors, Drs. Schildhouse and Lai independently screened studies to determine inclusion, excluding studies with weak methodology, very small sample sizes, and those only tangentially related to our aim. Disagreements regarding study inclusion were resolved by consensus. Drs. Lai, Barsuk, and Mourad identified additional studies by hand review of reference lists and content experts (Figure 1).

Conceptual Framework

All selected articles were categorized by temporal relationship to thoracentesis as pre-, intra-, or postprocedure. Pre-procedural topics were those outcomes that had been identified and addressed before attempting thoracentesis, such as physician training or perceived risks of harm. Intraprocedural considerations included aspects such as use of bedside US, pleural manometry, and large-volume drainage. Finally, postprocedural factors were those related to evaluation after thoracentesis, such as follow-up imaging. This conceptual framework is outlined in Figure 2.

The PubMed search returned a total of 1170 manuscripts, of which 56 articles met inclusion criteria. Four additional articles were identified by experts and included in the study.^4-7 Therefore, 60 articles were identified and included in this review. Study designs included cohort studies, case control studies, systematic reviews, meta-analyses, narrative reviews, consensus guidelines, and randomized controlled trials. A summary of all included articles by topic can be found in the Table.
 

PRE-PROCEDURAL CONSIDERATIONS

Physician Training

Studies indicate that graduate medical education may not adequately prepare clinicians to perform thoracentesis.⁸ In fact, residents have the least exposure and confidence in performing thoracentesis when compared to other bedside procedures.^9,10 In 1 survey, 69% of medical trainees desired more exposure to procedures, and 98% felt that procedural skills were important to master.¹¹ Not surprisingly, then, graduating internal medicine residents perform poorly when assessed on a thoracentesis simulator.¹²

Supplemental training outside of residency is useful to develop and maintain skills for thoracentesis, such as simulation with direct observation in a zero-risk environment. In 1 study, “simulation-based mastery learning” combined an educational video presentation with repeated, deliberate practice on a simulator until procedural competence was acquired, over two 2-hour sessions. In this study, 40 third-year medicine residents demonstrated a 71% improvement in clinical skills performance after course completion, with 93% achieving a passing score. The remaining 7% also achieved passing scores with extra practice time.¹² Others have built upon the concept of simulation-based training. For instance, 2 studies suggest that use of a simulation-based curriculum improved both thoracentesis knowledge and performance skills in a 3-hour session.^13,14 Similarly, 1 prospective study reported that a half-day thoracentesis workshop using simulation and 1:1 direct observation successfully lowered pneumothorax rates from 8.6% to 1.8% in a group of practicing clinicians. Notably, additional interventions including use of bedside US, limiting operators to a focused group, and standardization of equipment were also a part of this quality improvement initiative.⁷ Although repetition is required to gain proficiency when using a simulator, performance and confidence appear to plateau with only 4 simulator trials. In medical students, improvements derived through simulator-based teaching were sustained when retested 6 months following training.¹⁵

An instrument to ensure competency is necessary, given variability in procedural experience among both new graduates and practicing physicians,. Our search did not identify any clinically validated tools that adequately assessed thoracentesis performance. However, some have been proposed¹⁶ and 1 validated in a simulation environment.¹² Regarding the incorporation of US for effusion markup, 1 validated tool used an 11-domain assessment covering knowledge of US machine manipulation, recognition of images with common pleural effusion characteristics, and performance of thoracic US with puncture-site marking on a simulator. When used on 22 participants, scores with the tool could reliably differentiate between novice, intermediate, and advanced groups (P < 0.0001).¹⁷

Patient Selection

Coagulopathies and Anticoagulation. Historically, the accepted cutoff for performing thoracentesis is an international normalized ratio (INR) less than 1.5 and a platelet count greater than 50,000/µL. McVay et al.¹⁸ first showed in 1991 that use of these cutoffs was associated with low rates of periprocedural bleeding, leading to endorsement in the British Thoracic Society (BTS) Pleural Disease Guideline 2010.¹⁹ Other recommendations include the 2012 Society for Interventional Radiology guidelines that endorse correction of an INR greater than 2, or platelets less than 50,000/µL, based almost exclusively on expert opinion.⁵

However, data suggest that thoracentesis may be safely performed outside these parameters. For instance, a prospective study of approximately 9000 thoracenteses over 12 years found that patients with an INR of 1.5-2.9 or platelets of 20,000 - 49,000/µL experienced rates of bleeding complications similar to those with normal values.²⁰ Similarly, a 2014 review²¹ found that the overall risk of hemorrhage during thoracentesis in the setting of moderate coagulopathy (defined as an INR of 1.5 - 3 or platelets of 25,000-50,000/µL), was not increased. In 1 retrospective study of more than 1000 procedures, no differences in hemorrhagic events were noted in patients with bleeding diatheses that received prophylactic fresh frozen plasma or platelets vs. those who did not.²² Of note, included studies used a variety of criteria to define a hemorrhagic complication, which included: an isolated 2 g/dL or more decrement in hemoglobin, presence of bloody fluid on repeat tap with associated hemoglobin decrement, rapid re-accumulation of fluid with a hemoglobin decrement, or transfusion of 2 units or more of whole blood.

Whether it is safe to perform thoracentesis on patients taking antiplatelet therapy is less well understood. Although data are limited, a few small-scale studies^23,24 suggest that hemorrhagic complications following thoracentesis in patients receiving clopidogrel are comparable to the general population. We found no compelling data regarding the safety of thoracentesis in the setting of direct oral anticoagulants, heparin, low-molecular weight heparin, or intravenous direct thrombin inhibitors. Current practice is to generally avoid thoracentesis while these therapeutic anticoagulants are used.

Invasive mechanical ventilation. Pleural effusion is common in patients in the intensive care unit, including those requiring mechanical ventilation.²⁵ Thoracentesis in this population is clinically important: fluid analysis in 1 study was shown to aid the diagnosis in 45% of cases and changes in treatment in 33%.²⁶ However, clinicians may be reluctant to perform thoracentesis on patients who require mechanical ventilation, given the perception of a greater risk of pneumothorax from positive pressure ventilation.

Despite this concern, a 2011 meta-analysis including 19 studies and more than 1100 patients revealed rates of pneumothorax and hemothorax comparable to nonventilated patients.²⁵ Furthermore, a 2015 prospective study that examined thoracentesis in 1377 mechanically ventilated patients revealed no difference in complication rates as well.²⁰ Therefore, evidence suggests that performance of thoracentesis in mechanically ventilated patients is not contraindicated.

Skin Disinfection and Antisepsis Precautions

The 2010 BTS guidelines list empyema and wound infection as possible complications of thoracentesis.¹⁹ However, no data regarding incidence are provided. Additionally, an alcohol-based skin cleanser (such as 2% chlorhexidine gluconate/70% isopropyl alcohol), along with sterile gloves, field, and dressing are suggested as precautionary measures.¹⁹ In 1 single-center registry of 2489 thoracenteses performed using alcohol or iodine-based antiseptic and sterile drapes, no postprocedure infections were identified.²⁷ Of note, we did not find other studies (including case reports) that reported either incidence or rate of infectious complications such as wound infection and empyema. In an era of modern skin antiseptics that have effectively reduced complications such as catheter-related bloodstream infection,²⁸ the incidence of this event is thus likely to be low.

INTRAPROCEDURAL CONSIDERATIONS

Use of Bedside Ultrasound

Portable US has particular advantages for evaluation of pleural effusion vs other imaging modalities. Compared with computerized tomography (CT), bedside US offers similar performance but is less costly, avoids both radiation exposure and need for patient transportation, and provides results instantaneously.^29,30 Compared to chest x-ray (CXR), US is more sensitive at detecting the presence, volume, and characteristics of pleural fluid^30,31 and can be up to 100% sensitive for effusions greater than 100 mL.²⁹ Furthermore, whereas CXR typically requires 200 mL of fluid to be present for detection of an effusion, US can reliably detect as little as 20 mL of fluid.²⁹ When US was used to confirm thoracentesis puncture sites in a study involving 30 physicians of varying experience and 67 consecutive patients, 15% of sites found by clinical exam were inaccurate (less than 10 mm fluid present), 10% were at high risk for organ puncture, and a suitable fluid pocket was found 54% of times when exam could not.⁴

A 2010 meta-analysis of 24 studies and 6605 thoracenteses estimated the overall rate of pneumothorax at 6%; however, procedures performed with US guidance were associated with a 70% reduced risk of this event (odds ratio, 0.30; 95% confidence interval, 0.20 - 0.70).³² In a 2014 randomized control trial of 160 patients that compared thoracentesis with US guidance for site marking vs no US use, 10 pneumothoraces occurred in the control group vs 1 in the US group (12.5% vs 1.25%, P = 0.009).³³ Similarly, another retrospective review of 445 consecutive patients with malignant effusions revealed a pneumothorax rate of 0.97% using US in real time during needle insertion compared to 8.89% for unguided thoracenteses (P < 0.0001).³⁴ Several other studies using US guidance for either site markup or in real time reported similar pneumothorax rates, ranging from 1.1% - 4.8%.^35-37 However, it is unclear if real-time US specifically provides an additive effect vs site marking alone, as no studies directly comparing the 2 methods were found.

Benefits of US also include a higher rate of procedural success, with 1 study demonstrating a 99% success rate when using US vs. 90% without (P = 0.030).³³ A larger volume of fluid removed has been observed with US use as well, and methods have been described using fluid-pocket depth to guide puncture site localization and maximize drainage.³⁸ Finally, US use for thoracentesis has been associated with lower costs and length of stay.^39,40

Intercostal Artery Localization

Although rare (incidence, 0.18%-2%^20,21,39), the occurrence of hemothorax following thoracentesis is potentially catastrophic. This serious complication is often caused by laceration of the intercostal artery (ICA) or 1 of its branches during needle insertion.⁴¹

While risk of injury is theoretically reduced by needle insertion superior to the rib, studies using cadaver dissection and 3D angiography show significant tortuosity of the ICA.^6,41-43 The degree of tortuosity is increased within 6 cm of the midline, in more cephalad rib spaces, and in the elderly (older than 60 years).^41-43 Furthermore, 1 cadaveric study also demonstrated the presence of arterial collaterals branching off the ICA at multiple intercostal spaces, ranging between 8 cm and 11 cm from the midline.⁴¹ This anatomic variability may explain why some have observed low complication and hemothorax rates with an extreme lateral approach.³⁵ Bedside US with color flow Doppler imaging has been used to identify the ICA, with 88% sensitivity compared to CT imaging while adding little to exam time.^44,45 Of note, a 37% drop in the rate of hemothorax was observed in 1 study with routine US guidance alone.³⁹

Pleural Pressure Monitoring and Large-Volume Thoracentesis

While normal intrapleural pressures are approximately -5 to -10 cm H₂O,⁴⁶ the presence of a pleural effusion creates a complex interaction between fluid, compressed lung, and chest wall that can increase these pressures.⁴⁷ During drainage of an effusion, pleural pressures may rapidly drop, provoking re-expansion pulmonary edema (REPE). While rare (0 -1%), clinically-diagnosed REPE is a serious complication that can lead to rapid respiratory failure and death.^20,48 REPE is postulated to be caused by increased capillary permeability resulting from inflammation, driven by rapid re-inflation of the lung when exposed to highly negative intrapleural pressures.^47,49

Measurement of intrapleural pressure using a water manometer during thoracentesis may minimize REPE by terminating fluid drainage when intrapleural pressure begins to drop rapidly.^50,51 A cutoff of -20 cm H₂O has been cited repeatedly as safe since being suggested by Light in 1980, but this is based on animal models.^50,52 In 1 prospective study of 185 thoracenteses in which manometry was performed, 15% of patients had intrapleural pressure drop to less than -20 cm H₂O (at which point the procedure was terminated) but suffered no REPE.⁵⁰

Manometry is valuable in the identification of an unexpandable or trapped lung when pleural pressures drop rapidly with only minimal fluid volume removal.^47,53 Other findings correlated with an unexpandable lung include a negative opening pressure⁴⁷ and large fluctuations in pressure during the respiratory cycle.⁵⁴

While development of symptoms (eg, chest pain, cough, or dyspnea) is often used as a surrogate, the correlation between intrapleural pressure and patient symptoms is inconsistent and not a reliable proxy.⁵⁵ One study found that 22% of patients with chest pain during thoracentesis had intrapleural pressures lower than -20 cm H₂O compared with 8.6% of asymptomatic patients,⁵⁶ but it is unclear if the association is causal.

Thoracentesis is often performed for symptomatic relief and removal of large fluid volume. However, it remains common to halt fluid removal after 1.5 L, a threshold endorsed by BTS.¹⁹ While some investigators have suggested that removal of 2 L or more of pleural fluid does not compromise safety,^57,58 a 4- to 5-fold rise in the risk of pneumothorax was noted in 2 studies.^20,59 when more than 1.5 L of fluid was removed. The majority of these may be related to pneumothorax ex vacuo, a condition in which fluid is drained from the chest, but the lung is unable to expand and fill the space (eg, “trapped lung”), resulting in a persistent pneumothorax. This condition generally does not require treatment.⁶⁰ When manometry is employed at 200-mL intervals with termination at an intrapleural pressure of less than 20 mm H₂O, drainage of 3 L or more has been reported with low rates of pneumothorax and very low rates of REPE.^50,51 However, whether this is cause and effect is unknown because REPE is rare, and more work is needed to determine the role of manometry for its prevention.

POSTPROCEDURAL CONSIDERATIONS

Postprocedure Imaging

Performing an upright CXR following thoracentesis is a practice that remains routinely done by many practitioners to monitor for complications. Such imaging was also endorsed by the American Thoracic Society guidelines.⁶¹ However, more recent data question the utility of this practice. Multiple studies have confirmed that post-thoracentesis CXR is unnecessary unless clinical suspicion for pneumothorax or REPE is present.^36,58,62,63 The BTS guidelines also advocate this approach.¹⁹ Interestingly, a potentially more effective way to screen for postprocedure complications is through bedside US, which has been shown to be more sensitive than CXR in detecting pneumothorax.⁶⁴ In 1 study of 185 patients, bedside US demonstrated a sensitivity of 88% and a specificity of 97% for diagnosing pneumothorax in patients with adequate quality scans, with positive and negative likelihood ratios of 55 and 0.17, respectively.⁶⁵

Thoracentesis remains a core procedural skill for hospitalists, critical care physicians, and emergency physicians. It is the foundational component when investigating and treating pleural effusions. When the most current training, techniques, and technology are used, data suggest this procedure is safe to perform at the bedside. Our review highlights these strategies and evaluates which aspects might be most applicable to clinical practice.

Our findings have several implications for those who perform this procedure. First, appropriate training is central to procedural safety, and both simulation and direct observation by procedural experts have been shown by multiple investigators to improve knowledge and skill. This training should integrate the use of US in performing a focused thoracic exam.

Second, recommendations regarding coagulopathy and a “safe cutoff” of an INR less than 1.5 or platelets greater than 50,000/µL had limited evidentiary support. Rather, multiple studies suggest no difference in bleeding risk following thoracentesis with an INR as high as 3.0 and platelets greater than 25,000/µL. Furthermore, prophylactic transfusion with fresh frozen plasma or platelets before thoracentesis did not alter bleeding risk and exposes patients to transfusion complications. Thus, routine use of this practice can no longer be recommended. Third, further research is needed to understand the bleeding risk for patients on antiplatelet medications, heparin products, and also direct oral anticoagulants, given the growing popularity in their use and the potential consequences of even temporary cessation. Regarding patients on mechanical ventilation, thoracentesis demonstrated no difference in complication rates vs. the general population, and its performance in this population is encouraged when clinically indicated.

Intraprocedural considerations include the use of bedside US. Due to multiple benefits including effusion characterization, puncture site localization, and significantly lower rates of pneumothorax, the standard of care should be to perform thoracentesis with US guidance. Both use of US to mark an effusion immediately prior to puncture or in real time during needle insertion demonstrated benefit; however, it is unclear if 1 method is superior because no direct comparison studies were found. Further work is needed to investigate this potential.

Our review suggests that the location and course of the ICA is variable, especially near the midline, in the elderly, and in higher intercostal spaces, leaving it vulnerable to laceration. We recommend physicians only attempt thoracentesis at least 6 cm lateral to the midline due to ICA tortuosity and, ideally, 12 cm lateral, to avoid the presence of collaterals. Although only 2 small-scale studies were found pertaining to the use of US in identifying the ICA, we encourage physicians to consider learning how to screen for its presence as a part of their routine thoracic US exam in the area underlying the planned puncture site.

Manometry is beneficial because it can diagnose a nonexpandable lung and allows for pleural pressure monitoring.^52,53 A simple U-shaped manometer can be constructed from intravenous tubing included in most thoracentesis kits, which adds little to overall procedure time. While low rates of REPE have been observed when terminating thoracentesis if pressures drop below -20 cm H₂O or chest pain develops, neither measure appears to have reliable predictive value, limiting clinical utility. Further work is required to determine if a “safe pressure cutoff” exists. In general, we recommend the use of manometry when a nonexpandable (trapped) lung is suspected, because large drops in intrapleural pressure, a negative opening pressure, and respiratory variation can help confirm the diagnosis and avoid pneumothorax ex vacuo or unnecessary procedures in the future. As this condition appears to be more common in the setting of larger effusions, use of manometry when large-volume thoracenteses are planned is also reasonable.

Postprocedurally, routine imaging after thoracentesis is not recommended unless there is objective concern for complication. When indicated, bedside US is better positioned for this role compared with CXR, because it is more sensitive in detecting pneumothorax, provides instantaneous results, and avoids radiation exposure.

Our review has limitations. First, we searched only for articles between defined time periods, restricted our search to a single database, and excluded non-English articles. This has the potential to introduce selection bias, as nonprimary articles that fall within our time restrictions may cite older studies that are outside our search range. To minimize this effect, we performed a critical review of all included studies, especially nonprimary articles. Second, despite the focus of our search strategy to identify any articles related to patient safety and adverse events, we cannot guarantee that all relevant articles for any particular complication or risk factor were captured given the lack of more specific search terms. Third, although we performed a systematic search of the literature, we did not perform a formal systematic review or formally grade included studies. As the goal of our review was to categorize and operationalize clinical aspects, this approach was necessary, and we acknowledge that the quality of studies is variable. Lastly, we aimed to generate clinical recommendations for physicians performing thoracentesis at the bedside; others reviewing this literature may find or emphasize different aspects relevant to practice outside this setting.

In conclusion, evaluation and treatment of pleural effusions with bedside thoracentesis is an important skill for physicians of many disciplines. The evidence presented in this review will help inform the process and ensure patient safety. Physicians should consider incorporating these recommendations into their practice.

Acknowledgments

The authors thank Whitney Townsend, MLIS, health sciences informationist, for assistance with serial literature searches.

Disclosure

Nothing to report.

Pleural effusion can occur in myriad conditions including infection, heart failure, liver disease, and cancer.¹ Consequently, physicians from many disciplines routinely encounter both inpatients and outpatients with this diagnosis. Often, evaluation and treatment require thoracentesis to obtain fluid for analysis or symptom relief.

Although historically performed at the bedside without imaging guidance or intraprocedural monitoring, thoracentesis performed in this fashion carries considerable risk of complications. In fact, it has 1 of the highest rates of iatrogenic pneumothorax among bedside procedures.² However, recent advances in practice and adoption of newer technologies have helped to mitigate risks associated with this procedure. These advances are relevant because approximately 50% of thoracenteses are still performed at the bedside.³ In this review, we aim to identify the most recent key practices that enhance the safety and the effectiveness of thoracentesis for practicing clinicians.

Information Sources and Search Strategy

With the assistance of a research librarian, we performed a systematic search of PubMed-indexed articles from January 1, 2000 to September 30, 2015. Articles were identified using search terms such as thoracentesis, pleural effusion, safety, medical error, adverse event, and ultrasound in combination with Boolean operators. Of note, as thoracentesis is indexed as a subgroup of paracentesis in PubMed, this term was also included to increase the sensitivity of the search. The full search strategy is available in the Appendix. Any references cited in this review outside of the date range of our search are provided only to give relevant background information or establish the origin of commonly performed practices.

Study Eligibility and Selection Criteria

Studies were included if they reported clinical aspects related to thoracentesis. We defined clinical aspects as those strategies that focused on operator training, procedural techniques, technology, management, or prevention of complications. Non-English language articles, animal studies, case reports, conference proceedings, and abstracts were excluded. As our intention was to focus on the contemporary advances related to thoracentesis performance, (eg, ultrasound [US]), our search was limited to studies published after the year 2000. Two authors, Drs. Schildhouse and Lai independently screened studies to determine inclusion, excluding studies with weak methodology, very small sample sizes, and those only tangentially related to our aim. Disagreements regarding study inclusion were resolved by consensus. Drs. Lai, Barsuk, and Mourad identified additional studies by hand review of reference lists and content experts (Figure 1).

Conceptual Framework

All selected articles were categorized by temporal relationship to thoracentesis as pre-, intra-, or postprocedure. Pre-procedural topics were those outcomes that had been identified and addressed before attempting thoracentesis, such as physician training or perceived risks of harm. Intraprocedural considerations included aspects such as use of bedside US, pleural manometry, and large-volume drainage. Finally, postprocedural factors were those related to evaluation after thoracentesis, such as follow-up imaging. This conceptual framework is outlined in Figure 2.

The PubMed search returned a total of 1170 manuscripts, of which 56 articles met inclusion criteria. Four additional articles were identified by experts and included in the study.^4-7 Therefore, 60 articles were identified and included in this review. Study designs included cohort studies, case control studies, systematic reviews, meta-analyses, narrative reviews, consensus guidelines, and randomized controlled trials. A summary of all included articles by topic can be found in the Table.
 

PRE-PROCEDURAL CONSIDERATIONS

Physician Training

Studies indicate that graduate medical education may not adequately prepare clinicians to perform thoracentesis.⁸ In fact, residents have the least exposure and confidence in performing thoracentesis when compared to other bedside procedures.^9,10 In 1 survey, 69% of medical trainees desired more exposure to procedures, and 98% felt that procedural skills were important to master.¹¹ Not surprisingly, then, graduating internal medicine residents perform poorly when assessed on a thoracentesis simulator.¹²

Supplemental training outside of residency is useful to develop and maintain skills for thoracentesis, such as simulation with direct observation in a zero-risk environment. In 1 study, “simulation-based mastery learning” combined an educational video presentation with repeated, deliberate practice on a simulator until procedural competence was acquired, over two 2-hour sessions. In this study, 40 third-year medicine residents demonstrated a 71% improvement in clinical skills performance after course completion, with 93% achieving a passing score. The remaining 7% also achieved passing scores with extra practice time.¹² Others have built upon the concept of simulation-based training. For instance, 2 studies suggest that use of a simulation-based curriculum improved both thoracentesis knowledge and performance skills in a 3-hour session.^13,14 Similarly, 1 prospective study reported that a half-day thoracentesis workshop using simulation and 1:1 direct observation successfully lowered pneumothorax rates from 8.6% to 1.8% in a group of practicing clinicians. Notably, additional interventions including use of bedside US, limiting operators to a focused group, and standardization of equipment were also a part of this quality improvement initiative.⁷ Although repetition is required to gain proficiency when using a simulator, performance and confidence appear to plateau with only 4 simulator trials. In medical students, improvements derived through simulator-based teaching were sustained when retested 6 months following training.¹⁵

An instrument to ensure competency is necessary, given variability in procedural experience among both new graduates and practicing physicians,. Our search did not identify any clinically validated tools that adequately assessed thoracentesis performance. However, some have been proposed¹⁶ and 1 validated in a simulation environment.¹² Regarding the incorporation of US for effusion markup, 1 validated tool used an 11-domain assessment covering knowledge of US machine manipulation, recognition of images with common pleural effusion characteristics, and performance of thoracic US with puncture-site marking on a simulator. When used on 22 participants, scores with the tool could reliably differentiate between novice, intermediate, and advanced groups (P < 0.0001).¹⁷

Patient Selection

Coagulopathies and Anticoagulation. Historically, the accepted cutoff for performing thoracentesis is an international normalized ratio (INR) less than 1.5 and a platelet count greater than 50,000/µL. McVay et al.¹⁸ first showed in 1991 that use of these cutoffs was associated with low rates of periprocedural bleeding, leading to endorsement in the British Thoracic Society (BTS) Pleural Disease Guideline 2010.¹⁹ Other recommendations include the 2012 Society for Interventional Radiology guidelines that endorse correction of an INR greater than 2, or platelets less than 50,000/µL, based almost exclusively on expert opinion.⁵

However, data suggest that thoracentesis may be safely performed outside these parameters. For instance, a prospective study of approximately 9000 thoracenteses over 12 years found that patients with an INR of 1.5-2.9 or platelets of 20,000 - 49,000/µL experienced rates of bleeding complications similar to those with normal values.²⁰ Similarly, a 2014 review²¹ found that the overall risk of hemorrhage during thoracentesis in the setting of moderate coagulopathy (defined as an INR of 1.5 - 3 or platelets of 25,000-50,000/µL), was not increased. In 1 retrospective study of more than 1000 procedures, no differences in hemorrhagic events were noted in patients with bleeding diatheses that received prophylactic fresh frozen plasma or platelets vs. those who did not.²² Of note, included studies used a variety of criteria to define a hemorrhagic complication, which included: an isolated 2 g/dL or more decrement in hemoglobin, presence of bloody fluid on repeat tap with associated hemoglobin decrement, rapid re-accumulation of fluid with a hemoglobin decrement, or transfusion of 2 units or more of whole blood.

Whether it is safe to perform thoracentesis on patients taking antiplatelet therapy is less well understood. Although data are limited, a few small-scale studies^23,24 suggest that hemorrhagic complications following thoracentesis in patients receiving clopidogrel are comparable to the general population. We found no compelling data regarding the safety of thoracentesis in the setting of direct oral anticoagulants, heparin, low-molecular weight heparin, or intravenous direct thrombin inhibitors. Current practice is to generally avoid thoracentesis while these therapeutic anticoagulants are used.

Invasive mechanical ventilation. Pleural effusion is common in patients in the intensive care unit, including those requiring mechanical ventilation.²⁵ Thoracentesis in this population is clinically important: fluid analysis in 1 study was shown to aid the diagnosis in 45% of cases and changes in treatment in 33%.²⁶ However, clinicians may be reluctant to perform thoracentesis on patients who require mechanical ventilation, given the perception of a greater risk of pneumothorax from positive pressure ventilation.

Despite this concern, a 2011 meta-analysis including 19 studies and more than 1100 patients revealed rates of pneumothorax and hemothorax comparable to nonventilated patients.²⁵ Furthermore, a 2015 prospective study that examined thoracentesis in 1377 mechanically ventilated patients revealed no difference in complication rates as well.²⁰ Therefore, evidence suggests that performance of thoracentesis in mechanically ventilated patients is not contraindicated.

Skin Disinfection and Antisepsis Precautions

The 2010 BTS guidelines list empyema and wound infection as possible complications of thoracentesis.¹⁹ However, no data regarding incidence are provided. Additionally, an alcohol-based skin cleanser (such as 2% chlorhexidine gluconate/70% isopropyl alcohol), along with sterile gloves, field, and dressing are suggested as precautionary measures.¹⁹ In 1 single-center registry of 2489 thoracenteses performed using alcohol or iodine-based antiseptic and sterile drapes, no postprocedure infections were identified.²⁷ Of note, we did not find other studies (including case reports) that reported either incidence or rate of infectious complications such as wound infection and empyema. In an era of modern skin antiseptics that have effectively reduced complications such as catheter-related bloodstream infection,²⁸ the incidence of this event is thus likely to be low.

INTRAPROCEDURAL CONSIDERATIONS

Use of Bedside Ultrasound

Portable US has particular advantages for evaluation of pleural effusion vs other imaging modalities. Compared with computerized tomography (CT), bedside US offers similar performance but is less costly, avoids both radiation exposure and need for patient transportation, and provides results instantaneously.^29,30 Compared to chest x-ray (CXR), US is more sensitive at detecting the presence, volume, and characteristics of pleural fluid^30,31 and can be up to 100% sensitive for effusions greater than 100 mL.²⁹ Furthermore, whereas CXR typically requires 200 mL of fluid to be present for detection of an effusion, US can reliably detect as little as 20 mL of fluid.²⁹ When US was used to confirm thoracentesis puncture sites in a study involving 30 physicians of varying experience and 67 consecutive patients, 15% of sites found by clinical exam were inaccurate (less than 10 mm fluid present), 10% were at high risk for organ puncture, and a suitable fluid pocket was found 54% of times when exam could not.⁴

A 2010 meta-analysis of 24 studies and 6605 thoracenteses estimated the overall rate of pneumothorax at 6%; however, procedures performed with US guidance were associated with a 70% reduced risk of this event (odds ratio, 0.30; 95% confidence interval, 0.20 - 0.70).³² In a 2014 randomized control trial of 160 patients that compared thoracentesis with US guidance for site marking vs no US use, 10 pneumothoraces occurred in the control group vs 1 in the US group (12.5% vs 1.25%, P = 0.009).³³ Similarly, another retrospective review of 445 consecutive patients with malignant effusions revealed a pneumothorax rate of 0.97% using US in real time during needle insertion compared to 8.89% for unguided thoracenteses (P < 0.0001).³⁴ Several other studies using US guidance for either site markup or in real time reported similar pneumothorax rates, ranging from 1.1% - 4.8%.^35-37 However, it is unclear if real-time US specifically provides an additive effect vs site marking alone, as no studies directly comparing the 2 methods were found.

Benefits of US also include a higher rate of procedural success, with 1 study demonstrating a 99% success rate when using US vs. 90% without (P = 0.030).³³ A larger volume of fluid removed has been observed with US use as well, and methods have been described using fluid-pocket depth to guide puncture site localization and maximize drainage.³⁸ Finally, US use for thoracentesis has been associated with lower costs and length of stay.^39,40

Intercostal Artery Localization

Although rare (incidence, 0.18%-2%^20,21,39), the occurrence of hemothorax following thoracentesis is potentially catastrophic. This serious complication is often caused by laceration of the intercostal artery (ICA) or 1 of its branches during needle insertion.⁴¹

While risk of injury is theoretically reduced by needle insertion superior to the rib, studies using cadaver dissection and 3D angiography show significant tortuosity of the ICA.^6,41-43 The degree of tortuosity is increased within 6 cm of the midline, in more cephalad rib spaces, and in the elderly (older than 60 years).^41-43 Furthermore, 1 cadaveric study also demonstrated the presence of arterial collaterals branching off the ICA at multiple intercostal spaces, ranging between 8 cm and 11 cm from the midline.⁴¹ This anatomic variability may explain why some have observed low complication and hemothorax rates with an extreme lateral approach.³⁵ Bedside US with color flow Doppler imaging has been used to identify the ICA, with 88% sensitivity compared to CT imaging while adding little to exam time.^44,45 Of note, a 37% drop in the rate of hemothorax was observed in 1 study with routine US guidance alone.³⁹

Pleural Pressure Monitoring and Large-Volume Thoracentesis

While normal intrapleural pressures are approximately -5 to -10 cm H₂O,⁴⁶ the presence of a pleural effusion creates a complex interaction between fluid, compressed lung, and chest wall that can increase these pressures.⁴⁷ During drainage of an effusion, pleural pressures may rapidly drop, provoking re-expansion pulmonary edema (REPE). While rare (0 -1%), clinically-diagnosed REPE is a serious complication that can lead to rapid respiratory failure and death.^20,48 REPE is postulated to be caused by increased capillary permeability resulting from inflammation, driven by rapid re-inflation of the lung when exposed to highly negative intrapleural pressures.^47,49

Measurement of intrapleural pressure using a water manometer during thoracentesis may minimize REPE by terminating fluid drainage when intrapleural pressure begins to drop rapidly.^50,51 A cutoff of -20 cm H₂O has been cited repeatedly as safe since being suggested by Light in 1980, but this is based on animal models.^50,52 In 1 prospective study of 185 thoracenteses in which manometry was performed, 15% of patients had intrapleural pressure drop to less than -20 cm H₂O (at which point the procedure was terminated) but suffered no REPE.⁵⁰

Manometry is valuable in the identification of an unexpandable or trapped lung when pleural pressures drop rapidly with only minimal fluid volume removal.^47,53 Other findings correlated with an unexpandable lung include a negative opening pressure⁴⁷ and large fluctuations in pressure during the respiratory cycle.⁵⁴

While development of symptoms (eg, chest pain, cough, or dyspnea) is often used as a surrogate, the correlation between intrapleural pressure and patient symptoms is inconsistent and not a reliable proxy.⁵⁵ One study found that 22% of patients with chest pain during thoracentesis had intrapleural pressures lower than -20 cm H₂O compared with 8.6% of asymptomatic patients,⁵⁶ but it is unclear if the association is causal.

Thoracentesis is often performed for symptomatic relief and removal of large fluid volume. However, it remains common to halt fluid removal after 1.5 L, a threshold endorsed by BTS.¹⁹ While some investigators have suggested that removal of 2 L or more of pleural fluid does not compromise safety,^57,58 a 4- to 5-fold rise in the risk of pneumothorax was noted in 2 studies.^20,59 when more than 1.5 L of fluid was removed. The majority of these may be related to pneumothorax ex vacuo, a condition in which fluid is drained from the chest, but the lung is unable to expand and fill the space (eg, “trapped lung”), resulting in a persistent pneumothorax. This condition generally does not require treatment.⁶⁰ When manometry is employed at 200-mL intervals with termination at an intrapleural pressure of less than 20 mm H₂O, drainage of 3 L or more has been reported with low rates of pneumothorax and very low rates of REPE.^50,51 However, whether this is cause and effect is unknown because REPE is rare, and more work is needed to determine the role of manometry for its prevention.

POSTPROCEDURAL CONSIDERATIONS

Postprocedure Imaging

Performing an upright CXR following thoracentesis is a practice that remains routinely done by many practitioners to monitor for complications. Such imaging was also endorsed by the American Thoracic Society guidelines.⁶¹ However, more recent data question the utility of this practice. Multiple studies have confirmed that post-thoracentesis CXR is unnecessary unless clinical suspicion for pneumothorax or REPE is present.^36,58,62,63 The BTS guidelines also advocate this approach.¹⁹ Interestingly, a potentially more effective way to screen for postprocedure complications is through bedside US, which has been shown to be more sensitive than CXR in detecting pneumothorax.⁶⁴ In 1 study of 185 patients, bedside US demonstrated a sensitivity of 88% and a specificity of 97% for diagnosing pneumothorax in patients with adequate quality scans, with positive and negative likelihood ratios of 55 and 0.17, respectively.⁶⁵

Thoracentesis remains a core procedural skill for hospitalists, critical care physicians, and emergency physicians. It is the foundational component when investigating and treating pleural effusions. When the most current training, techniques, and technology are used, data suggest this procedure is safe to perform at the bedside. Our review highlights these strategies and evaluates which aspects might be most applicable to clinical practice.

Our findings have several implications for those who perform this procedure. First, appropriate training is central to procedural safety, and both simulation and direct observation by procedural experts have been shown by multiple investigators to improve knowledge and skill. This training should integrate the use of US in performing a focused thoracic exam.

Second, recommendations regarding coagulopathy and a “safe cutoff” of an INR less than 1.5 or platelets greater than 50,000/µL had limited evidentiary support. Rather, multiple studies suggest no difference in bleeding risk following thoracentesis with an INR as high as 3.0 and platelets greater than 25,000/µL. Furthermore, prophylactic transfusion with fresh frozen plasma or platelets before thoracentesis did not alter bleeding risk and exposes patients to transfusion complications. Thus, routine use of this practice can no longer be recommended. Third, further research is needed to understand the bleeding risk for patients on antiplatelet medications, heparin products, and also direct oral anticoagulants, given the growing popularity in their use and the potential consequences of even temporary cessation. Regarding patients on mechanical ventilation, thoracentesis demonstrated no difference in complication rates vs. the general population, and its performance in this population is encouraged when clinically indicated.

Intraprocedural considerations include the use of bedside US. Due to multiple benefits including effusion characterization, puncture site localization, and significantly lower rates of pneumothorax, the standard of care should be to perform thoracentesis with US guidance. Both use of US to mark an effusion immediately prior to puncture or in real time during needle insertion demonstrated benefit; however, it is unclear if 1 method is superior because no direct comparison studies were found. Further work is needed to investigate this potential.

Our review suggests that the location and course of the ICA is variable, especially near the midline, in the elderly, and in higher intercostal spaces, leaving it vulnerable to laceration. We recommend physicians only attempt thoracentesis at least 6 cm lateral to the midline due to ICA tortuosity and, ideally, 12 cm lateral, to avoid the presence of collaterals. Although only 2 small-scale studies were found pertaining to the use of US in identifying the ICA, we encourage physicians to consider learning how to screen for its presence as a part of their routine thoracic US exam in the area underlying the planned puncture site.

Manometry is beneficial because it can diagnose a nonexpandable lung and allows for pleural pressure monitoring.^52,53 A simple U-shaped manometer can be constructed from intravenous tubing included in most thoracentesis kits, which adds little to overall procedure time. While low rates of REPE have been observed when terminating thoracentesis if pressures drop below -20 cm H₂O or chest pain develops, neither measure appears to have reliable predictive value, limiting clinical utility. Further work is required to determine if a “safe pressure cutoff” exists. In general, we recommend the use of manometry when a nonexpandable (trapped) lung is suspected, because large drops in intrapleural pressure, a negative opening pressure, and respiratory variation can help confirm the diagnosis and avoid pneumothorax ex vacuo or unnecessary procedures in the future. As this condition appears to be more common in the setting of larger effusions, use of manometry when large-volume thoracenteses are planned is also reasonable.

Postprocedurally, routine imaging after thoracentesis is not recommended unless there is objective concern for complication. When indicated, bedside US is better positioned for this role compared with CXR, because it is more sensitive in detecting pneumothorax, provides instantaneous results, and avoids radiation exposure.

Our review has limitations. First, we searched only for articles between defined time periods, restricted our search to a single database, and excluded non-English articles. This has the potential to introduce selection bias, as nonprimary articles that fall within our time restrictions may cite older studies that are outside our search range. To minimize this effect, we performed a critical review of all included studies, especially nonprimary articles. Second, despite the focus of our search strategy to identify any articles related to patient safety and adverse events, we cannot guarantee that all relevant articles for any particular complication or risk factor were captured given the lack of more specific search terms. Third, although we performed a systematic search of the literature, we did not perform a formal systematic review or formally grade included studies. As the goal of our review was to categorize and operationalize clinical aspects, this approach was necessary, and we acknowledge that the quality of studies is variable. Lastly, we aimed to generate clinical recommendations for physicians performing thoracentesis at the bedside; others reviewing this literature may find or emphasize different aspects relevant to practice outside this setting.

In conclusion, evaluation and treatment of pleural effusions with bedside thoracentesis is an important skill for physicians of many disciplines. The evidence presented in this review will help inform the process and ensure patient safety. Physicians should consider incorporating these recommendations into their practice.

Acknowledgments

The authors thank Whitney Townsend, MLIS, health sciences informationist, for assistance with serial literature searches.

Disclosure

Nothing to report.