Nita Shrikant Kulkarni, MD

Clinical question: Does acetazolamide decrease the duration of mechanical ventilation for patients with chronic obstructive pulmonary disease and metabolic alkalosis?

Bottom line: Although acetazolamide effectively decreased the levels of serum bicarbonate and the number of days with metabolic alkalosis in critically ill patients with chronic obstructive pulmonary disease (COPD) on mechanical ventilation, it did not produce a statistically significant difference in the duration of mechanical ventilation. However, this lack of statistical significance may have been due to an underpowered study. (LOE = 1b-)

Reference: Faisy C, Meziani F, Planquette B, et al, for the DIABOLO Investigators. Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease. JAMA 2016;315(5):480-488.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis:

Acetazolamide is used as a respiratory stimulant for patients with COPD and metabolic alkalosis because of its ability to reduce serum bicarbonate, which may lead to a rise in minute ventilation. However, its clinical benefit has not been demonstrated previously in controlled trials.

Using concealed allocation, these investigators randomized patients with COPD who required invasive mechanical ventilation to receive either acetazolamide 500 mg intravenously twice daily (1000 mg if loop diuretics were also prescribed) or matching placebo up to 28 days. Only those patients found to have pure or mixed metabolic alkalosis received the treatment. The intention-to-treat population consisted of 380 patients and baseline characteristics were similar in both groups. The use of acetazolamide led to decreased levels of serum bicarbonate and fewer days with metabolic alkalosis but did not improve respiratory parameters such as respiratory rate, tidal volume, or minute ventilation.

For the primary outcome of duration of mechanical ventilation, the magnitude of the difference between the 2 groups was large, suggesting a clinically important effect, but the difference did not reach statistical significance (between-group difference -16 hours with acetazolamide; 95% CI -36.5 to 4.0 hours). The lack of statistical significance may be due to an underpowered study because of fewer-than-expected patients who received the treatment (more than 20% of patients in each group did not receive the assigned treatment because of lack of metabolic alkalosis or temporary contraindications) and a shorter-than-anticipated duration of mechanical ventilation in the placebo group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does acetazolamide decrease the duration of mechanical ventilation for patients with chronic obstructive pulmonary disease and metabolic alkalosis?

Bottom line: Although acetazolamide effectively decreased the levels of serum bicarbonate and the number of days with metabolic alkalosis in critically ill patients with chronic obstructive pulmonary disease (COPD) on mechanical ventilation, it did not produce a statistically significant difference in the duration of mechanical ventilation. However, this lack of statistical significance may have been due to an underpowered study. (LOE = 1b-)

Reference: Faisy C, Meziani F, Planquette B, et al, for the DIABOLO Investigators. Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease. JAMA 2016;315(5):480-488.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis:

Acetazolamide is used as a respiratory stimulant for patients with COPD and metabolic alkalosis because of its ability to reduce serum bicarbonate, which may lead to a rise in minute ventilation. However, its clinical benefit has not been demonstrated previously in controlled trials.

Using concealed allocation, these investigators randomized patients with COPD who required invasive mechanical ventilation to receive either acetazolamide 500 mg intravenously twice daily (1000 mg if loop diuretics were also prescribed) or matching placebo up to 28 days. Only those patients found to have pure or mixed metabolic alkalosis received the treatment. The intention-to-treat population consisted of 380 patients and baseline characteristics were similar in both groups. The use of acetazolamide led to decreased levels of serum bicarbonate and fewer days with metabolic alkalosis but did not improve respiratory parameters such as respiratory rate, tidal volume, or minute ventilation.

For the primary outcome of duration of mechanical ventilation, the magnitude of the difference between the 2 groups was large, suggesting a clinically important effect, but the difference did not reach statistical significance (between-group difference -16 hours with acetazolamide; 95% CI -36.5 to 4.0 hours). The lack of statistical significance may be due to an underpowered study because of fewer-than-expected patients who received the treatment (more than 20% of patients in each group did not receive the assigned treatment because of lack of metabolic alkalosis or temporary contraindications) and a shorter-than-anticipated duration of mechanical ventilation in the placebo group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does acetazolamide decrease the duration of mechanical ventilation for patients with chronic obstructive pulmonary disease and metabolic alkalosis?

Bottom line: Although acetazolamide effectively decreased the levels of serum bicarbonate and the number of days with metabolic alkalosis in critically ill patients with chronic obstructive pulmonary disease (COPD) on mechanical ventilation, it did not produce a statistically significant difference in the duration of mechanical ventilation. However, this lack of statistical significance may have been due to an underpowered study. (LOE = 1b-)

Reference: Faisy C, Meziani F, Planquette B, et al, for the DIABOLO Investigators. Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease. JAMA 2016;315(5):480-488.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis:

Acetazolamide is used as a respiratory stimulant for patients with COPD and metabolic alkalosis because of its ability to reduce serum bicarbonate, which may lead to a rise in minute ventilation. However, its clinical benefit has not been demonstrated previously in controlled trials.

Using concealed allocation, these investigators randomized patients with COPD who required invasive mechanical ventilation to receive either acetazolamide 500 mg intravenously twice daily (1000 mg if loop diuretics were also prescribed) or matching placebo up to 28 days. Only those patients found to have pure or mixed metabolic alkalosis received the treatment. The intention-to-treat population consisted of 380 patients and baseline characteristics were similar in both groups. The use of acetazolamide led to decreased levels of serum bicarbonate and fewer days with metabolic alkalosis but did not improve respiratory parameters such as respiratory rate, tidal volume, or minute ventilation.

For the primary outcome of duration of mechanical ventilation, the magnitude of the difference between the 2 groups was large, suggesting a clinically important effect, but the difference did not reach statistical significance (between-group difference -16 hours with acetazolamide; 95% CI -36.5 to 4.0 hours). The lack of statistical significance may be due to an underpowered study because of fewer-than-expected patients who received the treatment (more than 20% of patients in each group did not receive the assigned treatment because of lack of metabolic alkalosis or temporary contraindications) and a shorter-than-anticipated duration of mechanical ventilation in the placebo group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is tamsulosin effective in the management of distal ureteric stones?

Bottom line: Tamsulosin promotes stone passage of ureteric stones that are 5 mm to 10 mm. You would need to treat 5 patients with tamsulosin to cause the expulsion of one such stone. Stones smaller than 5 mm have a high rate of spontaneous passage without any intervention. (LOE = 1b-)

Reference: Furyk JS, Chu K, Banks C et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67(1):86-95.

Study design: Randomized controlled trial (double-blinded)

Funding source: Foundation

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis: These authors recruited adult patients who presented to the emergency department with symptoms and imaging consistent with distal ureteric stones. Patients with fever, hypotension, stones larger than 10 mm, or kidney disease were excluded. Using concealed allocation, the investigators randomized the patients to receive either tamsulosin 0.4 mg daily or matching placebo for 28 days or until stone passage. The 2 groups had similar baseline characteristics and analysis was by intention to treat.

The primary outcome was stone expulsion as confirmed by computed tomography (CT) and time to stone expulsion was defined by self-reported passage of stone or 48-hour pain-free period. Compliance to the study medications was poor in both groups, and almost one-fifth of the patients did not have follow-up imaging. Of the approximately 80% of patients in each group who underwent follow-up CT, there was no difference in the percentage of patients with passed stones (87% in the tamsulosin group vs 82% in the placebo group; P = .22). In the subset of patients with larger stones (5 mm -10 mm), the tamsulosin group had a significantly higher rate of stone passage than the placebo group (83% vs 61%; P = .03). There were no significant differences detected in time to stone passage, pain, analgesia requirements, need for urological intervention, or adverse events.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is tamsulosin effective in the management of distal ureteric stones?

Bottom line: Tamsulosin promotes stone passage of ureteric stones that are 5 mm to 10 mm. You would need to treat 5 patients with tamsulosin to cause the expulsion of one such stone. Stones smaller than 5 mm have a high rate of spontaneous passage without any intervention. (LOE = 1b-)

Reference: Furyk JS, Chu K, Banks C et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67(1):86-95.

Study design: Randomized controlled trial (double-blinded)

Funding source: Foundation

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis: These authors recruited adult patients who presented to the emergency department with symptoms and imaging consistent with distal ureteric stones. Patients with fever, hypotension, stones larger than 10 mm, or kidney disease were excluded. Using concealed allocation, the investigators randomized the patients to receive either tamsulosin 0.4 mg daily or matching placebo for 28 days or until stone passage. The 2 groups had similar baseline characteristics and analysis was by intention to treat.

The primary outcome was stone expulsion as confirmed by computed tomography (CT) and time to stone expulsion was defined by self-reported passage of stone or 48-hour pain-free period. Compliance to the study medications was poor in both groups, and almost one-fifth of the patients did not have follow-up imaging. Of the approximately 80% of patients in each group who underwent follow-up CT, there was no difference in the percentage of patients with passed stones (87% in the tamsulosin group vs 82% in the placebo group; P = .22). In the subset of patients with larger stones (5 mm -10 mm), the tamsulosin group had a significantly higher rate of stone passage than the placebo group (83% vs 61%; P = .03). There were no significant differences detected in time to stone passage, pain, analgesia requirements, need for urological intervention, or adverse events.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is tamsulosin effective in the management of distal ureteric stones?

Bottom line: Tamsulosin promotes stone passage of ureteric stones that are 5 mm to 10 mm. You would need to treat 5 patients with tamsulosin to cause the expulsion of one such stone. Stones smaller than 5 mm have a high rate of spontaneous passage without any intervention. (LOE = 1b-)

Reference: Furyk JS, Chu K, Banks C et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67(1):86-95.

Study design: Randomized controlled trial (double-blinded)

Funding source: Foundation

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis: These authors recruited adult patients who presented to the emergency department with symptoms and imaging consistent with distal ureteric stones. Patients with fever, hypotension, stones larger than 10 mm, or kidney disease were excluded. Using concealed allocation, the investigators randomized the patients to receive either tamsulosin 0.4 mg daily or matching placebo for 28 days or until stone passage. The 2 groups had similar baseline characteristics and analysis was by intention to treat.

The primary outcome was stone expulsion as confirmed by computed tomography (CT) and time to stone expulsion was defined by self-reported passage of stone or 48-hour pain-free period. Compliance to the study medications was poor in both groups, and almost one-fifth of the patients did not have follow-up imaging. Of the approximately 80% of patients in each group who underwent follow-up CT, there was no difference in the percentage of patients with passed stones (87% in the tamsulosin group vs 82% in the placebo group; P = .22). In the subset of patients with larger stones (5 mm -10 mm), the tamsulosin group had a significantly higher rate of stone passage than the placebo group (83% vs 61%; P = .03). There were no significant differences detected in time to stone passage, pain, analgesia requirements, need for urological intervention, or adverse events.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Do peripherally inserted central catheters increase the risk for upper- and lower-extremity deep venous thromboses?

Bottom line: Although the association between peripherally inserted central catheters (PICCs) and upper-extremity deep venous thromboses (DVTs) was already known, this study shows that PICCs are also associated with a greater risk of lower-extremity DVTs, suggesting that PICC insertion in itself may be a trigger for thrombosis. (LOE = 2b)

Reference: Greene MT, Flander SA, Woller SC, Bernstein SJ, Chopra V. The association between PICC use and venous thromboembolism in upper and lower extremities. Am J Med 2015;128(9):986–993.

Study design: Cohort (retrospective)

Funding source: Industry

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using a statewide registry as well as individual medical records, these investigators collected data for 76,242 hospitalized patients to examine the association between PICC placement and venous thromboembolism (VTE). Patients with a history of VTE, those undergoing surgery, those admitted to an intensive care unit, and those under observation were excluded. Patients were followed up for 90 days after index hospitalization to identify the development of symptomatic pulmonary emboli or upper- or lower-extremity proximal DVTs.

Overall, 5% of the cohort had PICCs present on admission or placed during the hospitalization. As compared with those without PICCs, patients with PICCs were more likely to be older than 70 years; have recent surgery or history of VTE; and have diabetes, inflammatory bowel disease, sepsis, or pneumonia. After adjusting for other risk factors for VTE, the presence of a PICC was not only associated with risk of upper-extremity DVT (hazard ratio [HR] = 10.49; 95% CI 7.79-14.11; P < .001), but also modestly associated with risk of lower-extremity DVT (HR = 1.48; 1.02-2.15; P = .038). The authors hypothesize that PICC line insertion may trigger a systemic thrombosis leading to DVTs in different locations, including the lower extremities. There was no significant association with pulmonary embolism.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Do peripherally inserted central catheters increase the risk for upper- and lower-extremity deep venous thromboses?

Bottom line: Although the association between peripherally inserted central catheters (PICCs) and upper-extremity deep venous thromboses (DVTs) was already known, this study shows that PICCs are also associated with a greater risk of lower-extremity DVTs, suggesting that PICC insertion in itself may be a trigger for thrombosis. (LOE = 2b)

Reference: Greene MT, Flander SA, Woller SC, Bernstein SJ, Chopra V. The association between PICC use and venous thromboembolism in upper and lower extremities. Am J Med 2015;128(9):986–993.

Study design: Cohort (retrospective)

Funding source: Industry

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using a statewide registry as well as individual medical records, these investigators collected data for 76,242 hospitalized patients to examine the association between PICC placement and venous thromboembolism (VTE). Patients with a history of VTE, those undergoing surgery, those admitted to an intensive care unit, and those under observation were excluded. Patients were followed up for 90 days after index hospitalization to identify the development of symptomatic pulmonary emboli or upper- or lower-extremity proximal DVTs.

Overall, 5% of the cohort had PICCs present on admission or placed during the hospitalization. As compared with those without PICCs, patients with PICCs were more likely to be older than 70 years; have recent surgery or history of VTE; and have diabetes, inflammatory bowel disease, sepsis, or pneumonia. After adjusting for other risk factors for VTE, the presence of a PICC was not only associated with risk of upper-extremity DVT (hazard ratio [HR] = 10.49; 95% CI 7.79-14.11; P < .001), but also modestly associated with risk of lower-extremity DVT (HR = 1.48; 1.02-2.15; P = .038). The authors hypothesize that PICC line insertion may trigger a systemic thrombosis leading to DVTs in different locations, including the lower extremities. There was no significant association with pulmonary embolism.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Do peripherally inserted central catheters increase the risk for upper- and lower-extremity deep venous thromboses?

Bottom line: Although the association between peripherally inserted central catheters (PICCs) and upper-extremity deep venous thromboses (DVTs) was already known, this study shows that PICCs are also associated with a greater risk of lower-extremity DVTs, suggesting that PICC insertion in itself may be a trigger for thrombosis. (LOE = 2b)

Reference: Greene MT, Flander SA, Woller SC, Bernstein SJ, Chopra V. The association between PICC use and venous thromboembolism in upper and lower extremities. Am J Med 2015;128(9):986–993.

Study design: Cohort (retrospective)

Funding source: Industry

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using a statewide registry as well as individual medical records, these investigators collected data for 76,242 hospitalized patients to examine the association between PICC placement and venous thromboembolism (VTE). Patients with a history of VTE, those undergoing surgery, those admitted to an intensive care unit, and those under observation were excluded. Patients were followed up for 90 days after index hospitalization to identify the development of symptomatic pulmonary emboli or upper- or lower-extremity proximal DVTs.

Overall, 5% of the cohort had PICCs present on admission or placed during the hospitalization. As compared with those without PICCs, patients with PICCs were more likely to be older than 70 years; have recent surgery or history of VTE; and have diabetes, inflammatory bowel disease, sepsis, or pneumonia. After adjusting for other risk factors for VTE, the presence of a PICC was not only associated with risk of upper-extremity DVT (hazard ratio [HR] = 10.49; 95% CI 7.79-14.11; P < .001), but also modestly associated with risk of lower-extremity DVT (HR = 1.48; 1.02-2.15; P = .038). The authors hypothesize that PICC line insertion may trigger a systemic thrombosis leading to DVTs in different locations, including the lower extremities. There was no significant association with pulmonary embolism.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For pleurodesis, do nonsteroidal anti-inflammatory drugs and smaller chest tubes, as compared with opioids and larger tubes, provide better pain relief while maintaining efficacy of the procedure?

Bottom line: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are not necessarily more effective than opiates for pain relief after pleurodesis, they should be considered a safe and effective analgesic option for these patients. NSAIDs do not lead to higher rates of pleurodesis failure. Using a smaller chest tube, on the other hand, does not provide a clinically significant pain benefit and may ultimately lead to a higher rate of pleurodesis failure. (LOE = 1b)

Reference: Rahman NM, Pepperell J, Rehal S, et al. Effect of opioids vs NSAIDs and larger vs smaller chest tube size on pain control and pleurodesis efficacy among patients with malignant pleural effusion. JAMA 2015;314(24):2614–2653.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using concealed allocation, these investigators randomized 320 patients requiring pleurodesis for malignant pleural effusions to receive either NSAIDs or opioids and small or large (12F vs 24F) chest tubes. Patients who underwent thoracoscopy, which necessitates a 24F tube postprocedure, were randomized to receive either NSAIDs or opiates but were not included in the chest tube size analysis. Those who did not undergo thoracoscopy were randomized into both arms of the trial, either NSAIDs or opiates and either 12F or 24F chest tubes.

The NSAID groups received 800 mg ibuprofen 3 times daily as needed; the opiate groups received 10 mg to 20 mg oral morphine up to 4 times daily. The patients were not masked to any of the interventions. All patients also received scheduled 1g acetaminophen 4 times daily and intravenous morphine as needed for breakthrough pain. Pain was measured using a 100-mm visual analog scale. Pleurodesis failure was defined as requiring another pleural intervention within 3 months after randomization. Patients had similar baseline characteristics in all treatment groups, except for more men in the larger chest tube group.

Overall, there was no significant difference detected in mean pain scores while the chest tube was in place in the NSAID group as compared with the opiate group, but the NSAID group required more breakthrough intravenous morphine than the opiate group (38% vs 26%; P = .003). Patients in the smaller chest tube group reported less pain than the larger tube group (mean visual analog scale score = 22 mm vs 27 mm; P = .04). Although this finding was statistically significant, the absolute difference in pain scores was small and not necessarily clinically meaningful. For pleurodesis failure, the NSAID group was noninferior to the opiate group; however, the smaller chest tube group had a higher rate of pleurodesis failure and did not meet noninferiority criteria. Pain scores at 1 or 3 months, adverse events, and mortality did not differ for either of the comparisons.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For pleurodesis, do nonsteroidal anti-inflammatory drugs and smaller chest tubes, as compared with opioids and larger tubes, provide better pain relief while maintaining efficacy of the procedure?

Bottom line: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are not necessarily more effective than opiates for pain relief after pleurodesis, they should be considered a safe and effective analgesic option for these patients. NSAIDs do not lead to higher rates of pleurodesis failure. Using a smaller chest tube, on the other hand, does not provide a clinically significant pain benefit and may ultimately lead to a higher rate of pleurodesis failure. (LOE = 1b)

Reference: Rahman NM, Pepperell J, Rehal S, et al. Effect of opioids vs NSAIDs and larger vs smaller chest tube size on pain control and pleurodesis efficacy among patients with malignant pleural effusion. JAMA 2015;314(24):2614–2653.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using concealed allocation, these investigators randomized 320 patients requiring pleurodesis for malignant pleural effusions to receive either NSAIDs or opioids and small or large (12F vs 24F) chest tubes. Patients who underwent thoracoscopy, which necessitates a 24F tube postprocedure, were randomized to receive either NSAIDs or opiates but were not included in the chest tube size analysis. Those who did not undergo thoracoscopy were randomized into both arms of the trial, either NSAIDs or opiates and either 12F or 24F chest tubes.

The NSAID groups received 800 mg ibuprofen 3 times daily as needed; the opiate groups received 10 mg to 20 mg oral morphine up to 4 times daily. The patients were not masked to any of the interventions. All patients also received scheduled 1g acetaminophen 4 times daily and intravenous morphine as needed for breakthrough pain. Pain was measured using a 100-mm visual analog scale. Pleurodesis failure was defined as requiring another pleural intervention within 3 months after randomization. Patients had similar baseline characteristics in all treatment groups, except for more men in the larger chest tube group.

Overall, there was no significant difference detected in mean pain scores while the chest tube was in place in the NSAID group as compared with the opiate group, but the NSAID group required more breakthrough intravenous morphine than the opiate group (38% vs 26%; P = .003). Patients in the smaller chest tube group reported less pain than the larger tube group (mean visual analog scale score = 22 mm vs 27 mm; P = .04). Although this finding was statistically significant, the absolute difference in pain scores was small and not necessarily clinically meaningful. For pleurodesis failure, the NSAID group was noninferior to the opiate group; however, the smaller chest tube group had a higher rate of pleurodesis failure and did not meet noninferiority criteria. Pain scores at 1 or 3 months, adverse events, and mortality did not differ for either of the comparisons.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For pleurodesis, do nonsteroidal anti-inflammatory drugs and smaller chest tubes, as compared with opioids and larger tubes, provide better pain relief while maintaining efficacy of the procedure?

Bottom line: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are not necessarily more effective than opiates for pain relief after pleurodesis, they should be considered a safe and effective analgesic option for these patients. NSAIDs do not lead to higher rates of pleurodesis failure. Using a smaller chest tube, on the other hand, does not provide a clinically significant pain benefit and may ultimately lead to a higher rate of pleurodesis failure. (LOE = 1b)

Reference: Rahman NM, Pepperell J, Rehal S, et al. Effect of opioids vs NSAIDs and larger vs smaller chest tube size on pain control and pleurodesis efficacy among patients with malignant pleural effusion. JAMA 2015;314(24):2614–2653.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Using concealed allocation, these investigators randomized 320 patients requiring pleurodesis for malignant pleural effusions to receive either NSAIDs or opioids and small or large (12F vs 24F) chest tubes. Patients who underwent thoracoscopy, which necessitates a 24F tube postprocedure, were randomized to receive either NSAIDs or opiates but were not included in the chest tube size analysis. Those who did not undergo thoracoscopy were randomized into both arms of the trial, either NSAIDs or opiates and either 12F or 24F chest tubes.

The NSAID groups received 800 mg ibuprofen 3 times daily as needed; the opiate groups received 10 mg to 20 mg oral morphine up to 4 times daily. The patients were not masked to any of the interventions. All patients also received scheduled 1g acetaminophen 4 times daily and intravenous morphine as needed for breakthrough pain. Pain was measured using a 100-mm visual analog scale. Pleurodesis failure was defined as requiring another pleural intervention within 3 months after randomization. Patients had similar baseline characteristics in all treatment groups, except for more men in the larger chest tube group.

Overall, there was no significant difference detected in mean pain scores while the chest tube was in place in the NSAID group as compared with the opiate group, but the NSAID group required more breakthrough intravenous morphine than the opiate group (38% vs 26%; P = .003). Patients in the smaller chest tube group reported less pain than the larger tube group (mean visual analog scale score = 22 mm vs 27 mm; P = .04). Although this finding was statistically significant, the absolute difference in pain scores was small and not necessarily clinically meaningful. For pleurodesis failure, the NSAID group was noninferior to the opiate group; however, the smaller chest tube group had a higher rate of pleurodesis failure and did not meet noninferiority criteria. Pain scores at 1 or 3 months, adverse events, and mortality did not differ for either of the comparisons.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does an early invasive strategy for acute coronary syndrome improve short-term outcomes?

Bottom line: According to this real-world observational study, an early invasive strategy—coronary angiogram within 72 hours of presentation—is associated with lower risks of short-term cardiac death and rehospitalization for myocardial infarction (MI). However, this inference may not be valid because of a lack of key clinical information that may have influenced the data. (LOE = 2b-)

Reference: Hansen KW, Sorensen R, Madsen M, et al. Effectiveness of an early versus a conservative invasive treatment strategy in acute coronary syndromes. Ann Intern Med. 2015;163(10):737-746.

Study design: Cohort (retrospective)

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data from a Danish national registry, these investigators included patients aged 30 years to 90 years who were hospitalized with a first episode of unstable angina or acute MI. Patients were identified as having had an early invasive strategy (diagnostic coronary angiogram within 72 hours of hospitalization) or a conservative invasive strategy (coronary angiogram after 72 hours or no angiogram). The primary outcome was cardiac death or rehospitalization for MI within 60 days.

The investigators used propensity score matching to balance the baseline characteristics of the 2 groups in the initial cohort of 54,000 patients, resulting in 9852 matched patient-pairs. Notably, 42% of the conservative-strategy patients in the propensity-matched cohort received no cardiac catheterization. Overall, treatment with an early invasive strategy was associated with lower risks of cardiac death (5.9% vs 7.6%; number needed to treat [NNT] = 59; P < .001), all-cause death (7.3% vs 10.6%; NNT = 30; P < .001), and rehospitalization for MI (3.4% vs 5%; NNT = 63; P < .001).

However, as an accompanying editorial suggests, the causal inference is not necessarily valid. Given the use of an administrative database, the investigators lacked important clinical information, including indications for the angiograms performed, troponin levels, ejection fractions, and electrocardiogram findings. Without these key data, it is difficult to say whether they were comparing apples to apples, even after propensity score matching. Additionally, the study really just measures the timing of the initial angiogram without taking into account procedures done later that may have affected outcomes. As such, the validity of this study is questionable and, although the results agree with previous randomized clinical trial outcomes, it neither strengthens nor weakens what is already known.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does an early invasive strategy for acute coronary syndrome improve short-term outcomes?

Bottom line: According to this real-world observational study, an early invasive strategy—coronary angiogram within 72 hours of presentation—is associated with lower risks of short-term cardiac death and rehospitalization for myocardial infarction (MI). However, this inference may not be valid because of a lack of key clinical information that may have influenced the data. (LOE = 2b-)

Reference: Hansen KW, Sorensen R, Madsen M, et al. Effectiveness of an early versus a conservative invasive treatment strategy in acute coronary syndromes. Ann Intern Med. 2015;163(10):737-746.

Study design: Cohort (retrospective)

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data from a Danish national registry, these investigators included patients aged 30 years to 90 years who were hospitalized with a first episode of unstable angina or acute MI. Patients were identified as having had an early invasive strategy (diagnostic coronary angiogram within 72 hours of hospitalization) or a conservative invasive strategy (coronary angiogram after 72 hours or no angiogram). The primary outcome was cardiac death or rehospitalization for MI within 60 days.

The investigators used propensity score matching to balance the baseline characteristics of the 2 groups in the initial cohort of 54,000 patients, resulting in 9852 matched patient-pairs. Notably, 42% of the conservative-strategy patients in the propensity-matched cohort received no cardiac catheterization. Overall, treatment with an early invasive strategy was associated with lower risks of cardiac death (5.9% vs 7.6%; number needed to treat [NNT] = 59; P < .001), all-cause death (7.3% vs 10.6%; NNT = 30; P < .001), and rehospitalization for MI (3.4% vs 5%; NNT = 63; P < .001).

However, as an accompanying editorial suggests, the causal inference is not necessarily valid. Given the use of an administrative database, the investigators lacked important clinical information, including indications for the angiograms performed, troponin levels, ejection fractions, and electrocardiogram findings. Without these key data, it is difficult to say whether they were comparing apples to apples, even after propensity score matching. Additionally, the study really just measures the timing of the initial angiogram without taking into account procedures done later that may have affected outcomes. As such, the validity of this study is questionable and, although the results agree with previous randomized clinical trial outcomes, it neither strengthens nor weakens what is already known.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does an early invasive strategy for acute coronary syndrome improve short-term outcomes?

Bottom line: According to this real-world observational study, an early invasive strategy—coronary angiogram within 72 hours of presentation—is associated with lower risks of short-term cardiac death and rehospitalization for myocardial infarction (MI). However, this inference may not be valid because of a lack of key clinical information that may have influenced the data. (LOE = 2b-)

Reference: Hansen KW, Sorensen R, Madsen M, et al. Effectiveness of an early versus a conservative invasive treatment strategy in acute coronary syndromes. Ann Intern Med. 2015;163(10):737-746.

Study design: Cohort (retrospective)

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data from a Danish national registry, these investigators included patients aged 30 years to 90 years who were hospitalized with a first episode of unstable angina or acute MI. Patients were identified as having had an early invasive strategy (diagnostic coronary angiogram within 72 hours of hospitalization) or a conservative invasive strategy (coronary angiogram after 72 hours or no angiogram). The primary outcome was cardiac death or rehospitalization for MI within 60 days.

The investigators used propensity score matching to balance the baseline characteristics of the 2 groups in the initial cohort of 54,000 patients, resulting in 9852 matched patient-pairs. Notably, 42% of the conservative-strategy patients in the propensity-matched cohort received no cardiac catheterization. Overall, treatment with an early invasive strategy was associated with lower risks of cardiac death (5.9% vs 7.6%; number needed to treat [NNT] = 59; P < .001), all-cause death (7.3% vs 10.6%; NNT = 30; P < .001), and rehospitalization for MI (3.4% vs 5%; NNT = 63; P < .001).

However, as an accompanying editorial suggests, the causal inference is not necessarily valid. Given the use of an administrative database, the investigators lacked important clinical information, including indications for the angiograms performed, troponin levels, ejection fractions, and electrocardiogram findings. Without these key data, it is difficult to say whether they were comparing apples to apples, even after propensity score matching. Additionally, the study really just measures the timing of the initial angiogram without taking into account procedures done later that may have affected outcomes. As such, the validity of this study is questionable and, although the results agree with previous randomized clinical trial outcomes, it neither strengthens nor weakens what is already known.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Should steroids be used as adjunctive therapy for patients with community-acquired pneumonia?

Bottom line: Moderate-quality to high-quality evidence suggests that steroids, when added to antibiotics and usual care, can improve outcomes in the treatment of community-acquired pneumonia (CAP). Benefits include reduced hospital length of stay, decreased time to clinical stability, and lower rates of mechanical ventilation and acute respiratory distress syndrome. Steroids may also play a role in preventing deaths, especially in patients with severe CAP; however, the certainty of this evidence is not as clear. Given varying treatment regimens used in the individual studies, the appropriate steroid formulation, dose, and duration of steroids cannot be elucidated from the current set of data. (LOE = 1a)

Reference: Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med. 2015;163(7):519-528.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These authors searched MEDLINE, EMBASE, and the Cochrane Register to find randomized controlled trials that compared the use of steroids with placebo in adults with CAP. Two reviewers independently evaluated studies for eligibility, extracted data, and assessed the included studies for risk of bias. Five of the 13 included studies, whose population made up 70% of the total sample population, had low risk of bias. The treatment groups in the individual studies received different steroid preparations, routes of administration, dosages, and duration of treatment. All groups otherwise received antibiotics and usual care for CAP.

High-quality evidence showed that the use of steroids decreased hospital length of stay by 1 day (3 studies: mean difference: -1.0 day; 95% CI -1.79 to -0.21 days) and decreased time to clinical stability by 1.22 days (5 studies, mean difference: -1.22 days; -2.08 to -0.35 days). Moderate-quality evidence showed that the use of steroids decreased the need for mechanical ventilation (5 studies: relative risk [RR] = 0.45; 0.26-0.79) and the incidence of acute respiratory distress syndrome (4 studies: RR = 0.24; 0.10-0.56).

Finally, data from the 12 trials that assessed all-cause mortality revealed a trend toward decreased risk of death in the steroid group. The difference between the two groups for this end point became statistically significant when only the trials that met the criteria for severe pneumonia were included (6 studies: RR = 0.39; 0.20-0.77). Although steroid use, not surprisingly, increased the risk of significant hyperglycemia (6 studies: RR = 1.49;1.01-2.19), there were no differences detected in the rates of gastrointestinal bleeds, severe neuropsychiatric complications, or rehospitalizations.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular thrombectomy improve clinical outcomes in patients presenting with acute ischemic stroke?

Bottom line: High-quality evidence shows that endovascular therapy using mechanical thrombectomy for the treatment of acute ischemic stroke leads to improved functional outcomes as compared with standard medical therapy with intravenous tissue plasminogen activator (tPA). You would have to treat 8 patients with endovascular therapy to achieve functional independence for 1 patient. (LOE = 1a)

Reference: Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314(17):1832–1843.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including MEDLINE, EMBASE, Google Scholar, and the Cochrane Library to find randomized clinical trials that compared endovascular mechanical thrombectomy with tPA for the treatment of acute ischemic stroke. Three reviewers independently evaluated the studies for eligibility, extracted data from the included studies, and assessed study quality using the Cochrane Collaboration's tool for risk of bias. Ultimately, 8 studies with a total of 2423 patients were included in the review. Most studies used a time window of 6 hours from stroke onset for time to endovascular therapy. The primary outcome was the modified Rankin Scale (mRS) score, which measures the degree of functional disability (a scale of 0 to 6, where 0 = no symptoms, 1 = symptoms but no disability, 5 = severe disability, and 6 = death).

Endovascular thrombectomy led to reduced disability at 90 days (odds ratio = 1.56; 95% CI 1.14-2.13; P = .005). Furthermore, those who received endovascular thrombectomy were more likely to be functionally independent (mRS score of 0, 1, or 2) than those who received tPA (45% vs 32%; P = .005; number needed to treat = 8). There were no significant differences detected in mortality, symptomatic intracranial bleeds, or in-hospital medical complications. Given the high degree of heterogeneity noted in the primary end point, subgroup and sensitivity analyses were performed that showed better functional outcomes in patients with confirmed proximal arterial occlusion, those who received combined tPA and endovascular interventions, and those who had the newer retrievable stent devices used for thrombectomy. More recent studies, as compared with earlier studies, were also more likely to favor endovascular thrombectomy.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of sliding-scale insulin improve blood glucose control in hospitalized patients?

Bottom line: Sliding-scale insulin is commonly used to manage hyperglycemia in hospitalized patients. The evidence suggests that this regimen does not result in better blood glucose control. (LOE = 1a-)

Reference: Lee Y, Lin Y, Leu W et al. Sliding-scale insulin used for blood glucose control: a meta-analysis of randomized controlled trials. Metabolism 2015;64:1183-1192.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including PubMed, EMBASE, and the Cochrane Library to find randomized controlled trials that evaluated the efficacy of sliding-scale insulin to manage hyperglycemia in hospitalized patients. Two authors independently evaluated the studies for inclusion, extracted the data, and performed quality assessments.

Eight of the 11 included studies compared regular insulin sliding scale (RISS) regimens with non–sliding-scale regimens. All RISS regimens consisted of subcutaneous regular insulin injections according to patients' blood glucose levels. Non–sliding-scale regimens consisted of basal-bolus or basal insulin regimens, continuous intravenous insulin infusions, and closed-loop artificial pancreas systems. Target blood glucose levels for individual studies varied greatly and included a range of 100 mg/dL to 150 mg/dL, a goal of less than 140 mg/dL, and a goal of less than 180 mg/dL. Hypoglycemia was generally defined as a glucose level of less than 70 mg/dL, though three of the studies had an even lower cut-off.

In the two studies that evaluated hyperglycemia, one defined it as a glucose level greater than 180 mg/dL while the other defined it as greater than 240 mg/dL. A meta-analysis of relevant data showed no significant difference in the percentage of patients who achieved an average blood glucose level in the target range when comparing RISS with non–sliding-scale regimens. The trend, however, favored the non–sliding-scale group and the difference became significant (relative risk 1.48, 95% CI 1.09-2.02) after one study with a very wide confidence interval was removed. Furthermore, the incidence of hyperglycemia and the mean blood glucose levels were significantly higher in the RISS group.

Although overall hypoglycemic episodes occurred more frequently in the non–sliding-scale group, there was no significant difference detected in the incidence of severe or symptomatic hypoglycemia. Length of hospital stay was also similar in both groups. Finally, one study compared the use of routine diabetes medications plus RISS with routine diabetes medications alone and found no difference in the number of hypoglycemic or hyperglycemic events.

Significant heterogeneity was detected in the results of this meta-analysis and can be attributed to the differing patient populations, insulin regimens, and working definitions in the individual studies as noted above.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of sliding-scale insulin improve blood glucose control in hospitalized patients?

Bottom line: Sliding-scale insulin is commonly used to manage hyperglycemia in hospitalized patients. The evidence suggests that this regimen does not result in better blood glucose control. (LOE = 1a-)

Reference: Lee Y, Lin Y, Leu W et al. Sliding-scale insulin used for blood glucose control: a meta-analysis of randomized controlled trials. Metabolism 2015;64:1183-1192.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including PubMed, EMBASE, and the Cochrane Library to find randomized controlled trials that evaluated the efficacy of sliding-scale insulin to manage hyperglycemia in hospitalized patients. Two authors independently evaluated the studies for inclusion, extracted the data, and performed quality assessments.

Eight of the 11 included studies compared regular insulin sliding scale (RISS) regimens with non–sliding-scale regimens. All RISS regimens consisted of subcutaneous regular insulin injections according to patients' blood glucose levels. Non–sliding-scale regimens consisted of basal-bolus or basal insulin regimens, continuous intravenous insulin infusions, and closed-loop artificial pancreas systems. Target blood glucose levels for individual studies varied greatly and included a range of 100 mg/dL to 150 mg/dL, a goal of less than 140 mg/dL, and a goal of less than 180 mg/dL. Hypoglycemia was generally defined as a glucose level of less than 70 mg/dL, though three of the studies had an even lower cut-off.

In the two studies that evaluated hyperglycemia, one defined it as a glucose level greater than 180 mg/dL while the other defined it as greater than 240 mg/dL. A meta-analysis of relevant data showed no significant difference in the percentage of patients who achieved an average blood glucose level in the target range when comparing RISS with non–sliding-scale regimens. The trend, however, favored the non–sliding-scale group and the difference became significant (relative risk 1.48, 95% CI 1.09-2.02) after one study with a very wide confidence interval was removed. Furthermore, the incidence of hyperglycemia and the mean blood glucose levels were significantly higher in the RISS group.

Although overall hypoglycemic episodes occurred more frequently in the non–sliding-scale group, there was no significant difference detected in the incidence of severe or symptomatic hypoglycemia. Length of hospital stay was also similar in both groups. Finally, one study compared the use of routine diabetes medications plus RISS with routine diabetes medications alone and found no difference in the number of hypoglycemic or hyperglycemic events.

Significant heterogeneity was detected in the results of this meta-analysis and can be attributed to the differing patient populations, insulin regimens, and working definitions in the individual studies as noted above.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of sliding-scale insulin improve blood glucose control in hospitalized patients?

Bottom line: Sliding-scale insulin is commonly used to manage hyperglycemia in hospitalized patients. The evidence suggests that this regimen does not result in better blood glucose control. (LOE = 1a-)

Reference: Lee Y, Lin Y, Leu W et al. Sliding-scale insulin used for blood glucose control: a meta-analysis of randomized controlled trials. Metabolism 2015;64:1183-1192.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: These investigators searched multiple databases including PubMed, EMBASE, and the Cochrane Library to find randomized controlled trials that evaluated the efficacy of sliding-scale insulin to manage hyperglycemia in hospitalized patients. Two authors independently evaluated the studies for inclusion, extracted the data, and performed quality assessments.

Eight of the 11 included studies compared regular insulin sliding scale (RISS) regimens with non–sliding-scale regimens. All RISS regimens consisted of subcutaneous regular insulin injections according to patients' blood glucose levels. Non–sliding-scale regimens consisted of basal-bolus or basal insulin regimens, continuous intravenous insulin infusions, and closed-loop artificial pancreas systems. Target blood glucose levels for individual studies varied greatly and included a range of 100 mg/dL to 150 mg/dL, a goal of less than 140 mg/dL, and a goal of less than 180 mg/dL. Hypoglycemia was generally defined as a glucose level of less than 70 mg/dL, though three of the studies had an even lower cut-off.

In the two studies that evaluated hyperglycemia, one defined it as a glucose level greater than 180 mg/dL while the other defined it as greater than 240 mg/dL. A meta-analysis of relevant data showed no significant difference in the percentage of patients who achieved an average blood glucose level in the target range when comparing RISS with non–sliding-scale regimens. The trend, however, favored the non–sliding-scale group and the difference became significant (relative risk 1.48, 95% CI 1.09-2.02) after one study with a very wide confidence interval was removed. Furthermore, the incidence of hyperglycemia and the mean blood glucose levels were significantly higher in the RISS group.

Although overall hypoglycemic episodes occurred more frequently in the non–sliding-scale group, there was no significant difference detected in the incidence of severe or symptomatic hypoglycemia. Length of hospital stay was also similar in both groups. Finally, one study compared the use of routine diabetes medications plus RISS with routine diabetes medications alone and found no difference in the number of hypoglycemic or hyperglycemic events.

Significant heterogeneity was detected in the results of this meta-analysis and can be attributed to the differing patient populations, insulin regimens, and working definitions in the individual studies as noted above.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Which insertion site for central venous catheterization results in fewer complications?

Bottom line: Central venous catheterization via a subclavian insertion site, as compared with femoral and jugular sites, decreases the risk of bloodstream infections and symptomatic deep vein thromboses (DVTs), but results in more pneumothoraces. This risk could potentially be mitigated with the use of ultrasound guidance during catheter insertion. ((LOE = 1b)

Reference: Parienti JJ, Mongardon N, Mégarbane B, et al. Intravascular complications of central venous catheterization by insertion site. N Engl J Med 2015;373(13):1220-1229.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators randomized 3027 patients in the intensive care unit who required nontunneled central venous access to receive 3471 intravenous catheters at one of three insertion sites: subclavian, jugular, or femoral. The catheters were placed by residents or staff physicians who had prior experience in the procedure. All patients had peripheral blood cultures and catheter tip cultures sent at the time of catheter removal. Patients also underwent compression ultrasonography at the insertion site within two days of catheter removal to assess for DVT. The three groups were well-balanced at baseline and the median duration of catheter use was five days. Analysis was by intention to treat.

The primary composite endpoint of catheter-related bloodstream infections and symptomatic DVTs occurred less frequently in the subclavian group than in the other two groups (1.5 events per 1000 catheter-days in the subclavian group, 3.6 in the jugular group, 4.6 in the femoral group). The risk of this outcome was greater in both the femoral and jugular groups when compared directly with the subclavian group (femoral vs subclavian: hazard ratio [HR] = 3.5; 95% CI 1.5-7.8; P = .003; femoral vs jugular: HR = 2.1; 1.0-4.3; P = .04). The subclavian group, however, did have the highest risk of mechanical complications, mainly pneumothoraces.

When all three bad outcomes (infections, DVTs, mechanical complications) are pooled together, the differences between the three groups are not as compelling (percentage of catheters with overall complications: 3.1% subclavian, 3.7% jugular, 3.4% femoral).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Which insertion site for central venous catheterization results in fewer complications?

Bottom line: Central venous catheterization via a subclavian insertion site, as compared with femoral and jugular sites, decreases the risk of bloodstream infections and symptomatic deep vein thromboses (DVTs), but results in more pneumothoraces. This risk could potentially be mitigated with the use of ultrasound guidance during catheter insertion. ((LOE = 1b)

Reference: Parienti JJ, Mongardon N, Mégarbane B, et al. Intravascular complications of central venous catheterization by insertion site. N Engl J Med 2015;373(13):1220-1229.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators randomized 3027 patients in the intensive care unit who required nontunneled central venous access to receive 3471 intravenous catheters at one of three insertion sites: subclavian, jugular, or femoral. The catheters were placed by residents or staff physicians who had prior experience in the procedure. All patients had peripheral blood cultures and catheter tip cultures sent at the time of catheter removal. Patients also underwent compression ultrasonography at the insertion site within two days of catheter removal to assess for DVT. The three groups were well-balanced at baseline and the median duration of catheter use was five days. Analysis was by intention to treat.

The primary composite endpoint of catheter-related bloodstream infections and symptomatic DVTs occurred less frequently in the subclavian group than in the other two groups (1.5 events per 1000 catheter-days in the subclavian group, 3.6 in the jugular group, 4.6 in the femoral group). The risk of this outcome was greater in both the femoral and jugular groups when compared directly with the subclavian group (femoral vs subclavian: hazard ratio [HR] = 3.5; 95% CI 1.5-7.8; P = .003; femoral vs jugular: HR = 2.1; 1.0-4.3; P = .04). The subclavian group, however, did have the highest risk of mechanical complications, mainly pneumothoraces.

When all three bad outcomes (infections, DVTs, mechanical complications) are pooled together, the differences between the three groups are not as compelling (percentage of catheters with overall complications: 3.1% subclavian, 3.7% jugular, 3.4% femoral).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Which insertion site for central venous catheterization results in fewer complications?

Bottom line: Central venous catheterization via a subclavian insertion site, as compared with femoral and jugular sites, decreases the risk of bloodstream infections and symptomatic deep vein thromboses (DVTs), but results in more pneumothoraces. This risk could potentially be mitigated with the use of ultrasound guidance during catheter insertion. ((LOE = 1b)

Reference: Parienti JJ, Mongardon N, Mégarbane B, et al. Intravascular complications of central venous catheterization by insertion site. N Engl J Med 2015;373(13):1220-1229.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators randomized 3027 patients in the intensive care unit who required nontunneled central venous access to receive 3471 intravenous catheters at one of three insertion sites: subclavian, jugular, or femoral. The catheters were placed by residents or staff physicians who had prior experience in the procedure. All patients had peripheral blood cultures and catheter tip cultures sent at the time of catheter removal. Patients also underwent compression ultrasonography at the insertion site within two days of catheter removal to assess for DVT. The three groups were well-balanced at baseline and the median duration of catheter use was five days. Analysis was by intention to treat.

The primary composite endpoint of catheter-related bloodstream infections and symptomatic DVTs occurred less frequently in the subclavian group than in the other two groups (1.5 events per 1000 catheter-days in the subclavian group, 3.6 in the jugular group, 4.6 in the femoral group). The risk of this outcome was greater in both the femoral and jugular groups when compared directly with the subclavian group (femoral vs subclavian: hazard ratio [HR] = 3.5; 95% CI 1.5-7.8; P = .003; femoral vs jugular: HR = 2.1; 1.0-4.3; P = .04). The subclavian group, however, did have the highest risk of mechanical complications, mainly pneumothoraces.

When all three bad outcomes (infections, DVTs, mechanical complications) are pooled together, the differences between the three groups are not as compelling (percentage of catheters with overall complications: 3.1% subclavian, 3.7% jugular, 3.4% femoral).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is coronary computed tomography angiography better than stress testing for detecting coronary artery disease?

Bottom line: For the evaluation of chest pain in intermediate-risk patients, coronary computed tomography angiography (CCTA) is comparable with myocardial perfusion imaging (MPI) in its ability to select patients for invasive management. Both modalities are also similar when it comes to downstream resource use and adverse cardiovascular events. CCTA is associated with less radiation exposure (LOE = 1b).

Reference: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry. Ann Intern Med 2015;163(3):174-183.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The effectiveness of a noninvasive coronary imaging modality lies in its ability to identify patients who will need invasive management. In this study, intermediate-risk patients admitted to telemetry for the evaluation of chest pain who clinically required noninvasive imaging were randomized, using concealed allocation, to receive either CCTA or radionuclide stress MPI.

At baseline, the mean age in both groups was 57 years, two-thirds of the patients were female, and more than 90% were ethnic minorities. Analysis was by intention to treat. The primary outcome was the rate of cardiac catheterization that did not lead to revascularization within one year of the imaging test. There was no significant difference between the two groups for this outcome. However, in a subgroup analysis of patients with signficantly abnormal results on their imaging test, there was a nonsignificant trend toward fewer catheterizations without revascularization in the CCTA group (25% vs 52%; P=0.083).

For secondary outcomes, there were no differences detected between the two groups in length of stay, major adverse cardiovascular events, or downstream resource use, including rehospitalizations and further imaging. The CCTA group had less radiation exposure and reported a better patient experience.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is coronary computed tomography angiography better than stress testing for detecting coronary artery disease?

Bottom line: For the evaluation of chest pain in intermediate-risk patients, coronary computed tomography angiography (CCTA) is comparable with myocardial perfusion imaging (MPI) in its ability to select patients for invasive management. Both modalities are also similar when it comes to downstream resource use and adverse cardiovascular events. CCTA is associated with less radiation exposure (LOE = 1b).

Reference: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry. Ann Intern Med 2015;163(3):174-183.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The effectiveness of a noninvasive coronary imaging modality lies in its ability to identify patients who will need invasive management. In this study, intermediate-risk patients admitted to telemetry for the evaluation of chest pain who clinically required noninvasive imaging were randomized, using concealed allocation, to receive either CCTA or radionuclide stress MPI.

At baseline, the mean age in both groups was 57 years, two-thirds of the patients were female, and more than 90% were ethnic minorities. Analysis was by intention to treat. The primary outcome was the rate of cardiac catheterization that did not lead to revascularization within one year of the imaging test. There was no significant difference between the two groups for this outcome. However, in a subgroup analysis of patients with signficantly abnormal results on their imaging test, there was a nonsignificant trend toward fewer catheterizations without revascularization in the CCTA group (25% vs 52%; P=0.083).

For secondary outcomes, there were no differences detected between the two groups in length of stay, major adverse cardiovascular events, or downstream resource use, including rehospitalizations and further imaging. The CCTA group had less radiation exposure and reported a better patient experience.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is coronary computed tomography angiography better than stress testing for detecting coronary artery disease?

Bottom line: For the evaluation of chest pain in intermediate-risk patients, coronary computed tomography angiography (CCTA) is comparable with myocardial perfusion imaging (MPI) in its ability to select patients for invasive management. Both modalities are also similar when it comes to downstream resource use and adverse cardiovascular events. CCTA is associated with less radiation exposure (LOE = 1b).

Reference: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry. Ann Intern Med 2015;163(3):174-183.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The effectiveness of a noninvasive coronary imaging modality lies in its ability to identify patients who will need invasive management. In this study, intermediate-risk patients admitted to telemetry for the evaluation of chest pain who clinically required noninvasive imaging were randomized, using concealed allocation, to receive either CCTA or radionuclide stress MPI.

At baseline, the mean age in both groups was 57 years, two-thirds of the patients were female, and more than 90% were ethnic minorities. Analysis was by intention to treat. The primary outcome was the rate of cardiac catheterization that did not lead to revascularization within one year of the imaging test. There was no significant difference between the two groups for this outcome. However, in a subgroup analysis of patients with signficantly abnormal results on their imaging test, there was a nonsignificant trend toward fewer catheterizations without revascularization in the CCTA group (25% vs 52%; P=0.083).

For secondary outcomes, there were no differences detected between the two groups in length of stay, major adverse cardiovascular events, or downstream resource use, including rehospitalizations and further imaging. The CCTA group had less radiation exposure and reported a better patient experience.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.