The Hospitalist

The Food and Drug Administration has approved Baqsimi nasal powder, the first glucagon therapy approved for the treatment of severe hypoglycemia that is administrable without an injection, in patients aged 4 years and older.

Olivier Le Moal/Getty Images

Injectable glucagon has been approved in the United States for several decades.

The safety and efficacy of the Baqsimi powder was assessed in two studies with adults with diabetes and one with pediatric patients. In all three studies, a single dose of Baqsimi was compared with a single dose of glucagon injection, and Baqsimi adequately raised blood sugar levels in response to insulin-induced hypoglycemia.

The most common adverse events associated with Baqsimi include nausea, vomiting, headache, upper respiratory tract irritation, watery eyes, redness of eyes, and itchiness. The safety profile is similar to that of injectable glucagon, with the addition of nasal- and eye-related symptoms because of the method of delivery.

“There are many products on the market for those who need insulin, but until now, people suffering from a severe hypoglycemic episode had to be treated with a glucagon injection that first had to be mixed in a several-step process. This new way to administer glucagon may simplify the process, which can be critical during an episode, especially since the patient may have lost consciousness or may be having a seizure. In those situations, we want the process to treat the suffering person to be as simple as possible,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved Baqsimi nasal powder, the first glucagon therapy approved for the treatment of severe hypoglycemia that is administrable without an injection, in patients aged 4 years and older.

Olivier Le Moal/Getty Images

Injectable glucagon has been approved in the United States for several decades.

The safety and efficacy of the Baqsimi powder was assessed in two studies with adults with diabetes and one with pediatric patients. In all three studies, a single dose of Baqsimi was compared with a single dose of glucagon injection, and Baqsimi adequately raised blood sugar levels in response to insulin-induced hypoglycemia.

The most common adverse events associated with Baqsimi include nausea, vomiting, headache, upper respiratory tract irritation, watery eyes, redness of eyes, and itchiness. The safety profile is similar to that of injectable glucagon, with the addition of nasal- and eye-related symptoms because of the method of delivery.

“There are many products on the market for those who need insulin, but until now, people suffering from a severe hypoglycemic episode had to be treated with a glucagon injection that first had to be mixed in a several-step process. This new way to administer glucagon may simplify the process, which can be critical during an episode, especially since the patient may have lost consciousness or may be having a seizure. In those situations, we want the process to treat the suffering person to be as simple as possible,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved Baqsimi nasal powder, the first glucagon therapy approved for the treatment of severe hypoglycemia that is administrable without an injection, in patients aged 4 years and older.

Olivier Le Moal/Getty Images

Injectable glucagon has been approved in the United States for several decades.

The safety and efficacy of the Baqsimi powder was assessed in two studies with adults with diabetes and one with pediatric patients. In all three studies, a single dose of Baqsimi was compared with a single dose of glucagon injection, and Baqsimi adequately raised blood sugar levels in response to insulin-induced hypoglycemia.

The most common adverse events associated with Baqsimi include nausea, vomiting, headache, upper respiratory tract irritation, watery eyes, redness of eyes, and itchiness. The safety profile is similar to that of injectable glucagon, with the addition of nasal- and eye-related symptoms because of the method of delivery.

“There are many products on the market for those who need insulin, but until now, people suffering from a severe hypoglycemic episode had to be treated with a glucagon injection that first had to be mixed in a several-step process. This new way to administer glucagon may simplify the process, which can be critical during an episode, especially since the patient may have lost consciousness or may be having a seizure. In those situations, we want the process to treat the suffering person to be as simple as possible,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.

[email protected]

Background: Prophylactic proton pump inhibitors (PPIs) are used frequently in an ICU setting for acid suppression, but this is an off-label use and the evidence in support of using PPI prophylactically is limited. In fact, PPIs have been associated with adverse effects in recent literature including Clostridium difficile infection, myocardial ischemia, and pneumonia.

The researchers also used a composite outcome comprising clinically important gastrointestinal bleeding, Clostridium difficile infection, new onset pneumonia, and acute myocardial ischemia. Overall, 21.9% in the pantoprazole group and 22.6% participants in the placebo group had the composite outcome – a relative risk of 0.96 (95% CI, 0.83-1.11). Clinically important gastrointestinal bleeding was the only component of the composite outcome that was significantly different between groups, occurring less often in the pantoprazole group – the relative risk was 0.58 (95% CI, 0.40-0.86).

Bottom line: Pantoprazole does not differ significantly, compared with placebo, with regard to 90-day mortality and a composite outcome of clinically significant events.

Citation: Krag M et al. Pantoprazole in patients at risk of gastrointestinal bleeding in the ICU. N Eng J Med. 2018 Dec 6;379(23):2199-208.

Dr. Puri is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Prophylactic proton pump inhibitors (PPIs) are used frequently in an ICU setting for acid suppression, but this is an off-label use and the evidence in support of using PPI prophylactically is limited. In fact, PPIs have been associated with adverse effects in recent literature including Clostridium difficile infection, myocardial ischemia, and pneumonia.

The researchers also used a composite outcome comprising clinically important gastrointestinal bleeding, Clostridium difficile infection, new onset pneumonia, and acute myocardial ischemia. Overall, 21.9% in the pantoprazole group and 22.6% participants in the placebo group had the composite outcome – a relative risk of 0.96 (95% CI, 0.83-1.11). Clinically important gastrointestinal bleeding was the only component of the composite outcome that was significantly different between groups, occurring less often in the pantoprazole group – the relative risk was 0.58 (95% CI, 0.40-0.86).

Bottom line: Pantoprazole does not differ significantly, compared with placebo, with regard to 90-day mortality and a composite outcome of clinically significant events.

Citation: Krag M et al. Pantoprazole in patients at risk of gastrointestinal bleeding in the ICU. N Eng J Med. 2018 Dec 6;379(23):2199-208.

Dr. Puri is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Prophylactic proton pump inhibitors (PPIs) are used frequently in an ICU setting for acid suppression, but this is an off-label use and the evidence in support of using PPI prophylactically is limited. In fact, PPIs have been associated with adverse effects in recent literature including Clostridium difficile infection, myocardial ischemia, and pneumonia.

The researchers also used a composite outcome comprising clinically important gastrointestinal bleeding, Clostridium difficile infection, new onset pneumonia, and acute myocardial ischemia. Overall, 21.9% in the pantoprazole group and 22.6% participants in the placebo group had the composite outcome – a relative risk of 0.96 (95% CI, 0.83-1.11). Clinically important gastrointestinal bleeding was the only component of the composite outcome that was significantly different between groups, occurring less often in the pantoprazole group – the relative risk was 0.58 (95% CI, 0.40-0.86).

Bottom line: Pantoprazole does not differ significantly, compared with placebo, with regard to 90-day mortality and a composite outcome of clinically significant events.

Citation: Krag M et al. Pantoprazole in patients at risk of gastrointestinal bleeding in the ICU. N Eng J Med. 2018 Dec 6;379(23):2199-208.

Dr. Puri is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Nearly all clinicians who are eligible to participate in the Merit-Based Incentive Payment System (MIPS) track of the Quality Payment Program did so in 2018; most scored above the performance threshold and got a bonus.

According to the most recent data released this month by the Centers for Medicare & Medicaid Services, 98.37% of MIPS-eligible clinicians participated in the program. In the small/solo practice space, 89.20% of MIPS-eligible clinicians participated.

But more importantly, the clinicians are performing better one year later with the program, even though fewer are participating.

In 2018, 97.63% of clinicians scored above the performance threshold, up from 93.12% in 2017. There also were fewer clinicians performing at the threshold (0.42% in 2018, down from 2.01% in the previous year) and fewer clinicians scoring below the threshold (1.95%, down from 4.87%).

Exceeding the performance threshold resulted in a bonus to fee schedule payments in 2018, although the agency did not disclose how much money was paid out in performance bonuses.

MIPS scored “improved across performance categories, with the biggest gain in the Quality performance category, which highlights the program’s effectiveness in measuring outcomes for beneficiaries,” CMS Administrator Seema Verma wrote in a blog post.

The total number of eligible clinicians decreased in 2018 to 916,058, down from 1,057,824 in 2017 because CMS broadened the low-volume threshold to exempt providers from participation requirements.

Participants in a MIPS alternative payment model saw even more success in 2018. Participation increased from 341,220 clinicians in 2017 to 356,828 clinicians in 2018, while virtually all performed above the performance threshold (100% in 2017 and 99.99% in 2018). The 0.01% that was not above the threshold still met it, while no clinicians in either year that participated in a MIPS alternative payment model performed below the threshold.

Participation in the advanced alternative payment model track increased as well, going from 99,026 in 2017 to 183,306 in 2018.

[email protected]

Nearly all clinicians who are eligible to participate in the Merit-Based Incentive Payment System (MIPS) track of the Quality Payment Program did so in 2018; most scored above the performance threshold and got a bonus.

According to the most recent data released this month by the Centers for Medicare & Medicaid Services, 98.37% of MIPS-eligible clinicians participated in the program. In the small/solo practice space, 89.20% of MIPS-eligible clinicians participated.

But more importantly, the clinicians are performing better one year later with the program, even though fewer are participating.

In 2018, 97.63% of clinicians scored above the performance threshold, up from 93.12% in 2017. There also were fewer clinicians performing at the threshold (0.42% in 2018, down from 2.01% in the previous year) and fewer clinicians scoring below the threshold (1.95%, down from 4.87%).

Exceeding the performance threshold resulted in a bonus to fee schedule payments in 2018, although the agency did not disclose how much money was paid out in performance bonuses.

MIPS scored “improved across performance categories, with the biggest gain in the Quality performance category, which highlights the program’s effectiveness in measuring outcomes for beneficiaries,” CMS Administrator Seema Verma wrote in a blog post.

The total number of eligible clinicians decreased in 2018 to 916,058, down from 1,057,824 in 2017 because CMS broadened the low-volume threshold to exempt providers from participation requirements.

Participants in a MIPS alternative payment model saw even more success in 2018. Participation increased from 341,220 clinicians in 2017 to 356,828 clinicians in 2018, while virtually all performed above the performance threshold (100% in 2017 and 99.99% in 2018). The 0.01% that was not above the threshold still met it, while no clinicians in either year that participated in a MIPS alternative payment model performed below the threshold.

Participation in the advanced alternative payment model track increased as well, going from 99,026 in 2017 to 183,306 in 2018.

[email protected]

Nearly all clinicians who are eligible to participate in the Merit-Based Incentive Payment System (MIPS) track of the Quality Payment Program did so in 2018; most scored above the performance threshold and got a bonus.

According to the most recent data released this month by the Centers for Medicare & Medicaid Services, 98.37% of MIPS-eligible clinicians participated in the program. In the small/solo practice space, 89.20% of MIPS-eligible clinicians participated.

But more importantly, the clinicians are performing better one year later with the program, even though fewer are participating.

In 2018, 97.63% of clinicians scored above the performance threshold, up from 93.12% in 2017. There also were fewer clinicians performing at the threshold (0.42% in 2018, down from 2.01% in the previous year) and fewer clinicians scoring below the threshold (1.95%, down from 4.87%).

Exceeding the performance threshold resulted in a bonus to fee schedule payments in 2018, although the agency did not disclose how much money was paid out in performance bonuses.

MIPS scored “improved across performance categories, with the biggest gain in the Quality performance category, which highlights the program’s effectiveness in measuring outcomes for beneficiaries,” CMS Administrator Seema Verma wrote in a blog post.

The total number of eligible clinicians decreased in 2018 to 916,058, down from 1,057,824 in 2017 because CMS broadened the low-volume threshold to exempt providers from participation requirements.

Participants in a MIPS alternative payment model saw even more success in 2018. Participation increased from 341,220 clinicians in 2017 to 356,828 clinicians in 2018, while virtually all performed above the performance threshold (100% in 2017 and 99.99% in 2018). The 0.01% that was not above the threshold still met it, while no clinicians in either year that participated in a MIPS alternative payment model performed below the threshold.

Participation in the advanced alternative payment model track increased as well, going from 99,026 in 2017 to 183,306 in 2018.

[email protected]

Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?

Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.

Study design: Double-blind, randomized controlled trial.

Setting: Single center trial in Melbourne.

Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.

The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.

The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.

Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.

Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?

Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.

Study design: Double-blind, randomized controlled trial.

Setting: Single center trial in Melbourne.

Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.

The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.

The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.

Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.

Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?

Background: Lower back pain is the leading cause of disability globally and effective treatments are limited. Furthermore, opioid usage for lower back pain is a large contributor to the current opioid epidemic. A recent Cochrane review showed no clear evidence that antidepressant use in the treatment of back pain is effective, but it did note a lack of high-quality trials of sufficient rigor or length.

Study design: Double-blind, randomized controlled trial.

Setting: Single center trial in Melbourne.

Synopsis: Overall, 146 patients aged 18-75 with chronic lower back pain of no specific cause for more than 3 months were included. Exclusions included pathological cause, major coexisting illness, psychosis, or diagnosed depression. Patients were given amitriptyline 25 mg daily or benztropine mesylate 1 mg daily. Benztropine has similar anticholinergic side effects, without the antidepressant effect. Participants were assessed and followed by calls at 2 weeks, 1-2 months, 3 months, 4-5 months, and 6 months. Adherence was noted by the return of empty medication bottles at 6 months. Six-month surveys were completed by 81% and found that 70% of each group was adherent and 12% in each group withdrew because of adverse effects.

The primary outcome was level of pain at 6 months using a visual analog and descriptor scales. Secondary outcomes were measurement of disability, work missed, global improvement, general health, fear of movement, and depression.

The primary outcome was reduction in pain intensity of 12.6 (standard error, 2.7) with amitriptyline at 6 months, compared with 4.8 (SE 2.9) with benztropine, which did not meet statistical significance. There was a statistically significant difference in disability at 3 months, but not at 6 months.

Bottom line: This trial suggests that there may be a place for prescribed amitriptyline for chronic lower back pain, but it failed to show statistical significance. The study may not have been sufficiently powered to detect the difference.

Citations: Urquhart DM et al. Efficacy of low-dose amitriptyline for chronic low back pain: A randomized clinical trial. JAMA Intern Med. 2018;178(11):1474-81.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Is 6 months of dual antiplatelet therapy (DAPT) therapy noninferior to 12 months, following ST-elevation myocardial infarction (STEMI) with placement of second-generation drug-eluting stents?

Background: DAPT has been the standard of care to prevent abrupt thrombotic closure of vessels following percutaneous coronary intervention (PCI) and placement of stents. The recommended duration of DAPT was lengthened from at least 30 days in bare metal stents to at least 12 months in earlier-generation drug-eluting stents after observation of high rates of in-stent thrombosis of drug-eluting stents.

Trials have shown that there is no difference in outcomes comparing 6 month vs. 12 months in DAPT for PCI in the cases of non-ST-elevation MI and unstable angina. However, there are no randomized controlled studies comparing 6 vs. 12 months of DAPT with newer drug-eluting stents following STEMI. Newer drug-eluting stents are made of biocompatible polymers with thinner struts and are thought to be fully absorbed by 3 months. International guidelines still recommend 12 months of DAPT following drug-eluting stent placement following STEMI.

Study design: Prospective, unblinded, randomized, multicenter noninferiority trial.

Setting: The study was performed at 17 sites in the Netherlands, Norway, Poland, and Switzerland.

Synopsis: This study enrolled 1100 patients with STEMI started on DAPT during December 2011-June 2015. Overall, 870 patients were randomized to continue DAPT or to change to single antiplatelet therapy (SAPT) at 6 months. Exclusions included embolic events, cardiogenic shock, revascularization, bleeding, or being on anticoagulation. Patients were followed for 24 months.

The primary endpoint was a composite of all-cause mortality, any MI, any revascularization, stroke, or thrombolysis. Incidence of the composite endpoint was 4.8% of SAPT cases, and 6.6% of DAPT cases. Noninferiority was met (P = .004) because the upper 95% confidence interval of 1.27 was smaller than the prespecified noninferiority margin of 1.66. The secondary endpoint of safety and bleeding at 18 months was 3.2% for SAPT, and 4.3% for DAPT with HR of 0.75.

Medtronic’s new stent was used in 92% of the cases of this industry-sponsored study. Despite usage of a composite endpoint, there was no difference in the individual elements of the composite in subgroup analyses. There was a low event rate in both arms likely because of the exclusions that led to a lower-risk population. The individual operators were able to choose the P2Y12 inhibitor.

Bottom line: This industry-sponsored randomized, control trial showed noninferiority of 6 months of DAPT to 12 months of therapy following STEMI to prevent in-stent thrombosis with newer second- generation drug-eluting stents. However, the study’s results may be limited to lower-risk patients, without need for revascularization, oral anticoagulation, or with stroke or cardiogenic shock.

Citation: Kedhi E et al. Six months versus 12 months of dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): Randomised, multicenter, noninferiority trial. BMJ. 2018;363:k3793.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Is 6 months of dual antiplatelet therapy (DAPT) therapy noninferior to 12 months, following ST-elevation myocardial infarction (STEMI) with placement of second-generation drug-eluting stents?

Background: DAPT has been the standard of care to prevent abrupt thrombotic closure of vessels following percutaneous coronary intervention (PCI) and placement of stents. The recommended duration of DAPT was lengthened from at least 30 days in bare metal stents to at least 12 months in earlier-generation drug-eluting stents after observation of high rates of in-stent thrombosis of drug-eluting stents.

Trials have shown that there is no difference in outcomes comparing 6 month vs. 12 months in DAPT for PCI in the cases of non-ST-elevation MI and unstable angina. However, there are no randomized controlled studies comparing 6 vs. 12 months of DAPT with newer drug-eluting stents following STEMI. Newer drug-eluting stents are made of biocompatible polymers with thinner struts and are thought to be fully absorbed by 3 months. International guidelines still recommend 12 months of DAPT following drug-eluting stent placement following STEMI.

Study design: Prospective, unblinded, randomized, multicenter noninferiority trial.

Setting: The study was performed at 17 sites in the Netherlands, Norway, Poland, and Switzerland.

Synopsis: This study enrolled 1100 patients with STEMI started on DAPT during December 2011-June 2015. Overall, 870 patients were randomized to continue DAPT or to change to single antiplatelet therapy (SAPT) at 6 months. Exclusions included embolic events, cardiogenic shock, revascularization, bleeding, or being on anticoagulation. Patients were followed for 24 months.

The primary endpoint was a composite of all-cause mortality, any MI, any revascularization, stroke, or thrombolysis. Incidence of the composite endpoint was 4.8% of SAPT cases, and 6.6% of DAPT cases. Noninferiority was met (P = .004) because the upper 95% confidence interval of 1.27 was smaller than the prespecified noninferiority margin of 1.66. The secondary endpoint of safety and bleeding at 18 months was 3.2% for SAPT, and 4.3% for DAPT with HR of 0.75.

Medtronic’s new stent was used in 92% of the cases of this industry-sponsored study. Despite usage of a composite endpoint, there was no difference in the individual elements of the composite in subgroup analyses. There was a low event rate in both arms likely because of the exclusions that led to a lower-risk population. The individual operators were able to choose the P2Y12 inhibitor.

Bottom line: This industry-sponsored randomized, control trial showed noninferiority of 6 months of DAPT to 12 months of therapy following STEMI to prevent in-stent thrombosis with newer second- generation drug-eluting stents. However, the study’s results may be limited to lower-risk patients, without need for revascularization, oral anticoagulation, or with stroke or cardiogenic shock.

Citation: Kedhi E et al. Six months versus 12 months of dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): Randomised, multicenter, noninferiority trial. BMJ. 2018;363:k3793.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Is 6 months of dual antiplatelet therapy (DAPT) therapy noninferior to 12 months, following ST-elevation myocardial infarction (STEMI) with placement of second-generation drug-eluting stents?

Background: DAPT has been the standard of care to prevent abrupt thrombotic closure of vessels following percutaneous coronary intervention (PCI) and placement of stents. The recommended duration of DAPT was lengthened from at least 30 days in bare metal stents to at least 12 months in earlier-generation drug-eluting stents after observation of high rates of in-stent thrombosis of drug-eluting stents.

Trials have shown that there is no difference in outcomes comparing 6 month vs. 12 months in DAPT for PCI in the cases of non-ST-elevation MI and unstable angina. However, there are no randomized controlled studies comparing 6 vs. 12 months of DAPT with newer drug-eluting stents following STEMI. Newer drug-eluting stents are made of biocompatible polymers with thinner struts and are thought to be fully absorbed by 3 months. International guidelines still recommend 12 months of DAPT following drug-eluting stent placement following STEMI.

Study design: Prospective, unblinded, randomized, multicenter noninferiority trial.

Setting: The study was performed at 17 sites in the Netherlands, Norway, Poland, and Switzerland.

Synopsis: This study enrolled 1100 patients with STEMI started on DAPT during December 2011-June 2015. Overall, 870 patients were randomized to continue DAPT or to change to single antiplatelet therapy (SAPT) at 6 months. Exclusions included embolic events, cardiogenic shock, revascularization, bleeding, or being on anticoagulation. Patients were followed for 24 months.

The primary endpoint was a composite of all-cause mortality, any MI, any revascularization, stroke, or thrombolysis. Incidence of the composite endpoint was 4.8% of SAPT cases, and 6.6% of DAPT cases. Noninferiority was met (P = .004) because the upper 95% confidence interval of 1.27 was smaller than the prespecified noninferiority margin of 1.66. The secondary endpoint of safety and bleeding at 18 months was 3.2% for SAPT, and 4.3% for DAPT with HR of 0.75.

Medtronic’s new stent was used in 92% of the cases of this industry-sponsored study. Despite usage of a composite endpoint, there was no difference in the individual elements of the composite in subgroup analyses. There was a low event rate in both arms likely because of the exclusions that led to a lower-risk population. The individual operators were able to choose the P2Y12 inhibitor.

Bottom line: This industry-sponsored randomized, control trial showed noninferiority of 6 months of DAPT to 12 months of therapy following STEMI to prevent in-stent thrombosis with newer second- generation drug-eluting stents. However, the study’s results may be limited to lower-risk patients, without need for revascularization, oral anticoagulation, or with stroke or cardiogenic shock.

Citation: Kedhi E et al. Six months versus 12 months of dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): Randomised, multicenter, noninferiority trial. BMJ. 2018;363:k3793.

Dr. Lennon is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Delirium is commonly seen in the ICU and has been associated with increased morbidity and mortality. While haloperidol, as well as atypical antipsychotics, often are used to manage ICU delirium, evidence has been mixed as to whether these medications shorten the duration of either hyperactive or hypoactive delirium.

Only 11% of patients experienced hyperactive delirium, which makes these results less generalizable to patients whose delirium presents as agitation.

Bottom line: The use of antipsychotics in ICU delirium does not affect the duration of delirium in patient with respiratory failure or shock.

Citation: Girard TD et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Eng J Med. 2018 Dec 27;379(26):2506-16.

Dr. Defoe is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Delirium is commonly seen in the ICU and has been associated with increased morbidity and mortality. While haloperidol, as well as atypical antipsychotics, often are used to manage ICU delirium, evidence has been mixed as to whether these medications shorten the duration of either hyperactive or hypoactive delirium.

Only 11% of patients experienced hyperactive delirium, which makes these results less generalizable to patients whose delirium presents as agitation.

Bottom line: The use of antipsychotics in ICU delirium does not affect the duration of delirium in patient with respiratory failure or shock.

Citation: Girard TD et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Eng J Med. 2018 Dec 27;379(26):2506-16.

Dr. Defoe is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Delirium is commonly seen in the ICU and has been associated with increased morbidity and mortality. While haloperidol, as well as atypical antipsychotics, often are used to manage ICU delirium, evidence has been mixed as to whether these medications shorten the duration of either hyperactive or hypoactive delirium.

Only 11% of patients experienced hyperactive delirium, which makes these results less generalizable to patients whose delirium presents as agitation.

Bottom line: The use of antipsychotics in ICU delirium does not affect the duration of delirium in patient with respiratory failure or shock.

Citation: Girard TD et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Eng J Med. 2018 Dec 27;379(26):2506-16.

Dr. Defoe is an instructor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.

Bruce Jancin/MDedge News

Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.

This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.

He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.

Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.

Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.

In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.

Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.

The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).

As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.

Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.

He reported having no financial conflicts regarding the study, conducted free of commercial support.

[email protected]

SOURCE: Matsubara S et al. IEC 219, Abstract P002.

BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.

Bruce Jancin/MDedge News

Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.

This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.

He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.

Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.

Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.

In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.

Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.

The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).

As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.

Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.

He reported having no financial conflicts regarding the study, conducted free of commercial support.

[email protected]

SOURCE: Matsubara S et al. IEC 219, Abstract P002.

BANGKOK – Statin therapy, even when initiated only upon hospitalization for acute ischemic stroke, was associated with a striking reduction in the risk of early poststroke symptomatic seizure in a large observational study.

Bruce Jancin/MDedge News

Using propensity-score matching to control for potential confounders, use of a statin during acute stroke management was associated with a “robust” 77% reduction in the risk of developing a symptomatic seizure within 7 days after hospital admission, Soichiro Matsubara, MD, reported at the International Epilepsy Congress.

This is an important finding because early symptomatic seizure (ESS) occurs in 2%-7% of patients following an acute ischemic stroke. Moreover, an Italian meta-analysis concluded that ESS was associated with a 4.4-fold increased risk of developing poststroke epilepsy (Epilepsia. 2016 Aug;57[8]:1205-14), noted Dr. Matsubara, a neurologist at the National Cerebral and Cardiovascular Center in Suita, Japan, as well as at Kumamoto (Japan) University.

He presented a study of 2,969 consecutive acute ischemic stroke patients with no history of epilepsy who were admitted to the Japanese comprehensive stroke center, of whom 2.2% experienced ESS. At physician discretion, 19% of the ESS cohort were on a statin during their acute stroke management, as were 55% of the no-ESS group. Four-fifths of patients on a statin initiated the drug only upon hospital admission.

Strokes tended to be more severe in the ESS group, with a median initial National Institutes of Health Stroke Scale score of 12.5, compared with 4 in the seizure-free patients. A cortical stroke lesion was evident upon imaging in 89% of the ESS group and 55% of no-ESS patients. Among ESS patients, 46% had a cardiometabolic stroke, compared with 34% of the no-ESS cohort. Mean C-reactive protein levels and white blood cell counts were significantly higher in the ESS cohort as well. Their median hospital length of stay was 25.5 days, versus 18 days in the no-ESS group, Dr. Matsubara said at the congress sponsored by the International League Against Epilepsy.

Of the 76 ESSs that occurred in 66 patients, 37% were focal awareness seizures, 35% were focal to bilateral tonic-clonic seizures, and 28% were focal impaired awareness seizures.

In a multivariate analysis adjusted for age, sex, body mass index, stroke subtype, and other potential confounders, statin therapy during acute management of stroke was independently associated with a 56% reduction in the relative risk of ESS. In contrast, a cortical stroke lesion was associated with a 2.83-fold increased risk.

Since this wasn’t a randomized trial of statin therapy, Dr. Matsubara and his coinvestigators felt the need to go further in analyzing the data. After extensive propensity score matching for atrial fibrillation, current smoking, systolic blood pressure, the presence or absence of a cortical stroke lesion, large vessel stenosis, and other possible confounders, they were left with two closely comparable groups: 886 statin-treated stroke patients and an equal number who were not on statin therapy during their acute stroke management. The key finding: The risk of ESS was reduced by a whopping 77% in the patients on statin therapy.

The neurologist observed that these new findings in acute ischemic stroke patients are consistent with an earlier study in a U.S. Veterans Affairs population, which demonstrated that statin therapy was associated with a significantly lower risk of new-onset geriatric epilepsy (J Am Geriatr Soc. 2009 Feb;57[2]:237-42).

As to the possible mechanism by which statins may protect against ESS, Dr. Matsubara noted that acute ischemic stroke causes toxic neuronal excitation because of blood-brain barrier disruption, ion channel dysfunction, altered gene expression, and increased release of neurotransmitters. In animal models, statins provide a neuroprotective effect by reducing glutamate levels, activating endothelial nitric oxide synthase, and inhibiting production of interleukin-6, tumor necrosis factor-alpha, and other inflammatory cytokines.

Asked about the intensity of the statin therapy, Dr. Matsubara replied that the target was typically an LDL cholesterol below 100 mg/dL.

He reported having no financial conflicts regarding the study, conducted free of commercial support.

[email protected]

SOURCE: Matsubara S et al. IEC 219, Abstract P002.

I had just received my sign-out for the day. My pager beeped, and I heard it overhead “Code Blue Room X.” Hospitalist physicians lead the code team in our hospital; I quickly headed to the room.

A young man in his forties was found to be unconscious on the floor. One of the nurses had started cardiopulmonary resuscitation (CPR) as the patient was unconscious and had no palpable pulse. It was a long, drawn-out battle: CPR, cracking bones, shouting, lots of needles – an extreme roller-coaster-style situation. The patient had recently had a hip surgery and our suspicion was a massive pulmonary embolism. We ran the exhaustive code for more than an hour and then I started to debrief with my code team; discussed that treatment was getting futile and asked for opinions. Finally, I asked the team to stop and pronounced the patient dead. I felt terrible. Later that day I returned to my house, tossed my bag in the corner, and sympathized with myself – “Hello Dr. B, It was a tough one.”

Stopping resuscitation was one of the toughest decisions I had ever made, and I wondered if I would be able to make such a decision the next day. What if I had carried on? I had led code teams during my residency training and as an attending physician; but there was something different that day. This patient was a young man with no history of medical problems. Every physician knows how to initiate resuscitation for cardiopulmonary arrest (CPA); only a few know when to stop it. Did I miss this learning during my internal medicine training? I checked my red pocket leaflet with advanced cardiac life support (ACLS) algorithms, and it had no mention of it. I searched Google Scholar, PubMed, and UpToDate and surprisingly, I found no predetermined rule but only a few recommendations on when CPR should be stopped. The American Heart Association is clear that the decision to terminate resuscitative efforts rests with the treating physician in the hospital.

In my experience, the length of time to continue a code can vary widely and is mostly dependent on the physician running the code. I have seen it last 15 minutes (which is reasonable) and I have seen it last for 50 minutes when the initial rhythm was ventricular fibrillation. And if perhaps the patient regains a pulse temporarily, only to lose it again, we restart the clock. One needs to take into account various factors including time to CPR, time to defibrillation, comorbid disease, prearrest state, and initial arrest rhythm in making these decisions. It’s well understood that none of these factors alone or in combination is clearly predictive of outcome.¹

Some selected patients potentially have good outcomes with prolonged, aggressive resuscitation. So when should we stop, and when should we continue resuscitation? This is always challenging. Physicians hate to stop CPR even when they know it’s time. We are guided by the Hippocratic Oath to save lives. Sometimes, even if we want to stop, we tend to continue to avoid being criticized for stopping; we are systematically biased against stopping CPR. We routinely run long codes, in part because we are not sure which patients we can bring back.

A 2012 Lancet study highlighted that the median duration of resuscitation was 12 minutes for patients achieving the return of spontaneous circulation and 20 minutes for nonsurvivors.² The ethical guidelines issued by AHA in 2018 highlight that, in the absence of mitigating factors, prolonged resuscitative efforts for adults and children are unlikely to be successful and can be discontinued if there is no return of spontaneous circulation at any time during 30 minutes of cumulative ACLS. If the return of spontaneous circulation of any duration occurs at any time, however, it may be appropriate to consider extending the resuscitative effort.³

I believe a careful balance of the patient’s prognosis for both length of life and quality of life will determine whether continued CPR is appropriate. The responsible clinician should stop the resuscitative effort when he or she determines with a high degree of certainty that the arrest victim will not respond to further efforts. But what will help me guide my decisions next time if I ever come across this situation again?

I discussed my dilemma with one of our intensivist physicians; he expressed that in a similar scenario he would ask for opinions from other members of the code team. The role of good communication among code team members is necessary to exchange relevant knowledge in real time in a collaborative, nonhierarchical environment. The code team can provide the team leader with quick, accurate information about the patient’s clinical history that is critical to good decision making.

Family support is also an essential part of any resuscitation. Health care providers need to offer the opportunity to be present to family members during the resuscitation attempts whenever possible. One team member should be assigned to the family to answer questions, clarify information, and offer comfort, but physicians should not be asking family members to decide to stop the code. It is important to note that the decision should be made by the team leader and not the patient’s family members. Regardless of the age or condition of the patient, the loss of a loved one is difficult to deal with, even if expected. The issue becomes more difficult with changes in legal, cultural, or personal perspectives.

The AHA in 2018 stated that the treating physician is expected to understand the patient and the arrest features, and the system factors that have prognostic importance for resuscitation.³ For clinicians who work in critical care settings, the framework presented by AHA is intuitive. As a code leader, I can always give more epinephrine, try a clot-busting drug or deliver another shock. Situations vary greatly during a code, and the amount of time spent resuscitating a patient before terminating efforts is not set in stone. In many cases, it is a judgment call. The process of CPR is almost as disheartening as its bleak outcomes.

In-hospital CPAs are inevitably gruesome. Each day as an attending physician, we are faced with difficult decisions, but experiencing these incredibly difficult and life-changing events can make for good learning. A CPA situation in action is very difficult for all concerned, particularly when there is almost no chance of success. But an unsuccessful or aborted resuscitation is also a huge loss for both the family and the code team. One of the critical functions of the code team leader is to review the events of a code and exercise judgment while evaluating the length of a code. This can be an intense and emotional experience, but with these principles in mind, we can feel reassured that we are making the best decision possible, for the patient, the family, and our team.

Dr. Basnet is a hospitalist physician in the department of internal medicine at Eastern New Mexico Medical Center, Roswell.

References

1. Part 2: Ethical aspects of CPR and ECC. Circulation. 2000;102(8):I12.

2. Goldberger ZD et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: An observational study. The Lancet. 2012;380(9852):1473-81.

3. Sirbaugh PE et al. A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med. 1999;33(2):174-84.

I had just received my sign-out for the day. My pager beeped, and I heard it overhead “Code Blue Room X.” Hospitalist physicians lead the code team in our hospital; I quickly headed to the room.

A young man in his forties was found to be unconscious on the floor. One of the nurses had started cardiopulmonary resuscitation (CPR) as the patient was unconscious and had no palpable pulse. It was a long, drawn-out battle: CPR, cracking bones, shouting, lots of needles – an extreme roller-coaster-style situation. The patient had recently had a hip surgery and our suspicion was a massive pulmonary embolism. We ran the exhaustive code for more than an hour and then I started to debrief with my code team; discussed that treatment was getting futile and asked for opinions. Finally, I asked the team to stop and pronounced the patient dead. I felt terrible. Later that day I returned to my house, tossed my bag in the corner, and sympathized with myself – “Hello Dr. B, It was a tough one.”

Stopping resuscitation was one of the toughest decisions I had ever made, and I wondered if I would be able to make such a decision the next day. What if I had carried on? I had led code teams during my residency training and as an attending physician; but there was something different that day. This patient was a young man with no history of medical problems. Every physician knows how to initiate resuscitation for cardiopulmonary arrest (CPA); only a few know when to stop it. Did I miss this learning during my internal medicine training? I checked my red pocket leaflet with advanced cardiac life support (ACLS) algorithms, and it had no mention of it. I searched Google Scholar, PubMed, and UpToDate and surprisingly, I found no predetermined rule but only a few recommendations on when CPR should be stopped. The American Heart Association is clear that the decision to terminate resuscitative efforts rests with the treating physician in the hospital.

In my experience, the length of time to continue a code can vary widely and is mostly dependent on the physician running the code. I have seen it last 15 minutes (which is reasonable) and I have seen it last for 50 minutes when the initial rhythm was ventricular fibrillation. And if perhaps the patient regains a pulse temporarily, only to lose it again, we restart the clock. One needs to take into account various factors including time to CPR, time to defibrillation, comorbid disease, prearrest state, and initial arrest rhythm in making these decisions. It’s well understood that none of these factors alone or in combination is clearly predictive of outcome.¹

Some selected patients potentially have good outcomes with prolonged, aggressive resuscitation. So when should we stop, and when should we continue resuscitation? This is always challenging. Physicians hate to stop CPR even when they know it’s time. We are guided by the Hippocratic Oath to save lives. Sometimes, even if we want to stop, we tend to continue to avoid being criticized for stopping; we are systematically biased against stopping CPR. We routinely run long codes, in part because we are not sure which patients we can bring back.

A 2012 Lancet study highlighted that the median duration of resuscitation was 12 minutes for patients achieving the return of spontaneous circulation and 20 minutes for nonsurvivors.² The ethical guidelines issued by AHA in 2018 highlight that, in the absence of mitigating factors, prolonged resuscitative efforts for adults and children are unlikely to be successful and can be discontinued if there is no return of spontaneous circulation at any time during 30 minutes of cumulative ACLS. If the return of spontaneous circulation of any duration occurs at any time, however, it may be appropriate to consider extending the resuscitative effort.³

I believe a careful balance of the patient’s prognosis for both length of life and quality of life will determine whether continued CPR is appropriate. The responsible clinician should stop the resuscitative effort when he or she determines with a high degree of certainty that the arrest victim will not respond to further efforts. But what will help me guide my decisions next time if I ever come across this situation again?

I discussed my dilemma with one of our intensivist physicians; he expressed that in a similar scenario he would ask for opinions from other members of the code team. The role of good communication among code team members is necessary to exchange relevant knowledge in real time in a collaborative, nonhierarchical environment. The code team can provide the team leader with quick, accurate information about the patient’s clinical history that is critical to good decision making.

Family support is also an essential part of any resuscitation. Health care providers need to offer the opportunity to be present to family members during the resuscitation attempts whenever possible. One team member should be assigned to the family to answer questions, clarify information, and offer comfort, but physicians should not be asking family members to decide to stop the code. It is important to note that the decision should be made by the team leader and not the patient’s family members. Regardless of the age or condition of the patient, the loss of a loved one is difficult to deal with, even if expected. The issue becomes more difficult with changes in legal, cultural, or personal perspectives.

The AHA in 2018 stated that the treating physician is expected to understand the patient and the arrest features, and the system factors that have prognostic importance for resuscitation.³ For clinicians who work in critical care settings, the framework presented by AHA is intuitive. As a code leader, I can always give more epinephrine, try a clot-busting drug or deliver another shock. Situations vary greatly during a code, and the amount of time spent resuscitating a patient before terminating efforts is not set in stone. In many cases, it is a judgment call. The process of CPR is almost as disheartening as its bleak outcomes.

In-hospital CPAs are inevitably gruesome. Each day as an attending physician, we are faced with difficult decisions, but experiencing these incredibly difficult and life-changing events can make for good learning. A CPA situation in action is very difficult for all concerned, particularly when there is almost no chance of success. But an unsuccessful or aborted resuscitation is also a huge loss for both the family and the code team. One of the critical functions of the code team leader is to review the events of a code and exercise judgment while evaluating the length of a code. This can be an intense and emotional experience, but with these principles in mind, we can feel reassured that we are making the best decision possible, for the patient, the family, and our team.

Dr. Basnet is a hospitalist physician in the department of internal medicine at Eastern New Mexico Medical Center, Roswell.

References

1. Part 2: Ethical aspects of CPR and ECC. Circulation. 2000;102(8):I12.

2. Goldberger ZD et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: An observational study. The Lancet. 2012;380(9852):1473-81.

3. Sirbaugh PE et al. A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med. 1999;33(2):174-84.

I had just received my sign-out for the day. My pager beeped, and I heard it overhead “Code Blue Room X.” Hospitalist physicians lead the code team in our hospital; I quickly headed to the room.

A young man in his forties was found to be unconscious on the floor. One of the nurses had started cardiopulmonary resuscitation (CPR) as the patient was unconscious and had no palpable pulse. It was a long, drawn-out battle: CPR, cracking bones, shouting, lots of needles – an extreme roller-coaster-style situation. The patient had recently had a hip surgery and our suspicion was a massive pulmonary embolism. We ran the exhaustive code for more than an hour and then I started to debrief with my code team; discussed that treatment was getting futile and asked for opinions. Finally, I asked the team to stop and pronounced the patient dead. I felt terrible. Later that day I returned to my house, tossed my bag in the corner, and sympathized with myself – “Hello Dr. B, It was a tough one.”

Stopping resuscitation was one of the toughest decisions I had ever made, and I wondered if I would be able to make such a decision the next day. What if I had carried on? I had led code teams during my residency training and as an attending physician; but there was something different that day. This patient was a young man with no history of medical problems. Every physician knows how to initiate resuscitation for cardiopulmonary arrest (CPA); only a few know when to stop it. Did I miss this learning during my internal medicine training? I checked my red pocket leaflet with advanced cardiac life support (ACLS) algorithms, and it had no mention of it. I searched Google Scholar, PubMed, and UpToDate and surprisingly, I found no predetermined rule but only a few recommendations on when CPR should be stopped. The American Heart Association is clear that the decision to terminate resuscitative efforts rests with the treating physician in the hospital.

In my experience, the length of time to continue a code can vary widely and is mostly dependent on the physician running the code. I have seen it last 15 minutes (which is reasonable) and I have seen it last for 50 minutes when the initial rhythm was ventricular fibrillation. And if perhaps the patient regains a pulse temporarily, only to lose it again, we restart the clock. One needs to take into account various factors including time to CPR, time to defibrillation, comorbid disease, prearrest state, and initial arrest rhythm in making these decisions. It’s well understood that none of these factors alone or in combination is clearly predictive of outcome.¹

Some selected patients potentially have good outcomes with prolonged, aggressive resuscitation. So when should we stop, and when should we continue resuscitation? This is always challenging. Physicians hate to stop CPR even when they know it’s time. We are guided by the Hippocratic Oath to save lives. Sometimes, even if we want to stop, we tend to continue to avoid being criticized for stopping; we are systematically biased against stopping CPR. We routinely run long codes, in part because we are not sure which patients we can bring back.

A 2012 Lancet study highlighted that the median duration of resuscitation was 12 minutes for patients achieving the return of spontaneous circulation and 20 minutes for nonsurvivors.² The ethical guidelines issued by AHA in 2018 highlight that, in the absence of mitigating factors, prolonged resuscitative efforts for adults and children are unlikely to be successful and can be discontinued if there is no return of spontaneous circulation at any time during 30 minutes of cumulative ACLS. If the return of spontaneous circulation of any duration occurs at any time, however, it may be appropriate to consider extending the resuscitative effort.³

I believe a careful balance of the patient’s prognosis for both length of life and quality of life will determine whether continued CPR is appropriate. The responsible clinician should stop the resuscitative effort when he or she determines with a high degree of certainty that the arrest victim will not respond to further efforts. But what will help me guide my decisions next time if I ever come across this situation again?

I discussed my dilemma with one of our intensivist physicians; he expressed that in a similar scenario he would ask for opinions from other members of the code team. The role of good communication among code team members is necessary to exchange relevant knowledge in real time in a collaborative, nonhierarchical environment. The code team can provide the team leader with quick, accurate information about the patient’s clinical history that is critical to good decision making.

Family support is also an essential part of any resuscitation. Health care providers need to offer the opportunity to be present to family members during the resuscitation attempts whenever possible. One team member should be assigned to the family to answer questions, clarify information, and offer comfort, but physicians should not be asking family members to decide to stop the code. It is important to note that the decision should be made by the team leader and not the patient’s family members. Regardless of the age or condition of the patient, the loss of a loved one is difficult to deal with, even if expected. The issue becomes more difficult with changes in legal, cultural, or personal perspectives.

The AHA in 2018 stated that the treating physician is expected to understand the patient and the arrest features, and the system factors that have prognostic importance for resuscitation.³ For clinicians who work in critical care settings, the framework presented by AHA is intuitive. As a code leader, I can always give more epinephrine, try a clot-busting drug or deliver another shock. Situations vary greatly during a code, and the amount of time spent resuscitating a patient before terminating efforts is not set in stone. In many cases, it is a judgment call. The process of CPR is almost as disheartening as its bleak outcomes.

In-hospital CPAs are inevitably gruesome. Each day as an attending physician, we are faced with difficult decisions, but experiencing these incredibly difficult and life-changing events can make for good learning. A CPA situation in action is very difficult for all concerned, particularly when there is almost no chance of success. But an unsuccessful or aborted resuscitation is also a huge loss for both the family and the code team. One of the critical functions of the code team leader is to review the events of a code and exercise judgment while evaluating the length of a code. This can be an intense and emotional experience, but with these principles in mind, we can feel reassured that we are making the best decision possible, for the patient, the family, and our team.

Dr. Basnet is a hospitalist physician in the department of internal medicine at Eastern New Mexico Medical Center, Roswell.

References

1. Part 2: Ethical aspects of CPR and ECC. Circulation. 2000;102(8):I12.

2. Goldberger ZD et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: An observational study. The Lancet. 2012;380(9852):1473-81.

3. Sirbaugh PE et al. A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med. 1999;33(2):174-84.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.

Both systolic and diastolic hypertension independently predict myocardial infarction and strokes, but systolic blood pressure is more strongly linked to adverse outcomes.

That’s according to a study of more than 1 million patients and 36 million outpatient blood pressure measurements published in the New England Journal of Medicine.

Systolic and diastolic hypertension predicted adverse outcomes at cutpoints of 140/90 and 130/80 mm Hg in the large retrospective cohort study, supporting the recent guideline changes that made blood pressure targets more stringent for higher-risk patients, said lead investigator Alexander C. Flint, MD, of Kaiser Permanente Northern California (KPNC) in Oakland.

“While systolic does count for more, in the fact that it is a stronger driver of the risk of heart attack and stroke, diastolic absolutely does as well, and it does so independently. So we ignore our diastolic hypertension at our own peril,” Dr. Flint said in an interview.

Systolic hypertension began to overshadow diastolic after the Framingham Heart Study and others that suggested it is a more important predictor of adverse cardiovascular outcomes, Dr. Flint and coauthors said in a report on their study.

Those findings caused some to say diastole should be abandoned, and led to a “near-exclusive focus” on systolic hypertension in a 2000 advisory statement from the National High Blood Pressure Education Program, they say in their report.

While current guidelines emphasize the importance of both systolic and diastolic targets, many clinicians today often assign little importance to diastolic blood pressure values, the report adds.

“The pendulum needs to swing back, right down in the middle,” Dr. Flint said in the interview.

The study by Dr. Flint and colleagues comprised a cohort of approximately 1.3 million outpatients from KPNC who had at least one baseline blood pressure reading in during 2007-2008, and two or more follow-up measurements between 2009 and 2016, for a total of about 36.8 million data points.

Systolic hypertension burden was linked to the composite of MI or stroke, with a hazard ratio of 1.18 (95% confidence interval, 1.17-1.18; P less than .001) per unit increase in z score, according to results of a multivariable regression analysis. Likewise, diastolic hypertension burden was linked to those adverse outcomes, with a hazard ratio of 1.06 (95% CI, 1.06-1.07; P less than .001).

Put in terms of estimated risk of MI or stroke, patients with a systolic blood pressure around 160 mm Hg – 3 standard deviations from the mean – was 4.8%, compared to a predicted risk of just 1.9% for a systolic blood pressure near 136 mm Hg, the investigators said in their report.

Similarly, predicted risk was 3.6% for a diastolic pressure of about 96 mm Hg, also 3 standard deviations from the mean, and 1.9% for a diastolic BP near 81 mm Hg.

“The two are not that separate,” Dr. Flint said of the risks associated with systolic and diastolic hypertension at that 3-standard-deviation point. Beyond that, increased systolic blood pressure is associated with more risk relative to increased diastolic blood pressure, the logistic regression modeling shows.

Taken together, findings from this large cohort study emphasize the importance of making lifestyle modifications and adjusting medication to ensure that both systolic and diastolic targets are met, according to Dr. Flint.

“Rises in systolic blood pressure count for more in influencing the risk of heart attack and stroke,” he said, “but diastolic independently counts for quite a lot. It’s a close second.”

Dr. Flint reported no disclosures. Senior author Deepak L. Bhatt, MD, MPH, reported disclosures with Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, Takeda, The Medicines Company, and others. The remaining authors had no disclosures.

SOURCE: Flint AC et al. N Engl J Med. 2019 Jul 18. doi: 10.1056/NEJMoa1803180.