SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

[email protected]

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

[email protected]

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

SAN DIEGO – For patients with severe rib injuries, low-dose ketamine infusions kept pain under control while reducing opioid consumption.

Michele G Sullivan/MDedge News

The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.

“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.

The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.

All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.

The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.

In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).

Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.

However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.

This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.

“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.

This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.

Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.

[email protected]

SOURCE: Carver T et al. AAST 2018, Oral abstract 2

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: B 
 
Rationale  
This patient has large varices, which should be treated. In patients with cirrhosis and medium/large varices that have never bled, nonselective beta-blockers reduce the risk of first variceal hemorrhage by 50%. In high-quality randomized-controlled trials, endoscopic variceal ligation (EVL) is as effective as nonselective beta-blockers in preventing first variceal hemorrhage. Therefore, either of these therapies should be used for the prevention of first variceal bleeding. In this case, propranolol is not the best choice in the setting of diabetes, asthma as well as a blood pressure and pulse that are low already. Endoscopic variceal band ligation would be preferred in this patient. It is also more effective than sclerotherapy and is associated with fewer side effects. TIPS would be effective, but more invasive and not first-line for treatment of nonbleeding varices and comes with increased risk of hepatic encephalopathy and potentially mortality. The combination of nadolol and endoscopic variceal band ligation may have more side effects without a further reduction in the risk of first variceal hemorrhage beyond either therapy alone. 
 
References  
1. Gluud L.L., Klingenberg S., Nikolova D., Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol. 2007;102(12):2842-8.  
2. Gluud L.L., Krag A. Banding ligation versus betablockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev. 2012;8:CD004544. doi: 10.1002/14651858. CD004544. 
3. Villanueva C., Piqueras M., Aracil C., et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45(4):560-7.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Correct Answer: A 
 
Rationale 
This patient has an idiopathic, nonNSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers. 
 
References 
1. Wong G.L.H., Wong V.W.S., Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31. 
2. Laine L., Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
 

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
 

Background: Health care costs are on the rise, and previous studies have found that PCC can reduce hospital costs. Timing of consultation and allocation of palliative care intervention to a certain population of patients may reveal a more significant cost reduction.

Only six samples were evaluated, and causation could not be established because all samples had observational designs. There also was potential interpretation bias because the private investigator for each of the samples contributed to interpretation of the data and participated as an author. Overall evaluation of the economic value of PCC in this study was limited because analysis was focused to a single index hospital admission rather than including additional hospitalizations and outpatient costs.

Bottom line: Acute care hospitals might reduce hospital costs by increasing resources to allow palliative care consultations in patients with serious illnesses.

Citation: May P et al. Economics of palliative care for hospitalized adults with serious illness. JAMA Intern Med. 2018;178(6):820-9.

Dr. Libot is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
 

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

EVIDENCE SUMMARY

No head-to-head studies or umbrella meta-analyses assess all the main treatments for VTE against each other.

Long-term LMWH decreases VTE recurrence compared with VKA

Two meta-analyses of RCTs evaluating LMWH and VKA for long-term treatment (3-12 months) of confirmed VTE in patients with cancer found that LMWH didn’t change mortality, but reduced the rate of VTE recurrence compared with VKA (40% relative reduction).^1,2 The comparison showed no differences in major or minor bleeding or thrombocytopenia between LMWH and VKA (TABLE^1-5).

The studies included patients with any solid or hematologic cancer at any stage and from any age group, including children. Overall, the mean age of patients was in the mid 60s; approximately 50% were male when specified. Investigators rated the evidence quality as moderate for VTE, but low for the other outcomes.¹

The most recent meta-analysis of the same RCTs comparing LMWH with VKA evaluated intracranial hemorrhage rates and found no difference.³

Initial therapy with LMWH: A look at mortality

A meta-analysis of RCTs that compared LMWH with UFH/VKA for initial treatment of confirmed VTE in adult cancer patients (any type or stage of cancer, mean ages not specified) found that LMWH reduced mortality by 30%, but didn’t affect VTE recurrence or major bleeding.⁴

The control groups received UFH for 5 to 10 days and then continued with VKA, whereas the experimental groups received different types of LMWH (reviparin, nadroparin, tinzaparin, enoxaparin) initially and for 3 months thereafter. Investigators rated all studies low quality because of imprecision and publication bias favoring LMWH.

Fondaparinux shows no advantage for initial therapy

The same meta-analysis compared initial treatment with fondaparinux and initial therapy with enoxaparin or UFH transitioning to warfarin.⁴ It found no differences in any outcomes at 3 months. Investigators rated both studies as low quality for recurrent VTE and moderate for mortality and bleeding.

Continue to: Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA

 

 

Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA: No differences

A meta-analysis of RCTs comparing NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) with VKA for 6 months found no differences in recurrent VTE or major bleeding.²

A second meta-analysis of RCTs that compared NOACs (rivaroxaban, dabigatran, apixaban) with control (LMWH followed by VKA) in adult cancer patients (mean ages, 54-66 years; 50%-60% men) reported no difference in the composite outcome of recurrent VTE or VTE-related death nor clinically significant bleeding over 1 to 36 months (most RCTs ran 3-12 months).⁵ Separate comparisons for rivaroxaban and dabigatran found no difference in the composite outcome, and rivaroxaban also produced no difference in clinically-significant bleeding.

RECOMMENDATIONS

The 2016 CHEST guidelines recommend LMWH as first-line treatment for VTE in patients with cancer and indicate no preference between NOACs and VKA for second-line treatment.⁶

EVIDENCE SUMMARY

No head-to-head studies or umbrella meta-analyses assess all the main treatments for VTE against each other.

Long-term LMWH decreases VTE recurrence compared with VKA

Two meta-analyses of RCTs evaluating LMWH and VKA for long-term treatment (3-12 months) of confirmed VTE in patients with cancer found that LMWH didn’t change mortality, but reduced the rate of VTE recurrence compared with VKA (40% relative reduction).^1,2 The comparison showed no differences in major or minor bleeding or thrombocytopenia between LMWH and VKA (TABLE^1-5).

The studies included patients with any solid or hematologic cancer at any stage and from any age group, including children. Overall, the mean age of patients was in the mid 60s; approximately 50% were male when specified. Investigators rated the evidence quality as moderate for VTE, but low for the other outcomes.¹

The most recent meta-analysis of the same RCTs comparing LMWH with VKA evaluated intracranial hemorrhage rates and found no difference.³

Initial therapy with LMWH: A look at mortality

A meta-analysis of RCTs that compared LMWH with UFH/VKA for initial treatment of confirmed VTE in adult cancer patients (any type or stage of cancer, mean ages not specified) found that LMWH reduced mortality by 30%, but didn’t affect VTE recurrence or major bleeding.⁴

The control groups received UFH for 5 to 10 days and then continued with VKA, whereas the experimental groups received different types of LMWH (reviparin, nadroparin, tinzaparin, enoxaparin) initially and for 3 months thereafter. Investigators rated all studies low quality because of imprecision and publication bias favoring LMWH.

Fondaparinux shows no advantage for initial therapy

The same meta-analysis compared initial treatment with fondaparinux and initial therapy with enoxaparin or UFH transitioning to warfarin.⁴ It found no differences in any outcomes at 3 months. Investigators rated both studies as low quality for recurrent VTE and moderate for mortality and bleeding.

Continue to: Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA

 

 

Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA: No differences

A meta-analysis of RCTs comparing NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) with VKA for 6 months found no differences in recurrent VTE or major bleeding.²

A second meta-analysis of RCTs that compared NOACs (rivaroxaban, dabigatran, apixaban) with control (LMWH followed by VKA) in adult cancer patients (mean ages, 54-66 years; 50%-60% men) reported no difference in the composite outcome of recurrent VTE or VTE-related death nor clinically significant bleeding over 1 to 36 months (most RCTs ran 3-12 months).⁵ Separate comparisons for rivaroxaban and dabigatran found no difference in the composite outcome, and rivaroxaban also produced no difference in clinically-significant bleeding.

RECOMMENDATIONS

The 2016 CHEST guidelines recommend LMWH as first-line treatment for VTE in patients with cancer and indicate no preference between NOACs and VKA for second-line treatment.⁶

EVIDENCE SUMMARY

No head-to-head studies or umbrella meta-analyses assess all the main treatments for VTE against each other.

Long-term LMWH decreases VTE recurrence compared with VKA

Two meta-analyses of RCTs evaluating LMWH and VKA for long-term treatment (3-12 months) of confirmed VTE in patients with cancer found that LMWH didn’t change mortality, but reduced the rate of VTE recurrence compared with VKA (40% relative reduction).^1,2 The comparison showed no differences in major or minor bleeding or thrombocytopenia between LMWH and VKA (TABLE^1-5).

The studies included patients with any solid or hematologic cancer at any stage and from any age group, including children. Overall, the mean age of patients was in the mid 60s; approximately 50% were male when specified. Investigators rated the evidence quality as moderate for VTE, but low for the other outcomes.¹

The most recent meta-analysis of the same RCTs comparing LMWH with VKA evaluated intracranial hemorrhage rates and found no difference.³

Initial therapy with LMWH: A look at mortality

A meta-analysis of RCTs that compared LMWH with UFH/VKA for initial treatment of confirmed VTE in adult cancer patients (any type or stage of cancer, mean ages not specified) found that LMWH reduced mortality by 30%, but didn’t affect VTE recurrence or major bleeding.⁴

The control groups received UFH for 5 to 10 days and then continued with VKA, whereas the experimental groups received different types of LMWH (reviparin, nadroparin, tinzaparin, enoxaparin) initially and for 3 months thereafter. Investigators rated all studies low quality because of imprecision and publication bias favoring LMWH.

Fondaparinux shows no advantage for initial therapy

The same meta-analysis compared initial treatment with fondaparinux and initial therapy with enoxaparin or UFH transitioning to warfarin.⁴ It found no differences in any outcomes at 3 months. Investigators rated both studies as low quality for recurrent VTE and moderate for mortality and bleeding.

Continue to: Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA

 

 

Non-vitamin K oral anticoagulants vs LMWH/VKA or VKA: No differences

A meta-analysis of RCTs comparing NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) with VKA for 6 months found no differences in recurrent VTE or major bleeding.²

A second meta-analysis of RCTs that compared NOACs (rivaroxaban, dabigatran, apixaban) with control (LMWH followed by VKA) in adult cancer patients (mean ages, 54-66 years; 50%-60% men) reported no difference in the composite outcome of recurrent VTE or VTE-related death nor clinically significant bleeding over 1 to 36 months (most RCTs ran 3-12 months).⁵ Separate comparisons for rivaroxaban and dabigatran found no difference in the composite outcome, and rivaroxaban also produced no difference in clinically-significant bleeding.

RECOMMENDATIONS

The 2016 CHEST guidelines recommend LMWH as first-line treatment for VTE in patients with cancer and indicate no preference between NOACs and VKA for second-line treatment.⁶

Astonished by physician hourly rate calculation 

I always enjoy the articles and incredible insights presented in OBG Management. Some very sophisticated, well-founded ideas are presented in the article on deciding on purchasing medical equipment. Then, however, you get to the calculations: $50 for 30 minutes of physician time!

My plumber charges me $100 for the first half hour of a visit (okay, there are lots of cliched jokes about this), but on average a physician assistant costs almost that much. It is a sad day in the business of medicine when experts value the time of highly educated physicians at $100 per hour. Maybe someday we can expect to be reasonably compensated for our efforts and training. When I advise my colleagues, I calculate their time, depending on their practice model, between $300 and $400 per hour.

Hamid Banooni, MD
Farmington Hills, Michigan

Dr. Kim responds

I thank Dr. Banooni for his comment. I agree that physicians are highly skilled and educated and that their time deserves to be valued at more than $100 per hour. In the article and the example provided, the values (revenues, costs, and so on) were not meant to be exactly representative of the marketplace, but instead were used merely as an example for understanding the calculation tools for purchasing medical equipment. That being said, I arrived at the $100 per hour cost for physician time (included in the variable cost in the Figure, “Breakeven analysis for hysteroscope purchase for use in tubal sterilization”) for 2 primary reasons. First, to simplify the calculation, and second, to use an equivalent universal hourly salary ($100 per hour) for a physician’s comparative labor cost in the marketplace. Currently, the median hourly compensation for an ObGyn laborist is $110 per hour.¹ To simplify, I rounded down to $100. I wholeheartedly agree with Dr. Banooni, however, that a physician’s time should be valued higher in society.
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Astonished by physician hourly rate calculation 

I always enjoy the articles and incredible insights presented in OBG Management. Some very sophisticated, well-founded ideas are presented in the article on deciding on purchasing medical equipment. Then, however, you get to the calculations: $50 for 30 minutes of physician time!

My plumber charges me $100 for the first half hour of a visit (okay, there are lots of cliched jokes about this), but on average a physician assistant costs almost that much. It is a sad day in the business of medicine when experts value the time of highly educated physicians at $100 per hour. Maybe someday we can expect to be reasonably compensated for our efforts and training. When I advise my colleagues, I calculate their time, depending on their practice model, between $300 and $400 per hour.

Hamid Banooni, MD
Farmington Hills, Michigan

Dr. Kim responds

I thank Dr. Banooni for his comment. I agree that physicians are highly skilled and educated and that their time deserves to be valued at more than $100 per hour. In the article and the example provided, the values (revenues, costs, and so on) were not meant to be exactly representative of the marketplace, but instead were used merely as an example for understanding the calculation tools for purchasing medical equipment. That being said, I arrived at the $100 per hour cost for physician time (included in the variable cost in the Figure, “Breakeven analysis for hysteroscope purchase for use in tubal sterilization”) for 2 primary reasons. First, to simplify the calculation, and second, to use an equivalent universal hourly salary ($100 per hour) for a physician’s comparative labor cost in the marketplace. Currently, the median hourly compensation for an ObGyn laborist is $110 per hour.¹ To simplify, I rounded down to $100. I wholeheartedly agree with Dr. Banooni, however, that a physician’s time should be valued higher in society.
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Astonished by physician hourly rate calculation 

I always enjoy the articles and incredible insights presented in OBG Management. Some very sophisticated, well-founded ideas are presented in the article on deciding on purchasing medical equipment. Then, however, you get to the calculations: $50 for 30 minutes of physician time!

My plumber charges me $100 for the first half hour of a visit (okay, there are lots of cliched jokes about this), but on average a physician assistant costs almost that much. It is a sad day in the business of medicine when experts value the time of highly educated physicians at $100 per hour. Maybe someday we can expect to be reasonably compensated for our efforts and training. When I advise my colleagues, I calculate their time, depending on their practice model, between $300 and $400 per hour.

Hamid Banooni, MD
Farmington Hills, Michigan

Dr. Kim responds

I thank Dr. Banooni for his comment. I agree that physicians are highly skilled and educated and that their time deserves to be valued at more than $100 per hour. In the article and the example provided, the values (revenues, costs, and so on) were not meant to be exactly representative of the marketplace, but instead were used merely as an example for understanding the calculation tools for purchasing medical equipment. That being said, I arrived at the $100 per hour cost for physician time (included in the variable cost in the Figure, “Breakeven analysis for hysteroscope purchase for use in tubal sterilization”) for 2 primary reasons. First, to simplify the calculation, and second, to use an equivalent universal hourly salary ($100 per hour) for a physician’s comparative labor cost in the marketplace. Currently, the median hourly compensation for an ObGyn laborist is $110 per hour.¹ To simplify, I rounded down to $100. I wholeheartedly agree with Dr. Banooni, however, that a physician’s time should be valued higher in society.
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EVIDENCE SUMMARY

A network meta-analysis of 179 placebo-controlled trials of medications to treat migraine¹ headache identified 3 trials involving ACE inhibitors and 3 involving ARBs (TABLE¹). The authors of the meta-analysis gave 2 trials (one of lisinopril and one of candesartan) relatively high scores for methodologic quality.

Lisinopril reduces hours, days with headache and days with migraine

The first, a placebo-controlled lisinopril crossover trial, included 60 patients, 19 to 59 years of age, who experienced migraines with or without auras 2 to 6 times per month.² Thirty patients received lisinopril 10 mg once daily for 1 week followed by 20 mg once daily (using 10-mg tablets) for 11 weeks. The other 30 patients received a similarly titrated placebo for 12 weeks. After a 2-week washout period, the groups were given the other therapy. Patients took triptan medications and analgesics as needed. Primary outcomes, extracted from headache diaries, included the number of hours and days with headache (of any type) and number of days with migraine specifically.

Out of the initial 60 participants, 47 completed the study. Using intention-to-treat analysis, lisinopril therapy resulted in fewer hours with headache (162 vs 138, a 15% difference; 95% confidence interval [CI], 0-30), fewer days with headache (25 vs 21, a 16% difference; 95% CI, 5-27), and fewer days with migraine (19 vs 15, a 22% change; 95% CI, 11-33), compared with placebo. Three patients discontinued lisinopril because of adverse events. Mean blood pressure reduction with lisinopril was 7 mm Hg systolic and 5 mm Hg diastolic more than placebo (P<.0001 for both comparisons).

Candesartan also decreases headaches and migraine

The other study given a high methodologic quality score by the network-meta-analysis authors was a placebo-controlled candesartan crossover trial.³ It enrolled 60 patients, 18 to 65 years of age, who experienced migraines with or without auras 2 to 6 times per month.

Thirty patients received 16 mg candesartan daily for 12 weeks, followed by a 4-week washout period before taking a placebo tablet daily for 12 weeks. The other 30 received placebo followed by candesartan. Patients took triptan medications and analgesics as needed. The primary outcome measure was days with headache, recorded by patients using daily diaries. Three patients didn’t complete the study.

Using intention-to-treat analysis, the mean number of days with headache was 18.5 with placebo and 13.6 with candesartan (P=.001). Secondary end points that also favored candesartan were hours with migraine (92 vs 59; P<.001), hours with headache (139 vs 95; P<.001), days with migraine (13 vs 9; P<.001), and days of sick leave (3.9 vs 1.4; P=.01). Adverse events, including dizziness, were similar with candesartan and placebo. Mean blood pressure reduction with candesartan was 11 mm Hg systolic and 7 mm Hg diastolic over placebo (P<.001 for both comparisons).

Continue to: Overall both drugs have a significant effect on number of headaches

 

 

Overall both drugs have a significant effect on number of headaches

Among all ACE inhibitor and ARB trials in the review, a network meta-analysis (designed to compare interventions never studied head-to-head) could be performed only on candesartan, which had a small effect size on headache frequency relative to placebo (2 trials, 118 patients; standardized mean difference [SMD]= −0.33; 95% CI, −0.59 to −0.7).¹ (An SMD of 0.2 is considered small, 0.6 moderate, and 1.2 large). Combining data from all ACE inhibitor and ARB trials together in a standard meta-analysis yielded a large effect size on number of headaches per month compared with placebo (6 trials, 351 patients; SMD= −1.12; 95% CI, −1.97 to −0.27).¹

RECOMMENDATIONS

In 2012, the American Academy of Neurology and the American Headache Society published guidelines on pharmacologic treatment for episodic migraine prevention in adults.⁴ The guidelines stated that lisinopril and candesartan were “possibly effective” for migraine prevention (level C recommendation based on a single lower-quality randomized clinical trial). They further advised clinicians to be “mindful of comorbid and coexistent conditions in patients with migraine to maximize potential treatment efficacy.”

EVIDENCE SUMMARY

A network meta-analysis of 179 placebo-controlled trials of medications to treat migraine¹ headache identified 3 trials involving ACE inhibitors and 3 involving ARBs (TABLE¹). The authors of the meta-analysis gave 2 trials (one of lisinopril and one of candesartan) relatively high scores for methodologic quality.

Lisinopril reduces hours, days with headache and days with migraine

The first, a placebo-controlled lisinopril crossover trial, included 60 patients, 19 to 59 years of age, who experienced migraines with or without auras 2 to 6 times per month.² Thirty patients received lisinopril 10 mg once daily for 1 week followed by 20 mg once daily (using 10-mg tablets) for 11 weeks. The other 30 patients received a similarly titrated placebo for 12 weeks. After a 2-week washout period, the groups were given the other therapy. Patients took triptan medications and analgesics as needed. Primary outcomes, extracted from headache diaries, included the number of hours and days with headache (of any type) and number of days with migraine specifically.

Out of the initial 60 participants, 47 completed the study. Using intention-to-treat analysis, lisinopril therapy resulted in fewer hours with headache (162 vs 138, a 15% difference; 95% confidence interval [CI], 0-30), fewer days with headache (25 vs 21, a 16% difference; 95% CI, 5-27), and fewer days with migraine (19 vs 15, a 22% change; 95% CI, 11-33), compared with placebo. Three patients discontinued lisinopril because of adverse events. Mean blood pressure reduction with lisinopril was 7 mm Hg systolic and 5 mm Hg diastolic more than placebo (P<.0001 for both comparisons).

Candesartan also decreases headaches and migraine

The other study given a high methodologic quality score by the network-meta-analysis authors was a placebo-controlled candesartan crossover trial.³ It enrolled 60 patients, 18 to 65 years of age, who experienced migraines with or without auras 2 to 6 times per month.

Thirty patients received 16 mg candesartan daily for 12 weeks, followed by a 4-week washout period before taking a placebo tablet daily for 12 weeks. The other 30 received placebo followed by candesartan. Patients took triptan medications and analgesics as needed. The primary outcome measure was days with headache, recorded by patients using daily diaries. Three patients didn’t complete the study.

Using intention-to-treat analysis, the mean number of days with headache was 18.5 with placebo and 13.6 with candesartan (P=.001). Secondary end points that also favored candesartan were hours with migraine (92 vs 59; P<.001), hours with headache (139 vs 95; P<.001), days with migraine (13 vs 9; P<.001), and days of sick leave (3.9 vs 1.4; P=.01). Adverse events, including dizziness, were similar with candesartan and placebo. Mean blood pressure reduction with candesartan was 11 mm Hg systolic and 7 mm Hg diastolic over placebo (P<.001 for both comparisons).

Continue to: Overall both drugs have a significant effect on number of headaches

 

 

Overall both drugs have a significant effect on number of headaches

Among all ACE inhibitor and ARB trials in the review, a network meta-analysis (designed to compare interventions never studied head-to-head) could be performed only on candesartan, which had a small effect size on headache frequency relative to placebo (2 trials, 118 patients; standardized mean difference [SMD]= −0.33; 95% CI, −0.59 to −0.7).¹ (An SMD of 0.2 is considered small, 0.6 moderate, and 1.2 large). Combining data from all ACE inhibitor and ARB trials together in a standard meta-analysis yielded a large effect size on number of headaches per month compared with placebo (6 trials, 351 patients; SMD= −1.12; 95% CI, −1.97 to −0.27).¹

RECOMMENDATIONS

In 2012, the American Academy of Neurology and the American Headache Society published guidelines on pharmacologic treatment for episodic migraine prevention in adults.⁴ The guidelines stated that lisinopril and candesartan were “possibly effective” for migraine prevention (level C recommendation based on a single lower-quality randomized clinical trial). They further advised clinicians to be “mindful of comorbid and coexistent conditions in patients with migraine to maximize potential treatment efficacy.”

EVIDENCE SUMMARY

A network meta-analysis of 179 placebo-controlled trials of medications to treat migraine¹ headache identified 3 trials involving ACE inhibitors and 3 involving ARBs (TABLE¹). The authors of the meta-analysis gave 2 trials (one of lisinopril and one of candesartan) relatively high scores for methodologic quality.

Lisinopril reduces hours, days with headache and days with migraine

The first, a placebo-controlled lisinopril crossover trial, included 60 patients, 19 to 59 years of age, who experienced migraines with or without auras 2 to 6 times per month.² Thirty patients received lisinopril 10 mg once daily for 1 week followed by 20 mg once daily (using 10-mg tablets) for 11 weeks. The other 30 patients received a similarly titrated placebo for 12 weeks. After a 2-week washout period, the groups were given the other therapy. Patients took triptan medications and analgesics as needed. Primary outcomes, extracted from headache diaries, included the number of hours and days with headache (of any type) and number of days with migraine specifically.

Out of the initial 60 participants, 47 completed the study. Using intention-to-treat analysis, lisinopril therapy resulted in fewer hours with headache (162 vs 138, a 15% difference; 95% confidence interval [CI], 0-30), fewer days with headache (25 vs 21, a 16% difference; 95% CI, 5-27), and fewer days with migraine (19 vs 15, a 22% change; 95% CI, 11-33), compared with placebo. Three patients discontinued lisinopril because of adverse events. Mean blood pressure reduction with lisinopril was 7 mm Hg systolic and 5 mm Hg diastolic more than placebo (P<.0001 for both comparisons).

Candesartan also decreases headaches and migraine

The other study given a high methodologic quality score by the network-meta-analysis authors was a placebo-controlled candesartan crossover trial.³ It enrolled 60 patients, 18 to 65 years of age, who experienced migraines with or without auras 2 to 6 times per month.

Thirty patients received 16 mg candesartan daily for 12 weeks, followed by a 4-week washout period before taking a placebo tablet daily for 12 weeks. The other 30 received placebo followed by candesartan. Patients took triptan medications and analgesics as needed. The primary outcome measure was days with headache, recorded by patients using daily diaries. Three patients didn’t complete the study.

Using intention-to-treat analysis, the mean number of days with headache was 18.5 with placebo and 13.6 with candesartan (P=.001). Secondary end points that also favored candesartan were hours with migraine (92 vs 59; P<.001), hours with headache (139 vs 95; P<.001), days with migraine (13 vs 9; P<.001), and days of sick leave (3.9 vs 1.4; P=.01). Adverse events, including dizziness, were similar with candesartan and placebo. Mean blood pressure reduction with candesartan was 11 mm Hg systolic and 7 mm Hg diastolic over placebo (P<.001 for both comparisons).

Continue to: Overall both drugs have a significant effect on number of headaches

 

 

Overall both drugs have a significant effect on number of headaches

Among all ACE inhibitor and ARB trials in the review, a network meta-analysis (designed to compare interventions never studied head-to-head) could be performed only on candesartan, which had a small effect size on headache frequency relative to placebo (2 trials, 118 patients; standardized mean difference [SMD]= −0.33; 95% CI, −0.59 to −0.7).¹ (An SMD of 0.2 is considered small, 0.6 moderate, and 1.2 large). Combining data from all ACE inhibitor and ARB trials together in a standard meta-analysis yielded a large effect size on number of headaches per month compared with placebo (6 trials, 351 patients; SMD= −1.12; 95% CI, −1.97 to −0.27).¹

RECOMMENDATIONS

In 2012, the American Academy of Neurology and the American Headache Society published guidelines on pharmacologic treatment for episodic migraine prevention in adults.⁴ The guidelines stated that lisinopril and candesartan were “possibly effective” for migraine prevention (level C recommendation based on a single lower-quality randomized clinical trial). They further advised clinicians to be “mindful of comorbid and coexistent conditions in patients with migraine to maximize potential treatment efficacy.”

Agrees that OC use clearly reduces mortality

Recent evidence from long-term observations of hundreds of thousands of women, in 10 European countries, clearly demonstrated that the use of oral contraceptives (OCs) reduced mortality by roughly 10%.^1,2 Newer OCs increase women’s overall survival. 

In comparison, reducing obesity by 5 body mass index points would reduce mortality by only 5%, from 1.05 to 1.³

Dr. Stavros Saripanidis
Thessaloniki, Greece

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Agrees that OC use clearly reduces mortality

Recent evidence from long-term observations of hundreds of thousands of women, in 10 European countries, clearly demonstrated that the use of oral contraceptives (OCs) reduced mortality by roughly 10%.^1,2 Newer OCs increase women’s overall survival. 

In comparison, reducing obesity by 5 body mass index points would reduce mortality by only 5%, from 1.05 to 1.³

Dr. Stavros Saripanidis
Thessaloniki, Greece

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Agrees that OC use clearly reduces mortality

Recent evidence from long-term observations of hundreds of thousands of women, in 10 European countries, clearly demonstrated that the use of oral contraceptives (OCs) reduced mortality by roughly 10%.^1,2 Newer OCs increase women’s overall survival. 

In comparison, reducing obesity by 5 body mass index points would reduce mortality by only 5%, from 1.05 to 1.³

Dr. Stavros Saripanidis
Thessaloniki, Greece

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE 1

A 94-year-old white woman, who had been in excellent health (other than pernicious anemia, treated with monthly cyanocobalamin injections), suddenly developed gastrointestinal distress 2 weeks earlier. A work-up performed by her physician revealed advanced pancreatic cancer.

Over the next 2 weeks, she experienced pain and nausea. A left-sided fistula developed externally at her flank that drained feces and induced considerable discomfort. An indwelling drain was placed, which provided some relief, but the patient’s dyspepsia, pain, and nausea escalated.

One month into her disease course, an oncologist reported on her potential treatment options and prognosis. Her life expectancy was about 3 months without treatment. This could be extended by 1 to 2 months with extensive surgical and chemotherapeutic interventions, but would further diminish her quality of life. The patient declined further treatment.

Her clinical status declined, and her quality of life significantly deteriorated. At 3 months, she felt life had lost meaning and was not worth living. She began asking for a morphine overdose, stating a desire to end her life.

After several discussions with the oncologist, one of the patient’s adult children suggested that her mother stop eating and drinking in order to diminish discomfort and hasten her demise. This plan was adopted, and the patient declined food and drank only enough to swish for oral comfort. At 4 months, she reported less physical discomfort and an improved mood. She died otherwise uneventfully 2 weeks later.

CASE 2

An 83-year-old woman with advanced Parkinson’s disease had become increasingly disabled. Her gait and motor skills were dramatically and progressively compromised. Pharmacotherapy yielded only transient improvement and considerable adverse effects of choreiform hyperkinesia and hallucinations, which were troublesome and embarrassing. Her social, physical, and personal well-being declined to the point that she was placed in a nursing home.

Despite this help, worsening parkinsonism progressively diminished her physical capacity. She became largely bedridden and developed decubitus ulcerations, especially at the coccyx, which produced severe pain and distress.

Continue to: The confluence of pain...

The confluence of pain, bedfastness, constipation, and social isolation yielded a loss of interest and joy in life. The patient required assistance with almost every aspect of daily life, including eating. As the illness progressed, she prayed at night that God would “take her.” Each morning, she spoke of disappointment upon reawakening. She overtly expressed her lack of desire to live to her family. Medical interventions were increasingly ineffective.

After repeated family and physician discussions had focused on her death wishes, one adult daughter recommended her mother stop eating and drinking; her food intake was already minimal. Although she did not endorse this plan verbally, the patient’s oral intake significantly diminished. Within 2 weeks, her physical state had declined, and she died one night during sleep.

Adequate hydration is stressed in physician education and practice. A conventional expectation to normalize fluid balance is important to restore health and improve well-being. In addition to being good medical practice, it can also show patients (and their families) that we care about their well-being.^1-3

Do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.

Treating dehydration in individuals with terminal illness is controversial from both medical and ethical standpoints. While the natural tendency of physicians is to restore full hydration to their patients, in select cases of imminent death, being fully hydrated may prolong discomfort.^1,2 Emphasis in this population should be consistently placed on improving comfort care and quality of life, rather than prolonging life or delaying death.^3-5

Continue to: A multifactorial, patient-based decision

 

 

A multifactorial, patient-based decision

Years ago, before the advent of hospitalizing people with terminal illnesses, dying at home amongst loved ones was believed to be peaceful. Nevertheless, questions arise about the practical vs ethical approach to caring for patients with terminal illness.² Sometimes it is difficult to find a balance between potential health care benefits and the burdens induced by medical, legal, moral, and/or social pressures. Our medical communities and the general population uphold preserving dignity at the end of life, which is supported by organizations such as Compassion & Choices (a nonprofit group that seeks to improve and expand options for end of life care; https://www.compassionandchoices.org).

Allowing for voluntary, patient-determined dehydration in those with terminal illness can offer greater comfort than maintaining the physiologic degrees of fluid balance. There are 3 key considerations to bear in mind:

• Hydration is usually a standard part of quality medical care.¹
• Selectively allowing dehydration in patients who are dying can facilitate comfort.^1-5
• Dehydration may be a deliberate strategy to hasten death.⁶

When is dehydration appropriate?

Hydration is not favored whenever doing so may increase discomfort and prolong pain without meaningful life.³ In people with terminal illness, hydration may reduce quality of life.⁷

The data support dehydration in certain patients. A randomized controlled trial involving 129 patients receiving hospice care compared parenteral hydration with placebo, documenting that rehydration did not improve symptoms or quality of life; there was no significant difference between patients who were hydrated and those who were dehydrated.⁷ In fact, dehydration may even yield greater patient comfort.⁸

Case reports, retrospective chart reviews, and testimonials from health care professionals have reported that being less hydrated can diminish nausea, vomiting, diarrhea, ascites, edema, and urinary or bowel incontinence, with less skin breakdown.⁸ Hydration, on the other hand, may exacerbate dyspnea, coughing, and choking, increasing the need for suctioning.

Continue to: A component of palliative care

A component of palliative care. When death is imminent, palliation becomes key. Pain may be more manageable with less fluids, an important goal for this population.^6,8 Dehydration is associated with an accumulation of opioids throughout body fluid volumes, which may decrease pain, consciousness, and/or agony.² Pharmacotherapies might also have greater efficacy in a dehydrated patient.⁹ In addition, tissue shrinkage might mitigate pain from tumors, especially those in confined spaces.⁸

Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients.

Hospice care and palliative medicine confirm that routine hydration is not always advisable; allowing for dehydration is a conventional practice, especially in older adults with terminal illness.⁷ However, do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.⁸ Facilitate oral care in the form of swishing fluids, elective drinking, or providing mouth lubrication for any patients selectively allowed to become dehydrated.^3,8

The role of the physician in decision-making

Patients with terminal illness sometimes do not want fluids and may actively decline food and drink.¹⁰ This can be emotionally distressing for family members and/or caregivers to witness. Physicians can address this concern by compassionately explaining: “I know you are concerned that your relative is not eating or drinking, but there is no indication that hydration or parenteral feeding will improve function or quality of life.”¹⁰ This can generate a discussion between physicians and families by acknowledging concerns, relieving distress, and leading to what is ultimately best for the patient.

Implications for practice: Individualized autonomy

Physicians must identify patients who wish to die by purposely becoming dehydrated and uphold the important physician obligation to hydrate those with a recoverable illness. Allowing for a moderate degree of dehydration might provide greater comfort in select people with terminal illness. Some individuals for whom life has lost meaning may choose dehydration as a means to hasten their departure.^4-6 Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients. It can be difficult for caregivers, but it is medically indicated to comply with a patient’s desire for comfort when death is imminent.

Providing palliation as a priority over treatment is sometimes challenging, but comfort care takes preference and is always coordinated with the person’s own wishes. Facilitating dehydration removes assisted-suicide issues or requests and thus affords everyone involved more emotional comfort. An advantage of this method is that a decisional patient maintains full control over the direction of their choices and helps preserve dignity during the end of life.

CORRESPONDENCE
Steven Lippmann, MD, Department of Psychiatry, University of Louisville School of Medicine, 401 East Chestnut Street, Suite 610, Louisville, KY 40202; [email protected]

CASE 1

A 94-year-old white woman, who had been in excellent health (other than pernicious anemia, treated with monthly cyanocobalamin injections), suddenly developed gastrointestinal distress 2 weeks earlier. A work-up performed by her physician revealed advanced pancreatic cancer.

Over the next 2 weeks, she experienced pain and nausea. A left-sided fistula developed externally at her flank that drained feces and induced considerable discomfort. An indwelling drain was placed, which provided some relief, but the patient’s dyspepsia, pain, and nausea escalated.

One month into her disease course, an oncologist reported on her potential treatment options and prognosis. Her life expectancy was about 3 months without treatment. This could be extended by 1 to 2 months with extensive surgical and chemotherapeutic interventions, but would further diminish her quality of life. The patient declined further treatment.

Her clinical status declined, and her quality of life significantly deteriorated. At 3 months, she felt life had lost meaning and was not worth living. She began asking for a morphine overdose, stating a desire to end her life.

After several discussions with the oncologist, one of the patient’s adult children suggested that her mother stop eating and drinking in order to diminish discomfort and hasten her demise. This plan was adopted, and the patient declined food and drank only enough to swish for oral comfort. At 4 months, she reported less physical discomfort and an improved mood. She died otherwise uneventfully 2 weeks later.

CASE 2

An 83-year-old woman with advanced Parkinson’s disease had become increasingly disabled. Her gait and motor skills were dramatically and progressively compromised. Pharmacotherapy yielded only transient improvement and considerable adverse effects of choreiform hyperkinesia and hallucinations, which were troublesome and embarrassing. Her social, physical, and personal well-being declined to the point that she was placed in a nursing home.

Despite this help, worsening parkinsonism progressively diminished her physical capacity. She became largely bedridden and developed decubitus ulcerations, especially at the coccyx, which produced severe pain and distress.

Continue to: The confluence of pain...

The confluence of pain, bedfastness, constipation, and social isolation yielded a loss of interest and joy in life. The patient required assistance with almost every aspect of daily life, including eating. As the illness progressed, she prayed at night that God would “take her.” Each morning, she spoke of disappointment upon reawakening. She overtly expressed her lack of desire to live to her family. Medical interventions were increasingly ineffective.

After repeated family and physician discussions had focused on her death wishes, one adult daughter recommended her mother stop eating and drinking; her food intake was already minimal. Although she did not endorse this plan verbally, the patient’s oral intake significantly diminished. Within 2 weeks, her physical state had declined, and she died one night during sleep.

Adequate hydration is stressed in physician education and practice. A conventional expectation to normalize fluid balance is important to restore health and improve well-being. In addition to being good medical practice, it can also show patients (and their families) that we care about their well-being.^1-3

Do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.

Treating dehydration in individuals with terminal illness is controversial from both medical and ethical standpoints. While the natural tendency of physicians is to restore full hydration to their patients, in select cases of imminent death, being fully hydrated may prolong discomfort.^1,2 Emphasis in this population should be consistently placed on improving comfort care and quality of life, rather than prolonging life or delaying death.^3-5

Continue to: A multifactorial, patient-based decision

 

 

A multifactorial, patient-based decision

Years ago, before the advent of hospitalizing people with terminal illnesses, dying at home amongst loved ones was believed to be peaceful. Nevertheless, questions arise about the practical vs ethical approach to caring for patients with terminal illness.² Sometimes it is difficult to find a balance between potential health care benefits and the burdens induced by medical, legal, moral, and/or social pressures. Our medical communities and the general population uphold preserving dignity at the end of life, which is supported by organizations such as Compassion & Choices (a nonprofit group that seeks to improve and expand options for end of life care; https://www.compassionandchoices.org).

Allowing for voluntary, patient-determined dehydration in those with terminal illness can offer greater comfort than maintaining the physiologic degrees of fluid balance. There are 3 key considerations to bear in mind:

• Hydration is usually a standard part of quality medical care.¹
• Selectively allowing dehydration in patients who are dying can facilitate comfort.^1-5
• Dehydration may be a deliberate strategy to hasten death.⁶

When is dehydration appropriate?

Hydration is not favored whenever doing so may increase discomfort and prolong pain without meaningful life.³ In people with terminal illness, hydration may reduce quality of life.⁷

The data support dehydration in certain patients. A randomized controlled trial involving 129 patients receiving hospice care compared parenteral hydration with placebo, documenting that rehydration did not improve symptoms or quality of life; there was no significant difference between patients who were hydrated and those who were dehydrated.⁷ In fact, dehydration may even yield greater patient comfort.⁸

Case reports, retrospective chart reviews, and testimonials from health care professionals have reported that being less hydrated can diminish nausea, vomiting, diarrhea, ascites, edema, and urinary or bowel incontinence, with less skin breakdown.⁸ Hydration, on the other hand, may exacerbate dyspnea, coughing, and choking, increasing the need for suctioning.

Continue to: A component of palliative care

A component of palliative care. When death is imminent, palliation becomes key. Pain may be more manageable with less fluids, an important goal for this population.^6,8 Dehydration is associated with an accumulation of opioids throughout body fluid volumes, which may decrease pain, consciousness, and/or agony.² Pharmacotherapies might also have greater efficacy in a dehydrated patient.⁹ In addition, tissue shrinkage might mitigate pain from tumors, especially those in confined spaces.⁸

Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients.

Hospice care and palliative medicine confirm that routine hydration is not always advisable; allowing for dehydration is a conventional practice, especially in older adults with terminal illness.⁷ However, do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.⁸ Facilitate oral care in the form of swishing fluids, elective drinking, or providing mouth lubrication for any patients selectively allowed to become dehydrated.^3,8

The role of the physician in decision-making

Patients with terminal illness sometimes do not want fluids and may actively decline food and drink.¹⁰ This can be emotionally distressing for family members and/or caregivers to witness. Physicians can address this concern by compassionately explaining: “I know you are concerned that your relative is not eating or drinking, but there is no indication that hydration or parenteral feeding will improve function or quality of life.”¹⁰ This can generate a discussion between physicians and families by acknowledging concerns, relieving distress, and leading to what is ultimately best for the patient.

Implications for practice: Individualized autonomy

Physicians must identify patients who wish to die by purposely becoming dehydrated and uphold the important physician obligation to hydrate those with a recoverable illness. Allowing for a moderate degree of dehydration might provide greater comfort in select people with terminal illness. Some individuals for whom life has lost meaning may choose dehydration as a means to hasten their departure.^4-6 Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients. It can be difficult for caregivers, but it is medically indicated to comply with a patient’s desire for comfort when death is imminent.

Providing palliation as a priority over treatment is sometimes challenging, but comfort care takes preference and is always coordinated with the person’s own wishes. Facilitating dehydration removes assisted-suicide issues or requests and thus affords everyone involved more emotional comfort. An advantage of this method is that a decisional patient maintains full control over the direction of their choices and helps preserve dignity during the end of life.

CORRESPONDENCE
Steven Lippmann, MD, Department of Psychiatry, University of Louisville School of Medicine, 401 East Chestnut Street, Suite 610, Louisville, KY 40202; [email protected]

CASE 1

A 94-year-old white woman, who had been in excellent health (other than pernicious anemia, treated with monthly cyanocobalamin injections), suddenly developed gastrointestinal distress 2 weeks earlier. A work-up performed by her physician revealed advanced pancreatic cancer.

Over the next 2 weeks, she experienced pain and nausea. A left-sided fistula developed externally at her flank that drained feces and induced considerable discomfort. An indwelling drain was placed, which provided some relief, but the patient’s dyspepsia, pain, and nausea escalated.

One month into her disease course, an oncologist reported on her potential treatment options and prognosis. Her life expectancy was about 3 months without treatment. This could be extended by 1 to 2 months with extensive surgical and chemotherapeutic interventions, but would further diminish her quality of life. The patient declined further treatment.

Her clinical status declined, and her quality of life significantly deteriorated. At 3 months, she felt life had lost meaning and was not worth living. She began asking for a morphine overdose, stating a desire to end her life.

After several discussions with the oncologist, one of the patient’s adult children suggested that her mother stop eating and drinking in order to diminish discomfort and hasten her demise. This plan was adopted, and the patient declined food and drank only enough to swish for oral comfort. At 4 months, she reported less physical discomfort and an improved mood. She died otherwise uneventfully 2 weeks later.

CASE 2

An 83-year-old woman with advanced Parkinson’s disease had become increasingly disabled. Her gait and motor skills were dramatically and progressively compromised. Pharmacotherapy yielded only transient improvement and considerable adverse effects of choreiform hyperkinesia and hallucinations, which were troublesome and embarrassing. Her social, physical, and personal well-being declined to the point that she was placed in a nursing home.

Despite this help, worsening parkinsonism progressively diminished her physical capacity. She became largely bedridden and developed decubitus ulcerations, especially at the coccyx, which produced severe pain and distress.

Continue to: The confluence of pain...

The confluence of pain, bedfastness, constipation, and social isolation yielded a loss of interest and joy in life. The patient required assistance with almost every aspect of daily life, including eating. As the illness progressed, she prayed at night that God would “take her.” Each morning, she spoke of disappointment upon reawakening. She overtly expressed her lack of desire to live to her family. Medical interventions were increasingly ineffective.

After repeated family and physician discussions had focused on her death wishes, one adult daughter recommended her mother stop eating and drinking; her food intake was already minimal. Although she did not endorse this plan verbally, the patient’s oral intake significantly diminished. Within 2 weeks, her physical state had declined, and she died one night during sleep.

Adequate hydration is stressed in physician education and practice. A conventional expectation to normalize fluid balance is important to restore health and improve well-being. In addition to being good medical practice, it can also show patients (and their families) that we care about their well-being.^1-3

Do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.

Treating dehydration in individuals with terminal illness is controversial from both medical and ethical standpoints. While the natural tendency of physicians is to restore full hydration to their patients, in select cases of imminent death, being fully hydrated may prolong discomfort.^1,2 Emphasis in this population should be consistently placed on improving comfort care and quality of life, rather than prolonging life or delaying death.^3-5

Continue to: A multifactorial, patient-based decision

 

 

A multifactorial, patient-based decision

Years ago, before the advent of hospitalizing people with terminal illnesses, dying at home amongst loved ones was believed to be peaceful. Nevertheless, questions arise about the practical vs ethical approach to caring for patients with terminal illness.² Sometimes it is difficult to find a balance between potential health care benefits and the burdens induced by medical, legal, moral, and/or social pressures. Our medical communities and the general population uphold preserving dignity at the end of life, which is supported by organizations such as Compassion & Choices (a nonprofit group that seeks to improve and expand options for end of life care; https://www.compassionandchoices.org).

Allowing for voluntary, patient-determined dehydration in those with terminal illness can offer greater comfort than maintaining the physiologic degrees of fluid balance. There are 3 key considerations to bear in mind:

• Hydration is usually a standard part of quality medical care.¹
• Selectively allowing dehydration in patients who are dying can facilitate comfort.^1-5
• Dehydration may be a deliberate strategy to hasten death.⁶

When is dehydration appropriate?

Hydration is not favored whenever doing so may increase discomfort and prolong pain without meaningful life.³ In people with terminal illness, hydration may reduce quality of life.⁷

The data support dehydration in certain patients. A randomized controlled trial involving 129 patients receiving hospice care compared parenteral hydration with placebo, documenting that rehydration did not improve symptoms or quality of life; there was no significant difference between patients who were hydrated and those who were dehydrated.⁷ In fact, dehydration may even yield greater patient comfort.⁸

Case reports, retrospective chart reviews, and testimonials from health care professionals have reported that being less hydrated can diminish nausea, vomiting, diarrhea, ascites, edema, and urinary or bowel incontinence, with less skin breakdown.⁸ Hydration, on the other hand, may exacerbate dyspnea, coughing, and choking, increasing the need for suctioning.

Continue to: A component of palliative care

A component of palliative care. When death is imminent, palliation becomes key. Pain may be more manageable with less fluids, an important goal for this population.^6,8 Dehydration is associated with an accumulation of opioids throughout body fluid volumes, which may decrease pain, consciousness, and/or agony.² Pharmacotherapies might also have greater efficacy in a dehydrated patient.⁹ In addition, tissue shrinkage might mitigate pain from tumors, especially those in confined spaces.⁸

Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients.

Hospice care and palliative medicine confirm that routine hydration is not always advisable; allowing for dehydration is a conventional practice, especially in older adults with terminal illness.⁷ However, do not deny access to liquids if a patient wants them, and never force unwanted fluids by any route.⁸ Facilitate oral care in the form of swishing fluids, elective drinking, or providing mouth lubrication for any patients selectively allowed to become dehydrated.^3,8

The role of the physician in decision-making

Patients with terminal illness sometimes do not want fluids and may actively decline food and drink.¹⁰ This can be emotionally distressing for family members and/or caregivers to witness. Physicians can address this concern by compassionately explaining: “I know you are concerned that your relative is not eating or drinking, but there is no indication that hydration or parenteral feeding will improve function or quality of life.”¹⁰ This can generate a discussion between physicians and families by acknowledging concerns, relieving distress, and leading to what is ultimately best for the patient.

Implications for practice: Individualized autonomy

Physicians must identify patients who wish to die by purposely becoming dehydrated and uphold the important physician obligation to hydrate those with a recoverable illness. Allowing for a moderate degree of dehydration might provide greater comfort in select people with terminal illness. Some individuals for whom life has lost meaning may choose dehydration as a means to hasten their departure.^4-6 Allowing individualized autonomy over life and death choices is part of a physician’s obligation to their patients. It can be difficult for caregivers, but it is medically indicated to comply with a patient’s desire for comfort when death is imminent.

Providing palliation as a priority over treatment is sometimes challenging, but comfort care takes preference and is always coordinated with the person’s own wishes. Facilitating dehydration removes assisted-suicide issues or requests and thus affords everyone involved more emotional comfort. An advantage of this method is that a decisional patient maintains full control over the direction of their choices and helps preserve dignity during the end of life.

CORRESPONDENCE
Steven Lippmann, MD, Department of Psychiatry, University of Louisville School of Medicine, 401 East Chestnut Street, Suite 610, Louisville, KY 40202; [email protected]