ALL patient

Photo by Bill Branson

New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).

Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.

The team reported these findings in Leukemia & Lymphoma.

With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.

“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.

“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”

To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.

The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.

The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.

And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.

“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.

“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”

ALL patient

Photo by Bill Branson

New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).

Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.

The team reported these findings in Leukemia & Lymphoma.

With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.

“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.

“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”

To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.

The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.

The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.

And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.

“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.

“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”

ALL patient

Photo by Bill Branson

New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).

Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.

The team reported these findings in Leukemia & Lymphoma.

With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.

“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.

“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”

To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.

The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.

The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.

And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.

“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.

“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”

 

 

Doctor consulting with

a cancer patient

Photo courtesy of NCI/

Mathews Media Group

 

The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).

The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.

It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.

The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.

It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.

“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.

“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”

The consultation closes on March 11, 2016, with the final guideline expected in the summer.

 

 

Doctor consulting with

a cancer patient

Photo courtesy of NCI/

Mathews Media Group

 

The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).

The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.

It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.

The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.

It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.

“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.

“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”

The consultation closes on March 11, 2016, with the final guideline expected in the summer.

 

 

Doctor consulting with

a cancer patient

Photo courtesy of NCI/

Mathews Media Group

 

The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).

The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.

It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.

The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.

It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.

“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.

“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”

The consultation closes on March 11, 2016, with the final guideline expected in the summer.

A Boston Bowel Preparation Scale (BBPS) score of 2 – indicating mild residual staining and small stool fragments – was as good as the optimal preparation score of 3 for visualizing polyps and adenomas larger than 5 mm and advanced adenomas during colonoscopy, researchers said.

A score of 2 might increase the chances of missing smaller polyps, but is adequate for detecting clinically significant masses, Dr. Brian Clark of Yale University, New Haven, Conn., and his associates reported in the February issue of Gastroenterology. But a score of 1 – meaning that there is enough staining or stool to obscure the mucosa – significantly increased the chances of missing adenomas larger than 5 mm, they said. Patients should undergo early repeat colonoscopy if their BBPS score is 1 or 0 in any colon segment, they emphasized.

Source: American Gastroenterological Association

Bowel preparation for colonoscopy is considered adequate if endoscopists can detect polyps larger than 5 mm, but no prior study had quantified the amount of preparation needed. This prospective observational study assessed adequate preparation in terms of the BBPS, which scores each of three colon segments on a scale of 0 (solid stool covering the mucosa) to 3 points (entire mucosa seen well, with no residual staining). Study participants included 438 men aged 50-75 years who underwent screening or surveillance colonoscopy at a single Veterans Affairs center, followed by repeat colonoscopies within 60 days performed by different blinded endoscopists. The investigators excluded patients who scored 0 in all colon segments or had familial polyposis syndrome, inflammatory bowel disease, polyps so large that they could not be completely removed, or a history of colonic or rectal resection. In all, they analyzed 1,161 colon segments (Gastroenterology. 2015 Dec 7. doi: 10.1053/j.gastro.2015.09.041).

Endoscopists missed about 5% of adenomas greater than 5 mm, regardless of whether BBPS scores were 2 or 3 in a model that accounted for age, reason for colonoscopy, colon segment, number of polyps removed in the first examination, and endoscopist performing the procedure, the researchers said. But when BBPS scores were 1, endoscopists missed 16% of adenomas larger than 5 mm, a difference of about 10%. Furthermore, 43% of screening and surveillance intervals would have been incorrect had they been based solely on an initial examination for which scores were 1 in at least one segment. In contrast, only about 15% of intervals would have been incorrect for patients who scored 2 or 3 in all segments.

In all, 80% of patients were sufficiently prepared, having scored at least 2 in all segments on the first examination. “Determining whether a patient’s preparation quality is adequate is one of the most common and important decisions made by gastroenterologists each day,” the researchers said. Between 25% and 30% of screening and surveillance colonoscopies occur at “inappropriately shortened intervals,” often because of uncertainty about what constitutes adequate visualization, they added. Defining adequate visualization based on bowel preparation could save billions of dollars in health care costs every year, minimize complications from unnecessary procedures, and pinpoint those patients who truly need an early repeat colonoscopy to help prevent interval colorectal cancer, they emphasized.

The National Institutes of Health funded the study. The investigators had no disclosures.

A Boston Bowel Preparation Scale (BBPS) score of 2 – indicating mild residual staining and small stool fragments – was as good as the optimal preparation score of 3 for visualizing polyps and adenomas larger than 5 mm and advanced adenomas during colonoscopy, researchers said.

A score of 2 might increase the chances of missing smaller polyps, but is adequate for detecting clinically significant masses, Dr. Brian Clark of Yale University, New Haven, Conn., and his associates reported in the February issue of Gastroenterology. But a score of 1 – meaning that there is enough staining or stool to obscure the mucosa – significantly increased the chances of missing adenomas larger than 5 mm, they said. Patients should undergo early repeat colonoscopy if their BBPS score is 1 or 0 in any colon segment, they emphasized.

Source: American Gastroenterological Association

Bowel preparation for colonoscopy is considered adequate if endoscopists can detect polyps larger than 5 mm, but no prior study had quantified the amount of preparation needed. This prospective observational study assessed adequate preparation in terms of the BBPS, which scores each of three colon segments on a scale of 0 (solid stool covering the mucosa) to 3 points (entire mucosa seen well, with no residual staining). Study participants included 438 men aged 50-75 years who underwent screening or surveillance colonoscopy at a single Veterans Affairs center, followed by repeat colonoscopies within 60 days performed by different blinded endoscopists. The investigators excluded patients who scored 0 in all colon segments or had familial polyposis syndrome, inflammatory bowel disease, polyps so large that they could not be completely removed, or a history of colonic or rectal resection. In all, they analyzed 1,161 colon segments (Gastroenterology. 2015 Dec 7. doi: 10.1053/j.gastro.2015.09.041).

Endoscopists missed about 5% of adenomas greater than 5 mm, regardless of whether BBPS scores were 2 or 3 in a model that accounted for age, reason for colonoscopy, colon segment, number of polyps removed in the first examination, and endoscopist performing the procedure, the researchers said. But when BBPS scores were 1, endoscopists missed 16% of adenomas larger than 5 mm, a difference of about 10%. Furthermore, 43% of screening and surveillance intervals would have been incorrect had they been based solely on an initial examination for which scores were 1 in at least one segment. In contrast, only about 15% of intervals would have been incorrect for patients who scored 2 or 3 in all segments.

In all, 80% of patients were sufficiently prepared, having scored at least 2 in all segments on the first examination. “Determining whether a patient’s preparation quality is adequate is one of the most common and important decisions made by gastroenterologists each day,” the researchers said. Between 25% and 30% of screening and surveillance colonoscopies occur at “inappropriately shortened intervals,” often because of uncertainty about what constitutes adequate visualization, they added. Defining adequate visualization based on bowel preparation could save billions of dollars in health care costs every year, minimize complications from unnecessary procedures, and pinpoint those patients who truly need an early repeat colonoscopy to help prevent interval colorectal cancer, they emphasized.

The National Institutes of Health funded the study. The investigators had no disclosures.

A Boston Bowel Preparation Scale (BBPS) score of 2 – indicating mild residual staining and small stool fragments – was as good as the optimal preparation score of 3 for visualizing polyps and adenomas larger than 5 mm and advanced adenomas during colonoscopy, researchers said.

A score of 2 might increase the chances of missing smaller polyps, but is adequate for detecting clinically significant masses, Dr. Brian Clark of Yale University, New Haven, Conn., and his associates reported in the February issue of Gastroenterology. But a score of 1 – meaning that there is enough staining or stool to obscure the mucosa – significantly increased the chances of missing adenomas larger than 5 mm, they said. Patients should undergo early repeat colonoscopy if their BBPS score is 1 or 0 in any colon segment, they emphasized.

Source: American Gastroenterological Association

Bowel preparation for colonoscopy is considered adequate if endoscopists can detect polyps larger than 5 mm, but no prior study had quantified the amount of preparation needed. This prospective observational study assessed adequate preparation in terms of the BBPS, which scores each of three colon segments on a scale of 0 (solid stool covering the mucosa) to 3 points (entire mucosa seen well, with no residual staining). Study participants included 438 men aged 50-75 years who underwent screening or surveillance colonoscopy at a single Veterans Affairs center, followed by repeat colonoscopies within 60 days performed by different blinded endoscopists. The investigators excluded patients who scored 0 in all colon segments or had familial polyposis syndrome, inflammatory bowel disease, polyps so large that they could not be completely removed, or a history of colonic or rectal resection. In all, they analyzed 1,161 colon segments (Gastroenterology. 2015 Dec 7. doi: 10.1053/j.gastro.2015.09.041).

Endoscopists missed about 5% of adenomas greater than 5 mm, regardless of whether BBPS scores were 2 or 3 in a model that accounted for age, reason for colonoscopy, colon segment, number of polyps removed in the first examination, and endoscopist performing the procedure, the researchers said. But when BBPS scores were 1, endoscopists missed 16% of adenomas larger than 5 mm, a difference of about 10%. Furthermore, 43% of screening and surveillance intervals would have been incorrect had they been based solely on an initial examination for which scores were 1 in at least one segment. In contrast, only about 15% of intervals would have been incorrect for patients who scored 2 or 3 in all segments.

In all, 80% of patients were sufficiently prepared, having scored at least 2 in all segments on the first examination. “Determining whether a patient’s preparation quality is adequate is one of the most common and important decisions made by gastroenterologists each day,” the researchers said. Between 25% and 30% of screening and surveillance colonoscopies occur at “inappropriately shortened intervals,” often because of uncertainty about what constitutes adequate visualization, they added. Defining adequate visualization based on bowel preparation could save billions of dollars in health care costs every year, minimize complications from unnecessary procedures, and pinpoint those patients who truly need an early repeat colonoscopy to help prevent interval colorectal cancer, they emphasized.

The National Institutes of Health funded the study. The investigators had no disclosures.

A 12-week, ribavirin-free regimen achieved sustained virologic response for 85% of patients with genotype 1 hepatitis C virus (HCV) infection, researchers reported in the February issue of Gastroenterology.

“This represents one of the first applications of a highly effective HCV regimen outside clinical trials,” said Dr. Mark S. Sulkowski of John Hopkins University in Baltimore and his associates. Adding ribavirin to the simeprevir and sofosbuvir combination regimen did not improve sustained virologic response (SVR), but patients were less likely to achieve it if they had cirrhosis, current or prior hepatic decompensation, or a history of failing other protease inhibitors, the investigators said.

Novel hepatitis C therapies have yielded “substantially lower” rates of SVR and more side effects in everyday practice than in clinical trials, the investigators noted. To better understand how some of newest HCV drugs perform in the real world, they conducted an observational cohort study of the safety, tolerability, and efficacy of simeprevir plus sofosbuvir for treating genotype 1 HCV infections in academic and nonacademic settings (HCV-TARGET) (Gastroenterology 2015 doi: 10.1053/j.gastro.2015.10.013).

A total of 836 patients received once-daily simeprevir (150 mg) and sofosbuvir (400 mg), and 169 of them also received ribavirin. Most (61%) patients had genotype 1a infection and were white (76%), male (61%), and cirrhotic (59%); 13% were black. Patients usually were treatment experienced, having failed peginterferon and ribavirin either with (12%) or without (46%) telaprevir or boceprevir, the researchers said.

In all, 675 (84%) patients achieved SVR after 12 weeks of treatment (SVR12; 95% confidence interval, 81%-87%). Adding ribavirin to the combination PI regimen did not improve SVR, regardless of cirrhosis status, genetic subtype, or treatment history. However, crude SVR12 rates were only 75% for patients with hepatic decompensation and 81% for those with cirrhosis, and these patients had significantly lower adjusted odds of achieving SVR, compared with other patients. In hindsight, decompensated and cirrhotic patients might have needed 24 weeks of treatment, as the Food and Drug Administration now recommends based on the COSMOS trial results (Lancet. 2014;384[9956]:1756-65), the investigators said.

The adjusted model did not uncover a link between genotype 1 subtype and SVR, but only about 10% of patients were tested for the Q80K polymorphism, which is more common in genotype 1a infections and is associated with treatment resistance, the investigators noted. Crude SVR12 rates were 92% for patients with genotype 1b infection and 86% for those with 1a infection, they said.

Only 3% of patients stopped treatment; 2% did so because of side effects, and ribavirin did not significantly affect rates of treatment discontinuation, said the investigators. The most common side effects were fatigue, headache, nausea, rash, and insomnia. Serious adverse events affected 5% of patients and included gastrointestinal bleeding (0.5%), hepatic failure or encephalopathy (1.2%), and infections (1.1%).

Taken together, these results show that simeprevir and sofosbuvir effectively translate from the clinical trial setting into clinical practice, said the researchers. “Additional research is needed to understand which patients may benefit from different treatment regimens or longer treatment durations,” they emphasized.

The study was supported by the University of Florida at Gainesville, the University of North Carolina at Chapel Hill, AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, Vertex, and the National Institutes of Health. Dr. Sulkowski reported grants and personal fees from Gilead, Janssen, Achillion, Abbvie, Merck, and Bristol-Myers Squibb. Of 14 coinvestigators, 13 reported financial relationships with a number of pharmaceutical companies.

A 12-week, ribavirin-free regimen achieved sustained virologic response for 85% of patients with genotype 1 hepatitis C virus (HCV) infection, researchers reported in the February issue of Gastroenterology.

“This represents one of the first applications of a highly effective HCV regimen outside clinical trials,” said Dr. Mark S. Sulkowski of John Hopkins University in Baltimore and his associates. Adding ribavirin to the simeprevir and sofosbuvir combination regimen did not improve sustained virologic response (SVR), but patients were less likely to achieve it if they had cirrhosis, current or prior hepatic decompensation, or a history of failing other protease inhibitors, the investigators said.

Novel hepatitis C therapies have yielded “substantially lower” rates of SVR and more side effects in everyday practice than in clinical trials, the investigators noted. To better understand how some of newest HCV drugs perform in the real world, they conducted an observational cohort study of the safety, tolerability, and efficacy of simeprevir plus sofosbuvir for treating genotype 1 HCV infections in academic and nonacademic settings (HCV-TARGET) (Gastroenterology 2015 doi: 10.1053/j.gastro.2015.10.013).

A total of 836 patients received once-daily simeprevir (150 mg) and sofosbuvir (400 mg), and 169 of them also received ribavirin. Most (61%) patients had genotype 1a infection and were white (76%), male (61%), and cirrhotic (59%); 13% were black. Patients usually were treatment experienced, having failed peginterferon and ribavirin either with (12%) or without (46%) telaprevir or boceprevir, the researchers said.

In all, 675 (84%) patients achieved SVR after 12 weeks of treatment (SVR12; 95% confidence interval, 81%-87%). Adding ribavirin to the combination PI regimen did not improve SVR, regardless of cirrhosis status, genetic subtype, or treatment history. However, crude SVR12 rates were only 75% for patients with hepatic decompensation and 81% for those with cirrhosis, and these patients had significantly lower adjusted odds of achieving SVR, compared with other patients. In hindsight, decompensated and cirrhotic patients might have needed 24 weeks of treatment, as the Food and Drug Administration now recommends based on the COSMOS trial results (Lancet. 2014;384[9956]:1756-65), the investigators said.

The adjusted model did not uncover a link between genotype 1 subtype and SVR, but only about 10% of patients were tested for the Q80K polymorphism, which is more common in genotype 1a infections and is associated with treatment resistance, the investigators noted. Crude SVR12 rates were 92% for patients with genotype 1b infection and 86% for those with 1a infection, they said.

Only 3% of patients stopped treatment; 2% did so because of side effects, and ribavirin did not significantly affect rates of treatment discontinuation, said the investigators. The most common side effects were fatigue, headache, nausea, rash, and insomnia. Serious adverse events affected 5% of patients and included gastrointestinal bleeding (0.5%), hepatic failure or encephalopathy (1.2%), and infections (1.1%).

Taken together, these results show that simeprevir and sofosbuvir effectively translate from the clinical trial setting into clinical practice, said the researchers. “Additional research is needed to understand which patients may benefit from different treatment regimens or longer treatment durations,” they emphasized.

The study was supported by the University of Florida at Gainesville, the University of North Carolina at Chapel Hill, AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, Vertex, and the National Institutes of Health. Dr. Sulkowski reported grants and personal fees from Gilead, Janssen, Achillion, Abbvie, Merck, and Bristol-Myers Squibb. Of 14 coinvestigators, 13 reported financial relationships with a number of pharmaceutical companies.

A 12-week, ribavirin-free regimen achieved sustained virologic response for 85% of patients with genotype 1 hepatitis C virus (HCV) infection, researchers reported in the February issue of Gastroenterology.

“This represents one of the first applications of a highly effective HCV regimen outside clinical trials,” said Dr. Mark S. Sulkowski of John Hopkins University in Baltimore and his associates. Adding ribavirin to the simeprevir and sofosbuvir combination regimen did not improve sustained virologic response (SVR), but patients were less likely to achieve it if they had cirrhosis, current or prior hepatic decompensation, or a history of failing other protease inhibitors, the investigators said.

Novel hepatitis C therapies have yielded “substantially lower” rates of SVR and more side effects in everyday practice than in clinical trials, the investigators noted. To better understand how some of newest HCV drugs perform in the real world, they conducted an observational cohort study of the safety, tolerability, and efficacy of simeprevir plus sofosbuvir for treating genotype 1 HCV infections in academic and nonacademic settings (HCV-TARGET) (Gastroenterology 2015 doi: 10.1053/j.gastro.2015.10.013).

A total of 836 patients received once-daily simeprevir (150 mg) and sofosbuvir (400 mg), and 169 of them also received ribavirin. Most (61%) patients had genotype 1a infection and were white (76%), male (61%), and cirrhotic (59%); 13% were black. Patients usually were treatment experienced, having failed peginterferon and ribavirin either with (12%) or without (46%) telaprevir or boceprevir, the researchers said.

In all, 675 (84%) patients achieved SVR after 12 weeks of treatment (SVR12; 95% confidence interval, 81%-87%). Adding ribavirin to the combination PI regimen did not improve SVR, regardless of cirrhosis status, genetic subtype, or treatment history. However, crude SVR12 rates were only 75% for patients with hepatic decompensation and 81% for those with cirrhosis, and these patients had significantly lower adjusted odds of achieving SVR, compared with other patients. In hindsight, decompensated and cirrhotic patients might have needed 24 weeks of treatment, as the Food and Drug Administration now recommends based on the COSMOS trial results (Lancet. 2014;384[9956]:1756-65), the investigators said.

The adjusted model did not uncover a link between genotype 1 subtype and SVR, but only about 10% of patients were tested for the Q80K polymorphism, which is more common in genotype 1a infections and is associated with treatment resistance, the investigators noted. Crude SVR12 rates were 92% for patients with genotype 1b infection and 86% for those with 1a infection, they said.

Only 3% of patients stopped treatment; 2% did so because of side effects, and ribavirin did not significantly affect rates of treatment discontinuation, said the investigators. The most common side effects were fatigue, headache, nausea, rash, and insomnia. Serious adverse events affected 5% of patients and included gastrointestinal bleeding (0.5%), hepatic failure or encephalopathy (1.2%), and infections (1.1%).

Taken together, these results show that simeprevir and sofosbuvir effectively translate from the clinical trial setting into clinical practice, said the researchers. “Additional research is needed to understand which patients may benefit from different treatment regimens or longer treatment durations,” they emphasized.

The study was supported by the University of Florida at Gainesville, the University of North Carolina at Chapel Hill, AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, Vertex, and the National Institutes of Health. Dr. Sulkowski reported grants and personal fees from Gilead, Janssen, Achillion, Abbvie, Merck, and Bristol-Myers Squibb. Of 14 coinvestigators, 13 reported financial relationships with a number of pharmaceutical companies.

Opt-out scheduling protocols and long appointment lead times contributed significantly to missed and canceled colonoscopy appointments at Veterans Health Administration facilities, researchers reported in the February issue of Clinical Gastroenterology and Hepatology.

These factors are within the control of the Veterans Affairs and could be altered to improve productivity and efficiency, said Melissa Partin, Ph.D., of the Center for Chronic Disease Outcomes Research at the Minneapolis Veterans Affairs Health Care System in Minneapolis, and her associates.

Source: American Gastroenterological Association

Missed and canceled medical appointments are always a concern, but particularly so for colonoscopy clinics, where they incur an average daily net loss of $725, the investigators noted. Most clinics have limited colonoscopy capacity, and even a 30-day wait for diagnostic colonoscopy has been linked to “modest but significantly elevated” chances of detecting cancer on exam, they added. To better understand these problems, they separately examined predictors of missed and canceled appointments among 27,994 patients who had positive fecal occult blood tests with diagnostic colonoscopies scheduled at 69 VA facilities between 2009 and 2011 (Clin Gastroenterol Hepatol. 2015 Aug 21. doi: 10.1016/j.cgh.2015.07.051).

Having a life expectancy of 6 months or less and no personal history of polyps best predicted missing an appointment, with odds ratios of 2.74 for each factor, the researchers said. However, only 0.47% of patients had such a short life expectancy. Other significant predictors of missed appointments included being seen at the largest and most complex facilities (odds ratio, 2.69; P = .007), having both psychiatric and substance abuse disorders (OR, 1.82; P less than .0001), and the use of opt-out scheduling, in which patients were automatically scheduled rather than having to schedule appointments themselves (OR, 1.57; P = .02). Canceled appointments also were linked to opt-out scheduling, as well as to older age and having no history of polyps.

Most appointment lead times were 28 days, and each 12-day increase in lead time increased the odds of missing or canceling appointments by about 15% (P less than .0001). The problem could be curtailed by the Veterans Access, Choice and Accountability Act of 2014, which allows those who cannot schedule VA appointments within 30 days to receive care from eligible non–VA providers, the investigators said. “Future research should focus on assessing the effect of the Choice Act on colonoscopy appointment lead time and on developing and evaluating efficient and effective approaches to implementing the other clinic-level changes supported by our findings,” they added.

The study might have oversimplified or missed changes in protocols because it used single-item survey measures at one point in time, the investigators said. For some patients, the first appointment after the fecal occult blood test may have been for another procedure besides colonoscopy, they added. Furthermore, they did not distinguish between appointments canceled by patients versus clinics. “The VHA is a unique context, characterized by a predominantly male, low-income population with high rates of mental health and substance abuse diagnoses. Therefore, our findings may not generalize to other settings,” they added. “However, our findings do have important implications for a substantial population of health providers and consumers in this country, because the VHA is the largest integrated health care system in the United States.”

The study was funded by the Department of Veterans Affairs Clinical Science Service and Health Services Research & Development Service. The investigators had no disclosures.

Opt-out scheduling protocols and long appointment lead times contributed significantly to missed and canceled colonoscopy appointments at Veterans Health Administration facilities, researchers reported in the February issue of Clinical Gastroenterology and Hepatology.

These factors are within the control of the Veterans Affairs and could be altered to improve productivity and efficiency, said Melissa Partin, Ph.D., of the Center for Chronic Disease Outcomes Research at the Minneapolis Veterans Affairs Health Care System in Minneapolis, and her associates.

Source: American Gastroenterological Association

Missed and canceled medical appointments are always a concern, but particularly so for colonoscopy clinics, where they incur an average daily net loss of $725, the investigators noted. Most clinics have limited colonoscopy capacity, and even a 30-day wait for diagnostic colonoscopy has been linked to “modest but significantly elevated” chances of detecting cancer on exam, they added. To better understand these problems, they separately examined predictors of missed and canceled appointments among 27,994 patients who had positive fecal occult blood tests with diagnostic colonoscopies scheduled at 69 VA facilities between 2009 and 2011 (Clin Gastroenterol Hepatol. 2015 Aug 21. doi: 10.1016/j.cgh.2015.07.051).

Having a life expectancy of 6 months or less and no personal history of polyps best predicted missing an appointment, with odds ratios of 2.74 for each factor, the researchers said. However, only 0.47% of patients had such a short life expectancy. Other significant predictors of missed appointments included being seen at the largest and most complex facilities (odds ratio, 2.69; P = .007), having both psychiatric and substance abuse disorders (OR, 1.82; P less than .0001), and the use of opt-out scheduling, in which patients were automatically scheduled rather than having to schedule appointments themselves (OR, 1.57; P = .02). Canceled appointments also were linked to opt-out scheduling, as well as to older age and having no history of polyps.

Most appointment lead times were 28 days, and each 12-day increase in lead time increased the odds of missing or canceling appointments by about 15% (P less than .0001). The problem could be curtailed by the Veterans Access, Choice and Accountability Act of 2014, which allows those who cannot schedule VA appointments within 30 days to receive care from eligible non–VA providers, the investigators said. “Future research should focus on assessing the effect of the Choice Act on colonoscopy appointment lead time and on developing and evaluating efficient and effective approaches to implementing the other clinic-level changes supported by our findings,” they added.

The study might have oversimplified or missed changes in protocols because it used single-item survey measures at one point in time, the investigators said. For some patients, the first appointment after the fecal occult blood test may have been for another procedure besides colonoscopy, they added. Furthermore, they did not distinguish between appointments canceled by patients versus clinics. “The VHA is a unique context, characterized by a predominantly male, low-income population with high rates of mental health and substance abuse diagnoses. Therefore, our findings may not generalize to other settings,” they added. “However, our findings do have important implications for a substantial population of health providers and consumers in this country, because the VHA is the largest integrated health care system in the United States.”

The study was funded by the Department of Veterans Affairs Clinical Science Service and Health Services Research & Development Service. The investigators had no disclosures.

Opt-out scheduling protocols and long appointment lead times contributed significantly to missed and canceled colonoscopy appointments at Veterans Health Administration facilities, researchers reported in the February issue of Clinical Gastroenterology and Hepatology.

These factors are within the control of the Veterans Affairs and could be altered to improve productivity and efficiency, said Melissa Partin, Ph.D., of the Center for Chronic Disease Outcomes Research at the Minneapolis Veterans Affairs Health Care System in Minneapolis, and her associates.

Source: American Gastroenterological Association

Missed and canceled medical appointments are always a concern, but particularly so for colonoscopy clinics, where they incur an average daily net loss of $725, the investigators noted. Most clinics have limited colonoscopy capacity, and even a 30-day wait for diagnostic colonoscopy has been linked to “modest but significantly elevated” chances of detecting cancer on exam, they added. To better understand these problems, they separately examined predictors of missed and canceled appointments among 27,994 patients who had positive fecal occult blood tests with diagnostic colonoscopies scheduled at 69 VA facilities between 2009 and 2011 (Clin Gastroenterol Hepatol. 2015 Aug 21. doi: 10.1016/j.cgh.2015.07.051).

Having a life expectancy of 6 months or less and no personal history of polyps best predicted missing an appointment, with odds ratios of 2.74 for each factor, the researchers said. However, only 0.47% of patients had such a short life expectancy. Other significant predictors of missed appointments included being seen at the largest and most complex facilities (odds ratio, 2.69; P = .007), having both psychiatric and substance abuse disorders (OR, 1.82; P less than .0001), and the use of opt-out scheduling, in which patients were automatically scheduled rather than having to schedule appointments themselves (OR, 1.57; P = .02). Canceled appointments also were linked to opt-out scheduling, as well as to older age and having no history of polyps.

Most appointment lead times were 28 days, and each 12-day increase in lead time increased the odds of missing or canceling appointments by about 15% (P less than .0001). The problem could be curtailed by the Veterans Access, Choice and Accountability Act of 2014, which allows those who cannot schedule VA appointments within 30 days to receive care from eligible non–VA providers, the investigators said. “Future research should focus on assessing the effect of the Choice Act on colonoscopy appointment lead time and on developing and evaluating efficient and effective approaches to implementing the other clinic-level changes supported by our findings,” they added.

The study might have oversimplified or missed changes in protocols because it used single-item survey measures at one point in time, the investigators said. For some patients, the first appointment after the fecal occult blood test may have been for another procedure besides colonoscopy, they added. Furthermore, they did not distinguish between appointments canceled by patients versus clinics. “The VHA is a unique context, characterized by a predominantly male, low-income population with high rates of mental health and substance abuse diagnoses. Therefore, our findings may not generalize to other settings,” they added. “However, our findings do have important implications for a substantial population of health providers and consumers in this country, because the VHA is the largest integrated health care system in the United States.”

The study was funded by the Department of Veterans Affairs Clinical Science Service and Health Services Research & Development Service. The investigators had no disclosures.

Constipation

A 26-year-old woman presented to the ED with a chief complaint of chronic constipation. This was the patient’s fourth ED visit for the same complaint over the previous 12 days. The patient stated that, at the prior visits, she was prescribed stool softeners and instructed to increase the amount of green vegetables in her diet and to drink plenty of fluids. She further noted that although constipation had been a long-standing problem for her, the condition had become worse over the past several weeks.

The patient described some lower abdominal discomfort, but denied nausea, vomiting, fevers, or chills. She also denied any genitourinary complaints or flank pain. Her last menstrual period was 2 weeks prior and normal. Her medical history was unremarkable; she denied smoking cigarettes or drinking alcohol and had no known drug allergies.

On physical examination, the patient’s vital signs were normal and she did not appear to be in any distress. The lung and heart examinations were also normal. Her abdomen was found to be soft, with slight tenderness in the lower abdomen, but with no guarding, rebound, or distention. Bowel sounds were present and hypoactive. A rectal examination revealed minimal stool in the vault, which was heme negative.

The patient sued the EP and the hospital, stating that the enema was not only contraindicated, but also caused the colon perforation. She further alleged that the EP failed to properly diagnose the sigmoid volvulus. The defense argued that the patient suffered from an uncommon condition, and the treatment provided was appropriate given her symptoms. The defense further stated that the perforation was present prior to the administration of the enema. At trial, a defense verdict was returned.

Discussion

Sigmoid volvulus is a relatively rare cause of bowel obstruction, accounting for only 2% of intestinal obstructions in the United States between 2002 and 2010.¹ The majority of cases occur in older patients (mean age, 70 years).¹ Risk factors for development include a history of laxative abuse, chronic constipation, and institutionalized patients with underlying neurological or psychiatric disease. There also appears to be an increased incidence during pregnancy. When observed in the pediatric population and in young adults, sigmoid volvulus is frequently due to an underlying colonic motility disorder.

A volvulus occurs when the colon twists on its mesenteric axis with greater than 180° rotation, resulting in obstruction of the intestinal lumen and mesenteric vessels.² The most common locations for volvulus are the sigmoid colon, followed by the cecum. Though rare, the condition can occur in other locations.

The patient in this case presented very atypically for someone with a sigmoid volvulus as the majority of patients present with progressive abdominal pain, nausea, vomiting, and constipation. On physical examination, the abdomen is frequently distended and tympanitic with diffuse tenderness. If perforation has occurred, then peritoneal signs predominate (eg, guarding, rigidity, rebound tenderness) and abnormal vital signs (eg, fever, tachycardia, hypotension) are frequently present.

While a diagnosis of sigmoid volvulus may be suspected through the history and physical examination, it is confirmed through imaging studies, with abdominal/pelvic CT being the modality of choice. On CT scan, the “whirl sign” is frequently present, representing the dilated sigmoid colon twisted around its mesocolon and vessels.³ The tightness of the whirl is proportional to the degree of torsion. If rectal contrast is administered, the “bird-beak” sign is often present, representing the afferent and efferent colonic segments.³

As with this patient, if the colon has been perforated, IV fluid resuscitation, IV antibiotics, and immediate surgery are indicated. In cases in which there is no evidence of gangrene or perforation, sigmoidoscopy can be attempted to detorse the twisted bowel segment. This technique is successful in correcting torsion in the majority of cases. However, if detorsion attempts fail, emergent surgery is indicated.

Even when nonsurgical detorsion is successful, controversy exists over its use as the sole treatment for sigmoid volvulus. Due to a 50% to 60% chance of recurrent sigmoid volvulus, some experts recommend surgery immediately following detorsion, while others advise a wait-and-see approach.

The risk of complications from administering a soapsuds enema to an immunocompetent ED patient without signs or symptoms of peritonitis is exceedingly low. While no good data exist on the rate of complications from enemas administered for constipation, perforation of the bowel from barium enemas occurs in only 0.02% to 0.04% of patients undergoing radiologic imaging.⁴ The jury appears to have come to the proper conclusion in this atypical presentation of an uncommon condition with a rare complication.

Missed Diabetes Mellitus

A 27-year-old man presented to the ED with a 3-day history of severe abdominal pain, nausea and vomiting. The patient denied fevers, chills, or diarrhea, as well as any sick contacts. The patient stated he was otherwise in good health, on no medications, and had no known drug allergies. He denied alcohol or tobacco use.

His vital signs at presentation were: temperature, 98.6°F; pulse, 116 beats/minute; blood pressure, 152/92 mm Hg; and respiratory rate, 24 breaths/minute. Oxygen saturation was 100% on room air. On head, eyes, ears, nose, and throat examination, the patient’s mucous membranes were noted to be dry. The lung examination revealed bilateral breath sounds clear to auscultation. The heart examination was remarkable for tachycardia, but the rhythm was regular and with no murmurs, rubs, or gallops. The abdomen was soft with slight diffuse tenderness, but no guarding, rebound, or masses.

The EP ordered 1 L normal saline IV and ondansetron 4 mg IV for the nausea and vomiting. No laboratory or imaging studies were ordered.

On reexamination approximately 1 hour later, the patient denied any abdominal pain and stated he felt improved and was no longer nauseous. The abdominal examination remained unchanged. The patient was discharged home with a prescription for ondansetron and instructed to return to the ED if his symptoms did not improve within the next 12 hours.

The patient did not return to the ED, but was found dead at home 3 days later. An autopsy revealed the patient died from metabolic consequences of diabetes mellitus (DM). The plaintiff’s family argued the standard of care required a complete set of laboratory studies, the results of which would have revealed the hyperglycemia, prompting further evaluation and treatment. The defense contended the standard of care did not require laboratory evaluation since the patient responded well to the IV fluids and ondansetron, reported an improvement in pain and nausea, and had no history of DM. At trial, a defense verdict was returned.

Discussion

Emergency physicians are well versed in diagnosing and treating DM and its complications. Typical symptoms of new-onset diabetes include polyuria, polydipsia, abdominal pain, nausea, vomiting, and lack of energy. Occasionally, the patient will present with more severe symptoms (eg, altered mental status) when diabetic ketoacidosis is the initial presentation of the disease. It is unclear from the medical records in this case whether additional history, such as polyuria, was obtained. If so, and the answers were in the affirmative, this information might have led the EP to order laboratory studies. Similarly, we do not know how many episodes of emesis the patient experienced—eg, only one to two episodes of emesis or more than 10. It is important to have an appreciation of the severity of the presenting symptoms.

Emergency physicians frequently diagnose and manage patients appropriately without ordering laboratory or imaging studies. Acute asthma attacks, migraine headaches, bronchitis, sprains, and upper respiratory tract infections are just a few examples of the many conditions that are frequently managed by EPs based solely on history and physical examination. However, it is important the EP take a thorough enough history and physical examination to ensure confidence in excluding more severe disease processes. The severity of the symptoms must also be considered in the decision to order laboratory or other evaluation.

In this day and age of point-of-care testing, one should consider checking the glucose and electrolytes in patients with symptoms consistent with fluid loss (ie, vomiting, diarrhea, decreased oral intake).

A Note about Diabetes Mellitus

Emergency physicians should be aware of the increasing incidence of DM in the United States and around the world. The global prevalence of diabetes in adults in 2013 was reportedly 8.3% (382 million people), with 14 million more men than women diagnosed with the disease.¹

Broadly defined, diabetes is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.¹ Type 1 DM constitutes approximately 5% to 10% of patients diagnosed with diabetes and is due to the destruction of beta cells in the pancreas.¹ It accounts for approximately 80% to 90% of DM in children and adolescents, and is thought to be present in approximately 3 million patients in the United States in 2010.¹ Type 2 DM is the most common form, with 90% to 95% of patients belonging to this category, most of whom are adults. The problem in type 2 DM is primarily insulin resistance, as opposed to a lack of insulin. Obesity is the most common cause of insulin resistance in type 2 DM.¹

Constipation

A 26-year-old woman presented to the ED with a chief complaint of chronic constipation. This was the patient’s fourth ED visit for the same complaint over the previous 12 days. The patient stated that, at the prior visits, she was prescribed stool softeners and instructed to increase the amount of green vegetables in her diet and to drink plenty of fluids. She further noted that although constipation had been a long-standing problem for her, the condition had become worse over the past several weeks.

The patient described some lower abdominal discomfort, but denied nausea, vomiting, fevers, or chills. She also denied any genitourinary complaints or flank pain. Her last menstrual period was 2 weeks prior and normal. Her medical history was unremarkable; she denied smoking cigarettes or drinking alcohol and had no known drug allergies.

On physical examination, the patient’s vital signs were normal and she did not appear to be in any distress. The lung and heart examinations were also normal. Her abdomen was found to be soft, with slight tenderness in the lower abdomen, but with no guarding, rebound, or distention. Bowel sounds were present and hypoactive. A rectal examination revealed minimal stool in the vault, which was heme negative.

The patient sued the EP and the hospital, stating that the enema was not only contraindicated, but also caused the colon perforation. She further alleged that the EP failed to properly diagnose the sigmoid volvulus. The defense argued that the patient suffered from an uncommon condition, and the treatment provided was appropriate given her symptoms. The defense further stated that the perforation was present prior to the administration of the enema. At trial, a defense verdict was returned.

Discussion

Sigmoid volvulus is a relatively rare cause of bowel obstruction, accounting for only 2% of intestinal obstructions in the United States between 2002 and 2010.¹ The majority of cases occur in older patients (mean age, 70 years).¹ Risk factors for development include a history of laxative abuse, chronic constipation, and institutionalized patients with underlying neurological or psychiatric disease. There also appears to be an increased incidence during pregnancy. When observed in the pediatric population and in young adults, sigmoid volvulus is frequently due to an underlying colonic motility disorder.

A volvulus occurs when the colon twists on its mesenteric axis with greater than 180° rotation, resulting in obstruction of the intestinal lumen and mesenteric vessels.² The most common locations for volvulus are the sigmoid colon, followed by the cecum. Though rare, the condition can occur in other locations.

The patient in this case presented very atypically for someone with a sigmoid volvulus as the majority of patients present with progressive abdominal pain, nausea, vomiting, and constipation. On physical examination, the abdomen is frequently distended and tympanitic with diffuse tenderness. If perforation has occurred, then peritoneal signs predominate (eg, guarding, rigidity, rebound tenderness) and abnormal vital signs (eg, fever, tachycardia, hypotension) are frequently present.

While a diagnosis of sigmoid volvulus may be suspected through the history and physical examination, it is confirmed through imaging studies, with abdominal/pelvic CT being the modality of choice. On CT scan, the “whirl sign” is frequently present, representing the dilated sigmoid colon twisted around its mesocolon and vessels.³ The tightness of the whirl is proportional to the degree of torsion. If rectal contrast is administered, the “bird-beak” sign is often present, representing the afferent and efferent colonic segments.³

As with this patient, if the colon has been perforated, IV fluid resuscitation, IV antibiotics, and immediate surgery are indicated. In cases in which there is no evidence of gangrene or perforation, sigmoidoscopy can be attempted to detorse the twisted bowel segment. This technique is successful in correcting torsion in the majority of cases. However, if detorsion attempts fail, emergent surgery is indicated.

Even when nonsurgical detorsion is successful, controversy exists over its use as the sole treatment for sigmoid volvulus. Due to a 50% to 60% chance of recurrent sigmoid volvulus, some experts recommend surgery immediately following detorsion, while others advise a wait-and-see approach.

The risk of complications from administering a soapsuds enema to an immunocompetent ED patient without signs or symptoms of peritonitis is exceedingly low. While no good data exist on the rate of complications from enemas administered for constipation, perforation of the bowel from barium enemas occurs in only 0.02% to 0.04% of patients undergoing radiologic imaging.⁴ The jury appears to have come to the proper conclusion in this atypical presentation of an uncommon condition with a rare complication.

Missed Diabetes Mellitus

A 27-year-old man presented to the ED with a 3-day history of severe abdominal pain, nausea and vomiting. The patient denied fevers, chills, or diarrhea, as well as any sick contacts. The patient stated he was otherwise in good health, on no medications, and had no known drug allergies. He denied alcohol or tobacco use.

His vital signs at presentation were: temperature, 98.6°F; pulse, 116 beats/minute; blood pressure, 152/92 mm Hg; and respiratory rate, 24 breaths/minute. Oxygen saturation was 100% on room air. On head, eyes, ears, nose, and throat examination, the patient’s mucous membranes were noted to be dry. The lung examination revealed bilateral breath sounds clear to auscultation. The heart examination was remarkable for tachycardia, but the rhythm was regular and with no murmurs, rubs, or gallops. The abdomen was soft with slight diffuse tenderness, but no guarding, rebound, or masses.

The EP ordered 1 L normal saline IV and ondansetron 4 mg IV for the nausea and vomiting. No laboratory or imaging studies were ordered.

On reexamination approximately 1 hour later, the patient denied any abdominal pain and stated he felt improved and was no longer nauseous. The abdominal examination remained unchanged. The patient was discharged home with a prescription for ondansetron and instructed to return to the ED if his symptoms did not improve within the next 12 hours.

The patient did not return to the ED, but was found dead at home 3 days later. An autopsy revealed the patient died from metabolic consequences of diabetes mellitus (DM). The plaintiff’s family argued the standard of care required a complete set of laboratory studies, the results of which would have revealed the hyperglycemia, prompting further evaluation and treatment. The defense contended the standard of care did not require laboratory evaluation since the patient responded well to the IV fluids and ondansetron, reported an improvement in pain and nausea, and had no history of DM. At trial, a defense verdict was returned.

Discussion

Emergency physicians are well versed in diagnosing and treating DM and its complications. Typical symptoms of new-onset diabetes include polyuria, polydipsia, abdominal pain, nausea, vomiting, and lack of energy. Occasionally, the patient will present with more severe symptoms (eg, altered mental status) when diabetic ketoacidosis is the initial presentation of the disease. It is unclear from the medical records in this case whether additional history, such as polyuria, was obtained. If so, and the answers were in the affirmative, this information might have led the EP to order laboratory studies. Similarly, we do not know how many episodes of emesis the patient experienced—eg, only one to two episodes of emesis or more than 10. It is important to have an appreciation of the severity of the presenting symptoms.

Emergency physicians frequently diagnose and manage patients appropriately without ordering laboratory or imaging studies. Acute asthma attacks, migraine headaches, bronchitis, sprains, and upper respiratory tract infections are just a few examples of the many conditions that are frequently managed by EPs based solely on history and physical examination. However, it is important the EP take a thorough enough history and physical examination to ensure confidence in excluding more severe disease processes. The severity of the symptoms must also be considered in the decision to order laboratory or other evaluation.

In this day and age of point-of-care testing, one should consider checking the glucose and electrolytes in patients with symptoms consistent with fluid loss (ie, vomiting, diarrhea, decreased oral intake).

A Note about Diabetes Mellitus

Emergency physicians should be aware of the increasing incidence of DM in the United States and around the world. The global prevalence of diabetes in adults in 2013 was reportedly 8.3% (382 million people), with 14 million more men than women diagnosed with the disease.¹

Broadly defined, diabetes is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.¹ Type 1 DM constitutes approximately 5% to 10% of patients diagnosed with diabetes and is due to the destruction of beta cells in the pancreas.¹ It accounts for approximately 80% to 90% of DM in children and adolescents, and is thought to be present in approximately 3 million patients in the United States in 2010.¹ Type 2 DM is the most common form, with 90% to 95% of patients belonging to this category, most of whom are adults. The problem in type 2 DM is primarily insulin resistance, as opposed to a lack of insulin. Obesity is the most common cause of insulin resistance in type 2 DM.¹

Constipation

A 26-year-old woman presented to the ED with a chief complaint of chronic constipation. This was the patient’s fourth ED visit for the same complaint over the previous 12 days. The patient stated that, at the prior visits, she was prescribed stool softeners and instructed to increase the amount of green vegetables in her diet and to drink plenty of fluids. She further noted that although constipation had been a long-standing problem for her, the condition had become worse over the past several weeks.

The patient described some lower abdominal discomfort, but denied nausea, vomiting, fevers, or chills. She also denied any genitourinary complaints or flank pain. Her last menstrual period was 2 weeks prior and normal. Her medical history was unremarkable; she denied smoking cigarettes or drinking alcohol and had no known drug allergies.

On physical examination, the patient’s vital signs were normal and she did not appear to be in any distress. The lung and heart examinations were also normal. Her abdomen was found to be soft, with slight tenderness in the lower abdomen, but with no guarding, rebound, or distention. Bowel sounds were present and hypoactive. A rectal examination revealed minimal stool in the vault, which was heme negative.

The patient sued the EP and the hospital, stating that the enema was not only contraindicated, but also caused the colon perforation. She further alleged that the EP failed to properly diagnose the sigmoid volvulus. The defense argued that the patient suffered from an uncommon condition, and the treatment provided was appropriate given her symptoms. The defense further stated that the perforation was present prior to the administration of the enema. At trial, a defense verdict was returned.

Discussion

Sigmoid volvulus is a relatively rare cause of bowel obstruction, accounting for only 2% of intestinal obstructions in the United States between 2002 and 2010.¹ The majority of cases occur in older patients (mean age, 70 years).¹ Risk factors for development include a history of laxative abuse, chronic constipation, and institutionalized patients with underlying neurological or psychiatric disease. There also appears to be an increased incidence during pregnancy. When observed in the pediatric population and in young adults, sigmoid volvulus is frequently due to an underlying colonic motility disorder.

A volvulus occurs when the colon twists on its mesenteric axis with greater than 180° rotation, resulting in obstruction of the intestinal lumen and mesenteric vessels.² The most common locations for volvulus are the sigmoid colon, followed by the cecum. Though rare, the condition can occur in other locations.

The patient in this case presented very atypically for someone with a sigmoid volvulus as the majority of patients present with progressive abdominal pain, nausea, vomiting, and constipation. On physical examination, the abdomen is frequently distended and tympanitic with diffuse tenderness. If perforation has occurred, then peritoneal signs predominate (eg, guarding, rigidity, rebound tenderness) and abnormal vital signs (eg, fever, tachycardia, hypotension) are frequently present.

While a diagnosis of sigmoid volvulus may be suspected through the history and physical examination, it is confirmed through imaging studies, with abdominal/pelvic CT being the modality of choice. On CT scan, the “whirl sign” is frequently present, representing the dilated sigmoid colon twisted around its mesocolon and vessels.³ The tightness of the whirl is proportional to the degree of torsion. If rectal contrast is administered, the “bird-beak” sign is often present, representing the afferent and efferent colonic segments.³

As with this patient, if the colon has been perforated, IV fluid resuscitation, IV antibiotics, and immediate surgery are indicated. In cases in which there is no evidence of gangrene or perforation, sigmoidoscopy can be attempted to detorse the twisted bowel segment. This technique is successful in correcting torsion in the majority of cases. However, if detorsion attempts fail, emergent surgery is indicated.

Even when nonsurgical detorsion is successful, controversy exists over its use as the sole treatment for sigmoid volvulus. Due to a 50% to 60% chance of recurrent sigmoid volvulus, some experts recommend surgery immediately following detorsion, while others advise a wait-and-see approach.

The risk of complications from administering a soapsuds enema to an immunocompetent ED patient without signs or symptoms of peritonitis is exceedingly low. While no good data exist on the rate of complications from enemas administered for constipation, perforation of the bowel from barium enemas occurs in only 0.02% to 0.04% of patients undergoing radiologic imaging.⁴ The jury appears to have come to the proper conclusion in this atypical presentation of an uncommon condition with a rare complication.

Missed Diabetes Mellitus

A 27-year-old man presented to the ED with a 3-day history of severe abdominal pain, nausea and vomiting. The patient denied fevers, chills, or diarrhea, as well as any sick contacts. The patient stated he was otherwise in good health, on no medications, and had no known drug allergies. He denied alcohol or tobacco use.

His vital signs at presentation were: temperature, 98.6°F; pulse, 116 beats/minute; blood pressure, 152/92 mm Hg; and respiratory rate, 24 breaths/minute. Oxygen saturation was 100% on room air. On head, eyes, ears, nose, and throat examination, the patient’s mucous membranes were noted to be dry. The lung examination revealed bilateral breath sounds clear to auscultation. The heart examination was remarkable for tachycardia, but the rhythm was regular and with no murmurs, rubs, or gallops. The abdomen was soft with slight diffuse tenderness, but no guarding, rebound, or masses.

The EP ordered 1 L normal saline IV and ondansetron 4 mg IV for the nausea and vomiting. No laboratory or imaging studies were ordered.

On reexamination approximately 1 hour later, the patient denied any abdominal pain and stated he felt improved and was no longer nauseous. The abdominal examination remained unchanged. The patient was discharged home with a prescription for ondansetron and instructed to return to the ED if his symptoms did not improve within the next 12 hours.

The patient did not return to the ED, but was found dead at home 3 days later. An autopsy revealed the patient died from metabolic consequences of diabetes mellitus (DM). The plaintiff’s family argued the standard of care required a complete set of laboratory studies, the results of which would have revealed the hyperglycemia, prompting further evaluation and treatment. The defense contended the standard of care did not require laboratory evaluation since the patient responded well to the IV fluids and ondansetron, reported an improvement in pain and nausea, and had no history of DM. At trial, a defense verdict was returned.

Discussion

Emergency physicians are well versed in diagnosing and treating DM and its complications. Typical symptoms of new-onset diabetes include polyuria, polydipsia, abdominal pain, nausea, vomiting, and lack of energy. Occasionally, the patient will present with more severe symptoms (eg, altered mental status) when diabetic ketoacidosis is the initial presentation of the disease. It is unclear from the medical records in this case whether additional history, such as polyuria, was obtained. If so, and the answers were in the affirmative, this information might have led the EP to order laboratory studies. Similarly, we do not know how many episodes of emesis the patient experienced—eg, only one to two episodes of emesis or more than 10. It is important to have an appreciation of the severity of the presenting symptoms.

Emergency physicians frequently diagnose and manage patients appropriately without ordering laboratory or imaging studies. Acute asthma attacks, migraine headaches, bronchitis, sprains, and upper respiratory tract infections are just a few examples of the many conditions that are frequently managed by EPs based solely on history and physical examination. However, it is important the EP take a thorough enough history and physical examination to ensure confidence in excluding more severe disease processes. The severity of the symptoms must also be considered in the decision to order laboratory or other evaluation.

In this day and age of point-of-care testing, one should consider checking the glucose and electrolytes in patients with symptoms consistent with fluid loss (ie, vomiting, diarrhea, decreased oral intake).

A Note about Diabetes Mellitus

Emergency physicians should be aware of the increasing incidence of DM in the United States and around the world. The global prevalence of diabetes in adults in 2013 was reportedly 8.3% (382 million people), with 14 million more men than women diagnosed with the disease.¹

Broadly defined, diabetes is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.¹ Type 1 DM constitutes approximately 5% to 10% of patients diagnosed with diabetes and is due to the destruction of beta cells in the pancreas.¹ It accounts for approximately 80% to 90% of DM in children and adolescents, and is thought to be present in approximately 3 million patients in the United States in 2010.¹ Type 2 DM is the most common form, with 90% to 95% of patients belonging to this category, most of whom are adults. The problem in type 2 DM is primarily insulin resistance, as opposed to a lack of insulin. Obesity is the most common cause of insulin resistance in type 2 DM.¹

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 34-year-old man with a history of polysubstance abuse presented to the ED after he had a seizure during his regular methadone-treatment program meeting. While at the clinic, attendees witnessed the patient experience a loss of consciousness accompanied by generalized shaking movements of his extremities, which lasted for several minutes.

Upon arrival in the ED, the patient stated that he had a mild headache; he was otherwise asymptomatic. Initial vital signs were: blood pressure, 126/80 mm Hg; heart rate, 82 beats/minute; respiratory rate, 16 breaths/minute; and temperature, 97.3°F. Oxygen saturation was 98% on room air, and a finger-stick glucose test was 140 mg/dL. 

Physical examination revealed a small right-sided parietal hematoma. The patient had no tremors and his neurological examination, including mental status, was normal. When reviewing the patient’s medical history and medications in the health record, it was noted that the patient had a prescription for alprazolam for an anxiety disorder. On further questioning, the patient admitted that he had sold his last alprazolam prescription and had not been taking the drug for the past week.

What characterizes the  benzodiazepine withdrawal syndrome?

Although introduced into clinical practice in the 1960s, the potential for dependence and a withdrawal syndrome was not appreciated until the early 1980s. This clinical syndrome can manifest with a wide variety of findings, most commonly with what are termed “rebound effects” or “rebound hyperexcitability.” These effects include anxiety, insomnia or sleep disturbance, tremulousness, irritability, sweating, psychomotor agitation, difficulty in concentration, nausea, weight loss, palpitations, headache, muscular pain and stiffness, or generalized weakness.² More severe manifestations include delirium, seizures, or psychosis. Often, these symptoms and signs may be confused with the very manifestations that prompted the initial use of the BZD, a reemergence of which can exacerbate the withdrawal syndrome.

When does benzodiazepine withdrawal occur?

The exact time course of BZD withdrawal can vary considerably and, unlike alcohol withdrawal (which occurs from a single compound, ethanol), can be difficult to characterize. The onset of withdrawal symptoms is dependent on a number of factors, including the half-life of the BZD involved. For example, delayed onset withdrawal symptoms of up to 3 weeks after cessation of the medication are described with long-acting BZDs such as chlordiazepoxide and diazepam. Conversely, symptoms may present as early as 24 to 48 hours after abrupt termination of BZDs with shorter half-lives, alprazolam and lorazepam. This variable time of onset differs considerably from other withdrawal syndromes, notably ethanol withdrawal. While both syndromes correlate to the individual patient’s severity of dependence, alcohol withdrawal follows a more predictable time course.

Some authors distinguish a rebound syndrome from a true withdrawal syndrome, the former of which is self-limited in nature and the result of cessation of treatment for the primary disease process. In this model, rebound symptoms begin 1 to 4 days after the abrupt cessation or dose reduction of the BZD, and are relatively short-lived, lasting 2 to 3 days.²

What is the appropriate treatment for benzodiazepine withdrawal?

The standard therapy for almost all withdrawal syndromes is reinstitution of the causal agent. A number of non-BZD-based treatment strategies have been investigated, and all have met with limited success. Of these, anticonvulsant drugs such as carbamazepine and valproic acid were initially considered promising based on case reports and small case series.⁴ These medications ultimately proved ineffective in randomized, placebo-controlled studies.⁵ β-Adrenergic antagonists, such as propranolol, have been studied as a method to normalize a patient’s vital signs but also proved nonbeneficial in managing withdrawal.^5,6

The safest and most effective management approach for patients with BZD withdrawal is reinstitution of the BZD followed by a prolonged and gradual tapering until cessation, if that is desired.^1,2,5,6 While all BZDs share structural and mechanistic similarities, there are subtle variations within this class that can affect their pharmacologic effects. These structural differences may result in incomplete cross-tolerance, which may lead to inadequate mitigation of the withdrawal syndrome. For example, previous reports suggest that alprazolam and clonazepam are structurally unique and bind to the BZD receptor with higher affinity than other BZDs. Therefore, while in general any BZD can be used to treat withdrawal from another BZD, it is recommended to treat withdrawal from these two agents with the implicated BZD.

There are, however, limitations to this approach. Namely, some BZDs are only available in oral formulations (eg, alprazolam and clonazepam) or the BZD of choice may not be readily available or on formulary within a given institution. In a patient with a severe withdrawal syndrome where it is not feasible or potentially harmful to administer an oral medication, it is reasonable to provide parenteral (preferably intravenous [IV]) BZD therapy. The optimal approach is to start with a small “standard” dose and titrate to effect while monitoring for adverse effects (eg, oversedation, ventilatory depression). Redosing should be triggered by symptoms or signs, and not performed in a timed or standing-order fashion. If this approach proves ineffective and withdrawal symptoms persist despite adequate BZD therapy, a direct GABA agonist such as propofol is a sensible alternative or adjuvant treatment. This may sound similar to the management of patients with ethanol withdrawal; indeed, this approach is essentially the same, with the exception of the more drawn-out time course.

Case Conclusion

After arrival in the ED, the patient received diazepam 10 mg IV and was subsequently admitted to the hospital for further evaluation. During his hospitalization, the patient was re-started on his usual dose of oral alprazolam.  No further withdrawal syndrome was observed, and he was discharged on hospital day 2 with a plan to slowly taper his alprazolam dose with his outpatient psychiatrist.

Dr Repplinger is a senior medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.