ACS Surgery News

BOSTON – New and innovative methodologies for conducting minimally invasive esophagectomy (MIE) offer significantly lower rates of morbidity and mortality than those normally associated with the procedure, as presented by Dr. James D. Luketich at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting of the American Association for Thoracic Surgery.

While Dr. Luketich spent the bulk of his oral presentation going over the specifics of performing MIE, the accompanying literature of his presentation delved into four key studies – performed and published over the last 12 years – which show the efficacy of MIE over the more traditional approaches to esophagectomy.

“There are several different approaches to esophagectomy in general [but] the technique has evolved partly because the tumors have evolved in the United States,” explained Dr. Luketich, chairman of cardiothoracic surgery at the University of Pittsburgh. “We started off laparoscopic [and] thoracoscopic. In my opinion, that was kind of a bad idea [and] we gave that up pretty early on [...] we’re chest surgeons, we put a thoracoscope in, and we loved it.”

However, as Dr. Luketich explained, the increasing lack of experience from new general surgery residents and attendings caused esophagectomy to become the more attractive option, as it was a procedure that everyone had experience with. This began a search for an effective but minimally invasive approach, which has slowly been cultivated and refined over the years.

Luketich discussed the outcome of his 2003 study assessing 222 consecutive patients who have undergone MIE at the University of Pittsburgh. In that study, patients had lower mortality rates (1.4%) and shorter hospital stays (7 days) than those with “most open series” invasive esophagectomy procedures, with a quality of life score 19 months post operation that was similar to preoperative scores and population norms.

The success of this trial led to the development of the intergroup ECOG 222 trial to determine MIE’s viability in a multicenter setting. Out of 104 patients eligible for MIE, 95 underwent the procedure. Median length of stay in intensive care units was 2 days, and hospital stay was 9 days, with a 2.1% 30-day mortality rate. At 35.8 months (the median follow-up time), the estimated 3-year overall survival was 58.4%.

Similar work was done in 2012, also headed by Dr. Luketich. In this trial, outcomes were evaluated in 1,033 consecutive MIE patients in order to assess the differences between “the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach [and] a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]).” MIE-neck was performed on 481 (48%) subjects and MIE-chest on 530 (52%) subjects.

Both procedures had similar median length of stay in hospital (8 days) and in the intensive care unit (2 days), with slightly lower rates of recurrent nerve injury in the MIE-chest cohort and mortality rate of 0.9%. The median number of lymph nodes resected was 21, and total operative mortality was 1.68%, leading investigators to conclude that MIE was the “preferred approach” for resection (P less than .001).

Dr. Luketich also briefly discussed the findings of a 2012 study by Dr. S.S. Biere – an open-label, randomized controlled trial at five study centers spread across three countries from June 2009 through March 2011. Fifty-six patients were randomized into cohorts receiving open esophagectomy, and 59 received MIE; all patients were aged 18-75 years and had resectable cancer of the esophagus or gastroesophageal junction.

Results showed a statistically significant decrease in postoperative pneumonia in the MIE cohort (9% vs. 29%; relative risk 0.35, P = 0.005), compared with open esophagectomy in the first two weeks after surgery and lower postoperative pulmonary infection in the entire hospital stay. MIE patients also experienced shorter hospital stays (11 vs. 14 days), higher short-term quality of life scores at 6 weeks post surgery, lower postoperative pain scores, lower operative blood loss, and lower rates of early morbidity.

Dr. Luketich disclosed having a “shareholder relationship” with Express Scripts and Intuitive Surgical.

dchitnis@frontlinemedcom.com

BOSTON – New and innovative methodologies for conducting minimally invasive esophagectomy (MIE) offer significantly lower rates of morbidity and mortality than those normally associated with the procedure, as presented by Dr. James D. Luketich at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting of the American Association for Thoracic Surgery.

While Dr. Luketich spent the bulk of his oral presentation going over the specifics of performing MIE, the accompanying literature of his presentation delved into four key studies – performed and published over the last 12 years – which show the efficacy of MIE over the more traditional approaches to esophagectomy.

“There are several different approaches to esophagectomy in general [but] the technique has evolved partly because the tumors have evolved in the United States,” explained Dr. Luketich, chairman of cardiothoracic surgery at the University of Pittsburgh. “We started off laparoscopic [and] thoracoscopic. In my opinion, that was kind of a bad idea [and] we gave that up pretty early on [...] we’re chest surgeons, we put a thoracoscope in, and we loved it.”

However, as Dr. Luketich explained, the increasing lack of experience from new general surgery residents and attendings caused esophagectomy to become the more attractive option, as it was a procedure that everyone had experience with. This began a search for an effective but minimally invasive approach, which has slowly been cultivated and refined over the years.

Luketich discussed the outcome of his 2003 study assessing 222 consecutive patients who have undergone MIE at the University of Pittsburgh. In that study, patients had lower mortality rates (1.4%) and shorter hospital stays (7 days) than those with “most open series” invasive esophagectomy procedures, with a quality of life score 19 months post operation that was similar to preoperative scores and population norms.

The success of this trial led to the development of the intergroup ECOG 222 trial to determine MIE’s viability in a multicenter setting. Out of 104 patients eligible for MIE, 95 underwent the procedure. Median length of stay in intensive care units was 2 days, and hospital stay was 9 days, with a 2.1% 30-day mortality rate. At 35.8 months (the median follow-up time), the estimated 3-year overall survival was 58.4%.

Similar work was done in 2012, also headed by Dr. Luketich. In this trial, outcomes were evaluated in 1,033 consecutive MIE patients in order to assess the differences between “the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach [and] a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]).” MIE-neck was performed on 481 (48%) subjects and MIE-chest on 530 (52%) subjects.

Both procedures had similar median length of stay in hospital (8 days) and in the intensive care unit (2 days), with slightly lower rates of recurrent nerve injury in the MIE-chest cohort and mortality rate of 0.9%. The median number of lymph nodes resected was 21, and total operative mortality was 1.68%, leading investigators to conclude that MIE was the “preferred approach” for resection (P less than .001).

Dr. Luketich also briefly discussed the findings of a 2012 study by Dr. S.S. Biere – an open-label, randomized controlled trial at five study centers spread across three countries from June 2009 through March 2011. Fifty-six patients were randomized into cohorts receiving open esophagectomy, and 59 received MIE; all patients were aged 18-75 years and had resectable cancer of the esophagus or gastroesophageal junction.

Results showed a statistically significant decrease in postoperative pneumonia in the MIE cohort (9% vs. 29%; relative risk 0.35, P = 0.005), compared with open esophagectomy in the first two weeks after surgery and lower postoperative pulmonary infection in the entire hospital stay. MIE patients also experienced shorter hospital stays (11 vs. 14 days), higher short-term quality of life scores at 6 weeks post surgery, lower postoperative pain scores, lower operative blood loss, and lower rates of early morbidity.

Dr. Luketich disclosed having a “shareholder relationship” with Express Scripts and Intuitive Surgical.

dchitnis@frontlinemedcom.com

BOSTON – New and innovative methodologies for conducting minimally invasive esophagectomy (MIE) offer significantly lower rates of morbidity and mortality than those normally associated with the procedure, as presented by Dr. James D. Luketich at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting of the American Association for Thoracic Surgery.

While Dr. Luketich spent the bulk of his oral presentation going over the specifics of performing MIE, the accompanying literature of his presentation delved into four key studies – performed and published over the last 12 years – which show the efficacy of MIE over the more traditional approaches to esophagectomy.

“There are several different approaches to esophagectomy in general [but] the technique has evolved partly because the tumors have evolved in the United States,” explained Dr. Luketich, chairman of cardiothoracic surgery at the University of Pittsburgh. “We started off laparoscopic [and] thoracoscopic. In my opinion, that was kind of a bad idea [and] we gave that up pretty early on [...] we’re chest surgeons, we put a thoracoscope in, and we loved it.”

However, as Dr. Luketich explained, the increasing lack of experience from new general surgery residents and attendings caused esophagectomy to become the more attractive option, as it was a procedure that everyone had experience with. This began a search for an effective but minimally invasive approach, which has slowly been cultivated and refined over the years.

Luketich discussed the outcome of his 2003 study assessing 222 consecutive patients who have undergone MIE at the University of Pittsburgh. In that study, patients had lower mortality rates (1.4%) and shorter hospital stays (7 days) than those with “most open series” invasive esophagectomy procedures, with a quality of life score 19 months post operation that was similar to preoperative scores and population norms.

The success of this trial led to the development of the intergroup ECOG 222 trial to determine MIE’s viability in a multicenter setting. Out of 104 patients eligible for MIE, 95 underwent the procedure. Median length of stay in intensive care units was 2 days, and hospital stay was 9 days, with a 2.1% 30-day mortality rate. At 35.8 months (the median follow-up time), the estimated 3-year overall survival was 58.4%.

Similar work was done in 2012, also headed by Dr. Luketich. In this trial, outcomes were evaluated in 1,033 consecutive MIE patients in order to assess the differences between “the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach [and] a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]).” MIE-neck was performed on 481 (48%) subjects and MIE-chest on 530 (52%) subjects.

Both procedures had similar median length of stay in hospital (8 days) and in the intensive care unit (2 days), with slightly lower rates of recurrent nerve injury in the MIE-chest cohort and mortality rate of 0.9%. The median number of lymph nodes resected was 21, and total operative mortality was 1.68%, leading investigators to conclude that MIE was the “preferred approach” for resection (P less than .001).

Dr. Luketich also briefly discussed the findings of a 2012 study by Dr. S.S. Biere – an open-label, randomized controlled trial at five study centers spread across three countries from June 2009 through March 2011. Fifty-six patients were randomized into cohorts receiving open esophagectomy, and 59 received MIE; all patients were aged 18-75 years and had resectable cancer of the esophagus or gastroesophageal junction.

Results showed a statistically significant decrease in postoperative pneumonia in the MIE cohort (9% vs. 29%; relative risk 0.35, P = 0.005), compared with open esophagectomy in the first two weeks after surgery and lower postoperative pulmonary infection in the entire hospital stay. MIE patients also experienced shorter hospital stays (11 vs. 14 days), higher short-term quality of life scores at 6 weeks post surgery, lower postoperative pain scores, lower operative blood loss, and lower rates of early morbidity.

Dr. Luketich disclosed having a “shareholder relationship” with Express Scripts and Intuitive Surgical.

dchitnis@frontlinemedcom.com

The idea of performing a tricuspid valve repair during a mitral valve procedure has fueled considerable debate among cardiovascular surgeons largely because the grading of tricuspid regurgitation (TR) has been an unreliable marker, so now may be the time to use a new parameter, Dr. Robert Dion of Genk, Belgium, argues in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2015 Nov 20;150:1040-3).

“Therefore, we need a parameter hardly depending on preload,” Dr. Dion said. He noted that many authors have validated the use of annual dilatation of 40 mm or 21mm/m².

Further, preoperative functional New York Heart Association (NYHA) class plays a major role, Dr. Dion said. TR is progressive in nature and the existence of concomitant mitral valve disease can aggravate annular dilation. The earlier surgeons operate on the mitral valve, the less frequently patients will require tricuspid valve repair at the same time, he said.

The controversy was aired in a report at the 2015 American Association for Thoracic Surgery meeting when Dr. Joanna Chikwe of Mount Sinai Hospital in New York discussed an approach that led to tricuspid valve repair at the time of mitral valve surgery in almost two-thirds of patients. Dr. Chikwe and her coauthors opted for concomitant surgery when patients had moderate TR or tricuspid annular dilatation of 40 mm or greater – a strategy that Dr. Dion said was validated because they reported comparable outcomes in terms of death, morbidity, or pacemaker need. The concomitant repair cured TR and prevented progression at seven years of follow-up; and it induced right ventricle recovery and reduced pulmonary hypertension.

In this opinion piece, Dr. Dion took issue with comments made by Dr. Tirone E. David of the University of Toronto during Dr. Chikwe’s AATS presentation. Dr. David, for whom the David reimplantation technique for aortic root replacement is named, called the technique “overkill,” according to Dr. Dion.

Specifically, Dr. Dion questioned Dr. David’s assertions that the use of rigid rings in mitral valve repair causes TR and that no evidence validates the 40-mm diameter minimum in patients with degenerative mitral valve disease. On the first point, Dr. Dion said no evidence has linked the rigidity of the mitral valve ring and progression of tricuspid regurgitation. On the second, Dr. Dion cited eight studies of progressive tricuspid annular dilation with mitral regurgitation, most of which proposed the 40-mm threshold for concomitant tricuspid valve repair. Since then, the 40-mm threshold has been adopted for both European and American guidelines and validated by five reports from 2011 to 2014.

Dr. Dion said the rationale for using annular dilation rather than TR grade rests on “three poles”: annular dilation does not depend on preload whereas the right ventricle does; documented discrepancies between clinical and hemodynamic data (J Cardiol Surg. 1994 Mar;9(2 suppl):237-41; J Am Coll Cardiol. 2004 Feb. 4;43:405-9); and the idea that TR is “bad” for the patient. He also cited disparities in the number of concomitant repairs performed at leading centers: 7%-10% at the Mayo Clinic and Dr. David’s Toronto center, 25% in Leipzig, 40%-45% in his own clinic and two others, and 65% in Dr. Chikwe’s facility.

American Association for Thoracic Surgery/JTCVS

But early intervention for mitral valve dysfunction is a key indicator of the need for concomitant tricuspid valve repair, Dr. Dion said. “The earlier we operate on the MV, the less frequently patients will require tricuspid valve repair,” he said. In his own approach, Dr. Dion uses a transseptal approach of the mitral valve. For TR greater than grade 2, he performs tricuspid repair using a semirigid ring sized on the area of the anterior leaflet tissue; and if the tenting distance is 8 mm or greater, he includes anterior leaflet augmentation. When TR grade is 2 or less, he also performs concomitant tricuspid repair when the tricuspid annulus is 40 mm or greater or when the tricuspid annulus is 3.5-4 mm in the setting of a host of other cardiac problems, from atrial fibrillation to left valve dysfunction. “Otherwise: abstention,” he said.

“The major issue here is to do everything possible to avoid the risk and outcomes of reoperative tricuspid valve surgery,” Dr. Dion said, citing in-hospital death rates of 13.2% that Dr. David reported (Ann Thorac Surg. 2013 Jan;95:119-24.) and 14.6% the Leipzig group reported (J Thorac Cardiovasc Surg. 2013 Oct; 146:841-7).While he acknowledged calls for a prospective, randomized clinical trial, Dr. Dion said the contraindications for concomitant tricuspid valve repair with mitral valve repair have already been well documented.

Dr. Dion reports consulting fees from Sorin, Edwards, Johnson & Johnson, and St. Jude Medical.

The idea of performing a tricuspid valve repair during a mitral valve procedure has fueled considerable debate among cardiovascular surgeons largely because the grading of tricuspid regurgitation (TR) has been an unreliable marker, so now may be the time to use a new parameter, Dr. Robert Dion of Genk, Belgium, argues in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2015 Nov 20;150:1040-3).

“Therefore, we need a parameter hardly depending on preload,” Dr. Dion said. He noted that many authors have validated the use of annual dilatation of 40 mm or 21mm/m².

Further, preoperative functional New York Heart Association (NYHA) class plays a major role, Dr. Dion said. TR is progressive in nature and the existence of concomitant mitral valve disease can aggravate annular dilation. The earlier surgeons operate on the mitral valve, the less frequently patients will require tricuspid valve repair at the same time, he said.

The controversy was aired in a report at the 2015 American Association for Thoracic Surgery meeting when Dr. Joanna Chikwe of Mount Sinai Hospital in New York discussed an approach that led to tricuspid valve repair at the time of mitral valve surgery in almost two-thirds of patients. Dr. Chikwe and her coauthors opted for concomitant surgery when patients had moderate TR or tricuspid annular dilatation of 40 mm or greater – a strategy that Dr. Dion said was validated because they reported comparable outcomes in terms of death, morbidity, or pacemaker need. The concomitant repair cured TR and prevented progression at seven years of follow-up; and it induced right ventricle recovery and reduced pulmonary hypertension.

In this opinion piece, Dr. Dion took issue with comments made by Dr. Tirone E. David of the University of Toronto during Dr. Chikwe’s AATS presentation. Dr. David, for whom the David reimplantation technique for aortic root replacement is named, called the technique “overkill,” according to Dr. Dion.

Specifically, Dr. Dion questioned Dr. David’s assertions that the use of rigid rings in mitral valve repair causes TR and that no evidence validates the 40-mm diameter minimum in patients with degenerative mitral valve disease. On the first point, Dr. Dion said no evidence has linked the rigidity of the mitral valve ring and progression of tricuspid regurgitation. On the second, Dr. Dion cited eight studies of progressive tricuspid annular dilation with mitral regurgitation, most of which proposed the 40-mm threshold for concomitant tricuspid valve repair. Since then, the 40-mm threshold has been adopted for both European and American guidelines and validated by five reports from 2011 to 2014.

Dr. Dion said the rationale for using annular dilation rather than TR grade rests on “three poles”: annular dilation does not depend on preload whereas the right ventricle does; documented discrepancies between clinical and hemodynamic data (J Cardiol Surg. 1994 Mar;9(2 suppl):237-41; J Am Coll Cardiol. 2004 Feb. 4;43:405-9); and the idea that TR is “bad” for the patient. He also cited disparities in the number of concomitant repairs performed at leading centers: 7%-10% at the Mayo Clinic and Dr. David’s Toronto center, 25% in Leipzig, 40%-45% in his own clinic and two others, and 65% in Dr. Chikwe’s facility.

American Association for Thoracic Surgery/JTCVS

But early intervention for mitral valve dysfunction is a key indicator of the need for concomitant tricuspid valve repair, Dr. Dion said. “The earlier we operate on the MV, the less frequently patients will require tricuspid valve repair,” he said. In his own approach, Dr. Dion uses a transseptal approach of the mitral valve. For TR greater than grade 2, he performs tricuspid repair using a semirigid ring sized on the area of the anterior leaflet tissue; and if the tenting distance is 8 mm or greater, he includes anterior leaflet augmentation. When TR grade is 2 or less, he also performs concomitant tricuspid repair when the tricuspid annulus is 40 mm or greater or when the tricuspid annulus is 3.5-4 mm in the setting of a host of other cardiac problems, from atrial fibrillation to left valve dysfunction. “Otherwise: abstention,” he said.

“The major issue here is to do everything possible to avoid the risk and outcomes of reoperative tricuspid valve surgery,” Dr. Dion said, citing in-hospital death rates of 13.2% that Dr. David reported (Ann Thorac Surg. 2013 Jan;95:119-24.) and 14.6% the Leipzig group reported (J Thorac Cardiovasc Surg. 2013 Oct; 146:841-7).While he acknowledged calls for a prospective, randomized clinical trial, Dr. Dion said the contraindications for concomitant tricuspid valve repair with mitral valve repair have already been well documented.

Dr. Dion reports consulting fees from Sorin, Edwards, Johnson & Johnson, and St. Jude Medical.

The idea of performing a tricuspid valve repair during a mitral valve procedure has fueled considerable debate among cardiovascular surgeons largely because the grading of tricuspid regurgitation (TR) has been an unreliable marker, so now may be the time to use a new parameter, Dr. Robert Dion of Genk, Belgium, argues in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2015 Nov 20;150:1040-3).

“Therefore, we need a parameter hardly depending on preload,” Dr. Dion said. He noted that many authors have validated the use of annual dilatation of 40 mm or 21mm/m².

Further, preoperative functional New York Heart Association (NYHA) class plays a major role, Dr. Dion said. TR is progressive in nature and the existence of concomitant mitral valve disease can aggravate annular dilation. The earlier surgeons operate on the mitral valve, the less frequently patients will require tricuspid valve repair at the same time, he said.

The controversy was aired in a report at the 2015 American Association for Thoracic Surgery meeting when Dr. Joanna Chikwe of Mount Sinai Hospital in New York discussed an approach that led to tricuspid valve repair at the time of mitral valve surgery in almost two-thirds of patients. Dr. Chikwe and her coauthors opted for concomitant surgery when patients had moderate TR or tricuspid annular dilatation of 40 mm or greater – a strategy that Dr. Dion said was validated because they reported comparable outcomes in terms of death, morbidity, or pacemaker need. The concomitant repair cured TR and prevented progression at seven years of follow-up; and it induced right ventricle recovery and reduced pulmonary hypertension.

In this opinion piece, Dr. Dion took issue with comments made by Dr. Tirone E. David of the University of Toronto during Dr. Chikwe’s AATS presentation. Dr. David, for whom the David reimplantation technique for aortic root replacement is named, called the technique “overkill,” according to Dr. Dion.

Specifically, Dr. Dion questioned Dr. David’s assertions that the use of rigid rings in mitral valve repair causes TR and that no evidence validates the 40-mm diameter minimum in patients with degenerative mitral valve disease. On the first point, Dr. Dion said no evidence has linked the rigidity of the mitral valve ring and progression of tricuspid regurgitation. On the second, Dr. Dion cited eight studies of progressive tricuspid annular dilation with mitral regurgitation, most of which proposed the 40-mm threshold for concomitant tricuspid valve repair. Since then, the 40-mm threshold has been adopted for both European and American guidelines and validated by five reports from 2011 to 2014.

Dr. Dion said the rationale for using annular dilation rather than TR grade rests on “three poles”: annular dilation does not depend on preload whereas the right ventricle does; documented discrepancies between clinical and hemodynamic data (J Cardiol Surg. 1994 Mar;9(2 suppl):237-41; J Am Coll Cardiol. 2004 Feb. 4;43:405-9); and the idea that TR is “bad” for the patient. He also cited disparities in the number of concomitant repairs performed at leading centers: 7%-10% at the Mayo Clinic and Dr. David’s Toronto center, 25% in Leipzig, 40%-45% in his own clinic and two others, and 65% in Dr. Chikwe’s facility.

American Association for Thoracic Surgery/JTCVS

But early intervention for mitral valve dysfunction is a key indicator of the need for concomitant tricuspid valve repair, Dr. Dion said. “The earlier we operate on the MV, the less frequently patients will require tricuspid valve repair,” he said. In his own approach, Dr. Dion uses a transseptal approach of the mitral valve. For TR greater than grade 2, he performs tricuspid repair using a semirigid ring sized on the area of the anterior leaflet tissue; and if the tenting distance is 8 mm or greater, he includes anterior leaflet augmentation. When TR grade is 2 or less, he also performs concomitant tricuspid repair when the tricuspid annulus is 40 mm or greater or when the tricuspid annulus is 3.5-4 mm in the setting of a host of other cardiac problems, from atrial fibrillation to left valve dysfunction. “Otherwise: abstention,” he said.

“The major issue here is to do everything possible to avoid the risk and outcomes of reoperative tricuspid valve surgery,” Dr. Dion said, citing in-hospital death rates of 13.2% that Dr. David reported (Ann Thorac Surg. 2013 Jan;95:119-24.) and 14.6% the Leipzig group reported (J Thorac Cardiovasc Surg. 2013 Oct; 146:841-7).While he acknowledged calls for a prospective, randomized clinical trial, Dr. Dion said the contraindications for concomitant tricuspid valve repair with mitral valve repair have already been well documented.

Dr. Dion reports consulting fees from Sorin, Edwards, Johnson & Johnson, and St. Jude Medical.

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

Over the past 3 decades surgery for aortic root replacement has seen a dramatic decline in rates of death and complications, but there have been few studies comparing which technique would be best for specific patients, and those that have been done have been limited by selection bias or small patient numbers.

But a team of investigators from Weill Cornell Medical College in New York have analyzed results of three different aortic root replacement (ARR) procedures over a 17-year period and found that the rates of death during surgery and complications were less than 1% regardless of the technique. They published their results in the Journal of Thoracic and Cardiovascular Surgery (2015;150:1120-9).

American Association for Thoracic Surgery/JTCVS

“In the current era, aortic root replacement can be performed with very low perioperative risk in high-volume aortic centers,” said Dr. Mario Gaudino and coauthors. “The type of operation performed does not affect early or late survival.”

They compared results of three different approaches to ARR performed in 890 consecutive patients in their institution from May 1997 to January 2014: mechanical composite valved graft (mCVG) in 289 patients; biologic composite valved graft (bCVG) in 421; and valve-sparing reconstruction (VSR) in 180. Then the researchers applied propensity matching to neutralize the differences in the baseline characteristics between the different procedures.

The overall rate of death from the operation was 0.2%, but the two patients who died did so in the first 5 years of the study. There were no deaths in the VSR group, and the incidence of complications after surgery was less than 0.5%. Three-year survival was 94.8% and 5-year survival was 89.4%, and reintervention rates at 5 years were 0% for the mCVG group, 2.4% for the bCVG group, and 7.3% for those who had VSR. “Although mCVG remains the gold standard for durability, bCVG and VSR are excellent options for those who either cannot take or wish to avoid long-term anticoagulation,” Dr. Gaudino and colleagues said.

At the time of surgery, 332 patients (37.3%) had at least one associated cardiac procedure, led by arch replacement (149 patients) and coronary artery bypass (81 patients). Eighty-four patients (9.4%) had two or more associated procedures. The bCVG and mCVG groups had the highest rates of associated cardiac procedures.

Before propensity matching, bCVG patients were older and had more comorbidities and worse functional class, while the mCVG group had higher rates of redo procedures and urgent or emergent operations. Connective tissue disorders were most common in the VSR group.

The results paralleled data from the Society of Thoracic Surgery’s Adult Cardiac Surgery Database, Dr. Gaudino and colleagues said, including a fivefold increase in the number of root replacements performed annually during the study period and a shift away from the traditional mCVG operation to widespread adoption of the bCVG and VSR procedures in the later years of the study.

“Surgeons with extensive experience in aortic surgery can tailor their choice of ARR to the procedure that best suits the individual patient based on their baseline characteristics,” Dr. Gaudino and coauthors said.

Dr. Gaudino and his coauthors had no disclosures. 

SAN DIEGO – High-dose perioperative atorvastatin treatment did not reduce acute kidney injury following elective cardiac surgery, and it may increase risk in patients with chronic kidney disease (CKD) who are naive to statin treatment, results from a large, randomized trial showed.

“Despite advances in patient management that have reduced mortality during cardiac surgery, acute kidney injury continues to complicate the postoperative course in 20%-30% of patients,” Dr. Frederic Tremaine Billings said during a press briefing at a meeting sponsored by the American Society of Nephrology.

“Its diagnosis is independently associated with a fivefold increase in mortality following the surgery,” Dr. Tremaine added. “Statins affect several mechanisms underlying postoperative acute kidney injury. Widely prescribed to reduce cholesterol synthesis, these drugs also reduce lipid modification of intracellular signaling molecules, which have been shown to improve perfusion and reduce oxidative stress – both mechanisms important in acute kidney injury following cardiac surgery.”

Dr. Billings of the department of anesthesiology and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., and his associates tested the hypothesis that short-term, high-dose perioperative (preoperative, intraoperative, and postoperative) atorvastatin reduces acute kidney injury (AKI) following elective cardiac surgery.

The researchers randomly assigned preoperative statin-naive patients to 80 mg of atorvastatin on the morning before surgery, 40 mg on the morning of surgery, and 40 mg daily throughout hospitalization, or to a matching placebo regimen. In addition, they randomly assigned patients who were already using statins prior to surgery to 80 mg of atorvastatin the morning of surgery, and 40 mg on the morning after surgery, or to a matching placebo regimen.

“We felt it was important to not withhold statin treatment in patients already using statins prior to surgery, beyond what is typically done in clinical practice,” Dr. Billings explained. “For this reason, preoperative statin–using subjects continued their statin up until the day before surgery, and then resumed their statin use on postoperative day 2.”

The primary endpoint of the study was the incidence of AKI as determined by Acute Kidney Injury Network criteria (a 0.3 mg/dL increase in serum creatinine concentrations within 48 hours of surgery). Secondary endpoints included the maximum creatinine increase from baseline to 48 hours after surgery, ICU delirium diagnosed by the Confusion Assessment Method for the ICU, myocardial injury, and the incidence of atrial fibrillation, pneumonia, and stroke. Safety endpoints included liver toxicity, muscle toxicity, and adverse events.

The study was limited to adults having elective cardiac surgery and excluded those with statin intolerance, acute coronary syndrome, liver dysfunction, use of CYP3A4 inhibitors, kidney transplant recipients, those currently on dialysis, and those who were pregnant.

From November 2009 to October 2014, the researchers recruited 653 patients. But the trial was halted on recommendation of Vanderbilt’s data and safety monitoring board because of futility and an increased incidence of AKI among statin-naive patients with CKD randomized to atorvastatin.

Among all patients, AKI occurred in 20.8% of those randomized to atorvastatin, compared with 19.5% of those randomized to placebo, a difference that was neither clinically nor statistically significant (P = .75), Dr. Billings reported.

However, among the 199 patients who were statin naive, AKI occurred in 21.6% of those randomized to atorvastatin, compared with 13.4% of those randomized to placebo (P = .14). “An 8% difference in the incidence of AKI is of clinical importance, if true,” he said.

Among the 36 statin-naive patients with CKD, AKI occurred in 52.9% of those randomized to atorvastatin, compared with 15.8% of those randomized to placebo (P = .03). “While the number of patients in this subgroup is small, the magnitude of effect is striking,” Dr. Billings said.

Among the 416 patients who were using statins prior to surgery, AKI occurred in 20.4% of those randomized to atorvastatin, compared with 22.4% of those randomized to placebo (P = .63). Results were similar among the subset of those patients who had CKD (31.3% vs. 36.3%; P = .59).

Safety endpoints were similar between the two groups.

Strengths of the study, Dr. Billings said, include the fact that it’s the largest randomized, controlled trial to date to test this hypothesis, the pragmatic design of the protocol, and rigorous methodology.

Limitations include the “small number of patients in the statin-naive CKD subgroup,” he noted. “And the short duration of treatment among prestudy statin-using patients could limit the observation that short-term withdrawal is not harmful – although we felt it appropriate not to limit statins beyond what’s typical in clinical practice, based on prior reports that even short-term statin withdrawal may be harmful.”

The National Institutes of Health and the department of anesthesiology at Vanderbilt University supported the study. Dr. Billings reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – High-dose perioperative atorvastatin treatment did not reduce acute kidney injury following elective cardiac surgery, and it may increase risk in patients with chronic kidney disease (CKD) who are naive to statin treatment, results from a large, randomized trial showed.

“Despite advances in patient management that have reduced mortality during cardiac surgery, acute kidney injury continues to complicate the postoperative course in 20%-30% of patients,” Dr. Frederic Tremaine Billings said during a press briefing at a meeting sponsored by the American Society of Nephrology.

“Its diagnosis is independently associated with a fivefold increase in mortality following the surgery,” Dr. Tremaine added. “Statins affect several mechanisms underlying postoperative acute kidney injury. Widely prescribed to reduce cholesterol synthesis, these drugs also reduce lipid modification of intracellular signaling molecules, which have been shown to improve perfusion and reduce oxidative stress – both mechanisms important in acute kidney injury following cardiac surgery.”

Dr. Billings of the department of anesthesiology and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., and his associates tested the hypothesis that short-term, high-dose perioperative (preoperative, intraoperative, and postoperative) atorvastatin reduces acute kidney injury (AKI) following elective cardiac surgery.

The researchers randomly assigned preoperative statin-naive patients to 80 mg of atorvastatin on the morning before surgery, 40 mg on the morning of surgery, and 40 mg daily throughout hospitalization, or to a matching placebo regimen. In addition, they randomly assigned patients who were already using statins prior to surgery to 80 mg of atorvastatin the morning of surgery, and 40 mg on the morning after surgery, or to a matching placebo regimen.

“We felt it was important to not withhold statin treatment in patients already using statins prior to surgery, beyond what is typically done in clinical practice,” Dr. Billings explained. “For this reason, preoperative statin–using subjects continued their statin up until the day before surgery, and then resumed their statin use on postoperative day 2.”

The primary endpoint of the study was the incidence of AKI as determined by Acute Kidney Injury Network criteria (a 0.3 mg/dL increase in serum creatinine concentrations within 48 hours of surgery). Secondary endpoints included the maximum creatinine increase from baseline to 48 hours after surgery, ICU delirium diagnosed by the Confusion Assessment Method for the ICU, myocardial injury, and the incidence of atrial fibrillation, pneumonia, and stroke. Safety endpoints included liver toxicity, muscle toxicity, and adverse events.

The study was limited to adults having elective cardiac surgery and excluded those with statin intolerance, acute coronary syndrome, liver dysfunction, use of CYP3A4 inhibitors, kidney transplant recipients, those currently on dialysis, and those who were pregnant.

From November 2009 to October 2014, the researchers recruited 653 patients. But the trial was halted on recommendation of Vanderbilt’s data and safety monitoring board because of futility and an increased incidence of AKI among statin-naive patients with CKD randomized to atorvastatin.

Among all patients, AKI occurred in 20.8% of those randomized to atorvastatin, compared with 19.5% of those randomized to placebo, a difference that was neither clinically nor statistically significant (P = .75), Dr. Billings reported.

However, among the 199 patients who were statin naive, AKI occurred in 21.6% of those randomized to atorvastatin, compared with 13.4% of those randomized to placebo (P = .14). “An 8% difference in the incidence of AKI is of clinical importance, if true,” he said.

Among the 36 statin-naive patients with CKD, AKI occurred in 52.9% of those randomized to atorvastatin, compared with 15.8% of those randomized to placebo (P = .03). “While the number of patients in this subgroup is small, the magnitude of effect is striking,” Dr. Billings said.

Among the 416 patients who were using statins prior to surgery, AKI occurred in 20.4% of those randomized to atorvastatin, compared with 22.4% of those randomized to placebo (P = .63). Results were similar among the subset of those patients who had CKD (31.3% vs. 36.3%; P = .59).

Safety endpoints were similar between the two groups.

Strengths of the study, Dr. Billings said, include the fact that it’s the largest randomized, controlled trial to date to test this hypothesis, the pragmatic design of the protocol, and rigorous methodology.

Limitations include the “small number of patients in the statin-naive CKD subgroup,” he noted. “And the short duration of treatment among prestudy statin-using patients could limit the observation that short-term withdrawal is not harmful – although we felt it appropriate not to limit statins beyond what’s typical in clinical practice, based on prior reports that even short-term statin withdrawal may be harmful.”

The National Institutes of Health and the department of anesthesiology at Vanderbilt University supported the study. Dr. Billings reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – High-dose perioperative atorvastatin treatment did not reduce acute kidney injury following elective cardiac surgery, and it may increase risk in patients with chronic kidney disease (CKD) who are naive to statin treatment, results from a large, randomized trial showed.

“Despite advances in patient management that have reduced mortality during cardiac surgery, acute kidney injury continues to complicate the postoperative course in 20%-30% of patients,” Dr. Frederic Tremaine Billings said during a press briefing at a meeting sponsored by the American Society of Nephrology.

“Its diagnosis is independently associated with a fivefold increase in mortality following the surgery,” Dr. Tremaine added. “Statins affect several mechanisms underlying postoperative acute kidney injury. Widely prescribed to reduce cholesterol synthesis, these drugs also reduce lipid modification of intracellular signaling molecules, which have been shown to improve perfusion and reduce oxidative stress – both mechanisms important in acute kidney injury following cardiac surgery.”

Dr. Billings of the department of anesthesiology and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., and his associates tested the hypothesis that short-term, high-dose perioperative (preoperative, intraoperative, and postoperative) atorvastatin reduces acute kidney injury (AKI) following elective cardiac surgery.

The researchers randomly assigned preoperative statin-naive patients to 80 mg of atorvastatin on the morning before surgery, 40 mg on the morning of surgery, and 40 mg daily throughout hospitalization, or to a matching placebo regimen. In addition, they randomly assigned patients who were already using statins prior to surgery to 80 mg of atorvastatin the morning of surgery, and 40 mg on the morning after surgery, or to a matching placebo regimen.

“We felt it was important to not withhold statin treatment in patients already using statins prior to surgery, beyond what is typically done in clinical practice,” Dr. Billings explained. “For this reason, preoperative statin–using subjects continued their statin up until the day before surgery, and then resumed their statin use on postoperative day 2.”

The primary endpoint of the study was the incidence of AKI as determined by Acute Kidney Injury Network criteria (a 0.3 mg/dL increase in serum creatinine concentrations within 48 hours of surgery). Secondary endpoints included the maximum creatinine increase from baseline to 48 hours after surgery, ICU delirium diagnosed by the Confusion Assessment Method for the ICU, myocardial injury, and the incidence of atrial fibrillation, pneumonia, and stroke. Safety endpoints included liver toxicity, muscle toxicity, and adverse events.

The study was limited to adults having elective cardiac surgery and excluded those with statin intolerance, acute coronary syndrome, liver dysfunction, use of CYP3A4 inhibitors, kidney transplant recipients, those currently on dialysis, and those who were pregnant.

From November 2009 to October 2014, the researchers recruited 653 patients. But the trial was halted on recommendation of Vanderbilt’s data and safety monitoring board because of futility and an increased incidence of AKI among statin-naive patients with CKD randomized to atorvastatin.

Among all patients, AKI occurred in 20.8% of those randomized to atorvastatin, compared with 19.5% of those randomized to placebo, a difference that was neither clinically nor statistically significant (P = .75), Dr. Billings reported.

However, among the 199 patients who were statin naive, AKI occurred in 21.6% of those randomized to atorvastatin, compared with 13.4% of those randomized to placebo (P = .14). “An 8% difference in the incidence of AKI is of clinical importance, if true,” he said.

Among the 36 statin-naive patients with CKD, AKI occurred in 52.9% of those randomized to atorvastatin, compared with 15.8% of those randomized to placebo (P = .03). “While the number of patients in this subgroup is small, the magnitude of effect is striking,” Dr. Billings said.

Among the 416 patients who were using statins prior to surgery, AKI occurred in 20.4% of those randomized to atorvastatin, compared with 22.4% of those randomized to placebo (P = .63). Results were similar among the subset of those patients who had CKD (31.3% vs. 36.3%; P = .59).

Safety endpoints were similar between the two groups.

Strengths of the study, Dr. Billings said, include the fact that it’s the largest randomized, controlled trial to date to test this hypothesis, the pragmatic design of the protocol, and rigorous methodology.

Limitations include the “small number of patients in the statin-naive CKD subgroup,” he noted. “And the short duration of treatment among prestudy statin-using patients could limit the observation that short-term withdrawal is not harmful – although we felt it appropriate not to limit statins beyond what’s typical in clinical practice, based on prior reports that even short-term statin withdrawal may be harmful.”

The National Institutes of Health and the department of anesthesiology at Vanderbilt University supported the study. Dr. Billings reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

dchitnis@frontlinemedcom.com