Nephrology

The Food and Drug Administration is warning that hydroxyethyl starch solutions should no longer be used in the treatment of critically ill adult patients –including patients with sepsis and those admitted to an intensive care unit – after completing an analysis of data indicating that treatment with these solutions increases the risk of death and renal injury in these groups.

In a statement, the agency also recommended that the use of hydroxyethyl starch (HES) solutions, used as plasma volume expanders, be avoided in patients who are having open heart surgery with cardiopulmonary bypass, because of an increased risk of excessive bleeding.

The FDA is making these recommendations after completing an analysis of data from randomized controlled trials, meta-analyses, and observational studies in thousands of critically ill patients, and from a meta-analysis of 18 randomized controlled trials of almost 1,000 patients undergoing open heart surgery with cardiopulmonary bypass. The risks and benefits of HES products were the focus of a meeting in September 2012 convened by the FDA.

"Based on the totality of the evidence, [the] FDA considers increased mortality and renal injury requiring RRT [renal replacement therapy] in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and excess bleeding in patients undergoing open heart surgery in association with cardiopulmonary bypass, to be HES class effects," according to the statement. The agency also recommended that health care professionals avoid the use of these products in patients with preexisting renal dysfunction, discontinue their use at the first sign of renal injury, and monitor renal function for at least 90 days in all patients. In addition, HES products should be discontinued "at the first sign of coagulopathy."

The data on critically ill adults included three double-blind, multicenter, randomized controlled studies published in 2012, which compared HES with saline solution or Ringer’s acetate, in patients with severe sepsis (two studies), or patients in the ICU who had sepsis, had undergone elective surgery, and had an APACHE II score of at least 25. In these studies, which monitored patients for 90 days, HES was associated with increased mortality and/or renal injury requiring RRT, the FDA statements said. The results of meta-analyses and observational studies in similar populations lend additional support to these findings, the statement added.

But there was no evidence of an increased risk of renal injury associated with these products in a review of 59 randomized controlled studies of adult and pediatric surgical patients who received HES in the operating room and were followed for less than a week. This could have been due to less exposure to the product, a relatively short follow-up, being relatively healthy, or some unknown factor, the statement said.

In the meta-analysis of studies of patients undergoing open heart surgery with cardiopulmonary bypass, the "use of different HES products, irrespective of molecular weight or degree of molar substitution, was associated with increased bleeding," according to the statement. The meta-analysis was published in 2012 (J. Thoracic Cardiovasc. Surg. 2012:144;223-30).

A boxed warning about the risk in ICU and septic patients is being added to the labels of HES products, and the information about the excessive bleeding risk in open heart surgery patients is being added to the warnings and precautions section.

There are four FDA-approved HES products for treating and preventing hypovolemia; they are used when plasma volume expansion is needed: HESPAN (6% HES 450/0.7^a in sodium chloride injection) manufactured by B. Braun Medical); Hetastarch (6%) in 0.9% sodium chloride injection, a generic equivalent of Hespan, manufactured by Teva Pharmaceuticals USA; Hextend (6% HES 450/0.7 in physiologic solution), manufactured by BioTime; and Voluven (6% HES 130/0.4 in normal saline), manufactured by Fresenius Kabi USA.

The advisory is available at www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm358271.htm. Adverse events associated with HES solutions should be reported to the FDA’s MedWatch program at 80-332-1088 or www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

The Food and Drug Administration is warning that hydroxyethyl starch solutions should no longer be used in the treatment of critically ill adult patients –including patients with sepsis and those admitted to an intensive care unit – after completing an analysis of data indicating that treatment with these solutions increases the risk of death and renal injury in these groups.

In a statement, the agency also recommended that the use of hydroxyethyl starch (HES) solutions, used as plasma volume expanders, be avoided in patients who are having open heart surgery with cardiopulmonary bypass, because of an increased risk of excessive bleeding.

The FDA is making these recommendations after completing an analysis of data from randomized controlled trials, meta-analyses, and observational studies in thousands of critically ill patients, and from a meta-analysis of 18 randomized controlled trials of almost 1,000 patients undergoing open heart surgery with cardiopulmonary bypass. The risks and benefits of HES products were the focus of a meeting in September 2012 convened by the FDA.

"Based on the totality of the evidence, [the] FDA considers increased mortality and renal injury requiring RRT [renal replacement therapy] in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and excess bleeding in patients undergoing open heart surgery in association with cardiopulmonary bypass, to be HES class effects," according to the statement. The agency also recommended that health care professionals avoid the use of these products in patients with preexisting renal dysfunction, discontinue their use at the first sign of renal injury, and monitor renal function for at least 90 days in all patients. In addition, HES products should be discontinued "at the first sign of coagulopathy."

The data on critically ill adults included three double-blind, multicenter, randomized controlled studies published in 2012, which compared HES with saline solution or Ringer’s acetate, in patients with severe sepsis (two studies), or patients in the ICU who had sepsis, had undergone elective surgery, and had an APACHE II score of at least 25. In these studies, which monitored patients for 90 days, HES was associated with increased mortality and/or renal injury requiring RRT, the FDA statements said. The results of meta-analyses and observational studies in similar populations lend additional support to these findings, the statement added.

But there was no evidence of an increased risk of renal injury associated with these products in a review of 59 randomized controlled studies of adult and pediatric surgical patients who received HES in the operating room and were followed for less than a week. This could have been due to less exposure to the product, a relatively short follow-up, being relatively healthy, or some unknown factor, the statement said.

In the meta-analysis of studies of patients undergoing open heart surgery with cardiopulmonary bypass, the "use of different HES products, irrespective of molecular weight or degree of molar substitution, was associated with increased bleeding," according to the statement. The meta-analysis was published in 2012 (J. Thoracic Cardiovasc. Surg. 2012:144;223-30).

A boxed warning about the risk in ICU and septic patients is being added to the labels of HES products, and the information about the excessive bleeding risk in open heart surgery patients is being added to the warnings and precautions section.

There are four FDA-approved HES products for treating and preventing hypovolemia; they are used when plasma volume expansion is needed: HESPAN (6% HES 450/0.7^a in sodium chloride injection) manufactured by B. Braun Medical); Hetastarch (6%) in 0.9% sodium chloride injection, a generic equivalent of Hespan, manufactured by Teva Pharmaceuticals USA; Hextend (6% HES 450/0.7 in physiologic solution), manufactured by BioTime; and Voluven (6% HES 130/0.4 in normal saline), manufactured by Fresenius Kabi USA.

The advisory is available at www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm358271.htm. Adverse events associated with HES solutions should be reported to the FDA’s MedWatch program at 80-332-1088 or www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

The Food and Drug Administration is warning that hydroxyethyl starch solutions should no longer be used in the treatment of critically ill adult patients –including patients with sepsis and those admitted to an intensive care unit – after completing an analysis of data indicating that treatment with these solutions increases the risk of death and renal injury in these groups.

In a statement, the agency also recommended that the use of hydroxyethyl starch (HES) solutions, used as plasma volume expanders, be avoided in patients who are having open heart surgery with cardiopulmonary bypass, because of an increased risk of excessive bleeding.

The FDA is making these recommendations after completing an analysis of data from randomized controlled trials, meta-analyses, and observational studies in thousands of critically ill patients, and from a meta-analysis of 18 randomized controlled trials of almost 1,000 patients undergoing open heart surgery with cardiopulmonary bypass. The risks and benefits of HES products were the focus of a meeting in September 2012 convened by the FDA.

"Based on the totality of the evidence, [the] FDA considers increased mortality and renal injury requiring RRT [renal replacement therapy] in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and excess bleeding in patients undergoing open heart surgery in association with cardiopulmonary bypass, to be HES class effects," according to the statement. The agency also recommended that health care professionals avoid the use of these products in patients with preexisting renal dysfunction, discontinue their use at the first sign of renal injury, and monitor renal function for at least 90 days in all patients. In addition, HES products should be discontinued "at the first sign of coagulopathy."

The data on critically ill adults included three double-blind, multicenter, randomized controlled studies published in 2012, which compared HES with saline solution or Ringer’s acetate, in patients with severe sepsis (two studies), or patients in the ICU who had sepsis, had undergone elective surgery, and had an APACHE II score of at least 25. In these studies, which monitored patients for 90 days, HES was associated with increased mortality and/or renal injury requiring RRT, the FDA statements said. The results of meta-analyses and observational studies in similar populations lend additional support to these findings, the statement added.

But there was no evidence of an increased risk of renal injury associated with these products in a review of 59 randomized controlled studies of adult and pediatric surgical patients who received HES in the operating room and were followed for less than a week. This could have been due to less exposure to the product, a relatively short follow-up, being relatively healthy, or some unknown factor, the statement said.

In the meta-analysis of studies of patients undergoing open heart surgery with cardiopulmonary bypass, the "use of different HES products, irrespective of molecular weight or degree of molar substitution, was associated with increased bleeding," according to the statement. The meta-analysis was published in 2012 (J. Thoracic Cardiovasc. Surg. 2012:144;223-30).

A boxed warning about the risk in ICU and septic patients is being added to the labels of HES products, and the information about the excessive bleeding risk in open heart surgery patients is being added to the warnings and precautions section.

There are four FDA-approved HES products for treating and preventing hypovolemia; they are used when plasma volume expansion is needed: HESPAN (6% HES 450/0.7^a in sodium chloride injection) manufactured by B. Braun Medical); Hetastarch (6%) in 0.9% sodium chloride injection, a generic equivalent of Hespan, manufactured by Teva Pharmaceuticals USA; Hextend (6% HES 450/0.7 in physiologic solution), manufactured by BioTime; and Voluven (6% HES 130/0.4 in normal saline), manufactured by Fresenius Kabi USA.

The advisory is available at www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm358271.htm. Adverse events associated with HES solutions should be reported to the FDA’s MedWatch program at 80-332-1088 or www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

Asymptomatic microscopic hematuria is a clinical challenge fraught with uncertainty, risk, and expense. With an estimated hematuria prevalence of 9%-18% and a threshold of at least 3 red blood cells per high-power field (RBC/HPF) as a cutoff for evaluation, we are all dealing with this problem – a lot. CT urograms, urine cytologies, and cystoscopies commonly compose the evaluation algorithm for this relatively low-prevalence disease.

What we need is a reliable and predictable way to place patients into different risk categories.

Dr. Ronald K. Loo of the Southern California Permanente Medical Group, Los Angeles, and his colleagues tried to answer this need by evaluating the performance of the Hematuria Risk Index (Mayo Clin. Proc. 2013;88:129-38).

The investigators assembled a prospective cohort of patients who were in the Kaiser Permanente system and had been referred to a urologist to undergo a full evaluation for asymptomatic microscopic hematuria. They derived the risk index from a "test cohort" composed of 2,630 patients, among whom 2.1% had a cancer detected and 1.9% had a pathologically confirmed urinary tract cancer.

The Hematuria Risk Index they developed is scored as follows: 4 points for gross hematuria and/or age at least 50 years and 1 point for a history of smoking, male gender, and/or greater than 25 RBC/HPF on recent urinalysis. The range is from 0 to 11 points, with patients stratified as low risk (0-4 points), moderate risk (5-8 points), or high risk (9-11 points).

Applying this risk index to a validation cohort, cancer was detected in 10.7% of the high-risk patients, 2.5% of the moderate-risk patients, and 0% of the low-risk patients.

Importantly, Dr. Loo and his associates concluded that microscopic hematuria is an unreliable indicator of urothelial malignancy. They further concluded that the risk of identifying a urinary tract cancer in anyone younger than 50 years without a history of gross hematuria is close to zero. Non-neoplastic findings included urinary stones, prostatic bleeding, urinary tract infection, and glomerular disease

This is a fantastically helpful study. Now, getting this Hematuria Risk Index as an app on my smartphone will make my year.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author. Reply via e-mail at [email protected].

Asymptomatic microscopic hematuria is a clinical challenge fraught with uncertainty, risk, and expense. With an estimated hematuria prevalence of 9%-18% and a threshold of at least 3 red blood cells per high-power field (RBC/HPF) as a cutoff for evaluation, we are all dealing with this problem – a lot. CT urograms, urine cytologies, and cystoscopies commonly compose the evaluation algorithm for this relatively low-prevalence disease.

What we need is a reliable and predictable way to place patients into different risk categories.

Dr. Ronald K. Loo of the Southern California Permanente Medical Group, Los Angeles, and his colleagues tried to answer this need by evaluating the performance of the Hematuria Risk Index (Mayo Clin. Proc. 2013;88:129-38).

The investigators assembled a prospective cohort of patients who were in the Kaiser Permanente system and had been referred to a urologist to undergo a full evaluation for asymptomatic microscopic hematuria. They derived the risk index from a "test cohort" composed of 2,630 patients, among whom 2.1% had a cancer detected and 1.9% had a pathologically confirmed urinary tract cancer.

The Hematuria Risk Index they developed is scored as follows: 4 points for gross hematuria and/or age at least 50 years and 1 point for a history of smoking, male gender, and/or greater than 25 RBC/HPF on recent urinalysis. The range is from 0 to 11 points, with patients stratified as low risk (0-4 points), moderate risk (5-8 points), or high risk (9-11 points).

Applying this risk index to a validation cohort, cancer was detected in 10.7% of the high-risk patients, 2.5% of the moderate-risk patients, and 0% of the low-risk patients.

Importantly, Dr. Loo and his associates concluded that microscopic hematuria is an unreliable indicator of urothelial malignancy. They further concluded that the risk of identifying a urinary tract cancer in anyone younger than 50 years without a history of gross hematuria is close to zero. Non-neoplastic findings included urinary stones, prostatic bleeding, urinary tract infection, and glomerular disease

This is a fantastically helpful study. Now, getting this Hematuria Risk Index as an app on my smartphone will make my year.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author. Reply via e-mail at [email protected].

Asymptomatic microscopic hematuria is a clinical challenge fraught with uncertainty, risk, and expense. With an estimated hematuria prevalence of 9%-18% and a threshold of at least 3 red blood cells per high-power field (RBC/HPF) as a cutoff for evaluation, we are all dealing with this problem – a lot. CT urograms, urine cytologies, and cystoscopies commonly compose the evaluation algorithm for this relatively low-prevalence disease.

What we need is a reliable and predictable way to place patients into different risk categories.

Dr. Ronald K. Loo of the Southern California Permanente Medical Group, Los Angeles, and his colleagues tried to answer this need by evaluating the performance of the Hematuria Risk Index (Mayo Clin. Proc. 2013;88:129-38).

The investigators assembled a prospective cohort of patients who were in the Kaiser Permanente system and had been referred to a urologist to undergo a full evaluation for asymptomatic microscopic hematuria. They derived the risk index from a "test cohort" composed of 2,630 patients, among whom 2.1% had a cancer detected and 1.9% had a pathologically confirmed urinary tract cancer.

The Hematuria Risk Index they developed is scored as follows: 4 points for gross hematuria and/or age at least 50 years and 1 point for a history of smoking, male gender, and/or greater than 25 RBC/HPF on recent urinalysis. The range is from 0 to 11 points, with patients stratified as low risk (0-4 points), moderate risk (5-8 points), or high risk (9-11 points).

Applying this risk index to a validation cohort, cancer was detected in 10.7% of the high-risk patients, 2.5% of the moderate-risk patients, and 0% of the low-risk patients.

Importantly, Dr. Loo and his associates concluded that microscopic hematuria is an unreliable indicator of urothelial malignancy. They further concluded that the risk of identifying a urinary tract cancer in anyone younger than 50 years without a history of gross hematuria is close to zero. Non-neoplastic findings included urinary stones, prostatic bleeding, urinary tract infection, and glomerular disease

This is a fantastically helpful study. Now, getting this Hematuria Risk Index as an app on my smartphone will make my year.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author. Reply via e-mail at [email protected].

LAS VEGAS – Vancomycin is as safe on the kidneys of critically ill patients as linezolid, so long as trough levels don’t exceed the recommended upper limit of 20 mcg/mL, according to researchers from the University of Virginia in Charlottesville.

"When correct dosing is performed, the use of alternative agents to treat Gram-positive infections – specifically to avoid [vancomycin] nephrotoxicity – is unnecessary. Vancomycin use in critically ill patients is no different than linezolid use regarding nephrotoxicity or new-onset need for hemodialysis," said lead investigator Stephen Davies, a resident in the department of surgery, said at the annual meeting of the Surgical Infection Society.

The kidney safety of vancomycin has been in doubt, with mixed results from prior studies. To shed light on the issue, Dr. Davies and his team compared renal outcomes in 298 critically ill patients treated with vancomycin for 571 Gram-positive infections with outcomes in 247 patients treated with linezolid for 475 Gram-positive infections.

Infection sites included the lungs, peritoneum, blood stream, and urinary tract, among others, and isolates included Staphylococcus aureus (77 methicillin-resistant S. aureus), Enterococcus faecium (67 vancomycin-resistant Enterococcus), E. faecalis, and Streptococcus species. Vancomycin patients were dosed at 15-20 mg/kg, with serial trough monitoring, and treated for a mean of 16.2 days, vs. 14.3 days for linezolid. Patients were on no other nephrotoxic agents.

In the end, "there were no [statistically significant] differences between the two groups regarding maximum creatinine during treatment, final creatinine after treatment, change in creatinine maximum and initial values, and final and initial creatinine values." There were also no differences "in new-onset hemodialysis or death," Dr. Davies said.

APACHE II (Acute Physiology and Chronic Health Evaluation II) scores above 30 and initial creatinine levels above 1.2 mg/dL both predicted the need for new-onset hemodialysis, but antibiotic choice did not.

Those same two variables also predicted an increase in creatinine of more than 1.0 mg/dl during treatment; vancomycin use did, as well (relative risk, vancomycin 0.49; 95% confidence interval: 0.25-0.94). Concerned, the team looked into the issue. "What we found was that a rise in creatinine was typically not encountered until trough levels greater than 20 mg/dL were reached. As long as you stay within the recommended doses, you should be safe," Dr. Davies said.

There were no statistically significant baseline differences between the two groups in renal function, hemodialysis, creatinine levels, or APACHE II scores.

Despite the results, Dr. Philip Barie, who helped moderate Dr. Davies’ talk, said in an interview that he’s still concerned about vancomycin kidney safety.

"We are having to use higher doses to treat tougher bugs, and whereas nephrotoxicity pretty much went away with vancomycin after they purified the drug [decades ago], now we are having to use higher doses more, and nephrotoxicity is beginning to creep back into the picture. You have to dose really carefully, and if you have an organism that is among the more resistant to vancomycin, the safest thing to do with vancomycin is to use linezolid," said Dr. Barie, a professor of surgery and public heath at Cornell University, New York.

Dr. Davies and Dr. Barie reported no relevant disclosures.

[email protected]

LAS VEGAS – Vancomycin is as safe on the kidneys of critically ill patients as linezolid, so long as trough levels don’t exceed the recommended upper limit of 20 mcg/mL, according to researchers from the University of Virginia in Charlottesville.

"When correct dosing is performed, the use of alternative agents to treat Gram-positive infections – specifically to avoid [vancomycin] nephrotoxicity – is unnecessary. Vancomycin use in critically ill patients is no different than linezolid use regarding nephrotoxicity or new-onset need for hemodialysis," said lead investigator Stephen Davies, a resident in the department of surgery, said at the annual meeting of the Surgical Infection Society.

The kidney safety of vancomycin has been in doubt, with mixed results from prior studies. To shed light on the issue, Dr. Davies and his team compared renal outcomes in 298 critically ill patients treated with vancomycin for 571 Gram-positive infections with outcomes in 247 patients treated with linezolid for 475 Gram-positive infections.

Infection sites included the lungs, peritoneum, blood stream, and urinary tract, among others, and isolates included Staphylococcus aureus (77 methicillin-resistant S. aureus), Enterococcus faecium (67 vancomycin-resistant Enterococcus), E. faecalis, and Streptococcus species. Vancomycin patients were dosed at 15-20 mg/kg, with serial trough monitoring, and treated for a mean of 16.2 days, vs. 14.3 days for linezolid. Patients were on no other nephrotoxic agents.

In the end, "there were no [statistically significant] differences between the two groups regarding maximum creatinine during treatment, final creatinine after treatment, change in creatinine maximum and initial values, and final and initial creatinine values." There were also no differences "in new-onset hemodialysis or death," Dr. Davies said.

APACHE II (Acute Physiology and Chronic Health Evaluation II) scores above 30 and initial creatinine levels above 1.2 mg/dL both predicted the need for new-onset hemodialysis, but antibiotic choice did not.

Those same two variables also predicted an increase in creatinine of more than 1.0 mg/dl during treatment; vancomycin use did, as well (relative risk, vancomycin 0.49; 95% confidence interval: 0.25-0.94). Concerned, the team looked into the issue. "What we found was that a rise in creatinine was typically not encountered until trough levels greater than 20 mg/dL were reached. As long as you stay within the recommended doses, you should be safe," Dr. Davies said.

There were no statistically significant baseline differences between the two groups in renal function, hemodialysis, creatinine levels, or APACHE II scores.

Despite the results, Dr. Philip Barie, who helped moderate Dr. Davies’ talk, said in an interview that he’s still concerned about vancomycin kidney safety.

"We are having to use higher doses to treat tougher bugs, and whereas nephrotoxicity pretty much went away with vancomycin after they purified the drug [decades ago], now we are having to use higher doses more, and nephrotoxicity is beginning to creep back into the picture. You have to dose really carefully, and if you have an organism that is among the more resistant to vancomycin, the safest thing to do with vancomycin is to use linezolid," said Dr. Barie, a professor of surgery and public heath at Cornell University, New York.

Dr. Davies and Dr. Barie reported no relevant disclosures.

[email protected]

LAS VEGAS – Vancomycin is as safe on the kidneys of critically ill patients as linezolid, so long as trough levels don’t exceed the recommended upper limit of 20 mcg/mL, according to researchers from the University of Virginia in Charlottesville.

"When correct dosing is performed, the use of alternative agents to treat Gram-positive infections – specifically to avoid [vancomycin] nephrotoxicity – is unnecessary. Vancomycin use in critically ill patients is no different than linezolid use regarding nephrotoxicity or new-onset need for hemodialysis," said lead investigator Stephen Davies, a resident in the department of surgery, said at the annual meeting of the Surgical Infection Society.

The kidney safety of vancomycin has been in doubt, with mixed results from prior studies. To shed light on the issue, Dr. Davies and his team compared renal outcomes in 298 critically ill patients treated with vancomycin for 571 Gram-positive infections with outcomes in 247 patients treated with linezolid for 475 Gram-positive infections.

Infection sites included the lungs, peritoneum, blood stream, and urinary tract, among others, and isolates included Staphylococcus aureus (77 methicillin-resistant S. aureus), Enterococcus faecium (67 vancomycin-resistant Enterococcus), E. faecalis, and Streptococcus species. Vancomycin patients were dosed at 15-20 mg/kg, with serial trough monitoring, and treated for a mean of 16.2 days, vs. 14.3 days for linezolid. Patients were on no other nephrotoxic agents.

In the end, "there were no [statistically significant] differences between the two groups regarding maximum creatinine during treatment, final creatinine after treatment, change in creatinine maximum and initial values, and final and initial creatinine values." There were also no differences "in new-onset hemodialysis or death," Dr. Davies said.

APACHE II (Acute Physiology and Chronic Health Evaluation II) scores above 30 and initial creatinine levels above 1.2 mg/dL both predicted the need for new-onset hemodialysis, but antibiotic choice did not.

Those same two variables also predicted an increase in creatinine of more than 1.0 mg/dl during treatment; vancomycin use did, as well (relative risk, vancomycin 0.49; 95% confidence interval: 0.25-0.94). Concerned, the team looked into the issue. "What we found was that a rise in creatinine was typically not encountered until trough levels greater than 20 mg/dL were reached. As long as you stay within the recommended doses, you should be safe," Dr. Davies said.

There were no statistically significant baseline differences between the two groups in renal function, hemodialysis, creatinine levels, or APACHE II scores.

Despite the results, Dr. Philip Barie, who helped moderate Dr. Davies’ talk, said in an interview that he’s still concerned about vancomycin kidney safety.

"We are having to use higher doses to treat tougher bugs, and whereas nephrotoxicity pretty much went away with vancomycin after they purified the drug [decades ago], now we are having to use higher doses more, and nephrotoxicity is beginning to creep back into the picture. You have to dose really carefully, and if you have an organism that is among the more resistant to vancomycin, the safest thing to do with vancomycin is to use linezolid," said Dr. Barie, a professor of surgery and public heath at Cornell University, New York.

Dr. Davies and Dr. Barie reported no relevant disclosures.

[email protected]

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

DENVER – Catheter ablation of atrial fibrillation in patients with comorbid moderate chronic kidney disease may have a side benefit: improved renal function, according to Dr. Nazem W. Akoum.

Among 81 patients with stage 3 or 4 chronic kidney disease (CKD) who underwent successful AF ablation, the mean estimated glomerular filtration rate (eGFR) improved significantly, from 46.7 mL/min per 1.73 m² at baseline to 53 mL/min per 1.73 m² at follow-up 3 months post procedure, Dr. Akoum reported at the annual meeting of the Heart Rhythm Society.

In contrast, the eGFR in 382 patients with stage 1 or 2 CKD who underwent AF ablation didn’t change significantly, from a baseline mean of 103.6 mL/min per 1.73 m², added Dr. Akoum, an electrophysiologist at the University of Utah, Salt Lake City.

Patients with AF and stage 5 or 6 CKD were excluded from participation in this study. Given the requirement for preablation quantification of the extent of atrial fibrosis via delayed-enhancement MRI with gadolinium contrast, there were safety concerns regarding exposing patients with advanced CKD to gadolinium.

Patients with stage 1 or 2 CKD averaged 15.8% left atrial fibrosis, while stage 3 or 4 patients averaged 19.1%.

The improvement in eGFR noted in the group with stage 3 or 4 CKD following restoration of sinus rhythm appeared to be independent of left ventricular systolic performance or medication effects. The postablation regularization of ventricular activation and the resultant improvement in endothelial function may have contributed to the welcome renal side benefit, Dr. Akoum said.

He reported having no relevant financial conflicts.

[email protected]

DENVER – Catheter ablation of atrial fibrillation in patients with comorbid moderate chronic kidney disease may have a side benefit: improved renal function, according to Dr. Nazem W. Akoum.

Among 81 patients with stage 3 or 4 chronic kidney disease (CKD) who underwent successful AF ablation, the mean estimated glomerular filtration rate (eGFR) improved significantly, from 46.7 mL/min per 1.73 m² at baseline to 53 mL/min per 1.73 m² at follow-up 3 months post procedure, Dr. Akoum reported at the annual meeting of the Heart Rhythm Society.

In contrast, the eGFR in 382 patients with stage 1 or 2 CKD who underwent AF ablation didn’t change significantly, from a baseline mean of 103.6 mL/min per 1.73 m², added Dr. Akoum, an electrophysiologist at the University of Utah, Salt Lake City.

Patients with AF and stage 5 or 6 CKD were excluded from participation in this study. Given the requirement for preablation quantification of the extent of atrial fibrosis via delayed-enhancement MRI with gadolinium contrast, there were safety concerns regarding exposing patients with advanced CKD to gadolinium.

Patients with stage 1 or 2 CKD averaged 15.8% left atrial fibrosis, while stage 3 or 4 patients averaged 19.1%.

The improvement in eGFR noted in the group with stage 3 or 4 CKD following restoration of sinus rhythm appeared to be independent of left ventricular systolic performance or medication effects. The postablation regularization of ventricular activation and the resultant improvement in endothelial function may have contributed to the welcome renal side benefit, Dr. Akoum said.

He reported having no relevant financial conflicts.

[email protected]

DENVER – Catheter ablation of atrial fibrillation in patients with comorbid moderate chronic kidney disease may have a side benefit: improved renal function, according to Dr. Nazem W. Akoum.

Among 81 patients with stage 3 or 4 chronic kidney disease (CKD) who underwent successful AF ablation, the mean estimated glomerular filtration rate (eGFR) improved significantly, from 46.7 mL/min per 1.73 m² at baseline to 53 mL/min per 1.73 m² at follow-up 3 months post procedure, Dr. Akoum reported at the annual meeting of the Heart Rhythm Society.

In contrast, the eGFR in 382 patients with stage 1 or 2 CKD who underwent AF ablation didn’t change significantly, from a baseline mean of 103.6 mL/min per 1.73 m², added Dr. Akoum, an electrophysiologist at the University of Utah, Salt Lake City.

Patients with AF and stage 5 or 6 CKD were excluded from participation in this study. Given the requirement for preablation quantification of the extent of atrial fibrosis via delayed-enhancement MRI with gadolinium contrast, there were safety concerns regarding exposing patients with advanced CKD to gadolinium.

Patients with stage 1 or 2 CKD averaged 15.8% left atrial fibrosis, while stage 3 or 4 patients averaged 19.1%.

The improvement in eGFR noted in the group with stage 3 or 4 CKD following restoration of sinus rhythm appeared to be independent of left ventricular systolic performance or medication effects. The postablation regularization of ventricular activation and the resultant improvement in endothelial function may have contributed to the welcome renal side benefit, Dr. Akoum said.

He reported having no relevant financial conflicts.

[email protected]

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

[email protected]

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

[email protected]

SAN DIEGO – Prostate-specific antigen peptidase activity is higher in patients with less-aggressive prostate cancer than in patients with advanced disease, results from a pilot study demonstrated.

If the finding is confirmed by larger studies, this marker "may improve identification of men who may be better candidates for active surveillance," Dr. William J. Catalona said at the annual meeting of the American Urological Association. "In our study, if you considered those patients, it may have delayed or prevented surgery in 22% of this study population."

The marker, an assay developed by Ohmx under a National Institutes of Health small-business grant, "is a completely different approach to PSA testing," said Dr. Catalona, professor of urology at Northwestern University, Chicago.

"Current prostate cancer detection techniques generally suffer from a limited ability to differentiate indolent from aggressive prostate cancers," he explained. "We’re looking for tests that would detect life-threatening prostate cancer. That’s the real challenge in front of us today."

PSA peptidase activity was measured in a blinded study of 100 randomly selected patients who were treated with radical retropubic prostatectomy. Of the 100 patients, 50 had aggressive disease (defined as cancer resulting in prostate cancer–specific death, lymph node or distant metastases, seminal vesicle invasion, or extracapsular tumor extension), and 50 had nonaggressive disease (defined as cancer with a Gleason score of 6 or lower, pathologic stage T2, and no evidence of clinical or biochemical tumor recurrence on follow-up of 2-5 years). At surgery, fluid from the excised gland was gently milked from the apical urethral stump into a 2-mL conical vial and was immediately frozen at –80° C.

Next, researchers used a fluorogenic peptide probe to measure the level of proteolytic enzyme activity of PSA (aPSA) in each sample.

"All PSA tests measure the amount of PSA," said Dr. Catalona, who developed the PSA as a screening test for prostate cancer. "What this test focuses on is the enzymatic activity of PSA in prostatic fluid."

The aPSA value was significantly higher in patients with nonaggressive disease, compared with their counterparts who had advanced disease (a mean of 865 mcg/mL vs. a mean of 518 mcg/mL), a difference Dr. Catalona described as "striking." This reciprocal relationship between the PSA peptidase activity among the two patient groups "may improve identification of men who may be better candidates for active surveillance."

On receiver operating characteristic analysis, aPSA and the normalized ratio of aPSA to serum total PSA had the highest discriminatory power for predicting the presence of aggressive prostate cancer. Dr. Catalona estimated that using aPSA as an aggressiveness biomarker could result in 22% of the patients diagnosed with nonaggressive prostate cancer being able to avoid or delay radical prostatectomy.

Dr. Catalona said he and his associates plan to expand studies of the biomarker to include samples collected retrospectively before surgery, during attentive digital rectal exam.

The study was supported in part by a grant from the National Institutes of Health. Dr. Catalona disclosed that he received grant and research support from Beckman Coulter, Ohmx, and deCODE Genetics.

[email protected]

NATIONAL HARBOR, MD. – Angiotensin receptor blockade on the morning of a major orthopedic surgery was associated with a tripling in the risk of acute kidney injury – a link probably driven by the drugs’ association with perioperative hypotension, a retrospective analysis has found.

"Our study does support the idea of withholding beta-blockers on the morning of these major procedures," Dr. Eileen Hennrikus reported at the annual meeting of the Society of Hospital Medicine.

Extant literature has confirmed a link between beta-blockers and hypotension in connection with cardiovascular surgery, but not orthopedic surgery. Dr. Hennrikus, of the Milton S. Hershey Medical Center, Hershey, Penn., examined the link in patients undergoing elective spine fusions, total hip or total knee replacement – procedures typically associated with greater blood loss than cardiovascular surgeries.

She used retrospective data from 922 patients who had undergone any of the three surgeries during 2010. Induction hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes within a half hour of anesthesia induction. Intraoperative hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes during maintenance anesthesia. The measure of acute kidney injury was an increase in serum creative of at least 0.3 mg/dL, or a 50% increase over preoperative levels.

Of the entire cohort, 37% (343) patients received their prescribed angiotensin receptor blocker or angiotensin converting enzyme inhibitor on the morning of their surgery. The incidence of induction hypotension was significantly greater in those patients in patients who took the medication than in those who did not (12% vs. 6.7%; OR 1.93). Acute kidney injury was also significantly more common among those who had the medications, however (8% vs. 2%; OR 5.4). Intraoperative hypotension was not significantly different between the groups.

Dr. Hennrikus conducted a multivariate analysis to further tease out the relationship between the medications and acute kidney injury. The regression controlled for age, medical comorbidities (diabetes, coronary artery disease, hypertension, and congestive heart failure), body mass index, medications (diuretics, beta-blockers, calcium channel blockers, general anesthesia-induction agents, and vasopressors), and blood loss.

After adjustment for all of those factors, angiotensin blockade conferred a threefold increase in the risk of acute kidney injury (OR 2.97). Although in the primary analysis, intraoperative hypotension had not been significantly associated with the drugs, it more than doubled the risk of kidney injury the risk (OR 2.6) in the multivariate analysis.

The model also revealed something of a surprise, Dr. Hennrikus said: Body mass index was an independent risk factor for acute kidney injury. For every 5 kg/m² increase in BMI, the risk increased by 29% (OR 1.29).

Acute kidney injury exerted its own influence over hospital length of stay and mortality. The length of stay was significantly longer in patients who had kidney injury (6. days vs. 3 days). Two-year mortality was also significantly higher (6% vs. 2%).

Neither Dr. Hennrikus nor her coinvestigators reported having any financial conflicts.

[email protected]

NATIONAL HARBOR, MD. – Angiotensin receptor blockade on the morning of a major orthopedic surgery was associated with a tripling in the risk of acute kidney injury – a link probably driven by the drugs’ association with perioperative hypotension, a retrospective analysis has found.

"Our study does support the idea of withholding beta-blockers on the morning of these major procedures," Dr. Eileen Hennrikus reported at the annual meeting of the Society of Hospital Medicine.

Extant literature has confirmed a link between beta-blockers and hypotension in connection with cardiovascular surgery, but not orthopedic surgery. Dr. Hennrikus, of the Milton S. Hershey Medical Center, Hershey, Penn., examined the link in patients undergoing elective spine fusions, total hip or total knee replacement – procedures typically associated with greater blood loss than cardiovascular surgeries.

She used retrospective data from 922 patients who had undergone any of the three surgeries during 2010. Induction hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes within a half hour of anesthesia induction. Intraoperative hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes during maintenance anesthesia. The measure of acute kidney injury was an increase in serum creative of at least 0.3 mg/dL, or a 50% increase over preoperative levels.

Of the entire cohort, 37% (343) patients received their prescribed angiotensin receptor blocker or angiotensin converting enzyme inhibitor on the morning of their surgery. The incidence of induction hypotension was significantly greater in those patients in patients who took the medication than in those who did not (12% vs. 6.7%; OR 1.93). Acute kidney injury was also significantly more common among those who had the medications, however (8% vs. 2%; OR 5.4). Intraoperative hypotension was not significantly different between the groups.

Dr. Hennrikus conducted a multivariate analysis to further tease out the relationship between the medications and acute kidney injury. The regression controlled for age, medical comorbidities (diabetes, coronary artery disease, hypertension, and congestive heart failure), body mass index, medications (diuretics, beta-blockers, calcium channel blockers, general anesthesia-induction agents, and vasopressors), and blood loss.

After adjustment for all of those factors, angiotensin blockade conferred a threefold increase in the risk of acute kidney injury (OR 2.97). Although in the primary analysis, intraoperative hypotension had not been significantly associated with the drugs, it more than doubled the risk of kidney injury the risk (OR 2.6) in the multivariate analysis.

The model also revealed something of a surprise, Dr. Hennrikus said: Body mass index was an independent risk factor for acute kidney injury. For every 5 kg/m² increase in BMI, the risk increased by 29% (OR 1.29).

Acute kidney injury exerted its own influence over hospital length of stay and mortality. The length of stay was significantly longer in patients who had kidney injury (6. days vs. 3 days). Two-year mortality was also significantly higher (6% vs. 2%).

Neither Dr. Hennrikus nor her coinvestigators reported having any financial conflicts.

[email protected]

NATIONAL HARBOR, MD. – Angiotensin receptor blockade on the morning of a major orthopedic surgery was associated with a tripling in the risk of acute kidney injury – a link probably driven by the drugs’ association with perioperative hypotension, a retrospective analysis has found.

"Our study does support the idea of withholding beta-blockers on the morning of these major procedures," Dr. Eileen Hennrikus reported at the annual meeting of the Society of Hospital Medicine.

Extant literature has confirmed a link between beta-blockers and hypotension in connection with cardiovascular surgery, but not orthopedic surgery. Dr. Hennrikus, of the Milton S. Hershey Medical Center, Hershey, Penn., examined the link in patients undergoing elective spine fusions, total hip or total knee replacement – procedures typically associated with greater blood loss than cardiovascular surgeries.

She used retrospective data from 922 patients who had undergone any of the three surgeries during 2010. Induction hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes within a half hour of anesthesia induction. Intraoperative hypotension was defined as a systolic blood pressure of 80 mm Hg for at least 10 minutes during maintenance anesthesia. The measure of acute kidney injury was an increase in serum creative of at least 0.3 mg/dL, or a 50% increase over preoperative levels.

Of the entire cohort, 37% (343) patients received their prescribed angiotensin receptor blocker or angiotensin converting enzyme inhibitor on the morning of their surgery. The incidence of induction hypotension was significantly greater in those patients in patients who took the medication than in those who did not (12% vs. 6.7%; OR 1.93). Acute kidney injury was also significantly more common among those who had the medications, however (8% vs. 2%; OR 5.4). Intraoperative hypotension was not significantly different between the groups.

Dr. Hennrikus conducted a multivariate analysis to further tease out the relationship between the medications and acute kidney injury. The regression controlled for age, medical comorbidities (diabetes, coronary artery disease, hypertension, and congestive heart failure), body mass index, medications (diuretics, beta-blockers, calcium channel blockers, general anesthesia-induction agents, and vasopressors), and blood loss.

After adjustment for all of those factors, angiotensin blockade conferred a threefold increase in the risk of acute kidney injury (OR 2.97). Although in the primary analysis, intraoperative hypotension had not been significantly associated with the drugs, it more than doubled the risk of kidney injury the risk (OR 2.6) in the multivariate analysis.

The model also revealed something of a surprise, Dr. Hennrikus said: Body mass index was an independent risk factor for acute kidney injury. For every 5 kg/m² increase in BMI, the risk increased by 29% (OR 1.29).

Acute kidney injury exerted its own influence over hospital length of stay and mortality. The length of stay was significantly longer in patients who had kidney injury (6. days vs. 3 days). Two-year mortality was also significantly higher (6% vs. 2%).

Neither Dr. Hennrikus nor her coinvestigators reported having any financial conflicts.

[email protected]

Surveillance is sufficient for most men with stage I seminoma after successful orchiectomy, according to the findings of the largest study ever performed to address the issue.

The 1,822 men followed only with surveillance in Denmark had an excellent disease-specific survival of 99.5%, Dr. Mette Saskø Mortensen said at a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology annual meeting. Only 10 men died of testicular cancer or treatment-related causes during a median follow-up of 15.4 years.

This finding means that for every 1,000 men followed by a surveillance program, only 4 will die within 10 years, said incoming ASCO president Dr. Clifford Hudis, chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York.

He described the study as one of several recent reminders that sometimes "less is more" in patient care and noted that opting for surveillance spares patients from the harmful side effects of chemotherapy and radiation without diminishing their chances for long-term survival.

Seminoma is a relatively rare cancer, but it is the most common solid tumor among young men. Initial treatment is typically orchiectomy, but no standard postoperative management strategy has been established. The current results will likely accelerate the trend toward surveillance in the United States, where roughly 50% of men undergo either radiotherapy or chemotherapy with carboplatin after surgery.

Overall, 355 (19.5%) of the 1,822 men experienced a relapse during surveillance, said Dr. Mortensen, a PhD student in the oncology department at Copenhagen University Hospital.

The median time to relapse was 13.7 months, with the majority of patients (72.4%) relapsing within the first 2 years. Another 20.3% relapsed within years 2-5 and 7.3% after 5 years.

"With only 19.5% of the patients relapsing, the surveillance strategy spares the remaining 80% of patients from unnecessary treatment after orchiectomy," Dr. Mortensen said. "Surveillance is a safe strategy for stage I seminoma patients."

Surveillance has been the main follow-up strategy for stage I seminoma in Denmark since 1984, and consists of 5 years of scheduled clinical visits, computed tomography scans/chest x-rays, and blood measurements of tumor markers. Men in the analysis were diagnosed from 1984 to 2008, and their data were collected up to December 2012 from patient files and linked national registries.

As observed in other smaller studies, the risk for relapse was increased with elevated human chorionic gonadotropin levels of more than 200 IU/L, vascular invasion, and tumors larger than 4 cm, Dr. Mortensen said.

The study was supported in part by the Danish Cancer Society, Danish Research Foundation and the Preben and Anna Simonsen Foundation. Dr. Mortensen reported having no financial disclosures.

[email protected]

Surveillance is sufficient for most men with stage I seminoma after successful orchiectomy, according to the findings of the largest study ever performed to address the issue.

The 1,822 men followed only with surveillance in Denmark had an excellent disease-specific survival of 99.5%, Dr. Mette Saskø Mortensen said at a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology annual meeting. Only 10 men died of testicular cancer or treatment-related causes during a median follow-up of 15.4 years.

This finding means that for every 1,000 men followed by a surveillance program, only 4 will die within 10 years, said incoming ASCO president Dr. Clifford Hudis, chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York.

He described the study as one of several recent reminders that sometimes "less is more" in patient care and noted that opting for surveillance spares patients from the harmful side effects of chemotherapy and radiation without diminishing their chances for long-term survival.

Seminoma is a relatively rare cancer, but it is the most common solid tumor among young men. Initial treatment is typically orchiectomy, but no standard postoperative management strategy has been established. The current results will likely accelerate the trend toward surveillance in the United States, where roughly 50% of men undergo either radiotherapy or chemotherapy with carboplatin after surgery.

Overall, 355 (19.5%) of the 1,822 men experienced a relapse during surveillance, said Dr. Mortensen, a PhD student in the oncology department at Copenhagen University Hospital.

The median time to relapse was 13.7 months, with the majority of patients (72.4%) relapsing within the first 2 years. Another 20.3% relapsed within years 2-5 and 7.3% after 5 years.

"With only 19.5% of the patients relapsing, the surveillance strategy spares the remaining 80% of patients from unnecessary treatment after orchiectomy," Dr. Mortensen said. "Surveillance is a safe strategy for stage I seminoma patients."

Surveillance has been the main follow-up strategy for stage I seminoma in Denmark since 1984, and consists of 5 years of scheduled clinical visits, computed tomography scans/chest x-rays, and blood measurements of tumor markers. Men in the analysis were diagnosed from 1984 to 2008, and their data were collected up to December 2012 from patient files and linked national registries.

As observed in other smaller studies, the risk for relapse was increased with elevated human chorionic gonadotropin levels of more than 200 IU/L, vascular invasion, and tumors larger than 4 cm, Dr. Mortensen said.

The study was supported in part by the Danish Cancer Society, Danish Research Foundation and the Preben and Anna Simonsen Foundation. Dr. Mortensen reported having no financial disclosures.

[email protected]

Surveillance is sufficient for most men with stage I seminoma after successful orchiectomy, according to the findings of the largest study ever performed to address the issue.

The 1,822 men followed only with surveillance in Denmark had an excellent disease-specific survival of 99.5%, Dr. Mette Saskø Mortensen said at a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology annual meeting. Only 10 men died of testicular cancer or treatment-related causes during a median follow-up of 15.4 years.

This finding means that for every 1,000 men followed by a surveillance program, only 4 will die within 10 years, said incoming ASCO president Dr. Clifford Hudis, chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York.

He described the study as one of several recent reminders that sometimes "less is more" in patient care and noted that opting for surveillance spares patients from the harmful side effects of chemotherapy and radiation without diminishing their chances for long-term survival.

Seminoma is a relatively rare cancer, but it is the most common solid tumor among young men. Initial treatment is typically orchiectomy, but no standard postoperative management strategy has been established. The current results will likely accelerate the trend toward surveillance in the United States, where roughly 50% of men undergo either radiotherapy or chemotherapy with carboplatin after surgery.

Overall, 355 (19.5%) of the 1,822 men experienced a relapse during surveillance, said Dr. Mortensen, a PhD student in the oncology department at Copenhagen University Hospital.

The median time to relapse was 13.7 months, with the majority of patients (72.4%) relapsing within the first 2 years. Another 20.3% relapsed within years 2-5 and 7.3% after 5 years.

"With only 19.5% of the patients relapsing, the surveillance strategy spares the remaining 80% of patients from unnecessary treatment after orchiectomy," Dr. Mortensen said. "Surveillance is a safe strategy for stage I seminoma patients."

Surveillance has been the main follow-up strategy for stage I seminoma in Denmark since 1984, and consists of 5 years of scheduled clinical visits, computed tomography scans/chest x-rays, and blood measurements of tumor markers. Men in the analysis were diagnosed from 1984 to 2008, and their data were collected up to December 2012 from patient files and linked national registries.

As observed in other smaller studies, the risk for relapse was increased with elevated human chorionic gonadotropin levels of more than 200 IU/L, vascular invasion, and tumors larger than 4 cm, Dr. Mortensen said.

The study was supported in part by the Danish Cancer Society, Danish Research Foundation and the Preben and Anna Simonsen Foundation. Dr. Mortensen reported having no financial disclosures.

[email protected]

An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.

The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.

The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.

The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.

The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."

The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.

The prescribing information is available here.

Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.

[email protected]

An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.

The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.

The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.

The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.

The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."

The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.

The prescribing information is available here.

Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.

[email protected]

An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.

The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.

The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.

The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.

The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."

The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.

The prescribing information is available here.

Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.

[email protected]