Wednesday, December 16, 2015

Ketamine and refractory status epilepticus

Ketamine has been gaining as rescue therapy for the most refractory cases of status epilepticus in kids, researchers reported here.

In an analysis of data from the PHIS network, the number of cases treated with ketamine rose from four in 2010 to 18 in 2014, according to Zachary Grinspan, MD, and Sotirios Keros, MD, of Weill Cornell Medical College in New York. They reported their findings at the American Epilepsy Society meeting her

First-line treatment is a benzodiazepine, typically midazolam, followed by a second-line anti-epileptic agent if that doesn't work. Pentobarbital is typically used as a third-line agent, but it has several drawbacks, including the potential to cause cardiac depression.

Ketamine is increasingly being used either in place of or after pentobarbital in children with status epilepticus, particularly because of its good safety profile. It's also being increasingly used in other conditions, including depression...

Overall, there were a total of 711 cases of refractory status epilepticus: 630 kids were treated with pentobarbital, 33 with ketamine, and 48 with both drugs.

They found that ketamine use in the condition rose from 2010 to 2014, both in terms of the number of centers using it and the number of patients treated with it. In 2010, it was used at two hospitals, but by 2014 it was used in seven hospitals, and cases grew from two per half year to nine per half year during that time, they reported.

They also noted that their study doesn't begin to get at whether the drug is actually effective in this population. Nor does it shed light on where in the treatment algorithm ketamine should be used -- although Grinspan said it isn't likely to be used as a first-line agent any time soon.
"We know very well that the first-line treatment should be a benzodiazepine, and we have pretty good data on second-line treatments, which involve a variety of anti-epileptic drugs. After that, we don't know, " Grinspan said.

"I think the role for ketamine is third-, fourth-, or fifth-line, but that's going to take several years to work out," he said. "While ketamine shows promise for moving up the chain, we want to be cautious that if we change our practice, we do so based on evidence."
  • Ketamine for Refractory Status Epilepticus (RSE) in Children, A Retrospective Cohort Study in the Pediatric Health Information System (PHIS) database
  • Authors: Sotirios Keros, Ersida Buraniqi, Byron Alex, Annalee Antonetty, Hugo Fialho, Baria Hafeez, Michele Jackson, Stephanie Kjelleren, Jacquelyn Klehm, Elizabeth Stewart, Tobias Loddenkemper, Zachary Grinspan
  • Content:
    Rationale: RSE in children often requires medical induction of coma for management. Pentobarbital is widely used for this purpose, but has a long half-life, and can cause cardiac depression. Several recent reports suggest ketamine is a safe and effective treatment for RSE. It is unknown if use of ketamine for RSE has increased. Furthermore, outcomes after treatment for RSE with ketamine are understudied. We conducted a retrospective cohort study of children with RSE, comparing treatment with ketamine versus treatment with pentobarbital but not ketamine.Methods: The PHIS database includes demographics, diagnostic codes, and daily billing information for procedures, laboratory tests, and medications for children at 45 children’s hospitals in North America. From this database, we created a list of candidate visits representing children who may have been treated with either ketamine or pentobarbital (or both) for the treatment of RSE. The criteria were: age 0–21 years, any diagnosis of 345.x (epilepsy) OR 780.39 (convulsions), at least 2 day stay in the pediatric ICU, at least two days with a charge for pentobarbital OR ketamine, at least one day on a ventilator, and discharge date from Jan 2010 through Sept 2014. From these, we manually abstracted charts from two institutions to determine which children 1) had RSE, 2) were treated with pentobarbital for RSE, and 3) were treated with ketamine for RSE. Through discussion and review of visualizations of the PHIS data, we created and validated preliminary definitions for two groups: 1) “RSE ketamine” is RSE treated with ketamine and/or pentobarbital and 2) “RSE pentobarbital” is RSE treated with pentobarbital but not ketamine. We applied these definitions to the remaining candidate patients.Results: At our two centers, the definition of “RSE ketamine” (two consecutive days of ketamine use, EEG, and endotracheal ventilation) had a positive predictive value (PPV) of 75% and sensitivity of 100%; and “RSE pentobarbital” (two consecutive days of pentobarbital use, EEG, and endotracheal ventilation) had a PPV of 82% and sensitivity of 93%. These definitions identified 630 “RSE pentobarbital” cases and 81 “RSE ketamine” cases. Demographics were similar between the groups. Children in the “RSE ketamine” group required more days in the ICU, on EEG, and on the ventilator. In-hospital mortality was similar between the groups. (Table 1) In 2014, significantly more of the 45 PHIS hospitals used ketamine for RSE (5 of 45 in 2010 vs 14 of 45 through Sept 2014). Furthermore, the number of cases per year in the RSE ketamine group grew from 6 to 35 (2011 to 2014 estimated), while the number in the RSE pentobarbital group dropped from 159 to 121. (Table 2)Conclusions: Children treated with ketamine have longer, more intensive hospital stays, which is consistent with our own practice to reserve ketamine for the most challenging cases. From 2010–2014, ketamine was used for RSE at more hospitals and for more children. Further research is indicated to understand safety and clinical outcomes of ketamine for RSE.
  • - See more at: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2327703#sthash.PDZaikAI.dpuf
  • Ketamine for Refractory Status Epilepticus (RSE) in Children, A Retrospective Cohort Study in the Pediatric Health Information System (PHIS) database
  • Authors: Sotirios Keros, Ersida Buraniqi, Byron Alex, Annalee Antonetty, Hugo Fialho, Baria Hafeez, Michele Jackson, Stephanie Kjelleren, Jacquelyn Klehm, Elizabeth Stewart, Tobias Loddenkemper, Zachary Grinspan
  • Content:
    Rationale: RSE in children often requires medical induction of coma for management. Pentobarbital is widely used for this purpose, but has a long half-life, and can cause cardiac depression. Several recent reports suggest ketamine is a safe and effective treatment for RSE. It is unknown if use of ketamine for RSE has increased. Furthermore, outcomes after treatment for RSE with ketamine are understudied. We conducted a retrospective cohort study of children with RSE, comparing treatment with ketamine versus treatment with pentobarbital but not ketamine.Methods: The PHIS database includes demographics, diagnostic codes, and daily billing information for procedures, laboratory tests, and medications for children at 45 children’s hospitals in North America. From this database, we created a list of candidate visits representing children who may have been treated with either ketamine or pentobarbital (or both) for the treatment of RSE. The criteria were: age 0–21 years, any diagnosis of 345.x (epilepsy) OR 780.39 (convulsions), at least 2 day stay in the pediatric ICU, at least two days with a charge for pentobarbital OR ketamine, at least one day on a ventilator, and discharge date from Jan 2010 through Sept 2014. From these, we manually abstracted charts from two institutions to determine which children 1) had RSE, 2) were treated with pentobarbital for RSE, and 3) were treated with ketamine for RSE. Through discussion and review of visualizations of the PHIS data, we created and validated preliminary definitions for two groups: 1) “RSE ketamine” is RSE treated with ketamine and/or pentobarbital and 2) “RSE pentobarbital” is RSE treated with pentobarbital but not ketamine. We applied these definitions to the remaining candidate patients.Results: At our two centers, the definition of “RSE ketamine” (two consecutive days of ketamine use, EEG, and endotracheal ventilation) had a positive predictive value (PPV) of 75% and sensitivity of 100%; and “RSE pentobarbital” (two consecutive days of pentobarbital use, EEG, and endotracheal ventilation) had a PPV of 82% and sensitivity of 93%. These definitions identified 630 “RSE pentobarbital” cases and 81 “RSE ketamine” cases. Demographics were similar between the groups. Children in the “RSE ketamine” group required more days in the ICU, on EEG, and on the ventilator. In-hospital mortality was similar between the groups. (Table 1) In 2014, significantly more of the 45 PHIS hospitals used ketamine for RSE (5 of 45 in 2010 vs 14 of 45 through Sept 2014). Furthermore, the number of cases per year in the RSE ketamine group grew from 6 to 35 (2011 to 2014 estimated), while the number in the RSE pentobarbital group dropped from 159 to 121. (Table 2)Conclusions: Children treated with ketamine have longer, more intensive hospital stays, which is consistent with our own practice to reserve ketamine for the most challenging cases. From 2010–2014, ketamine was used for RSE at more hospitals and for more children. Further research is indicated to understand safety and clinical outcomes of ketamine for RSE.
  • - See more at: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2327703#sthash.PDZaikAI.dpuf
  • Ketamine for Refractory Status Epilepticus (RSE) in Children, A Retrospective Cohort Study in the Pediatric Health Information System (PHIS) database
  • Authors: Sotirios Keros, Ersida Buraniqi, Byron Alex, Annalee Antonetty, Hugo Fialho, Baria Hafeez, Michele Jackson, Stephanie Kjelleren, Jacquelyn Klehm, Elizabeth Stewart, Tobias Loddenkemper, Zachary Grinspan
  • Content:
    Rationale: RSE in children often requires medical induction of coma for management. Pentobarbital is widely used for this purpose, but has a long half-life, and can cause cardiac depression. Several recent reports suggest ketamine is a safe and effective treatment for RSE. It is unknown if use of ketamine for RSE has increased. Furthermore, outcomes after treatment for RSE with ketamine are understudied. We conducted a retrospective cohort study of children with RSE, comparing treatment with ketamine versus treatment with pentobarbital but not ketamine.Methods: The PHIS database includes demographics, diagnostic codes, and daily billing information for procedures, laboratory tests, and medications for children at 45 children’s hospitals in North America. From this database, we created a list of candidate visits representing children who may have been treated with either ketamine or pentobarbital (or both) for the treatment of RSE. The criteria were: age 0–21 years, any diagnosis of 345.x (epilepsy) OR 780.39 (convulsions), at least 2 day stay in the pediatric ICU, at least two days with a charge for pentobarbital OR ketamine, at least one day on a ventilator, and discharge date from Jan 2010 through Sept 2014. From these, we manually abstracted charts from two institutions to determine which children 1) had RSE, 2) were treated with pentobarbital for RSE, and 3) were treated with ketamine for RSE. Through discussion and review of visualizations of the PHIS data, we created and validated preliminary definitions for two groups: 1) “RSE ketamine” is RSE treated with ketamine and/or pentobarbital and 2) “RSE pentobarbital” is RSE treated with pentobarbital but not ketamine. We applied these definitions to the remaining candidate patients.Results: At our two centers, the definition of “RSE ketamine” (two consecutive days of ketamine use, EEG, and endotracheal ventilation) had a positive predictive value (PPV) of 75% and sensitivity of 100%; and “RSE pentobarbital” (two consecutive days of pentobarbital use, EEG, and endotracheal ventilation) had a PPV of 82% and sensitivity of 93%. These definitions identified 630 “RSE pentobarbital” cases and 81 “RSE ketamine” cases. Demographics were similar between the groups. Children in the “RSE ketamine” group required more days in the ICU, on EEG, and on the ventilator. In-hospital mortality was similar between the groups. (Table 1) In 2014, significantly more of the 45 PHIS hospitals used ketamine for RSE (5 of 45 in 2010 vs 14 of 45 through Sept 2014). Furthermore, the number of cases per year in the RSE ketamine group grew from 6 to 35 (2011 to 2014 estimated), while the number in the RSE pentobarbital group dropped from 159 to 121. (Table 2)Conclusions: Children treated with ketamine have longer, more intensive hospital stays, which is consistent with our own practice to reserve ketamine for the most challenging cases. From 2010–2014, ketamine was used for RSE at more hospitals and for more children. Further research is indicated to understand safety and clinical outcomes of ketamine for RSE.
  • - See more at: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2327703#sthash.PDZaikAI.dpuf
  • Ketamine for Refractory Status Epilepticus (RSE) in Children, A Retrospective Cohort Study in the Pediatric Health Information System (PHIS) database
  • Authors: Sotirios Keros, Ersida Buraniqi, Byron Alex, Annalee Antonetty, Hugo Fialho, Baria Hafeez, Michele Jackson, Stephanie Kjelleren, Jacquelyn Klehm, Elizabeth Stewart, Tobias Loddenkemper, Zachary Grinspan
  • Content:
    Rationale: RSE in children often requires medical induction of coma for management. Pentobarbital is widely used for this purpose, but has a long half-life, and can cause cardiac depression. Several recent reports suggest ketamine is a safe and effective treatment for RSE. It is unknown if use of ketamine for RSE has increased. Furthermore, outcomes after treatment for RSE with ketamine are understudied. We conducted a retrospective cohort study of children with RSE, comparing treatment with ketamine versus treatment with pentobarbital but not ketamine.Methods: The PHIS database includes demographics, diagnostic codes, and daily billing information for procedures, laboratory tests, and medications for children at 45 children’s hospitals in North America. From this database, we created a list of candidate visits representing children who may have been treated with either ketamine or pentobarbital (or both) for the treatment of RSE. The criteria were: age 0–21 years, any diagnosis of 345.x (epilepsy) OR 780.39 (convulsions), at least 2 day stay in the pediatric ICU, at least two days with a charge for pentobarbital OR ketamine, at least one day on a ventilator, and discharge date from Jan 2010 through Sept 2014. From these, we manually abstracted charts from two institutions to determine which children 1) had RSE, 2) were treated with pentobarbital for RSE, and 3) were treated with ketamine for RSE. Through discussion and review of visualizations of the PHIS data, we created and validated preliminary definitions for two groups: 1) “RSE ketamine” is RSE treated with ketamine and/or pentobarbital and 2) “RSE pentobarbital” is RSE treated with pentobarbital but not ketamine. We applied these definitions to the remaining candidate patients.Results: At our two centers, the definition of “RSE ketamine” (two consecutive days of ketamine use, EEG, and endotracheal ventilation) had a positive predictive value (PPV) of 75% and sensitivity of 100%; and “RSE pentobarbital” (two consecutive days of pentobarbital use, EEG, and endotracheal ventilation) had a PPV of 82% and sensitivity of 93%. These definitions identified 630 “RSE pentobarbital” cases and 81 “RSE ketamine” cases. Demographics were similar between the groups. Children in the “RSE ketamine” group required more days in the ICU, on EEG, and on the ventilator. In-hospital mortality was similar between the groups. (Table 1) In 2014, significantly more of the 45 PHIS hospitals used ketamine for RSE (5 of 45 in 2010 vs 14 of 45 through Sept 2014). Furthermore, the number of cases per year in the RSE ketamine group grew from 6 to 35 (2011 to 2014 estimated), while the number in the RSE pentobarbital group dropped from 159 to 121. (Table 2)Conclusions: Children treated with ketamine have longer, more intensive hospital stays, which is consistent with our own practice to reserve ketamine for the most challenging cases. From 2010–2014, ketamine was used for RSE at more hospitals and for more children. Further research is indicated to understand safety and clinical outcomes of ketamine for RSE.
  • - See more at: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2327703#sthash.PDZaikAI.dpuf
    https://neurologistconnect.com/newsdetail/56693f199d3e6970338b456b

    ·  Ketamine for Refractory Status Epilepticus (RSE) in Children, A Retrospective Cohort Study in the Pediatric Health Information System (PHIS) database

    ·  Authors: Sotirios Keros, Ersida Buraniqi, Byron Alex, Annalee Antonetty, Hugo Fialho, Baria Hafeez, Michele Jackson, Stephanie Kjelleren, Jacquelyn Klehm, Elizabeth Stewart, Tobias Loddenkemper, Zachary Grinspan

    ·  Content:
    Rationale: RSE in children often requires medical induction of coma for management. Pentobarbital is widely used for this purpose, but has a long half-life, and can cause cardiac depression. Several recent reports suggest ketamine is a safe and effective treatment for RSE. It is unknown if use of ketamine for RSE has increased. Furthermore, outcomes after treatment for RSE with ketamine are understudied. We conducted a retrospective cohort study of children with RSE, comparing treatment with ketamine versus treatment with pentobarbital but not ketamine.
     
    Methods: The PHIS database includes demographics, diagnostic codes, and daily billing information for procedures, laboratory tests, and medications for children at 45 children’s hospitals in North America. From this database, we created a list of candidate visits representing children who may have been treated with either ketamine or pentobarbital (or both) for the treatment of RSE. The criteria were: age 0–21 years, any diagnosis of 345.x (epilepsy) OR 780.39 (convulsions), at least 2 day stay in the pediatric ICU, at least two days with a charge for pentobarbital OR ketamine, at least one day on a ventilator, and discharge date from Jan 2010 through Sept 2014. From these, we manually abstracted charts from two institutions to determine which children 1) had RSE, 2) were treated with pentobarbital for RSE, and 3) were treated with ketamine for RSE. Through discussion and review of visualizations of the PHIS data, we created and validated preliminary definitions for two groups: 1) “RSE ketamine” is RSE treated with ketamine and/or pentobarbital and 2) “RSE pentobarbital” is RSE treated with pentobarbital but not ketamine. We applied these definitions to the remaining candidate patients.
     
    Results: At our two centers, the definition of “RSE ketamine” (two consecutive days of ketamine use, EEG, and endotracheal ventilation) had a positive predictive value (PPV) of 75% and sensitivity of 100%; and “RSE pentobarbital” (two consecutive days of pentobarbital use, EEG, and endotracheal ventilation) had a PPV of 82% and sensitivity of 93%. These definitions identified 630 “RSE pentobarbital” cases and 81 “RSE ketamine” cases. Demographics were similar between the groups. Children in the “RSE ketamine” group required more days in the ICU, on EEG, and on the ventilator. In-hospital mortality was similar between the groups. (Table 1) In 2014, significantly more of the 45 PHIS hospitals used ketamine for RSE (5 of 45 in 2010 vs 14 of 45 through Sept 2014). Furthermore, the number of cases per year in the RSE ketamine group grew from 6 to 35 (2011 to 2014 estimated), while the number in the RSE pentobarbital group dropped from 159 to 121. (Table 2)
     
    Conclusions: Children treated with ketamine have longer, more intensive hospital stays, which is consistent with our own practice to reserve ketamine for the most challenging cases. From 2010–2014, ketamine was used for RSE at more hospitals and for more children. Further research is indicated to understand safety and clinical outcomes of ketamine for RSE.
     

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