Joe Kossowsky1,2, Carolina Donado1, Charles B Berde1. 1. Department of Anesthesiology Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Clinical Psychology & Psychotherapy, University of Basel, Switzerland.
Abstract
BACKGROUND: Designing analgesic clinical trials in pediatrics requires a balance between scientific, ethical, and practical concerns. A previous consensus group recommended immediate rescue designs using opioid sparing as a surrogate measure of analgesic efficacy. The authors summarize the performance of rescue analgesic designs in pediatric trials of four commonly used classes of analgesics: opioids, nonsteroidal antiinflammatory drugs, acetaminophen, and local anesthetics. METHODS: MEDLINE, Embase, CINAHL, The Cochrane Library, and Web of science were searched in April 2013. The 85 studies selected were randomized or controlled clinical trials using immediate rescue paradigms in postoperative pain settings. A random-effects meta-analysis was used to synthesize predefined outcomes using Hedges' g. Difference between the means of the treatment arms were also expressed as a percentage of the corresponding value in the placebo group (placebo-treatment/placebo). Distributions of pain scores in study and control groups and relationships between opioid sparing and pain scores were examined. RESULTS: For each of the four study drug classes, significant opioid sparing was demonstrated in a majority of studies by one or more of the following endpoints: (1) total dose (milligram per kilogram per hour), (2) percentage of children requiring rescue medication, and (3) time to first rescue medication (minutes). Pain scores averaged 2.4/10 in study groups, 3.4/10 in control groups. CONCLUSIONS: Opioid sparing is a feasible pragmatic endpoint for pediatric pain analgesic trials. This review serves to guide future research in pediatric analgesia trials, which could test whether some specific design features may improve assay sensitivity while minimizing the risk of unrelieved pain.
BACKGROUND: Designing analgesic clinical trials in pediatrics requires a balance between scientific, ethical, and practical concerns. A previous consensus group recommended immediate rescue designs using opioid sparing as a surrogate measure of analgesic efficacy. The authors summarize the performance of rescue analgesic designs in pediatric trials of four commonly used classes of analgesics: opioids, nonsteroidal antiinflammatory drugs, acetaminophen, and local anesthetics. METHODS: MEDLINE, Embase, CINAHL, The Cochrane Library, and Web of science were searched in April 2013. The 85 studies selected were randomized or controlled clinical trials using immediate rescue paradigms in postoperative pain settings. A random-effects meta-analysis was used to synthesize predefined outcomes using Hedges' g. Difference between the means of the treatment arms were also expressed as a percentage of the corresponding value in the placebo group (placebo-treatment/placebo). Distributions of pain scores in study and control groups and relationships between opioid sparing and pain scores were examined. RESULTS: For each of the four study drug classes, significant opioid sparing was demonstrated in a majority of studies by one or more of the following endpoints: (1) total dose (milligram per kilogram per hour), (2) percentage of children requiring rescue medication, and (3) time to first rescue medication (minutes). Pain scores averaged 2.4/10 in study groups, 3.4/10 in control groups. CONCLUSIONS: Opioid sparing is a feasible pragmatic endpoint for pediatric pain analgesic trials. This review serves to guide future research in pediatricanalgesia trials, which could test whether some specific design features may improve assay sensitivity while minimizing the risk of unrelieved pain.
Authors: Sara Zarnegar-Lumley; Katharine R Lange; Melissa D Mathias; Miho Nakajima-Hatano; Katharine M Offer; Ugochi O Ogu; Michael V Ortiz; Kay See Tan; Michael Kellick; Shakeel Modak; Stephen S Roberts; Ellen M Basu; R Scott Dingeman Journal: Pediatrics Date: 2019-08 Impact factor: 7.124
Authors: Kanesha Simmons; Robin Ortiz; Joe Kossowsky; Peter Krummenacher; Christian Grillon; Daniel Pine; Luana Colloca Journal: Pain Date: 2014-08-29 Impact factor: 6.961
Authors: Gary A Walco; Ernest A Kopecky; Steven J Weisman; Jennifer Stinson; Bonnie Stevens; Paul J Desjardins; Charles B Berde; Elliot J Krane; Kanwaljeet J S Anand; Myron Yaster; Carlton D Dampier; Robert H Dworkin; Ian Gilron; Anne M Lynn; Lynne G Maxwell; Srinivasa Raja; Bernard Schachtel; Dennis C Turk Journal: Pain Date: 2018-02 Impact factor: 7.926
Authors: R Page; P Baneux; D Vail; L Duda; P Olson; L Anestidou; N Dybdal; G Golab; W Shelton; M Salgaller; C Hardy Journal: J Vet Intern Med Date: 2016-03-07 Impact factor: 3.333