PMID- 34534923
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220531
IS  - 1873-4529 (Electronic)
IS  - 0952-8180 (Linking)
VI  - 75
DP  - 2021 Dec
TI  - A multicenter study to evaluate the pharmacokinetics and safety of liposomal 
      bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 
      17 years (PLAY).
PG  - 110503
LID - S0952-8180(21)00345-7 [pii]
LID - 10.1016/j.jclinane.2021.110503 [doi]
AB  - STUDY OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal 
      bupivacaine in pediatric patients undergoing spine or cardiac surgery. DESIGN: 
      Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). SETTING: 
      Operating room. PATIENTS: Two separate age groups were evaluated (age group 1: 
      patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to 
      <12 years undergoing spine or cardiac surgery). INTERVENTION: Randomized 
      allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 
      2 mg/kg via local infiltration at the end of spine surgery (age group 1); 
      liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or 
      cardiac surgery (age group 2). MEASUREMENTS: The primary and secondary objectives 
      were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine 
      concentrations [C(max)], time to C(max)) and safety of liposomal bupivacaine, 
      respectively. MAIN RESULTS: Baseline characteristics were comparable across 
      groups. Mean C(max) after liposomal bupivacaine administration was lower versus 
      bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C(max) in age group 2 was 
      320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to 
      C(max) of liposomal bupivacaine occurred later with cardiac surgery versus spine 
      surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) 
      was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl 
      (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing 
      spine and cardiac surgery experienced AEs, respectively. AEs were generally mild 
      or moderate, with no discontinuations due to AEs or deaths. CONCLUSIONS: Plasma 
      bupivacaine levels following local infiltration with liposomal bupivacaine 
      remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups 
      and procedures. AEs were mild to moderate, supporting the safety of liposomal 
      bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical 
      trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Tirotta, Christopher F
AU  - Tirotta CF
AD  - Nicklaus Children's Hospital, Miami, FL, United States of America. Electronic 
      address: Christopher.Tirotta@Nicklaushealth.org.
FAU - de Armendi, Alberto J
AU  - de Armendi AJ
AD  - University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States 
      of America.
FAU - Horn, Nicole D
AU  - Horn ND
AD  - Indiana University School of Medicine, Indianapolis, IN, United States of 
      America.
FAU - Hammer, Gregory B
AU  - Hammer GB
AD  - Stanford University School of Medicine, Stanford, CA, United States of America.
FAU - Szczodry, Michal
AU  - Szczodry M
AD  - Shriners Hospital for Children, Chicago, IL, United States of America.
FAU - Matuszczak, Maria
AU  - Matuszczak M
AD  - University of Texas, McGovern Medical School, Houston, TX, United States of 
      America.
FAU - Wang, Natalie Q
AU  - Wang NQ
AD  - Pacira BioSciences, Inc., Parsippany, NJ, United States of America.
FAU - Scranton, Richard
AU  - Scranton R
AD  - Lyndra Therapeutics, Watertown, MA, United States of America.
FAU - Ballock, Robert Tracy
AU  - Ballock RT
AD  - Cleveland Clinic, Cleveland, OH, United States of America.
LA  - eng
SI  - ClinicalTrials.gov/NCT03682302
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20210914
PL  - United States
TA  - J Clin Anesth
JT  - Journal of clinical anesthesia
JID - 8812166
RN  - 0 (Anesthetics, Local)
RN  - 0 (Liposomes)
RN  - Y8335394RO (Bupivacaine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Analgesia
MH  - *Anesthetics, Local/adverse effects
MH  - Bupivacaine/adverse effects
MH  - Child
MH  - Humans
MH  - Liposomes
MH  - Pain, Postoperative/drug therapy
OTO - NOTNLM
OT  - Analgesia
OT  - Anesthesia
OT  - Bupivacaine
OT  - Cardiac surgical procedures
OT  - Pediatrics
OT  - Pharmacokinetics
EDAT- 2021/09/18 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/09/17 20:27
PHST- 2021/05/14 00:00 [received]
PHST- 2021/08/12 00:00 [revised]
PHST- 2021/09/03 00:00 [accepted]
PHST- 2021/09/18 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/09/17 20:27 [entrez]
AID - S0952-8180(21)00345-7 [pii]
AID - 10.1016/j.jclinane.2021.110503 [doi]
PST - ppublish
SO  - J Clin Anesth. 2021 Dec;75:110503. doi: 10.1016/j.jclinane.2021.110503. Epub 2021 
      Sep 14.