1
|
Patel AK, Gai J, Trujillo-Rivera E, Faruqe F, Kim D, Bost JE, Pollack MM. National Intravenous Acetaminophen Use in Pediatric Inpatients From 2011–2016. J Pediatr Pharmacol Ther 2022; 27:358-365. [DOI: 10.5863/1551-6776-27.4.358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/17/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVE
To 1) determine current intravenous (IV) acetaminophen use in pediatric inpatients; and 2) determine the association between opioid medication duration when used with or without IV acetaminophen.
METHODS
A retrospective analysis of pediatric inpatients exposed to IV acetaminophen from January 2011 to June 2016, using the national database Health Facts.
RESULTS
Eighteen thousand one hundred ninety-seven (2.0%) of 893,293 pediatric inpatients received IV acetaminophen for a median of 14 doses per patient (IQR, 8–56). A greater proportion of IV acetaminophen patients were admitted to the intensive care unit (ICU) (14.8% vs 5.1%, p < 0.0001), received positive pressure ventilation (2.0% vs 1.5%, p < 0.0001), had a higher hospital mortality rate (0.9% vs 0.3%, p < 0.0001), and were operative (35.5% vs 12.8%, p < 0.001) than those not receiving IV acetaminophen. The most common operations associated with IV acetaminophen use were musculoskeletal and digestive system operations. Prescription of IV acetaminophen increased over time, both in prescription rates and number of per patient doses. Of the 18,197 patients prescribed IV acetaminophen, 16,241 (89.2%) also were prescribed opioids during their hospitalization. A multivariate analysis revealed patients prescribed both IV acetaminophen and opioids had a 54.8% increase in opioid duration as compared with patients who received opioids alone.
CONCLUSIONS
This is the first study to assess IV acetaminophen prescription practices for pediatric inpatients. Intravenous acetaminophen prescription was greater in the non-operative pediatric inpatient population than operative patients. Intravenous acetaminophen prescription was associated with an increase in opioid duration as compared with patients who received opioids alone, suggesting that it is commonly used to supplement opioids for pain relief.
Collapse
Affiliation(s)
- Anita K. Patel
- Department of Pediatrics, Division of Critical Care Medicine DC (AKP, MMP), Children's National Health System, Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| | - Jiaxiang Gai
- Children's National Health System (JG, FF, DK, JEB), Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| | - Eduardo Trujillo-Rivera
- Department of Pediatrics, Division of Critical Care Medicine DC (AKP, MMP), Children's National Health System, Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| | - Farhana Faruqe
- Children's National Health System (JG, FF, DK, JEB), Washington, DC
| | - Dongkyu Kim
- Children's National Health System (JG, FF, DK, JEB), Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| | - James E. Bost
- Children's National Health System (JG, FF, DK, JEB), Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| | - Murray M. Pollack
- Department of Pediatrics, Division of Critical Care Medicine DC (AKP, MMP), Children's National Health System, Washington, DC
- George Washington University School of Medicine and Health Sciences (AKP, MMP, JG, ET-R, DK, JEB), Washington, DC
| |
Collapse
|
2
|
Zempsky WT, Bhagat PK, Siddiqui K. Practical Challenges-Use of Paracetamol in Children and Youth Who are Overweight or Obese: A Narrative Review. Paediatr Drugs 2020; 22:525-534. [PMID: 32918268 PMCID: PMC7529628 DOI: 10.1007/s40272-020-00417-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Worldwide, > 380 million children and adolescents are overweight or obese, including 41 million children aged < 5 years. Obesity can change the pharmacokinetic properties of drugs by altering their distribution, metabolism, and elimination. Thus, children who are overweight or obese are at increased risk for receiving inappropriate doses of commonly used drugs, which can result in treatment failure, adverse events, and/or drug toxicity. This review analyzes available data on paracetamol dosing for pain and fever in children and adolescents who are overweight or obese to identify gaps and challenges in optimal dosing strategies. Literature searches using Medline, Embase, and ClinicalTrials.gov were conducted to identify English-language articles reporting paracetamol pharmacokinetics, dosing practices, and guidelines in children and adolescents who are overweight or obese. Of 24 relevant studies identified, 20 were specific to overweight/obese individuals and 15 were specific to children and/or adolescents. Data on paracetamol pharmacokinetics in children and adolescents who are overweight or obese are lacking, and there is no high-quality evidence to guide paracetamol prescribing practices in these patients. Adult data have been extrapolated to pediatric populations; however, extrapolation does not address differences in paracetamol metabolism in adults versus children; the efficacy and safety effects of such differences are unknown. Given the growing worldwide prevalence of obesity in children and adolescents and the likelihood that paracetamol use in this population will increase accordingly, obesity-specific pediatric dosing guidelines for paracetamol are urgently needed. High-quality research is necessary to inform such guidelines.
Collapse
Affiliation(s)
- William T Zempsky
- Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut, 282 Washington St, Hartford, CT, 06106, USA.
| | - Preeti K Bhagat
- Consumer Healthcare R & D, GlaxoSmithKline Consumer Healthcare, Singapore, Singapore
| | - Kamran Siddiqui
- Consumer Healthcare R & D, GlaxoSmithKline Consumer Healthcare, Singapore, Singapore
| |
Collapse
|
3
|
Statelova M, Holm R, Fotaki N, Reppas C, Vertzoni M. Successful Extrapolation of Paracetamol Exposure from Adults to Infants After Oral Administration of a Pediatric Aqueous Suspension Is Highly Dependent on the Study Dosing Conditions. AAPS JOURNAL 2020; 22:126. [DOI: 10.1208/s12248-020-00504-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 08/18/2020] [Indexed: 01/10/2023]
|
4
|
Hagen M, Alchin J. Nonprescription drugs recommended in guidelines for common pain conditions. Pain Manag 2020; 10:117-129. [DOI: 10.2217/pmt-2019-0057] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Evidence-based pain guidelines allow recommendation of nonprescription analgesics to patients, facilitating self-care. We researched clinical practice guidelines for common conditions on websites of pain associations, societies, health institutions and organizations, PubMed, ProQuest, Embase, Google Scholar until April 2019. We wanted to determine whether there is a consensus between guidelines. From 114 identified guidelines, migraine (27) and osteoarthritis (26) have been published most around the world, while dysmenorrhea (14) is mainly discussed in developing countries. Specific recommendations to pregnant women, children and older people predominantly come from the UK and USA. We found that acetaminophen and oral nonsteroidal anti-inflammatory drugs (NSAIDs) represent first-line management across all pain conditions in adults and children. In osteoarthritis, topical NSAIDs should be considered before oral NSAIDs. This knowledge might persuade patients that using these drugs first could enable fast and effective pain relief.
Collapse
Affiliation(s)
| | - John Alchin
- Pain Management Centre, Burwood Hospital, Christchurch, New Zealand
| |
Collapse
|
5
|
Facile HPTLC-densitometric determination of ertapenem and paracetamol in pharmaceuticals and rabbit plasma with pharmacokinetic insights. Microchem J 2019. [DOI: 10.1016/j.microc.2019.104093] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
6
|
Newman N, Kogan S, Stavsky M, Pintov S, Lior Y. The impact of medical clowns exposure over postoperative pain and anxiety in children and caregivers: An Israeli experience. Pediatr Rep 2019; 11:8165. [PMID: 31579203 PMCID: PMC6769359 DOI: 10.4081/pr.2019.8165] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 06/05/2019] [Indexed: 12/27/2022] Open
Abstract
While postoperative pain management was shown to reduce unwanted physiological and emotional outcomes, pediatric postoperative pain management remains suboptimal. Medical-clowns were shown to be beneficial in many medical contexts including reduction of stress, anxiety and pain. This study was set to assess the effectiveness of medical-clowns on pediatric postoperative pain reduction. Children age 4 or above, planned for elective hernia repair surgery were recruited. Children were randomly divided to a control or medicalclown escorted groups. Demographical and clinical data were collected using questionnaires and electronic sheets. Children escorted by clowns reported lower levels of pain upon admittance, discharge and 12- hours post-surgery. Statistically significant reduction of parental distress and significantly higher serum cortisol levels were observed in the clown-therapy group. Although small, our study supports the possibility that preoperative medical-clown therapy might be a cheap, safe and yet beneficial method for postoperative pain reduction.
Collapse
Affiliation(s)
- Nitza Newman
- Pediatric Surgery Department, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva
| | - Slava Kogan
- Joyce and Irwing Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva
- Soroka Clinical Research Center, Soroka University Medical Center, Beer-Sheva
| | - Moshe Stavsky
- Joyce and Irwing Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva
- Soroka Clinical Research Center, Soroka University Medical Center, Beer-Sheva
| | - Shay Pintov
- The Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Yotam Lior
- Joyce and Irwing Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva
- Soroka Clinical Research Center, Soroka University Medical Center, Beer-Sheva
| |
Collapse
|
7
|
Zeilmaker-Roest GA, van Rosmalen J, van Dijk M, Koomen E, Jansen NJG, Kneyber MCJ, Maebe S, van den Berghe G, Vlasselaers D, Bogers AJJC, Tibboel D, Wildschut ED. Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants: a study protocol for a randomized controlled trial. Trials 2018; 19:318. [PMID: 29895289 PMCID: PMC5998570 DOI: 10.1186/s13063-018-2705-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 05/24/2018] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement. METHODS This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%. DISCUSSION This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36 months old. TRIAL REGISTRATION Dutch Trial Registry ( www.trialregister.nl ): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015-646), current protocol version: July 3, 2017.
Collapse
Affiliation(s)
- Gerdien A Zeilmaker-Roest
- Department of Pediatric Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. .,Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands.
| | | | - Monique van Dijk
- Department of Pediatric Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Erik Koomen
- Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Nicolaas J G Jansen
- Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Martin C J Kneyber
- Department of Pediatrics, division of Pediatric Critical Care Medicine, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
| | - Sofie Maebe
- Department of Intensive Care Medicine, UZ Leuven, Leuven, Belgium
| | | | - Dirk Vlasselaers
- Department of Intensive Care Medicine, UZ Leuven, Leuven, Belgium
| | - Ad J J C Bogers
- Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands
| | - Dick Tibboel
- Department of Pediatric Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Enno D Wildschut
- Department of Pediatric Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| |
Collapse
|
8
|
Tian X, Yang P, Su T, Yu J, Zhao S, Xiang G, Yu D, Zhang W, Manyande A, Gao F, Tian Y, Yang H. Intraperitoneal ropivacaine and early postoperative pain and postsurgical outcomes after laparoscopic herniorrhaphy in toddlers: a randomized clinical trial. Paediatr Anaesth 2016; 26:891-8. [PMID: 27346807 DOI: 10.1111/pan.12953] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/27/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Postoperative pain can cause physiological distress, postoperative complications, and extended lengths of hospitalized stay. In children, management of postoperative pain is still recognized as being inadequate. OBJECTIVE The aim of this trial was to investigate the effects of intraperitoneal ropivacaine on postoperative pain, and recovery of bowel function and emetic events after laparoscopic herniorrhaphy in toddlers. METHODS Seventy-six children aged from 9 months to 3 years were recruited between August 2013 and June 2014 at Tongji Hospital and randomly assigned into two groups. One group received intraperitoneal ropivacaine right before surgery and the control group received intraperitoneal saline. A standard combined general anesthesia procedure was performed under regular monitoring. Postoperative pain was assessed by the FLACC scale. Postoperative analgesic consumption, time to flatus, time to first stool, and postoperative emetic events were also recorded. RESULTS When compared with the control group, children who received intraperitoneal ropivacaine experienced less pain 0-4 h after surgery [P < 0.001, difference in median FLACC (95% CI) for 2 h time point is 2.00 (0.87-3.13), for 4 h time point is 1.00 (0.55-1.45)]. In addition, the number of toddlers who received analgesia 0-24 h after surgery in the ropivacaine group was lower than that in the control group [P < 0.001, difference in proportions (95% CI) is 0.575 (0.3865-0.7638)]. Compared with the control group, time to flatus in ropivacaine group was also much shorter [21.1 h vs 16.7 h, P = 0.04, difference in mean (95% CI) is 4.4 (1.49-7.28)], and the time to first stool after surgery was earlier in the ropivacaine group [30.7 h vs 25.6 h, P = 0.003, difference in mean (95% CI) is 5.1 (1.78-8.45)]. Furthermore, the incidence of emetic events in the ropivacaine group was significantly lower than the control group [32.4% vs 11.1%, P = 0.03, difference in proportions (95% CI) is 0.212 (0.0246-0.4002)]. CONCLUSION The present results indicate that intraperitoneal ropivacaine reduces early postoperative pain and improves recovery after laparoscopic herniorrhaphy in toddlers. Therefore, IPLA is a good stratagem for postoperative pain management after laparoscopic surgery in toddlers.
Collapse
Affiliation(s)
- Xuebi Tian
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ping Yang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tiefen Su
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing Yu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shiwen Zhao
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Guifang Xiang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Donghai Yu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wen Zhang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Anne Manyande
- School of Psychology, Social Work and Human Sciences, University of West London, London, UK
| | - Feng Gao
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuke Tian
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hui Yang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| |
Collapse
|
9
|
Villiger A, Stillhart C, Parrott N, Kuentz M. Using Physiologically Based Pharmacokinetic (PBPK) Modelling to Gain Insights into the Effect of Physiological Factors on Oral Absorption in Paediatric Populations. AAPS JOURNAL 2016; 18:933-47. [DOI: 10.1208/s12248-016-9896-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Accepted: 02/21/2016] [Indexed: 12/27/2022]
|
10
|
Song IK, Park YH, Lee JH, Kim JT, Choi IH, Kim HS. Randomized controlled trial on preemptive analgesia for acute postoperative pain management in children. Paediatr Anaesth 2016; 26:438-43. [PMID: 26890267 DOI: 10.1111/pan.12864] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/28/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Preemptive analgesia is an anti-nociceptive treatment that starts before surgery and prevents the establishment of central sensitization. Whether preemptive analgesia is more effective than conventional regimens for managing postoperative pain remains controversial. This study evaluated the efficacy of intravenous preemptive analgesia for acute postoperative pain control in pediatric patients. METHODS In this prospective randomized controlled trial, 51 children aged 3-7 years, scheduled for corrective osteotomy were randomized into control (group C) or preemptive (group P) group. Both groups received standardized general anesthesia, including intravenous patient-controlled analgesia (IV-PCA) with fentanyl, which was started before skin incision in group P or 5 min thereafter in group C. IV-PCA data, pain scores using verbal rating scale (VRS) and Wong-Baker FACES(®) pain rating scale (WBFS), emergence agitation score (EAS) using the Pediatric Anesthesia Emergence Delirium (PAED) scale, analgesic requirements, and complications were recorded. RESULTS The primary outcome, pain score at postoperative 1 h, showed no difference between the groups. Both groups did not demonstrate emergence agitation (PAED cutoff value ≥ 12), although the EAS at admission to the postanesthetic care unit (PACU) was lower in group P than in group C (P = 0.002; mean difference 4.85, 95% CI 1.97-7.73). There were no differences in the delivered volume of IV-PCA, frequency of pushing the IV-PCA button, effective push attempts, VRS, WBFS, EAS at discharge from the PACU, additional analgesic requirements, and complications. CONCLUSION Preemptive analgesia using IV-PCA with fentanyl showed no significant advantages for postoperative analgesia after corrective osteotomy in pediatric patients.
Collapse
Affiliation(s)
- In-Kyung Song
- Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, Korea
| | - Yong-Hee Park
- Department of Anesthesiology and Pain medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Ji-Hyun Lee
- Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, Korea
| | - Jin-Tae Kim
- Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, Korea
| | - In Ho Choi
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Hee-Soo Kim
- Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, Korea
| |
Collapse
|
11
|
DBS sampling: a journey. Bioanalysis 2015; 7:1967-70. [PMID: 26327177 DOI: 10.4155/bio.15.140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
|
12
|
Single-dose systemic acetaminophen to prevent postoperative pain: a meta-analysis of randomized controlled trials. Clin J Pain 2015; 31:86-93. [PMID: 25485955 DOI: 10.1097/ajp.0000000000000081] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES The effect of a single-dose systemic acetaminophen to treat postoperative pain has been previously quantified, but the effect of systemic acetaminophen to prevent postoperative pain is currently not well defined. The preventive analgesic effect of acetaminophen has yet to be quantified in a meta-analysis. The objective of the current investigation was to evaluate the effect of a single preventive dose of systemic acetaminophen on postoperative pain outcomes. MATERIALS AND METHODS A wide search was performed to identify randomized controlled trials that evaluated the effects of a single dose of systemic acetaminophen on pain outcomes in a large variety of surgical procedures. Meta-analysis was performed using a random-effect model. RESULTS Eleven randomized clinical trials evaluating 740 patients were included in the analysis. The weighted mean difference (95% confidence interval [CI]) of the combined effects favored acetaminophen over control for early pain at rest (≤4 h, -1.1 (-2.0 to -0.2)) and early pain at movement (24 h, -1.9 (-2.8 to -1.0)) Postoperative opioid consumption was decreased in the systemic acetaminophen group compared with control. Weighted mean difference (95% CI) of -9.7 (-13.0 to -6.4) mg morphine intravenous equivalents systemic acetaminophen also reduced postoperative nausea and vomiting compared with control, odds ratio (95% CI) of 0.25 (0.13 to 0.47), numbers needed to treat (95% CI)=3.3 (2.3 to 5.9). DISCUSSION Systemic acetaminophen, when used as a single-dose preventive regimen, is an effective intervention to reduce postoperative pain. It also reduces postoperative nausea and/or vomiting. Doses >1 g were not associated with greater reduction in pain outcomes.
Collapse
|
13
|
Mohammed BS, Engelhardt T, Hawwa AF, Cameron GA, McLay JS. The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis†. J Pharm Pharmacol 2015; 67:1179-87. [DOI: 10.1111/jphp.12418] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 02/13/2015] [Indexed: 11/27/2022]
Abstract
Abstract
Objective
To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay.
Methods
Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters.
Key findings
Data from 11 children (1.7–15.6 years, weight 10.7–67.4 kg) were best described by a two-compartment model for R(+), S(−) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)0.75, V1 = 8.2 × (WT/46), Q = 3.4 × (WT/46)0.75, V2 = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1 = 13.2 × (WT/46), Q = 2.8 × (WT/46)0.75, V2 = 51.5 × (WT/46), and CL = 1.1 × (WT/46)0.75, V1 = 4.9 × (WT/46), Q = 1.7 × (WT/46)0.75 and V2 = 6.3 × (WT/46)for R(+), S(−) and racemic ketorolac.
Conclusions
Only body weight influenced the PK parameters for R(+) and S(−) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).
Collapse
Affiliation(s)
- Baba S Mohammed
- Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Thomas Engelhardt
- Department of Anaesthesiology, Royal Aberdeen Children's Hospital, Aberdeen, UK
| | - Ahmed F Hawwa
- School of Pharmacy, Aston University, Birmingham, UK
| | - Garry A Cameron
- Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - James S McLay
- Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| |
Collapse
|
14
|
Yuan LG, Tang YZ, Zhang YX, Sun J, Luo XY, Zhu LX, Zhang Z, Wang R, Liu YH. Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation. J Vet Pharmacol Ther 2015; 38:400-9. [PMID: 25604162 DOI: 10.1111/jvp.12199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Accepted: 11/21/2014] [Indexed: 11/27/2022]
Abstract
To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C(i,v) = X(0 )(8.4191 × 10(-4) × e(-0.2371t) + 1.2788 × 10(-5) × e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 × 10(-4) × e(-0.5840t) + 8.4195 × e(-0.2371t) + 7.6869 × 10(-6) × e(-0.0069t)) after p.o. Monte Carlo simulation showed that T(>MIC) was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.
Collapse
Affiliation(s)
- L G Yuan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China.,Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, China
| | - Y Z Tang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China.,Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, China
| | - Y X Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China.,Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, China
| | - J Sun
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| | - X Y Luo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| | - L X Zhu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| | - Z Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| | - R Wang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| | - Y H Liu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
| |
Collapse
|
15
|
Brasher C, Gafsous B, Dugue S, Thiollier A, Kinderf J, Nivoche Y, Grace R, Dahmani S. Postoperative pain management in children and infants: an update. Paediatr Drugs 2014; 16:129-40. [PMID: 24407716 DOI: 10.1007/s40272-013-0062-0] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Many factors contribute to suboptimal pain management in children. Current evidence suggests that severe pain in children has significant long-lasting effects, even more so than in adults. In particular, recent evidence suggests a lack of optimal postoperative pain management in children, especially following ambulatory surgery. This review provides simple guidelines for the management of postoperative pain in children. It discusses the long-term effects of severe pain and how to evaluate pain in both healthy and neurologically impaired children, including neonates. Currently available treatment options are discussed with reference to the efficacy and side effects of opioid and non-opioid and regional analgesic techniques. The impact of preoperative anxiety on postoperative pain, and the efficacy of some nonpharmacological techniques such as hypnosis or distraction, are also discussed. Finally, basic organizational strategies are described, aiming to promote safer and more efficient postoperative pain management in children.
Collapse
Affiliation(s)
- Christopher Brasher
- Department of Anesthesiology, Intensive Care, Robert Debré Hospital, 48 Bd Sérurier, 75019, Paris, France
| | | | | | | | | | | | | | | |
Collapse
|
16
|
Wang C, Allegaert K, Tibboel D, Danhof M, van der Marel CD, Mathot RAA, Knibbe CAJ. Population pharmacokinetics of paracetamol across the human age-range from (pre)term neonates, infants, children to adults. J Clin Pharmacol 2014; 54:619-29. [PMID: 24375166 DOI: 10.1002/jcph.259] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 12/26/2013] [Indexed: 11/11/2022]
Abstract
In order to characterize the variation in pharmacokinetics of paracetamol across the human age span, we performed a population pharmacokinetic analysis from preterm neonates to adults with specific focus on clearance. Concentration-time data obtained in 220 neonates (post-natal age 1-76 days, gestational age 27-42 weeks), infants (0.11-1.33 yrs), children (2-7 yrs) and adults (19-34 yrs) were analyzed using NONMEM 7.2. In the covariate analysis, linear functions, power functions, and a power function with a bodyweight-dependent exponent were tested. Between preterm neonates and adults, linear bodyweight functions were identified for Q2, Q3, V1, V2, and V3, while for CL a power function with a bodyweight-dependent exponent k was identified (CLi = CLp × (BW/70)(k) ). The exponent k was found to decrease in a sigmoidal manner with bodyweight from 1.2 to 0.75, with half the decrease in exponent reached at 12.2 kg. No other covariates such as age were identified. A pharmacokinetic model for paracetamol characterizing changes in pharmacokinetic parameters across the pediatric age-range was developed. Clearance was found to change in a nonlinear manner with bodyweight. Based on the final model, dosing guidelines are proposed from preterm neonates to adolescents resulting in similar exposure across all age ranges.
Collapse
Affiliation(s)
- Chenguang Wang
- Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands; Erasmus MC Sophia Children's Hospital, Intensive Care and Department of Paediatric Intensive Care, Rotterdam, The Netherlands
| | | | | | | | | | | | | |
Collapse
|
17
|
|
18
|
Holford N, Heo YA, Anderson B. A pharmacokinetic standard for babies and adults. J Pharm Sci 2013; 102:2941-52. [PMID: 23650116 DOI: 10.1002/jps.23574] [Citation(s) in RCA: 283] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 04/12/2013] [Accepted: 04/12/2013] [Indexed: 01/01/2023]
Abstract
The pharmacokinetic behavior of medicines used in humans follows largely predictable patterns across the human age range from premature babies to elderly adults. Most of the differences associated with age are in fact due to differences in size. Additional considerations are required to describe the processes of maturation of clearance processes and postnatal changes in body composition. Application of standard approaches to reporting pharmacokinetic parameters is essential for comparative human pharmacokinetic studies from babies to adults. A standardized comparison of pharmacokinetic parameters obtained in children and adults is shown for 46 drugs. Appropriate size scaling shows that children (over 2 years old) are similar to adults. Maturation changes are generally completed within the first 2 years of postnatal life; consequently babies may be considered as immature children, whereas children are just small adults.
Collapse
Affiliation(s)
- Nick Holford
- Department of Pharmacology & Clinical Pharmacology, University of Auckland, New Zealand.
| | | | | |
Collapse
|
19
|
Allegaert K. Clinical pharmacology of intravenous paracetamol in perinatal medicine. World J Anesthesiol 2013; 2:1-7. [DOI: 10.5313/wja.v2.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Accepted: 04/16/2013] [Indexed: 02/06/2023] Open
Abstract
Clinical pharmacology aims to predict drug-related effects based on compound and population specific pharmacokinetics (PK, concentration-time), and pharmacodynamics (PD, concentration-effect). Consequently, dosing needs to be based on the physiological characteristics of the individual patient. Pregnancy and early infancy hereby warrant focused assessment. The specific characteristics of both subpopulations will be illustrated based on observations on intravenous (iv) paracetamol PK and PD collected in these specific populations. At delivery, there is a significant higher paracetamol clearance (+ 45%, L/h) when compared to non-pregnant observations. This higher clearance is in part explained by a proportional increase in oxidative metabolite production, but mainly an increase in glucuronidation. When focusing on PD, an association between maternal paracetamol exposure and atopy in infancy and fetal gastroshizis has been reported. In early infancy, paracetamol clearance is significantly lower and mainly depends on size (weight 0.75), while also the distribution volume is higher (L/kg). Reports on hepatic tolerance, haemodynamic stability and impact of body temperature have been published while the concentration effect profile for analgesia seems to be similar between neonates and children. Similar to maternal exposure, there are reports on the association with atopy. Studies on the use of paracetamol to close the patent ductus arteriosus are ongoing. At least, these observations provide evidence on the need to study commonly administered anesthetics in such specific subpopulations with specific focus on both population specific PK and PD to further improve patient tailored pharmacotherapy.
Collapse
|
20
|
Sumpter A, Anderson BJ. Unraveling Pharmacokinetics and Pharmacodynamics in Infants and Children. CURRENT ANESTHESIOLOGY REPORTS 2012. [DOI: 10.1007/s40140-012-0001-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
|
21
|
Anderson B, McLay J, Allegaert K, Engelhardt T. Do old pharmacokinetic parameter estimates predict new data? Br J Anaesth 2012; 109:1013-4. [DOI: 10.1093/bja/aes414] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
|
22
|
Gillogly A, Kilbourn C, Waldvogel J, Martin J, Annich G, Wagner D. In vitro clearance of intravenous acetaminophen in extracorporeal membrane oxygenation. Perfusion 2012. [PMID: 23201817 DOI: 10.1177/0267659112467825] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Extracorporeal membrane oxygenation (ECMO) is a life support system used as a bridge to transplantation in critically ill patients who suffer from acute respiratory or cardiac failure with resultant hypoxemia and tissue hypoxia. This is not amendable to conventional support intervention. Previous studies have shown significant drug losses in the components of an ECMO circuit, leading to decreased plasma drug levels. An in vitro study was conducted to determine: (1) changes in intravenous acetaminophen levels over time and (2) changes in concentration observed between different sites of the ECMO circuit. A single bolus dose of intravenous (IV) acetaminophen was injected into a standard blood-primed ECMO circuit. Plasma drug concentrations in the circuit were then measured at specific time points at three different locations to determine concentrations of the drug at time 0, 15, 30, 60, 240 and 360 minutes. The three samples were drawn pre- and post-membrane oxygenator and the polyvinyl chloride (PVC) tubing. A second bolus dose was administered 24 hours after the first in order to compare "new" and "old" circuits. This entire process was repeated a total of three times. The results show that acetaminophen concentrations do not change significantly over time, with consistent levels seen in both new and old circuits (N=9). Average old circuit concentrations were approximately two times greater than the average new circuit concentrations after the circuit was re-dosed at 24 hours. Drug sequestration in the circuit was not significant in any of the three sites measured. It appears that, while acetaminophen levels remain relatively constant over a six hour period, dosing adjustments may be required for use in a circuit beyond the initial 24 hour period, depending on physiologic clearance of the drug. Assuming a six-hour dosing interval, levels should remain constant.
Collapse
Affiliation(s)
- A Gillogly
- College of Pharmacy, University of Michigan, Ann Arbor, MI, USA
| | | | | | | | | | | |
Collapse
|