scholarly journals P50 Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants

2019 ◽  
Vol 104 (6) ◽  
pp. e37.3-e38
Author(s):  
J Kindblom ◽  
E Norman ◽  
A Rane ◽  
A-C Berg ◽  
U Schubert ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Low Dose ◽  
Volume Of Distribution ◽  
High Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Pain Scores ◽  
Individual Variations ◽  
Physiologic Parameters ◽  
New Formulation ◽  
Study Inclusion

BackgroundFentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 mg/mL for procedural pain.MethodsPreterm infants were given 0.5 (n=20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 mg/kg (n=8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.ResultsThe median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35ng/mL at 15–31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low and high dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman´s r = -0.9, p< 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low dose group (n=9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.ConclusionThe inter-individual variation of fentanyl pharmacokinetics is large in preterm infants and the dose of 0.5 mg/kg seems too small for skin-breaking procedures.Disclosure(s)Nothing to disclose

Does Single, Low-Dose Preoperative Dexamethasone Improve Outcomes after Colorectal Surgery Based on an Enhanced Recovery Protocol? Double-Blind, Randomized Clinical Trial

2008 ◽  
Vol 74 (2) ◽  
pp. 160-167 ◽  
Author(s):  
Turkay Kirdak ◽  
Aysun Yilmazlar ◽  
Sinan Cavun ◽  
Ilker Ercan ◽  
Tuncay Yilmazlar
Keyword(s):  
Colorectal Surgery ◽  
Hospital Stay ◽  
Interleukin 6 ◽  
Low Dose ◽  
Postoperative Outcomes ◽  
High Dose ◽  
C Reactive Protein ◽  
Double Blind ◽  
Reactive Protein ◽  
Pain Scores

Preoperative single, high-dose methylprednisolone administration improves postoperative outcomes after colonic surgery. Several randomized studies, including major surgeries, assessed various high-dose steroid regimens; however, evidence about the effect of administration of lower doses on postoperative outcomes in colorectal surgery is not available. The aim of the present study is to determine whether the administration of a single, low dose of dexamethasone before surgery would confer an outcome advantage after colorectal surgery. Thirty patients undergoing colorectal surgery were included in this randomized, double-blind study. Patients received 8 mg dexamethasone or serum physiologic preoperatively. Levels of Interleukin-6 and C-reactive protein, pain scores, postoperative nausea and vomiting, mobilization, complications, hospital stay, and readmissions were compared. Age, sex, indications, and operations were similar in both groups ( P > 0.05). C-reactive protein and Interleukin-6 levels increased significantly postoperatively in each group ( P < 0.05), but there were no differences between groups when compared ( P > 0.05). There were also no significant differences between pain scores, bowel functions, mobilization, hospital stay, complication rates, and readmission rates between the two groups ( P > 0.05). Preoperative 8 mg dexamethasone administration has no significant effect on reducing postoperative inflammatory response and also does not improve outcomes of colorectal surgery.

scholarly journals Low Dose Hyperoxia Primes Airways for Fibrosis in Mice after Influenza A Infection

2020 ◽  
Author(s):  
Andrew M. Dylag ◽  
Jeannie Haak ◽  
Rachel Warren ◽  
Min Yee ◽  
Gloria S. Pryhuber ◽  
...  
Keyword(s):  
Lung Function ◽  
Viral Infection ◽  
Preterm Infants ◽  
Influenza A ◽  
Low Dose ◽  
Viral Infections ◽  
Airway Hyperreactivity ◽  
Normal Lung ◽  
High Dose ◽  
Neonatal Hyperoxia

AbstractIt is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection suggesting neonatal oxygen may have induced hidden molecular changes that may prime to the lung for disease. We discovered that thrombospondin-1 (TSP-1) is elevated in adult mice exposed to high-dose neonatal hyperoxia that is known to cause alveolar simplification and fibrotic lung disease following IAV infection. TSP-1 was also elevated in a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that we recently reported causes a transient change in lung function that resolves by 8 weeks of age. Elevated TSP-1 was also identified in human autopsy samples of BPD-affected former preterm infants. Consistent with TSP-1 being a master TGFβ regulator, an early transient activation of TGFβ signaling, increased airway hyperreactivity, and peribronchial inflammation and fibrosis were seen when 40×8 mice were infected with IAV, which was not seen in infected room air controls. These findings reveal low dose of neonatal hyperoxia that does not affect lung function or structure may still change expression of genes, such as TSP-1, that may prime the lung for disease following respiratory viral infections, and may help explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.

Pharmacokinetics Anesthesiologists, and Pharmacodynamics of Remifentanil in Persons with Renal Failure Compared with Healthy Volunteers

1997 ◽  
Vol 87 (3) ◽  
pp. 533-541 ◽  
Author(s):  
Frank J. Hoke ◽  
David Shlugman ◽  
Mark Dershwitz ◽  
Piotr Michalowski ◽  
Sherry Malthouse-Dufore ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Minute Ventilation ◽  
Opioid Analgesic ◽  
Volume Of Distribution ◽  
High Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Remifentanil Infusion ◽  
Ester Linkage ◽  
State Concentration

Background Remifentanil is an opioid analgesic for use in anesthesia. An ester linkage renders it susceptible to rapid metabolism by blood and tissue esterases. Thus it was hypothesized that remifentanil elimination would be independent of renal function. Because its principal metabolite (GR90291) is eliminated renally, it would depend on renal function. This study was designed to evaluate the pharmacokinetics and pharmacodynamics of remifentanil and its metabolite in persons with and without renal failure. Methods Two groups of volunteers received two-stage infusions of remifentanil: low dose with 0.0125 microg x kg(-1) x min(-1) for 1 h followed by 0.025 microg x kg(-1) x min(-1) for 3 h; and high dose with 0.025 microg x kg(-1) x min(-1) for 1 h followed by 0.05 microg x kg(-1) x min(-1) for 3 h. Blood samples were collected for analysis of remifentanil and GR90291 concentrations. The pharmacokinetics of remifentanil were fit using a one-compartment pharmacokinetic model. Remifentanil's effect was determined intermittently using minute ventilation during a hypercapnic (7.5% CO2) challenge. Results Fifteen patients with renal failure and eight control participants were enrolled. The clearance and volume of distribution of remifentanil were not different between those with renal failure and the controls. Patients with renal failure showed a marked reduction in the elimination of GR90291; the half-life of the metabolite increased from 1.5 h in the controls to more than 26 h in patients with renal failure. The steady-state concentration of GR90291 is likely to be more than 25 times higher in persons with renal failure. There were no obvious differences in opioid effects on minute ventilation in the controls and in patients with renal failure. Conclusions The pharmacokinetics and pharmacodynamics of remifentanil were not altered in patients with renal disease, but the elimination of its principal metabolite, GR90291, was markedly reduced. Based on simulations, the concentration of GR90291 at the end of a 12-h remifentanil infusion of 2 microg x kg(-1) x min(-1) is not likely to produce significant opioid effects.

Site-Specific Pharmacokinetics and Pharmacodynamics of Intramuscular Meperidine in Elderly Postoperative Patients

1997 ◽  
Vol 31 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Brian L Erstad ◽  
Mimi L Meeks ◽  
Hsiao-Hui Chow ◽  
William D Rappaport ◽  
Miriam L Levinson
Keyword(s):  
Breakthrough Pain ◽  
Tertiary Care ◽  
Volume Of Distribution ◽  
University Teaching ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Pain Scores ◽  
Concentration Time ◽  
Pain Scales

OBJECTIVE: To examine and compare the pharmacokinetics and pharmacodynamics of meperidine when administered intramuscularly at gluteal and deltoid sites in elderly postoperative patients. DESIGN: Prospective, randomized investigation. SETTING: Tertiary care university teaching hospital. PATIENTS: Fourteen patients 60 years of age or older who were undergoing general surgery. INTERVENTION: A single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or gluteal site. MAIN OUTCOME MEASURES: Pharmacokinetic (based on concentration—time curves) and pharmacodynamic (i.e., pain scales, need for additional pain medication) comparisons were made, based on site of meperidine injection. RESULTS: No statistically significant differences were found in the maximum plasma concentration, volume of distribution, or clearance of meperidine by site of injection. Substantial interpatient variability in pharmacokinetic parameters was noted for both sites (range of maximum concentrations: 191–500 ng/mL gluteal, 166–374 ng/mL deltoid). Although pain scores were similar for the two groups, four of the patients in the group given gluteal injection required additional breakthrough pain management within 4 hours of meperidine injection compared with one patient in the group given deltoid injection. CONCLUSIONS: There is no obvious relationship between meperidine pharmacokinetic and pharmacodynamic parameters, regardless of intramuscular injection site. Breakthrough pain is common when patients are given intramuscular injections postoperatively, particularly when the gluteal route is used. When meperidine is used for analgesia in elderly postoperative patients, consideration should be given to more rapid and predictable routes (e.g., intravenous injection) of meperidine administration.

scholarly journals Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice

2021 ◽  
Author(s):  
Caroline E Blevins ◽  
Natalie A Celeste ◽  
James O Marx
Keyword(s):  
Low Dose ◽  
Supplemental Oxygen ◽  
High Dose ◽  
Oxygen Supplementation ◽  
Pilot Studies ◽  
Long Duration ◽  
Oxygen Oxygen ◽  
Physiologic Parameters ◽  
High Doses ◽  
Medium Dose

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundlyhypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

scholarly journals The ALOHA Trial: (Intra-Articular Local Anaesthetic in Hip Arthroscopy) – A Double-Blinded, 3-Arm Randomised Controlled Clinical Trial Comparing Pre-Emptive, High- and Low-Dose Intra-Articular Local Anaesthetic in Hip Arthroscopy

2019 ◽  
Author(s):  
Chong Oon Tan ◽  
Phong Tran ◽  
YewMing Chong ◽  
William Howard ◽  
Laurence Weinberg
Keyword(s):  
Local Anaesthetic ◽  
Hip Arthroscopy ◽  
Low Dose ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Multimodal Analgesia ◽  
Optimum Dose ◽  
Controlled Clinical Trial ◽  
High Dose ◽  
Pain Scores

Abstract Background Pain after hip arthroscopy is variable but can be severe [11-point Numerical Rating Scale (NRS-11) pain scores of 10] despite multimodal analgesia. Although postoperative rescue regional analgesia is useful in these cases its efficacy may be limited by the maximum safe dose of local anaesthetic (LA) permissible when high-dose intra-articular local anaesthetic (IALA) has already been used. IALA may reduce acute postoperative pain after hip arthroscopy, however neither its optimum dose nor timing of administration have been systematically evaluated. Methods In 132 randomly assigned adult patients scheduled for therapeutic hip arthroscopy we compared the effects of two different doses of IALA given at procedure end (Group L [low-dose]: 100mg ropivacaine; Group H [high-dose]: 200mg ropivacaine). We also investigated the effect of an additional pre-emptive dose at the beginning of the procedure (Group P [pre-emptive]: 100mg ropivacaine at procedure start and end). Results There were no statistically significant differences between groups for NRS-11 pain scores in recovery (mean[SD]: Group L – 2.2[1.9]; Group H – 2.3[2.1]; Group P – 2.7[2.5]; lowest p = 0.6), or post recovery Visual Analogue Scale (VAS) pain scores [largest mean difference VAS 1.5 hours: 5mm (p = 0.32); VAS 2 hours: 5mm (p = 0.35); VAS 4 hours: 2mm (p = 0.7); VAS 6 hours: 3mm (p = 0.7)]. There were also no significant differences in antiemetic usage and requirement for rescue fascia iliaca block (FIB) between groups. Conclusions Compared to a single 100 mg dose of ropivacaine at the end of the procedure, we were unable to demonstrate any advantage of either a higher dose IALA or a pre-emptive dose IALA when multimodal analgesia is used. Lower-dose IALA could reduce total systemic LA absorption if a given rescue regional analgesic LA dose is used postoperatively.

scholarly journals Fluorophores Use in Pituitary Surgery: A Pharmacokinetics and Pharmacodynamics Appraisal

2021 ◽  
Vol 11 (5) ◽  
pp. 565
Author(s):  
Daniele Bongetta ◽  
Fulvio Tartara ◽  
Fabio Pagella ◽  
Teresa Somma ◽  
Marilou Cavaliere ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Low Dose ◽  
Tumor Resection ◽  
Pituitary Surgery ◽  
Volume Of Distribution ◽  
Vascular Density ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Actual Knowledge ◽  
Pituitary Tissue ◽  
Technological Advances

(1) Background: Despite many surgical and technological advances, pituitary adenoma surgery is still burdened by non-negligible rates of incomplete tumor resection, mainly due to difficulties in differentiating pathology from normal pituitary tissue. Some fluorescent agents have been recently investigated as intraoperative contrast agents in pituitary surgery. The aim of this study is to evaluate the actual knowledge about the usefulness of such fluorophores with a particular focus on both the pharmacokinetics and pharmacodynamics issues of the pituitary gland. (2) Methods: We reviewed the current literature about fluorophores use in pituitary surgery and reported the first fully endoscopic experience with fluorescein. (3) Results: The studies investigating 5-ALA use reported contrasting results. ICG showed encouraging results, although with some specificity issues in identifying pathological tissue. Low-dose fluorescein showed promising results in differentiating pathology from normal pituitary tissue. Apart from the dose and timing of administration, both the fluorophores’ volume of distribution and the histological variability of the interstitial space and vascular density played a crucial role in optimizing intraoperative contrast enhancement. (4) Conclusions: Both pharmacokinetics and pharmacodynamics issues determine the potential usefulness of fluorophores in pituitary surgery. ICG and fluorescein showed the most promising results, although further studies are needed.

A Weekly Dose of Pegylated Interpheron alpha-2b (Pegintron®) as Maintenance Treatment after Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) in Multiple Myeloma (MM): Preliminary Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5174-5174
Author(s):  
A. Alegre ◽  
B. Aguado ◽  
J. San Miguel ◽  
J. Garcia-Laraña ◽  
F. Lara ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Low Dose ◽  
Survival Curve ◽  
Common Adverse Effect ◽  
New Drugs ◽  
High Dose ◽  
Weekly Dose ◽  
Oral Steroids ◽  
Autologous Pbsct ◽  
New Formulation

Abstract Introduction In spite of the favourable results observed after autologous PBSCT in MM there is no clear plateau in the survival curve and eventually most patients relapse with a median EFS between 40–50 months postransplant. To improve these results and sustain remission, various maintenance treatments have been proposed with minimal and discrepant benefits. Interpheron alpha2b s.c. at low dose and steroids on alternate days, have demonstrated modest improvements in EFS and OS times (5–12 months) after standad-dose therapya but its role in the setting of high dose therapy (HDT) needs confirmation. Recently a new formulation of interpheron alpha2b is available conjugated with polietilenglicol (Pegintron®), that need only one dose weekly and has not been evaluated in MM. We present the preliminary and interim results of a spanish, open study, no comparative, multicentric with Pegintron® (Schering-Plough) as maintenance treatment after autologous PBSCT. Patients y Methods 17 patients with MM received Pegintron® once wekly subcutaneously as maintenance treatment after favourable response post-HDT with autologous PBSCT when the engraftement was completed (7 CR and 10 PR). The initial dose was 15 mg/week x 2 week and this dose was escalated to 25 mg/week and then 35 mg/week. The final dose was adopted according clinical and hematological tolerance. Intermitent oral steroids were allowed. The maintenance treatment was continued until toxicity, relapse or progressión. Results Of the 17 patients included so far in the study, 2 patients suspended the treatment. One case by personal decision an the other for progression, 14 months after transplant. The remainder 15 patients follow the treatment with a median of 10.7± 5 months (1.5–18.6). Most patients received also zolendronate iv/months and oral low dose dexamethasone (20 mg x 4 x months) associated to Pegintron. Mild bone pain, “flu-lyke syndrome” and grade I thrombopenia and neutropenia, were the most common adverse effect.. The best tolerated dose was 15 mg/week. With the exception of one case, all patients maintain the response achieved with HDT with a median of 15 months (3–22) after transplant. Comments and Conclusions These prelimiar results show that maintenance treatment with a weekly dose of Interpheron-a2b conjugated with Polietilenglicol (Pegintron®) is effective and well tolerated after autologous PBSCT in MM. No major adverse effects were observed and no relevant negative effecst was presented on the autologous graft. Pegintron® could be an alternative to sc standar interpheron with the main advantage of therapy simplification (one dose weekly). More experience and longer follow up are needed to evaluate the role of this strategy in the global treatment of MM and new approaches for maintenance have to be investigated, including new drugs as bortezomib, thalidomide an lenalidomide, associated or not with bisphosphonates, Pegintron and steroids.

scholarly journals A Population Pharmacokinetic Model of Intravenous Dexmedetomidine for Mechanically Ventilated Children after Neurosurgery

2019 ◽  
Vol 8 (10) ◽  
pp. 1563 ◽  
Author(s):  
In-Kyung Song ◽  
SoJeong Yi ◽  
Hyeong-Seok Lim ◽  
Ji-Hyun Lee ◽  
Eun-Hee Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Dose Group ◽  
Adverse Reactions ◽  
Low Dose ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Loading Dose ◽  
Mechanically Ventilated

Dexmedetomidine is a selective alpha-2 adrenergic agonist with concurrent sedative and analgesic effects, and it is being increasingly used in pediatric anesthesia and intensive care. This study aimed to investigate the pharmacokinetics of intravenous dexmedetomidine in mechanically ventilated children in the intensive care unit (ICU) after neurosurgery. Pediatric patients aged 2–12 years, who were mechanically ventilated in ICU after neurosurgery, were allocated into a low-dose (n = 15) or high-dose (n = 14) group. The low-dose group received dexmedetomidine at a loading dose of 0.25 µg/kg for 10 min, followed by a maintenance dose of 0.25 µg/kg/h for 50 min, whereas the high-dose group received dexmedetomidine at a loading dose of 0.5 µg/kg for 10 min, followed by a maintenance dose of 0.5 µg/kg/h for 50 min. Serial blood samples were collected for a pharmacokinetic analysis up to 480 min after the end of the infusion. The sedative effect of dexmedetomidine was assessed using the Bispectral Index and University of Michigan Sedation Scale. Adverse reactions, electrocardiography findings, and vital signs were monitored for a safety assessment. A population pharmacokinetic analysis was performed using non-linear mixed effects modeling. Dexmedetomidine induced a moderate-to-deep degree of sedation during infusion in both groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment disposition model with first-order elimination kinetics. The parameters were standardized for a body weight of 70 kg using an allometric power model. The population estimates (95% confidence interval) per 70 kg body weight were as follows: clearance of 81.0 (72.9–90.9) L/h, central volume of distribution of 64.2 (50.6–81.0) L, intercompartment clearance of 116.4 (90.6–156.0) L/h, and peripheral volume of distribution of 167 (132–217) L. No serious adverse reactions or hemodynamic changes requiring the discontinuation of dexmedetomidine were observed. Dexmedetomidine had increased clearance and volume of distribution in mechanically ventilated children in ICU after neurosurgery, thereby indicating the need to adjust the dosage to obtain a target plasma concentration.

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