Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management
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SUBMITTER: Nakano T
PROVIDER: S-EPMC11251383 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC6513586 | biostudies-literature
Project description:Intrathecal trialing is used as a screening prognostic measure prior to intrathecal drug delivery system implant. The purpose of this study was to determine the efficacy of a continuous intrathecal infusion of an admixture of bupivacaine and fentanyl in patients with chronic low back pain. Patients with refractory chronic low back pain in the setting of previous lumbar spine surgery and/or chronic vertebral compression fracture(s) were enrolled in a randomized double blind cross-over study comparing saline infusion to infusion of a solution containing bupivacaine combined with low-dose fentanyl over a 14-18 hour period. The primary outcome measure was the change in pain intensity at the end of the screening trial. Patients who experienced significant pain reduction from either infusion relative to baseline pain were offered a permanent implant. In total, 36 patients were enrolled, with 31 patients trialed and 25 implanted. At the end of the screening trial, pain scores, at rest or with activity, decreased appreciably in both groups; however, significantly better improvements occurred in the fentanyl/bupivacaine group compared to saline both with activity and at rest (P = .016 and .006, respectively). Treatment order appeared to affect outcome with saline demonstrating a placebo response. At 12 months following implant, primary and secondary outcome measures continued to be significantly reduced from baseline. Continuous intrathecal delivery of a combination of zlow-dose fentanyl with bupivacaine is superior to saline in screening intrathecal trialing for back pain reduction. With longer term delivery, a sustained reduction of chronic low back pain was also observed.
| S-EPMC10321766 | biostudies-literature
Project description:Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (Css ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.
| S-EPMC7591270 | biostudies-literature
Project description:PurposeBelinostat is a second-generation histone deacetylase inhibitor (HDI) predominantly metabolized by UGT1A1-mediated glucuronidation. Two common polymorphisms (UGT1A1*28 and UGT1A1*60) were previously associated with impaired drug clearance and thrombocytopenia risk, likely from increased drug exposure. This latter phenomenon has been observed with other HDIs such as abexinostat, panobinostat, romidepsin, and vorinostat. It was the intention of this brief report to expand a population pharmacokinetic (PPK) model to include a pharmacodynamic (PD) model describing the change in platelet levels in patients with cancer administered belinostat as a 48-h continuous intravenous infusion, along with cisplatin and etoposide.MethodsThe PPK/PD model developed here introduced an additional rate constant to a commonly used mechanistic myelosuppression model to better describe the maturation of megakaryocytes into platelets before degradation and a feedback mechanism. The model employed a proportional error model to describe the observed circulating platelet data.ResultsSeveral covariates were explored, including sex, body weight, UGT1A1 genotype status, liver, and kidney function, but none significantly improved the model. Platelet levels rebounded to baseline within 21 days, before the next cycle of therapy. Simulations predicted that higher belinostat drug exposure does cause lower thrombocyte nadirs compared to lower belinostat levels. However, platelet levels rebound by the start of the next belinostat cycle.ConclusionsThis model suggests a q3week schedule allows for sufficient platelet recovery before the next belinostat infusion is optimal.
| S-EPMC6410699 | biostudies-literature
Project description:BackgroundA combination of opioids and adjunctive drugs can be used for intravenous patient-controlled analgesia (PCA) to minimize opioid-related side effects. We investigated whether two different analgesics administered separately via a dual-chamber PCA have fewer side effects with adequate analgesia than a single fentanyl PCA in gynecologic pelviscopic surgery.MethodsThis prospective, double-blind, randomized, and controlled study included 68 patients who underwent pelviscopic gynecological surgery. Patients were allocated to either the dual (ketorolac and fentanyl delivered by a dual-chamber PCA) or the single (fentanyl alone) group. Postoperative nausea and vomiting (PONV) and analgesic quality were compared between the two groups at 2, 6, 12, and 24 h postoperatively.ResultsThe dual group showed a significantly lower incidence of PONV during postoperative 2-6 h (P = 0.011) and 6-12 h (P = 0.009). Finally, only two patients (5.7%) in the dual group and 18 (54.5%) in the single group experienced PONV during the entire postoperative 24 h and could not maintain intravenous PCA (odds ratio: 0.056, 95% CI [0.007, 0.229], P < 0.001). Despite the administration of less fentanyl via intravenous PCA during the postoperative 24 h in the dual group than in the single group (66.0 ± 77.8 vs. 383.6 ± 70.1 μg, P < 0.001), postoperative pain had no significant intergroup difference.ConclusionsTwo different analgesics, continuous ketorolac and intermittent fentanyl bolus, administered via dual-chamber intravenous PCA, showed fewer side effects with adequate analgesia than conventional intravenous fentanyl PCA in gynecologic patients undergoing pelviscopic surgery.
| S-EPMC10834721 | biostudies-literature
Project description:BackgroundThis is an update of the review on "Lidocaine for pain relief in burn injured patients" first published in Issue 3, 2007, and first updated in 2012. Pain is a major issue for people with many different types of wounds, in particular those people with burn injuries. Prompt, aggressive use of opioid analgesics such as morphine has been suggested as critical to avert the cycle of pain and anxiety, but adverse effects are encountered. It has been proposed that newer agents such as lidocaine could be effective in reducing pain and alleviating the escalating opioid dosage requirements in people with burn injury.ObjectivesTo assess the safety and effectiveness of intravenous lidocaine as a means of pain relief versus no therapy, placebo, other drugs, or a combination of these therapies in people with burn injury.Search methodsFor this third update, we searched the Cochrane Central Register of Controlled Trials (Issue 11, 2013), and Ovid MEDLINE, MEDLINE in Process and Ovid EMBASE (up to December 2013).Selection criteriaWe included randomised controlled trials (RCTs) and controlled clinical trials (CCTs), published and unpublished, which assessed the efficacy of intravenous lidocaine in varying doses as a single-agent therapy with no therapy, placebo, other analgesics (such as opioids), lidocaine plus another drug, or a combination of these therapies as a means of pain relief in people with burn injury.Data collection and analysisTwo review authors independently abstracted data and assessed the risk of bias of the studies identified.Main resultsIn this 2014 update, we found no new studies. The one small randomised double-blind placebo-controlled cross-over trial found in 2012, which included only 45 participants and compared intravenous lidocaine against placebo as a means of pain relief in people with burns still remains central to this review. We assessed this study as being at a high risk of bias due to its small size (fewer than 50 participants per treatment arm). Subjective pain ratings, as measured by the verbal rating scale, increased during procedures for both treatment arms; however, the increase was less in the lidocaine treatment group. There were no significant clinical or statistical differences regarding the effects of lidocaine and placebo on opioid requests and consumption, anxiety or level of satisfaction during a wound care procedure, but the small included study provided insufficient data to draw any conclusions.Authors' conclusionsAs current clinical evidence is based on only one RCT as well as case series and reports, intravenous lidocaine must be considered a pharmacological agent under investigation in burns care, the effectiveness of which is yet to be determined with further well-designed and conducted clinical trials.
| S-EPMC6508369 | biostudies-literature
Project description:Very few studies have compared continuous wound infiltration (CWI), continuous epidural infusion (CEI) and intravenous Patient Controlled Analgesia (PCA) with morphine in spine surgery. This study compared these modalities in patients undergoing microdissectomy.This prospective, randomized control trial was conducted on 75 patients of American Society of Anesthesiologists' physical status I or II undergoing microdiscectomy. Patients in all the three groups received morphine 1 mg IV, with a lockout period of 10 min after each bolus, and the maximum allowed dose was 15 mg/5 h postoperatively. Patients in Group A received CWI with 0.25% levobupivacaine 20 mL as bolus after extubation followed by infusion at 5 mL/h. Group B received CEI with 0.25% levobupivacaine at 5 mL/h. Patients in Group C received intravenous (IV) morphine by PCA pump only. The primary end points were static and dynamic visual analogue scores (VAS) and postoperative pain scores. Secondary observations were postoperative morphine consumption at 8 h, 24 h and 48 h, and patient satisfaction.Group A showed greater analgesic effects at 12 h (P < 0.02), 24 h (P < 0.03), 36 h (P < 0.008) and 48 h (P < 0.007) when compared to the other two techniques, as pain scores were less in group A as compared to group B and C. The requirement of postoperative intravenous morphine (mg) was 18 ± 12.82, 22.92 ± 9.88, 41.56 ± 8.83 for groups A, B and C after 48 h (P < 0.001).Continuous wound infiltration is an effective postoperative pain control technique with minimal side effects, after spinal surgery.
| S-EPMC5530741 | biostudies-other
Project description:Tacrolimus is a cornerstone of immunosuppression after lung transplantation. However, there are no clear guidelines on how to administer the drug and the duration to achieve the required therapeutic range in the early phase of lung transplantation. This is a single-center cohort study of adult patients who had lung transplantation. Tacrolimus was administered beginning with a low dose of 0.01 mg/kg/day immediately after transplantation. In addition, the designated clinical pharmacist conducted a daily intervention with trough concentrations to achieve the target of 10-15 ng/mL. Time in the therapeutic range (TTRin, %), time to the therapeutic range (TTRto, days), and coefficient of variation (CoV) of tacrolimus were evaluated for the 2-week post-transplant period. A total of 67 adult patients who had received first-time lung transplantation were included in the analysis. The median percentage of tacrolimus TTRin was 35.7% (21.4-42.9%) for the 2-week postoperative period. The median day of TTRto was 7 days (5-9 days), and the median tacrolimus trough concentration was 10.02 ng/mL (7.87-12.26 ng/mL) for the 2-week postoperative period. The median CoV of tacrolimus was 49.7% (40.8-61.6%). Acute kidney injury following tacrolimus infusion occurred in 23 (34.3%) patients, but there was no neurotoxicity or acute cellular rejection within 1 month of the postoperative period. In conclusion, continuous intravenous administration with the daily measure and dose titration of tacrolimus trough concentrations allowed the therapeutic range of tacrolimus to be reached within 1 week without significant adverse events, although the pharmacokinetic parameters were highly variable over time.
| S-EPMC10323585 | biostudies-literature
Project description:AimsThe aim of this study was to explore whether continuous infusion causing lubrication can effectively alleviate pain during male urethral catheterization.MethodsThis prospective, multicenter, double-blinded study included 190 male patients scheduled for urethral catheterization. Patients were randomly allocated into four groups: Group A: the catheter was lubricated with paraffin; Group B: the catheter was lubricated with compound lidocaine gel; Group C: the pump continuously infusing with sterilized water; Group D: the pump continuously infusing with 2% lidocaine. The primary outcome was the visual analogue scale (VAS) scores. Statistical analysis system (SAS) (version 9.4) was used to perform all the statistical analyses. Significance for all results was set at P < 0.05.ResultsThe VAS of Group D was the lowest (18.90 ± 11.44), followed by the Group C (33.00 ± 11.07), and the VAS of Group A was the highest (53.98 ± 14.76). There were significant differences in VAS in Group D compared to Group A(P < 0.0001), Group B(P < 0.0001) and Group C (P < 0.0001), Group C compared to Group A (P < 0.0001) and Group B(P < 0.0001), Group B compared to Group A (P < 0.0001), indicating that patients treated with lidocaine infusion (Group D) experienced significantly less pain than did those in the other three groups.ConclusionsContinuous infusion with sterilized water during catheterization is an efficient method for lubricating the urethral mucosa; furthermore, infusion with 2% lidocaine provides better analgesia as well as lubrication.Trial registrationThe study protocol was registered in the Chinese Clinical Trial Registry (ChiCTR2300070866) ( https://www.chictr.org.cn/showproj.html?proj=194591 ) on Apr. 25th, 2023.
| S-EPMC11657273 | biostudies-literature
Project description:Fentanyl was administered as a single intravenous bolus injection at 5 µg/kg to five koalas and fentanyl plasma concentrations for a minimum of 2 h were quantified by an enzyme-linked immunosorbent assay (ELISA). The median (range) fentanyl elimination half-life and clearance were 0.53 (0.38-0.91) h, and 10.01 (7.03-11.69) L/kg/h, respectively. Assuming an analgesic therapeutic plasma concentration of 0.23 ng/mL (extrapolated from human studies), an intravenous constant infusion rate was estimated at approximately between 1.7 to 2.7 µg/kg/h (using the clearance 95% confidence intervals). A transdermal fentanyl patch was applied to the antebrachium of an additional two koalas for 72 h. Fentanyl plasma concentrations were determined during the patch application and after patch removal at 80 h. The fentanyl plasma concentration was greater than 0.23 ng/mL after 12 to 16 h. While the patch was applied, the maximum fentanyl concentration was approximately 0.7 ng/mL from 32 to 72 h. Fentanyl plasma concentrations increased to 0.89 ng/mL 1 h after the patch was removed, and then decreased to a mean of 0.47 ng/mL at 80 h. The transdermal fentanyl patch is likely to provide some level of analgesia but should be initially co-administered with another faster acting analgesic for the first 12 h.
| S-EPMC8698108 | biostudies-literature