BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vom...BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.展开更多
BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors ...BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.展开更多
文摘BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.
基金Supported by Veloxis Pharmaceuticals,Inc.1001 Winstead Drive Suite 310,Cary,NC 27513.
文摘BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.
