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Population pharmacokinetic model of cefazolin in total hip arthroplasty.

ABSTRACT: Cefazolin is an antibiotic recommended for infection prevention in total hip arthroplasty (THA). However, the dosing regimen necessary to achieve therapeutic concentrations in obese patients remains unclear. The aim of this study was to conduct a population analysis of cefazolin pharmacokinetics (PK) and assess whether cefazolin administration should be weight adapted in THA. Adult patients undergoing THA surgery received an injection of 2000 mg of cefazolin, doubled in the case of BMI > 35 kg/m² and total body weight > 100 kg. A population PK study was conducted to quantify cefazolin exposure over time compared to the therapeutic concentration threshold. A total of 484 cefazolin measurements were acquired in 100 patients, of whom 29% were obese. A 2-compartment model best fitted the data, and creatinine clearance determined interpatient variability in elimination clearance. Our PK simulations using a 2000 mg cefazolin bolus showed that cefazolin concentrations remained above the threshold throughout surgery, regardless of weight or renal function. A 2000 mg cefazolin single injection without adaptation to weight or renal function and without intraoperative reinjection was efficient in maintaining therapeutic concentrations throughout surgery. The optimal target concentration and necessary duration of its maintenance remain unclear.

SUBMITTER: Lanoiselee J

PROVIDER: S-EPMC8492877 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo determine whether the use of total hip arthroplasty (THA) among individuals with a displaced intracapsular fracture of the femoral neck is based on national guidelines or if there are systematic inequalities.DesignObservational cohort study using the National Hip Fracture Database (NHFD).SettingAll hospitals that treat adults with hip fractures in England, Wales, and Northern Ireland.ParticipantsPatients within the national database (all aged ≥60) who received operative treatment for a non-pathological displaced intracapsular hip fracture from 1 July 2011 to 31 April 2015.Main outcome measuresProvision of THA to patients considered eligible under criteria published by the National Institute for Health and Care Excellence (NICE).Results114 119 patients with hip fracture were included, 11 683 (10.2%) of whom underwent THA. Of those who satisfied the NICE criteria, 32% (6780) : received a THA. Of patients who underwent THA, 42% (4903) did not satisfy the NICE criteria. A recursive partitioning algorithm found that the NICE eligibility criteria did not optimally explain which patients underwent THA. A model with superior explanatory power drew distinctions that are not supported by NICE, which were an age cut off at 76 and a different ambulation cut off. Among patients who satisfied the NICE eligibility, the use of THA was less likely with higher age (odds ratio 0.88, 95% confidence interval 0.87 to 0.88), worsening abbreviated mental test scores (0.49 (0.41 to 0.58) for normal cognition v borderline cognitive impairment)), worsening American Society of Anesthesiologists score (0.74, 0.66 to 0.84), male sex (0.85, 0.77 to 0.93), worsening ambulatory status (0.32, 0.28 to 0.35 for walking with a stick v independent ambulation), and fifths of worsening socioeconomic area deprivation (0.76 (0.66 to 0.88) for least v most deprived fifth). Patients receiving treatment during the working week were more likely to receive THA than at the weekend (0.90, 0.83 to 0.98).ConclusionsThere are wide disparities in the use of THA among individuals with hip fractures, and compliance with NICE guidance is poor. Patients with higher levels of socioeconomic deprivation and those who require surgery at the weekend were less likely to receive THA. Inconsistent compliance with NICE recommendations means that the optimal treatment for older adults with hip fractures can depend on where and when they present to hospital.

Project description:BackgroundTraditional principles for successful outcomes in Total Hip Arthroplasty (THA) have relied largely on placing the socket in the native position and trying to restore static anatomical femoral parameters gauged on X-rays or intra-operative measurement. Stability is conventionally achieved by making appropriate changes during the time of trial reduction. Post-operative complications of dislocation and significant Limb Length Discrepancy (LLD) requiring foot wear modification represents opposite ends of the spectrum from a biomechanical perspective and these continue to be relatively high. A move towards giving more importance to functional dynamic parameters rather than static anatomical parameters and less reliance on stability testing at trial reduction is warranted.MethodsIntraoperative 3D functional balancing of THA without stability testing at trial reduction was practiced in all subjects undergoing THA in our unit from April 2014. To date 1019 patients have had their hips replaced with the same technique. They were followed up till April 2020 for post-operative complications of dislocation and significant LLD needing footwear modification. A secondary cohort of 114 patients from 1st January to December 31st 2017 within this primary group were analyzed clinically and radiologically to ascertain the implications of functional 3D balancing on X-ray parameters, clinical outcome scores (Harris Hip Score and Oxford Hip Score), ability to squat, and subtle subjective post-operative perception of limb lengthening (POPLL).ResultsIn the primary group of 1019 patients, there were only two dislocations and no patient needed footwear modification for LLD. In the detailed analysis of the secondary cohort of 114 patients, the correlation with restoration of static radiological parameters was inconsistent. 40 patients could not squat and 4 patients had subtle subjective post-operative perceived limb lengthening (POPLL). Measured outcomes such as HHS and OHS were improved in all patients with significant statistical significance (P < 0.001).ConclusionThis study underlines the fact that more importance must be given to functional dynamic parameters by 3D balancing of the THA and not on static anatomical X-rays parameters and stability testing during trial reduction. This represents a paradigm shift in the evolution of total hip arthroplasty.Level of evidenceA Level II study. (Data collected from the ongoing prospective study) (http://www.spine.org/Documents/LevelsofEvidenceFinal.pdf).Supplementary informationThe online version contains supplementary material available at 10.1007/s43465-021-00505-3.

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Population pharmacokinetic model of cefazolin in total hip arthroplasty.

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