Pharmacokinetic Model for Cefuroxime Dosing during Cardiac Surgery under Cardiopulmonary Bypass.

Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines. In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fit the data, with total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to body weight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/liter. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/liter. Our individualized dosing strategy was capable of ensuring therapeutic CXM concentrations conforming to each target threshold. Our model yielded an optimized CXM dosing regimen adapted to body weight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.

Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass.

BACKGROUND: High-dose heparin is used during cardiopulmonary bypass (CPB) to prevent thrombosis in the circuits used for extracorporeal circulation. The aim of this study was, initially, to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD parameters and their correlation with the results of the routine haemostatic test activated clotting time (ACT) and thereafter to develop a Bayesian estimator enabling an individualized dosing strategy. METHODS: Fifty consecutive patients undergoing cardiac surgery with CPB were included in the study. Heparin was administered as an initial bolus of 300 IU kg -1 followed by additional boluses of 5000 IU to maintain ACT <400 s. In total, 361 blood samples were collected. The PK and PD data were analysed using a non-linear mixed effect model. RESULTS: A two-compartment model with a linear elimination link to an E max model best described heparin anti-factor Xa activities and ACT. Covariate analysis showed that body weight was positively correlated with clearance and central compartment volume. Inclusion of body weight with these parameters decreased their variability by 11 and 15%, respectively. The Bayesian estimator performed well in predicting individual parameters in an independent group of patients. CONCLUSIONS: A population PK/PD analysis of heparin during CPB, using a routine haemostatic test, shows that Bayesian estimation might help to predict ACT on the basis of only one or two blood samples.

Population pharmacokinetic model of cefazolin in total hip arthroplasty.

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.

[Chronic lower back pain: a new therapeutic approach]. / Lombalgies chroniques: une autre approche thérapeutique.

Lower back pain is a common complaint of patients seen in our consultations. Despite progress, surgical procedures are still often unsuccessful in relieving pain. Blocks performed in the epidural spaces or more often in the articular facets have provided poor relief of chronic lower back pain. The pain has vegetative components. Considering anatomic findings, we describe the innervation of the peridiscal tIssues which suffer during degenarative conditions. We analyze the course of the autogenic nerves mediating lumbar pain, and select the site of the blocks necessary to obtain optimal selective pain relief. A well-defined block at the level of the communicating rami is described.

[Pseudo-spondylodiscitis as manifestation of diffuse articular chondrocalcinosis (author's transl)]. / Les pseudo-spondylodiscites de la chondrocalcinose articulaire diffuse.

Articular chondrocalcinosis (ACC), which is due to the precipitation of calcium pyrophosphate microcrystals, is known to produce symptom of acute arthritis or chronic degenerative polyarticular lesions. It is more rarely responsible for rapidly destructive lesions of the joints suggesting a metabolic or neurological process. The case reported here of a 66 year old woman with major lesions of the L1-L2 intervertebral space, together with other cases already published, shows that the destructive spinal forms of ACC may also present as subacute spondylodiscitis. The latter, however, merely represents 4.9% of all destructive articular lesions of ACC and 5.2% of the vertebral localizations of all forms of the disease.

Detrusor inhibition in suprasacral spinal cord injuries: is it due to sympathetic overactivity?

The authors report five patients with detrusor inactivity in suprasacral spinal cord lesions with perineal spasticity. In all of these cases with cervical or high thoracic lesions treatment with an alpha-blocking drug (Phenoxybenzamine) allowed bladder activity to return. These results suggest that the sacral parasympathetic centre is under the inhibitory influence of the sympathetic nervous system.