ABSTRACT
Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the characterization of the pharmacokinetics of piperacillin and tazobactam and its association with the concentrations of inflammatory markers and adrenal steroids during CAP therapy will be investigated in up to 40 critically ill patients. The serum concentrations of piperacillin and tazobactam, cortisol, cortisone, corticosterone and 11-deoxycortisol and interleukin-6 levels, as well as routine clinical chemistry and hematology parameters will be monitored from the beginning of treatment for up to five days. Nonparametric population pharmacokinetic modeling and Monte-Carlo simulations will be performed to make estimates of the pharmacokinetics of piperacillin and tazobactam and the probability of pharmacokinetic-pharmacodynamic target attainment. The observed individual characteristics and changes will be correlated with clinical and laboratory findings. The protocol of the observational study will be designed following the STROBE guideline.
ABSTRACT
OBJECTIVES: The aim of this study was to analyze the postoperative effects of extended nerve blocks and local infiltration analgesia (LIA) on postoperative pain control, muscle weakness, and blood loss after total knee arthroplasty (TKA). PATIENTS AND METHODS: Between February 24th 2020 and July 10th 2020, a total of 161 patients (55 males, 106 females; median age: 69.0 years [IQR 63.0-75.0], range, 41 to 81 years) who underwent primary TKA were randomly allocated into three parallel groups according to their concomitant procedure in a double-blind fashion: (i) those to whom nerve blockade was performed after competition of surgery under the duration of spinal anesthesia (n=50); (ii) those to whom LIA was performed during surgery (n=52), and (iii) control group (n=59). The content of LIA was 10-10 mL of 20 mg lidocaine with 0.01 mg adrenalin and 100 mg ropivacaine, 1 mL (30 mg) ketorolac, and 5 mL (500 mg) tranexamic acid was diluted by 50 mL 0.9% NaCl under aseptic conditions. Outcome parameters were the evaluation of pain until the evening of first postoperative day (24 to 36 h), mobilization, and blood loss within the first three postoperative days. RESULTS: The pain was maximal between 4 and 8 h postoperatively, when the effect of the spinal anesthetic drugs disappeared. During this critical period, tolerable pain (Numerical Rating Scale, NRS ≤3) was observed in 52%, 42%, and 19% of nerve blockade in LIA and control groups, respectively. None of the patients complained of high-intensity pain (NRS >8) in the LIA group, which was a significant difference from the block and control groups (10% and 14%, p<0.008, respectively). There was no significant muscle weakness associated with the use of this extended block. The decrease in hemoglobin level was significantly lower in the LIA group than in the control and block groups (odds ratio [OR]: 0.379, 95% confidence interval [CI]: 0.165-0.874 for nerve blockade vs. LIA, OR: 1.189, 95% CI: 0.491-2.880 for nerve blockade vs. control, OR: 0.319, 95% CI: 0.140-0.727, respectively). The common language effect size for pain in each referred interval in each group and for decrease of hemoglobin between the first and third postoperative days fell between 0.507 and 0.680. CONCLUSION: This study demonstrates that LIA technique offers a fast and safe treatment option for pain relief after TKA. No clinically relevant muscle weakness was observed among groups according to field block applications. Significant advantages were also achieved in blood loss.
