Background Ropivacaine is a widely used local anaesthetic drug, highly bound to plasma proteins with a free plasma fraction of about 5%. Therefore, the monitoring of free drug concentration is most relevant to perform pharmacokinetic studies and to understand the drug pharmacokinetic/pharmacodynamic (PK/PD) relationship. Methods A high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using reverse-phase LC and electrospray ionisation mass spectrometry with multiple reaction monitoring (MRM) is described for the quantitation of both free and total ropivacaine in human plasma. Ropivacaine-d7 was used as an internal standard (IS). Results The method was validated in the range 0.5-3000 ng/mL, with five levels of QC samples and according to the European Medicine Agency and Food and Drug Administration guidelines. The performance of the method was excellent with a precision in the range 6.2%-14.7%, an accuracy between 93.6% and 113.7% and a coefficient of variation (CV) of the IS-normalised matrix factor below 15%. This suitability of the method for the quantification of free and total ropivacaine in clinical samples was demonstrated with the analysis of samples from patients undergoing knee arthroplasty and receiving a local ropivacaine infiltration. Conclusions A method was developed and validated for the quantification of free and total ropivacaine in human plasma and was shown suitable for the analysis of clinical samples.

A computed tomographic scan was obtained in 35 patients to measure the depth and the relationship of the branches of the lumbar plexus to the posterior superior iliac spine projection and the vertebral column. In addition, we prospectively studied 80 patients scheduled for total hip arthroplasty who received a continuous psoas compartment block (CPCB) in the postoperative period. CPCB was performed after surgical procedures by using modified Winnie\'s landmarks and nerve stimulation. From 5 to 8 cm of catheter was inserted. Radiographs were obtained after injection of 10 mL of contrast medium. An initial loading dose (0.4 mL/kg) of 0.2% ropivacaine was injected, followed by continuous infusion of 0.2% ropivacaine for 48 h. The depth of the lumbar plexus and the distance between the lumbar plexus and the L4 transverse process were measured. Visual analog scale values of pain at 1, 12, 24, and 48 h were obtained at rest and during mobilization. Amounts of rescue analgesia were also recorded. Sensory blockade of the principal branches of the lumbosacral plexus was noted at 1 and 24 h, as were adverse events related to the technique. There was a significant difference between men and women in depth of the lumbar plexus (median values, 85 vs 70 mm for men and women, respectively). There was a positive correlation between the body mass index and skin-lumbar plexus distances. In contrast, there was no difference regarding the distance between the transverse process of L4 and the lumbar plexus. The catheter tip lay within the psoas major muscle in 74% of the patients and between the psoas and quadratus lumborum muscles in 22%. In three patients, the catheter was improperly positioned. At 1 h, sensory blockade of the femoral, obturator, and lateral femoral cutaneous nerves was successful in, respectively, 95%, 90%, and 85% of patients. At 24 h, these rates were 88%, 88%, and 83%, respectively. During the 48-h study period, median visual analog scale values of pain were approximately 10 mm at rest and from 18 to 25 mm during physiotherapy. Five patients received 5 mg of morphine at 1 h. Five cases of unilateral epidural anesthesia were noted after the bolus injection. We conclude that CPCB with 0.2% ropivacaine allows optimal analgesia after hip arthroplasty, with few side effects and a small failure rate. Before lumbar plexus branch stimulation and catheter insertion, anesthesiologists should be aware of the L4 transverse process location and lumbar plexus depth.
CONCLUSIONS: Lumbar plexus depth is correlated with the patient\'s body mass index and differs between men and women, but this is not true of the lumbar plexus-transverse process distance. Considering new landmarks, a continuous psoas compartment block promotes optimal analgesia after hip arthroplasty, with few side effects.