Comparison of Ropivacaine Plasma Concentration With or Without Epinephrine for Posterior Quadratus Lumborum Block in Cesarean Section

BACKGROUND The posterior Quadratus Lumborum Block (pQLB) is a posterior abdominal wall block in which local anesthetic (LA), administered posteriorly to Quadratus Lumborum (QL) muscle, spreads underneath intermedium layer of thoracolumbar fascia, into a triangular space named lumbar interfacial triangle. This interfascial plane is in close relation to thoracic paravertebral (PV) space. Local anesthetic spread into this space could explain analgesic efficacy of pQLB1. Compared to lateral QLB, in which LA is administered laterally to QL muscle, pQLB is safer (needle tip is separated from the peritoneum by QL muscle) and easier to perform (injection point is more superficial). Posterior QLB efficacy has been demonstrated in major abdominal surgery. In Cesarean Section (CS) pQLB efficacy vs placebo and superior efficacy vs TAP block was showed. Ropivacaine arterial concentration after QLB, in laparoscopic gynaecological surgery has been studied. To the best of our knowledge no author investigated pQLB safety in obstetric population, at increased risk of local anesthetic systemic toxicity (LAST) because of physiological modifications occurring during pregnancy (increased cardiac output, increased arterial and venous blood tissue flow, decreased concentration of plasma binding protein). Adding epinephrine to local anesthetic, determining a delayed AL systemic reabsorption and a reduced plasmatic concentration, could improve pQLB efficacy and safety, as demonstrated for Transversus Abdominal Plain (TAP) block and sciatic and femoral block.

METHODS Patients were consecutively allocated into one of two groups: e-pQLB (0.375% ropivacaine+ 100 mcg epinephrine) or pQLB (0.375% ropivacaine). Before surgery, under local anesthesia, 2 venous accesses were founded, one for fluids and drugs injection and the second one, contralaterally, for venous samples only. During surgical procedure standard hemodynamic monitoring was provided; fetal wellbeing was registered by cardiotocographic monitoring. Supplemental oxygen has was provided by Venturi mask. SA was administered in sitting position, at L3-4 lumbar interspace, using hyperbaric bupivacaine 0.5% 9 mg plus sufentanil 5 mcg. Surgical procedure started when T4 level has been reached. Posterior QLB was administered at the end of surgical procedure, with patient in supine position, under monitoring and after cleaning the skin with surgical solution (ChloraPrep, Carefusion, 244 LTD, UK). A Sonosite M-Turbo echograph ( FUJIFILM Sonosite Europe, Amsterdam, Netherlands) and a broadband (5-8 MHz) convex probe covered with a sterile plastic sheath have been used. The probe was placed at the level of the anterior superior iliac spine and moved cranially until the three abdominal wall muscles were identified. The external oblique muscle was followed posterolaterally until its posterior border was found. The probe was tilted down to identify the bright hyperechoic line that corresponds with the intermediate layer of the thoracolumbar fascia. The needle (Ultraplex 360, B.Braun Melsungen, Germany) was inserted in plane from medial (anterior) to lateral (posterior). The optimal point of injection was determined using hydrodissection. In e-pQLB group ropivacaine 0.375%+epinephrine 100 mcg 20 ml for each side was administered; in pQLB group ropivacaine 0.375% 20 ml for each side was administered. After block, venous samples (2 ml each) were performed at 10, 30, 45, 60, 120 minutes. The ropivacaine concentration was set at 2.2 mcg/ml, which represents the venous threshold value of systemic toxicity14. To evaluate LAST patients have been asked for perioral tingling, metallic taste, tinnitus, visual disturbance or slurred speech at the time that each blood sample has been obtained.

Intraoperative ketorolac 30 mg and acetaminophen 1 g were administered. After surgery, in Post Anesthesia Care Unit (PACU), a PCA pump was connected to patients and programmed to deliver 1 mg morphine bolus on demand with a lock out interval of 8 min and no background infusion. All patients received regular intravenous paracetamol 1g 6 hourly and intravenous ketorolac 30 mg 12 hourly.

Experimental procedure Chemicals, reagents and equipment Methanol and acetonitrile were HPLC grade and were purchased from VWR Chemicals (Radnor, PA, USA). Water was purified by Millipore Synergy-UV-System (Bedford, MA, USA). 20 % ammonium hydroxide solution was provided by Carlo Erba Reagents (Milan, Italy), acetic acid 99-100% and phosphoric acid ≥ 85% were provided by Sigma-Aldrich (St. Louis, MO, USA). Ropivacaine and Ropivacaine-d7 hydrochloride (used as internal standard, IS) were purchased by USP (Rockville, MD, USA) and Toronto Research Chemicals (North York, ON, Canada), respectively. Neostigmine methylsulphate was provided by LGC Standards (Luckenwalde, Germany).OASIS HLB SPE cartridges (3 mL, 60 mg) were supplied by Waters (Milford, MA, USA). PTFE disposable filters (0.45 µm) were purchased from Membrane solutions (Plano, TX, USA). Visiprep DL SPE Vacuum Manifold was purchased by Supelco/Sigma-Aldrich (St. Louis, MO, USA). The heating block "Pierce - Reacti-Therm III" was purchased from ThermoFisher Scientific (Waltham, MA, USA). Centrifuge 5415D supplied by Eppendorf (Hamburg, Germany).1 mg mL-1 stock solutions of ropivacaine and ropivacaine-d7 were prepared in methanol. Working standard solution dilutions were prepared from these latter solutions and were finally diluted by serial dilution to spike blank plasma samples for the construction of matrix-matched calibration curve in order to have final ropivacaine concentrations in the interval of 0.8 - 13.2 ng mL-1. Working solutions were stored at -20 °C and prepared daily. Stock solutions were analysed regularly up to six month after the preparation to assess their stability in the time and whether there was degradation of the analytes.

Plasma sampling Patients' blood samples (5 mL) were collected in tubes containing ethylenediaminetetraacetic acid (EDTA) and were added to 25 µL of 20 mg mL-1 neostigmine methylsulfate solution to block esterase activity in the plasma14. The samples were stored in ice-water bath for 10-15 min and then centrifuged at 1300 × g at 4°C for 5 min to obtain plasma. Collected plasma samples were stored at -20 °C until analyzed.