Study Pinpoints Ropivacaine Dose and Positioning Time for One-Sided Spinal Anesthesia

Patients undergoing varicose vein surgery on one leg often receive a technique called unilateral spinal anesthesia, in which the numbing drug is steered toward only the operated limb while the other leg keeps its strength. A new dose- and time-finding study from the Affiliated Hospital of North Sichuan Medical College in Nanchong, China, has now quantified two key numbers behind that strategy: the median effective dose of 0.5% hyperbaric ropivacaine that produces motor block in the non-surgical leg, and the median duration of side-lying positioning needed to keep that leg free of block. The work, published in Frontiers in Pharmacology, was registered as a clinical trial (ChiCTR2400088340) and prospectively enrolled patients between 15 August and 1 November 2024.

The research team, led by Jun Xu and corresponding author FangJun Wang, enrolled sixty adults aged 18 to 65 years with American Society of Anesthesiologists physical status I to III and a body mass index between 18.5 and 23.9 kg·m−2. All were scheduled for elective unilateral lower extremity varicose vein surgery under combined spinal-epidural anesthesia. The study ran in two sequential phases of thirty analyzable patients each: a dose-finding phase and a time-finding phase. Patients with spinal or nerve root disease, spinal deformity, coagulopathy, raised intracranial pressure, allergy to the study drugs, or other exclusion conditions were not eligible, and anyone needing epidural rescue anesthesia or conversion to general anesthesia was withdrawn from the dose-response analysis.

Hyperbaric ropivacaine is denser than cerebrospinal fluid, so gravity pulls the solution toward the dependent, operative side when the patient lies with the surgical leg down. The investigators prepared the solution immediately before injection by mixing 10 mL of 1% ropivacaine with 10 mL of 10% glucose, yielding 20 mL of 0.5% ropivacaine with 5% glucose. After ultrasound-guided identification of the L3-4 interspace, the anesthesiologist directed the needle orifice toward the surgical side and injected the drug at 0.1 mL·s−1, with the operating table tilted 30 degrees into the Trendelenburg position. Once the sensory block reached the T10 dermatome on the surgical side, the table was returned to horizontal.

The core of the design was a modified Dixon up-and-down method, a sequential technique in which the dose or time given to each patient depends on the response observed in the previous one. In the dose-finding phase, patients stayed in the lateral decubitus position for a fixed 20 minutes, and the starting dose was 12 mg. If the non-surgical leg showed motor block, defined as a modified Bromage score of 1 or higher, the next patient received 0.5 mg less; if not, the next patient received 0.5 mg more. Motor block was scored every minute for the first 15 minutes after injection and then every 10 minutes, by an independent investigator blinded to both the dose and the positioning duration.

Probit regression on the dose-finding data showed that the probability of motor block in the non-surgical extremity rose with increasing ropivacaine dose, with a slope of 2.264 (95% confidence interval, 0.707 to 3.821; P = 0.004). The median effective dose, or ED50, corresponding to a 50% probability of motor block in the non-surgical leg, was 12.683 mg (95% CI, 12.367 to 12.997 mg). The authors treated this ED50 as the primary estimate of the study, with additional quantile estimates from the fitted model considered exploratory.

In the second phase, the team fixed the intrathecal dose at the exploratory ED5 of 11.956 mg, the dose associated with only a 5% probability of motor block in the non-surgical leg (95% CI, 10.304 to 12.303 mg), and instead varied the lateral decubitus time, starting at 15 minutes and adjusting in 1-minute steps. Here the coding was reversed: successful prevention of motor block in the non-surgical leg, again a modified Bromage score below 1, counted as the positive response. The probability of preventing motor block increased with longer positioning time, with a slope of 1.536 (95% CI, 0.531 to 2.541; P = 0.003). The median effective time, or ET50, was 13.887 minutes (95% CI, 13.390 to 14.338 min), and the exploratory ET95, the time associated with a 95% probability of prevention, was 14.957 minutes (95% CI, 14.455 to 17.016 min).

Safety and hemodynamic data were reassuring within the limits of this small, narrowly defined cohort. No patient in either group developed hypotension, nausea and vomiting, shivering, or respiratory depression; bradycardia occurred in one patient per group (3.3%) and urinary retention in two per group (6.7%). Mean arterial pressure and heart rate both declined significantly over time relative to baseline, but the authors report that the changes stayed within clinically manageable ranges, with reductions of less than 20% from baseline. Sensory block onset was 4.8 ± 0.7 minutes in the dose group and 5.0 ± 0.7 minutes in the time group, with sensory block durations of roughly 150 minutes and motor block durations of roughly 130 to 132 minutes in both groups.

The reported ED50 is considerably higher than the 7.036 mg dose that a previous study by Wang and colleagues found for 0.5% hyperbaric ropivacaine in older patients undergoing hip arthroplasty. The authors attribute this to several differences: the earlier study assessed block only in the surgical extremity and targeted a T10 sensory level for the first hour of surgery rather than avoiding bilateral motor block; its patients averaged about 80 years of age versus around 60 in the present study, and advanced age is known to lower intrathecal dose requirements; and a substantial share of those earlier patients reported inadequate analgesia, whereas in the present study all procedures were completed under unilateral spinal anesthesia without epidural supplementation. The authors also note that their ED50 aligns with a prior finding that the dose needed to prevent motor block in the non-surgical leg, 11.13 mg of 0.4% hypobaric ropivacaine in older hip arthroplasty patients, exceeds the dose needed for conventional unilateral spinal anesthesia.

On positioning time, the authors place their ET50 of roughly 14 minutes against a variable literature: 10 minutes of lateral positioning with 11.25 mg of hyperbaric ropivacaine reduced the proportion of truly unilateral block after repositioning in one study, while longer times of 20 to 30 minutes have been reported to improve unilateral motor block selectivity at the cost of operating-room efficiency. Because hyperbaric solutions distribute by gravity, the density gradient between the glucose-containing injectate and cerebrospinal fluid drives the drug toward the dependent nerve roots, but this redistribution is not instantaneous, and insufficient positioning may allow contralateral spread after the patient is turned supine. The authors caution that the required duration may vary with dose, baricity, patient position, injection characteristics, and time-dependent redistribution within the cerebrospinal fluid.

The study carries explicit limitations. The findings apply primarily to patients with a body mass index of 18.5 to 23.9 kg·m−2, and the relationship between body mass index and dose or positioning requirements was not examined. The conventional Dixon up-and-down design primarily supports estimation of the 50% response level, so the ED5 and ET95 values are exploratory rather than clinically validated thresholds; the authors suggest that future work targeting a 95% probability of prevention should use a biased-coin sequential design. Because the included varicose vein procedures required limited muscle relaxation, applicability to operations needing greater relaxation remains uncertain, and baseline leg strength and functional recovery outcomes such as time to ambulation were not systematically assessed. Within those boundaries, the authors present the ED50 of 12.683 mg and the ET50 of 13.887 minutes as reference estimates for further investigation of dose and positioning strategies in unilateral spinal anesthesia, noting that intrathecal adjuvants such as dexmedetomidine, which have been shown to reduce the ED50 of hyperbaric ropivacaine, may offer another route to lowering dose requirements or shortening positioning time.

Subject of Research: Dose- and time-finding study of hyperbaric ropivacaine for unilateral spinal anesthesia in varicose vein surgery

Article Title: The median effective dose of hyperbaric ropivacaine and lateral decubitus time for unilateral spinal anesthesia in lower extremity varicose vein surgery: a dose- and time-finding study

Article References: Xu, J., Zhou, J., Chen, H., Lin, C., Xian, W., & Wang, F. (2026). The median effective dose of hyperbaric ropivacaine and lateral decubitus time for unilateral spinal anesthesia in lower extremity varicose vein surgery: a dose- and time-finding study. Frontiers in Pharmacology, 17, Article 1975353. https://doi.org/10.3389/fphar.2026.1975353

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1975353

Keywords: unilateral spinal anesthesia, hyperbaric ropivacaine, varicose vein surgery, motor block, ED50, lateral decubitus time, Dixon up-and-down design, probit regression, combined spinal-epidural anesthesia, regional anesthesia, anesthesiology, clinical trial