Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California
Dates
study started
estimated completion
Principal Investigator
by Brian M Ilfeld, MD, MS
Photo of Brian M Ilfeld
Brian M Ilfeld

Description

Summary

This will be a randomized comparison of continuous local anesthetic infusion with patient controlled boluses (PCA) to patient-titratable automated boluses with patient controlled boluses (PCA) for popliteal-sciatic perineural catheters. The overall goal is to determine the relationship between method of local anesthetic administration (continuous with PCA vs. titratable intermittent dosing with PCA) for popliteal-sciatic perineural catheters and the resulting pain control. The investigators hypothesize that, compared with a traditional fixed, continuous basal infusion initiated prior to discharge, perineural local anesthetic administered with titratable automated boluses at a lower dose and a 5-hour delay following discharge will (1) provide at least noninferior analgesia during the period that both techniques are functioning; and, (2) will result in a longer overall duration of administration [dual primary end points].

Details

Specific Aim: to determine the relationship between method of local anesthetic administration (continuous with PCA vs. titratable intermittent dosing with PCA) for popliteal-sciatic perineural catheters and the resulting pain control. Hypothesis: The investigators hypothesize that, compared with a traditional fixed, continuous basal infusion initiated prior to discharge, perineural local anesthetic administered with titratable automated boluses at a lower dose and a 5-hour delay following discharge will (1) provide at least noninferior analgesia during the period that both techniques are functioning; and, (2) will result in a longer overall duration of administration [dual primary end points]. This will be a randomized, controlled investigation. Enrollment: Consenting adults undergoing painful foot and/or ankle surgery with a planned popliteal-sciatic perineural catheter insertion will be offered enrollment. Block placement: The nerve block site will be cleaned with chlorhexidine gluconate and isopropyl alcohol (ChloraPrep One-Step, Medi-Flex Hospital Products, Inc., Overland Park, KS, USA), and a clear, sterile, fenestrated drape applied. The ultrasound probe will be readied for use and placed to visualize the short-axis (cross-section) of the target nerve. A skin wheal will be raised at the catheter-placement needle's anticipated point of entry. An 8.9 cm, 17-gauge, insulated needle (FlexTip, Arrow International, Reading, PA, USA) will be used to place all perineural catheters. The catheter-placement 17G needle will be inserted through the skin wheal, advanced in-plane beneath the US transducer and directed toward the target nerve. Normal saline (1-2 mL) will be administered via the needle to open the space around the nerve. A flexible non-stimulating perineural catheter (FlexTip, Arrow International, Reading, PA, USA) will be inserted 2-3 cm past the needle tip. After catheter insertion, Ropivacaine 0.5% (20 mL) will be administered via the catheter under ultrasound visualization. Sensation in the tibial and peroneal nerve distributions will be checked for anesthetic effect up to 15 minutes following initial local anesthetic bolus. A "successful" regional block will be defined as sensory- and motor-block onset in all expected nerve distributions within the 15 minutes following the local anesthetic injection. A saphenous nerve block with ropivacaine 0.5% may or may not be provided, depending on the surgical procedure, per standard of care. Intraoperative: The initial local anesthetic bolus may provide complete surgical anesthesia for the procedure. Patients who desire a general anesthetic or experience a partial block that is not adequate for surgical anesthesia will receive a general anesthetic, per standard of care. Randomization: Subjects will be randomized to one of two treatment groups: (1) titratable automated intermittent bolus or (2) continuous infusion in a computer generated 1:1 ratio using opaque envelopes opened only after successful catheter insertion is documented within 30 minutes of the local anesthetic injection. Postoperative Procedures: Following completion of the procedure in the operating room, an infusion pump (Infutronix, Natick, Massachusetts) with a 500 mL ropivacaine 0.2% reservoir will be attached to the perineural catheter. For patients in the continuous infusion group, the pump will provide a 6 mL/h basal infusion and a 4 mL patient-controlled bolus with a 30-minute lockout (standard at UCSD). For patients in the titratable automated intermittent bolus group, the pump will provide an automatic 8 mL bolus once every 2 hours and have a 4 mL patient-controlled bolus with a 30 minute lockout. In addition, for those in the titratable automated intermittent bolus group, the infusion pump will be set in a "pause" mode that delays initiation of the automated bolus doses by 5 hours (this can be over-ridden by patients if they would like to initiate their perineural infusion earlier than 5 hours). Lastly, subjects in the titratable automated intermittent bolus group will be able to titrate the volume of their automated bolus up or down within the range of 1-16 mL. Per standard of care, the pump will not administer more than 20 mL during each hour (below the current institutional maximum). Prior to discharge, the functioning of the infusion pump will be explained, so that they understand that they should push the bolus button if they have pain. This is accurate regardless of which treatment group the patient is randomized to, ensuring that all subjects will receive adequate analgesia. Data Collection: Subjects will be contacted via phone for the 9 days following surgery to collect information regarding surgical pain (Numeric Rating Scale of 0 to 10, with "0" being no pain and "10" being the worst pain ever experienced), analgesic use, sleep disturbances, infusion side effects, and satisfaction with pain control. When 500 mL has been infused or on Day 8-whichever comes first-subjects will remove the catheter and place the pump in a pre-addressed and -stamped package for return [note that it is standard of care for patients to remove the catheters at home; but, listed as experimental here due to the timing of catheter removal which will be later than is standard of care due to the experimental local anesthetic administration protocol]. Data Acquisition. Data will be gathered from the patients' electronic medical record, by telephone follow-up, and from the memory of each infusion pump. Subjects will be contacted by phone for the 9 days following surgery. Data will be recorded on paper Case Report Forms, including: patient name, medical record number, age, sex, height, weight, surgical procedure, data of procedure, anesthesiology attending overseeing/placing catheter, randomization number, whether a femoral/saphenous block was placed, if the catheter was placed per protocol, if the block set up successfully, intraoperative fentanyl, morphine and dilaudid, and the time of infusion initiation. Statistics: This study will be powered for two primary end points: (1) the average pain level measured with the Numeric Rating Scale queried on postoperative day 1; and (2) the duration of treatment from when the infusion pump was initially turned on until the local anesthetic reservoir was exhausted [recorded by the infusion pump memory]. The dual hypotheses will be tested with a serial testing strategy, such that Hypothesis 2 will not be formally tested unless the conclusion of Hypothesis 1 is at least "noninferiority". Following the approach described in Althunian et al, noninferiority will be assessed by comparing the lower limit of the 95% confidence interval for the difference (CB minus AB) on the NRS (range: 0 to 10) to a pre-specified noninferiority margin of 1.7 NRS units. This will provide evidence that the analgesia provided by the novel automated boluses is no worse than 1.7 NRS units compared to CB. Baseline characteristics of the randomized groups will be summarized with means, standard deviations, and quartiles. Balance between groups will be assessed following the approach described by Schober, et al. Specifically, standardized differences will be calculated using Cohen's d whereby the difference in means or proportions is divided by the pooled standard deviation estimates. Any key variables (age, sex, height, weight, and BMI) with an absolute standardized difference >0.47 (based on Austin, 2009 with 1.96×√(2/n)=0.47) will be noted and included in a linear regression model to obtain an estimate of the treatment group differences adjusted for the imbalanced covariate(s). If residuals from the linear regression indicate violations of key assumptions (i.e. homoscedasticity or Guassian distribution), data transformations and/or alternative generalized linear models will be applied as appropriate. Secondary outcomes will also be analyzed by Wilcoxon-Mann-Whitney test, or linear models (or generalized linear models) as appropriate with covariates for any imbalanced covariates. No multiplicity adjustments will be applied for these analyses. End points will be analyzed for each day (e.g., opioid consumption on Day 2) as well as all days combined (e.g., cumulative opioid consumption Days 1-9). Sample size estimate: Power is simulated based on the distribution of pain measured with the Numeric Rating Scale (NRS) observed in the "Above bifurcation" group in Monahan, et al. Specifically, the investigators simulate NRS scores from a discrete distribution as depicted in Figure 2. This results in an expected interquartile range 1 to 4, and a median of 3 NRS units. The investigators simulated 1000 trials in which the two groups, n=35 per group, were assumed to follow the same discrete distribution, submitted each trial to a Wilcoxon-Mann-Whitney test, and derived 95% confidence intervals (Bauer 1972; Hothorn, et al. 2008). Out of the 1000 trials, 792 (79.2%) correctly resulted in a conclusion of non-inferiority; suggesting that the probability that the trial correctly concludes non-inferiority is about 80% when the groups follow exactly equivalent distributions. If the test for Hypothesis 1 concludes noninferiority, the investigators will test for a difference in overall duration of administration again using the Wilcoxon-Mann-Whitney test. Power is approximated by a two-sample t-test calculation. Assuming a standard deviation of SD=37 hours (corresponding to an interquartile range of 50 to 100 hours), the investigators expect that a sample size of n=35 provides 80% power to detect a mean group difference of 25 hours with a two-sided alpha of 5%. Total enrollment: 70 subjects plus 30 for misplaced catheters or subjects otherwise unable to be randomized; and subjects who withdraw. This allows for a possible total of 100 subjects.

Keywords

Pain, Acute Postoperative Trauma Injury Acute Pain Pain, Postoperative Ropivacaine Anesthetics, Local Anesthetics Continuous Infusion of ropivacaine 0.2% Titratable Automated Intermittent Boluses of ropivacaine 0.2% Continuous Infusion Titratable Automated Boluses

Eligibility

You can join if…

Open to people ages 18 years and up

  • patients undergoing painful foot and/or ankle surgery with a planned popliteal sciatic perineural catheter for postoperative analgesia

You CAN'T join if...

  • daily opioid use within the previous 4 weeks
  • clinical neuromuscular deficit of either the sciatic nerve and its branches and/or innervating muscles
  • morbid obesity [body mass index > 35 kg/m2]
  • surgery outside of the ipsilateral sciatic and saphenous nerve distributions [e.g., iliac crest bone graft]
  • pregnancy
  • incarceration

Location

  • UCSD Medical Center
    San Diego California 92103 United States

Lead Scientist at UCSD

  • Brian M Ilfeld, MD, MS
    Professor In Residence, Anesthesiology. Authored (or co-authored) 185 research publications.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Diego
ID
NCT05091905
Phase
Phase 4
Study Type
Interventional
Last Updated