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van CCT (UK)

van CCT (UK)

Study to describe the processing of ropivacaine in the body when injected in the knee for pain treatment in total knee replacement surgery

- candidate number19261
- NTR NumberNTR4796
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR7-aug-2014
- Secondary IDs620 NL50074.048.14
- Public TitleStudy to describe the processing of ropivacaine in the body when injected in the knee for pain treatment in total knee replacement surgery
- Scientific TitlePharmacokinetic profile of ropivacaine after periarticular local infiltration analgesia for primary knee arthroplasty
- hypothesisThe objective of this study is to describe a pharmacokinetic profile of total and unbound plasma concentrations ropivacaine, when used for local infiltration analgesia in total knee arthroplasty
- Healt Condition(s) or Problem(s) studiedTotal knee arthroplasty, Total knee arthroplasty
- Inclusion criteria- age 50-80 years
- ASA physical Health Classification I-II
- Body Mass Index (BMI) <40
- Patient planned for a primary unilateral posterior stabilized tri-compartmental cemented total knee replacement under unilateral spinal anesthesia with 2 mL hyperbaric bupivacaine
- Scheduled for fast track protocol TKA
- Haemoglobin (Hb) concentration > 7.5 mMol/L
- Written informed consent
- Exclusion criteria- Placement of a surgical drain
- Contra-indications for spinal anesthesia
- Known hypersensitivity to amide-type local anesthetics
- Hepatic or renal insufficiency
- Use of fluvoxamine, ciprofloxacin, ketoconazole, erythromycin, clarithromycin, itraconazole or rifampicin because of their effect on ropivacaine clearance
- Any other reason which in the opinion of the investigator makes the patient unsuitable for participation in the study
- mec approval receivedno
- multicenter trialno
- randomisedno
- group[default]
- TypeSingle arm
- Studytypeintervention
- planned startdate 1-nov-2014
- planned closingdate1-mei-2015
- Target number of participants20
- InterventionsPatients will receive a total knee replacement under spinal anesthesia and Local Infiltration Analgesia (LIA) of the knee with 200 mL ropivacaine 0.2% and epinephrine.
- Primary outcomeMean total and unbound maximum serum concentration of ropivacaine (Cmax) and mean time to total and unbound maximum serum concentration of ropivacaine (Tmax)
- Secondary outcomeAge, weight, height, gender, co-medication, complications and signs of systemic toxicity will be recorded.
- TimepointsA venous blood sample of 2-5 mL will be taken by the investigator before surgery from a PIVC before any i.v.fluid or i.v. medication is administered to the patient. During surgery a second PIVC will be placed in the contralateral arm and venous blood samples will be drawn from this catheter at 20, 40, 60, 90, 120, 240 and 360 minutes after release of the tourniquet. A last sample will be taken at 24 hours after release of the tourniquet.
- Trial web site
- statusplanned
- Sponsor/Initiator Sint Maartenskliniek Nijmegen
- Funding
(Source(s) of Monetary or Material Support)
Sint Maartenskliniek Nijmegen
- Publications
- Brief summaryKnee osteoarthritis is a leading cause of disability in our ageing society. Total knee arthroplasty (TKA) has been shown to be an effective treatment in reducing pain and improving function and quality of life in individuals suffering from severe knee osteoarthritis. For an optimal and fast recovery after TKA, a fast track rehabilitation protocol has been developed. Fast track surgery results in quicker functional recovery, reduced morbidity, decreased length of convalescence, increased satisfaction and ľ as a secondary gain ľ reduced hospital costs. Finding the most appropriate analgesic technique for fast track TKA is challenging: the patient needs to be pain free to mobilize for physical therapy, while side effects of the pain treatment like drowsiness (opioids) and impaired motor function (femoral nerve block) impede the fast track protocol. Therefore, a technique for the control of pain following knee and hip surgery, to allow virtually immediate mobilization and earlier discharge from the hospital called ôlocal infiltration analgesiaö (LIA) has been developed. For the LIA a relatively high dose long acting local anesthestic, ropivacaine, is injected in the soft tissue surrounding the knee and the subcutis around the incision. Ropivacaine is slowly absorbed into the circulation from the injection site. Epinephrine is added to the ropivaca´ne injected in the soft tissue to decrease absorption speed and lower peak plasma concentrations by inducing vasoconstriction. A potential hazard of the LIA technique is the relatively high dose of local anesthetic used, increasing the risk of LAST (local anesthestic systemic toxicity). Usually a dose of 400 mg ropivaca´ne is used for LIA, which is in most cases above the recommended maximum dose of 3-4 mg/kg. Nevertheless, in the past few years thousands of patients have been undergoing LIA for knee surgery with high doses of ropivaca´ne, and only one case of LAST after LIA has been described. In the plasma, approximately 95% of the ropivaca´ne is bound to α1-glycoprotein [ref]. approximately 5% of the total plasma concentration of ropivaca´ne is the free, unionized form. The unbound ropivaca´ne interacts with receptors inducing its pharmacological properties. When the free, unbound ropivaca´ne concentration exceeds the toxic threshold in the central nervous system (CNS) or heart, symptoms of toxicity (LAST) occur. Typical CNS toxicity symptoms are perioral numbness, tinnitus and visual disturbances. More severe LAST symptoms of CNS toxicity are convulsions, coma and respiratory arrest. In ropivacaine induced LAST, cardiac toxicity symptoms may be mild or even absent, but when present they range from rhythm disturbances to circulatory arrest due to cardiac arrest. Although LIA with ropivacaine is frequently applied, little is known about the pharmacokinetic profile of ropivaca´ne applied for LIA of the knee. Knowledge of the pharmacokinetic parameters will give more insight in the onset (Tmax), duration (halve live) and extent (Cmax) of ropivacaine concentrations. Knowledge of the Tmax (time when highest plasma concentration is reached) can provide more insight to the time frame in which the patient is at risk of LAST and should be monitored. Cmax of ropivaca´ne for LIA gives insight in the range to toxic concentrations. Knudsen et al. administered ropivaca´ne intravenously in healthy volunteers and found that symptoms of toxicity occurred at arterial plasma concentrations of 4.3 mg/L for total and 0.56 mg/L for unbound ropivaca´ne concentrations. It is unclear whether this Ĺtoxic concentrationĺ of ropivaca´ne can also be applied to a situation where ropivaca´ne is injected in soft tissue (LIA) instead of injected intravenously. Serum concentrations of ropivaca´ne rise much slower in LIA, than when injected intravenously as did Knudsen et al., because of the slow drug uptake from the tissue site into the blood stream. Even so, the study of Knudsen et al. is the only study investigating toxic concentrations of ropivaca´ne in humans and therefore, it is generally accepted that serum concentrations of ropivaca´ne should remain below 4.3 mg/L for total and 0.56 mg/L for unbound ropivaca´ne.
The primary objective of this study is to describe a pharmacokinetic profile of bound and unbound plasma concentrations of ropivaca´ne, when used in the LIA technique for the knee. Especially describing the Cmax and Tmax gives arguments for dosage of ropivaca´ne when used for LIA and for monitoring time of patients after surgery in everyday medical practice.
- Main changes (audit trail)
- RECORD7-aug-2014 - 15-okt-2014

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