Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children.

BACKGROUND AND OBJECTIVES: The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr. METHODS: After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg(-1), was given over 4 min, followed immediately by an infusion of 2 mg mL(-1) ropivacaine 0.4 mg kg(-1) h(-1) for the next 24-72 h. RESULTS: Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L(-1) at 16-31 and 59-72 h, respectively) and alpha1-acid-glucoprotein (mean 13 and 25 micromol L(-1) at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L(-1) at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L(-1)). Apparent unbound clearance (mean 346, range 86-555 mL min(-1) kg(-1)) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine. CONCLUSION: Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg(-1) h(-1) in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.

Plasma levels of lidocaine and prilocaine after application of Oraqix, a new intrapocket anesthetic, in patients with advanced periodontitis.

BACKGROUND, AIMS: Oraqix, a new non-injection local anesthetic, lidocaine/prilocaine gel 5%, has been developed to provide pain relief in association with periodontal probing and scaling/root planing (SRP). The aim of this open study was to describe the plasma profiles of lidocaine and prilocaine following a single dose of Oraqix to patients with advanced periodontitis. METHODS: 10 patients with 18 to 28 teeth with pocket depths of at least 4 mm were included. Oraqix was applied in the pockets around all the teeth in the mouth by means of a blunt applicator. The total dose applied per patient was 0.9 to 3.5 g. Directly thereafter all the pockets were probed and 3 teeth subjected to SRP. The mouth was rinsed out with a glass of water 20-27 min after the application of the gel. Blood samples were collected before and up to 90 min after the start of application of Oraqix. RESULTS: Peak plasma concentrations of lidocaine (99-266 ng/ml) and prilocaine (46-118 ng/ml) occurred 20-40 min after the start of application. These levels were low compared to those reported to cause initial signs of CNS toxicity (5000-6000 ng/ml). Side-effects were few and mild local effects of short duration. DISCUSSION: In conclusion, there is a large safety margin with respect to systemic effects following the application of up to 3.5 g Oraqix in periodontal pockets.

Plasma concentrations of ropivacaine following a single-shot caudal block of 1, 2 or 3 mg/kg in children.

BACKGROUND: For documenting the properties of ropivacaine used for regional anaesthesia in children, the relationship between dose and resulting systemic exposure is essential. The aim of this pharmacokinetic part of a randomised, multicentre, double-blind study was to determine the free and total plasma levels of ropivacaine in children aged between 4 and 12 years following a single-shot caudal dose of 1, 2 or 3 mg/kg of ropivacaine for postoperative pain management. METHOD: Following induction of a standardised general anaesthetic (halothane; nitrous oxide: oxygen 60:40), a caudal block using 1 ml/kg ropivacaine in concentrations of 1, 2 or 3 mg/ml was performed in 43 ASA I children (body weight 12-25 kg) scheduled for elective inguinal surgery. Blood samples were collected prior to and 15, 30, 45, 60 and 240 min after placement of the caudal block for determination of total and free ropivacaine plasma concentrations. RESULTS: The peak plasma concentration of total ropivacaine, reached within 15-241 min after the block, increased in proportion to dose, with mean values at 0.27, 0.64 and 0.90 mg/l following 1, 2 and 3 mg/kg respectively. The peak plasma level of free ropivacaine also increased in a dose-proportional manner, with mean levels at 0.014, 0.030 and 0.042 mg/l. The highest individual peak plasma level of free ropivacaine was 0.070 mg/l, well below the threshold levels of CNS toxicity described in adults. No clinical signs of systemic toxicity were observed. CONCLUSION: Following single-shot caudal doses of 1-3 mg/kg in children up to 25 kg and aged between 4 and 12 years, plasma levels of free ropivacaine increase in proportion to dose and all were shown to be within safe limits.

Ropivacaine pharmacokinetics after caudal block in 1-8 year old children.

We studied the pharmacokinetics after caudal block of ropivacaine (2 mg ml-1, 1 ml kg-1) performed in 20 children aged 1-8 yr undergoing subumbilical surgery, in this open, non-comparative, multicentre study. Venous blood samples were collected up to 12-36 h. The mean (SD) peak plasma concentration, 0.47 (0.16) mg litre-1, was achieved after 12-249 min. The free fraction was 5% and the highest individual peak plasma concentration of free ropivacaine was 0.04 mg litre-1. Clearance was 7.4 (1.9) ml min-1 kg-1 and the terminal half-life 3.2 (0.8) h. Thus, the free plasma concentrations of ropivacaine were well below those associated with toxic symptoms in adults and the capacity to eliminate ropivacaine seems to be well developed in this age group. In this open study of 20 patients, ropivacaine was well tolerated and provided satisfactory postoperative pain relief without observable motor block.

Pharmacokinetics and analgesic effect of ropivacaine following ilioinguinal/iliohypogastric nerve block in children.

BACKGROUND: The aim was to investigate the efficacy, tolerance and pharmacokinetics of ropivavcaine when administered for ilioinguinal/iliohypogastric block in children. METHODS: We examined the pharmacokinetics and analgesic efficacy after ilioinguinal/iliohypogastric nerve block with 3 mg.kg-1 ropivacaine 5 mg.ml-1 in 22 children, aged 1-12 years, who were scheduled for inguinal surgery. Sixteen of 22 patients had a postoperative pain score < 4 (Objective Pain Scale). Nine children were given supplementary analgesics during the first six postoperative hours. RESULTS: The peak plasma concentration of total ropivacaine was 1.50 +/- 0.93 mg.l-1 (mean +/- SD) (range 0.64-4.77 mg.l-1) 15-64 min after the injection. The peak plasma concentration of free ropivacaine was 0.05 +/- 0.03 mg.l-1 (0.02-0.14 mg.l-1), which is well below the threshold for toxicity in adults. The terminal half-life was 2.0 +/- 0.7 h. No safety concerns or symptoms suggestive of systemic toxicity were observed. CONCLUSION: A dose of 3 mg.kg-1 of ropivacaine given as a single ilioinguinal/iliohypogastric nerve block in 1-12-year-old children provides satisfactory postoperative pain relief, and is well tolerated.

EMLA cream as a topical anesthetic for the repeated mechanical debridement of venous leg ulcers: a double-blind, placebo-controlled study.

BACKGROUND: A granulating surface is important for skin grafting and healing of leg ulcers. Mechanical debridement to remove necrotic tissue often must be stopped before completion because of pain. OBJECTIVE: Our purpose was to assess the effect of EMLA cream on the number of debridements required to obtain a clean ulcer and on pain during debridement and to determine its safety after repeated doses. METHODS: In this randomized double-blind, placebo-controlled study, 69 patients with venous leg ulcers received cream before debridement until a clean ulcer was obtained (or a maximum of 15 debridements). RESULTS: EMLA decreased the median number of debridements required for a clean ulcer (EMLA 11.5, placebo >15; P = .019) and decreased pain by 50% (P = .003). Plasma levels of lidocaine, prilocaine, and their main metabolites were low without any apparent accumulation. CONCLUSION: EMLA produces effective pain relief for the debridement of leg ulcers and shortens the time to a clean ulcer.