Rectal Paracetamol Research Articles

Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia

We have reviewed the analgesic efficacies of rectal and parenteral paracetamol and tested the evidence for a possible additive analgesic effect of the combination of paracetamol with a non-steroidal anti-inflammatory drug (NSAID) in postoperative pain. Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia. Eight studies compared rectal paracetamol with placebo. One study of single-dose administration of rectal paracetamol 40-60 mg kg(-1) and three studies of repeat dosing with 14-20 mg kg(-1) showed significant analgesic efficacy, while studies of a single dose of 10-20 mg kg(-1) were negative. Ten studies compared parenteral paracetamol with placebo and eight studies showed improved pain relief with paracetamol. Of the nine studies comparing paracetamol with a combination of paracetamol and an NSAID, six studies showed improved pain relief for the combination while only two of the six studies comparing an NSAID with a combination of an NSAID and paracetamol showed improved pain relief for the combination. Considering the few studies available, evidence was found of a clinically relevant analgesic effect of rectal and parenteral paracetamol. Concurrent use of paracetamol and an NSAID was superior to paracetamol alone but no evidence was found of superior analgesic effect of the combination compared with the NSAID alone.

Serum paracetamol concentrations in adult volunteers following rectal administration

Paracetamol is usually given in adults at a dose of 10-20 mg kg(-1) orally or rectally. Work in children suggests that doses of 40 mg kg(-1) are needed to provide therapeutic concentrations when this drug is used by the rectal route. We have investigated the dose of rectal paracetamol needed to achieve serum concentrations within the accepted therapeutic range of 10-20 microg ml(-1) in adults. Ten healthy adult volunteers received increasing doses of rectal paracetamol (15, 25, 35, and 45 mg kg(-1)). Following suppository administration, serum paracetamol concentrations were measured half hourly to 4 h then hourly to 8 h. Sustained concentrations within our therapeutic range were achieved with 35 and 45 mg kg(-1). Maximum measured concentrations were 12.5 (10-16), 16.5 (14-20), and 20 (17.5-23) microg ml(-1), median (inter-quartile range) after 25, 35, and 45 mg kg(-1), respectively. We conclude that doses of 35-45 mg kg(-1) of rectal paracetamol are needed to achieve sustained therapeutic plasma concentrations in healthy adult volunteers.

Anesthetic management of a child with Rubinstein-Taybi syndrome for cervical dermoid cyst excision.

which are characteristics of this syndrome (Fig. 1). Thyroid ultrasonography showed a multilocular cystic 33 3 20mm mass anterior to the thyroid gland. There was no mass activity on thyroid scintigraphy. The total blood count and other laboratory test results were within normal ranges. No gastroesophageal reflux was observed on esophagogastrography. The right testis had not descended, and the left testis was retractile. The results of cranial computerized tomography and chromosomal analysis were normal. He had no cardiac defects. He was diagnosed as having the autosomal dominant mutagenic form of RTS. There was an uneventful history of operation and anesthesia for a midline neck mass diagnosed as a thyroglossal cyst that was performed at another center 1 year previously. On this occasion, the midline neck mass was above the previous one and was thought to be a recurrent thyroglossal cyst preoperatively. The patient’s height was 90cm (,3 percentile), and his weight was 14kg (3–10 percentiles). He fasted for 8h and was not premedicated before induction of anesthesia. His heart rate was 130 beats·min21 and his SpO2 was 99%. After preoxygenation, anesthesia was induced by 50% N2O/O2 mixture in sevoflurane via a face mask. After intravenous access had been obtained, 0.5mg kg21 of atracurium was injected, and endotracheal intubation was performed without difficulty with an uncuffed tube that had an internal diameter of 4.5mm. Anesthesia was maintained with 50% N2O/O2 mixture in sevoflurane. The neck mass was excised. At the end of anesthesia, spontaneous ventilation was promptly reestablished. After reversal of residual muscle paralysis with 0.5mg of neostigmine and 0.25mg of atropine, the endotracheal tube was removed. Rectal paracetamol was administered for postoperative pain. No significant problem was encountered during induction, maintenance, and extubation. The pathologic diagnosis of the mass was dermoid cyst.

Pharmacokinetics of rectal paracetamol after repeated dosing in children

Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P < 0.05) between saliva and serum concentrations. A one-compartment linear model with first-order elimination and absorption and lag-time was fitted to the data (ADAPT II). At steady state, the mean (SD) concentration was 15.2 (6.8) mg litre-1. Mean (SD) time to reach 90% of the steady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P < 0.05) with clearance and apparent volume of distribution. There was no evidence of accumulation leading to supratherapeutic concentrations during this dosing schedule for a mean of approximately 2-3 days.

Rectal paracetamol: 'safe' in neonates following trauma?

Rectal paracetamol: 'safe' in neonates following trauma?

Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants.

Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants. Perioperatively, 17 neonates and infants < or =160 days of age received one rectal paracetamol dose (mean 23.9 mg/kg (+/-4.2 mg/kg)). Blood samples were drawn at 60, 120, 180, 240, 300 and 360 min, according to the infants' weights. Plasma paracetamol concentrations were measured by a Colorometric Assay, Ectachem Clinical Chemistry Slides (Johnson & Johnson Clinical Diagsnostics). The plasma paracetamol concentrations were mainly below the therapeutic (i.e. antipyretic) range of 66-132 micromol/l and did not exceed 160 micromol/l in any infant. The mean maximum plasma concentration (Cmax) was 72.4 micromol/l (+/-33.5 micromol/l) and the time to Cmax, i.e. the mean Tmax was 102.4 min (_+59.1 min). The mean "apparent" terminal half-life (n=10) was 243.6 min (+/-114.1 min). The absorption of rectal paracetamol (mean dose 23.9 mg/kg, +/-4.2mg/kg) in young infants <160 days is variable and often prolonged and achieves mainly subtherapeutic plasma concentrations.

Rectal paracetamol has a significant morphine-sparing effect after hysterectomy

We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo-controlled, double-blind study. We studied 72 patients receiving patient-controlled analgesia (PCA) with i.v. morphine after a standardized anaesthetic, allocated randomly to receive rectal paracetamol 1.3 g, diclofenac 50 mg or placebo, after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy. Study violations excluded data from seven patients. Patient data, morphine doses during anaesthesia and recovery, and sedation and nausea scores were comparable. Mean morphine consumption during PCA was 35.0 (SD 20.4) mg, 32.7 (27.4) mg and 54.9 (28.3) mg in the paracetamol (n = 24), diclofenac (n = 20) and placebo (n = 21) groups, respectively (P < 0.05). Morphine sparing during PCA for paracetamol and diclofenac (36% vs 40% over 24 h) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol (P < 0.01) and placebo (P = 0.08). We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing.

Adrenaline markedly improves thoracic epidural analgesia produced by a low‐dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double‐blind, cross‐over study with and without adrenaline

Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.

Rectal paracetamol dosing regimens: determination by computer simulation.

A pharmacokinetic dynamic simulation model was used to predict rectal paracetamol dosing schedules which would maintain steady state plasma concentrations of 10-20 mg.l-1. These plasma concentrations of paracetamol are known to reduce fever. The conventional dosing schedule of 15 mg.kg-1 four hourly was unsatisfactory. Steady state concentrations of 8-12 mg.l-1 were only reached after 16 h. A loading dose of 50 mg.kg-1 followed by 30 mg.kg-1 six hourly achieved plasma concentrations of 9-18 mg.l-1. Paracetamol is a mild analgesic. A higher plasma paracetamol concentration of 25 mg.l-1 is known to give satisfactory analgesia to 60% of children after tonsillectomy. This concentration can be reached after a loading dose of 70 mg.kg-1 and a maintenance dose of 50 mg.kg-1 8 hourly. Doses above 150 mg.kg-1.day-1 have been reported to cause reversible liver toxicity after 2-8 days and should not be sustained.

Morphine consumption in patients receiving rectal paracetamol and diclofenac alone and in combination

Paracetamol and diclofenac have different mechanisms of action, and the combination may be more effective than each drug used alone in treating postoperative pain. In a double-blind, controlled design, we studied 60 patients undergoing elective abdominal gynaecological surgery, who received suppositories of paracetamol 1.5 g, diclofenac 100 mg or a combination of the two before the start of surgery. Patients received morphine in the intraoperative period, and cumulative morphine use from a patient-controlled analgesia system was recorded to measure the analgesic effect of the suppositories. Morphine consumption was greatest in the group that received paracetamol alone and lowest in the group given the combination (P < 0.01). There was no difference in the incidence of morphine-related side effects between the groups. We conclude that a diclofenac-paracetamol combination reduced the amount of morphine used compared with paracetamol alone.