Plain articaine or prilocaine for spinal anaesthesia in day-case knee arthroscopy: a double-blind randomized trial.

BACKGROUND: Both prilocaine and articaine are short-acting local anaesthetics suited for spinal anaesthesia for day-case knee arthroscopy. Articaine is thought to have a faster onset and shorter duration of action than prilocaine, although no comparative study has been published in the anaesthetic literature. METHODS: In this prospective randomized double-blind study, spinal anaesthesia was performed in 72 ASA I-II patients undergoing knee arthroscopy with 50 mg of either plain prilocaine or plain articaine. The primary outcome variable was duration of motor block. Secondary outcomes were onset of sensory and motor blocks, maximum spread of the sensory block, time to spontaneous voiding, and side-effects. RESULTS: Time to full motor function recovery was shorter after articaine than prilocaine [mean (SD) 140 (33) vs 184 (46) min, respectively, P<0.001]. Time to spontaneous voiding was shorter after articaine than prilocaine [mean (SD) 184 (39) vs 227 (45) min, respectively, P<0.001]. One patient in the articaine group reported mild transient neurological symptoms (TNS) limited to the first postoperative day, but there were no significant differences in adverse effects between the groups. CONCLUSIONS: Spinal anaesthesia with plain articaine 50 mg resulted in a faster recovery of motor function and earlier spontaneous voiding compared with plain prilocaine 50 mg. Surgical anaesthesia was not different. The incidence of TNS was low.

Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age.

AIM: To investigate the pharmacokinetics and pharmacodynamics of single dose propacetamol in preterm and term infants on the first day of life. METHODS: Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41 weeks) infants received a single dose of propacetamol in the first 24 hours of life when they had minor, painful procedures or as additional treatment in infants receiving opioids. Blood samples were taken from an arterial line, and pain was evaluated by a multidimensional pain scale. Results were reported as mean (SD). Student's t and Wilcoxon tests were used to compare the groups. RESULTS: Thirty neonates were included, 10 of which were term infants. Serum half life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational age correlated with serum half life (r = -0.46). No effect of sex or administration of prenatal steroids was found on the pharmacokinetics of paracetamol. In neonates who only received propacetamol (n = 15), the level of analgesia seemed to be associated with the therapeutic (> 5 mg/l) level. CONCLUSIONS: A correlation was found between gestational age and the serum half life of propacetamol. The maturational trend of clearance and half life in preterm and term neonates is in line with data on the pharmacokinetics of propacetamol beyond the newborn period.

Acetaminophen in cerebrospinal fluid in children.

BACKGROUND: There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children--from neonates to adolescents--in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP. METHODS: Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30-40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models". RESULTS: Median (25-75th percentile) age and weight of the patients included in this study were 12 months (3-62 months) and 10.0 kg (5.8-20.0 kg). Median (25-75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25-75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95-210 min) and 133 min (33-202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l. CONCLUSION: Size rather than blood-brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.

[Clinical gene therapy: genes by prescription?]. / Klinische gentherapie: genen op recept?

Gene therapy is a medical intervention based on modification of the genetic material of living cells. This technique offers widespread possibilities in treating or preventing diseases. This applies to genetically determined diseases but also to diseases that occur later in life. Cells may be modified ex vivo for subsequent administration to patients, or may be altered in vivo by gene therapy given directly to the subject. To introduce the genetic material in cells, vectors are being used. Currently, most vectors are from viral origin. This requires special precautions when producing viral vectors. Gene therapy is apparently safe, when the proper indications and contra-indications are taken into account. Expectations regarding gene therapy are very high. However, more technological barriers are encountered than foreseen and therefore, the clinical success up to now is limited.

Analgesic efficacy of rectal versus oral acetaminophen in children after major craniofacial surgery.

BACKGROUND: Analgesic acetaminophen (INN, paracetamol) plasma concentrations after major surgery in neonates and infants have not yet been established in the literature. We therefore conducted a study in our intensive care unit. METHODS: Forty children, mean (standard deviation) age, 10.3 (2.3) months, received 20 mg/kg acetaminophen either orally (n = 20) or rectally (n = 20) every 6 hours after a rectal loading dose (40 mg/kg) during elective craniofacial correction. Blood samples were taken 1 hour before and 2 hours after administration of acetaminophen maintenance doses; pain scores were obtained every 3 hours. RESULTS: Acetaminophen plasma concentrations were higher in patients receiving rectal acetaminophen (mean area under the concentration-time curve [AUC], 171.2 mg x h/L) than in patients receiving oral acetaminophen (mean AUC, 111.9 mg x h/L). Pain scores were higher in patients receiving oral acetaminophen. However, after exclusion of the patients who vomited from the group receiving oral acetaminophen, acetaminophen plasma concentrations and pain scores did not differ between the groups. There was no relation between acetaminophen plasma concentrations and pain scores. Although 9 of all 40 patients (22.5%) did not reach the expected analgesic acetaminophen plasma concentrations of 10- to 20 mg/L, <7.5% of the visual analog scale pain scores exceeded 4 cm, which was considered as a cutoff point. CONCLUSION: These are the first data showing that the analgesic acetaminophen plasma concentration after major surgery in this age group does not always reach the 10 to 20 mg/L level. These data also show that, after a rectal loading dose of 40 mg/kg has been given during surgery, the best way of administering acetaminophen after craniofacial surgery is the rectal route.

Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine.

The suitability of tramadol suppositories for inclusion in our hospital formulary for the treatment of mild to moderate post-operative pain was evaluated. In an open randomized trial, rectal tramadol was compared with our standard treatment acetaminophen/codeine suppositories. We expected tramadol to be equally effective as our current standard but with fewer side effects. Forty patients were treated with either tramadol suppositories 100 mg 6 hourly (qds) or acetaminophen/codeine suppositories 1000/20 mg qds. Patients were comparable with regard to demographic data and type of surgery and anaesthesia. Post-operative pain was scored with the aid of a Visual Analogue Scale before each drug administration, at rest and during movement. Side effects, notably nausea and vomiting, were recorded by interviewing the patients and by inspecting the nursing report. There was no difference in pain scores between the two groups. The incidence of nausea and vomiting was significantly higher in the tramadol-treated (84%) than in the acetaminophen/codeine treated group (31%). The relative risk of experiencing an episode of nausea under treatment with tramadol was 2.7 (95% confidence interval: 1.3-5.3; P = 0.0001) as compared with acetaminophen/codeine. We conclude that for acute treatment of mild to moderate post-operative pain frequent nausea and vomiting makes tramadol suppositories less suitable than acetaminophen/codeine.