ABSTRACT
BACKGROUND: There is increasing interest in the use of intranasal naloxone to reverse adverse opioid effects during management of procedural pain in children and in adults after overdose. There are limited data on the pharmacokinetics of intranasal naloxone so in this study we aimed to detail the pharmacokinetic profile of the commercially marketed injectable solution of naloxone 0.4 mg/ml when administered as an intranasal spray. METHODS: Twenty healthy volunteers received naloxone as an intranasal spray at a dose of 10 µg/kg. Venous blood sampling was carried out for 90 min after administration to determine the time profile of the plasma concentrations of using tandem mass spectrometry. Pharmacokinetic parameters were calculated using a one-compartment model. RESULTS: Median time to maximum naloxone concentration (Tmax) was 14.5 (95% CI: 9.0-16.5) min, mean maximum naloxone concentration (Cmax) was 1.09 ± 0.56 ng/ml and mean AUC0-90 min was 37.1 ± 15.0 ng*min/ml. Elimination half-life estimated from the median concentration data was 28.2 min. CONCLUSION: Our results show a faster uptake of intranasal naloxone to maximum concentration compared with previous studies although with a marked variation in maximum concentration. The findings are consistent with our clinical experience of the time profile for reversing the effects of sufentanil sedation in children.
Subject(s)
Naloxone/administration & dosage , Naloxone/pharmacokinetics , Narcotic Antagonists/administration & dosage , Narcotic Antagonists/pharmacokinetics , Administration, Intranasal , Adult , Area Under Curve , Chromatography, High Pressure Liquid , Cross-Over Studies , Female , Half-Life , Healthy Volunteers , Humans , Hypnotics and Sedatives/antagonists & inhibitors , Male , Middle Aged , Naloxone/adverse effects , Narcotic Antagonists/adverse effects , Nasal Sprays , Sufentanil/antagonists & inhibitors , Tandem Mass Spectrometry , Young AdultABSTRACT
For surgery on lumbar disks by the posterior route, patients are placed either on a Wilson frame or in genupectoral position. The aim of the prospective study was to record and describe the haemodynamic changes resulting from the patients' position. After written informed consent had been received, 80 neurosurgical patients undergoing lumbar disk surgery were randomly divided into two groups; group I--Wilson frame, group II--genupectoral position. In each group, 20 patients received total intravenous anaesthesia (Alfentanil or Remifentanil, Propofol) and 20 balanced anaesthesia with Isoflurane and Alfentanil or Remifentanil. Haemodynamic parameters (mean arterial pressure--MAP and heart rate--HR) were recorded automatically at three measuring times (MT): firstly, after induction of anaesthesia; secondly, before re-direction; thirdly, after re-direction on the Wilson frame or in the genupectoral position. Induction of anaesthesia did not lead to a significant decrease in MAP (MT 1: 92.5 +/- 15.2 mmHg, MT 2: 89 +/- 13.4 mmHg, n = 80). In group I (n = 40), no significant changes were observed in MAP and HR at MT 3 (p = 0.882, p = 0.051). In comparison to group I, the genupectoral position was associated with significant drops in MAP and HR. The genupectoral position caused a significant decrease in MAP (p < 0.001) and HR (p = 0.016) at MT 3. Our data suggest that body weight or body mass index do not necessarily lead to a preference for one of the two possible positions of the patient. Complications resulting from haemodynamic changes were not seen in either group. We recommend the Wilson frame for neurosurgical lumbar disk surgery in cases of cardiovascular or cerebrovascular disorders. The adaptive capacities in the genupectoral position as a result of the modifying distribution of blood volume are limited in these patients. Furthermore, the dose-dependent effects of different anaesthetics on haemodynamic parameters in these prone positions should be explored.
