Long-term effect of oxycodone/naloxone on the management of postoperative pain after hysterectomy: a randomized prospective study.

BACKGROUND: The analgesic efficacy of oxycodone prolonged-release (PR) combined with naloxone PR (OXN) in postoperative pain management is recognized, however, few studies have examined the efficacy of OXN on pain relief and bowel function following hysterectomy. This study compared the effect of OXN vs. standard treatment for post-operative pain management and bowel function following hysterectomy. METHODS: This randomized prospective study included 83 women who underwent laparoscopic/laparotomic hysterectomy. General anesthesia was induced by propofol (1.5-2 mg/kg), fentanyl (50-100 µg) and rocuronium (0.6-1 mg/kg) and maintained with sevoflurane (MAC 0.8-1) and fentanyl (1-2 µg/kg). Intraoperative analgesia was performed with ketorolac (30 mg), paracetamol (1 g) and morphine (0.1 mg/kg). Postoperative analgesia in the control group (N.=41) included morphine (0.2-0.4 mg/kg/day), whereas the OXN (N.=42) group only received oxycodone (10 mg)/naloxone (5 mg) for the first 48 hours. As rescue analgesic, both groups received paracetamol (3 mg). Bowel Function Index (BFI) and pain numeric rating scales (NRS) were measured at day 0, 1, 2, 3, 5 and 7, whereas vital parameters, rescue medication and side effects were recorded for the first three days only. RESULTS: Bowel function indices were significantly improved in OXN-treated patients at all time points compared to morphine-treated patients. Mean static pain NRS was significantly decreased at day 2 and day 3 and dynamic pain NRS at day 3 in the OXN group. Side effects, rescue analgesic and antiemetics were more frequent in the control group. CONCLUSIONS: Improved pain control, bowel function and reduced side effects were observed with OXN compared to morphine in patients who underwent hysterectomy.

Minimally invasive fetal surgery for myelomeningocele: preliminary report from a single center.

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.

Intercellular adhesion molecule-1 mediates cellular cross-talk between parenchymal and immune cells after lipopolysaccharide neutralization.

The mechanisms by which parenchymal cells interact with immune cells, particularly after removal of LPS, remain unknown. Lung explants from rats, mice deficient in the TNF gene, or human lung epithelial A549 cells were treated with LPS and washed, before naive alveolar macrophages, bone marrow monocytes, or PBMC, respectively, were added to the cultures. When the immune cells were cocultured with LPS-challenged explants or A549 cells, TNF production was greatly enhanced. This was not affected by neutralization of LPS with polymyxin B. The LPS-induced increase in the expression of ICAM-1 on A549 cells correlated with TNF production by PBMC. The cellular cross talk leading to the TNF response was blunted by an anti-ICAM-1 Ab and an ICAM-1 antisense oligonucleotide. In A549 cells, a persistent decrease in the concentration of intracellular cAMP was associated with colocalization of LPS into Toll-like receptor 4 and the Golgi apparatus, resulting in increased ICAM-1 expression. Inhibition of LPS internalization by cytochalasin D or treatment with dibutyryl cAMP attenuated ICAM-1 expression and TNF production by PBMC. In conclusion, lung epithelial cells are not bystanders, but possess memory of LPS through the expression of ICAM-1 that interacts with and activates leukocytes. This may provide an explanation for the failure of anti-LPS therapies in sepsis trials.