Wound Infusion of 0.35% Levobupivacaine Reduces Mechanical Secondary Hyperalgesia and Opioid Consumption After Cesarean Delivery: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: Some patients still report moderate-to-severe postoperative pain after cesarean delivery. Local anesthetic wound infusion improves acute pain and might act on peripheral and central sensitization mechanisms; however, no studies have proved this hypothesis. We evaluated the potential benefits of continuous wound infusion of levobupivacaine after cesarean delivery on secondary hyperalgesia (primary end point) and primary hyperalgesia, pain relief, persistent pain, and inflammatory and metabolic stress response. METHODS: Healthy women scheduled for elective cesarean delivery participated in this prospective, randomized, triple-blind, placebo-controlled trial (NCT01458431). All patients received spinal anesthesia with 0.5% hyperbaric bupivacaine with fentanyl and a multiholed wound catheter placed under the fascia. Women were randomized to receive continuous wound infusion (0.35% levobupivacaine 7 mL/h for 48 hours; group L) or an equal volume of saline (group S). Secondary hyperalgesia to punctate mechanical stimuli was evaluated using dynamic tests, and primary hyperalgesia was evaluated using an electronic von Frey anesthesiometer; both were assessed at 24, 48, and 72 hours. The following variables were collected: intensity of postoperative parietal and visceral pain at rest and on movement rated on a visual analog scale >72 hours, time to first bolus of patient-controlled analgesia (PCA), cumulative dose of rescue morphine (PCA) and acetaminophen, ability to sleep and sleep quality, and patient satisfaction. Persistent postoperative pain was evaluated during a telephone interview at 1, 3, 6, and 12 months after surgery. C-reactive protein, acid glycoprotein, preprandial glucose, insulin, cortisol, prolactin, growth hormone, and interleukin-6 were measured before cesarean delivery and at 8, 24, and 48 hours. Adverse events and patient outcomes were recorded. RESULTS: Seventy women were included. In group L, the area of secondary hyperalgesia was significantly reduced (43.4 [18.5-80] vs 68.4 [39.0-136] cm2 and 45.1 [0.9-89.8] vs 67.3 [31.3-175] cm2 at 24 and 48 hours, respectively; group:time interaction P value < .001), the mechanical pain threshold was significantly higher at 24 hours (633 [441-802] vs 417 [300-572] g.mm-2; P = .001), and morphine consumption was significantly lower at 24 hours (4 [2-11] vs 11[6-23]; P = .003) compared with group S. Levobupivacaine had no effect on persistent postoperative pain at 1, 3, 6, and 12 months. Plasma insulin levels in the immediate postoperative period and at 8, 24, and 48 hours were significantly lower in group L (P < .001). There were no significant differences in other biochemical parameters of inflammatory and endocrine-metabolic response. CONCLUSIONS: Levobupivacaine wound infusion provides adequate analgesia and might be an effective antihyperalgesic adjunct.

Peritoneal total protein transport assessed from peritoneal equilibration tests using different dialysate glucose concentrations.

BACKGROUND: The peritoneal equilibration test (PET) permits assessment of peritoneal protein transport, but this potential marker of outcome in peritoneal dialysis (PD) patients lacks adequate standardization. ♢ OBJECTIVES: To assess various approaches for estimation of peritoneal protein transport in PD patients during 2.27% and 3.86% glucose-based PETs, and to uncover the demographic, clinical, and biochemical correlates of this phenomenon. ♢ PATIENTS AND METHODS: We studied 90 PD patients who underwent 2.27% and 3.86% PETs in random order, and we used multivariate analysis to compare assessments of peritoneal protein transport in both tests, searching for correlations between D240' - D0' protein concentration (PETΔPConc), total peritoneal protein excretion (PET-PPE), or total protein clearance (PET-PC) on the one hand (the main study variables), and PET-derived markers of peritoneal function and selected demographic, clinical, and biochemical variables on the other. ♢ RESULTS: The PETΔPConc was higher during the 2.27% PET (mean: 45.2 mg/dL vs 37.0 mg/dL for the 3.86% test; p = 0.003); the PET-PPE and PET-PC were comparable (1121.8 mg vs 1168.9 mg, p = 0.52, and 17.1 mL vs 17.8 mL, p = 0.66, respectively). All three variables sustained a significant, yet moderate correlation (all r² values < 0.30) with the 24-hour PPE rate. Multivariate analysis identified dialysate-to-plasma ratio (D/P240') of creatinine, end-to-initial dialysate ratio (D240'/D0') of glucose, current daily peritoneal glucose load, ultrafiltration during PET, systolic blood pressure, and previous cardiovascular events (3.86% test only) as independent predictors of protein transport during PET. ♢ CONCLUSIONS: Either PET-PPE or PET-PC seems preferable to PETΔPConc for characterization of peritoneal protein transport. Small-solute transport characteristics, ultrafiltration, and current peritoneal glucose load sustain independent correlations with peritoneal protein transport. The latter variable shows also a moderate association with markers of cardiovascular disease in PD patients.

One example on how colloidal nano- and microparticles could contribute to medicine.

Nanomedicine, nowadays, is a popular keyword in the media, although everyone seems to associate it with different visions, hopes and even fears. This article gives a perspective from two sides. From the point of view of a materials scientist, it will be pointed out what new materials will be possible, how they will be designed and which properties they could offer for diagnosis and treatment. From the point of view of a medical doctor, it will be pointed out which properties are actually desired and what materials are hoped for practical applications. The two different points of view indicate that, although sophisticated materials with advanced novel properties will be available in the future, they do not automatically match the requirements and demands of clinicians. The discussion is centerd around one example, multifunctional polyelectrolyte capsules, which might act as a 'nanosubmarine' for in vivo sensing and delivery, which is used to highlight promising interfaces between both disciplines.