The measurement of esophageal pressure during maximal sniffs (sniff Pes) has been shown useful to assess inspiratory muscle strength. The aim of this study was to validate a noninvasive method for estimating sniff Pes. The sniff nasal inspiratory pressure (SNIP) was measured through a plug occluding one nostril during sniffs performed through the contralateral nostril. Sniff Pes was simultaneously measured with an esophageal balloon. Ten normal subjects performed 338 sniffs of variable intensity. The correlation coefficient of SNIP and sniff Pes was 0.99 +/- 0.01 (p < 0.001). The ratio SNIP/sniff Pes was 0.91 (range, 0.82 to 0.99) and the mean difference between the two measures (SNIP - sniff Pes) was -4.56 cm H2O (-1.2 to -8.6 cm H2O). Twelve patients with neuromuscular or skeletal disorders performed 181 maximal sniffs. The correlation coefficient of SNIP and sniff Pes was 0.96 +/- 0.04 (p < 0.001). The ratio SNIP/sniff Pes was 0.93 (0.77 to 1.07) and the mean difference (SNIP - sniff Pes) was -4.66 cm H2O (+0.47 to -14.26 cm H2O). Nasal mucosal congestion was induced by nebulization of increasing doses of histamine in four normal subjects. The ratio SNIP/sniff Pes was 0.93 (0.72 to 1.02) when nasal peak flow was > 100 L/min, and 0.49 (0.36 to 0.57 L/min) when nasal peak flow fell below 100 L/min. We conclude that SNIP provides a reliable and noninvasive estimation of sniff Pes in normal subjects and in patients with neuromuscular or skeletal disorders. The validity of this method may by impaired by severe nasal congestion.

In a geriatric population, age, the decrease of maximum inspiratory pressure and PIF as well as cognitive functions, limit the use of dry powder inhalers.

No abstract

AIMSThe aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. METHODSThis work is based on a single-centre, double-blinded, randomized, placebocontrolled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. RESULTSThe free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. CONCLUSIONSAlthough large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery. WHAT THIS STUDY ADDS• The free ropivacaine fraction is low after liver resection surgery (<2%).• The size of the liver resection affects the free ropivacaine clearance.• The pharmacokinetics of free and total ropivacaine could be analysed effectively even without α 1 -acid glycoprotein measurements. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Ropivacaine is highly bound to plasma proteins (α 1 -acid glycoprotein).• Ropivacaine is mainly metabolized by the liver.• Liver resection affects the protein binding and metabolism of ropivacaine.

Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.

Pain in cancer therapy is a common condition and there is a need for new options in therapeutic management. While phytochemicals have been proposed as one pain management solution, knowledge of their utility is limited. The objective of this study was to perform a systematic review of the biomedical literature for the use of phytochemicals for management of cancer therapy pain in human subjects. Of an initial database search of 1,603 abstracts, 32 full-text articles were eligible for further assessment. Only 7 of these articles met all inclusion criteria for this systematic review. The average relative risk of phytochemical versus control was 1.03 [95% CI 0.59 to 2.06]. In other words (although not statistically significant), patients treated with phytochemicals were slightly more likely than patients treated with control to obtain successful management of pain in cancer therapy. We identified a lack of quality research literature on this subject and thus were unable to demonstrate a clear therapeutic benefit for either general or specific use of phytochemicals in the management of cancer pain. This lack of data is especially apparent for psychotropic phytochemicals, such as the Cannabis plant (marijuana). Additional implications of our findings are also explored.

No abstract

No abstract