Laparoscopic surgery technology continues to advance. However, much less attention has been focused on how alteration of the laparoscopic surgical environment might improve clinical outcomes. We conducted a randomized, 2 × 2 factorial trial to evaluate whether low intraperitoneal pressure (IPP) (8 mmHg) and/or warmed, humidified CO2 (WH) gas are better for minimizing the adverse impact of a CO2 pneumoperitoneum on the peritoneal environment during laparoscopic surgery and for improving clinical outcomes compared to the standard IPP (12 mmHg) and/or cool and dry CO2 (CD) gas. Herein we show that low IPP and WH gas may decrease inflammation in the laparoscopic surgical environment, resulting in better clinical outcomes. Low IPP and/or WH gas significantly lowered expression of inflammation-related genes in peritoneal tissues compared to the standard IPP and/or CD gas. The odds ratios of a visual analogue scale (VAS) pain score >30 in the ward was 0.18 (95% CI: 0.06, 0.52) at 12 hours and 0.06 (95% CI: 0.01, 0.26) at 24 hours in the low IPP group versus the standard IPP group, and 0.16 (95% CI: 0.05, 0.49) at 0 hours and 0.29 (95% CI: 0.10, 0.79) at 12 hours in the WH gas group versus the CD gas group.
AIMSNefopam is a nonmorphinic central analgesic, for which no recommendation exists concerning adaptation of regimen in aged patients with or without renal impairment. The objective was to describe the pharmacology of nefopam in aged patients to obtain guidelines for practical use.
METHODSElderly patients (n = 48), 65-99 years old, with severe or moderate renal impairment or with normal renal function, were recruited. Nefopam (20 mg) was administered as a 30 min infusion postoperatively. Simultaneously, a 1 min intravenous infusion of iohexol was performed, in order to calculate the glomerular filtration rate. Blood samples were drawn to determine nefopam, desmethyl-nefopam and iohexol plasma concentrations. Nefopam and desmethyl-nefopam concentrations were analysed using a nonlinear mixed-effects modelling approach with Monolix version 4.1.3. The association between pharmacokinetic parameters and treatment response was assessed using logistic regression.
RESULTSA two-compartment open model was selected to describe the pharmacokinetics of nefopam. The typical population estimates (between-subject variability) for clearance, volume of distribution, intercompartmental clearance and peripheral volume were, respectively, 17.3 l h −1 (53.2%), 114 l (121%), 80.7 l h −1 (79%) and 208 l (63.6%). Morphine requirement was related to exposure of nefopam. Tachycardia and postoperative nausea and vomiting were best associated with maximal concentration and the rate of increase in nefopam plasma concentration.
CONCLUSIONSWe identified the nefopam pharmacokinetic predictors for morphine requirement and side-effects, such as tachycardia and postoperative nausea and vomiting. In order to maintain morphine sparing and decrease side-effects following a single dose of nefopam (20 mg), simulations suggest an infusion time of >45 min in elderly patients with or without renal impairment.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Nefopam is a centrally acting non-opioid analgesic indicated for treatment of postoperative pain after abdominal, urological or orthopaedic surgery, either alone or in combination with other drugs.• There is limited knowledge about nefopam pharmacology in the elderly. This is a challenging patient group to study.
WHAT THIS STUDY ADDS• This study describes nefopam pharmacology in the elderly to propose guidelines for practical use. Nefopam pharmacokinetic predictors of morphine requirement and side effects were determined.• A single dose of nefopam (20 mg) should be infused over a period >45 min in aged patients with or without renal impairment.
Comme toute intervention chirurgicale, la césa-rienne nécessite la réalisation d'une anesthésie et l'application de sa réglementation. L'anesthésie locorégionale est la technique de référence pour les situations non urgentes et semi-urgentes et comporte la rachianesthésie, la rachianesthésie avec péridurale combinée et l'anesthésie péridurale. L'anesthésie générale, pourvoyeuse d'une forte morbimortalité maternelle, reste réservée aux situations bien particulières de la césarienne en urgence et aux contre-indications de l'anesthésie locorégionale.Mots clés Césarienne · Anesthésie générale · Rachianesthésie · Rachianesthésie avec péridurale combinée · Anesthésie péridurale Abstract As for any surgical procedure, caesarean delivery requires anaesthesia and the application of related regulations. Regional anaesthesia is the reference technique for elective or semi urgent caesarean delivery and includes spinal anaesthesia, combined spinal epidural anaesthesia and epidural anaesthesia. General anaesthesia may be associated with severe maternal morbidity and mortality and is mainly used for emergency caesarean delivery or when regional anaesthesia is contra-indicated.
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