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Background: Spontaneous breathing during mechanical ventilation improves gas exchange by redistribution of ventilation to dependent lung regions. Neurally adjusted ventilatory assist (NAVA) supports spontaneous breathing in proportion to the electrical activity of the diaphragm (EAdi). NAVA has never been used in the operating room and no studies have systematically addressed the influence of different anaesthetic drugs on EAdi.Objectives: The aim of this study was to test the feasibility of NAVA under sedation and anaesthesia with two commonly used anaesthetics, sevoflurane and propofol, with and without remifentanil, and to study their effects on EAdi and breathing mechanics.Design: A crossover study with factorial design of NAVA during sedation and anaesthesia in pigs.Setting: University basic science laboratory in Uppsala, Sweden, from March 2009 to February 2011.Animals: Nine juvenile pigs were used for the experiment.Interventions: The lungs were ventilated using NAVA while the animals were sedated and anaesthetised with continuous low-dose ketamine combined with sevoflurane and propofol, with and without remifentanil.Main Outcome Measures: During the last 5  min of each study period (total eight steps) EAdi, breathing pattern, blood gas analysis, neuromechanical efficiency (NME) and neuroventilatory efficiency (NVE) during NAVA were determined.Results: EAdi was preserved and normoventilation was reached with both sevoflurane and propofol during sedation as well as anaesthesia. Tidal volume (Vt) was significantly lower with sevoflurane anaesthesia than with propofol. NME was significantly higher with sevoflurane than with propofol during anaesthesia with and without remifentanil. NVE was significantly higher with sevoflurane than with propofol during sedation and anaesthesia.Conclusion: NAVA is feasible during ketamine-propofol and ketamine-sevoflurane anaesthesia in pigs. Sevoflurane promotes lower Vt, and affects NME and NVE less than propofol. Our data warrant studies of NAVA in humans undergoing anaesthesia. [ABSTRACT FROM AUTHOR]

Tumors are considered to be possible targets of immunotherapy using stimulated and expanded cytotoxic T-lymphocytes (CTL). It is important to consider the drug-induced effects when chemotherapeutic regimens and CTL-mediated immunotherapy is planned to be used in parallel. In this study, we characterized the effect of 29 frequently used chemotherapeutic agents on the cytotoxic activity of autologous and allogeneic CTLs. We found that treatment of CTLs with the following drugs: docetaxel, vincristine, chlorambucil, mitomycin C, oxaliplatin, doxorubicin, and bleomycin effectively inhibited CTL-mediated killing, without affecting their viability. On the other hand, the following drugs enhanced or permitted efficient CTL-mediated killing in vitro at concentrations comparable with the maximally achieved therapeutic concentration in vivo in humans: daunorubicin, prednisolone, vinorelbine, cisplatin, methotrexate, hydroxyurea, cytarabine, cyclophosphamide, topotecan, epirubicin, fluorouracil, carboplatin, asparaginase, 6-mercaptopurine, and bortezomib. Our results could potentially be used in the future to design new CTL-based adjuvant immunotherapy protocols.

Purpose of Review: The aim of this review is to summarize the use of clonidine for paediatric premedication and to make a comparison with benzodiazepines. A routine clonidine premedication protocol is also presented., Recent Findings: In the US 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug. The number of trials that compare midazolam with active controls are few and this premedicant is not adequately validated. Clonidine is still used as premedication in a small number of centres but the literature on paediatric use of clonidine is steadily growing. A recent review article has concluded that the use of clonidine does enhance the quality of perioperative management in infants and children and more recent publications support the use of clonidine for premedication. Its effect on the circulation is mild but routine atropine administration is recommended. Contraindications to the use of clonidine are few. Apart from a general overview on the effects of clonidine this article will also summarise the published trials that have compared clonidine with benzodiazepines for premedication in children., Summary: Midazolam the most commonly used drug for paediatric premedication worldwide. Despite having a number of beneficial effects it is far from an ideal premedicant, especially concerning its effect on cognition/amnesia, confusion and long-term behavioural disturbances. Clonidine lacks the majority of the negative effects associated with midazolam and is associated with a number of beneficial perioperative effects. Our clinical experience of replacing midazolam with clonidine as premedicant in children, including also outpatients, has been favourable.

In this prospective, randomized, observer-blinded clinical trial, we compared the incidence of unwanted lower extremity motor blockade and the analgesic efficacy between small-dose (0.125%; 0.2 mg x kg(-1) x h(-1)) postoperative epidural infusions of bupivacaine (Group B; n = 28), levobupivacaine (Group L; n = 27), and ropivacaine (Group R; n = 26) in children after hypospadias repair. Motor blockade and pain were assessed at predetermined time points during 48 h by using a modified Bromage scale and the Children's and Infant's Postoperative Pain Scale (CHIPPS). Postoperative analgesia was almost identical in all three study groups (CHIPPS range, 0-3), with no need for the administration of supplemental analgesia in any patient. However, significantly more patients in Group B (n = 6; P = 0.03) displayed signs of unwanted motor blockade during the observation period compared with Group L (n = 0) and Group R (n = 0). In conclusion, significantly less unwanted motor blockade was associated with postoperative epidural infusions of 0.125% levobupivacaine or ropivacaine in children after hypospadias repair as compared with a similar infusion of bupivacaine. However, no difference with regard to postoperative analgesia could be detected among the three different local anesthetics studied.

Pharmacokinetics of dexamphetamine was studied in 26 patients with cerebral infarct, aged 37 to 84 years. Capsules were administered orally twice daily (at 8 am and 12 am) in three doses (2.5 mg, 5 mg, and 10 mg) for 5 consecutive days (day 1 to day 5). Blood samples were collected immediately before and 1, 2, 3, 4, 5, 6, 7, 8, and 9 hours after first administration on day 1 and before, and 4 and 8 hours after administration on days 2 through 5. The dose normalized area under the plasma concentration time curve, AUC/mg/kg, was only correlated with s-creatinine (P = 0.013) but not with age, sex, body mass index, neurologic prognosis, or dose (mg/kg), as established by multiple stepwise linear regression. The median terminal half life time was 14.3 hours (inter quartile range, IQR: 11.9-6.9), 13.1 (IQR: 10.8-15.9) and 14.0 (IQR: 7.4-16.4) in the 2.5 mg, 5 mg, and 10 mg groups, respectively. The median maximal plasma concentration (Cmax) was 6.6 ng/mL (IQR: 5.1-7.0), 11.6 (IQR: 7.8-12.8), and 16.9 (IQR: 14.9-20.2) in the 2.5 mg, 5 mg, and the 10 mg groups, respectively. Differences in Cmax between the 2.5 mg and 10 mg group were significant (P < 0.001). The median time to Cmax (Tmax) was 1.83 hours (IQR: 1.79-3.94), 2.59 (IQR: 1.32-3.83), and 3.86 (IQR: 1.82-5.77) in the 2.5, 5, and 10 mg groups, respectively. In the present patient population, a predetermined AUC value can be obtained by a dosing regimen of dexamphetamine based on body weight (ie, mg/kg), with precautions for patients with elevated s-creatinine.

Unlabelled: We investigated three different concentrations of levobupivacaine (0.125%, 0.20%, and 0.25%; n = 20 in each group) for caudal blockade in a prospective, randomized, observer-blinded fashion in children (1-7 yr) undergoing subumbilical surgery. The duration of postoperative analgesia was assessed as the time to first administration of supplemental analgesia (based on a Childrens and Infants Postoperative Pain Scale score of >or=4), and the degree of immediate postoperative motor blockade was determined by use of a 3-point scale. A dose-response relationship was observed both with regard to median duration of postoperative analgesia (0.125%, 60 min; 0.20%, 118 min; 0.25%, 158 min) and the number of patients with evidence of early postoperative motor blockade (0.125%, 0; 0.20%, 4; 0.25%, 8). The 0.125% concentration was associated with significantly less early motor blockade (P = 0.003) but was found to result in a significantly shorter duration of postoperative analgesia (P < 0.05). Based on these results, the use of 0.20% levobupivacaine might represent the best clinical option if a plain levobupivacaine solution is to be used for caudal blockade in children., Implications: The use of 0.125% levobupivacaine for caudal blockade (1 mL/kg) in children (1-7 yr) was associated with less early postoperative motor blockade but a shorter duration of postoperative analgesia compared with 0.20% and 0.25% solutions.