piperidines and Tetanus

Inadequate antinociception can cause haemodynamic instability. The nociception level (NOL) index measures response to noxious stimuli, but its capacity to predict optimal antinociception is unknown.. To determine if NOL index change to a tetanic stimulus in cardiac and noncardiac surgery patients could predict the required remifentanil concentration for haemodynamic stability at skin incision.. A prospective two-phase cohort study.. University hospital.. Patients undergoing remifentanil-propofol target controlled infusion (TCI) anaesthesia.. During the calibration phase, investigators evaluated the tetanic stimulus induced NOL index change under standardised TCI remifentanil-propofol anaesthesia during a no-touch period [bispectral index (BIS) between 40 and 60, NOL index under 15]. If the NOL index change was 20 or greater following tetanic stimulation, investigators repeated the tetanus at higher remifentanil concentrations until the response was blunted. Surgeons incised the skin at this remifentanil concentration. The investigators derived a prediction model and in the validation phase calculated, using the NOL response to a single tetanus, the required incision remifentanil concentration for the start of surgery.. Haemodynamic stability at incision [i.e. maximum heart rate (HR) < 20% increase from baseline, minimum HR (40 bpm) and mean arterial pressure (MAP) ± <20% of baseline].. During the calibration phase, no patient had hypertension. Two patients had a HR increase slightly greater than 20% (25.4 and 26.7%) within the first 2 min of surgery, but neither of these two patients had a HR above 76 bpm. Two patients were slightly hypotensive after incision (MAP 64 and 73 mmHg). During the validation phase, neither tachycardia nor hypotension occurred, but MAP increased to 21.5% above baseline for one patient.. During a no-touch period in patients under steady-state general anaesthesia [propofol effect site concentration (Ce) required for BIS between 40 and 60], the NOL index response to a tetanic stimulus under remifentanil antinociception can be used to personalise remifentanil Ce for the start of surgery and ensure stable haemodynamics.. ClinicalTrials.gov: NCT03324269.

Topics: Calibration; Cohort Studies; Heart Rate; Humans; Nociception; Piperidines; Propofol; Prospective Studies; Remifentanil; Surgical Wound; Tetanus

Acetylcholinesterase (AChE) inhibitor donepezil is widely used for the treatment of Alzheimer's disease (AD). The mechanisms of therapeutic effects of the drug are not well understood. The ability of donepezil to reverse a known pathogenic effect of β-amyloid peptide (Abeta), namely, the impairment of hippocampal long-term potentiation (LTP), was not studied yet. The goal of the present study was to study the influence of donepezil in 0.1-10 μM concentrations on control and Abeta-impaired hippocampal LTP. Possible involvement of N-methyl-D: -aspartate receptors (NMDARs) into mechanisms of donepezil action was also studied. LTP of population spike (PS) was studied in the CA1 region of rat hippocampal slices. Change of LTP by donepezil treatment had a bell-shaped dose-response curve. The drug in concentrations of 0.1 and 1 μM did not change LTP while in concentration of 0.5 μM significantly increased it, and in concentration of 5 and 10 μM suppressed LTP partially or completely. Abeta (200 nM) markedly suppressed LTP. Addition of 0.1, 0.5 or 1 μM donepezil to Abeta solution caused a restoration of LTP. N-methyl-D: -aspartate (NMDA) currents were studied in acutely isolated pyramidal neurons from CA1 region of rat hippocampus. Neither Abeta, nor 0.5 μM donepezil were found to change NMDA currents, while 10 μM donepezil rapidly and reversibly depressed it. Results suggest that donepezil augments control and impaired by Abeta hippocampal LTP in NMDAR-independent manner. In general, our findings extend the understanding of mechanisms of therapeutic action of donepezil, especially at an early stage of AD, and maybe taken into account while considering the possibility of donepezil overdose.

Topics: Action Potentials; Amyloid beta-Peptides; Animals; Donepezil; Dose-Response Relationship, Drug; Hippocampus; Indans; Ion Channel Gating; Long-Term Potentiation; Male; Piperidines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Tetanus

A 61-yr-old woman presented with severe tetanus. Her intensive care management was complicated by severe generalized tetanic spasms despite the use of propofol, midazolam, alfentanil, magnesium sulphate, and atracurium. We describe the management of this problem with a variable dose remifentanil infusion.

Topics: Analgesics, Opioid; Drug Administration Schedule; Fatal Outcome; Female; Humans; Hypoxia, Brain; Infusions, Intravenous; Middle Aged; Piperidines; Remifentanil; Tetanus

Topics: Aged; Androstanes; Coma; Diazepam; Female; Humans; Neuromuscular Nondepolarizing Agents; Piperidines; Respiration, Artificial; Tetanus

Topics: Adult; Alkaloids; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bandages; Burns; Burns, Chemical; Burns, Electric; Child; Electrolytes; Eye Injuries; Facial Injuries; First Aid; Humans; Pain; Piperidines; Plasma Substitutes; Pyrazoles; Respiratory System; Shock; Tetanus; Transportation of Patients; Wounds and Injuries