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Neuropharmacology: Age-related changes
Published in Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor, Essentials of Geriatric Neuroanesthesia, 2019
Katleen Wyatt Chester, Olivia Johnson Morgan, Kruti Shah
Anticipated actions of paralytic agents are also altered in geriatric patients. Elderly patients have fewer motor units and less muscle volume compared to adult patients. Older adults experience longer times to onset of paralysis from reduced cardiac output and blood flow to muscles (41). Great responses are seen with NMBAs that are hydrophilic, since the plasma compartment and total body water are reduced in this population (41). Clearance of the agents and duration of effects are prolonged from age-related changes of the renal and hepatic systems. Changes in blood flow to the liver combined with reduced renal function can alter vecuronium clearance by as much as 50% (41). The reduced clearance rates yield higher recovery indices in elderly patients. The recovery index is defined as the time from 75% block to 25% block. In elderly patients, these times can be increased as much as 200%. Vecuronium recovery times increased from 15 to 50 minutes and rocuronium times from 13 to 22 minutes from increasing age. Unlike vecuronium or rocuronium, cisatracurium is cleared by plasma esterases, and no appreciable differences in the actions of this paralytic have been noted in elderly patients (41).
Pharmacokinetic-Pharmacodynamic Correlations of Anesthetic Agents
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Virginia D. Schmith, Keith T. Muir
Neonates, infants, and children may have different dosing requirements of NMB agents based on changes in pharmacokinetics (e.g., changes in volume of distribution) and pharmacodynamics (e.g., receptor sensitivity). For atracurium, the volume of distribution at steady state (Vdss) and clearance decreased with increasing age (from 4 months to 4 years of age). Neither the half-lives nor the EC50 values varied with age.34 For vecuronium, the Vdss values were larger and EC50 values were lower in infants than in children or adults.59 Similarly, Vdss values for d-tubocurarine decreased with increasing age; clearances were similar in neonates, infants, children, and adults; and EC50 values were lower in neonates and infants than in children and adults.45 These studies showed that the initial dose requirements may not differ in neonates, infants, and children for vecuronium and d-tub-ocurarine; however, because of the larger volumes of distribution and longer half-lives, subsequent doses should be given at less frequent intervals.45,59 For atracurium, Fisher et al.34 reported that maintenance dose requirements remain essentially unchanged. PK/PD modeling, therefore, has provided insight into the differences in dosing requirements of various NMB agents in neonates and children.
Neuromuscular care
Published in Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor, Essentials of Anesthesia for Neurotrauma, 2018
Ankur Khandelwal, Hemanshu Prabhakar
Rocuronium is approximately six to 10 times less potent than pancuronium and vecuronium, respectively. The usual intubating dose ranges from 0.6 to 1 mg/kg and the duration of action is similar to vecuronium. However, increasing the dosage of rocuronium from 0.6 mg/kg to 1.2 mg/kg shortens the onset time of complete NM block from 89 seconds to 55 seconds, but essentially doubles the clinical duration of recovery from 37 minutes to 73 minutes.2 Continuous infusion dosing ranges from 8 to 12 µg/kg/min. Rocuronium is eliminated primarily by the liver (>70%), with a small percentage (≈10%) eliminated in the urine. The putative metabolite, 17-desacetylrocuronium has not been detected in significant quantities.
Regulation of cytochrome P450 enzyme activity and expression by nitric oxide in the context of inflammatory disease
Published in Drug Metabolism Reviews, 2020
Edward T. Morgan, Cene Skubic, Choon-myung Lee, Kaja Blagotinšek Cokan, Damjana Rozman
Hepatic heme-nitrosyl complexes have also been detected in the livers of mice treated with killed Corynebacterium parvum bacteria in the presence or absence of LPS (Chamulitrat et al. 1995). In rats treated with C. parvum, the clearance of vecuronium and antipyrine was reduced and this was partially reversed by NOS inhibition (Blobner et al. 1999). However, levels of P450 proteins were not measured. In a model of sterile inflammation caused by turpentine injection in rabbits, a NO-dependent reduction in the clearance of antipyrine was observed in the absence of changes in CYP1A2 (Barakat et al. 2001). Similarly, a NO-dependent reduction of antipyrine clearance in rats treated with type II Shiga-like toxin was not accompanied by changes in CYP2C11 and CYP3A2 proteins (Kitaichi et al. 2004). In a model of Type I allergy in mice, an NO scavenger blocked the observed decreases in Cyp1a2, Cyp2c, Cyp2e1 and Cyp3a activities, whereas there were no changes in Cyp protein levels (Tanino et al. 2016). On the other hand, decreases in P450-dependent activities in the livers of mice treated with polyinosinic. polycytidylic acid (a toll-like receptor 3 agonist) were not affected by NOS inhibition (Hodgson and Renton 1994).
Propofol post-conditioning after temporary clipping reverses oxidative stress in aneurysm surgery
Published in International Journal of Neuroscience, 2019
Di Guo, Yanli Li, Haiyun Wang, Xinyue Wang, Wei Hua, Qingkai Tang, Lumin Miao, Guolin Wang
Midazolam (0.03 mg/kg) was used as premedication for all patients. Induction of anesthesia in both groups was performed using intravenous propofol 1.5 mg/kg, fentanyl 5 µg/kg, and rocuronium 0.8 mg/kg. Patients were monitored throughout the duration of general anesthesia with electrocardiogram, peripheral oxygen saturation (SpO2), invasive arterial blood pressure, end-tidal CO2 (PETCO2), and bispectral index (BIS). After endotracheal intubation, mechanical ventilation was set to maintain a PETCO2 between 38 and 45 mmHg. Maintenance anesthesia differed between the two groups. For Group S, 0.5–2% sevoflurane was inhaled to keep the BIS value between 40 and 60. In Group P, 0.5–2% sevoflurane was administered prior to and during clipping of the parent artery. Immediately after clip removal, 1.2 µg/mL propofol (TCI, plasma target concentration) was given while the concentration of sevoflurane was simultaneously decreased to maintain a BIS value between 40 and 60 until the surgery was completed. Vecuronium was given as needed.
Analgesic efficacy of dexmedetomidine versus fentanyl as an adjunct to thoracic epidural in patients undergoing upper abdominal surgery: a randomized controlled trial
Published in Southern African Journal of Anaesthesia and Analgesia, 2018
Neerja Bharti, Shweta N Pokale, Indu Bala, Vikas Gupta
Anaesthesia was induced with morphine 0.1 mg/kg followed by propofol 2–3 mg/kg until loss of verbal response. Muscle relaxation was achieved with vecuronium bromide 0.1 mg/kg and the patient’s trachea was intubated when train of four (TOF) count reached 0. Anaesthesia was maintained by isoflurane with 60% nitrous oxide in oxygen titrated to maintain a Bispectral index (BIS) value of 40–60. Muscle relaxation was maintained with top-ups of vecuronium bromide guided by neuromuscular monitoring. The lungs were ventilated with positive pressure ventilation to maintain end-tidal carbon dioxide (EtCO2) between 32 and 36 mmHg. The epidural drug was administered according to the group allocation immediately after intubation over a period of 10 minutes. Patients’ heart rate, electrocardiography (ECG), SpO2, BIS, nasopharyngeal temperature and EtCO2 were monitored continuously and blood pressure was taken at five-minute intervals. The data were recorded every 5 minutes for the first 30 minutes and then every 15 minutes till completion of surgery.