Time constant or half time of a breathing system?
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Biomedical subjects
Publications and source records attributed to G H Meakin.
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It has been estimated that more than 60% of all paediatric surgery is performed on a day case basis. The benefits of this type of surgery in children include reduced costs, avoidance of the stress of hospitalization and less disruption to family life. The growth of day surgery in children has been facilitated by the development of non-depolarizing neuromuscular blocking agents characterized by short and intermediate duration of action and fewer side-effects. The more rapid onset and shorter duration of action of non-depolarizing neuromuscular blocking agents in children should facilitate the use of these agents in place of succinylcholine for day case procedures.
We studied the neuromuscular and cardiovascular effects of a single, rapidly administered intravenous dose of cisatracurium 0.15 mg.kg(-1) in 27 infants (aged 1-23 months) and 24 children (aged 2-12.5 years). After midazolam premedication, anaesthesia was induced and maintained with thiopental and alfentanil in addition to nitrous oxide in oxygen. Neuromuscular function was monitored by evoked adductor pollicis electromyography. At least 15 min after intubation, each patient received cisatracurium 0.15 mg.kg(-1) over 5 s. Complete neuromuscular blockade was produced by this dose in all but one infant. The mean (SD) onset time of maximal blockade was more rapid in infants [2.0 (0.8) min] than in children [3.0 (1.2) min], p = 0. 0011. The clinical duration of action of cisatracurium (recovery of evoked response to 25% of control) was significantly longer in infants [43.3 (6.2) min] than in children [36.0 (5.4) min], p < 0.0001. Once neuromuscular function started to recover, the rate of recovery was similar in both age groups. Changes in blood pressure and heart rate after the administration of cisatracurium were negligible in both age groups. Cisatracurium, at a dose of 0.15 mg. kg(-1), was effective and well tolerated in infants and children.
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BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.
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We have used phrenic nerve-hemidiaphragm preparations from rats aged 11-28 days to determine the electrophysiological basis of the three-fold increase in sensitivity of the neonatal neuromuscular junction to non-depolarizing neuromuscular blocking drugs. The mean resting membrane potential (RMP) of intact muscle fibres at 19-21 degrees C increased from -67.1 (SEM 0.6) mV at 11 days to -75.8 (0.06) mV at 28 days. Over the same age range the mean size of miniature endplate potentials (MEPP) decreased from 1.7 (0.1) mV to 1.4 (0.03) mV, and the threshold depolarization to produce a muscle action potential increased from 6.8 (0.4) mV to 9.5 (0.6) mV. The quantal content of the evoked endplate potential (EPP) calculated from EPP and MEPP measured in cut muscle fibres was only 6.6 (0.9) at 11 days, but this increased to 21.1 (2.3) at 21 days. As a result of the low quantal content of the EPP, the safety factor for neuromuscular transmission was only 1.7 at 11 days, compared with 2.8 at 20 days. A safety factor of 1.7 in the youngest rats indicates that block of only about 40% of postjunctional acetylcholine receptors would result in failure of neuromuscular transmission. Hence, a low quantal content of EPP, leading to a low safety factor for neuromuscular transmission, probably underlies the increased sensitivity to non-depolarizing neuromuscular blocking drugs of young rats and, by inference, human neonates.
Fifty-four children aged 1-10 years, scheduled for day-case anaesthesia were prescribed either oral midazolam 0.5 mg.kg-1 or a placebo preparation 30-60 min pre-operatively on a double-blind basis. On arrival at the induction room, anxiolysis was satisfactory in 23 out of 24 (96%) children who received midazolam compared with 12 out of 27 (44%) of those who received placebo (p < 0.001); at induction of anaesthesia these proportions were 21 out of 24 (88%) and nine out of 27 (33%) respectively (p < 0.001). The time to early recovery from anaesthesia was somewhat longer in children premedicated with midazolam compared with controls (28.2 vs 21.9 min) (p < 0.05). Similarly, the time to hospital discharge was longer in the midazolam group (244 vs 185 min) (p < 0.01). Analysis of behavioural questionnaires completed by parents 2 weeks after hospitalisation indicated that there were fewer postoperative behavioural disturbances in children premedicated with midazolam compared with controls (p < 0.05).