Total Duration Of Action Research Articles

Rokuronyumla Başlangıç Dozu Sonrasında İki Farklı Ajanla Nöromusküler Blokajın Kıyaslanması: Randomize Klinik Çalışma

Objective: The purpose of this study was to assess the pharmacological effects of a priming dose of rocuronium in combination with the non-depolarizing blockers rocuronium or vecuronium during the perioperative period. Material and Methods: Sixty patients with American Society of Anesthesiologists (ASA) risk status I or II scheduled to receive anesthesia for elective surgery were included in the study. Patients were randomly divided into four groups. Patients in Group I (n=15) received a priming dose of normal saline and rocuronium bromide 0.6 mg/kg following induction of anesthesia; patients in Group II (n=15) received a priming dose of normal saline and vecuronium bromide 0.1 mg/kg following induction; patients in Group III (n=15) received a priming dose of rocuronium bromide 0.1 mg/kg followed by rocuronium bromide 0.6 mg/kg after induction; and Group IV (n=15) patients received a priming dose of rocuronium bromide 0.1 mg/kg followed by vecuronium bromide 0,1 mg/kg. T95 (time to onset of action), T25 (clinical duration of action), T75 (total duration of action) and recovery index (RI) were measured and recorded. Patients were monitored for possible side effects. Results: In Group III, in which patients were primed with rocuronium and maintained with rocuronium, the time to onset of action was significantly shorter than for patients in Group I. Similarly, this parameter was significantly shorter in Group IV patients than in Group II patients. T25 and T75 was significantly longer in Group II and Group IV than in the other groups. There was no significant difference in RI values between the groups. Conclusion: Using rocuronium as a priming agent accelerates the neuromuscular blocking effects of both rocuronium and vecuronium and provides ideal intubation conditions when safe and quick intubation is required.

Influence of acute hypervolemic hemodilution on pharmacodynamics of cisatracurium in patients undergoing general anesthesia

Objective To investigate the influence of acute hypervolemic hemodilution (AHH) on pharmacodaynamics of cisatracurium in patients undergoing general anesthesia. Methods Sixty ASA Ⅰ or Ⅱ patients aged 18-60 yr scheduled for major abdominal surgery under general anesthesia were randomly allocated into 2 groups (n = 30 each): control group and AHH group. Each group was further divided into 3 subgroups according to the initial dose of cisatracurium (30, 40, 50 μg/kg) . The radial artery and right internal jugular vein were cannulated. BP, HR, CVP, SpO_2, P_(ET) CO_2 and body temperature were continuously monitored. The response of left adductor pollicis muscle to TOF stimulation of ulna nerve was monitored using TOF- Watch~R SX (Organon). Both groups received 10 ml/kg multiple electrolyte solution (plasma-Lyte A) during induction of anesthesia. In group AHH 15 ml/kg 6% hydroxyethyl starch (HES) 130/0.4 solution was infused via internal jugular vein over 30-40 min in addition to plasma-Lyte A. Five minutes after completion of plasma-Lyte A or HES, cisatracurium 30, 40 or SO fig/kg was injected iv in the respective subgroups. After the maximal T_1 block was achieved, the second dose was given to reach a total dose of 100 μg/kg. The onset time, duration of clinical action, total duration of action and recovery index were recorded. The doses for 50% , 90% and 95% T_1 depression (ED_(50), ED_(90), ED_(95)) were calculated by Probit method. Results The ED_(50), ED_(90), ED_(95) of cisatracurium were significantly higher in AHH group than in control group. The onset time of cisatracurium was significantly longer but clinical and total duration of action was significantly shorter in AHH group than in control group. There was no significant difference in recovery index between the two groups. Conclusion AHH can decrease the potency of cisatracurium. Key words: Atracurium; Hemoodilution; Neruomuscular blockade

Dose-response and time-course of the effect of rocuronium bromide during sevoflurane anaesthesia

To evaluate the influence of sevoflurane on the dose–response relationship and on the time-course of the effect of rocuronium, 60 adult patients undergoing elective plastic surgery were randomly allocated to either the control or the sevoflurane group. Anaesthesia was maintained with 60% nitrous oxide in oxygen and thiopentone in the control group and with 60% nitrous oxide in oxygen and an end-tidal concentration of 1.75% sevoflurane in the sevoflurane group. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s and the percentage depression of the first twitch of the train-of-four was used as the study parameter. The dose–response relationship of rocuronium in the two groups was determined by the cumulative dose–response technique. The dose–response curve of rocuronium in the sevoflurane group was shifted to the left compared to the control group, indicating a potentiation of rocuronium-induced neuromuscular block. The effective doses of rocuronium required to produce 50%, 90% and 95% twitch depression in the sevoflurane group were decreased by 30.5%, 26.7% and 25.2%, respectively, compared to the control group. Following the administration of a total dose of rocuronium of 400 μgkg−1, the duration of action of, and the recovery from, rocuronium were both significantly prolonged by sevoflurane. There were significant differences in the duration of peak effect, clinical duration, recovery index and the total duration of action between the control and the sevoflurane groups.

Neuromuscular and cardiovascular effects of atracurium in isoflurane-anesthetized chickens

Summary Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered to 24 isoflurane-anesthetized domestic chickens. Birds were randomly assigned to 4 groups, and atracurium was administered at dosage of 0.15, 0.25, 0.35 or 0.45 mg/kg of body weight. The time of onset of twitch depression, the amount of maximal twitch depression, and the duration of muscular relaxation were recorded. After return to control twitch height, atracurium was further administered to achieve > 75% twitch depression. When twitch depression reached 75% during noninduced recovery, 0 5 mg of edrophonium/kg was administered to reverse the muscle relaxation. Throughout the experimental period, cardiovascular, arterial blood gas, and acid-base variables were monitored. The effective dosage of atracurium to result in 95% twitch depression in 50% of birds, (ed95/50) was calculated, using probit analysis, to be 0.25 mg/kg, whereas the ed95/95, the dosage of atracurium to result in 95% twitch depression in 95% of birds, was calculated by probit analysis to be 0.46 mg/kg. The total duration of action at dosage of 0.25 mg/kg was 34.5 ± 5.8 minutes; at the highest dosage (0 45 mg/kg), total duration increased 0 47.8 ± 10.3 minutes. The return to control twitch height was greatly hastened by administration of edrophonium. Small, but statistically significant changes in heart rate and systolic blood pressure, were associated with administration of atracurium and edrophonium. These changes would not be clinically relevant. In this study, atracurium was found to be safe and reliable for induction of muscle relaxation in isoflurane-anesthetized chickens.

The neuromuscular blocking effect of Org 9426

Org 9426, a new steroidal non-depolarising muscle relaxant, which is stable in solution, was studied in 30 anaesthetised (thiopentone, fentanyl, nitrous oxide) male patients, ASA 1 or 2. A dose-response curve for Org 9426 was constructed and the ED90, mean (SD), was found to be 0.36 (0.031) mg/kg. The onset of action was 3.8 (1.8) minutes, the clinical duration 17.4 (3.2) minutes, the total duration of action 31.9 (6.2) minutes and the recovery time 9.96 (3.2) minutes. No signs of histamine release or cardiovascular effects were observed. Org 9426 thus has a faster onset of action than vecuronium bromide or atracurium dibesylate.

Pharmacokinetics and Pharmacodynamics of Edrophonium in Elderly Surgical Patients

The effect of age (over 70 yr) on the pharmacokinetics and pharmacodynamics of edrophonium was evaluated in seven patients aged 76-87 yr and in seven patients aged 27-57 yr. When elderly patients were compared with younger controls, the elderly exhibited a statistically significant decreased plasma clearance (5.9 +/- 2 versus 12.1 +/- 4 mL.kg-1.min-1) and a prolonged elimination half-life (84.2 +/- 17 versus 56.6 +/- 16 min). Pharmacodynamically, a higher concentration of edrophonium is required in elderly patients to produce the same effect as in the younger controls. This observation may be explained in part by changes in neuromuscular transmission that are a function of the aging process. In addition, even though plasma concentrations were significantly greater at every sampling point in the elderly than the younger group, there was no difference between either the maximum duration or the total duration of action of edrophonium in the two groups. The maximum duration of action of edrophonium in both groups was very brief (1.3-2.2 min). These results contrast with a previous study of the anticholinesterases neostigmine and pyridostigmine, in which the action of these drugs was significantly prolonged in elderly patients. Explanations for the observed differences between edrophonium and other anticholinesterases may relate to differences in chemical structure and the possibility that edrophonium produces antagonism of neuromuscular blockade by a different mechanism than neostigmine or pyridostigmine.

Cardiovascular Properties of MS-857, a New and Potent Cardiotonic Agent, on Normal and Failing Hearts

The cardiovascular properties of MS-857 [4-acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone ], a novel cardiotonic agent, were investigated in anesthetized and conscious dogs. MS-857 (1-100 micrograms/kg i.v.) produced a significant and dose-dependent increase in cardiac contractility with relatively small changes in heart rate and blood pressure. This indicates a sizable separation between positive inotropic and other effects of MS-857. Oral administration of MS-857 to conscious dogs (0.1-1 mg/kg) also produced a sustained increase in cardiac contractility in a dose-dependent manner. The total duration of action was longer than 7 h at a dose of 1 mg/kg p.o. There occurred no arrhythmias and no changes in animal behavior. After chronic oral administration, MS-857 completely retained its activities, indicating the lack of tachyphylaxis. In the acute heart failure models induced by either propranolol or pentobarbital, MS-857 reversed the cardiac depressant effects of these drugs. Moreover, MS-857 also significantly improved the pentobarbital-induced heart failure in the heart-lung preparation. MS-857 did not inhibit the Na+, K+-ATPase, but inhibited the phosphodiesterase (PDE) III selectively, both of which were prepared from the dog ventricular muscle. Thus, MS-857 can be characterized as a potent nonsympathomimetic, nonglycoside cardiotonic drug with a selective inhibitory activity on PDE III. The cardiovascular properties revealed by this study strongly suggest that MS-857 will exert a beneficial effect in the treatment of congestive heart failure.