The effect of priming with vecuronium and rocuronium on young and elderly patients

The priming principle consists of administering a subparalyzing dose of nondepolarizing neuromuscular blocking drug 3-6 min before giving a second dose for tracheal intubation. This study was performed to observe the effects of priming doses of vecuronium and rocuronium on pulmonary function tests and muscular weaknesses in young (25-35 yr of age) and elderly (65-73 yr of age) patients. Ten young and 10 elderly patients were each placed in vecuronium and rocuronium groups. Oxygen saturation and train-of-four (TOF) ratio were determined, and pulmonary function tests were performed. Then 20% of the 95% effective dose (ED95) of the muscle relaxants was given intravenously. All tests were performed again 4 min after vecuronium and 3 min after rocuronium. Other signs of muscular weaknesses were also recorded. Elderly patients showed more signs of muscle weakness in both groups. The TOF ratio was 0.77 and 0.79 in the elderly rocuronium and vecuronium groups, respectively, and 0.89 and 0.90 in the young rocuronium and vecuronium groups, respectively. Dynamic spirometry revealed decreases in forced expiratory volume in 1 s and forced vital capacity in both groups, and no significant changes in peak expiratory flow rate. The expiratory reserve volume was reduced more in the elderly groups. Oxygen saturation decreased in both groups. We conclude that oxygen saturation, pulmonary function, and muscle strength decrease more in the elderly than in their younger counterparts from priming doses of vecuronium or rocuronium. IMPLICATIONS: The priming principle consists of giving a subparalyzing dose of muscle relaxant 3-6 min before giving a second dose for tracheal intubation. We found that priming doses of vecuronium and rocuronium produced greater decreases in oxygen saturation and pulmonary function in the elderly (aged 65-73 yr) than their younger (aged 25-35 yr) counterparts. Priming may not be a safe approach in elderly patients.     

Extended duration of action of rocuronium in postpartum patients

Nine perylenequinones (PQ), including some familiar naturally occurring pigments, were compared for their light-mediated antiviral efficacies. Calphostin C was the most active compound against the two target viruses, herpes simplex virus type 1 and Sindbis virus. Hypocrellins A and B were also very active. However, three cercosporin-like PQ were substantially less active in spite of their high quantum yields of singlet oxygen, whereas phleichrome, another efficient singlet oxygen producer, showed no detectable antiviral activity. One other PQ, which was a very weak singlet oxygen producer, also showed no antiviral activity. None of the active compounds showed significant antiviral activity in the dark. Thus, for some groups of PQ there was correlation between quantum yield of singlet oxygen (1O2) and antiviral efficacy, but there are evidently other structural features of PQ that influence activity.     

Potentiation of mivacurium by rocuronium is age- and time-dependent: a study in children, adolescents, and young and elderly adults

Potentiation occurs when the steroidal muscle relaxant, rocuronium, is coadministered with the benzylisoquinolinium relaxant, mivacurium. The effect of time and age on this interaction was evaluated in four predetermined groups: children, adolescents, young adults, and elderly adults (15 per group) by monitoring the ulnar nerve-evoked force of contraction of the adductor pollicis (twitch response). During recovery from paralysis induced by 800 micrograms/kg of rocuronium, an infusion of mivacurium was started and maintained for at least 90 minutes to retain the twitch response at 1% to 9% of baseline tension (95 +/- 4% paralysis). Rocuronium at 600 micrograms/kg induced greater than 95% paralysis in 57 of the 60 patients within 2.2 +/- 0.4 (mean +/- SE) minutes. The period of recovery from rocuronium-induced paralysis to 5% of baseline twitch height was longest in the elderly (30.1 +/- 2.9 minutes) and shortest in the adolescents (16.5 +/- 2.4 minutes). The mivacurium infusion requirements to maintain 95 +/- 4% paralysis was highest in children and progressively increased with time. In young and elderly adults, the infusion rates remained lower than that of children and did not change with time. The incidence of satisfactory spontaneous recovery within 20 minutes (train-of-four ratio > 75%) was the highest in children, followed by adolescents and young adults, and was least in the elderly. The residual neuromuscular effect of rocuronium on the subsequent mivacurium infusion was most pronounced in the elderly, followed by young adults, then adolescents, and was least in children.     

Pharmacokinetics of rocuronium during the three stages of liver transplantation

BACKGROUND: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function. METHODS: Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined. RESULTS: During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1) x min(-1) and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl. CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepatic period, apparently a result of prolonged graft warm ischemia. The authors' finding of preservation of hepatic drug elimination in the hepatic allograft is consistent with limited data for other drugs evaluated during anesthesia.     

Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients

OBJECTIVE: To increase the knowledge about pregnancy and delivery in women with certain muscle diseases, which is important for obstetric management and family planning of affected women. DESIGN: The obstetric histories of patients with facioscapulohumeral (FSH) muscular dystrophy, limb-girdle (LG) muscular dystrophy, and congenital myopathies (CM) were retrospectively evaluated using questionnaires and medical reports. PATIENTS: The condition of 27 patients with different myopathies (FSH muscular dystrophy, n = 11; LG muscular dystrophy, n = 9; and CM, n = 7 [subdivided into 5 patients with central core disease, 1 patient with cytoplasmic bodies, and 1 patient with unspecified myopathy]) were ascertained from January 1, 1992, to December 31, 1994, through departments of neurology and human genetics, and the German self-support group for muscle diseases. Fifty-eight gestations resulting in 52 live births were reviewed. RESULTS: Miscarriages were reported in 3 of 26 gestations in 11 patients with FSH dystrophy, whereas 3 of 15 pregnancies in patients with LG dystrophy were terminated. Preterm births occurred in 2 patients with FSH dystrophy and in 3 patients with CM. Operative deliveries (vaginal operation or cesarean section) were performed in 6 of 23 gestations in patients with FSH dystrophy (1 emergency section), in 5 of 12 patients with LG dystrophy (2 emergency sections), and in 3 of 17 deliveries in patients with CM. Patients with FSH dystrophy generally coped well with their muscle disease in pregnancy and after delivery; however, 4 women were stated to have difficulties in caring for their families. The situation differed in LG dystrophy, where most women (5 of 9) experienced worsening of weakness in pregnancy and required assistance after delivery. In the patients with CM, 3 women experienced a deterioration during pregnancy, and 4 patients reported difficulties after delivery. CONCLUSIONS: No deleterious outcome of pregnancy and labor was observed in this series of patients with muscular dystrophy or CM, although operative deliveries were more frequent. A significant aggravation of symptoms in gestation is more likely to occur in patients with early-onset and progressive myopathy than in those with stable disease courses.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination

BACKGROUND: The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. METHODS: Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. RESULTS: The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. CONCLUSIONS: Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.     

Spontaneous movements associated with rocuronium: is pain on injection the cause?

Spontaneous movements are sometimes observed of the arm into which rocuronium is administered. In order to assess a possible relationship between these movements and pain, we injected in 10 awake, ASA I patients, in a double-blind manner, both rocuronium 1 ml (10 mg) and 0.9% NaCI 1 ml (placebo), with a 30-s interval in between. None of the patients receiving placebo complained of pain, but eight of 10 patients reported a strong burning pain during injection of rocuronium with brisk flexion of the elbow and wrist, similar to those observed in patients after induction of anaesthesia. A second injection of rocuronium did not produce such pain and no movements were observed. We conclude that injection of rocuronium is associated with severe, burning pain of short duration, responsible for the spontaneous movements in the arm observed after induction of anaesthesia.     

Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium

Haemodynamic variables were measured following administration of rocuronium 0.6 mg.kg-1 or vecuronium 0.08 mg.kg-1 (approximately equivalent to 2 x ED95 doses) in patients anaesthetized with fentanyl 50 micrograms.kg-1 and scheduled to undergo elective coronary artery bypass grafting. There were increases in stroke volume index (+15%) and cardiac index (+11%), and a decrease in pulmonary capillary wedge pressure (-25%) following administration of rocuronium (P < 0.05). The changes in heart rate (+7%), mean arterial pressure (-5%), systemic vascular resistance (-12%) and other measured or derived indices were insignificant. In comparison the administration of vecuronium was associated with decreases in heart rate (-7%), mean pulmonary artery pressure (-17%), central venous pressure (-15%) and the rate-pressure product (-9%) (P < 0.05). The changes in mean arterial pressure (-7%), cardiac index (-6%) and systemic vascular resistance (-8%) following vecuronium were insignificant. There were no differences in any of the variables between rocuronium and vecuronium. The absolute values of all variables were, however, within acceptable clinical limits. There was no evidence of histamine release in any patient. The present study shows that rocuronium 0.6 mg.kg-1 is associated with changes of only small magnitude in haemodynamic variables.     

Pharmacodynamic comparison of the acute effects of nomifensine, amphetamine and placebo in healthy volunteers

In a double blind cross over trial the effects of single doses of 100 mg nomifensine, 15 mg racemic amphetamine and placebo were compared in 9 healthy volunteers. Assessments of choice reaction behavior, simple reaction time, critical flicker fusion and attention on continuous calculations were performed together with a series of self rating scales, a side-effect list and vital signs before and 90 min., 180 min. and 360 min. after each administration. While the only significant nomifensine effect was an increase of correct solutions in the continuous calculation task, amphetamine differed from nomifensine and placebor in a number of subjective variables which describe emotional changes typical for drug stimulation. Subjects also expressed the will to have amphetamine prescribed for fatigue and loss of drive, whereas preferences for nomifensine were virtually the same as for placebo. Under amphetamine heart rate and blood pressure were increased and side-effects were frequent. It is concluded that nomifensine showed none of those subjectively pleasant amphetamine effects which are responsible for the reinforcement function leading to amphetamine dependence.     

Arthroscopy in the elderly

The uptake rate of oxygen and nitrous oxide were studied during low flow anaesthesia with enflurane or isoflurane in nitrous oxide with either spontaneous or controlled ventilation. The excess gas flow and composition were analysed. The nitrous oxide uptake rate was in agreement with Severinghaus' formula VN20 1000.t-0.5. The composition of excess gas was predictable and the following formula for oxygen uptake could be derived: VO2 = VfgO2-0.45 (VfgN2(0)-(kg: 70.1000.t-0.5)) where oxygen uptake rate (VO2, ml.min-1) equals oxygen fresh gas flow (VfgO2) minus 0.45 times the difference between the fresh gas flow of nitrous oxide (VfgN2O), ml.min-1 and estimated uptake of nitrous oxide. The equation assumes constant inspired gas concentrations of 30% oxygen and 65-70% nitrous oxide. The oxygen uptake rates calculated from this formula were in good agreement with measured uptake rates. Thus, continuous monitoring of oxygen uptake rates is possible by using only reliable flowmeters and analysis of inspired oxygen concentration.     

Polytrauma in the elderly

As the elderly population grows, a concomitant increase in polytrauma in the geriatric sector is predicted. Diminished physiologic reserve and deficiencies in management contribute to higher rates of morbidity and mortality in the elderly patient with trauma as compared with the young patient with equivalent trauma. Currently, traditional trauma scoring systems are insufficient in directing triage and predicting survival for these elderly patients. This may be related to the effects of aging and associated comorbidities. Age, therefore, should be considered in contemporary scoring systems and treatment algorithms. The benefits of prompt identification and treatment of musculoskeletal, neurologic, abdominal, and cardiopulmonary trauma, and maintenance of adequate nutritional status are well established in the polytrauma setting, in general. For the elderly patient with polytrauma, early invasive hemodynamic and cardiac monitoring are advisable to identify occult shock, limit end organ hypoperfusion, prevent multiorgan failure, and ultimately improve survival.     

Hypertension in the elderly

Residents living near a polyurethane foam manufacturing facility expressed concern to health officials over chemical emissions from the plant. Environmental monitoring of ambient air near the plant indicated the presence of toluene diisocyanate (TDI), which was used in foam production. Health officials collected blood samples from 113 residents and analyzed the blood sera for antibodies to TDI and related diisocyanates. Ten of the 113 residents (9%) had elevated levels of IgG or IgE antibodies specific for one or more diisocyanates. Exposure histories were taken from antibody-positive individuals to identify possible occupational exposure to TDI or the use of diisocyanate-containing consumer products. Exposure to TDI in ambient air may be responsible for the positive antibody responses detected in some residents of the community.     

Constipation in the elderly

Constipation affects as many as 26 percent of elderly men and 34 percent of elderly women and is a problem that has been related to diminished perception of quality of life. Constipation may be the sign of a serious problem such as a mass lesion, the manifestation of a systemic disorder such as hypothyroidism or a side effect of medications such as narcotic analgesics. The patient with constipation should be questioned about fluid and food intake, medications, supplements and homeopathic remedies. The physical examination may reveal local masses or thrombosed hemorrhoids, which may be contributing to the constipation. Visual inspection of the colon is useful when no obvious cause of constipation can be determined. Treatment should address the underlying abnormality. The chronic use of certain treatments, such as laxatives, should be avoided. First-line therapy should include bowel retraining, increased dietary fiber and fluid intake, and exercise when possible. Laxatives, stool softeners and nonabsorbable solutions may be needed in some patients with chronic constipation.     

Hypertension in the elderly

Elevated blood pressure, especially isolated systolic hypertension, is increasingly frequent with advancing age, affecting 1/4 of all 80-year-olds. Systolic hypertension is associated with increased cardiovascular morbidity and mortality. Recent studies have clearly demonstrated that antihypertensive treatment in the elderly decreases cardiovascular morbidity and mortality (in absolute numbers several times more than in younger patients), without more frequent side effects or a decrease in quality of life. Hypertension in the elderly thus deserves proper attention and should be taken seriously.     

Stapedectomy in the elderly

Clinical records were reviewed to examine the effectiveness of stapedectomy in patients 70 years and older. A total of 154 patients was studied, including 11 with profound hearing loss with long-standing otosclerosis. Ages at the time of surgery ranged from 70 to 92 years (mean, 76.3 years). The mean pure-tone average (500, 1,000, 2,000, and 4,000 Hz) improved 30.6 dB after surgery for the 143 patients in the main otosclerotic group and 26.8 dB for the patients in the profound-hearing-loss group. The rate of successful stapedectomies for the 70(+)-year-old patients (90.9%) and the younger comparison group (90.0%) were similar. These findings extend the documented range of stapedectomy as a safe and effective procedure through the eighth decade of life.