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PubMed1999

Neuromuscular blocking agents in paediatric anaesthesia.

Neuromuscular blocking agents are used commonly in paediatric anaesthesia, both to facilitate tracheal intubation and during surgery. Paediatric patients differ from adults in certain pharmacokinetic and pharmacodynamic characteristics. However, because maturational changes in certain of these characteristics counterbalance, dosing requirements do not differ markedly with age. In general, onset is more rapid in paediatric patients than in adults. Succinylcholine is still used commonly in children, despite restrictions by regulatory authorities, because of its rapid onset and offset. However, newer non-depolarizing neuromuscular blocking agents, particularly mivacurium, rocuronium and rapacuronium, offer many of the advantages of succinylcholine without its severe adverse effects: rocuronium and rapacuronium have an onset comparable with that of succinylcholine whereas the onset of mivacurium is slightly longer. In addition, recovery from an intubating dose of either mivacurium or rapacuronium is nearly comparable with that of succinylcholine. If rapacuronium i.m. proves to have a rapid onset without prolonged duration, the remaining value of succinylcholine will diminish.

Adult↗
PubMed2001

Increased sensitivity to depolarization and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms.

BACKGROUND: Newborn neuromuscular junctions are more sensitive to d-tubocurarine than more mature preparations. It is unclear whether the same modifications occur with newer nondepolarizing agents and depolarizing agent succinylcholine. The purpose of this study was to determine the relative sensitivity of newborn neuromuscular junctions to succinylcholine and five nondepolarizing agents. METHODS: The phrenic nerve-hemidiaphragm preparation from 60 rats was used, 30 aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats from each group were exposed to one of six neuromuscular blocking agents (d-tubocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine). Indirectly elicited twitch tension was measured during control conditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed and the EC50 (concentration required to produce 50% depression of twitch tension) was obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent. RESULTS: Newborn preparations were significantly (P < 0.001) more sensitive than their adult counterparts for all six agents tested. For nondepolarizing agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM; cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium, 9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The ratio for succinylcholine was significantly less than for all nondepolarizing drugs (P < 0.02). CONCLUSION: The newborn neuromuscular junction of the rat shows an increased sensitivity to all neuromuscular blocking agents tested, including succinylcholine. However, the potency ratio was greater for nondepolarizing than depolarizing drugs. The optimal dose of these agents for certain situations such as cesarean section and anesthesia in neonates should be reassessed.

Animals↗
PubMed2005

Cyclodextrins as new formulation entities and therapeutic agents.

PURPOSE OF REVIEW: This review is focused on recent advances in the application of cyclodextrins to new drug formulations, with emphasis on the field of anesthesia. RECENT FINDINGS: Cyclodextrins are well-known excipients in the pharmaceutical industry. Their recent application to the anesthetic induction agent propofol as a means of creating a non-lipid formulation may lead to their introduction into anesthesia pharmacology. The development of a novel cyclodextrin as specific reversal agent for the neuromuscular blocker rocuronium (that acts as an in-vivo scavenging system to bind free rocuronium in the circulation) will also increase the likelihood that cyclodextrins will have a greater clinical presence in anesthesiology in the future. Cyclodextrin-containing polymers are also finding a role in the delivery of nucleic acids and protein therapeutic agents. SUMMARY: Recent developments in cyclodextrins as excipients for anesthetics may soon culminate in their introduction into anesthesiology, although more research is necessary to better define their potential.

Journal Article↗
PubMed1994

The effect of CO2-induced acid-base changes on the potencies of muscle relaxants and antagonism of neuromuscular block by neostigmine in rat in vitro.

We investigated the influence of CO2-induced acid-base changes on the potencies of the monoquaternary relaxants (rocuronium, vecuronium, and d-tubocurarine) and bisquaternary relaxants (pancuronium, pipecuronium, and metocurine), and on the antagonism of their neuromuscular block by neostigmine. Phrenic nerve-hemidiaphragm preparations of rats were used. The pH changes were induced by changing the CO2 concentration aerating the modified Krebs solution. The potencies of the monoquaternary relaxants increased at 9% CO2 (pH 7.2) and decreased at 2.5% CO2 (pH 7.6) from those of 5% CO2 (pH 7.4) both with and without neostigmine (P < 0.05), whereas the potencies of the bisquaternary drugs did not change significantly at different pH levels from control (pH 7.4) both with and without neostigmine. The slopes of the log concentration-percent response curves of each drug were not significantly different at each pH level. The ratios of inhibitory concentrations, 50% (IC50) values with and without neostigmine at each pH value for each drug were not significantly different indicating that the neostigmine-induced antagonism for each drug was not affected by the CO2-induced acid-base changes. But the ratios of the IC50 values of the steroidal relaxants (rocuronium, vecuronium, pancuronium, and pipecuronium) were significantly lower (P < 0.05) than those of the isoquinolinium drugs (d-tubocurarine and metocurine) at each pH level, suggesting that the antagonism is enhanced at each pH level for the isoquinolinium relaxants. The difference was independent of their monoquaternary or bisquaternary nature. These results suggest that CO2 increases the potency of the monoquaternary relaxants but does not affect the bisquaternary relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed2005

Train-of-four stimulation for adductor pollicis neuromuscular monitoring can be applied at the wrist or over the hand.

Adductor pollicis stimulation over the ulnar nerve at the wrist is the standard method of monitoring neuromuscular function. Stimulation over a muscle is believed to cause direct muscle contraction, but evidence for this is lacking. In this study we sought to determine whether direct muscle stimulation occurred during stimulation of the adductor pollicis in the hand and whether the responses were comparable to those observed with stimulation at the wrist. In 20 patients anesthetized with sevoflurane, 1 pair of stimulating electrodes was positioned over the ulnar nerve at the wrist. A second pair was placed between the first and second metacarpals on the palmar and dorsal aspects of the hand. The acceleromyographic response was monitored. Rocuronium 0.6 mg/kg was administered. Train-of-four (TOF) stimulations were applied at the wrist site until maximal blockade. Then, stimulation was applied to the hand site. During recovery, both sites were monitored alternately. After injection of rocuronium, 17 of 20 patients showed no twitch response at either site. One patient had a response at both stimulation sites, and two patients had responses only at the wrist site. With a Bland and Altman analysis, TOF ratios during recovery at the hand showed a bias of 0.5% and limits of agreement of +/-11.8% as compared with the wrist. Stimulation in the hand causes no direct muscle stimulation because the response is no more than that produced by stimulation at the wrist. Both sites yield comparable TOF ratios.

Adult↗
PubMedDate not supplied

Perioperative management and monitoring of a super-obese patient.

Anesthetic management of super-obese patients is inferred from evidence which has been based on obese or morbidly obese patients. We present the perioperative management and monitoring of a 44-year-old 232-kg patient (BMI 70) admitted for laparoscopic gastric bypass surgery. Awake fiberoptic endotracheal intubation preceded induction with propofol and rocuronium. Anesthesia was maintained with desflurane and remifentanil. Desflurane was titrated on BIS values, whereas remifentanil was based on hemodynamic monitoring (invasive arterial pressure and HemoSonic). Rocuronium was administered based on ideal body weight and recovery of twitch tension. Safe and rapid extubation in the operating theatre was made possible by the use of short-acting agents coupled with continuous intraoperative monitoring. Recovery in the post-anesthesia care unit was uneventful, pain was managed with meperidine, and after 5 hours the patient was discharged to the surgical ward. Oxygen therapy and SpO2 monitoring were continued overnight. No desaturation episodes were recorded. Pain was managed with I.V. drip of ketorolac and tramadole.

Adult↗
PubMed2006

[Life-threatening serotonin syndrome following a single dose of a serotonin reuptake inhibitor during maintenance therapy with a monoamine oxidase inhibitor].

A 72-year-old man presented to the emergency clinic with motor restlessness and diminished consciousness 24 hours after he had mistakenly been given venlafaxine. He was referred from the psychiatric clinic where he was treated with tranylcypromine. Shortly after arrival, a severe serotonin syndrome developed with generalised myoclonic seizures, hyperreflexia, hypertonia, a rapid increase in temperature to 40.9 degrees C, hypertension, tachycardia, respiratory insufficiency, hyperkalaemia and metabolic acidosis. The patient was treated with the sedative propofol and the muscle relaxant rocuronium, followed by intubation and artificial respiration. He was cooled on a cooling mattress. Twenty-four hours later the airway tube could be removed and after 48 hours he was returned to the psychiatric ward in good condition. Tranylcypromine is a monoamine oxidase inhibitor and venlafaxine is a serotonin and noradrenaline reuptake inhibitor. When two serotoninergic agents are combined, the serotonin syndrome may develop, and this may be life-threatening. The treatment of this syndrome with propofol and rocuronium can be given quickly and safely in practically every hospital.

Aged↗
PubMed2006

Seizure attack during partial hepatectomy in a living donor for liver transplantation under sevoflurane anesthesia.

We report a case of generalized convulsion during partial hepatectomy for the purpose of organ donation for syngenesioplastic liver transplantation under sevoflurane anesthesia. This 23-year-old male Taiwanese living donor had no history of epilepsy. Anesthesia was inducted with fentanyl, propofol and rocuronium was used to facilitate endotracheal intubation. Sevoflurane in the mixture of oxygen and air and rocuronium were used for maintenance of anesthesia. Generalized convulsion with mild fever was observed 11 hours after the start of surgery when the surgeons happened to take a recess pending the removal of the recipient's liver. Convulsive episode subsided after aggressive management. Another 3 hours were required to complete the operation and the patient woke up in the postanesthesia room uneventfully.

Adult↗
PubMedDate not supplied

New developments in nondepolarizing muscle relaxants.

Anesthesiologists perceive that the ideal muscle relaxant is not yet available, particularly the nondepolarizing one with a rapid onset and a short duration of action. There is also a need for relaxants with different durations of action but which would be free from side effects. During the process of this development several new compounds have been tested and four have reached an advanced state of study; three of these, doxacurium, pipecuronium, and mivacurium are already licensed and rocuronium is likely to be licensed in the near future. Doxacurium and pipecuronium are slow onset and long duration of action compounds but singularly free from cardiovascular side effects. Mivacurium has an onset comparable to that of atracurium and vecuronium but with a duration of action which is intermediate in duration between these drugs and succinylcholine. Rocuronium is a drug with a fast onset of action capable of being used in place of succinylcholine but with a duration of action which is similar to that of vecuronium.

Anesthesiology↗
PubMed1998

Anaesthetic management of an adult patient with X-linked adrenoleukodystrophy.

PURPOSE: Adrenoleukodystrophy (ALD) is a rare genetic disorder. Findings include various central nervous system problems in addition to adrenal insufficiency. We present a case of an adult man with X-linked ALD undergoing surgery. CLINICAL FEATURES: A 40-yr-old man with X-linked ALD presented with an intertrochanteric femoral fracture. Past medical history included recurrent lung atelectasis, urinary incontinence, mental retardation, seizure disorder, and adrenal insufficiency. No sedative pre-medications were ordered, but perioperative steroid coverage with 100 mg hydrocortisone was initiated. In the operating room, the patient would not allow placement of all monitors. Therefore, 1 mg midazolam then 275 mg thiopentone followed immediately by 40 mg rocuronium were used to induce anesthesia with the application of cricoid pressure and the remaining monitors. Fentanyl 50 micrograms i.v. was given soon after induction, and anaesthesia was maintained with nitrous oxide and isoflurane. No further muscle relaxant or opioid was administered and anaesthesia was uneventful. The trachea was extubated with the patient awake and he was taken to the recovery area in stable condition. CONCLUSION: Patients with X-linked ALD are rarely seen in a clinical setting because the condition is so uncommon. Adrenal insufficiency, mental retardation, and osteoporosis are major considerations for these patients. In addition, these patients are at risk for reflux, seizures, and major post-operative complications.

Adrenoleukodystrophy↗
PubMed1998

Maintenance and recovery characteristics after sevoflurane or propofol during ambulatory surgery in children with epidural blockade.

PURPOSE: To compare the maintenance and recovery characteristics after sevoflurane with those after propofol in children with epidural blockade. METHODS: Fifty unpremedicated, children ASA I-II, 2-8 yr of age, scheduled for elective urological surgery as outpatients, were randomly allocated to receive either: 1) sevoflurane for induction and maintenance of anaesthesia or 2) propofol for induction (2-3 mg.kg-1 i.v.) and for maintenance (5-10 mg.kg-1.hr-1 i.v.). All children received N2O 70% in oxygen before induction and throughout the anaesthetic, rocuronium for neuromuscular blockade and a lumbar or caudal epidural block before incision. Heart rate (HR), systolic blood pressure (SBP), recovery times and all side effects during maintenance and recovery were recorded by a blinded observer. Adverse events during the first 24 hr were also recorded. RESULTS: Mean HR increased 5-10% after induction in both groups reaching a maximum by five minutes. Heart rate returned to baseline by skin incision in the sevoflurane group and by 10 min after induction in the propofol group. During maintenance, HR decreased by 10-20% below baseline values by 20 min in the propofol group only, where it remained for the remainder of the anaesthetic. Similarly, SBP increased by 10% after induction of anaesthesia in both groups, but returned to baseline by 10 min. Light anaesthesia occurred in four (16%) children, all in the propofol group. Emergence and recovery indices were similar in the two groups. DISCUSSION: Sevoflurane and propofol exhibit similar maintenance and recovery profiles when combined with epidural analgesia in children undergoing ambulatory surgery.

Ambulatory Surgical Procedures↗
PubMed2004

Phonomyographic measurements of neuromuscular blockade are similar to mechanomyography for hand muscles.

PURPOSE: Phonomyography consists of recording low frequency sounds created during muscle contraction. In this study, phonomyography of three regions of the hand was compared to mechanomyography of the adductor pollicis. METHODS: In 12 patients, phonomyography was recorded via small condenser microphones taped over the thenar mass, the hypothenar eminence, and the dorsal groove between the first and second metacarpal bones to record the acoustic signals of adductor pollicis and the hypothenar and first dorsal interosseus muscles, respectively. Mechanomyography of the adductor pollicis was recorded simultaneously using a force transducer. After induction of anesthesia, the ulnar nerve was stimulated supramaximally using train-of-four (TOF) stimulation every 12 sec. Onset, maximum effect, and offset of neuromuscular block after rocuronium 0.6 mg x kg(-1) were measured using phonomyography and compared to mechanomyography using ANOVA and the Bland-Altman test. RESULTS: Phonomyographic measurements of onset and maximum effect of neuromuscular blockade were not significantly different from mechanomyographic measurements. Phonomyographic measurements of offset (T25%, T75 %, TOF 0.8) of neuromuscular block at the thenar muscles and first dorsal interosseus muscles were not significantly different from mechanomyographic measurements at adductor pollicis; however, T50%, T75% and T90% phonomyographic measurements at the hypothenar muscle were significantly shorter than at any other muscle site. CONCLUSION: There was good agreement between mechanomyographic measurements at the adductor pollicis muscle and phonomyographic measurements at the thenar and the first dorsal interosseus muscles. Phonomyography of those two muscles could be used interchangeably with mechanomyography of adductor pollicis for clinical purposes.

Analysis of Variance↗
PubMed2005

Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: report of two cases.

PURPOSE: We examine two cases of prolonged neuromuscular blockade (NMB) after cardiac surgery. To the best of our knowledge, these are the first reported cases of complete paralysis lasting more than ten hours after surgery. CLINICAL FEATURES: We attribute the extended durations of NMB (more than ten hours) to high doses of NMB drugs in combination with magnesium sulphate and moderate renal failure. Advanced age, hepatic disease, aminoglycoside exposure, hypocalcemia, and possible interaction between rocuronium and pancuronium may have played minor roles. CONCLUSION: We should avoid administering large doses of NMB agents, even in the context of planned postoperative ventilation. If NMB is not monitored intraoperatively in patients who are at risk of prolonged NMB, then train-of-four response should be measured in the intensive care unit. Adequate sedation should be provided until proper recovery of neuromuscular function is documented.

Acute Kidney Injury↗
PubMed2004

Arousal with iv epinephrine depends on the depth of anesthesia.

PURPOSE: To investigate whether the depth of anesthesia affects the change in the bispectral index (BIS) caused by iv epinephrine during propofol anesthesia. METHODS: Forty women undergoing elective lower abdominal surgery received a propofol target controlled infusion (TCI) to maintain a modified Observer's Assessment of Alertness/Sedation (OAA/S) score of 2 (sedation period). Subsequently anesthesia was induced with propofol TCI 5 mug.mL(-1) and rocuronium 0.9 mg.kg(-1), and propofol continued so as to maintain general anesthesia at a BIS of 50 (general anesthesia period). Intravenous epinephrine at a dose of 10 mug.5 mL(-1) in normal saline (epinephrine group, n = 20) or normal saline 5 mL (control group, n = 20) was administered during both periods. The BIS, mean arterial pressure (MAP) and heart rate (HR) were measured immediately before, and one, two, three, four, six, eight, and ten minutes after injection. The modified OAA/S scale was evaluated during the sedation period. RESULTS: There was no significant change in the modified OAA/S scale, BIS, or hemodynamic variables compared to preinjection values during either sedation or general anesthesia in the control group. Intravenous epinephrine increased the BIS and modified OAA/S scale during sedation, but there was no increase in BIS during general anesthesia. Increases in HR and MAP were observed during both periods after iv epinephrine. CONCLUSION: Intravenous epinephrine 10 mug resulted in an arousal effect and an increase in BIS during sedation, but did not change the BIS during general anesthesia. These results suggest that the arousal effect of iv epinephrine during propofol anesthesia depends on anesthetic depth.

Adrenergic Agonists↗
PubMed2006

Modeling of twitch fade based on slow interaction of nondepolarizing muscle relaxants with the presynaptic receptors.

Nondepolarizing muscle relaxants (MRs) diminish the indirectly evoked single twitch due to their binding to the postsynaptic receptors. Additionally, the MRs produce progressive diminution of successive twitches upon repetitive stimulation (fade). Our study addresses the generation of fade as observed under clinical situation. The study was conducted in two phases. In the clinical part, we have evaluated the time course of twitch depression and fade following the administration of several doses of three MRs (rocuronium, pancuronium, and cisatracurium). In the second part, we have modified our model of neuromuscular transmission to simulate the time course of twitch depression and fade. The MR was assumed to bind to a single site on the presynaptic receptor to produce fade. The rates of interaction with the presynaptic receptors were characterized in terms of the arbitrarily assigned equilibrium dissociation constant and the half-life for dissociation of the presynaptic complex. A method was developed to relate the release of acetylcholine to the occupancy of the presynaptic receptors. The strength of the first and the fourth twitch was calculated from the peak concentration of the activated postsynaptic receptors, i.e., of those receptors with both sites occupied by acetylcholine. Our results indicate that, while the affinity of the MR for the presynaptic receptor plays little role in the time course of fade, the rate of dissociation of the complex between the presynaptic receptors and the muscle relaxant may be critical in determining the time course of fade. Tentative estimates of this parameter are offered.

Acetylcholine↗
PubMed2005

[Value of skin tests for the choice of a neuromuscular blocking agent after an anaphylactic reaction].

We report a grade III allergic hypersensitivity reaction occurring in a 72-year-old patient immediately after anaesthesia induction. Anaphylaxis to cisatracurium was diagnosed on clinical symptoms, biological tests and positivity of the cutaneous tests to this neuromuscular blocking agent. Five days after this allergological assessment, rocuronium, a muscle relaxant for which skin tests appeared negative was used during surgery without adverse effects. The authors underline the value of a detailed allergological assessment to identify the pathophysiologic mechanism, the culprit drug and to propose a safer alternate drug that might be used.

Adenocarcinoma↗
PubMed2004

Avenues of extrapulmonary oxygen uptake in western painted turtles (Chrysemys picta belli) at 10 degrees C.

The major avenues of extrapulmonary oxygen uptake were determined on submerged western painted turtles (Chrysemys picta bellii) at 10 degrees C by selectively blocking one or more potential pathways for exchange. Previous work indicated that the skin, the cloaca, and the buccopharyngeal cavity can all contribute significantly in various species of turtles. O(2) uptake was calculated from the rate of fall in water P(O(2)) in a closed chamber. Two series of experiments were conducted: in Series 1, each of the potential avenues was mechanically blocked either singly or in combination; in Series 2, active cloacal and buccal pumping were prevented pharmacologically using the paralytic agent rocuronium. In addition in Series 2, N(2)-breathing preceded submergence in some animals and in one set of Series 2 experiments arterial blood was sampled and analyzed for pH, lactate, P(O(2)), and P(CO(2)). Results in both Series 1 and Series 2 revealed that prevention of cloacal and/or buccopharyngeal exchange did not significantly affect total O(2) uptake. Interfering with skin diffusion in Series 1, however, significantly reduced O(2) uptake by 50%. N(2)-breathing prior to submergence in Series 2 did not affect O(2) uptake in paralyzed turtles but significantly increased uptake in unparalyzed turtles without catheters. Blood analysis revealed that all submerged turtles developed lactic acidosis, but the rate of rise in lactate was significantly lower in paralyzed animals. We conclude that passive diffusion through the integument is the principal avenue of aquatic O(2) uptake in this species.

Androstanols↗
PubMed2005

The importance of myorelaxants in anesthesia.

Neuromuscular blocking drugs were introduced into clinical practice in 1942. Although these drugs made new surgical techniques possible, they also led to morbidity and mortality owing to respiratory muscle paralysis and paralysis in the face of inadequate anesthesia. Newer competitive antagonists at the neuromuscular junction have been developed that have a more rapid onset of action, including rocuronium and mivacurium, making them suitable for use at the onset of anesthesia. Rapid titratable offset of action has been more difficult to achieve, but has been attempted with the inclusion of ester bonds (mivacurium) and binding agents that are in clinical trials. These novel approaches to pharmaceuticals, along with improved understanding of the physiology of the neuromuscular junction in health and disease, have made surgical treatment possible in a wide breadth of clinical situations.

Aged↗