piperidines and Muscle-Rigidity

Remifentanil is the newest of the fentanyl family of short-acting phenylpiperidine derivatives to be released into clinical practice. Remifentanil is a pure agonist at the mu opioid receptor with relatively little binding at the kappa, sigma or delta receptors. This is precisely the same profile as the other opioids currently popular in anaesthetic practice (fentanyl, alfentanil, sufentanil) and it offers the same advantages (profound analgesia, sedation, attenuation of the stress response). This has led to widespread use of remifentanil as an adjunct to general anaesthesia in a variety of clinical settings. The unique pharmacology of remifentanil, in particular its rapid offset, has more recently attracted clinicians and investigators to the use of remifentanil by bolus injection, especially for procedures requiring a brief, intense, opioid effect. The clinical effects of remifentanil, both therapeutic and adverse, are consistent with that of the other fentanyl congeners. However, the pharmacokinetic profile of remifentanil, that is, its rapid effect site equilibration, has also revealed a significant potential for therapeutic misadventure. The untoward effects of remifentanil, given by continuous infusion, are well-described in the literature. They are predictable and easily managed by experienced clinicians. This review will concentrate on the adverse effects of remifentanil given by bolus injection, either alone or in the context of a background infusion.

Topics: Analgesics, Opioid; Heart Rate; Humans; Injections, Intravenous; Muscle Rigidity; Piperidines; Remifentanil; Respiratory Insufficiency; Safety; Seizures

The unique features of remifentanil are its rapid clearance and rapid ke0, resulting in a rapid onset and offset of drug effect. It is tempting to speculate that these characteristics will make remifentanil an easy drug to titrate, and that clinicians will not need to consider patient covariates such as advanced age when choosing a dosing regimen. However, the rapid onset of drug effect may be accompanied by rapid onset of adverse events such as apnea and muscle rigidity. The rapid offset of drug effect can result in patients who are in severe pain at a time when the anesthesiologist is ill equipped to deal the problem, for example when the patient is in transit to the recovery room. It is thus important that when treating elderly patients anesthesiologists understand the proper dose adjustment required for the elderly. By adjusting the bolus and infusion doses, the anesthesiologist can hope to avoid the peaks and valleys that might expose these patients to risk. When the proper adjustment is made, the variability in remifentanil pharmacokinetics is considerably less than for any other intravenous opioid. This makes remifentanil the most predictable opioid for treatment of the elderly.

Topics: Adult; Aged; Aged, 80 and over; Aging; Analgesics, Opioid; Anesthesia Recovery Period; Anesthetics, Intravenous; Apnea; Female; Forecasting; Half-Life; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Middle Aged; Muscle Rigidity; Pain, Postoperative; Piperidines; Remifentanil; Risk Factors; Titrimetry

Topics: Adolescent; Adult; Aged; Basal Ganglia Diseases; Benzamides; Butyrophenones; Child; Drug-Related Side Effects and Adverse Reactions; Dystonia; Extrapyramidal Tracts; Female; Humans; Male; Middle Aged; Muscle Hypertonia; Muscle Rigidity; Parkinson Disease, Secondary; Phenothiazines; Piperazines; Piperidines; Reserpine; Thioxanthenes

Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Elective Surgical Procedures; Electroencephalography; Female; Humans; Male; Models, Biological; Muscle Rigidity; Piperidines; Propofol; Remifentanil

The aim of this study was to test our hypothesis that priming with rocuronium would prevent muscle rigidity and difficult ventilation due to remifentanil administration.. One hundred patients, American Society of Anesthesiologists (ASA) status I or II, were recruited into the study, and randomly allocated to one of four protocols (n = 25 each). Remifentanil was administered at 0.2 microg.kg(-1).min(-1) in group A and at 0.7 microg.kg(-1).min(-1) in groups B, C, and D. Priming with vecuronium (0.02 mg.kg(-1)) or rocuronium (0.06 mg.kg(-1)) was performed at the same time as the infusion of remifentanil in groups C and D, respectively. Anesthesia was induced with 1 mg.kg(-1)propofol 2 min after the start of remifentanil infusion. After the patient had lost consciousness, the anesthesiologist performed mask ventilation, and watched for the presence of muscle rigidity. Ventilation and rigidity were evaluated using a scoring system.. Of the 100 patients, 9 were excluded; the number of patients in group A was 24, while groups B and D had 22 patients each, and group C had 23 patients. A lower dose of remifentanil (group A) or priming with vecuronium or rocuronium (groups C, D) significantly reduced the incidence of some difficulty with ventilation (P = 0.0010, P = 0.0053, and P = 0.021, respectively, vs group B). Of the patients in group B, 10 (45.5%) developed some difficulty with ventilation, and ventilation was impossible in 2 of them. On the other hand, 1 (4.1%) of the patients in group A, 2 (8.7%) in group C, and 3 (13.6%) in group D developed some difficulty with ventilation.. The present study showed that priming with rocuronium or vecuronium reduced the incidence of difficult ventilation by avoiding the muscle rigidity caused by remifentanil.

Topics: Aged; Androstanols; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; Humans; Laryngeal Masks; Male; Middle Aged; Muscle Rigidity; Neuromuscular Nondepolarizing Agents; Oxygen; Piperidines; Remifentanil; Respiration, Artificial; Rocuronium; Vecuronium Bromide

To compare the efficacy and safety of 3 doses of remifentanil as part of a total intravenous anesthesia technique with low-dose propofol in patients undergoing coronary artery bypass graft (CABG) surgery.. Multicenter, multinational, double-blind, randomized, dose comparison study.. Nine hospitals in 5 countries.. One hundred forty-one patients undergoing first-time elective CABG surgery.. Patients were premedicated with a short-acting oral benzodiazepine up to 2 h before surgery and randomized to receive continuous infusions of remifentanil 1.0 microg/kg/min (n = 45), 1.5 microg/kg/min (n = 44), or 2.0 microg/kg/min (n = 43), in combination with propofol 3 mg/kg/h. Nine patients received remifentanil 1.0 microg/kg/min on an open-label basis. Three different induction sequences (IS) were used. In IS 1 (n = 31), induction was started with remifentanil infusion followed 5 minutes later by propofol 0.5 mg/kg bolus and infusion at 3 mg/kg/h. Further bolus doses of propofol (10 mg) were given if loss of consciousness (LOC) was not attained after 5 minutes; pancuronium, 0.04 to 0.1 mg/kg, was administered at LOC. In IS 2 (n = 68), a priming dose of pancuronium, 0.015 mg/kg, was administered just before starting remifentanil. In IS 3 (n = 42), bolus doses of propofol, 10 mg every 10 seconds, were given until LOC, followed by pancuronium, 0.04 to 0.1 mg/kg, and the remifentanil and propofol infusions were started.. There were no significant differences among the remifentanil dose groups with regard to the primary outcome measure, responses to sternotomy/sternal spread/maximal sternal spread. Responses to these stimuli were recorded in 11%, 11%, and 14% of patients in the remifentanil 1.0, 1.5, and 2.0 microg/kg/min dose groups, respectively. Similarly, there were no significant differences in the responses to other surgical stimuli. There was a high incidence of muscle rigidity when remifentanil was used to induce anesthesia.. All 3 remifentanil dose regimens provided profound suppression of responses to surgical stimuli in the majority of patients. There was no apparent advantage in starting the remifentanil infusion rate above 1.0 microg/kg/min. Remifentanil is not suitable for use as a sole induction agent.

Topics: Adult; Aged; Analgesics, Opioid; Anesthetics, Combined; Anesthetics, Intravenous; Coronary Artery Bypass; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscle Rigidity; Physical Stimulation; Piperidines; Propofol; Remifentanil; Time Factors

This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil.. Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1) thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals.. Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given.. Remifentanil is 15 times more potent than alfentanil, based on the ED50 to achieve loss of response to a verbal command and 20 times more potent than alfentanil based on the EC50. Neither opioid is suitable as a sole induction agent.

Topics: Adult; Aged; Alfentanil; Consciousness; Dose-Response Relationship, Drug; Hemodynamics; Humans; Middle Aged; Muscle Rigidity; Piperidines; Remifentanil

Topics: Anticholinergic Syndrome; Antiparkinson Agents; Antipsychotic Agents; Biperiden; Burns; Cholinesterase Inhibitors; Delirium; Diagnosis, Differential; Donepezil; Drug Administration Routes; Drug Synergism; Humans; Indans; Male; Middle Aged; Muscle Rigidity; Physostigmine; Piperidines; Risperidone; Treatment Outcome

Neurodegeneration associated with pantothenate kinase deficiency is an autosomal recessive condition caused by mutations in the pantothenate kinase 2 gene (PANK2). Clinical characteristics include progressive motor impairment and dementia. Medical treatment is limited and the dystonia tends to be refractory, making stereotactic surgery with placement of deep-brain electrodes an option that is being adopted with greater frequency in these patients. We report the case of a 32-year-old woman with severe dystonia associated with PANK2 protein deficiency. The patient was scheduled for stereotactic bilateral placement of electrodes in the medial globus pallidus, guided by computed tomography and under general anesthesia, to treat the debilitating dystonia and generalized stiffness associated with her condition. Anesthesia was maintained with propofol, rocuronium and remifentanil in perfusion during the intervention, which was uneventful. After the procedure, the patient was transferred to the intensive care unit and sedation was provided with remifentanil to allow slow, gradual emergence from anesthesia. The patient was discharged from hospital after placement of the implanted pulse generator, and subsequent follow-up showed improvement of the dystonia.

Topics: Adult; Androstanols; Anesthesia, Intravenous; Deep Brain Stimulation; Dystonic Disorders; Female; Globus Pallidus; Humans; Intubation, Intratracheal; Muscle Rigidity; Neuromuscular Nondepolarizing Agents; Pantothenate Kinase-Associated Neurodegeneration; Phosphotransferases (Alcohol Group Acceptor); Piperidines; Preanesthetic Medication; Propofol; Radiography, Interventional; Remifentanil; Rocuronium

Remifentanil induces a higher incidence of respiratory rigidity than other opioids, especially when it is given at bolus injection for anesthetic induction. A 71-year-old man underwent pharyngo-laryngeal surgery under general anesthesia with remifentanil and sevoflurane. At the end of surgery, the ventilation through a tracheal tube became difficult due to muscle rigidity simultaneously with the increased dose of remifentanil and the decreased sevoflurane concentration. It should be kept in mind that increased doses of remifentanil during as well as at the end of surgery cause difficult ventilation associated with muscle rigidity.

Topics: Aged; Analgesics, Opioid; Anesthesia Recovery Period; Anesthesia, General; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Male; Methyl Ethers; Muscle Rigidity; Otorhinolaryngologic Surgical Procedures; Piperidines; Remifentanil; Respiration Disorders; Respiratory Muscles; Sevoflurane

This report shows a rare case of muscle rigidity by remifentanil just before the end of surgery. A 71-year-old man was scheduled for microvascular decompression to cure trigeminal neuralgia. Anesthesia was induced with propofol, suxamethonium and remifentanil 0.26 microg x kg(-1) x min(-1). Thirty minutes before the end of surgery, intratracheal pressure suddenly increased over 40 cmH2O, which was induced by muscle rigidity and the patient was difficult to be ventilated under anesthesia with sevoflurane 1% and remifentanil 0.05 microg x kg(-1) x min(-1). After giving muscle relaxants, the patient was uneventful. We should pay attention to muscle rigidity even using low doses of remifentanil.

Topics: Aged; Anesthesia; Anesthetics, Intravenous; Decompression, Surgical; Humans; Intraoperative Complications; Male; Muscle Rigidity; Piperidines; Remifentanil; Respiration Disorders; Respiratory Muscles; Trigeminal Neuralgia

To evaluate the utility and safety of remifentanil for hemodynamic control during cesarean section in high-risk patients ineligible for spinal anesthesia.. One minute before induction we injected a bolus of 1 microg x kg(-1) of remifentanil, followed by propofol (2.5 mg x kg(-1)), succinylcholine (1 mg x kg(-1)), cisatracurium, sevoflurane in oxygen and nitrous oxide, and fentanyl (5 microg x kg(-1)) after clamping the umbilical cord. We recorded maternal hemodynamic variables, pulse oximetry, capnography, bispectral index, and presence of muscular rigidity. In the neonate we assessed fetal wellbeing, weight, and requirement for naloxone. Hemodynamic stability was defined as no more than 15% variation in arterial pressure with respect to baseline.. Twelve patients undergoing surgery because of placenta abruptio, subarachnoid hemorrhage, HELLP syndrome, or preeclampsia were enrolled. Hemodynamic variables were consistently stable during surgery in all patients. No cases of neonatal rigidity were noted and there was no need for naloxone. The mean Apgar score was 6.42 (1.5) at 1 minute and 8.42 (0.9) at 5 minutes.. Bolus injection of 1 microg x kg(-1) of remifentanil may be useful for maintaining maternal hemodynamic stability in high-risk obstetric cases. Given the risk of neonatal depression, this resource should be used selectively and the means for neonatal resuscitation should be available.

Topics: Adult; Anesthetics, Intravenous; Atracurium; Cesarean Section; Female; Fentanyl; Fetus; Hemodynamics; Humans; Infant, Newborn; Methyl Ethers; Muscle Rigidity; Naloxone; Nitrous Oxide; Piperidines; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Propofol; Remifentanil; Resuscitation; Retrospective Studies; Sevoflurane; Succinylcholine

Topics: Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Chlorpromazine; Cholinesterase Inhibitors; Cognition Disorders; Creatine Kinase; Dementia; Disease Progression; Donepezil; Female; Humans; Indans; Lorazepam; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Piperidines; Recurrence; Risperidone

The objective of the study is to explore the longitudinal course of patients with Alzheimer's disease (AD) with and without extrapyramidal signs (EPS) taking donepezil. A cohort of 106 community-dwelling patients with probable AD receiving donepezil in Sydney, Australia (n = 52) and Manchester, UK (n = 54) was followed over 12 months. Cognition was measured by the Mini-Mental State Exam (MMSE) and the Alzheimer Disease Assessment Scale-Cognitive test (ADAS-Cog) and function by the Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). A further follow-up at five years was conducted to examine mortality and institutionalisation. At baseline, EPS were correlated with MMSE (r = -0.467, p < 0.01), ADAS-Cog (r = 0.485, p < 0.01) and ADCS-ADL (r = -0.526, p < 0.01) scores. Patients with EPS had lower MMSE (F = 9.95, df = 1, p = 0.002) and ADCS-ADL (F = 9.41, df = 1, p = 0.003) scores than patients without EPS. Over one year no time main effects or time x group interaction effects were observed for either dependent variable. At five years patients with EPS were found to have a hazard of institution or death 2.2 times higher than those without EPS (p = 0.018; 95% CI: 1.2, 4.4). There was a positive association between EPS and cognitive and functional impairment. However, EPS did not predict more rapid cognitive or functional decline of patients taking donepezil or response to donepezil. The presence of EPS was a risk factor both for institutionalisation and for death.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cohort Studies; Disease Progression; Donepezil; Female; Humans; Indans; Male; Muscle Rigidity; New South Wales; Piperidines; United Kingdom

Topics: Aged; Diagnosis, Differential; Dyskinesias; Eye Movements; Female; Humans; Muscle Rigidity; Piperidines; Remifentanil; Serotonin Syndrome

Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Blood Pressure; Cesarean Section; Esophageal and Gastric Varices; Female; Heart Rate; Hepatitis, Autoimmune; Humans; Infant, Newborn; Male; Muscle Rigidity; Piperidines; Pregnancy; Remifentanil; Respiratory Insufficiency; Thoracic Wall; Thrombocytopenia

Topics: Analgesics, Opioid; Humans; Muscle Rigidity; Pain, Postoperative; Piperidines; Remifentanil

The ability of anticholinergic agents microinjected into the subthalamic nucleus to reduce reserpine-induced muscular rigidity was assessed in rats. The electromyographical activity of the gastrocnemius-soleus muscle was used as a parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4-DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had no effect. These results suggest that a high cholinergic tone in the subthalamic nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in reducing the muscular rigidity in reserpinized rats, a model of Parkinson's disease, by blocking the high cholinergic tone in the subthalamic nucleus.

Topics: Anesthetics, Intravenous; Animals; Chloral Hydrate; Cholinergic Antagonists; Electromyography; Locomotion; Male; Microinjections; Muscarinic Antagonists; Muscle Rigidity; Muscle, Skeletal; Piperidines; Pirenzepine; Rats; Rats, Wistar; Reserpine; Sympatholytics; Thalamic Nuclei

The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose-dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system.

Topics: Animals; Azepines; Decerebrate State; Excitatory Amino Acid Antagonists; Glutamic Acid; Male; Motor Endplate; Muscle Relaxants, Central; Muscle Rigidity; Neurons; Oxazoles; Oxazolidinones; Piperidines; Rats; Rats, Inbred Strains; Reflex; Tremor

Topics: Aged; Butyrophenones; Humans; Huntington Disease; Male; Middle Aged; Muscle Rigidity; Piperidines; Tranquilizing Agents