piperidines and Craniocerebral-Trauma

Remifentanil, an ultra-short-acting opioid, is used as an on-top analgesic in head trauma patients during transient painful procedures, e.g. endotracheal suctioning, physiotherapy, on the intensive care unit. However, previous studies have shown that opioids may increase intracranial pressure and decrease cerebral blood flow.. The present study investigates the effect of remifentanil on mean arterial blood pressure, intracranial pressure measured with intraparenchymal or epidural probes, and on cerebral blood flow velocity assessed by transcranial Doppler flowmetry in 20 head trauma patients sedated with propofol and sufentanil. Ventilation was adjusted for a target PaCO2 of 4.7-5.1 kPa. After baseline measurements a bolus of remifentanil (0.5 microg x kg(-1) i.v.) was administrated followed by a continuous infusion of remifentanil (0.25 microg x kg(-1) x min(-1) i.v.) for 20 min.. There was no change in mean arterial blood pressure, intracranial pressure, and cerebral blood flow velocity in response to remifentanil infusion over time. Statistical analysis was performed using the Wilcoxon Signed Rank test.. These data suggest that remifentanil can be used for on-top analgesia in head trauma patients without adverse effects on cerebrovascular haemodynamics, cerebral perfusion pressure or intracranial pressure.

Topics: Analgesics, Opioid; Blood Flow Velocity; Blood Pressure; Body Temperature; Cerebrovascular Circulation; Craniocerebral Trauma; Female; Humans; Intracranial Pressure; Male; Middle Aged; Pain; Piperidines; Remifentanil; Statistics, Nonparametric; Time Factors

Topics: Adult; Aged; Anti-Inflammatory Agents; Antiemetics; Benzimidazoles; Clinical Trials as Topic; Craniocerebral Trauma; Dihydroxyphenylalanine; Dysmenorrhea; Esophagoscopy; Female; Humans; Male; Middle Aged; Migraine Disorders; Nausea; Piperidines; Premedication; Radiotherapy; Renal Dialysis; Vomiting

Topics: Adult; Aged; Craniocerebral Trauma; Eye Manifestations; Female; Humans; Male; Middle Aged; Phenothiazines; Piperidines; Placebos; Tranquilizing Agents; Whiplash Injuries

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO2) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.. In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.. In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO2 (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO2 were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).. Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO2, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.

Topics: Adult; Anesthetics, Dissociative; Craniocerebral Trauma; Hemodynamics; Humans; Hypnotics and Sedatives; Infusion Pumps; Intracranial Pressure; Italy; Ketamine; Piperidines; Propofol; Remifentanil; Suction; Trachea

Effective prophylaxis for post-traumatic epilepsy currently does not exist, and clinical trials using anticonvulsant drugs have yielded no long-term antiepileptogenic effects. We report that a single, rapid post-traumatic application of the proconvulsant cannabinoid type-1 (CB1) receptor antagonist SR141716A (Rimonabant-Acomplia) abolishes the long-term increase in seizure susceptibility caused by head injury in rats. These results indicate that, paradoxically, a seizure-enhancing drug may disrupt the epileptogenic process if applied within a short therapeutic time window.

Topics: Animals; Animals, Newborn; Anticonvulsants; Craniocerebral Trauma; Disease Models, Animal; Electroencephalography; Epilepsy, Post-Traumatic; Pentobarbital; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant

Recent experimental and modeling results demonstrated that surviving mossy cells in the dentate gyrus play key roles in the generation of network hyperexcitability. Here we examined if mossy cells exhibit long-term plasticity in the posttraumatic, hyperexcitable dentate gyrus. Mossy cells 1 wk after fluid percussion head injury did not show alterations in their current-firing frequency (I-F) and current-membrane voltage (I-V) relationships. In spite of the unchanged I-F and I-V curves, mossy cells showed extensive modifications in Na(+), K(+) and h-currents, indicating the coordinated nature of these opposing modifications. Computational experiments in a realistic large-scale model of the dentate gyrus demonstrated that individually, these perturbations could significantly affect network activity. Synaptic inputs also displayed systematic, opposing modifications. Miniature excitatory postsynaptic current (EPSC) amplitudes were decreased, whereas miniature inhibitory postsynaptic current (IPSC) amplitudes were increased as expected from a homeostatic response to network hyperexcitability. In addition, opposing alterations in miniature and spontaneous synaptic event frequencies and amplitudes were observed for both EPSCs and IPSCs. Despite extensive changes in synaptic inputs, cannabinoid-mediated depolarization-induced suppression of inhibition was not altered in posttraumatic mossy cells. These data demonstrate that many intrinsic and synaptic properties of mossy cells undergo highly specific, long-term alterations after traumatic brain injury. The systematic nature of such extensive and opposing alterations suggests that single-cell properties are significantly influenced by homeostatic mechanisms in hyperexcitable circuits.

Topics: Animals; Animals, Newborn; Computer Simulation; Craniocerebral Trauma; Disease Models, Animal; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; In Vitro Techniques; Membrane Potentials; Models, Neurological; Mossy Fibers, Hippocampal; Nerve Net; Neurons; Patch-Clamp Techniques; Piperidines; Potassium Channel Blockers; Pyrazoles; Pyrimidines; Rats; Sodium Channel Blockers; Tetraethylammonium; Tetrodotoxin

Topics: Anesthetics, Intravenous; Bradycardia; Child, Preschool; Craniocerebral Trauma; Humans; Male; Piperidines; Remifentanil

In this paper a robust method is developed for the analysis of data consisting of repeated binary observations taken at up to three fixed time points on each subject. The primary objective is to compare outcomes at the last time point, using earlier observations to predict this for subjects with incomplete records. A score test is derived. The method is developed for application to sequential clinical trials, as at interim analyses there will be many incomplete records occurring in non-informative patterns. Motivation for the methodology comes from experience with clinical trials in stroke and head injury, and data from one such trial is used to illustrate the approach. Extensions to more than three time points and to allow for stratification are discussed.

Topics: Clinical Trials as Topic; Craniocerebral Trauma; Data Interpretation, Statistical; Excitatory Amino Acid Antagonists; Glasgow Outcome Scale; Humans; Models, Biological; Models, Statistical; Piperidines

We report the case of a 19-year-old man with a drug abuse history, admitted to the intensive care unit for head and chest trauma, who experienced an acute tolerance to sedative and respiratory depression effects of remifentanil, which was given as the sole agent for sedation. He did not exhibit any signs of drug tolerance or intraoperative awareness during prolonged remifentanil-based anesthesia using propofol or sevoflurane as adjuvants. Several recent studies support the hypothesis of a possible involvement of N-methyl-d-aspartate glutamate receptors. The clinical relevance of this report is that if a patient with a previously acute tolerance to remifentanil during sedation undergoes long-term surgery, and propofol or sevoflurane is coadministered in a remifentanil-based anesthesia, the patient will not necessarily develop opioid tolerance. It is of interest for anesthesiologists, given the high frequency of patients with drug abuse history who are admitted to intensive care units, often sedated with remifentanil, who undergo anesthesia for emergency surgery.

Topics: Adjuvants, Anesthesia; Adult; Analgesics, Opioid; Anesthesia, General; Anesthetics, Inhalation; Craniocerebral Trauma; Drug Tolerance; Humans; Hypnotics and Sedatives; Male; Methyl Ethers; Neurosurgery; Orthopedics; Piperidines; Propofol; Remifentanil; Sevoflurane; Substance-Related Disorders; Thoracic Injuries

In patients with severe traumatic brain injury, bronchotracheal toilet may be accompanied by deleterious variations in intracranial pressure (ICP). To avoid these effects, IV opioids have been proposed. Twenty mechanically-ventilated patients received 3 ascending IV doses of remifentanil: dose 1 (1 microg/kg bolus, 0.25 microg/kg/min infusion); dose 2 (2 microg/kg bolus, 0.5 microg/kg/min infusion); and dose 3: (4 microg/kg bolus, 1 microg/kg/min infusion). Endotracheal suction was performed 20 min after the beginning of infusion to assess coughing. Heart rate, ICP, mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (V(MCA)), and bispectral index were monitored throughout the 30-min study period. Twelve, 15, and 19 patients receiving dose 1, 2, and 3, respectively, required vasopressors to maintain CPP >60 mm Hg. Suctioning resulted in coughing in 16, 15, and 5 patients receiving dose 1, 2, and 3, respectively. An increase in ICP, without change in V(MCA), corresponded to the reduction in MAP consistent with the preservation of autoregulation. Remifentanil used as a continuous infusion in head-injured patients is not an effective drug to block responses to suctioning.

Topics: Adult; Blood Pressure; Cerebrovascular Circulation; Cough; Craniocerebral Trauma; Dose-Response Relationship, Drug; Electroencephalography; Female; Heart Rate; Homeostasis; Humans; Hypnotics and Sedatives; Intracranial Pressure; Male; Middle Cerebral Artery; Piperidines; Remifentanil; Suction

Between 1993 and 1996, a total of 452 patients were entered into a randomized trial evaluating eliprodil (a non-competitive NMDA receptor antagonist) in patients suffering from severe head injury. The primary efficacy analysis concerned the Glasgow Outcome Score (GOS), six months after randomization. This outcome was classified into three ordered categories: good recovery; moderate disability, and the worst category made up by combining severe disability, vegetative state and dead. A sample size calculation was performed prior to the commencement of the study, using a formula which depends on the anticipated proportions of patients in the three different outcome categories, the proportional odds assumption and on the relationship between outcome and prognostic factors such as Glasgow Coma Score at entry. Owing to uncertainty about the influence of prognostic factors, and about the proportion of patients in the three GOS categories, a blinded sample size review was planned. This review was performed on the basis of the first 93 patients to respond, and this led to an increase in the sample size from 400 to 450. In this paper the pre-trial simulations showing that the type I error rate would be influenced and the power would be preserved will be presented, and the implementation of the procedure will be described.

Topics: Craniocerebral Trauma; Glasgow Coma Scale; Humans; Models, Statistical; Piperidines; Prognosis; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Sample Size; Treatment Outcome

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Adult; Age Factors; Amino Alcohols; Craniocerebral Trauma; Deafness; Electrooculography; Humans; Injections, Intravenous; Ischemic Attack, Transient; Piperidines; Prognosis; Tinnitus; Vertigo; Vestibular Function Tests