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Midazolam
Kinds of Midazolam Terms modified by Midazolam Selected AbstractsPharmacokinetics of intravenous and oral midazolam in plasma and saliva in humans: usefulness of saliva as matrix for CYP3A phenotypingBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2008Bettina Link WHAT IS ALREADY KNOWN ABOUT THE SUBJECT , Midazolam is a frequently used probe drug for CYP3A phenotyping in plasma. Midazolam and its hydroxy-metabolites can be detected in saliva. WHAT THIS STUDY ADDS , The concentrations of midazolam and its hydroxy-metabolites are much lower in saliva than in plasma, but the midazolam concentrations in both matrices show a significant linear correlation. , Saliva appears to be a suitable matrix for CYP3A phenotyping with midazolam, but very sensitive methods are required due to the low concentrations of midazolam and its hydroxy-metabolites. AIMS To compare midazolam kinetics between plasma and saliva and to find out whether saliva is suitable for CYP3A phenotyping. METHODS This was a two way cross-over study in eight subjects treated with 2 mg midazolam IV or 7.5 mg orally under basal conditions and after CYP3A induction with rifampicin. RESULTS Under basal conditions and IV administration, midazolam and 1,-hydroxymidazolam (plasma, saliva), 4-hydroxymidazolam and 1,-hydroxymidazolam-glucuronide (plasma) were detectable. After rifampicin, the AUC of midazolam [mean differences plasma 53.7 (95% CI 4.6, 102.9) and saliva 0.83 (95% CI 0.52, 1.14) ng ml,1 h] and 1,-hydroxymidazolam [mean difference plasma 11.8 (95% CI 7.9 , 15.7) ng ml,1 h] had decreased significantly. There was a significant correlation between the midazolam concentrations in plasma and saliva (basal conditions: r = 0.864, P < 0.0001; after rifampicin: r = 0.842, P < 0.0001). After oral administration and basal conditions, midazolam, 1,-hydroxymidazolam and 4-hydroxymidazolam were detectable in plasma and saliva. After treatment with rifampicin, the AUC of midazolam [mean difference plasma 104.5 (95% CI 74.1, 134.9) ng ml,1 h] and 1,-hydroxymidazolam [mean differences plasma 51.9 (95% CI 34.8, 69.1) and saliva 2.3 (95% CI 1.9, 2.7) ng ml,1 h] had decreased significantly. The parameters separating best between basal conditions and post-rifampicin were: (1,-hydroxymidazolam + 1,-hydroxymidazolam-glucuronide)/midazolam at 20,30 min (plasma) and the AUC of midazolam (saliva) after IV, and the AUC of midazolam (plasma) and of 1,-hydroxymidazolam (plasma and saliva) after oral administration. CONCLUSIONS Saliva appears to be a suitable matrix for non-invasive CYP3A phenotyping using midazolam as a probe drug, but sensitive analytical methods are required. [source] DOSE,RESPONSE OF ROPIVACAINE ADMINISTERED CAUDALLY TO CHILDREN UNDERGOING SURGICAL PROCEDURES UNDER SEDATION WITH MIDAZOLAMCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2004F Tonatiu Aguirre-Garay SUMMARY 1.,In a double-blind randomized controlled design, 50 children were allocated to receive bupivacaine 0.25% or ropivacaine 0.25%, 0.32%, 0.40% or 0.50% by caudal block. 2.,Caudal block was performed after induction of anaesthesia with 2,5% sevoflurane, atropine 10 µg/kg and midazolam 100,300 µg/kg. During the surgical procedure, patients were maintained under spontaneous ventilation and no intravenous or inhalatory anaesthetic agent was administered. For transoperative sedation, midazolam 100,300 µg/kg was administered every 0.5,1.0 h. Transoperative cardiovascular response, postoperative analgesia and local and systemic complications were evaluated. 3.,Groups were similar (P > 0.05) in sex, age, weight and in the time elapsed from caudal block to the beginning of the surgical procedure. The surgical time was significantly lower in the ropivacaine 0.25% group. The duration of analgesia was 24 h with ropivacaine 0.25% and approximately 10 h in the other four groups (P < 0.001). Linear regression analysis revealed a significant relationship between the postoperative analgesic period produced by ropivacaine and the surgical time (r = , 0.48, two-sided P = 0.002). Systolic and diastolic blood pressures remained in the physiologically normal range for the duration of the transoperative period. Vomiting was present in only one patient receiving ropivacaine 0.50%. 4.,In children, the duration of analgesia produced by caudal block with ropivacaine may be affected by surgical time. At surgical times of 0.5,1 h, ropivacaine 0.25% produced at least 24 h postoperative analgesia. At similar surgical times, ropivacaine 0.32%, 0.40% and 0.50% produced similar analgesic times to bupivacaine 0.25%. [source] Intensive care unit management of patients with status epilepticusEPILEPSIA, Issue 2007Thomas P. Bleck Summary The intensive care unit management of status epilepticus focuses on patients who are refractory to initial treatment, who have an underlying condition that require critical care management, or who experience respiratory or cardiovascular complications of their therapies. The available data suggest that failure of a first-line anticonvulsant agent to terminate status should lead to the use of a definitive therapy in general anesthetic doses. Midazolam, propofol, and phenobarbital have been used most frequently; the place of newer agents (e.g., valproate, levetiracetam, or topiramate) remains to be determined. [source] Underdosing of Midazolam in Emergency Endotracheal IntubationACADEMIC EMERGENCY MEDICINE, Issue 4 2003Mark J. Sagarin MD Objectives: To determine whether midazolam, when used as an induction agent for emergency department (ED) rapid-sequence intubation (RSI), is used in adequate and recommended induction doses (0.1 to 0.3 mg/kg), and to compare the accuracy of the dosing of midazolam for ED RSI with the accuracy of dosing of other agents. Methods: The authors conducted a systematic query of a prospectively collected database of ED intubations using the National Emergency Airway Registry data, gathered in 11 participating EDs over a 16-month period. A data form completed at the time of emergency department intubation (EDI) enabled analysis of patients' ages, weights, and indications for EDI, as well as the techniques and drugs used to facilitate EDI. Data were analyzed to determine whether midazolam is used in recommended doses during RSI. Patients intubated with midazolam alone were compared with patients who received other induction agents for RSI. Results: Of 1,288 patients entered in the study, 1,023 (79%) underwent RSI. Of the 888 RSI patients with an age recorded, midazolam was used as the sole induction agent in 140 (16%). The mean (±SD) dosages of midazolam used in RSI were 2.6 (±1.7) mg in children (age , 18) and 3.7 (±2.5) mg in adults (age ,19); the mean (±SD) dosages by weight were 0.08 (±0.04) mg/kg in children and 0.05 (±0.03) mg/kg in adults. More than half (56%) of the children, and nearly all (92%) of the adults, received dosages lower than the minimum recommended dosage (0.1 mg/kg). Of patients who received barbiturates, only 21% of children and 21% of adults received a dose lower than the minimum recommended. When combined with another induction agent, midazolam was dosed similarly to when it was used alone: mean adult doses were 3.1 (±1.2) mg and 0.04 (±0.02) mg/kg. Conclusions: Underdosing of midazolam during ED RSI is frequent, and appears to be related to incorrect dosage selection, rather than to a deliberate intention to reduce the dose used. [source] Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal TransductionEPILEPSIA, Issue 3 2003Daniël M. Jonker Summary: ,Purpose: The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the ,-aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake. Methods: The in vivo concentration,response relation of TGB was determined through pharmacokinetic/pharmacodynamic (PK/PD) modeling. Rats received a single intravenous dose of 10 mg/kg TGB in the absence and the presence of a steady-state plasma concentration of MDL. The EEG response in the 11.5- to 30-Hz frequency band was used as the pharmacodynamic end point. Results: Infusion of MDL resulted in a mean steady-state plasma concentration of 66 ± 3 ng/ml. A significant pharmacokinetic interaction with TGB was observed. MDL inhibited TGB clearance by 20 ± 7 ml/min/kg from the original value of 89 ± 6 ml/min/kg. However, no changes in plasma protein binding of both drugs were observed. The concentration,EEG relation of TGB was described by the sigmoid- Emax model. The pharmacodynamic parameter estimates of TGB were: Emax = 327 ± 10 ,V, EC50 = 392 ± 20 ng/ml, and nH = 3.1 ± 0.3. These values were not significantly different in the presence of MDL. Factors that may explain the lack of synergism were identified by a mechanism-based interaction model that separates the receptor activation from the signal-transduction process. High efficiency of signal transduction and the presence of a baseline response were shown to diminish the degree of synergism. Conclusions: We conclude that the in vivo pharmacodynamic interaction between MDL and TGB is additive rather than synergistic. This strongly suggests that allosteric modulation of the antiseizure activity of a GAT-1 inhibitor by a benzodiazepine does not offer a therapeutic advantage. [source] A Combination of Midazolam and Ketamine for Procedural Sedation and Analgesia in Adult Emergency Department PatientsACADEMIC EMERGENCY MEDICINE, Issue 3 2000Carl R. Chudnofsky MD Abstract Objective: To describe the clinical characteristics of a combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department (ED) patients. Methods: This was a prospective, observational trial, conducted in the ED of an urban level II trauma center. Patients , 18 years of age requiring procedural sedation and analgesia were eligible, and enrolled patients received 0.07 mg/kg of intravenous midazolam followed by 2 mg/kg of intravenous ketamine. Vital signs were recorded at regular intervals. The adequacy of sedation, adverse effects, patient satisfaction, and time to reach discharge alertness were determined. Descriptive statistics were calculated using statistical analysis software. Results: Seventy-seven patients were enrolled. Three were excluded due to protocol violations, three due to lack of documentation, and one due to subcutaneous infiltration of ketamine, leaving 70 patients for analysis. The average age was 31 years, and 41 (59%) were female. Indications for procedural sedation and analgesia included abscess incision and drainage (66%), fracture/joint reduction (26%), and other (8%). The mean dose of midazolam was 5.6 ± 1.4 mg and the mean dose of ketamine was 159 ± 42 mg. The mean time to achieve discharge criteria was 64 ± 24 minutes. Fivepatients experienced mild emergence reactions, but there were no episodes of hallucinations, delirium, or other serious emergence reactions. Eighteen (25%) patients recalled dreaming while sedated; twelve (17%) were described as pleasant, two (3%) unpleasant, three (4%) both pleasant and unpleasant, and one (1%) neither pleasant nor unpleasant. There were four (6%) cases of respiratory compromise, two (3%) episodes of emesis, and one (1%) case of myoclonia. All of these were transient and did not result in a change in the patient's disposition. Only one (1%) patient indicated that she was not satisfied with the sedation regimen. Conclusions: The combination of midazolam and ketamine provides effective procedural sedation and analgesia in adult ED patients, and appears to be safe. [source] Sedation with midazolam versus local anaesthesia with lignocaine for transrectal prostate biopsiesINTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 2 2008Ilana Golan Abstract Transrectal ultrasound-guided needle biopsy of the prostate is the only method for diagnosing prostate cancer. Although tolerated by most patients, 65,90% of patients complain of pain during the procedure. Most urologists utilize ultrasound-guided transrectal injection of lignocaine. Intravenous sedation with short-acting medications such as midazolam has been successfully used during many invasive ambulatory procedures, reducing discomfort and anxiety. The aim of this study was to compare the efficacy of pain and anxiety reduction using intravenous sedation with midazolam versus local anaesthesia with lignocaine during transrectal biopsies of the prostate in a cross-sectional study. Ninety consecutive candidates for transrectal prostate biopsy were divided into 2 groups. Group A received periprostatic block with 2% lignocaine and group B received sedation with intravenous injection of 4 mg midazolam prior to insertion of the probe. Side-effects and patient satisfaction were documented by questionnaires, which included a pain visual analogue scale (VAS). Significant differences were found between the two groups with respect to the patient's perceived intensity of pain. Pain level expressed by a VAS was 4·2 in group A and 1·9 in group B (P < 0·001). Eighty-seven per cent of the patients in group B stated that they would be willing to repeat the procedure if necessary compared with 55% in group A (P = 0·002). There were no complications or side-effects as a result of midazolam sedation. Midazolam is more effective in relieving pain and anxiety during transrectal prostate biopsies and as safe as a local injection of lignocaine. [source] Conscious Sedation with Intermittent Midazolam and Fentanyl in Electrophysiology ProceduresJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2001F.A.C.C., ROMAN T. PACHULSKI M.D. Objectives: To determine the safety and efficacy of intermittent midazolam and fentanyl conscious sedation for electrophysiology procedures (EP). Background: Intermittent midazolam and fentanyl conscious sedation was administered in 700 consecutive cases (175 radiofrequency ablations, 163 EP studies, 261 pacemakers, and 101 implantable cardioverter-defibrillators) for 471 patients (239 males, 51%) mean age 65 ± 15 years. The mean dose of midazolam was 0.063 mg/kg/hr and fentanyl was 0.591,g/kg/hr. Methods: Cardiac rate and rhythm were monitored continuously, while blood pressure and arterial oxygen saturation were noninvasively assessed evevy 5 minutes. Drugs were administered in aliquots of 0.5 to 2.0 mg of midazolam and 6.25 to 25 ,g of fentanyl as determined by clinical condition every 15 to 30 minutes. Results: There were no deaths. In no case was endotracheal intubation required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning (12 cases, 1.7%), increased F1O2 (3 cases, 0.4%), or intravenous naloxone (2 cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mmHg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (4 cases, 0.6%). No patient stay was prolonged due to sedation. Only five patients (0.7%) had any recollection of the procedure, while two (0.3%) were aware of pain. All hypoxemic episodes occurred during the first hour, whereas 43% (6/14) of hypotensive episodes occurred after the first hour. Conclusion: Conscious sedation with intermittent midazolam and fentanyl is safe and eficacious for a broad range of EP procedures. (J Interven Cardiol 2001; 14:143,146) [source] In vitro assessment of cytochrome P450 inhibition: Strategies for increasing LC/MS-based assay throughput using a one-point IC50 method and multiplexing high-performance liquid chromatographyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2007Tong Lin Abstract A fast and robust LC/MS-based cytochrome P450 (CYP) inhibition assay, using human liver microsomes, has been fully developed and validated for the major human liver CYPs. Probe substrates were phenacetin, diclofenac, S-mephenytoin, and dextromethorphan for CYP1A2, CYP2C9, CYP2C19, and CYP2D6, respectively. Midazolam and testosterone were chosen for CYP3A4. Furafylline, sulfaphenazole, tranylcypromine, quinidine, and ketoconazole were identified as positive control inhibitors for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. To increase the throughput of the assay, a one-point method was developed, using data from CYP inhibition assays conducted at one concentration (i.e., 10 µM), to estimate the drug concentration at which the metabolism of the CYP probe substrate was reduced by 50% (IC50). The IC50 values from the one-point assay were validated by correlating the results with IC50 values that were obtained with a traditional eight-point concentration,response curve. Good correlation was achieved with the slopes of the trendlines between 0.95 and 1.02 and with R2 between 0.77 and 1.0. Throughput was increased twofold by using a Cohesive multiplexing high-performance liquid chromatography system. The one-point IC50 estimate is useful for initial compound screening, while the full concentration,response IC50 method provides detailed CYP inhibition data for later stages of drug development. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2485,2493, 2007 [source] Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedicationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2006H. Bergendahl Background:, Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri-operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri-operative management in infants and children. Later publications also support the use of clonidine for premedication (3,6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children. [source] Effects of midazolam on small bowel motility in humansALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2000Castedal Background: Benzodiazepines are used as sedatives for some intestinal procedures and as hypnotics, and this is the reason for studying their effects on duodenojejunal motility. Methods: Antroduodenojejunal manometry was performed in 13 healthy volunteers on two different occasions, when placebo or midazolam were given intravenously (randomized, double-blind). A bolus dose of midazolam 0.03 mg/kg was followed by 0.015 mg/kg after 1.5, 3 and 4.5 h. After 5 h observation of interdigestive motility, the volunteers were given a test meal and recording continued for another hour. Twenty-eight motility variables were compared. Results: With midazolam the median motility index of phase III in the proximal duodenum was increased by 37% (P < 0.05), which was a consequence of both a longer duration (P < 0.01) and higher pressure amplitudes (P < 0.05), compared with placebo. A longer duration (9%) of phase III was also seen in the distal duodenum (P < 0.05). With midazolam the duration of the migrating motor complex was shortened by 27% (P < 0.05). No statistically significant difference was found for the number of episodes of phase III registered (P=0.09), or for the other 22 motility variables compared including the duodenal retroperistalsis in late phase III. Conclusion: Midazolam does affect some aspects of duodenal motility, especially in the proximal part, but phase III-related retroperistalsis is not affected. [source] Complete Recovery From Intractable Complex Regional Pain Syndrome, CRPS-Type I, Following Anesthetic Ketamine and MidazolamPAIN PRACTICE, Issue 2 2007Ralph-Thomas Kiefer MD Abstract Objective: To describe the treatment of an intractable complex regional pain syndrome I (CRPS-I) patient with anesthetic doses of ketamine supplemented with midazolam. Methods: A patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3,5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. Results: On the second day of the ketamine and midazolam infusion, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. Conclusions: In a patient with severe spreading and refractory CRPS, a complete and long-term remission from CRPS has been obtained utilizing ketamine and midazolam in anesthetic doses. This intensive care procedure has very serious risks but no severe complications occurred. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment. This case report illustrates the effectiveness and safety of high-dose ketamine in a patient with generalized, refractory CRPS. [source] Midazolam as a sole sedative for computed tomography imaging in pediatric patientsPEDIATRIC ANESTHESIA, Issue 9 2009RANJU SINGH MD Summary Objective:, To evaluate the efficacy and adverse effects of i.v. midazolam as a sole agent for sedation in children for computed tomography (CT) imaging. Materials and Methods:, Prospective clinical trial in which 516 children under ASA classification II,IV (273 boys and 243 girls) in the age group of 6 months to 6 years for elective CT scan were enrolled over a 17-month period. Patients were administered i.v. midazolam 0.2 mg·kg,1 and further boluses of 0.1 mg·kg,1 (total 0.5 mg·kg,1) if required. Measurements included induction time, efficacy, side effects, complications, and degree of sedation. Sedation was graded on the basis of Ramsay sedation score (RSS) as over sedated (RSS 5,6), adequately sedated (AS, RSS 3,4), under sedated (RSS 1,2), or failed if the procedure could not be completed or another agent had to be administered. Results:, Of the 516 procedures, 483 brains, 16 chests, and 17 abdomens were scanned with a mean duration of 4.75 ± 1.75 min with a mean dose of 0.212 mg·kg,1 of i.v. midazolam. Four hundred and sixty-five (90.12%) patients were AS in 5.9 ± 0.7 min while 40 (7.75%) patients required additional boluses. Of these 40 patients, 24 (4.65%) required a single bolus, 12 (2.32%) required two boluses, whereas the remaining four (0.78%) required three boluses. In 11 (2.13%; P < 0.0001) patients, the scan could not be completed satisfactorily. Side effects were seen in 46 (9.11%) patients in the form of desaturation, hiccups (seven patients, 1.38%), and agitation (four patients, 0.79%). Desaturation (SpO2 90,95%) was seen in 35 (6.93%) patients, which was corrected by topical application of oxygen. None of the patients exhibited any complications such as pulmonary aspiration or need to maintain airway. The patients were kept under observation for 1 h after the procedure. Conclusion:, The level of sedation achieved in children with midazolam 0.2 mg·kg,1 is adequate for imaging with minimal side effects, no airway complications, and fast recovery. It can be recommended as the sole agent for sedation in pediatric patients for CT imaging. [source] Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgeryPEDIATRIC ANESTHESIA, Issue 7 2008SANDRA A. PRINS MD PhD Summary Background:, The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods:, During surgery all infants (6 months,2 years) received a rectal loading dose of 40 mg·kg,1 paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg·kg,1 propacetamol, a prodrug of paracetamol, or 20 mg·kg,1 paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0,10 cm) and COMFORT Behavior scale (score 6,30) were used to monitor analgesia in the 24-h period following surgery. Results:, Twelve infants received intravenous propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric ,1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, propacetamol hydrolysis half-life 0.028 h, clearance 12 l·h,1·70 kg,1, intercompartmental clearance 116 l·h,1·70 kg,1, central and peripheral volume of distribution 7.9 and 44 l·70 kg,1, respectively. During the 24-h study period 22 infants exhibited VAS scores <4 cm, which was considered a cutoff point. On single occasions four patients, two in each group, exhibited a VAS score ,4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P < 0.05). Conclusions:, Intravenous propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain. [source] Midazolam as premedication: is the emperor naked or just half-dressed?PEDIATRIC ANESTHESIA, Issue 4 2007Frederic A. Berry MD No abstract is available for this article. [source] Midazolam as premedication: Is the emperor naked or just half-dressed?PEDIATRIC ANESTHESIA, Issue 4 2005PER-ARNE LÖNNQVIST MD PhD No abstract is available for this article. [source] A comparison of dexmedetomidine and midazolam for sedation in third molar surgery,ANAESTHESIA, Issue 11 2007C. W. Cheung Summary This randomised, double-blind study compared dexmedetomidine and midazolam for intravenous sedation during third molar surgery under local anaesthesia. Sixty patients received either dexmedetomidine (up to 1 ,g.kg,1) or midazolam (up to 5 mg), which was infused until the Ramsay Sedation Score was four or the maximum dose limit was reached. Intra-operative vital signs, postoperative pain scores and analgesic consumption, amnesia, and satisfaction scores for patients and surgeons, were recorded. Sedation was achieved by median (IQR (range)) doses of 47 ,g (39,52 (25,76)) or 0.88 ,g.kg,1 (0.75,1.0 (0.6,1.0)) dexmedetomidine, and 3.6 mg (3.3,4.4 (1.9,5.0)) or 0.07 mg.kg,1 (0.055,0.085 (0.017,0.12)) midazolam. Heart rate and blood pressure during surgery were lower in dexmedetomidine group. There was no significant difference in satisfaction or pain scores. Midazolam was associated with greater amnesia. Dexmedetomidine produces comparable sedation to midazolam. [source] Thyroid storm prior to induction of anaesthesiaANAESTHESIA, Issue 10 2004E. A. Hirvonen Summary A 53- year-old woman without a previous history of thyroid disease was scheduled for mastectomy. On arrival in the operating theatre unpremedicated she appeared restless and tachycardic. Midazolam and fentanyl was administered intravenously. Concomitantly, sinus tachycardia developed and a flush reaction was observed in the skin of the thoracic region and neck. The blood pressure increased to 265/160 mmHg and the patient lost consciousness and became apnoeic. Unconsciousness and apnoea lasted for approximately 25 min and the operation was postponed. Further investigations revealed an elevated serum free thyroxine level and suppressed serum thyrotropin diagnostic of hyperthyroidism. The serum TSH receptor antibody concentration was elevated, indicating that the patient was suffering from Graves' disease. We present a case of a previously unknown hyperthyroid patient, with breast cancer, presenting as a thyroid crisis on induction of anaesthesia. Although being quite a rare occurrence, unsuspected thyroid disease should be borne in mind when an agitated patient enters the operating theatre. [source] Characterization of early plasma concentrations of midazolam in pigs after administration by an autoinjectorBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2004Aharon Levy Abstract The treatment of organophosphate-induced poisoning is based mainly on atropine and an oxime. Prompt anticonvulsive intervention is usually also required to terminate the ensuing seizure activity and to prevent delayed permanent brain damage. Midazolam, a water-soluble benzodiazepine agonist, has the advantage of rapid absorption following intramuscular administration. In mass casualty situations, the availability of an autoinjector, filled with midazolam, might be a further advantage. In the present study, the plasma pharmacokinetics of midazolam after administration by an autoinjector was compared with conventional intramuscular (i.m.) administration in two groups of four pigs each. During the first 15 min after injection, significantly higher plasma concentrations of midazolam were detected following autoinjector administration, compared with the i.m. injection. The physiological reflection of the accelerated midazolam absorption was a marked reduction in the time interval required for muscle relaxation, induced by midazolam. It is concluded that a midazolam autoinjector might be helpful in the mass casualty scenario following organophosphate poisoning. Copyright © 2004 John Wiley & Sons, Ltd. [source] Pharmacokinetics of intravenous and oral midazolam in plasma and saliva in humans: usefulness of saliva as matrix for CYP3A phenotypingBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2008Bettina Link WHAT IS ALREADY KNOWN ABOUT THE SUBJECT , Midazolam is a frequently used probe drug for CYP3A phenotyping in plasma. Midazolam and its hydroxy-metabolites can be detected in saliva. WHAT THIS STUDY ADDS , The concentrations of midazolam and its hydroxy-metabolites are much lower in saliva than in plasma, but the midazolam concentrations in both matrices show a significant linear correlation. , Saliva appears to be a suitable matrix for CYP3A phenotyping with midazolam, but very sensitive methods are required due to the low concentrations of midazolam and its hydroxy-metabolites. AIMS To compare midazolam kinetics between plasma and saliva and to find out whether saliva is suitable for CYP3A phenotyping. METHODS This was a two way cross-over study in eight subjects treated with 2 mg midazolam IV or 7.5 mg orally under basal conditions and after CYP3A induction with rifampicin. RESULTS Under basal conditions and IV administration, midazolam and 1,-hydroxymidazolam (plasma, saliva), 4-hydroxymidazolam and 1,-hydroxymidazolam-glucuronide (plasma) were detectable. After rifampicin, the AUC of midazolam [mean differences plasma 53.7 (95% CI 4.6, 102.9) and saliva 0.83 (95% CI 0.52, 1.14) ng ml,1 h] and 1,-hydroxymidazolam [mean difference plasma 11.8 (95% CI 7.9 , 15.7) ng ml,1 h] had decreased significantly. There was a significant correlation between the midazolam concentrations in plasma and saliva (basal conditions: r = 0.864, P < 0.0001; after rifampicin: r = 0.842, P < 0.0001). After oral administration and basal conditions, midazolam, 1,-hydroxymidazolam and 4-hydroxymidazolam were detectable in plasma and saliva. After treatment with rifampicin, the AUC of midazolam [mean difference plasma 104.5 (95% CI 74.1, 134.9) ng ml,1 h] and 1,-hydroxymidazolam [mean differences plasma 51.9 (95% CI 34.8, 69.1) and saliva 2.3 (95% CI 1.9, 2.7) ng ml,1 h] had decreased significantly. The parameters separating best between basal conditions and post-rifampicin were: (1,-hydroxymidazolam + 1,-hydroxymidazolam-glucuronide)/midazolam at 20,30 min (plasma) and the AUC of midazolam (saliva) after IV, and the AUC of midazolam (plasma) and of 1,-hydroxymidazolam (plasma and saliva) after oral administration. CONCLUSIONS Saliva appears to be a suitable matrix for non-invasive CYP3A phenotyping using midazolam as a probe drug, but sensitive analytical methods are required. [source] Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsionsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2008Simon N. Muchohi WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Midazolam (MDZ), a water-soluble benzodiazepine, can be administered via several routes, including intravenously (IV), intramuscularly (IM) and buccal routes to terminate convulsions. It may be a suitable alternative to diazepam to stop convulsions in children with severe malaria, especially at peripheral healthcare facilities. The pharmacokinetics of MDZ have not been described in African children, in whom factors such as the aetiology and nutritional status may influence the pharmacokinetics. WHAT THIS STUDY ADDS , Administration of MDZ (IV, IM, or buccal) at the currently recommended dose (0.3 mg kg,1) resulted in rapid achievement of median maximum plasma concentrations of MDZ within the range 64,616 ng ml,1, with few clinically significant cardio-respiratory effects. A single dose of MDZ rapidly terminated (within 10 min) seizures in all (100%), 9/12 (75%) and 5/8 (63%) children following IV, IM and buccal administration, respectively. Although IM and buccal MDZ may be the preferred treatment for children in the pre-hospital settings the efficacy appears to be poorer. AIM To investigate the pharmacokinetics and clinical efficacy of intravenous (IV), intramuscular (IM) and buccal midazolam (MDZ) in children with severe falciparum malaria and convulsions. METHODS Thirty-three children with severe malaria and convulsions lasting ,5 min were given a single dose of MDZ (0.3 mg kg,1) IV (n = 13), IM (n = 12) or via the buccal route (n = 8). Blood samples were collected over 6 h post-dose for determination of plasma MDZ and 1,-hydroxymidazolam concentrations. Plasma concentration,time data were fitted using pharmacokinetic models. RESULTS Median (range) MDZ Cmax of 481 (258,616), 253 (96,696) and 186 (64,394) ng ml,1 were attained within a median (range) tmax of 10 (5,15), 15 (5,60) and 10 (5,40) min, following IV, IM and buccal administration, respectively. Mean (95% confidence interval) of the pharmacokinetic parameters were: AUC(0,,) 596 (327, 865), 608 (353, 864) and 518 (294, 741) ng ml,1 h; Vd 0.85 l kg,1; clearance 14.4 ml min,1 kg,1, elimination half-life 1.22 (0.65, 1.8) h, respectively. A single dose of MDZ terminated convulsions in all (100%), 9/12 (75%) and 5/8 (63%) children following IV, IM and buccal administration. Four children (one in the IV, one in the IM and two in the buccal groups) had respiratory depression. CONCLUSIONS Administration of MDZ at the currently recommended dose resulted in rapid achievement of therapeutic MDZ concentrations. Although IM and buccal administration of MDZ may be more practical in peripheral healthcare facilities, the efficacy appears to be poorer at the dose used, and a different dosage regimen might improve the efficacy. [source] Safety and Clinical Effectiveness of Midazolam versus Propofol for Procedural Sedation in the Emergency Department: A Systematic ReviewACADEMIC EMERGENCY MEDICINE, Issue 1 2008Corinne Michèle Hohl MD Abstract Objectives:, To synthesize the evidence comparing the adverse event (AE) profile and clinical effectiveness of midazolam and propofol for procedural sedation (PS) in adults in the emergency care setting. Methods:, The authors conducted a systematic review of randomized controlled trials (RCTs) and observational studies reporting the use of either midazolam and/or propofol for adult PS in the emergency department (ED). A systematic search strategy was developed and applied to six bibliographic reference databases. Three emergency medicine journals, the Canadian Adverse Drug Reaction Newsletter, and conference proceedings were hand-searched. Retrieved articles were reviewed and data were abstracted using standardized data collection. Trial quality was assessed using the Jadad score. The outcomes assessed were the proportion of patients with AEs and the pooled mean difference in the proportion of patients with successful PS. Results:, Of 229 articles identified, 28 met the inclusion criteria for the analysis of AEs. Only one major AE to PS was found, resulting in no statistically significant difference in the proportion of major AEs between agents. Four studies were RCTs that met the inclusion criteria for the analysis of clinical effectiveness. Two trials met criteria for good quality. The RCTs enrolled between 32 and 86 patients, and the most common indications for PS were orthopedic reductions and cardioversions. There was a nonsignificant difference in the proportion of patients with successful PS in favor of propofol (effect difference 2.9%, 95% confidence interval (CI) = ,6.5 to 15.2). Conclusions:, The authors found no significant difference in the safety profile and the proportion of successful PS between midazolam and propofol for adults in the ED. [source] A Cost-effectiveness Analysis of Propofol versus Midazolam for Procedural Sedation in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 1 2008Corinne Michèle Hohl MD Abstract Objectives:, To determine the incremental cost-effectiveness of using propofol versus midazolam for procedural sedation (PS) in adults in the emergency department (ED). Methods:, The authors conducted a cost-effectiveness analysis from the perspective of the health care provider. The primary outcome was the incremental cost (or savings) to achieve one additional successful sedation with propofol compared to midazolam. A decision model was developed in which the clinical effectiveness and cost of a PS strategy using either agent was estimated. The authors derived estimates of clinical effectiveness and risk of adverse events (AEs) from a systematic review. The cost of each clinical outcome was determined by incorporating the baseline cost of the ED visit, the cost of the drug, the cost of labor of physicians and nurses, the cost and probability of an AE, and the cost and probability of a PS failure. A standard meta-analytic technique was used to calculate the weighted mean difference in recovery times and obtain mean drug doses from patient-level data from a randomized controlled trial. Probabilistic sensitivity analyses were conducted to examine the uncertainty around the estimated incremental cost-effectiveness ratio using Monte Carlo simulation. Results:, Choosing a sedation strategy with propofol resulted in average savings of $17.33 (95% confidence interval [CI] = $24.13 to $10.44) per sedation performed. This resulted in an incremental cost-effectiveness ratio of ,$597.03 (95% credibility interval ,$6,434.03 to $6,113.57) indicating savings of $597.03 per additional successful sedation performed with propofol. This result was driven by shorter recovery times and was robust to all sensitivity analyses performed. Conclusions:, These results indicate that using propofol for PS in the ED is a cost-saving strategy. [source] Midazolam Versus Diazepam for the Treatment of Status Epilepticus in Children and Young Adults: A Meta-analysisACADEMIC EMERGENCY MEDICINE, Issue 6 2010Jason McMullan MD Abstract Background:, Rapid treatment of status epilepticus (SE) is associated with better outcomes. Diazepam and midazolam are commonly used, but the optimal agent and administration route is unclear. Objectives:, The objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam, by any route, in terminating SE seizures in children and adults. Time to seizure cessation and respiratory complications was examined. Methods:, We performed a search of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, American College of Physicians Journal Club, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and International Pharmaceutical Abstracts for studies published January 1, 1950, through July 4, 2009. English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE, and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures, were eligible. Two reviewers independently screened studies for inclusion and extracted outcomes data. Administration routes were stratified as non-IV (buccal, intranasal, intramuscular, rectal) or IV. Fixed-effects models generated pooled statistics. Results:, Six studies with 774 subjects were included. For seizure cessation, midazolam, by any route, was superior to diazepam, by any route (relative risk [RR] = 1.52; 95% confidence interval [CI] = 1.27 to 1.82). Non-IV midazolam is as effective as IV diazepam (RR = 0.79; 95% CI = 0.19 to 3.36), and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 1.54; 95% CI = 1.29 to 1.85). Midazolam was administered faster than diazepam (mean difference = 2.46 minutes; 95% CI = 1.52 to 3.39 minutes) and had similar times between drug administration and seizure cessation. Respiratory complications requiring intervention were similar, regardless of administration route (RR = 1.49; 95% CI = 0.25 to 8.72). Conclusions:, Non-IV midazolam, compared to non-IV or IV diazepam, is safe and effective in treating SE. Comparison to lorazepam, evaluation in adults, and prospective confirmation of safety and efficacy is needed. ACADEMIC EMERGENCY MEDICINE 2010; 17:575,582 © 2010 by the Society for Academic Emergency Medicine [source] Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skillsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010E. GALVIN Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. Results: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05. Conclusion: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills. [source] Additives in intravenous anesthesia modulates pulmonary inflammation in a model of LPS-induced respiratory distressACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009J. J. HAITSMA Background: It has been suggested that propofol with ethylenediaminetetraacetic acid (EDTA) can modulate the systemic inflammatory response. Prolonged higher levels of pulmonary inflammation are associated with poor outcome of patients with acute lung injury. In the present study, we hypothesized that pulmonary inflammation could be modulated by propofol with EDTA compared with propofol with sulfite. Methods: Respiratory distress was induced in rats (n=25) by intratracheal nebulization of lipopolysaccharide (LPS). After 24 h, animals were randomized to either propofol with EDTA (PropofolEDTA), propofol with sulfite (Propofolsulfite) or ketamine/midazolam (Ket/Mid); control animals received saline (n=30). Animals were ventilated for 4 h and blood gases were measured hourly. Bronchoalveolar lavage (BAL) was performed for cytokine analysis of: tumor necrosis factor (TNF), interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2. Results: LPS led to increased pulmonary inflammation in all groups compared with the control groups. Gas exchange deteriorated over time only in the LPS Propofolsulfite group and was significantly lower than the Ket/Mid group. Only IL-6 was significantly higher in the LPS Propofolsulfite group compared with both the Ket/Mid group and the PropofolEDTA group. Conclusion: Pulmonary IL-6 can be modulated by additives in systemic anesthesia. Implication Statement: This study demonstrates that pulmonary inflammation caused by direct lung injury can be modulated by intravenous anesthesia used in critically ill patients. [source] DEXMEDETOMIDINE FOR SEDATION DURING UPPER GASTROINTESTINAL ENDOSCOPYDIGESTIVE ENDOSCOPY, Issue 4 2008Kazutoshi Hashiguchi Background:, A clinical study was conducted to investigate the safety and efficacy of dexmedetomidine for sedation of patients undergoing routine upper gastrointestinal (GI) endoscopy. Methods:, Forty middle-aged patients who were admitted for medical examination were randomized to receive an initial loading dose infusion of dexmedetomidine 6.0 µg/kg per h over 10 min followed by a maintenance infusion of 0.6 µg/kg per h (group A) or rapid infusion of midazolam 0.05 mg/kg (group B) as sedation for routine endoscopy. Sixty patients did not receive sedative agent (group C). Assessment included measurement of heart rate (HR), blood pressure (BP), oxygen saturation, and endoscopy duration. Results:, There were no statistically significant differences among the groups in baseline characteristics. The level of sedation was similar between groups A and B, and the gag response score was significantly lower in the sedated groups than in group C. Hemodynamic stability was also demonstrated in group A during and after the endoscopic procedure. Increased systolic/diastolic BP was significantly attenuated in group A compared with group C. Interestingly, HR was significantly suppressed in group A than in groups B and C. In groups A and B, SpO2 was decreased compared with group C during and after the procedures; however, there was no significant difference between the two groups. There was no significant difference among the groups with endoscopy duration. Conclusions:, For sedation during upper endoscopy, dexmedetomidine is as safe and effective as midazolam, and it significantly reduces HR and BP during and after the endoscopic procedures. [source] Procedural sedation in children in the emergency department: A PREDICT studyEMERGENCY MEDICINE AUSTRALASIA, Issue 1 2009Meredith Borland Abstract Objective: To investigate current procedural sedation practice and compare clinical practice guidelines (CPG) for procedural sedation at Paediatric Research in Emergency Departments International Collaborative (PREDICT) sites. This will determine areas for improvement and provide baseline data for future multicentre studies. Methods: A questionnaire of specialist emergency physicians regarding demographics, general procedural sedation practice and specific sedation agents given to children. CPG for general sedation and sedation agents were obtained for each site. Results: Seventy-five (71%) useable surveys returned from 105 potential respondents. Most commonly used agents were nitrous oxide (N2O) (75, 100%), ketamine (total 72, 96%; i.v. 59, 83% and i.m. 22, 31%) and midazolam (total 68, 91%; i.v. 52, 81%, oral 47, 73%, intranasal 26, 41% and i.m. 6, 9%). Sedation was used for therapeutic and diagnostic procedures. Forty-three (57%) used formal sedation records and sedation checklists and thirty-one (41%) respondents reported auditing sedations. Four sites ran staff education and competency programmes. Nine sites had general sedation CPG, eight for ketamine, nine for N2O, eight for midazolam (four parenteral, five oral and six intranasal) and three for fentanyl. No site had a guideline for propofol administration. Conclusion: Procedural sedation in this research network commonly uses N2O, ketamine and midazolam for a wide range of procedures. Areas of improvement are the lack of guidelines for certain agents, documentation, staff competency training and auditing processes. Multicentre research could close gaps in terms of age cut-offs, fasting times and optimal indications for various agents. [source] Bispectral Electroencephalographic Analysis of Patients Undergoing Procedural Sedation in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 6 2003James R. Miner MD Abstract Objective: To determine whether there is a correlation between the level of sedation achieved during procedural sedation (PS) in the emergency department as determined by bispectral electroencephalographic (EEG) analysis (BIS) and the rate of respiratory depression (RD), the patient's perception of pain, recall of the procedure, and satisfaction. Methods: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS using propofol, methohexital, etomidate, and the combination of fentanyl and midazolam. Consenting patients were monitored by vital signs, pulse oximetry, nasal-sample end-tidal carbon dioxide (ETCO2), and BIS monitors during PS. Respiratory depression (RD) was defined as an oxygen saturation <90%, a change from baseline ETCO2 of >10 mm Hg, or an absent ETCO2 waveform at any time during the procedure. After the procedure, patients were asked to complete three 100-mm visual analog scales (VASs) concerning their perception of pain, recall of the procedure, and satisfaction with the procedure. Patients were divided into four groups based on the lowest BIS score recorded during the procedure, group 1, >85; group 2, 70,85; group 3, 60,69; group 4, <60. Rates of RD and VAS outcomes were compared between groups using chi-square statistics. Results: One hundred eight patients were enrolled in the study. No serious adverse events were noted. RD was seen in three of 14 (21.4%) of the patients in group 1, seven of 34 (20.6%) in group 2, 16 of 26 (61.5%) in group 3, and 18 of 34 (52.9%) in group 4. The rate of RD in patients in group 2 was not significantly different from that in group 1 (p = 0.46). The rate of RD in group 2 was significantly lower than that in groups 3 (p = 0.0003) and 4 (p = 0.006). For the VAS data, when group 1 was compared with the combined groups 2, 3, and 4, it had significantly higher rates of pain (p = 0.003) and recall (p = 0.001), and a dissatisfaction rate (p = 0.085) that approached significance. When groups 2, 3, and 4 were compared with chi-square test, there was not a significant difference in pain (p = 0.151), recall (p = 0.27), or satisfaction (p = 0.25). Conclusions: Patients with a lowest recorded BIS score between 70 and 85 had the same VAS outcomes as more deeply sedated patients and the same rate of RD as less deeply sedated patients. This range of scores represented the optimally sedated patients in this study. [source] Effects of Antiepileptic Drugs on Refractory Seizures in the Intact Immature Corticohippocampal Formation In VitroEPILEPSIA, Issue 11 2003Pascale Paule Quilichini Summary:,Purpose: We developed a new in vitro preparation of immature rats, in which intact corticohippocampal formations (CHFs) depleted in magnesium ions become progressively epileptic. The better to characterize this model, we examined the effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice. Methods: Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact CHFs of P7,8 rats, and extracellular recordings were performed in the hippocampus and neocortex. AEDs were applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Their ability to prevent or to delay the next ILE was examined. Results: Valproic acid and benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam prevent the occurrence of seizures. In contrast, usual concentrations of carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In addition, LTG and CBZ aggravate seizures in one third of the cases. Conclusions: This intact in vitro preparation in immature animals appears to be quite resistant to most AEDs. Blockade of seizures was achieved with drugs acting mainly at the ,-aminobutyric acid (GABA)A -receptor site but not with those that increase the amount of GABA. Drugs with a broad spectrum of activity are efficient but not those preferentially used in partial seizures or absences. We suggest that this preparation may correspond to a model of epilepsy with generalized convulsive seizures and could be helpful to develop new AEDs for refractory infantile epilepsies. 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