Activity-dependent modulation of synaptic AMPA receptor accumulation.

Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.

Midazolam for sedation in the paediatric intensive care unit.

This retrospective study examines data from 55 patients sedated in a paediatric intensive care unit (PICU) with midazolam. Midazolam sedation was initiated with a bolus of 0.25 mg.kg-1 followed by a continuous infusion of 0.4-4 micrograms.kg-1.min-1. Physiological and metabolic parameters, infusion rates, duration, and sedation scores were monitored. Midazolam infusions were effective in sedating all the children studied during all or part of their PICU admission. The median duration of sedation was 74 h with a range of 4 to 1272 h. Haemodynamics were unchanged. Of the patients 46% were effectively alimented by the enteral route, and enteral alimentation was successful in all patients in whom it was attempted. Unassisted ventilation occurred in 44% of the patients during infusion. Oxygen consumption was 28% lower than in the control. Disadvantages of midazolam infusion have included inability to sedate during extracorporeal membrane oxygenation and development of acute tolerance.

Nalmefene to prevent epidural narcotic side effects in pediatric patients: a pharmacokinetic and safety study.

STUDY OBJECTIVE: To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects. DESIGN: Double-blind, placebo-controlled study. SETTING: University-affiliated children's hospital. PATIENTS: Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia. INTERVENTIONS: Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours, clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/-2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention. CONCLUSION: Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.

Caudal epidural morphine for control of pain following open heart surgery in children.

The safety and efficacy of epidural morphine injected into the caudal space for control of postoperative pain following open cardiac surgery in children was studied. Thirty-two children between the ages of 2-12 yr for whom early postoperative tracheal extubation was anticipated were randomly assigned to control and study groups. Study subjects received a caudal injection of preservative free morphine sulfate (0.075 mg/kg) in preservative-free normal saline (5-10 ml) following completion of surgery, but prior to awakening and extubation of the trachea. Supplemental intravenous morphine administration and pain scores were recorded for 24 h. Patients in the study group received significantly less (P less than 0.03) morphine (0.32 mg.kg-1.24 h-1) and had significantly lower pain scores than did patients in the control group (0.71 mg.kg-1.24 h-1). The mean duration of complete analgesia in patients receiving caudally administered morphine was 6 h (range 2-12), but decreased analgesic requirements were noted for the entire 24 h. No respiratory depression was evident by clinical variables or repeated arterial blood gas values. Nausea without vomiting occurred in 4/16 patients in the study group. No patient described pruritus. The authors were unable to evaluate the occurrence of urinary retention because all patients had indwelling urinary catheters. They found caudal epidural morphine to be safe and effective in the treatment of postoperative pain in children following open heart surgery.

Anaesthesia for diagnostic muscle biopsy in an infant with Pompe's disease.

The anaesthetic management of children with glycogen-storage disease type IIa (Pompe's disease) presents a variety of challenges. A modification of a femoral nerve block, the inguinal paravascular block, as described by Winnie, was used in conjunction with intravenous ketamine to provide anaesthesia for a diagnostic muscle biopsy in a 5.5-month-old infant with Pompe's disease. A peripheral nerve stimulator was used to locate the femoral nerve in lieu of eliciting a paraesthesia.

Elimination of drugs and toxins during cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) creates a myriad of pharmacological and physiological changes. Some of these changes have been studied in isolated in vitro studies. Integrating an in vitro system into an in vivo process is so complicated that many pharmacological studies simply avoid the bypass period. For the most part, the studies that do examine the bypass period deal with a single drug, reporting how it does or does not produce a predicted concentration on initiation, maintenance and termination of CPB. Based on the isolated results of these studies, this review hypothesizes a model that explains how different substances interact with the CPB system. A summary of the review's findings include the following: 1) drugs with a smaller volume of distribution are more likely to be effected; 2) the pharmacokinetic effects of lipophilic drugs undergo more alterations than hydrophilic drugs; and 3) protein binding minimizes alterations of lipophilic drugs and increase alterations of hydrophilic drugs.

Intravenous conscious sedation with midazolam in paediatric patients.

Intravenous midazolam has been widely used in paediatric patients for conscious sedation in procedures such as endoscopy, oesophageal manometry, biopsy, bone marrow aspiration and lumbar puncture. Its advantages include quick onset and short duration of action, and haemodynamic stability which may be associated with improved patient acceptance. The pharmacokinetic profile of midazolam compares favourably with that of diazepam, permitting more controlled sedation with a quicker recovery time. Midazolam has been associated with shorter recovery room stays and less vomiting in children who undergo outpatient surgery. The safety and tolerability profile of midazolam in paediatric patients is comparable or superior to that observed in adults. Patients who are haemodynamically unstable, as well as pre-term and term infants are at greater risk of hypotension while receiving sedation. Thus, the availability of i.v. midazolam for use in children provides an important additional option for providing i.v. conscious sedation.

Comparative flow rates for small bore peripheral intravenous catheters.

The ability to deliver fluid to the pediatric patient is a function of many variables. In addition to patient-specific factors such as patient age, size, and weight, and venous size, number, and character, there exist further universal limitations inherent in the equipment which is utilized. Mechanical variables include cannula number, length, brand, and gauge; tubing length, band, style, and gauge; use of extensions; and presence and type of pressure system. This study evaluated a few of these variables. The flow rates were determined for 10 brands of 20-, 22-, and 24-gauge peripheral intravenous catheters. The catheter brands were divided into two groups, slow or faster. The differences in flow between the two categories were statistically significant. The disparities between the slowest and most rapid catheters of the same gauge were only 6.6, 5.4, and 7.7 ml/min for the 20, 22, and 24 gauges, respectively. The tubing apparatus was also a significant determinant of flow. The addition of any extensions further decreased flow. The magnitude of this slowing was a function of both the tubing and the type of extension.

Basic and advanced life support, acute resuscitation, and cardiac resuscitation.

The global approach to resuscitation has changed dramatically in the past year. The groundwork for these changes began a decade ago with the development of the Utstein guidelines for uniform reporting of critical events. Consistency in data collection was necessary to enable evidence-based review and comparison of current practice. Resuscitation protocols have been significantly altered based upon these data. Basic life support (BLS) protocols have been simplified. Early access to electrical cardioversion is the key to survival. Mobilization of AED technology in the community is essential. Several issues were identified as crucial to future improvement of resuscitation statistics. Prevention strategies should be developed for high-risk patients. There is a need to identify cases in which resuscitation should not be started. Enhancement of educational methods to improve performance and retention of skills is key. Finally, the roadblocks for performance of ethical prospective research must be minimized.

In vitro variability in fentanyl absorption by different membrane oxygenators.

The membrane oxygenator has replaced the bubble oxygenator in a wide variety of clinical settings. The membrane oxygenators now manufactured can be grouped into three categories based on composition and design: (1) silicone with a true membrane structure; (2) polypropylene with a microporous sheet; and (3) polypropylene with a microtubular structure. The capacity for fentanyl uptake by membrane oxygenators from these three categories was studied in vitro. Representative membrane samples were incubated in solutions containing tritiated fentanyl in Normosol-R (Abbott, North Chicago, IL) with pH adjusted to 7.4 at 37 degrees C. Fentanyl analysis was performed using liquid scintillation and radioimmunoassay techniques. The uptake of fentanyl at various concentrations (340 to 10 ng/mL) was studied. The SciMed (type 1; SciMed, Minneapolis, MN) membrane showed the greatest capacity for fentanyl uptake at all concentrations. The SciMed oxygenator was capable of binding 130 ng fentanyl/cm2 membrane. When presented with a smaller concentration (less than or equal to 20 ng/mL) of fentanyl, the membrane was able to extract all available fentanyl from solution. All of the microporous polypropylene oxygenators (types 2 and 3) absorbed significantly less fentanyl than did the SciMed brand. When exposed to 10 or 20 ng/mL, the Shiley and Omnis brands (type 2) absorbed 0.1 and 0.4 ng/cm2, respectively. Using the higher fentanyl concentrations (greater than or equal to 200 ng/mL) uptake by the Omnis membrane was 11 ng/cm2 compared with only 2 ng/cm2 by the Shiley. The Bentley BCM 7 and Terumo Capiox II 08 microtubular microporous membranes (type 3) did not show absorption of fentanyl using isolated or intact membrane models.(ABSTRACT TRUNCATED AT 250 WORDS)

Outpatient sedation: an essential addition to gynecologic care for persons with mental retardation.

Routine gynecologic care for persons with mental retardation may be difficult to provide, especially to those women who do not allow a pelvic examination to be performed. Of 275 women referred to a multidisciplinary clinic addressing the reproductive health concerns of mentally retarded women, 61 patients (22%) did not allow a gynecologic examination to be performed. The administration of ketamine alone, midazolam alone, or a combination of midazolam and ketamine allowed for the successful performance of a gynecologic examination in 81% of previously uncooperative women. No adverse effects of the medications were noted. We conclude that sedation of difficult-to-examine, mentally handicapped women can be safely performed in the outpatient setting, thus avoiding the need for general anesthesia and its inherent risks.

Analgesia for pediatric thoracostomy tube removal.

Eutectic mixture of local anesthetics (EMLA; Astra Pharmaceuticals, Wayne, PA) has been shown to reduce the pain of blood draws in children. We investigated the use of EMLA versus IV morphine for providing analgesia during chest tube removal (CTR) in children. One hundred twenty pediatric cardiothoracic surgery patients were enrolled. Patients were randomly assigned to receive either morphine (0.1 mg/kg up to 10 mg IV 30 min before CTR) or EMLA cream (5 g per chest tube cutaneously 3 h before CTR). A single, trained observer rated the patient's pain before, during, and after CTR using a 10-cm visual analog scale. The sites were evaluated for adverse effect. Methylhemoglobin levels were monitored in infants. Before CTR, the pain scores of the children who received morphine were rated lower than those who received EMLA (P < 0.01). During CTR, there was no difference in the pain score between the morphine or EMLA group. The change from baseline pain score in the morphine group was significantly larger than in the EMLA group (P < 0.01). We conclude that EMLA is safe and useful for blunting the pain of CTR.