Fecal triiodothyronine and thyroxine concentrations change in response to thyroid stimulation in Steller sea lions (Eumetopias jubatus).

Variation in concentrations of thyroid hormones shed in feces may help to identify physiological states of animals, but the efficacy of the technique needs to be validated for each species. We determined whether a known physiological alteration to thyroid hormone production was reflected in hormone concentrations in the feces of Steller sea lions (Eumetopias jubatus). We quantified variation of triiodothyronine (T3) and thyroxine (T4) concentrations in feces following two intramuscular injections of thyrotropin (thyroid-stimulating hormone, TSH) at 24h intervals in four captive female sea lions. We found fecal T3 concentrations increased 18-57% over concentrations measured in the baseline sample collected closest to the time of the first TSH injection (p=0.03) and 1-75% over the mean baseline concentration (p=0.12) for each animal of all samples collected prior to injections. Peak T3 concentrations were greater than the upper bound of the baseline 95% confidence interval for three animals. The peak T3 response occurred 48h post-injection in three animals and 71h in the fourth. Post-injection T4 concentrations did not differ between the baseline sample collected closest to the time of the first TSH injection (p=0.29) or the mean baseline concentration (p=0.23) for each animal. These results indicate that induced physiological alterations to circulating thyroid hormone concentrations can be adequately detected through analyses of fecal T3 concentrations and that the technique may provide a means of non-invasively detecting metabolic changes in Steller sea lions.

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.

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.

Metabolic effects of low-energy diet on steller sea lions, Eumetopias jubatus.

Diets of six Steller sea lions (Eumetopias jubatus) were switched between a high (herring) and a low (squid) energy density food for 14 d to determine the effects on ingested prey mass, body mass, resting metabolic rate, and the heat increment of feeding. Body mass was measured daily, and resting metabolism was measured weekly by gas respirometry. Ingested food mass did not differ significantly between the squid diet and the control or the recovery herring diet periods. As a result of differences in energy density, gross energy intake was significantly lower during the squid diet phase than during either the control or recovery periods. As a result, sea lions lost an average of 1.1 kg/d, totaling 12.2% of their initial body mass by the end of the experimental period. The heat increment of feeding for a 4-kg squid meal was significantly lower than for a similarly sized meal of herring. Decreases in both absolute (24.0 to 18.0 MJ/d, -24%) and mass-corrected (903 to 697 kJ/d/kg0.67, -20%) metabolism were observed by the end of the squid feedings. This study suggests that sea lions can depress their resting metabolism in response to decreases in energy intake or body mass, regardless of satiation level.

Topical lidocaine-prilocaine cream (EMLA) for thoracostomy tube removal.

UNLABELLED: We prospectively studied topical lidocaine-prilocaine cream (EMLA) versus IV morphine in a double-blinded, randomized fashion for pain relief during thoracostomy tube (chest tube; CT) removal. Adult patients who had undergone thoracotomy or median sternotomy were randomized to receive either EMLA cream over CT sites transdermally for 3 h or IV morphine 0.5 h before CT removal. Pain behavior was observed and rated before, during, and after CT removal. Pain behavior increased less in the topical EMLA group (mean +/- SE, 4.4+/-0.39) compared with the IV morphine group (6.0+/-0.38; P < 0.01). No signs of infection were noted at the CT sites 24 or 48 h after CT removal. We conclude that EMLA cream is more effective than IV morphine in preventing the pain associated with CT removal. IMPLICATIONS: Postoperatively applying a topical anesthetic cream onto chest tube sites of chest surgery patients 3 h before chest tube removal is more effective than IV morphine in blunting pain response.

Sedation in children: current concepts.

Sedation in children poses a great challenge, with the main concern one of safety. The importance of providing adequate sedation to children was realized only in the last decade and a half, and relevant data are severely lacking. Use of potent sedative agents is not without risk. Children are given sedative agents in a wide variety of settings by practitioners with different degrees of experience with the drugs and management of adverse effects. Controversial issues must be addressed in this area, and appropriate tools developed to measure sedation and individualize treatment based on the drugs' pharmacokinetic and pharmacodynamic properties.

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.

Heat increment of feeding in Steller sea lions, Eumetopias jubatus.

The heat increment of feeding (HIF) was measured in six captive, juvenile Steller sea lions (Eumetopias jubatus), fed meals of either 2 or 4 kg of herring. HIF was calculated as the post-prandial increase in metabolism above baseline levels, and was measured using open-circuit (gas) respirometry. It averaged 12.4 +/- 0.9% (SE) of ingested energy intake for the 4-kg meal trials, and 9.9 +/- 0.9% for the 2-kg meal size. The effect lasted 8-10 hr for the larger meal size. Metabolism peaked 3.7 hr after feeding, and was 2.13 times higher than baseline levels. For the 2-kg meal size, the effect lasted 6-8 hr, with metabolism peaking 2.8 hr after ingestion at 1.76 times baseline levels. Our estimates of HIF for Steller sea lions are at the lower end of estimates for terrestrial mammals, and are consistent with estimates for other marine mammals.

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.

Chaetogaster limnaei (annelida: oligochaeta) as a parasite of the zebra mussel Dreissena polymorpha, and the quagga mussel Dreissena bugensis (mollusca: bivalvia).

Dreissenid mussels, Dreissena polymorpha and D. bugensis, were found to be infected by the naidid oligochaete Chaetogaster limnaei at four sites in the St. Lawrence River. This is the first report of this species infecting dreissenids anywhere in the world. Most worms inhabited the mantle cavity, where they caused erosion of the mantle and gill epithelia as determined by histopathological examination. Others penetrated various tissues; one had invaded the ovary and was feeding on oocytes and ovarian tissues. Of 606 mussels examined, 166 (27.4%) harbored at least 1 C. limnaei. The prevalence varied between 1% and 80%, depending on the collection site and date. The worms were slightly but significantly more prevalent in D. bugensis than in D. polymorpha. The intensity ranged from 1 to 18 worms per infected host. Variations in prevalence and intensity were not related to the size or sex of the host, but the data did suggest some seasonality.

Stability of propofol with parenteral nutrient solutions during simulated Y-site injection.

The stability of propofol in three parenteral nutrient (PN) solutions was studied. Nine combinations of three PN solutions (with amino acid concentrations of 1.5, 2.5, and 5.0%) and three propofol concentrations (0.5, 2.0, and 3.0 mg/mL) were prepared in triplicate and stored at 22 degrees C under fluorescent light. Duplicate samples were visually inspected for color changes, precipitation, or gas formation, and the pH of the samples was determined. These samples were evaluated for propofol content by high-performance liquid chromatography at zero, one, three, and five hours. The stability of the vehicle for propofol injection (similar in composition to fat emulsion) was evaluated by visual inspection, pH determination, and particle-size measurements at zero, one, three, and five hours. The concentration of propofol in all of the propofol-PN combinations remained greater than 90% of the initial concentration except for the combination of propofol 0.5 mg/mL and the 1.5% amino acid PN solution, which contained only 72% of the initial propofol concentration five hours after the start of the study. Visual examination revealed no evidence of color change, precipitation, gas formation, creaming, or streaking in any of the propofol-PN solution combinations. No substantial changes in pH occurred. The particle size of the vehicle for propofol remained relatively constant throughout the study period. Propofol 2 and 3 mg/mL was stable for five hours during simulated Y-site injection with PN solutions containing 1.5, 2.5, and 5% amino acids. Propofol 0.5 mg/mL was stable during simulated Y-site injection with the same PN nutrition solutions for five hours, except for the solution containing 1.5% amino acid.

Stability of midazolam hydrochloride in extemporaneously prepared flavored gelatin.

The stability of midazolam hydrochloride in flavored gelatin was evaluated after storage at 4 degrees C for 14 days and at -20 degrees C for 28 days. A flavored liquid gelatin mixture was prepared and mixed with midazolam hydrochloride injection in final concentrations of midazolam 1 and 2 mg/mL. Gelatin cups containing 5 and 15 mg of midazolam were prepared by measuring appropriate volumes of the gelatin stock solutions and were stored in a refrigerator at 4 degrees C or in a freezer at -20 degrees C. Immediately after preparation and at 7 and 14 days, three refrigerated and three frozen gelatin samples of each midazolam concentration were visually inspected, tested for pH, and assayed for midazolam concentration by high-performance liquid chromatography. The frozen gelatin samples were also evaluated at 21 and 28 days; three whole and three partial gelatin samples were assayed for midazolam content to determine the uniformity of drug distribution within each sample. All samples maintained greater than 96% of the initial midazolam concentration throughout the study. There was no appreciable change in color, odor, or pH. The midazolam content of the gelatin in the cups was uniform. An extemporaneously compounded preparation of midazolam hydrochloride in flavored gelatin was stable when stored for 14 days at 4 degrees C and for 28 days at -20 degrees C. Distribution of midazolam hydrochloride in the gelatin was uniform.

Stability of midazolam hydrochloride in parenteral nutrient solutions.

The compatibility and stability of midazolam hydrochloride in three parenteral nutrient (PN) solutions and the stability of 15 amino acids in the presence of midazolam hydrochloride were studied. Six combinations of three PN solutions with amino acid concentrations of 1.5%, 2.5%, and 5% and two midazolam concentrations (0.1 and 0.5 mg/mL) were prepared in triplicate and stored at room temperature under normal fluorescent lighting. Duplicate samples were visually inspected for color change, precipitation, or gas formation and tested for pH. The samples were evaluated for midazolam and amino acid content by high-performance liquid chromatography at zero, one, three, and five hours. Midazolam and amino acid concentrations did not change significantly during the study. There was no evidence of color change, precipitation, or gas formation with any midazolam-PN solution combination when the combinations were examined visually and under a microscope, and no substantial changes in pH occurred. Midazolam 0.1 and 0.5 mg/mL (as the hydrochloride salt) was stable in the three PN solutions studied; in addition, the amino acids present in the 1.5%, 2.5%, and 5% amino acid PN solutions were stable when combined with midazolam at concentrations of 0.1 and 0.5 mg/mL.

A balloon-dilatable pulmonary artery band in the dog. Results at one year.

Increased pulmonary blood flow and pulmonary hypertension are frequent problems in infants with congenital heart disease. Although the use of pulmonary artery banding to limit pulmonary blood flow has decreased, the procedure may still be beneficial in certain forms of complex heart disease. The ability to noninvasively relieve the obstruction caused by the band may significantly reduce later operative complexity or even avoid reoperation entirely. The present study evaluated the effectiveness of a balloon-dilatable pulmonary artery band. Twenty 1-week-old dogs had a band of an absorbable suture material (Vicryl; Ethicon, Inc., Somerville, N.J.) placed around the main pulmonary artery. Eight dogs underwent angioplasty 6 months after band placement and also underwent follow-up catheterizations 3 and 6 months after angioplasty. Balloon angioplasty acutely reduced both the right ventricle-pulmonary artery pressure gradient (from 37 +/- 7 mm Hg to 3 +/- 1 mm Hg, p less than 0.001) and the right ventricular systolic pressure (from 62 +/- 8 mm Hg to 32 +/- 2 mm Hg, p less than 0.01). At follow-up the gradient remained low, measuring 4 +/- 1 mm Hg at 3 months and 3 +/- 1 mm Hg at 6 months. Twelve dogs did not undergo balloon dilatation until 12 months after band placement to determine whether any obstruction persisted and whether the band could be relieved after long-term placement. These 12 dogs had progressive increases in right ventricle-pulmonary artery gradient, from 27 +/- 3 mm Hg at 6 months to 43 +/- 4 mm Hg at 12 months. Ten of these dogs underwent dilation 1 year after pulmonary artery band placement. This dilation significantly reduced the right ventricular outflow tract gradient (from 43 +/- 4 mm Hg to 1 +/- 1 mm Hg, p less than 0.001). The remaining two dogs underwent successful partial dilation of the band 12 months after placement. This study demonstrated that a pulmonary artery band of absorbable suture material maintains effective right ventricular outflow tract obstruction for at least 1 year. Additionally, the effect of the pulmonary band can be successfully and persistently relieved.

Management of acute pain in children.

The pathophysiology, assessment, and pharmacologic management of acute pain in infants and children are reviewed, and the mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and dosages of opioid analgesics, nonopioid analgesics, and local anesthetics used for regional blocks are discussed. The pathophysiology of pain and the physiologic rationale for treatment of pain are similar in children and adults. Severe pain can be controlled by i.v. or epidural administration of opioid analgesics. Neonates are more susceptible to the depressant effects of opioids, and opioid analgesia must be administered with caution in infants who are not receiving mechanical ventilation because of the associated risk of respiratory depression. Patient-controlled analgesia is a useful technique in older children. Acetaminophen and NSAIDs are useful for relieving milder pain of noninflammatory and inflammatory origin, respectively. Epidural or intrathecal administration of local anesthetics provides regional analgesia with minimal physiologic alterations. Topical application of local anesthetics is effective for many minor procedures. A variety of pain management techniques are available for the management of acute pain in pediatric patients. The development of drugs having fewer adverse effects and noninvasive administration techniques will be important research priorities in the coming years.

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.

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.

A guide to the EEOC's final regulations on the Americans with Disabilities Act.

The Equal Employment Opportunity Commission (EEOC) recently issued its final regulations on the Americans with Disabilities Act (ADA). Although the regulations offer some guidance for employers on how to comply with the Act, they fail to provide specific answers to the many complicated compliance questions that will surely arise. Further, the regulations are almost totally silent on certain critical issues related to insurance, workers' compensation, and potential conflicts between ADA obligations and terms of collective bargaining agreements. The EEOC has essentially left the resolution of many important ADA questions to case-by-case determination and the litigation process.