Evolution of practice patterns in the management of acute respiratory distress syndrome: A secondary analysis of two successive randomized controlled trials.

PURPOSE: We sought to examine changes in acute respiratory distress syndrome (ARDS) management over a 12-year period of two successive randomized trials. METHODS: Analyses included baseline data, from eligible patients, prior to influence of trial protocols, and daily study data, from randomized patients, of variables not determined by trial protocols. Mixed linear regressions examined changes in practice year-on-year. RESULTS: A total of 2376 patients met the inclusion criteria. Over the 12-year period, baseline tidal volume index decreased (9.0 to 7.0 ml/kg, p < 0.001), plateau pressures decreased (30.8 to 29.0 cmH2O, p < 0.05), and baseline positive end-expiratory pressures increased (10.8 to 13.2 cmH2O, p < 0.001). Volume-controlled ventilation declined from 29.4 to 14.0% (p < 0.01). Use of corticosteroids increased (baseline: 7.7 to 30.3%; on study: 32.6 to 61.2%; both p < 0.001), as did neuromuscular blockade (baseline: 12.3 to 24.5%; on study: 55.5 to 70.0%; both p < 0.01). Inhaled nitric oxide use increased (24.9 to 65.8%, p < 0.05). We observed no significant change in prone positioning (16.2 to 18.9%, p = 0.70). CONCLUSIONS: Clear trends were apparent in tidal volume, airway pressures, ventilator modes, adjuncts and rescue therapies. With the exception of prone positioning, and outside the context of rescue therapy, these trends appear consistent with the evolving literature on ARDS management.

Near-resolution of persistent idiopathic facial pain with low-dose lumbar intrathecal ziconotide: a case report.

PURPOSE: Persistent idiopathic facial pain (PIFP) is a poorly defined and debilitating chronic pain state with a challenging and often inadequate treatment course. This is the first case report identifying the novel use of low-dose lumbar intrathecal ziconotide to successfully treat PIFP with nearly complete resolution of pain and minimal to no side effects. METHODS: The patient was a 37 year-old female whose PIFP was refractory to multimodal medication management and multiple neurovascular surgical interventions. A single-shot lumbar intrathecal trial of ziconotide (2.5 mL, equivalent 2.5 µg) was injected when she was at her baseline pain level - VAS 7/10. She received complete resolution of her pain for about 9 hours, concordant with ziconotide's half-life. She was subsequently implanted with a lumbar intrathecal delivery system. RESULTS: The patient experienced complete resolution of her facial pain with a single-shot intrathecal trial of ziconotide. The intrathecal pump system has provided nearly complete (VAS 1/10) pain relief. Two flares of pain occurred 10 and 18 months after pump placement, which subsequently resolved after increasing the ziconotide dose by 0.5 µg/day on each occasion. The patient is currently maintained on a dose of 2.0 µg/day and is pain-free. CONCLUSION: This is the first case report describing the use of a single-shot lumbar intrathecal trial of ziconotide and subsequent placement of lumbar (as opposed to thoracic) intrathecal ziconotide pump for PIFP. A single-injection intrathecal trial is a low-risk, viable option for patients with this debilitating and frustrating pain condition. Successful trials and subsequent intrathecal pump placement with ziconotide may supplant multimodal medication management and/or invasive orofacial surgical intervention for PIFP.

Transfer of selenium from prey to predators in a simulated terrestrial food chain.

Little is known about the accumulation and effects of selenium in reptiles. We developed a simplified laboratory food chain where we fed commercial feed laden with seleno-D,L-methionine (30 microg/g dry mass) to crickets (Acheta domestica) for 5-7 d. Se-enriched crickets (approximately 15 microg/g Se [dry mass]) were fed to juvenile male and female lizards (Sceloporus occidentalis) for 98 d while conspecifics were fed uncontaminated crickets. Lizards fed contaminated prey accumulated Se concentrations ranging from 9.3 (in female carcass) to 14.1 (in female gonad) microg/g compared to <1.5 microg/g in tissues of controls. Female gonad concentrations approached the highest of thresholds for reproductive toxicity in oviparous vertebrates. However, we observed no consistent effect of dietary treatment on sublethal parameters or survival. Our simplified food chain proved to be an ecologically relevant method of exposing lizards to Se, and forms the foundation for future studies on maternal transfer and teratogenicity of Se.

Functional relationships among selenium concentrations in the diet, target tissues, and nondestructive tissue samples of two species of snakes.

Nondestructive sampling methods, such as removal of feathers for contaminant analysis, are desirable in ecological monitoring programs that seek to minimize the impacts of harvesting organisms. Although many reptiles are declining worldwide, nondestructive sampling techniques seldom have been employed for assessing contaminant exposure in these organisms. In this study, we examined the utility of nondestructive tissue sampling for assessing Se exposure in reptiles. We describe the functional relationships among dietary Se concentrations, target tissue Se concentrations, and Se concentrations in nondestructive tissue samples (blood and tail tissue biopsy) in two species of snakes that had been exposed to Se under very different experimental protocols. Using nonlinear regression, we found strong positive correlations (r2 > 0.92) in all comparisons among Se concentrations in nondestructive tissues, diet, and target tissues. Moreover, equations describing these relationships can be used to estimate concentrations of Se in diet and target organs, from known concentrations of Se in nondestructive tissue samples. Although the current paucity of toxicity data on reptiles precludes tests of our models, we demonstrate how the equations describing these relationships might be used to make predictions about Se accumulation in target organs for risk assessment. Future studies on reptiles that examine these relationships under different Se exposure conditions, and those that document physiological responses of reptiles to various concentrations of Se, will help to refine our models and test their efficacy for predicting health risk.

Effects of chronic dietary exposure to trace elements on banded water snakes (Nerodia fasciata).

Little currently is known about the accumulation or effects of contaminants on reptiles. To date, most studies examining reptile exposure to trace elements report tissue burdens of field-captured animals, but seldom provide insight into the dose, duration, or mode of exposure involved. For two years, we fed juvenile banded water snakes (Nerodia fasciata) prey items collected from a coal ash-contaminated site that contained elevated levels of As, Cd, Cu, Se, Sr, and V. With the exception of Cu, snakes accumulated significant concentrations of elements, usually in a dose-dependent manner. Accumulation varied significantly among liver, kidney, and gonads, and in most cases between sexes. Selenium accumulation was most notable, greatly exceeding established toxicity thresholds for other vertebrates. Despite the high concentrations of pollutants accumulated, snakes exposed to the contaminated diet survived through the study and exhibited normal food consumption, growth, condition factor, overwinter survival and mass loss, metabolic rate, and gonadosomatic index. The results of this study confirm that diet can be a significant route of exposure to trace elements in snakes and indicate that further studies on snakes are warranted to better understand their responses to contaminants.

Maternal transfer of selenium in Alligator mississippiensis nesting downstream from a coal-burning power plant.

Selenium (Se) is embryotoxic in many oviparous vertebrates, but little is known about maternal transfer of Se and its impact in reptiles. Over a four-year period, we collected three clutches of eggs of the American alligator (Alligator mississippiensis) from a single nest at a site contaminated with Se and compared egg and hatchling Se concentrations and clutch viability from this nest to nests downstream from the contaminated site (two clutches from two nests) and at a reference site (two clutches from two nests). Eggs and hatchlings from the nest at the Se-contaminated site and downstream nests had elevated Se concentrations (2.1-7.8 ppm) and lower viability (30-54%) compared to reference nests (1.4-2.3 ppm and 67-74% viability), but Se concentrations did not exceed reproductive toxicity thresholds established for other oviparous vertebrates. Selenium concentrations were higher in chorioallantoic membranes of eggs from Se-contaminated sites, suggesting that this tissue may be useful as a nondestructive index of Se exposure for embryos of A. mississippiensis. Examination of these data suggests that further studies on uptake, accumulation, and reproductive success of crocodilian embryos exposed to excessive Se are warranted.

Trophic and maternal transfer of selenium in brown house snakes (Lamprophis fuliginosus).

Excessive concentrations of dietary Se are toxic to oviparous vertebrates (i.e., fish and birds) but little is known about its accumulation and effects in reptiles. We exposed female brown house snakes, Lamprophis fuliginosus, to 10 and 20 microg/g Se by injecting seleno-D,L-methionine into their prey items and compared the snakes to individuals receiving background levels of approximately 1 microg/g dietary Se. Snakes were fed meals equaling 25% of their body mass 2-3 times a month for 10 months. Snakes exposed to excessive Se accumulated significant concentrations of Se in kidney, liver, and ovarian tissue, but accumulation had no effect on female survival, food consumption, growth, or body condition. Fewer females exposed to excessive Se reproduced than females exposed to 1 microg/g Se (67% vs. 91%, respectively), but the reduction in reproductive activity was not statistically significant. Total reproductive output of females did not differ among the three dietary treatments. However, snakes exposed to 10 and 20 microg/g Se transferred significant concentrations of Se to their eggs. In the 20 microg/g treatment, maternal transfer resulted in Se concentrations in eggs that surpassed all suggested reproductive toxicity thresholds for birds and fish. Further studies are needed to more rigorously determine whether maternal transfer of Se in this snake species affects the viability of developing embryos or the health of offspring.