Neosaxitoxin in Rat Sciatic Block: Improved Therapeutic Index Using Combinations with Bupivacaine, with and without Epinephrine.

BACKGROUND: Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker undergoing clinical trials as a prolonged-duration local anesthetic. Rat sciatic block and intravenous infusion models were used to assess efficacy and local and systemic toxicities for NeoSTX in saline (NeoSTX-Saline), bupivacaine (Bup), and their combination (NeoSTX-Bup). Exploratory studies evaluated the effects of addition of epinephrine to NeoSTX-Bup (NeoSTX-Bup-Epi). METHODS: Rats received percutaneous sciatic blocks with escalating doses of NeoSTX-Saline or NeoSTX-Bup. Sensory-nocifensive block was assessed using modified hotplate and Von Frey filaments. Motor-proprioceptive function was assessed by extensor postural thrust. Nerves were examined histologically after 7 days and scored on the Estebe-Myers scale. Median lethal dose was estimated for NeoSTX-Saline and in combinations. Accidental intravenous overdose was simulated in isoflurane-anesthetized, spontaneously breathing rats receiving NeoSTX-Saline (n = 6), Bup (n = 7), or NeoSTX-Bup (n = 13), with respiratory, hemodynamic, and electrocardiographic endpoints. Additional groups received blocks with NeoSTX-Bup-Epi (n = 80). Investigators were blinded for behavioral and histologic studies. RESULTS: NeoSTX-Bup produced more prolonged sensory and motor block compared with NeoSTX-Saline or Bup. NeoSTX-Bup-Epi further prolonged median time to near-complete recovery for 3 µg/kg NeoSTX-Bup (hotplate: 48 vs. 6 h, P < 0.001). With sciatic injections, addition of Bup did not worsen the systemic toxicity (median lethal dose) compared with NeoSTX-Saline. Intravenous NeoSTX-Saline infusion had significantly longer times to apnea, first arrhythmia, and asystole compared with Bup (P < 0.001 for each). Histologic injury scores overall were low for all groups, with median scores of 0 (interquartile range, 0 to 0) on a 5-point scale. CONCLUSION: NeoSTX-Bup and NeoSTX-Bup-Epi hold promise for prolonged-duration local anesthesia.

Imaging of pediatric head injury in the emergency department.

OBJECTIVES: Computed tomography (CT) is the standard for immediate imaging of head-injured children, but it uses radiation that predisposes to malignancy. The study goals were to describe imaging practices in this population and to identify barriers to rapid magnetic resonance imaging (MRI) use. METHODS: A cross-sectional survey of physicians who care for pediatric patients in emergency departments was conducted. Survey questions included hospital characteristics, access to imaging technology, use of imaging studies, and use of radiation reduction practices. RESULTS: A total of 459 eligible respondents completed the questionnaire, which represented a response rate of 24.1%. Almost all the respondents (97.7%) reported that radiation concerns influence clinical management of children and adolescents with head trauma. Head CT use was more frequently reported than MRI (55.3% vs 1.5% reported use in more than 10% of patients, respectively). Frequent CT use was associated with practice in community hospitals (P = 0.005), whereas pediatric residency training and pediatric volumes greater than 30,000 visits per year were associated with less frequent use (P = 0.015 and P = 0.028, respectively). In 94.5% of the respondents, reported CT was always available compared with 24.3% reporting MRI as always available (P < 0.001). Reported obstacles to MRI as a screening tool for head-injured children included limited scanner availability (93.5%), patient intolerance of MRI (87.2%), and longer acquisition times (83.3%). CONCLUSIONS: Concerns about radiation exposure motivate change of practice in the management of head-injured children and adolescents. Head CT use is greater at hospitals with lower pediatric volumes, community hospitals, and by providers without pediatric residency training. Obstacles to increased use of MRI or head-injured children include availability, patient intolerance, and long scan acquisition times.

Perceptions of electronic health record implementation: a statewide survey of physicians in Rhode Island.

OBJECTIVES: Although electronic health record use improves healthcare delivery, adoption into clinical practice is incomplete. We sought to identify the extent of adoption in Rhode Island and the characteristics of physicians and electronic health records associated with positive experience. METHODS: We performed a cross-sectional study of data collected by the Rhode Island Department of Health for the Health Information Technology Survey 2009 to 2013. Survey questions included provider and practice demographics, health record information, and Likert-type scaled questions regarding how electronic health record use affected clinical practice. RESULTS: The survey response rate ranged from 50% to 65%, with 62% in 2013. Increasing numbers of physicians in Rhode Island use an electronic health record. In 2013, 81% of physicians used one, and adoption varied by clinical subspecialty. Most providers think that electronic health record use improves billing and quality improvement but has not improved job satisfaction. Physicians with longer and more sophisticated electronic health record use report positive effects of introduction on all aspects of practice examined (P < .001). Older physician age is associated with worse opinion of electronic health record introduction (P < .001). Of the 18 electronic health record vendors most frequently used in Rhode Island, 5 were associated with improved job satisfaction. CONCLUSIONS: We report the largest statewide study of electronic health record adoption to date. We found increasing physician use in Rhode Island, and the extent of adoption varies by subspecialty. Although older physicians are less likely to be positive about electronic health record adoption, longer and more sophisticated use are associated with more positive opinions, suggesting acceptance will grow over time.

Respiratory, neuromuscular, and cardiovascular effects of neosaxitoxin in isoflurane-anesthetized sheep.

BACKGROUND: Neosaxitoxin (NeoSTX) is a potent site-1 sodium-channel blocker being developed as a local anesthetic. Doses of 100 µg have been used by local infiltration in anesthetized adult humans without adverse effect. We hypothesized that similar doses could cause significant respiratory, neuromuscular, and cardiovascular impairment and sought to test this hypothesis in sheep. METHODS: Procedures were approved by the Institutional Animal Care and Use Committee. In neuromuscular/respiratory experiments, 33 intubated, isoflurane-anesthetized sheep were randomized to 6 NeoSTX treatment groups: saline control, 1 µg/kg subcutaneous (SC), 1 µg/kg intravenous (IV), 2 µg/kg SC, 2 µg/kg SC with bupivacaine 0.25%, and 3 µg/kg SC. Primary outcome measures were doxapram-stimulated inspired volume (DSIV) and quantitative limb acceleration. In cardiovascular experiments, 8 sheep received escalating IV doses of NeoSTX (1, 2, and 3 µg), with hemodynamic and electrocardiographic measurements. Data were analyzed using repeated-measures analysis of variance with post hoc Bonferroni-corrected comparisons. RESULTS: NeoSTX 1 µg/kg IV and SC produced no significant reduction in DSIV or limb acceleration compared with baseline. NeoSTX 2 µg/kg SC produced clinically mild reduction in twitch and DSIV; animals recovered well postoperatively. Coadministration of bupivacaine did not worsen these effects. NeoSTX 3 µg/kg produced severe and prolonged impairment of DSIV and limb acceleration. Escalating IV doses of NeoSTX produced mild decrements in heart rate, systemic arterial pressure, and systemic vascular resistance; cardiac output was maintained. Transient interventricular conduction delay occurred without cardiac arrest or ventricular ectopy. CONCLUSIONS: In our sheep model, neuromuscular, respiratory, and cardiovascular effects of NeoSTX were dose dependent and mild using the dose range anticipated for clinical use.

Risk factors for central line-associated bloodstream infection in pediatric intensive care units.

OBJECTIVE: We sought to identify risk factors for central line-associated bloodstream infection (CLABSI) to describe children who might benefit from adjunctive interventions. DESIGN: Case-control study of children admitted to the medical-surgical intensive care unit (ICU) or cardiac ICU from January 1, 2004, through December 31, 2007. SETTING: Children's Hospital Boston is a freestanding, 396-bed quaternary care pediatric hospital with a 29-bed medical-surgical ICU and a 24-bed cardiac ICU. PATIENTS: Case patients were patients with CLABSI who were identified by means of prospective surveillance. Control subjects were patients with a central venous catheter who were matched by ICU admission date. METHODS: Multivariate conditional logistic regression models were used to identify independent risk factors for CLABSI and to derive and to validate a prediction rule. RESULTS: Two hundred three case patients were matched with 406 control subjects. Independent predictors of CLABSI included duration of ICU central access (odds ratio [OR] for 15 or more days, 18.41 [95% confidence interval {CI}, 4.10-82.56]; P < .001), central venous catheter placement in the ICU (OR for 2 or more ICU-placed catheters, 8.63 [95% CI, 2.63-28.38]; P = .001), nonoperative cardiovascular disease (OR, 7.44 [95% CI, 2.13-25.98]; P = .012), presence of gastrostomy tube (OR, 3.48 [95% CI, 1.55-7.79]; P = .003), receipt of parenteral nutrition (OR, 3.12 [95% CI, 1.55-6.32]; P = .002), and receipt of blood transfusion (OR, 2.55 [95% CI, 1.21-5.36]; P = .014). By use of risk factors known before central venous catheter placement, our model predicted CLABSI with a positive predictive value of 54% and a negative predictive value of 79%. CONCLUSIONS: Duration of central access, receipt of parenteral nutrition, and receipt of blood transfusion were confirmed as risk factors for CLABSI among children in the ICU. Newly identified risk factors include presence of gastrostomy tube, nonoperative cardiovascular disease, and ICU placement of central venous catheter. Children with these risk factors may be candidates for adjunctive interventions for CLABSI prevention.