Evaluation of propofol anesthesia in morbidly obese children and adolescents.

BACKGROUND: Poor characterization of propofol pharmacokinetics and pharmacodynamics in the morbidly obese (MO) pediatric population poses dosing challenges. This study was conducted to evaluate propofol total intravenous anesthesia (TIVA) in this population. METHODS: After IRB approval, a prospective study was conducted in 20 MO children and adolescents undergoing laparoscopic surgery under clinically titrated propofol TIVA. Propofol doses/infusion rates, hemodynamic variables, times to induction and emergence, and postoperative occurrence of respiratory adverse events (RAE) were recorded, along with intraoperative blinded Bispectral Index/BIS and postoperative Ramsay sedation scores (RSS). Study subjects completed awareness questionnaires on postoperative days 1 and 3. Propofol concentrations were obtained at predetermined intra- and post-operative time points. RESULTS: Study subjects ranged 9 - 18 years (age) and 97 - 99.9% (BMI for age percentiles). Average percentage variability of hemodynamic parameters from baseline was ≈ 20%. Patients had consistently below target BIS values (BIS < 40 for >90% of maintenance phase), delayed emergence (25.8 ± 22 minutes), increased somnolence (RSS ≥ 4) in the first 30 minutes of recovery from anesthesia and 30% incidence of postoperative RAE, the odds for which increased by 14% per unit increase in BMI (p ≤ 0.05). Mean propofol concentration was 6.2 mg/L during maintenance and 1.8 mg/L during emergence from anesthesia. CONCLUSIONS: Our findings indicate clinical overestimation of propofol requirements and highlight the challenges of clinically titrated propofol TIVA in MO adolescents. In this setting, it may be advantageous to titrate propofol to targeted BIS levels until more accurate weight-appropriate dosing regimens are developed, to minimize relative overdosing and its consequences.

Preclincial testing of sorafenib and RAD001 in the Nf(flox/flox) ;DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited disease predisposing affected patients to variable numbers of benign neurofibromas. To date there are no effective chemotherapeutic drugs available for this slow growing tumor. Molecularly targeted agents that aim to slow neurofibroma growth are being tested in clinical trials. So preclinical models for testing potential therapies are urgently needed to prioritize drugs for clinical trials of neurofibromas. PROCEDURE: We used magnetic resonance imaging (MRI) to monitor neurofibroma development in the Nf1(flox/flox) ;DhhCre mouse model of GEM grade I neurofibroma. Based on studies implicating mTOR and Raf signaling in NF1 mutant cells, we tested the therapeutic effect of RAD001 and Sorafenib in this model. Mice were scanned to establish growth rate followed by 8 weeks of drug treatment, then re-imaged after the last dose of drug treatment. Tumor volumes were determined by volumetric measurement. RESULTS: We found that rate of tumor growth varied among mice, as it does in human patients. RAD001 inhibited its predicted target pS6K, yet there was no significant decrease in the tumor volume in RAD001 treated mice compared to the vehicle control group. Sorafenib inhibited cyclinD1 expression and cell proliferation in tumors, and volumetric measurements identified significant decreases in tumor volume in some mice. CONCLUSION: The data demonstrate that volumetric MRI analysis can be used to monitor the therapeutic effect in the preclinical neurofibroma drug screening, and suggest that Sorafenib might have clinical activity in some neurofibromas.

Rising use of CT in child visits to the emergency department in the United States, 1995-2008.

PURPOSE: To describe nationwide trends and factors associated with the use of computed tomography (CT) in children visiting emergency departments (EDs) in the United States between 1995 and 2008. MATERIALS AND METHODS: This study was exempt from institutional review board oversight. Data from the 1995-2008 National Hospital Ambulatory Medical Care Survey were used to evaluate the number and percentage of visits associated with CT for patients younger than 18 years. A mean of 7375 visits were sampled each year. Data were subcategorized according to multiple patient and hospital characteristics. The Rao-Scott χ(2) test was performed to determine whether CT use was similar across subpopulations. RESULTS: From 1995 to 2008, the number of pediatric ED visits that included CT examination increased from 0.33 to 1.65 million, a fivefold increase, with a compound annual growth rate of 13.2%. The percentage of visits associated with CT increased from 1.2% to 5.9%, a 4.8-fold increase, with a compound annual growth rate of 12.8%. The number of visits associated with CT at pediatric-focused and non-pediatric-focused EDs increased from 14,895 and 316,133, respectively, in 1995 to 212,716 and 1,438,413, respectively, in 2008. By the end of the study period, top chief complaints among those undergoing CT included head injury, abdominal pain, and headache. CONCLUSION: Use of CT in children who visit the ED has increased substantially and occurs primarily at non-pediatric-focused facilities. This underscores the need for special attention to this vulnerable population to ensure that imaging is appropriately ordered, performed, and interpreted.

National trends in CT use in the emergency department: 1995-2007.

PURPOSE: To identify nationwide trends and factors associated with the use of computed tomography (CT) in the emergency department (ED). MATERIALS AND METHODS: This study was exempt from institutional review board approval. Data from the 1995-2007 National Hospital Ambulatory Medical Care Survey were used to evaluate the numbers and percentages of ED visits associated with CT. A mean of 30 044 visits were sampled each year. Data were also subcategorized according to multiple patient and hospital characteristics. The Rao-Scott χ(2) test was performed to determine whether CT use was similar across subpopulations. Data were evaluated according to exponential and logistic growth models. RESULTS: From 1995 to 2007, the number of ED visits that included a CT examination increased from 2.7 million to 16.2 million, constituting a 5.9-fold increase and a compound annual growth rate of 16.0%. The percentage of visits associated with CT increased from 2.8% to 13.9%, constituting a 4.9-fold increase and a compound annual growth rate of 14.2%. The exponential growth model provided the best fit for the trend in CT use. CT use was greater in older patients, white patients, patients admitted to the hospital, and patients at facilities in metropolitan regions. By the end of the study period, the top chief complaints among those who underwent CT were abdominal pain, headache, and chest pain. The percentage of patient visits associated with CT for all evaluated chief complaints increased-most substantially among those who underwent CT for flank, abdominal, or chest pain. CONCLUSION: Use of CT has increased at a higher rate in the ED than in other settings. The overall use of CT had not begun to taper by 2007.

Operating room traffic: is there any role of monitoring it?

BACKGROUND: Operating room (OR) human traffic has been implicated as a cause of surgical site infection. We first observed the normal human traffic pattern in our Pediatric Orthopedic ORs, and then examined the effect of surveillance on that traffic pattern. METHODS: This study consisted of 2 phases: phase I sought to observe the OR traffic pattern (number of door swings, maximum and minimum number of OR personnel, number of OR personnel at 30-minute intervals, or changes in nursing, anesthesia, or surgeon staff) during surgical cases without OR personnel being notified, and for phase II, the same traffic pattern was monitored with their knowledge. RESULTS: Two thousand four hundred forty-two minutes of surgical time were observed in phase I, and 1908 minutes were observed in phase II. There was no difference (P=0.06) in the time between door swings between phase I (1.39 min) and phase II (1.70 min), no difference (P=1.000) in the maximum number of people in the OR between phase I (11.5 people, range: 7-15 people) and phase II (11.5 people, range: 8-20 people), and no difference (P=1.000) in the minimum number of people in the OR between phase I (4.67 people, range: 4-6 people) and phase II (4.71 people, range: 3-6 people). There was a difference in the time between door swings (P=0.03) and maximum number of people in the OR (P=0.005) based on the length of the surgery (less or more than 120 min). There was no difference in the time between door swings (P=0.11), but there was a difference in the maximum number of people in the OR (P=0.002) based on type of surgery (spine vs. others). CONCLUSIONS: There was no role of surveillance of human traffic in the OR. To achieve any change in the OR traffic pattern, monitoring alone may not be sufficient; other novel techniques or incentives may need to be considered.

The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan.

We conducted a study to determine if soap containing 1.2% triclocarban would be effective in reducing the incidence of impetigo. We randomized 162 households in a low-income neighborhood of Karachi, Pakistan, to receive a regular supply of 1.2% triclocarban-containing soap (n = 81) or an identically appearing placebo (n = 81); 79 households in a nearby neighborhood were enrolled as standard practice controls. After adjustment for household clustering and covariates, the incidence of impetigo among children living in households receiving triclocarban-containing soap (1.10 episodes per 100 person-weeks) was 23% lower than in households receiving placebo soap (P = 0.28) and 43% lower than the standard habit and practice controls (P = 0.02). The routine use of triclocarban-containing soap by children living in a community with a high incidence of impetigo was associated with a reduced incidence of impetigo.