Intranasal Midazolam With Lidocaine for Sedation in Pediatric Myringotomy and Tube Surgery: A Randomized Controlled Trial.

BACKGROUND AND AIMS: Intranasal midazolam (INM) sedation for children has been associated with side effects. This prospective, double-blind, placebo-controlled trial assessed whether the addition of lidocaine to INM (INM+L) affected efficacy or discharge time among pediatric patients undergoing elective bilateral myringotomy and tube placement (BMT). METHODS: This trial enrolled children aged between 18 months to seven years undergoing BMT, physical status class 1 or 2, in a single academic medical center. Interventions were placebo (intranasal saline), INM only (0.2mg/kg of INM concentration 5mg/ml), and INM+L (0.2mg/kg INM with addition of lidocaine 4% based on 25% of midazolam volume). Outcomes included post-anesthesia care unit times, observed behavioral distress (OBD) visual analog scale (VAS) (by nurse and parent), and sedation scores by certified registered nurse anesthetist (CRNA) and registered nurse (RN). RESULTS: Forty-two subjects were included, 14 in each group, with 52% female, 41% physical status 2, and an average age of 2.7 years. Post-anesthesia care unit times averaged 36.5 minutes (range 15-132 minutes), with no delay in discharge with INM or INM+L versus placebo (p=0.88). Verbal complaints were highest among INM+L at the time of administration (p=0.01). RN-scored OBD at one minute post administration differed significantly across the three groups (p=0.01). Parental OBD scores did not differ across treatment groups. Agitation was greatest at time of induction of anesthesia in the placebo group (p=0.01). CONCLUSIONS: The addition of licodaine to INM does not adversely influence time to discharge and does not reduce side effects, improve efficacy, or change duration of action of INM.

Relation of viscous lidocaine combined with propofol deep sedation during elective upper gastrointestinal endoscopy to discharge.

Fusing topical pharyngeal anesthetics (TPAs) to intravenous sedation during esophagogastroduodenoscopy (EGD) has been controversial. This double-blind, randomized, placebo-controlled trial assessed the association of TPA with patient recovery time, post-EGD to discharge. Supplementary aims were to determine the association of TPA with patient and practitioner satisfaction (both measured on a 100-mm visual analog scale), total propofol dose, and side effects. The study included 93 patients (mean age 53.8 years, range 44-67; 37 men and 56 women) undergoing elective EGD at a single academic medical center from September 2015 to October 2016. Urgent or therapeutic EGDs were excluded. Interventions were 7.5 mL 2% lidocaine viscous solution and 7.5 mL placebo solution (3% methylcellulose). There were no statistically significant differences between the lidocaine (n = 46) and placebo (n = 47) groups with respect to recovery time (42 ± 17.8 vs 39 ± 15.9 minutes; P = 0.23), procedure time (6.5 ± 2.7 vs 7 ± 3.6 minutes; P = 0.77), endoscopist satisfaction (83.2 ± 24.4 vs 77 ± 27.7, P = 0.23), patient discomfort (16.6 ± 19.8 vs 24.0 ± 29.7, P = 0.37), or total propofol administered (2.3 ± 1.3 vs 2.3 ± 1.0 mg/kg, P = 0.55). Compared to placebo, topical viscous lidocaine does not appear to delay recovery time or adversely affect sedation-related outcomes.

Assessment of selenium in Roux-en-Y gastric bypass and gastric banding surgery.

BACKGROUND: Until recently, there was limited documented data on both dietary and serum selenium deficiency in bariatric surgery. We performed an evaluation of selenium intake and both serum selenium and glutathione peroxidase (GTP; as a functional measurement of selenium) before and after roux-en-Y (RNY) gastric bypass and gastric banding surgery. METHODS: The endpoints obtained from the subjects included dietary intake of selenium and vitamins E and C, as well as serum levels of selenium, GTP and vitamins E. These were analyzed at pre-surgery (baseline) and 3 and 12 months post surgery. RESULTS: Dietary deficiencies in selenium intake (38.2 % recommended daily allowance) were noted at 3 months, but not baseline or 12 months, in the gastric bypass group. No dietary deficiencies were noted in the lap band group. For both surgeries, there was a significant reduction from baseline to 3 months in both serum selenium and GTP levels (p = 0.033 and 0.0033 respectively). The serum selenium levels and GTP levels both trended back toward baseline values by 12 months without concomitant selenium supplementation. Mean GTP levels were below normal at all three time points while mean serum selenium levels were all at or above normal. CONCLUSIONS: This study shows that RNY gastric bypass and laparoscopic adjustable gastric banding procedures, and accompanying dietary restrictions, increases the risk for disturbances of selenium and GTP homeostasis. Consideration for selenium supplementation at higher levels than the current RDA of 55 mcg daily during the first 3 months and perhaps longer should be studied further.

The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation. We investigated whether the addition of 6-months' twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin. METHODS: Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited. In random order, patients received usual medications for 6 months, and usual medications plus oral azithromycin 500mg twice weekly for 6 months. Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase. Patients recorded weekly peak flow (PF) measurements. Pulmonary function tests (PFTs), 24-hour sputum volume, and needs for intervention with medication or ancillary support were collected at baseline and every 3 months. Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase. RESULTS: Twelve patients were enrolled; 11 were included in the analysis. Owing to randomization, most patients received the azithromycin first, which was fairly well tolerated. PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase. Azithromycin significantly decreased the incidence of exacerbations compared with usual medications (5 vs 16; p = 0.019). Mean 24-hour sputum volume significantly decreased (15% [p = 0.005]) during the active treatment phase, and remained decreased during the control phase (p = 0.028). Subjectively, patients reported increased energy and quality of life while receiving treatment with azithromycin. CONCLUSIONS: The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study. The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects.

Lack of bioequivalence when levofloxacin and calcium-fortified orange juice are coadministered to healthy volunteers.

Chelation interactions between drugs/supplements that contain large amounts of multivalent ions and the fluoroquinolones have been known for quite some time. However, there has been a lack of taking this interaction into account when they may be coadministered with foods that have been fortified with amounts of multiple multivalent ions that equal or exceed many supplement products. A previous study demonstrated that 12 ounces of calcium-fortified orange juice significantly decreased the bioequivalence of a dose of ciprofloxacin. This study examined, in 16 healthy volunteers, whether 12 ounces of orange juice with and without calcium fortification would demonstrate the same chelation interaction with single doses of levofloxacin. The results of the study demonstrated that both types of juice decreased levofloxacin Cmax values by 14% to 18% and prolonged tmax values by approximately 50%, with calcium-fortified orange juice decreasing Cmax enough to lose bioequivalence as compared to the control arm (89% [78.1%, 99.8%]). Due to the lack of change in overall exposure, it is thought that rather than a chelation interaction, levofloxacin and components of the orange juices competed for intestinal transport mechanisms such as P-glycoprotein and organic anion-transporting polypeptides, which resulted in the discovered interaction. These results further confirm the need to adjust regulatory studies to include bioequivalence/bioavailability studies that contain fortified foods more than high-calorie/high-fat foods to better reflect current American consumption habits.

Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers.

Previous work has demonstrated that the chelation interaction seen with ciprofloxacin when it is coadministered with antacids also happens when it is coadministered with calcium-fortified foods. This study was conducted to study whether this was a drug-specific finding or whether the interaction occurs with other members of the fluoroquinolone class of drugs. Sixteen healthy volunteers received single 400-mg oral doses of gatifloxacin with 12 ounces each of water, nonfortified orange juice, and calcium-fortified orange juice and had plasma samples drawn for assay over the subsequent 48 hours. Results demonstrated significant increases in total oral clearance (15%) and volume of distribution (13%) along with a matching significant decrease (12%) in exposure (AUC) when gatifloxacin was taken with the fortified juice. Although not statistically significant, peak concentrations decreased by 15% and were reached (tmax) approximately 38% later when gatifloxacin was coadministered with the calcium-fortified juice. Bioavailability testing indicated that although the 90% confidence intervals (CIs) for the ratio of the geometric means of the calcium-fortified juice and water arms' AUC stayed within the range of 80% to 125%, those for Cmax did not. This study demonstrated a chelation or adsorption interaction between the fortified juice and gatifloxacin that reached regulatory significance. As a result, clinicians may wish to instruct patients to take gatifloxacin either with nonfortified foods or on an empty stomach.

Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction.

Fluoroquinolones are known to interact with drugs containing multivalent ions. Current Food and Drug Administration (FDA) labeling states that ciprofloxacin and most other fluoroquinolones are safe to be given with food and dietary calcium but not calcium supplements. Although many of the currently marketed calcium fortified foods have calcium contents that usually exceed those in dietary calcium sources, it is unclear whether they represent a risk for less than optimal absorption of fluoroquinolones, which may result in subsequent clinical failures due to lack of bacterial eradication and antibiotic resistance. The purpose of this three-way, randomized, crossover study was to characterize and compare the bioequivalence of single doses of oral ciprofloxacin in 15 healthy volunteers when administered with water, concurrently with orange juice, and concurrently with calcium-fortified orange juice. Compared to the control arm, the Cmax of ciprofloxacin significantly decreased when it was given with orange juice (23%, p = 0.001) and with calcium-fortified orange juice (41%, p < 0.001). Twenty-four-hour ciprofloxacin AUCs were also decreased for both forms of the orange juice (22% [p < 0.001] and 38% [p < 0.001], respectively). When compared to each other, neither of the orange juice regimens were bioequivalent to each other, with the Cmax and AUC for the fortified form being 22% (p = 0.005) and 21% (p = 0.015) lower than those of the nonfortified form. By FDA standards, although ciprofloxacin is marginally bioequivalent when administered with orange juice, it is not when it is administered with calcium-fortified orange juice. The changes in Cmax and AUC have the potential to significantly decrease clinical efficacy and promote antibiotic resistance. Not warning patients about potential food-drug interactions with fortified foods may be a major unrealized and unstudied inadvertent source of clinical failures and resistance trends with fluoroquinolones.