Protein oxidation involved in Cys-Tyr post-translational modification.

Some post-translationally modified tyrosines can perform reversible redox chemistry similar to metal cofactors. The most studied of these tyrosine modifications is the intramolecular thioether-crosslinked 3'-(S-cysteinyl)-tyrosine (Cys-Tyr) in galactose oxidase. This Cu-mediated tyrosine modification in galactose oxidase involves direct electron transfer (inner-sphere) to the coordinated tyrosine. Mammalian cysteine dioxygenase enzymes also contain a Cys-Tyr that is formed, presumably, through outer-sphere electron transfer from a non-heme iron center ~6Å away from the parent residues. An orphan protein (BF4112), amenable to UV spectroscopic characterization, has also been shown to form Cys-Tyr between Tyr 52 and Cys 98 by an adjacent Cu2+ ion-loaded, mononuclear metal ion binding site. Native Cys-Tyr fluorescence under denaturing conditions provides a more robust methodology for Cys-Tyr yield determination. Cys-Tyr specificity, relative to 3,3'-dityrosine, was provided in this fluorescence assay by guanidinium chloride. Replacing Tyr 52 with Phe or the Cu2+ ion with a Zn2+ ion abolished Cys-Tyr formation. The Cys-Tyr fluorescence-based yields were decreased but not completely removed by surface Tyr mutations to Phe (Y4F/Y109F, 50%) and Cys 98 to Ser (25%). The small absorbance and fluorescence emission intensities for C98S BF4112 were surprising until a significantly red-shifted emission was observed. The red-shifted emission spectrum and monomer to dimer shift seen by reducing, denaturing SDS-PAGE demonstrate a surface tyrosyl radical product (dityrosine) when Cys 98 is replaced with Ser. These results demonstrate surface tyrosine oxidation in BF4112 during Cys-Tyr formation and that protein oxidation can be a significant side reaction in forming protein derived cofactors.

A randomized trial comparing the Ambu ® Aura-i ™ with the air-Q ™ intubating laryngeal airway as conduits for tracheal intubation in children.

OBJECTIVES: To assess the clinical performance of the Ambu Aura-i (Aura-i) in children. AIM: To compare the Aura-i with the air-Q intubating laryngeal airway (air-Q) for the purposes of fiberoptic-guided tracheal intubation. BACKGROUND: The Aura-i is a new supraglottic airway designed for tracheal intubation. MATERIALS/METHODS: One hundred twenty children, ages 1 month to 6 years, were randomized to receive either the Aura-i or air-Q, and divided into three equal subgroups (Group 1, 2, 3) based on weight. The time for successful tracheal intubation was primarily assessed. The ease, time, and number of attempts for successful device insertion, leak pressures, fiberoptic grade of laryngeal view, number of attempts time for removal of the device after tracheal intubation, and complications were secondarily assessed. RESULTS: Device placement, tracheal intubation, and removal after tracheal intubation were successful in all patients. There were no differences in the time to successful tracheal intubation through the Aura-i (32.9 ± 13.3 s), and the air-Q (33.9 ± 13 s; P = 0.68), or fiberoptic grade of view between devices. There was not a statistically significant correlation between the time to intubation and the fiberoptic grade of laryngeal view in any of the groups. There were no statistically significant differences in the overall leak pressures, air-Q (18.3 ± 6.1 cm H(2) O) vs Aura-i (16 ± 5.1 cm H(2) O; P = 0.05). In Group 1 (5-10 kg), leak pressures were higher with the air-Q (23.4 ± 7.2 cm H(2) O) than the Aura-i (16.1 ± 5.2 cm H(2) O; P = 0.001). There were no statistically significant differences in the time for removal between the two devices (P = 0.11). However, with the size 1.5 Aura-i, the pilot balloon of the tracheal tube was removed in order to facilitate the removal of the device after tracheal intubation. CONCLUSIONS: Both devices served as effective conduits for fiberoptic-guided tracheal intubation. The limitation of the narrower proximal airway tube of the size 1.5 Aura-i should be considered if cuffed tracheal tubes are to be utilized.

Prospective evaluation of the self-pressurized air-Q intubating laryngeal airway in children.

OBJECTIVES: To assess the clinical efficacy of the self-pressurized air-Q ILA™ (ILA-SP). AIM: The purpose of this prospective audit was to evaluate the feasibility of the ILA-SP in clinical practice and generate data for future comparison trials. BACKGROUND: The ILA-SP is a new first-generation supraglottic airway for children with a self-adjusting cuff and lack of a pilot balloon. METHODS: Over a 4-month period, 352 children with an ASA physical status of I-III, newborn to 18 years of age, undergoing various procedures were studied. Data points assessed included insertion success rates, airway leak pressures, quality of ventilation, and perioperative complications associated with the use of this device. RESULTS: In 349 of the 352 patients in this study, the ILA-SP was used successfully as a primary supraglottic airway device in a variety of patients. Three patients required conversion to a standard laryngeal mask airway or a tracheal tube. The mean initial airway leak pressure for all patients was 17.8 ± 5.4 cm H(2)O, and 20.4 ± 5.5 cm H(2)O when re-checked at 10 min, which was statistically significant (P < 0.001). Complications were limited to 14 patients and related to reflex activation of the airway (coughing, laryngospasm, and bronchospasm) (n = 10), sore throat (n = 3), and blood staining on removal of the device (n = 1). There were no episodes of regurgitation, aspiration, or hoarseness. CONCLUSIONS: Acceptable clinical performance was demonstrated with the ILA-SP for a variety of procedures in infants and children with spontaneous and positive pressure ventilation. Future studies comparing this device to other supraglottic airways may provide useful information regarding the safety of the ILA-SP in pediatric clinical practice.

A clinical evaluation of the intubating laryngeal airway as a conduit for tracheal intubation in children.

BACKGROUND: The air-Q Intubating Laryngeal Airway (ILA) (Cookgas LLC, Mercury Medical, Clearwater, FL) is a supraglottic airway device available in pediatric sizes, with design features to facilitate passage of cuffed tracheal tubes when used to guide tracheal intubation. We designed this prospective observational study of the ILA to assess the ease of its placement in paralyzed pediatric patients, determine its position and alignment to the larynx using a fiberoptic bronchoscope, gauge its efficacy as a conduit for fiberoptic intubation with cuffed tracheal tubes, and evaluate the ability to remove the ILA without dislodgement of the tracheal tube after successful tracheal intubation. METHODS: One hundred healthy children, aged 6 months to 8 years, ASA physical status I to II, and scheduled for elective surgery requiring general endotracheal anesthesia were enrolled in this prospective study. Based on the manufacturer's guidelines, each patient received either a size 1.5 or 2.0 ILA according to their weight. The number of attempts for successful insertion, leak pressures, fiberoptic grade of view, number of attempts and time for tracheal intubation, time for ILA removal, and complications were recorded. RESULTS: ILA placement, fiberoptic tracheal intubation, and ILA removal were successful in all patients. The size 1.5 ILA cohort had significantly higher rates of epiglottic downfolding compared with the size 2.0 ILA cohort (P < 0.001), despite adequate ventilation variables. When comparing fiberoptic grade of view to weight, a moderate negative correlation was found (r = -0.41, P < 0.001), indicating that larger patients tended to have better fiberoptic grades of view. The size 1.5 ILA cohort had a significantly longer time to intubation (P = 0.04) compared with the size 2.0 ILA cohort. However, this difference may not be clinically significant because there was a large overlap of confidence bounds in the average times of the size 1.5 ILA (27.0 ± 13.0 seconds) and size 2.0 ILA cohorts (22.7 ± 6.9 seconds). When comparing weight to time to tracheal intubation, a weak correlation that was not statistically significant was found (r = -0.17, P = 0.09), showing that time to intubation did not differ significantly according to weight, despite higher fiberoptic grades in smaller patients. CONCLUSIONS: The ILA was easy to place and provided an effective conduit for tracheal intubation with cuffed tracheal tubes in children with normal airways. Additionally, removal of the ILA after successful intubation could be achieved quickly and without dislodgement of the tracheal tube. Because of the higher incidence of epiglottic downfolding in smaller patients, the use of fiberoptic bronchoscopy is recommended to assist with tracheal intubation through this device.

The new air-Q intubating laryngeal airway for tracheal intubation in children with anticipated difficult airway: a case series.

The air-Q intubating laryngeal airway (ILA) is a new supraglottic airway device which may overcome some limitations inherent to the classic laryngeal mask airway for tracheal intubation. We present a case series of patients with anticipated difficult airway in whom the air-Q ILA was successfully used as a conduit for fiberoptic intubation.

There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.

BACKGROUND: Tonsillectomy is associated with postoperative nausea and vomiting (PONV) if no prophylaxis is administered. Previous studies have shown that a single dose of dexamethasone decreases the incidence of PONV. The most effective dose of dexamethasone to affect clinical outcome is yet to be defined. METHODS: One-hundred-twenty-five children were enrolled in a double-blind, prospective, randomized, dose-escalating study of dexamethasone: 0.0625, 0.125, 0.25, 0.5, or 1 mg/kg, maximum dose 24 mg. Nonparametric ANOVA was used to analyze the incidence of vomiting by treatment group for 0 to < or =5 h, >5 to 24 h. The Cox Proportional Likelihood Ratio Test was used to compare the time of first vomit and time to first pain medication across treatment groups. RESULTS: There was no difference in the incidence of vomiting for the five escalating doses of dexamethasone in the time period. There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups. CONCLUSION: We conclude that the lowest dose of dexamethasone (0.0625 mg/kg) was as effective as the highest dose of dexamethasone (1.0 mg/kg) for preventing PONV or reducing the incidence of other secondary outcomes following tonsillectomy or adenotonsillectomy. There is no justification for the use of high-dose dexamethasone for the prevention of PONV in this cohort of children.

A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.

UNLABELLED: We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). IMPLICATIONS: This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.

The addition of clonidine 2 microg.kg-1 does not enhance the postoperative analgesia of a caudal block using 0.125% bupivacaine and epinephrine 1:200,000 in children: a prospective, double-blind, randomized study.

BACKGROUND: In this prospective, randomized, double-blind study, we compared the efficacy of 0.125% bupivacaine and epinephrine 1:200,000 with and without clonidine 2 microg.kg-1 for 'single shot' pediatric caudal analgesia. METHODS: Thirty ASA I and II children, ages 2-8 years, undergoing outpatient surgical procedures below the umbilicus received 1 ml.kg-1 0.125% bupivacaine with fresh epinephrine 1:200,000 and clonidine 2 microg.kg-1 (group-C) or 1 ml.kg-1 0.125 % bupivacaine with epinephrine 1:200 000 (group-NC). All patients received a standardized general anesthetic (induction with 67% N2O in O2 and sevoflurane followed by isoflurane maintenance). Primary outcome measures were time to first rescue analgesic and number of patients requiring rescue analgesic at 4, 6, 8, 12, and 24 h after caudal placement. Secondary outcome measures included: extubation times, Objective Pain Scale (OPS) scores, sedation scores, time in postanesthesia care unit (PACU), discharge time, number of analgesic doses given in 24 h following caudal blockade, and adverse effects (vomiting, hypotension, and bradycardia). RESULTS: There were no differences in demographics, investigated parameters, or adverse effects between groups. CONCLUSIONS: We found that the addition of clonidine 2 microg.kg-1 to 0.125% bupivacaine with fresh epinephrine 1:200,000 for caudal analgesia did not significantly delay the time to first rescue analgesic or decrease the overall need for rescue analgesics in children 2-8 years undergoing surgical procedures below the umbilicus.

Teaching residents pediatric fiberoptic intubation of the trachea: traditional fiberscope with an eyepiece versus a video-assisted technique using a fiberscope with an integrated camera.

BACKGROUND: The authors' hypothesis was that a video-assisted technique should speed resident skill acquisition for flexible fiberoptic oral tracheal intubation (FI) of pediatric patients because the attending anesthesiologist can provide targeted instruction when sharing the view of the airway as the resident attempts intubation. METHODS: Twenty Clinical Anesthesia year 2 residents, novices in pediatric FI, were randomly assigned to either the traditional group (traditional eyepiece FI) or the video group (video-assisted FI). One of two attending anesthesiologists supervised each resident during FI of 15 healthy children, aged 1-6 yr. The time from mask removal to confirmation of endotracheal tube placement by end-tidal carbon dioxide detection was recorded. Intubation attempts were limited to 3 min; up to three attempts were allowed. The primary outcome measure, time to success or failure, was compared between groups. Failure rate and number of attempts were also compared between groups. RESULTS: Three hundred patient intubations were attempted; eight failed. On average, the residents in the video group were faster, were three times more likely to successfully intubate at any given time during an attempt, and required fewer attempts per patient compared to those in the traditional group. CONCLUSIONS: The video system seems to be superior for teaching residents fiberoptic intubation in children.

Traditional versus new needle retractable i.v. catheters in children: are they really safer, and whom are they protecting?

Retractable needle IV catheters are designed to reduce needle-stick injuries; their use is mandated by federal regulations. We undertook a prospective data collection with the "traditional" IV catheters (JELCO) versus the "new" (Angiocath Autoguard). Assignment of catheter type was randomized by week. Data collected included assessment of the difficulty of i.v. access; number of catheters used; and splatters or spills of blood on skin, linen, floor, clothing, and operating room table. There were 473 attempted insertions in 330 patients over 20 days. No needle-stick injuries occurred. Seventy-seven blood spills or splatters occurred in 42 patients. The number of splatters or spills was four times more with the new compared with the traditional catheters. There were significantly more total splatters or spills and patients who experienced splatters or spills with new catheters when they were placed by attendings but not when placed by trainees. Our study suggests that use of this technology by more experienced anesthesiologists may increase the risk of exposure of health care providers to blood-borne pathogens. Practitioners should choose the i.v. system that allows the most efficient venous access with the least potential for blood contamination. Hospitals should allow the choice to be made by the individuals using the devices.