Khaled Sedeek

Open-lung Protective Ventilation with Pressure Control Ventilation, High-frequency Oscillation, and Intratracheal Pulmonary Ventilation Results in Similar Gas Exchange, Hemodynamics, and Lung Mechanics

Background Pressure control ventilation (PCV), high-frequency oscillation (HFO), and intratracheal pulmonary ventilation (ITPV) may all be used to provide lung protective ventilation in acute respiratory distress syndrome, but the specific approach that is optimal remains controversial. Methods Saline lavage was used to produce acute respiratory distress syndrome in 21 sheep randomly assigned to receive PCV, HFO, or ITPV as follows: positive end-expiratory pressure (PCV and ITPV) and mean airway pressure (HFO) were set in a pressure-decreasing manner after lung recruitment that achieved a ratio of Pao2/Fio2 > 400 mmHg. Respiratory rates were 30 breaths/min, 120 breaths/min, and 8 Hz, respectively, for PCV, ITPV, and HFO. Eucapnia was targeted with peak carinal pressure of no more than 35 cm H2O. Animals were then ventilated for 4 h. Results There were no differences among groups in gas exchange, lung mechanics, or hemodynamics. Tidal volume (PCV, 8.9 ± 2.1 ml/kg; ITPV, 2.7 ± 0.8 ml/kg; HFO, approximately 2.0 ml/kg) and peak carinal pressure (PCV, 30.6 ± 2.6 cm H2O; ITPV, 22.3 ± 4.8 cm H2O; HFO, approximately 24.3 cm H2O) were higher in PCV. Pilot histologic data showed greater interstitial hemorrhage and alveolar septal expansion in PCV than in HFO or ITPV. Conclusion These data indicate that HFO, ITPV, and PCV when applied with an open-lung protective ventilatory strategy results in the same gas exchange, lung mechanics, and hemodynamic response, but pilot data indicate that lung injury may be greater with PCV.

Coupling Specificity of NOP Opioid Receptors to Pertussis-Toxin-Sensitive Gα Proteins in Adult Rat Stellate Ganglion Neurons Using Small Interference RNA

The opioid receptor-like 1 (NOP or ORL1) receptor is a G-protein-coupled receptor the endogenous ligand of which is the heptadecapeptide, nociceptin (Noc). NOP receptors are known to modulate pain processing at spinal, supraspinal, and peripheral levels. Previous work has demonstrated that NOP receptors inhibit N-type Ca2+ channel currents in rat sympathetic stellate ganglion (SG) neurons via pertussis toxin (PTX)-sensitive Galphai/o subunits. However, the identification of the specific Galpha subunit that mediates the Ca2+ current modulation is unknown. The purpose of the present study was to examine coupling specificity of Noc-activated NOP receptors to N-type Ca2+ channels in SG neurons. Small interference RNA (siRNA) transfection was employed to block the expression of PTX-sensitive Galpha subunits. RT-PCR results showed that siRNA specifically decreased the expression of the intended Galpha subunit. Evaluation of cell surface protein expression and Ca2+ channel modulation were assessed by immunofluorescence staining and electrophysiological recordings, respectively. Furthermore, the presence of mRNA of the intended siRNA target Galpha protein was examined by RT-PCR experiments. Fluorescence imaging showed that Galphai1, Galphai3, and Galphao were expressed in SG neurons. The transfection of Galphai1-specific siRNA resulted in a significant decrease in Noc-mediated Ca2+ current inhibition, while silencing of either Galphai3 or Galphao was without effect. Taken together, these results suggest that in SG neurons Galphai1 subunits selectively couple NOP receptors to N-type Ca2+ channels.

Randomized Prospective Evaluation of Intraoperative Intravenous Acetaminophen in Pediatric Adenotonsillectomy

Objective To establish the safety and efficacy of single-dose intraoperative intravenous (IV) acetaminophen in postoperative pain management following adenotonsillectomy in addition to a standardized regimen of oral pain medication. Study Design Randomized, controlled prospective clinical trial. Setting Single academic medical center. Subjects and Methods Patients between the ages of 3 and 17 years scheduled for tonsillectomy or adenotonsillectomy by a single surgeon between December 2014 and November 2016 were recruited. Patients were randomly assigned to 1 of 2 groups; group 1 received a single intraoperative dose of IV acetaminophen, and group 2 did not. Induction and maintenance of anesthesia, as well as operative technique, were standardized. Nursing pain scores, pain medications administered, and recovery times were reviewed during the 24-hour postoperative period. Postoperative pain regimen included standing alternating oral acetaminophen and ibuprofen. Results In total, 260 patients were included in the study, and 131 (50.4%) received a single intraoperative dose of IV acetaminophen. Patients receiving IV acetaminophen were more likely to experience postoperative nausea and vomiting than patients who did not receive IV acetaminophen (1.53% vs 0.00%, P = .016). There were no significant differences noted for postoperative pain scores, requirements for breakthrough pain medications, time to discharge from the recovery room or hospital, or postoperative complications. Conclusion The use of a single intraoperative dose of IV acetaminophen was associated with minimal additional adverse effects. However, a single intraoperative IV dose of acetaminophen added to standard narcotic and nonnarcotic pain medication does not provide a statistically significant improvement in pain control.

Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients

The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population.

Effect of single dose intraoperative IV acetaminophen in pediatric tonsillectomy or adenotonsillectomy

Abstract Background A number of different treatment regimens have been described for post-operative pain management for pediatric tonsillectomy following the widespread discontinuation of the use of codeine due to safety concerns. However, the literature is lacking with regard to the relative efficacy of the treatment regimens. This study is designed to determine the effectiveness of an intraoperative dose of intravenous acetaminophen for pediatric tonsillectomy pain management. Methods Records were reviewed for pediatric patients undergoing tonsillectomy with a single surgeon between 2012 and 2014. Pain scores, need for narcotic analgesics, and recovery times were reviewed for up to 24 postoperative hours. Patients were grouped based on whether they received an intraoperative dose of intravenous acetaminophen (Group 1) or did not receive it (Group 2). The primary outcome measure was pain score during the 24-h post-operative period. Secondary outcome measures include need for narcotic medications for breakthrough pain in the recovery room and time spent in the recovery room and hospital. Results 350 patients were included, of which 116 received an intraoperative dose of intravenous acetaminophen. Patients in Group 1 had lower pain scores during the second postoperative hour (1.27 vs. 2.06, p = 0.008). No significant differences were noted for pain scores during postoperative hours 1 or 3–24. Patients in Group 1 spent less time in the Recovery Room (59.08 min vs. 69.5 min, p = 0.016) but more time in the hospital (24.54 h vs. 19.66 h, p = 0.030). There was no difference between the groups based on whether the patients received narcotics for breakthrough pain in the recovery room (79.3% vs. 70.9%, p = 0.094). Conclusion Intraoperative intravenous acetaminophen may lead to improved pain scores in the early postoperative period and decreased time in the recovery room, but this group also had a longer hospital stay. This information should instigate randomized controlled trials of this intervention.

The management of neuraxial anesthesia in Henoch-Schonlein purpura (HSP) patient.

when an ilioinguinal nerve block is performed for orchidopexy. Postoperatively, however, following discharge, all 10 children remained completely pain free at home and required no further analgesia. This may indicate that TAP block provided analgesia of long duration but slow onset. Further investigation is warranted. M A R I A N N E F I T Z G E R A L D J A C I N T A M C G I N L E Y Department of Anaesthesia Our Lady’s Hospital for Sick Children, Dublin, Ireland (email: mariannefitz@gmail.com)

Does ketamine affect intraoperative electrophysiological monitoring in children undergoing selective posterior rhizotomy

Objective:  Direct dorsal rootlet stimulation with intraoperative electrophysiological monitoring is an adjunct to clinical evaluation during selective posterior rhizotomy. The purpose of this study was to evaluate the impact of ketamine on intraoperative electrophysiological monitoring during selective posterior rhizotomy. Specifically, we sought to determine if low dose ketamine given as part of the anesthesia was associated with changes in intraoperative electrophysiological monitoring in patients who underwent selective posterior rhizotomy.

Anesthesia for hypertrophic pyloric stenosis: a five-year review

INTRODUCTION The management of idiopathic hypertrophic pyloric stenosis (IHPS) has evolved with the introduction of various surgical approaches such as laparoscopy and the circumbilical incision, the increased use of ultrasonography as a diagnostic tool and the introduction of new anesthetic agents. The principal aim of this study was to assess the effect of anesthetic technique and new diagnostic and surgical approaches on outcome of infants undergoing pyloromyotomy.