Management of Neuraxial Analgesia in a Parturient with Factor XIII Deficiency: A Case Report and Proposed Management Algorithm.

Factor XIII (FXIII) deficiency is a rare coagulation defect that can be associated with significant bleeding. A 28-year-old pregnant woman, with a history of hemorrhagic stroke secondary to severe congenital FXIII deficiency, presented in active labor requesting an epidural. Factor XIII levels had been monitored throughout her pregnancy and treated with intermittent factor XIII infusions to maintain factor levels above 30% of normal. After careful multidisciplinary peripartum evaluation and FXIII replacement, neuraxial analgesia was performed without complication. Neuraxial analgesia can be performed without complication in patients with FXIII deficiency if FXIII levels are carefully managed and no other coagulopathy exists.

How Pediatric Anesthesiologists Manage Children with OSA Undergoing Tonsillectomy.

OBJECTIVE: The purpose of this study was to describe typical anesthesia practices for children with obstructive sleep apnea (OSA). STUDY DESIGN: Online survey. METHOD: A sample of pediatric anesthesiologists received the survey by email. RESULTS: 110 respondents were included. 46.4% worked in a free-standing children's hospital and 32.7% worked in a children's facility within a general hospital. 73.6% taught residents. 44.4% saw at least one child with OSA per week, 25.5% saw them daily. On a 100-mm visual analog scale, respondents rated their comfort with managing these children as 84.94 (SD 17.59). For children with severe OSA, 53.6% gave oral midazolam preoperatively, but 24.5% typically withheld premedication and had the parent present for induction. 68.2% would typically use nitrous oxide for inhalational induction. 68.2% used fentanyl intraoperatively, while 20.0% used morphine. 61.5% reduced their intraop narcotic dose for children with OSA. 98.2% used intraoperative dexamethasone, 58.2% used 0.5 mg/kg for the dose. 98.2% used ondansetron, 62.7% used IV acetaminophen, and 8.2% used IV NSAIDs. 83.6% extubated awake. 27.3% of respondents stated that their institution had standardized guidelines for perioperative management of children with OSA undergoing adenotonsillectomy. People who worked in children's hospitals, who had >10 years of experience, or who saw children with OSA frequently were significantly more comfortable dealing with children with OSA (P < 0.05). CONCLUSION: Apart from using intraoperative dexamethasone and ondansetron, management varied. These children would likely benefit from best practices perioperative management guidelines.

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.

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. METHODS: A retrospective cohort study was conducted using anesthetic records and electrophysiological records of 32 children who had intraoperative electrophysiological monitoring during selective posterior rhizotomy under general anesthesia. Administration and dosage of ketamine preceding the stimulation of dorsal roots was determined from the anesthetic record. A pediatric neurologist, blinded to patient, and to ketamine exposure, evaluated different electrophysiological criteria. RESULTS: Eight children received ketamine and 24 did not receive it. The mean average dose of ketamine was 0.18 mg x kg(-1) (sd: 0.04). We did not find any statistically significant difference in intraoperative electrophysiological response between the ketamine and the control groups. However, we noted some trends: Administration of ketamine preceding the stimulation of dorsal roots was associated with a lower maximal threshold (2.7 mA vs 3.5 mA, P = 0.663) and root thresholds compared with children who did not receive ketamine. In addition, the train response following delivery of the suprastimulation tended to last longer with the presence of ketamine. CONCLUSIONS: Administration of low dose ketamine preceding the stimulation of dorsal roots during selective posterior rhizotomy might be associated with lower maximal thresholds and a more sustained train response following stimulation. Physicians should be aware of this finding in order to avoid misinterpreting intraoperative electrophysiological monitoring.

Coupling specificity of NOP opioid receptors to pertussis-toxin-sensitive Galpha 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.

Peak volume history and peak pressure-volume curve pressures independently affect the shape of the pressure-volume curve of the respiratory system.

OBJECTIVE: To determine the specific effect of peak volume history pressure on the inflation limb of the pressure-volume curve and peak pressure-volume curve pressure on the deflation limb of the pressure-volume curve. DESIGN: Prospective assessment of pressure-volume curves in saline, lung lavage injured sheep. SETTING: Large animal laboratory of a university-affiliated hospital. SUBJECTS: Eight female Dorset sheep. INTERVENTIONS: : The effect of two volume history pressures (40 and 60 cm H2O) and three pressure-volume curve peak pressures (40, 50, and 60 cm H2O) were randomly compared. MEASUREMENTS AND MAIN RESULTS: Peak volume history pressure affected the inflation curve beyond the lower inflection point but did not affect the inflection point (Pflex). Peak pressure-volume curve pressure affected the deflation curve. Increased peak volume history pressure increased inflation compliance (p <.05). Increased peak pressure-volume curve pressure increased the point of maximum compliance change on the deflation limb and deflation compliance and decreased compliance between peak pressure and the point of maximum curvature on the deflation limb (p <.05). CONCLUSION: Peak volume history pressure must be considered when interpreting the inflation limb of the pressure-volume curve of the respiratory system beyond the inflection point. The peak pressure achieved during the pressure-volume curve is important during interpretation of deflation compliance and the point of maximum compliance change on the deflation limb.

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.

Determinants of tidal volume during high-frequency oscillation.

OBJECTIVE: High-frequency oscillation has been proposed for use in adult acute respiratory distress syndrome. However, limited data are available on the effect of pressure amplitude and rate (Hz) on tidal volumes delivered during high-frequency oscillation in adults. DESIGN: Prospective, animal model, lung injury study. SETTING: Large-animal laboratory of a university-affiliated medical center. SUBJECTS: Nine sheep (29.2 +/- 2.4 kg). INTERVENTIONS: Severe lung injury was induced by repeated saline lung lavage. After stabilization, high-frequency oscillation was initiated at a mean airway pressure equal to the point of maximum curvature on the deflation limb of the pressure-volume curve (26 +/- 1.9 cm H2O). Tidal volume at all combinations of rates of 4, 6, 8, and 10 Hz, pressure amplitudes of 30, 40, 50, and 60 cm H2O, and inspiratory/expiratory ratios of 1:1 and 1:2 (using the Sensormedics 3100B oscillator) were measured. Flow was measured by a pneumotachometer, amplified and digitized at 1000 Hz. Three breaths were analyzed at each setting. MEASUREMENTS AND MAIN RESULTS: At both inspiratory/expiratory ratios, tidal volume was directly proportional to pressure amplitude and inversely proportional to frequency. During an inspiratory/expiratory ratio of 1:1, at 60 cm H2O pressure amplitude and 4 Hz, a tidal volume of 129.1 +/- 34.8 mL (4.4 +/- 1.2 mL/kg) was delivered. CONCLUSIONS: At low rates and high-pressure amplitudes in this model, tidal volumes approaching conventional mechanical ventilation can be delivered during high-frequency oscillation.