Incorporation of the Transverse Thoracic Plane Block Into a Multimodal Early Extubation Protocol for Cardiac Surgical Patients.

BACKGROUND: The aim for early extubation remains an important goal in cardiac surgical patients. Therefore, employment of a multimodal approach to pain management that includes a transverse thoracic plane block was retrospectively examined at a single-center tertiary care hospital on the effects of time to extubation, opioid consumption, and length of stay in patients undergoing cardiac surgery via median sternotomy. METHODS: Blocks were performed on all cardiac surgical patients except for those undergoing left ventricular assist device placement, thoracic transplant, emergent surgery, or redo sternotomy. Following additional exclusions for intra- and postoperative complications unrelated to anesthesia, final analysis was conducted on 75 patients per group. Multimodal pain management included intravenous analgesics and transverse thoracic plane block where patients received 15 mL 0.5% bupivacaine + epinephrine bilaterally under ultrasound guidance prior to incision. RESULTS: Following transverse thoracic plane block and multimodal analgesics, 50.6% of patients were extubated in the operation room versus 8.6% in the control group. Intraoperative opioids were decreased, and intensive care unit and total length of stay were reduced by 5 hours and 1 day, respectively, in block patients as compared with controls. Postoperative opioids were not significantly different. There were no reported complications directly attributed to the block. CONCLUSIONS: The transverse thoracic plane block and multimodal regimen for patients undergoing median sternotomy resulted in a significant number of patients extubated in the operation room without an increase in postoperative re-intubations. Moreover, the block appears to be a quick and safe procedure to utilize on cardiac surgery patients.

Right-to-Left Shunt During Transseptal Mitral Valve-in-Valve Replacement: A Case Report.

The following case report details an 88-year-old woman with severe mitral stenosis and moderate mitral regurgitation who presented with worsening dyspnea on exertion. The patient had undergone 4-vessel coronary artery bypass graft and mitral valve replacement 14 years before and was deemed high risk for redo sternotomy. A transseptal mitral valve-in-valve replacement was performed which resulted in intraoperative hypoxia and hypotension after atrial septal defect creation for valve deployment. A right-to-left shunt had developed due to the patient's underlying pulmonary hypertension. Successful atrial septal defect closure resolved the hypoxia and hypotension. The patient had a brief and uncomplicated postoperative course.

Chloramphenicol biosynthesis: the structure of CmlS, a flavin-dependent halogenase showing a covalent flavin-aspartate bond.

Chloramphenicol is a halogenated natural product bearing an unusual dichloroacetyl moiety that is critical for its antibiotic activity. The operon for chloramphenicol biosynthesis in Streptomyces venezuelae encodes the chloramphenicol halogenase CmlS, which belongs to the large and diverse family of flavin-dependent halogenases (FDH's). CmlS was previously shown to be essential for the formation of the dichloroacetyl group. Here we report the X-ray crystal structure of CmlS determined at 2.2 A resolution, revealing a flavin monooxygenase domain shared by all FDHs, but also a unique 'winged-helix' C-terminal domain that creates a T-shaped tunnel leading to the halogenation active site. Intriguingly, the C-terminal tail of this domain blocks access to the halogenation active site, suggesting a structurally dynamic role during catalysis. The halogenation active site is notably nonpolar and shares nearly identical residues with Chondromyces crocatus tyrosyl halogenase (CndH), including the conserved Lys (K71) that forms the reactive chloramine intermediate. The exception is Y350, which could be used to stabilize enolate formation during substrate halogenation. The strictly conserved residue E44, located near the isoalloxazine ring of the bound flavin adenine dinucleotide (FAD) cofactor, is optimally positioned to function as a remote general acid, through a water-mediated proton relay, which could accelerate the reaction of the chloramine intermediate during substrate halogenation, or the oxidation of chloride by the FAD(C4alpha)-OOH intermediate. Strikingly, the 8alpha carbon of the FAD cofactor is observed to be covalently attached to D277 of CmlS, a residue that is highly conserved in the FDH family. In addition to representing a new type of flavin modification, this has intriguing implications for the mechanism of FDHs. Based on the crystal structure and in analogy to known halogenases, we propose a reaction mechanism for CmlS.

Expression, purification and preliminary diffraction studies of CmlS.

CmlS, a flavin-dependent halogenase (FDH) present in the chloramphenicol-biosynthetic pathway in Streptomyces venezuelae, directs the dichlorination of an acetyl group. The reaction mechanism of CmlS is of considerable interest as it will help to explain how the FDH family can halogenate a wide range of substrates through a common mechanism. The protein has been recombinantly expressed in Escherichia coli and purified to homogeneity. The hanging-drop vapour-diffusion method was used to produce crystals that were suitable for X-ray diffraction. Data were collected to 2.0 A resolution. The crystal belonged to space group C2, with unit-cell parameters a = 208.1, b = 57.7, c = 59.9 A, beta = 97.5 degrees .