Recommendations for anesthetic management for intraoperative neuromodulation cases

This paper performs a review of current literature as well as uses our single-center experience to discuss pre-operative, intra-operative and, briefly, postoperative management for dorsal column stimulators (DCSs), dorsal root ganglion (DRG) stimulators, peripheral nerve stimulators (PNSs) and intrathecal pumps. Generally, pre-operative antibiotics are recommended with discontinuation within 24 h postoperatively. For dorsal column and DRG stimulation, monitored anesthesia care or general anesthesia with intra-operative neuromonitoring is recommended; for peripheral nerve stimulation and intrathecal pump implementation, monitored anesthesia care is preferred. There is little information on appropriate anesthetic management during these forms of neuromodulation. More research is necessary to articulate specific pre-operative, intra-operative and postoperative management guidelines and recommendations for dorsal column stimulator, DRG stimulation, PNS and intrathecal pump implantation.

Preoperative evaluation of coagulation status in neuromodulation patients

OBJECTIVE The incidence of hemorrhage in patients who undergo deep brain stimulation (DBS) and spinal cord stimulation (SCS) is between 0.5% and 2.5%. Coagulation status is one of the factors that can predispose patients to the development of these complications. As a routine part of preoperative assessment, the authors obtain prothrombin time (PT), partial thromboplastin time (PTT), and platelet count. However, insurers often cover only PT/PTT laboratory tests if the patient is receiving warfarin/heparin. The authors aimed to examine their experience with abnormal coagulation parameters in patients who underwent neuromodulation. METHODS Patients who underwent neuromodulation (SCS, DBS, or intrathecal pump implantation) over a 9-year period and had preoperative laboratory values available were included. The authors determined abnormal values on the basis of a clinical protocol utilized at their practice, which combined the normal ranges of the laboratory tests and clinical relevance. This protocol had cutoff values of 12 seconds and 39 seconds for PT and PTT, respectively, and < 120,000 platelets/μl. The authors identified risk factors for these abnormalities and described interventions. RESULTS Of the 1767 patients who met the inclusion criteria, 136 had abnormal preoperative laboratory values. Five of these 136 patients had values that were misclassified as abnormal because they were within the normal ranges at the outside facility where they were tested. Fifty-one patients had laboratory values outside the ranges of our protocol, but the surgeons reviewed and approved these patients without further intervention. Of the remaining 80 patients, 8 had known coagulopathies and 24 were receiving warfarin/heparin. The remaining 48 patients were receiving other anticoagulant/antiplatelet medications. These included apixaban/rivaroxaban/dabigatran anticoagulants (n = 22; mean ± SD PT 13.7 ± 2.5 seconds) and aspirin/clopidogrel/other antiplatelet medications (n = 26; mean ± SD PT 14.4 ± 5.8 seconds). Eight new coagulopathies were identified and further investigated with hematological analysis. CONCLUSIONS New anticoagulants and antiplatelet medications are not monitored with PT/PTT, but they affect coagulation status and laboratory values. Although platelet function tests aid in a subset of medications, it is more difficult to assess the coagulation status of patients receiving novel anticoagulants. PT/PTT may provide value preoperatively.

Abstract MP47: Rho-related BTB Domain-containing Protein 1 (RhoBTB1) Attenuates Established Arterial Stiffness In Ang-ii-treated Mice

RhoBTB1 is a transcription target of PPARγ but its function remains unclear. Restoration ofRhoBTB1 by genetic complementation in S-P467L mice expressing dominant negative PPARγmutation reversed hypertension, arterial stiffness, and vascular dysfunction. Here, we asked ifrestoring RhoBTB1 can reverse Ang-II-mediated hypertension and arterial stiffness.To test this hypothesis, S-RhoBTB1 mice, which expressed smooth muscle-specific, tamoxifen(Tx)-inducible RhoBTB1, were implanted with minipumps which released Ang-II (490ng/kg/min, 6weeks) or vehicle. Concurrently, littermate ISM-Cre mice, which expressed smooth muscle-specific, Tx-inducible Cre (but not RhoBTB1), were used as control. Transgenes were induced by5 daily Tx injections 2 weeks after Ang-II pump implantation, and tissue was harvested 2 weeksafter Tx. Measurements were made during a 1 week baseline period, 2 weeks of Ang-II, and 2weeks after transgene activation.Aortic RhoBTB1 expression was decreased in Ang-II-treated ISM-Cre mice (ISM-Cre, Ang-II vs.ISM-Cre, vehicle dCT: 13.6±0.1 vs. 12.4±0.1, n=10), and restored to normal in Ang-II-treated S-RhoBTB1 mice (S-RhoBTB1, Ang-II vs. ISM-Cre, vehicle dCT: 12.8±0.2 vs. 12.4±0.1, n=10-12).Interestingly, pulse-wave velocity, a clinical indicator of arterial stiffness, was significantlydecreased upon RhoBTB1 restoration in Ang-II-treated mice (S-RhoBTB1 vs. ISM-Cre: 2.9±0.1vs. 3.8±0.2, n=22-26). Concomitantly, measures of both pressure-diameter and stress-strainshowed that aortic compliance was improved by RhoBTB1 restoration in Ang-II-treated mice.Interestingly, restoring RhoBTB1 was insufficient to attenuate Ang-II-mediated hypertension (S-RhoBTB1, Ang-II vs. ISM-Cre, Ang-II vs. ISM-Cre, vehicle SBP: 152.1±1.7 vs. 148.0±3.7 vs.115.4± 0.7 mmHg n=12, 8, 6). Currently, we are investigating the mechanism by which RhoBTB1attenuates arterial stiffness.In summary, RhoBTB1 restoration ameliorated Ang-II-mediated arterial stiffness but nothypertension, suggesting that arterial stiffness is not merely a consequence of hypertension butcan be independently regulated from blood pressure. Moreover, there may be novel targets ofRhoBTB1 that can regulate aortic stiffness and be therapeutic.

A NOVEL PREGNANT RAT MODEL FOR LABOR INDUCTION AND AUGMENTATION WITH OXYTOCIN

Background: Despite the widespread use of oxytocin for induction of labor, mechanistic insights into maternal and neonatal wellbeing are lacking because of the absence of an animal model that recapitulates modern obstetric practice. Objective: The objectives of this research were to create and validate a hi-fidelity animal model that mirrors labor induction with oxytocin in parturients and to assess its translational utility. Study Design: The study was performed in timed-pregnant Sprague Dawley dams. The model consisted of a subcutaneously implanted microprocessor-controlled infusion pump on gestational day 18 that was pre-programmed to deliver an escalating dose of intravenous oxytocin on gestational day 21 to induce birth. Once predictable delivery of healthy pups was achieved, we validated the model with molecular biological experiments on the uterine myometrium and telemetry-supported assessment of changes in intrauterine pressure. Finally, we applied this model to test the hypothesis that labor induction with oxytocin was associated with oxidative stress in the newborn brain with a comprehensive array of biomarker assays and oxidative stress gene expression studies. Results: During the iterative model development phase, we confirmed the optimal gestational age for pump implantation, the concentration of oxytocin, and the rate of oxytocin administration. Exposure to anesthesia and surgery during pump implantation was not associated with significant changes in the cortical transcriptome. Activation of pump with oxytocin on gestational day 21 resulted in predictable delivery of pups within 8-12 hours. Increased frequency of change of oxytocin infusion rate was associated with dystocic labor. Labor induction and augmentation with oxytocin was associated with increased expression of the oxytocin receptor gene in the uterine myometrium, decreased expression of the oxytocin receptor protein on the myometrial cell membrane, and cyclical increases in intrauterine pressure. Examination of the frontal cortex of vaginally delivered newborn pups born after oxytocin-induced labor did not reveal an increase in oxidative stress compared to saline-treated control pups. Specifically, there were no significant changes in oxidative stress biomarkers involving both the oxidative stress (reactive oxygen/nitrogen species, 4-hydroxynonenal, protein carbonyl) and the antioxidant response (total glutathione, total antioxidant capacity). In addition, there were no significant differences in the expression of 16 genes emblematic of the oxidative stress response pathway. Conclusions: Collectively, we provide a viable and realistic animal model for labor induction and augmentation with oxytocin. We demonstrate its utility in addressing clinically relevant questions in obstetric practice that could not be mechanistically ascertained otherwise. Based on our findings, labor induction with oxytocin is not likely to cause oxidative stress in the fetal brain. Adoption of our model by other researchers would enable new lines of investigation related to the impact of perinatal oxytocin exposure on the mother-infant dyad.

Periprocedural safety and outcome after pump implantation for intravenous treprostinil administration in patients with pulmonary arterial hypertension

Methods In this retrospective observational study, we analyzed all patients with pulmonary arterial hypertension undergoing LenusPro® pump implantation between November 2013 and October 2019 at our center. Periprocedural safety was assessed by describing all complications that occurred within 28 days after surgery; complications that occurred later were described to assess long-term safety. Clinical outcomes were measured by comparison of clinical parameters and echocardiographic measurements of right ventricular function from baseline to 6-months-follow-up. Results Fifty-four patients underwent LenusPro® pump implantation for intravenous treprostinil treatment during the investigation period. Periprocedural complications occurred in 5 patients; the only anesthesia-related complication (right heart failure with recovery after prolonged intensive care and death in the further course) occurred in the only patient who underwent general anesthesia. All other patients underwent local anesthesia with or without short-acting (analgo-) sedation. Eighteen long-term complications occurred in 15 patients, most notably pump pocket or catheter related problems. Transplant-free survival rates at 1, 2, and 3 years were 77 %, 56 %, and 48 %, respectively. Conclusions Subcutaneous pump implantation under local anesthesia and conscious analgosedation while avoiding intubation and mechanical ventilation is feasible in patients with advanced PAH. Controlled studies are needed to determine the safest anesthetic approach for this procedure. Background/Objectives Intravenous treprostinil treatment via a fully implantable pump is a treatment option for patients with advanced pulmonary arterial hypertension. However, there is no consensus on the preferred anesthetic approach for the implantation procedure. Primary objective was to assess periprocedural safety with particular attention to feasibility of local anesthesia and conscious analgosedation instead of general anesthesia. Long-term safety and clinical outcomes were secondary endpoints.