A retrospective review of 10-year trends in general anesthesia for cesarean delivery at a university hospital: the impact of a newly launched team on obstetric anesthesia practice.

BACKGROUND: The indications for general anesthesia (GA) in obstetric settings, which are determined in consideration of maternal and fetal outcome, could be affected by local patterns of clinical practice grounded in unique situations and circumstances that vary among medical institutions. Although the use of GA for cesarean delivery has become less common with more frequent adoption of neuraxial anesthesia, GA was previously chosen for pregnancy with placenta previa at our institution in case of unexpected massive hemorrhage. However, the situation has been gradually changing since formation of a team dedicated to obstetric anesthesia practice. Here, we report the results of a review of all cesarean deliveries performed under GA, and assess the impact of our newly launched team on trends in clinical obstetric anesthesia practice at our institution. METHODS: Our original database for obstetric GA during the period of 2010 to 2019 was analyzed. The medical records of all parturients who received GA for cesarean delivery were reviewed to collect detailed information. Interrupted time series analysis was used to evaluate the impact of the launch of our obstetric anesthesia team. RESULTS: As recently as 2014, more than 10% of cesarean deliveries were performed under GA, with placenta previa accounting for the main indication in elective and emergent cases. Our obstetric anesthesia team was formed in 2015 to serve as a communication bridge between the department of anesthesiology and the department of obstetrics. Since then, there has been a steady decline in the percentage of cesarean deliveries performed under GA, decreasing to a low of less than 5% in the latest 2 years. Interrupted time series analysis revealed a significant reduction in obstetric GA after 2015 (P = 0.04), which was associated with decreased use of GA for pregnancy with placenta previa. On the other hand, every year has seen a number of urgent cesarean deliveries requiring GA. CONCLUSIONS: There has been a trend towards fewer obstetric GA since 2015. The optimized use of GA for cesarean delivery was made possible mainly through strengthened partnerships between anesthesiologists and obstetricians with the support of our obstetric anesthesia team.

Sildenafil ameliorates right ventricular early molecular derangement during left ventricular pressure overload.

Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.

Reliability of cardiac output measurements using LiDCOrapid™ and FloTrac/Vigileo™ across broad ranges of cardiac output values.

Knowing a patient's cardiac output (CO) could contribute to a safe, optimized hemodynamic control during surgery. Precise CO measurements can serve as a guide for resuscitation therapy, catecholamine use, differential diagnosis, and intervention during a hemodynamic crisis. Despite its invasiveness and intermittent nature, the thermodilution technique via a pulmonary artery catheter (PAC) remains the clinical gold standard for CO measurements. LiDCOrapid™ (LiDCO, London, UK) and FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA) are less invasive continuous CO monitors that use arterial waveform analysis. Their calculations are based on arterial waveform characteristics and do not require calibration. Here, we evaluated LiDCOrapid™ and FloTrac/Vigileo™ during off-pump coronary artery bypass graft (OPCAB) and living-donor liver transplantation (LDLT) surgery. This observational, single-center study included 21 patients (11 OPCAB and 10 LDLT). We performed simultaneous measurements of CO at fixed sampling points during surgery using both devices (LiDCOrapid™ version 1.04-b222 and FloTrac/Vigileo™ version 3.02). The thermodilution technique via a PAC was used to obtain the benchmark data. LiDCOrapid™ and FloTrac/Vigileo™ were used in an uncalibrated fashion. We analyzed the measured cardiac index using a Bland-Altman analysis (the method of variance estimates recovery), a polar plot method (half-moon method), a 4-quadrant plot and compared the widths of the limits of agreement (LOA) using an F test. One OPCAB patient was excluded because of the use of an intra-aortic balloon pumping during surgery, and 20 patients (10 OPCAB and 10 LDLT) were ultimately analyzed. We obtained 149 triplet measurements with a wide range of cardiac index. For the FloTrac/Vigileo™, the bias and percentage error were -0.44 L/min/m2 and 74.4 %. For the LiDCOrapid™, the bias and percentage error were -0.38 L/min/m2 and 53.5 %. The polar plot method showed an angular bias (FloTrac/Vigileo™ vs. LiDCOrapid™: 6.6° vs. 5.8°, respectively) and radial limits of agreement (-63.9 to 77.1 vs. -41.6 to 53.1). A 4-quadrant plot was used to obtain concordance rates (FloTrac/Vigileo™ vs. PAC and LiDCOrapid™ vs. PAC: 84.0 and 92.4 %, respectively). We could compare CO measurement devices across broad ranges of CO and SVR using LDLT and OPCAB surgical patients. An F test revealed no significant difference in the widths of the LoA for both devices when sample sizes capable of detecting a more than two-fold difference were used. We found that both devices tended to underestimate the calculated CIs when the CIs were relatively high. These proportional bias produced large percentage errors in the present study.

[Anesthetic management for patients with mitochondrial disease].

Mitochondrial diseases are caused by a decrease in ATP production due to mutations of mitochondrial or mitochondria-related nuclear DNA. Their effects are likely to appear in tissues with a high energy demand, including skeletal muscle, nervous, and cardiovascular systems. Cardiac manifestations of mitochondrial diseases can be divided into cardiomyopathies, which are primarily hypertrophic and dilated cardiomyopathies, and electropathies, which are primarily conduction system disease and ventricular pre-excitation. The first principle of anesthesia for patients with mitochondrial diseases is to avoid any additional burden on the already declined metabolic functions. Appropriate oxygenation, minimization of the oxygen demand, stable cardiovascular management, maintenance of a normal blood glucose level and body temperature, and effective perioperative pain control are of importance. Most anesthetics have been reported to reduce mitochondrial functions, and although enhancement of the sensitivity and prolongation of the duration of action have been reported, they are clinically used with no major problems. Detailed preoperative evaluation of the disease condition and careful intraoperative monitoring are important for the prevention of perioperative complications.

[Coronary artery bypass graft (CABG) in a patient with chronic obstructive pulmonary disease (COPD) who showed difficulty in respiratory control].

We experienced a patient with severe COPD undergoing OPCAB who showed difficult perioperative respiratory and circulatory management. Since patients with severe COPDs are often complicated with not only respiratory but also circulatory problems such as right heart failure, it is necessary to assess preoperatively the method of intraoperative management including operative procedure.

Bortezomib and dexamethasone for Japanese patients with relapsed and refractory multiple myeloma: a single center experience.

Bortezomib is a novel proteasome inhibitor, which has shown high antimyeloma activity. APEX trial, phase III randomized study for relapsed or refractory myeloma established efficacy and feasibility of bortezomib. In our study, we retrospectively investigated 60 Japanese patients with relapsed or refractory multiple myeloma (MM) who underwent bortezomib and dexamethasone (BD) therapy in our institution. Overall response rate was 75%, including 7 cases (11.7%) of complete response and 13 cases (21.7%) of very good partial response. Stable disease and progressive disease were observed in 15 patients (25%). Major ≥ grade 3 adverse events were hematological toxicities and grade 3 non-hematological toxicities included appetite loss, diarrhea and peripheral neuropathy. BD therapy was well tolerated, and produced significant response in relapsed or refractory MM patients. Recently, many worldwide trials including bortezomib or other new agents are ongoing to evaluate its efficacy not only as a therapy for relapsed or refractory disease but also as a frontline therapy. Further investigations are required to define how to use new antimyeloma agents for Japanese MM patients.

[Anesthetic management of emergency total gastrectomy in a patient with mitochondrial encephalomyopathy: a case of gastric perforation accompanied by systemic inflammatory response syndrome].

There are several problems in anesthetic management for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); susceptibility to malignant hyperthermia, metabolic disorders such as lactic acidosis and diabetes, and dysfunction of vital organs such as cardiomyopathy. Here we report an anesthetic management of emergency laparotomy in a 58-year-old woman with MELAS and systemic inflammatory response syndrome (SIRS). Pre-operative examinations revealed lactic acidosis, hyperglycemia, moderate cardiac depression, and slightly decreased renal function. We chose total intravenous anesthesia to avoid risks of malignant hyperthermia. Anesthesia was induced by rapid-sequence fashion and maintained using midazolam, propofol, ketamine, fentanyl and vecuronium. Based on arterial blood gas analyses, we adjusted ventilator settings, restored blood volume using acetated-Ringer's solution and alubumin preparation with transfusion, and administered sodium bicarbonate and catecholamines, to keep adequate oxygen demand/supply balance and improve acid-base balance. We applied a patient warming system to avoid the progression of hypothermia. After the surgery, the patient was transferred to the intensive care unit, and underwent the endotoxin absorption therapy as well as antibiotics therapy for the treatment of SIRS. The post-operative course was almost uneventful. We consider that careful anesthetic management was essential for the uneventful peri-operative course of this patient.

Donor cell-derived acute lymphocytic leukemia after allogeneic stem cell transplantation for multiple myeloma.

Donor cell leukemia (DCL) is a rare, but well-known, complication after allogeneic hematopoietic cell transplantation. We report a case of donor cell-derived acute lymphocytic leukemia (ALL) occurring in a 55-year-old man after allogeneic bone marrow transplantation (allo-BMT) from an HLA-matched unrelated donor for refractory multiple myeloma (MM). Molecular analysis using short tandem repeat sequences proved the ALL to be of donor origin. He underwent combination chemotherapy and second allo-BMT from an alternative donor. After second allo-BMT, extramedullary myeloma relapsed as tumor, but was successfully treated with proteasome inhibitor, bortezomib. However, he died from severe graft-versus-host disease four months after the second transplantation. Although more than 50 cases of DCL have been reported, there have been only two reports of DCL developed in MM patients including our case. This rare complication may give some insights into leukemogenesis.

[Effects of general anesthesia using ketamine and remifentanil on postoperative pain management for patients undergoing laparotomy].

BACKGROUND: Co-administration of ketamine and remifentanil may offer preemptive analgesia and prevention of opioid-induced hyperalgesia, resulting in reduction of postoperative pain. METHODS: We retrospectively analyzed data concerning anesthetic management and postoperative pain management in 19 adult patients undergoing elective laparotomy with general anesthesia using ketamine and remifentanil. RESULTS: Ketamine and remifentanil were co-administered for both induction and maintenance of general anesthesia. Preoperative and total doses of ketamine were 1.4+/-0.5 and 1.9+/-0.4 mg x kg(-1). Infusion rate of remifentanil at the beginning of surgery was 0.24+/-0.02 microg x kg(-1) x min(-1), and minimal and maximal rate were 0.06+/-0.03 and 0.26+/-0.03 microg x kg(-1) min(-1). Pentazocine and nonsteroidal anti-inflammatory drugs (NSAIDs) were used for postoperative pain management. Consumption of pentazocine was 0.51+/-0.33 mg x kg(-1) on 1st postoperative day (1POD), and NSAIDs were co-administered on 1POD for 3 patients. Most patients could stand up and walk on 1POD. CONCLUSIONS: Results in this study suggest that anesthetic management using ketamine and remifentanil may be useful for postoperative pain management, probably by preemptive analgesic effects of both agents and preventive effects of ketamine against opioid-induced hyperalgesia.

Low voltage pulses can induce apoptosis.

Electroporation is used for gene transfection, drug delivery, and cell fusion. While studies have shown that high voltage electroporation induces apoptosis in vitro, a strong electric field can lower cell survival rates. As there are no published reports which have examined apoptotic properties associate with low voltage electric charges, we demonstrated for the first time that consecutive low voltage pulses with a voltage lower than the membrane breakdown threshold of human cells can increase the membrane potential to the threshold required to induce electroporation. This led to apoptosis through caspase pathways. Moreover, necrotic cell damage was less than that caused by high voltage pulses. Therefore, low voltage electroporation can be a suitable anticancer method.

Development of a wearable surveillance system using gait analysis.

An aging society is a reality in developed countries. An aging population requires more healthcare workers and facilities. To reduce this social problem, it is worthwhile to develop a wearable computer for elders or patients to watch over them. In this study, we developed a wearable computer, in which accelerometers were installed to detect variations of posture, falls, and gait disability. The advantages of this system include a designated database server in each patient's home, scalability and flexibility to adapt to patient's needs, and full patient access to their own information. As a first step, we adopted this system for healthy young volunteers with or without impediments to validate the system. The results show that this system can successfully detect variations in posture and falls. We also succeeded in real-time automatic gait analysis by using the Hampering Index. The present study gives useful knowledge for the development of a wearable computer to support the care of elders or other patients.