Anesthesia management for percutaneous mitral valve repair in a patient with mitochondrial cardiomyopathy and low cardiac function: a case report.

BACKGROUND: Mitochondrial cardiomyopathy occurs when impaired mitochondrial energy production leads to myocardial dysfunction. Anesthetic management in such cases is challenging due to risks of circulatory depression associated with anesthesia and mitochondrial dysfunction induced by anesthetics. Although there are reports of anesthetic management for patients with mitochondrial diseases, there are few reports specifically addressing cardiac anesthesia for patients with mitochondrial cardiomyopathy. We present a case where percutaneous mitral valve repair with MitraClip™ was successfully performed under remimazolam anesthesia in a patient with mitochondrial cardiomyopathy who developed functional mitral valve regurgitation due to low cardiac function and cardiomegaly. CASE PRESENTATION: A 57-year-old woman was diagnosed with chronic cardiac failure, with a 10-year history of dilated cardiomyopathy. She was diagnosed with mitochondrial cardiomyopathy 8 years ago. Over the past 2 years, her cardiac failure worsened, and mitral valve regurgitation gradually developed. Surgical intervention was considered but deemed too risky due to her low cardiac function, with an ejection fraction of 26%. Therefore, percutaneous MitraClip™ implantation was selected. After securing radial artery and central venous catheterization under sedation with dexmedetomidine, anesthesia was induced with a low dose of remimazolam 4 mg/kg/h. Anesthesia was maintained with remimazolam 0.35-1.0 mg/kg/h and remifentanil 0.1 µg/kg/min. Noradrenaline and dobutamine were administered intraoperatively, and the procedure was completed successfully without circulatory collapse. The patient recovered smoothly from anesthesia and experienced no complications. She was discharged on the eighth day after surgery. CONCLUSION: Anesthesia management with remimazolam appears to be a safe and effective for MitraClip™ implantation in patients with mitochondrial cardiomyopathy.

Comparison of the negative effect of remimazolam and propofol on cardiac contractility: Analysis of a randomised parallel-group trial and a preclinical ex vivo study.

Remimazolam is a newly developed ultra-short-acting benzodiazepine that exerts sedative effects. This study aimed to clarify the effects of remimazolam on cardiac contractility. In a randomised-parallel group trial, haemodynamic parameters were compared between propofol (n = 11) and remimazolam (n = 12) groups during the induction of general anaesthesia in patients undergoing non-cardiac surgery. In a preclinical study, the direct effects of remimazolam on cardiac contractility were also evaluated using isolated rat hearts. RNA sequence data obtained from rat and human hearts were analysed to assess the expression patterns of the cardiac γ-aminobutyric acid type A (GABAA ) receptor subunits. In a clinical study, the proportional change of the maximum rate of arterial pressure rise was milder during the study period in the remimazolam group (propofol: -52.6 [10.2] (mean [standard deviation])% vs. remimazolam: -39.7% [10.5%], p = 0.007). In a preclinical study, remimazolam did not exert a negative effect on left ventricle developed pressure, whereas propofol did exert a negative effect after bolus administration of a high dose (propofol: -26.9% [3.5%] vs. remimazolam: -1.1 [6.9%], p < 0.001). Analysis of the RNA sequence revealed a lack of γ subunits, which are part of the major benzodiazepine binding site of the GABAA receptor, in rat and human hearts. These results indicate that remimazolam does not have a direct negative effect on cardiac contractility, which might contribute to its milder effect on cardiac contractility during the induction of general anaesthesia. The expression patterns of cardiac GABAA receptor subunits might be associated with the unique pharmacokinetics of benzodiazepines in the heart.

Bilateral multiple stroke, left upper extremity ischemia, and transient complete atrioventricular block in transcatheter aortic valve implantation: a case report.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive surgery. However, there is a risk of surgical manipulation causing detachment of a lesion of the aortic valve, which can result in various embolisms. CASE PRESENTATION: An 87-year-old woman with symptomatic severe aortic valve stenosis was scheduled for transfemoral TAVI under monitored anesthesia. Preoperative examination revealed severe calcification of the aortic valve, but there was no calcification in the ascending aorta. After a delivery catheter system passed the aortic valve, left radial arterial pressure dropped significantly, and complete atrioventricular block (CAVB) occurred. Catecholamine administration and ventricular pacing improved hemodynamics, and a self-expandable valve was implanted. CAVB resolved after surgery, but her state of consciousness was poor, and her left hand became ischemic. Imaging studies revealed multiple embolic infarcts in her bilateral cerebrum and cerebellum. CONCLUSIONS: It should be noted that there is a risk of detachment of a calcified lesion of the aortic valve during TAVI, which can cause embolisms not only in the brain but also in the extremities and coronary arteries.

Apnea management during WATCHMAN device deployment with apneic oxygenation: A case report of three cases.

WATCHMAN is a percutaneous left atrial appendage closure device that is implanted in patients who are unsuitable for anticoagulation therapy for atrial fibrillation. During WATCHMAN implantation, inducing apnea in the patient is preferable to allow stable deployment. We present three cases in which apneic oxygenation was employed to maintain oxygenation during apnea, and oxygen reserve index (ORiTM) was measured to evaluate its safety and efficacy. Oxygen was administered continuously via the endotracheal tube during apnea. During all four apneic events in three patients (mean duration of 356 seconds), the ORi values maintained above 0.24, which is generally considered the threshold of partial pressure of arterial oxygen (PaO2) > 100 mmHg. Transcutaneous oxygen saturation and PaO2 remained above 99% and 300 mmHg, respectively. There were no respiratory or circulatory complications during or after the surgery.

Anesthetic management with remimazolam in very elderly patients undergoing hybrid surgery of transcatheter aortic valve implantation plus off-pump coronary artery bypass grafting: report of two cases.

BACKGROUND: Remimazolam is a short-acting benzodiazepine with small circulatory depression. We used remimazolam for general anesthesia management in two very elderly patients undergoing hybrid surgery of transcatheter aortic valve implantation (TAVI) plus off-pump coronary artery bypass grafting (OPCABG). CASE PRESENTATION: A 96-year-old man (case 1) and a 92-year-old woman (case 2) had complex coronary artery disease (CAD) and severe aortic stenosis (AS) and were scheduled for TAVI plus OPCAB. Anesthesia in both patients was induced with 6 mg/kg/h remimazolam and fentanyl and maintained with 0.3 mg/kg/h and 0.5 mg/kg/h remimazolam and fentanyl, respectively. Although catecholamines were required, we successfully maintained circulation during the induction of anesthesia and the procedures of OPCAB and TAVI. Both patients were discharged without complications. CONCLUSION: Remimazolam can be a useful option for safe general anesthesia in very elderly patients when performing hybrid surgery.

Dexmedetomidine as a cardioprotective drug: a narrative review.

Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but also a cardio-protective drug against ischemia-reperfusion injury (IRI). Numerous preclinical in vivo and ex vivo studies, mostly evaluating the effect of DEX pretreatment in healthy rodents, have shown the efficacy of DEX in protecting the hearts from IRI. However, whether DEX can maintain its cardio-protective effect in hearts with comorbidities such as diabetes has not been fully elucidated. Multiple clinical trials have reported promising results, showing that pretreatment with DEX can attenuate cardiac damage in patients undergoing cardiac surgery. However, evidence of the post-treatment effects of DEX in clinical practice remains limited. In this narrative review, we summarize the previously reported evidence of DEX-induced cardio-protection against IRI and clarify the condition of the hearts and the timing of DEX administration that has not been tested. With further investigations evaluating these knowledge gaps, the use of DEX as a cardio-protective drug could be further facilitated in the management of patients undergoing cardiac surgery and might be considered in a broader area of clinical settings beyond cardiac surgery, including patients with acute myocardial infarction.

Predictors of early postoperative cognitive dysfunction in middle-aged patients undergoing cardiac surgery: retrospective observational study.

PURPOSE: This study aimed to identify the incidence and risk factors of early post-operative cognitive dysfunction (POCD) in middle-aged patients undergoing cardiac surgery. METHODS: Data were examined retrospectively from 71 patients aged 46-64 years who underwent elective cardiac surgery. Magnetic resonance imaging (MRI) and MR angiography were obtained preoperatively to assess prior cerebral infarctions, carotid artery stenosis, and intracranial arterial stenosis. Patients also completed six neuropsychological tests of memory, attention, and executive function before and after surgery. Mild cognitive impairment (MCI) was defined as performance 1.5 standard deviations (SD) below the population means on any neurocognitive battery, whereas POCD was defined as a decrease of 1 SD population means on at least two in the test battery. Patient characteristics were analyzed using univariate analysis, and independent predictors were analyzed using multivariate logistic regression analysis. RESULTS: After surgery, 25 patients (35%) were assessed with POCD. Patients with POCD had significantly higher rates of preoperative MCI and cerebral infarcts on MRI. Multivariate logistic regression analysis identified preoperative MCI and cerebral infarctions detected by MRI as a predictor of POCD. CONCLUSION: More than one-third of middle-aged patients undergoing cardiac surgery developed POCD. Our findings suggested preoperative MCI and infarcts detected by MRI were risk factors for POCD in these middle-aged patients.

Transcatheter aortic valve implantation under lower activated clotting time in a patient with hemorrhagic gastric cancer: a case report.

BACKGROUND: Perioperative management of transcatheter aortic valve implantation (TAVI) in patients with a high risk of bleeding requires careful consideration. CASE PRESENTATION: A 74-year-old man complained of chest pain and was admitted to our hospital. Close examination revealed severe aortic stenosis (AS) and hemorrhagic gastric cancer. Hemorrhage from gastric cancer was controlled using endoscopic hemostasis. While both gastric cancer and AS required surgery, we decided to perform transfemoral transcatheter aortic valve implantation (TAVI) under monitored anesthesia. To reduce bleeding from gastric cancer, we carefully adjusted the heparin dose to maintain the activated clotting time (ACT) between 180 and 200 s. TAVI with a balloon-expandable valve was completed without thrombotic complications. Laparoscopic distal gastrectomy was performed on the 6th day after TAVI. CONCLUSIONS: We report the successful management of TAVI in a patient with hemorrhagic gastric cancer. In TAVI for patients with hemorrhagic diseases, careful consideration of antithrombotic therapy is required.

Risk factors of cardiac arrest and failure to achieve return of spontaneous circulation during anesthesia: a 20-year retrospective observational study from a tertiary care university hospital.

PURPOSE: There is still a lack of robust data on the epidemiology of cardiac arrest during anesthesia. We investigated the frequency and risk factors of cardiac arrest during anesthesia over the past two decades at a tertiary care university hospital in Japan. METHODS: We retrospectively analyzed 111,851 anesthesia records of patients who underwent surgery under anesthesia between 2000 and 2019. Cardiac arrest cases were classified according to the patient's background, surgical status, main cause and initial rhythm of cardiac arrest, and the presence of the return of spontaneous circulation (ROSC). Univariate and multivariate logistic regression analyses were used to identify the risk factors of cardiac arrest and failure to achieve ROSC. RESULTS: Ninety cardiac arrest cases during anesthesia were identified. The incidence of cardiac arrest was 8.05 per 10,000 anesthetics (95% CI, 6.54-9.90). There were 6 anesthesia-related cardiac arrests and 9 anesthesia-contributory cardiac arrests. The most common cause of cardiac arrest was blood loss. American Society of Anesthesiologists physical status 4-5, emergency surgery, and cardiovascular surgery were identified as independent risk factors of cardiac arrest. American Society of Anesthesiologists physical status 4-5, blood loss-induced cardiac arrest, and non-shockable rhythm were independently associated with failure to achieve ROSC. CONCLUSION: Blood loss was the most common cause of cardiac arrest and blood loss-induced cardiac arrest was independently associated with failure to achieve ROSC. Further improvements in treatment strategies for bleeding may reduce the future incidence of cardiac arrest and death during anesthesia.

Effect of remimazolam on intraoperative neuromonitoring during thyroid surgery: a case series.

Intraoperative neuromonitoring is widely used to prevent accidental injury during thyroid surgery. Anesthesia should be performed without muscle relaxant or agents with high muscle-relaxant potency. Remimazolam, a novel intravenous anesthetic, became available for clinical use in 2020. Remimazolam is an ultra-short-acting benzodiazepine with a very high clearance rate. However, there are very few data regarding its effect on currently used intraoperative neurological monitoring. Five patients underwent thyroid surgery using intraoperative recurrent laryngeal neuromonitoring. In all cases, intubation was performed after the administration of rocuronium. Anesthesia was maintained by continuous administration of remimazolam at the recommended dose and remifentanil, and no additional rocuronium or sugammadex was administered. Recurrent laryngeal nerve activity could be detected at the first stimulus after surgery was started, and monitoring continued thereafter. Intraoperative monitoring was performed without problems and all surgeries were completed without any complications. Anesthesia with remimazolam at the normal dose did not prolong the time to first positive electromyogram in patients undergoing thyroid surgery, and enables intraoperative recurrent laryngeal nerve monitoring to be performed without any serious perioperative adverse events. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for neuromonitoring during thyroid surgery.

Remimazolam Anesthesia for MitraClip Implantation in a Patient with Advanced Heart Failure.

Remimazolam, a novel and ultrashort-acting benzodiazepine, has been available for general anesthesia in Japan. The administration of remimazolam does not induce injection pain, has been reported to have less cardiovascular depressant effects during general anesthesia, and flumazenil can antagonize the effects of remimazolam. However, in clinical trials, no patient who is complicated with severe heart failure or undergoes cardiac surgery was included. We present anesthetic management with remimazolam for MitraClip® implantation in a patient with severe mitral regurgitation and advanced heart failure. Remimazolam was administered both in anesthetic induction and maintenance with less cardiovascular depressant effects. After surgical procedures were completed, the patient smoothly recovered from anesthesia and the tracheal was extubated just after administration of flumazenil. Remimazolam may be able to achieve appropriate anesthetic management in patients complicated with severe cardiovascular diseases.

Remimazolam anesthesia for cardiac surgery with cardiopulmonary bypass: a case report.

BACKGROUND: Remimazolam has less cardiovascular depressant effects than propofol in non-cardiac surgical patients. However, the efficacy and safety of remimazolam in cardiac surgery with cardiopulmonary bypass (CPB) have not been reported. We present a case of successful anesthetic management using remimazolam in cardiac surgery with CPB. CASE PRESENTATION: A 76-year-old female was scheduled for mitral valve repair, tricuspid annuloplasty, maze procedure, and left atrial appendage closure. We used remimazolam in induction (6.0 mg/kg/h) and maintenance (0.6-1.0 mg/kg/h) of general anesthesia, and the bispectral index value was maintained in the range of 36 to 48 including the period of CPB. Hemodynamics, mixed venous oxygen saturation, and bilateral regional cerebral oxygen saturation were maintained within acceptable ranges. There was no intraoperative awareness/recall or serious complications associated with remimazolam throughout the perioperative period. CONCLUSIONS: Remimazolam can be used the same as other existing anesthetics in cardiac surgery with CPB.

Cardiovascular considerations for anesthesiologists during the COVID-19 pandemic.

The coronavirus disease (COVID-19) pandemic has brought critical challenges to anesthesiologists and perioperative practice. Whereas anesthesiologists may be primarily concerned with airway and respiratory management, the COVID-19 data accumulated to date indicate that primary and/or secondary cardiovascular complications are common. Previous studies have demonstrated that the mortality rate is significantly higher in patients with cardiovascular disease (CVD) than in patients without CVD. Dysregulation of immune function in patients with CVD may be involved in the prognosis of COVID-19 patients. Anesthesia and surgical procedures can modulate the immune system, and some patients undergoing surgery, particularly those undergoing cardiovascular procedures, have CVD. In perioperative management for patients with suspected or diagnosed COVID-19 and those who have recovered from COVID-19, it is important for anesthesiologists to be concerned not only with airway and respiratory management, but also with cardiovascular complications and perioperative circulatory management to control the progression of the disease in patients with COVID-19.

Assessing the validity of a linear inflation method in noninvasive blood pressure monitoring during the induction period of general anaesthesia.

Inflationary noninvasive blood pressure (iNIBP) monitoring can determine BP in a shorter time compared to conventional deflationary NIBP (dNIBP) monitoring. We assessed the efficacy of iNIBP monitoring during induction of general anaesthesia and tracheal intubation, which can cause rapid changes in haemodynamics. Our study included 14 surgery patients receiving tracheal intubation under general anaesthesia. Blood pressure was continuously measured using iNIBP monitoring. We recorded the percentage of successful iNIBP monitoring (measurements made without switching to dNIBP mode) during anaesthesia induction. We obtained 326 BP-measurements from 14 patients. The iNIPB mode was able to perform 90.9% of the measurements during the induction of general anaesthesia. iNIBP could determine BP even during periods of high blood pressure variability (31.6% [interquartile range; 22-40]). Our results validate the utility of iNIBP monitoring during the induction period of general anaesthesia, despite the rapid haemodynamic changes.

Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial.

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam's efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery. METHODS: A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg-1 h-1-group A and 12 mg kg-1 h-1-group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg-1 h-1 for maintenance of anesthesia in both groups. RESULTS: The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s), p = 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs). CONCLUSION: Both induction regimens (6 and 12 mg kg-1 h-1) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage. Clinical trial registration This trial is registered with the Japan Pharmaceutical Information Center-Clinical Trials Information (JapicCTI). JapicCTI number: 121977.

Lipid emulsion, but not propofol, induces skeletal muscle damage and lipid peroxidation.

PURPOSE: Prolonged propofol infusion induces skeletal muscle damage. However, it is well known that the lipid emulsion that is the solvent of propofol causes various types of tissue damage via lipid peroxidation, and that propofol, conversely, has an anti-lipid peroxidative effect. The purpose of this study was to determine whether propofol or the lipid emulsion is the cause of muscle damage following prolonged administration. METHODS: Rats were divided into four groups: NI group (no intervention), Cath group (venous catheter insertion only), Prop group (1% propofol (Maruishi) intravenous infusion at 10 mg/kg/h), and Lipid group (10% Lipofundin® intravenous infusion at 100 mg/kg/h) (n = 10, each group). 1% Propofol (Maruishi) or Lipofundin was infused at 1 mL/kg/h for 72 h. The solvent of 1% propofol (Maruishi) is a 10% lipid emulsion. Lipofundin consists of 50% long-chain triacylglycerols and 50% medium-chain triacylglycerols, similar to the propofol solvent. Plasma concentrations of creatine kinase and myoglobin, superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the gastrocnemius muscle were evaluated 72 h after the interventions. RESULTS: Plasma concentrations of creatine kinase and myoglobin in the Lipid group were significantly higher than those in the other three groups. The superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the Lipid group were also significantly higher than in the other three groups. CONCLUSION: Lipofundin induces skeletal muscle damage via lipid peroxidation, and 1% propofol (Maruishi) conversely suppresses the muscle damage via antioxidant effects.

Identification of Candidate Genes and Pathways in Dexmedetomidine-Induced Cardioprotection in the Rat Heart by Bioinformatics Analysis.

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, directly protects hearts against ischemia/reperfusion (I/R) injury. However, the detailed mechanism has not been fully elucidated. We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. Dusp1 and Atm were associated with the GO term of MAP kinase tyrosine/serine/threonine phosphatase activity and the p53 pathway, respectively. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.