Successful treatment of bepridil-induced intraoperative torsades de pointes by isoproterenol infusion.

BACKGROUND: Several types of antiarrhythmic drugs are known to induce QT prolongation and torsades de pointes. CASE PRESENTATION: An 84-year-old man was scheduled for open gastrectomy for residual cancer. He had been prescribed bepridil for atrial fibrillation that converted to sinus rhythm with prolonged QT interval in the operating room. After the surgery was initiated under general and epidural anesthesia, the patient's heart rate decreased to 50/min and multifocal premature ventricular contractions appeared, followed by several episodes of torsades de pointes, each lasting for 5 to 15 s. Infusion of isoproterenol was started (0.01 µg/kg/min), and the heart rate was maintained at around 80/min. Premature ventricular contractions disappeared, and torsades de pointes did not recur during the surgery. The operation was completed uneventfully. The serum bepridil concentration was found to be extremely high postoperatively. CONCLUSIONS: Bepridil-induced intraoperative episodes of torsades de pointes were successfully treated by increasing the heart rate with isoproterenol.

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.

Synergistic cytoprotection by co-treatment with dexamethasone and rapamycin against proinflammatory cytokine-induced alveolar epithelial cell injury.

BACKGROUND: One of the main pathophysiological manifestations during the acute phase of sepsis is massive production of proinflammatory mediators. Clinical trials involving direct suppression of inflammatory mediators to relieve organ dysfunction in sepsis have been extensively performed; however, the clinical outcomes of such trials remain far from satisfactory. Given the need for better sepsis treatments, we have screened various agents with anti-inflammatory properties for cytoprotective effects. In this study, we identified dexamethasone and rapamycin as clinically applicable candidates with favorable synergistic effects against inflammatory cytokine-induced cytotoxicity in vitro and further explored the molecular mechanisms underlying the augmented cytoprotective effects exerted by co-treatment with both drugs. METHODS: Human alveolar epithelial cell-derived A549 cells were stimulated with a mixture of inflammatory cytokines, TNF-alpha, IL-1beta, and IFN-gamma, which induce cellular injury, including apoptosis. This in vitro model was designed to simulate acute lung injury (ALI) associated with sepsis. The cells were co-treated with dexamethasone and rapamycin under cytokine stimulation. Conditioned medium and cell lysates were subjected to further analysis. RESULTS: Either dexamethasone or rapamycin significantly attenuated cytokine-induced cytotoxicity in A549 cells in a dose-dependent manner. In addition, the simultaneous administration of dexamethasone and rapamycin had a synergistic cytoprotective effect. The applied doses of dexamethasone (10 nM) and rapamycin (1 nM) were considerably below the reported plasma concentrations of each drug in clinical setting. Interestingly, distinct augmentation of both of c-Jun inhibition and Akt activation were observed when the cells were co-treated with both drugs under cytokine stimulation. CONCLUSIONS: A synergistic protective effect of dexamethasone and rapamycin was observed against cytokine-induced cytotoxicity in A549 cells. Augmentation of both of c-Jun inhibition and Akt activation were likely responsible for the cytoprotective effect. The combined administration of anti-inflammatory drugs such as dexamethasone and rapamycin offers a promising treatment option for alveolar epithelial injury associated with sepsis.

A Case of a Cardiac Resynchronization Therapy-Defibrillator Exhibiting a Lower and Alternately Variable Basic Rate.

A cardiac resynchronization therapy defibrillator (CRT-D) (Medtronic Inc. Protecta XT) was implanted in a 67-year-old man who had cardiac sarcoidosis with extremely low cardiac function. He had ventricular tachycardia which was controlled by catheter ablation, medication and pacing. The programmed mode was DDI, lower rate was 90 beats/minute, paced AV delay was 150 ms, and the noncompetitive atrial pacing (NCAP) function was programmed as 300 ms.After his admission for pneumonia and heart failure, we changed his DDI mode to a DDD mode because he had atrial tachycardia, which led to inadequate bi-ventricular pacing. After a while, there were cycle lengths which were longer than his device setting and alternately varied. We were able to avoid this phenomenon with AV delay of 120 ms and NCAP of 200 ms.NCAP is an algorithm which creates a gap above a certain period after the detection of an atrial signal during the postventricular atrial refractory period of the pacemaker. This is to prevent atrial tachycardia and repetitive non-reentrant ventriculoatrial (VA) synchrony in the presence of retrograde VA conduction. But in this case, NCAP algorithm induced much lower rate than the programmed basic lower rate. This situation produced some arrhythmias and exacerbated symptoms of heart failure. This had to be paid attention to, especially when the device was programmed at high basic heart rate.

Early-phase Innate Immune Suppression in Murine Severe Sepsis Is Restored with Systemic Interferon-ß.

BACKGROUND: Sepsis is a leading cause of death in the intensive care unit. Immune modulatory therapy targeting sepsis-associated proinflammatory responses has not shown survival benefit. Here, the authors evaluated innate immunity at the early stage of murine mild or severe peritoneal sepsis induced by cecal ligation and puncture, and the effect of systemic interferon-ß, a potent inflammatory mediator, on severe sepsis as well as its mechanism of action. METHODS: Mild and severe sepsis was induced in C57BL/6 mice by cecal ligation and puncture with 22- and 18-gauge needles for puncture, respectively. Interferon-ß (700 U/g) was subcutaneously administered either before or 12 h after cecal ligation and puncture for the severe sepsis group. RESULTS: Severe sepsis resulted in significantly lower 6-day survival rates than mild sepsis (n = 48, 25% vs. n = 11, 81.8%, P = 0.002), significantly less phagocytic capacity of peritoneal exudate cells, and lower CXC chemokine receptor-2 expression on circulating neutrophils at 24 h after cecal ligation and puncture. Interferon-ß administration 12 h after cecal ligation and puncture associated with significantly improved survival (n = 34, 52.9%, P = 0.017) increased the number and function of peritoneal exudate cells, peritoneal/systemic inflammatory cytokine/chemokine concentrations, and CXC chemokine receptor-2 on neutrophils, compared with the severe sepsis controls. However, those responses were not observed in the prophylactic interferon-ß group (n = 24). Interferon-ß increased lipopolysaccharide-induced interleukin-6 messenger RNA/protein expression of lipopolysaccharide-tolerant murine peritoneal macrophages, which was not observed in nontolerant cells. CONCLUSIONS: In severe sepsis, immune suppression occurs within 24 h and is associated with worse mortality. Interferon-ß given after the onset of peritonitis restores impaired innate immunity in vivo and in vitro.

IFN-ß Improves Sepsis-related Alveolar Macrophage Dysfunction and Postseptic Acute Respiratory Distress Syndrome-related Mortality.

IFN-ß is reported to improve survival in patients with acute respiratory distress syndrome (ARDS), possibly by preventing sepsis-induced immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly understood. We investigated the therapeutic effects of IFN-ß for postseptic ARDS to better understand its pathogenesis in mice. Postseptic ARDS was reproduced in mice by cecal ligation and puncture to induce sepsis, followed 4 days later by intratracheal instillation of Pseudomonas aeruginosa to cause pneumonia with or without subcutaneous administration of IFN-ß 1 day earlier. Sepsis induced prolonged increases in alveolar TNF-α and IL-10 concentrations and innate immune reprogramming; specifically, it reduced alveolar macrophage (AM) phagocytosis and KC (CXCL1) secretion. Ex vivo AM exposure to TNF-α or IL-10 duplicated cytokine release impairment. Compared with sepsis or pneumonia alone, pneumonia after sepsis was associated with blunted alveolar KC responses and reduced neutrophil recruitment into alveoli despite increased neutrophil burden in lungs (i.e., "incomplete alveolar neutrophil recruitment"), reduced bacterial clearance, increased lung injury, and markedly increased mortality. Importantly, IFN-ß reversed the TNF-α/IL-10-mediated impairment of AM cytokine secretion in vitro, restored alveolar innate immune responsiveness in vivo, improved alveolar neutrophil recruitment and bacterial clearance, and consequently reduced the odds ratio for 7-day mortality by 85% (odds ratio, 0.15; 95% confidence interval, 0.03-0.82; P = 0.045). This mouse model of sequential sepsis → pneumonia infection revealed incomplete alveolar neutrophil recruitment as a novel pathogenic mechanism for postseptic ARDS, and systemic IFN-ß improved survival by restoring the impaired function of AMs, mainly by recruiting neutrophils to alveoli.

Development of a local anesthetic lidocaine-loaded redox-active injectable gel for postoperative pain management.

Although local anesthesia is commonly applied for pain relief, there are several issues such as its short duration of action and low effectiveness at the areas of inflammation due to the acidic pH. The presence of excessive amount of reactive oxygen species (ROS) is known to induce inflammation and aggravate pain. To resolve these issues, we developed a redox-active injectable gel (RIG) with ROS-scavenging activity. RIG was prepared by mixing polyamine-b-poly(ethylene glycol)-b-polyamine with nitroxide radical moieties as side chains on the polyamine segments (PMNT-b-PEG-b-PMNT) with a polyanion, which formed a flower-type micelle via electrostatic complexation. Lidocaine could be stably incorporated in its core. When the temperature of the solution was increased to 37°C, the PIC-type flower micelle transformed to gel. The continuous release of lidocaine from the gel was observed for more than three days, without remarkable initial burst, which is probably owing to the stable entrapment of lidocaine in the PIC core of the gel. We evaluated the analgesic effect of RIG in carrageenan-induced arthritis mouse model. Results showed that lidocaine-loaded RIG has stronger and longer analgesic effect when administered in inflamed areas. In contrast, while the use of non-complexed lidocaine did not show analgesic effect one day after its administration. Note that no effect was observed when PIC-type flower micelle without ROS-scavenging ability was used. These findings suggest that local anesthetic-loaded RIG can effectively reduce the number of injection times and limit the side effects associated with the use of anti-inflammatory drugs for postoperative pain management. STATEMENT OF SIGNIFICANCE: 1. We have been working on nanomaterials, which effectively eliminate ROS, avoiding dysfunction of mitochondria in healthy cells. 2. We designed redox injectable gel using polyion complexed flower type micelle, which can eliminates ROS locally. 3. We could prepare local anesthesia-loaded redox injectable gel (lido@RIG). 4. Drug release could be extended by local administration of lido@RIG. 5. Deprotonation of lidocaine improved anesthetic effect because ROS were eliminated locally by RIG. 6. Local inflammation could be also suppressed by lido@RIG.

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53.

Inflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously. Nuclear factor (NF)-κB and p53 are key regulators of inflammation and apoptosis, respectively. Sirt1 inhibits p65 NF-κB and p53 by deacetylating these transcription factors. Recently, we have shown that iNOS induces S-nitrosylation of Sirt1, which inactivates Sirt1 and thereby increases acetylation and activity of p65 NF-κB and p53 in various cell types, including skeletal muscle cells. Here, we show that iNOS enhances burn-induced inflammatory response and apoptotic change in mouse skeletal muscle along with S-nitrosylation of Sirt1. Burn injury induced robust expression of iNOS in skeletal muscle and gene disruption of iNOS significantly inhibited burn-induced increases in inflammatory gene expression and apoptotic change. In parallel, burn increased Sirt1 S-nitrosylation and acetylation and DNA-binding capacity of p65 NF-κB and p53, all of which were reversed or ameliorated by iNOS deficiency. These results indicate that iNOS functions not only as a downstream effector but also as an upstream enhancer of burn-induced inflammatory response, at least in part, by Sirt1 S-nitrosylation-dependent activation (acetylation) of p65 NF-κB. Our data suggest that Sirt1 S-nitrosylation may play a role in iNOS-mediated enhanced inflammatory response and apoptotic change, which, in turn, contribute to muscle wasting and supposedly to insulin resistance after burn injury.

Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65.

Inflammation increases the abundance of inducible nitric oxide synthase (iNOS), leading to enhanced production of nitric oxide (NO), which can modify proteins by S-nitrosylation. Enhanced NO production increases the activities of the transcription factors p53 and nuclear factor κB (NF-κB) in several models of disease-associated inflammation. S-nitrosylation inhibits the activity of the protein deacetylase SIRT1. SIRT1 limits apoptosis and inflammation by deacetylating p53 and p65 (also known as RelA), a subunit of NF-κB. We showed in multiple cultured mammalian cell lines that NO donors or inflammatory stimuli induced S-nitrosylation of SIRT1 within CXXC motifs, which inhibited SIRT1 by disrupting its ability to bind zinc. Inhibition of SIRT1 reduced deacetylation and promoted activation of p53 and p65, leading to apoptosis and increased expression of proinflammatory genes. In rodent models of systemic inflammation, Parkinson's disease, or aging-related muscular atrophy, S-nitrosylation of SIRT1 correlated with increased acetylation of p53 and p65 and activation of p53 and NF-κB target genes, suggesting that S-nitrosylation of SIRT1 may represent a proinflammatory switch common to many diseases and aging.

iNOS inhibitor, L-NIL, reverses burn-induced glycogen synthase kinase-3ß activation in skeletal muscle of rats.

OBJECTIVES: Recent studies suggest that activation of glycogen synthase kinase (GSK)-3ß may be involved in burn injury-induced metabolic derangements and protein breakdown in skeletal muscle. However, the mechanism for GSK-3ß activation after burn injury is unknown. To investigate the role of inducible nitric oxide synthase (iNOS) in this scenario, a major mediator of inflammation, we examined the effects of a specific inhibitor for iNOS, L-NIL, on GSK-3ß activity in skeletal muscle of burned rats. MATERIALS/METHODS: Full-thickness third degree burn injury comprising 40% of total body surface area was produced under anesthesia in male Sprague-Dawley rats (160-190g) by immersing the back of the trunk for 15s and the abdomen for 8s in 80°C water. Burned and sham-burned rats were treated with L-NIL (60mg/kg BW, b.i.d., IP) or phosphate-buffered saline for three days. GSK-3ß activity in skeletal muscle was evaluated by immune complex kinase assay, and by phosphorylation status of GSK-3ß and its endogenous substrate, glycogen synthase. RESULTS: GSK-3ß activity was increased in a time-dependent manner in skeletal muscle after burn injury, concomitant with the induction of iNOS expression. iNOS inhibitor, L-NIL, reverted the elevated GSK-3ß activity in skeletal muscle of burned rats, although L-NIL did not alter GSK-3ß activity in sham-burned rats. CONCLUSIONS: Our results clearly indicate that iNOS plays an important role in burn injury-induced GSK-3ß activation in skeletal muscle. These findings suggest that iNOS may contribute to burn injury-induced metabolic derangements, in part, by activating GSK-3ß.

Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549.

Epithelial cell injury under hyperinflammatory conditions is critical in the development of septic acute lung injury (ALI). The aim of the present study is to analyze the cytotoxic effects of a mixture of proinflammatory cytokines in the human alveolar epithelial cell line A549. The cytotoxicity of proinflammatory cytokines were assessed in A549 cells by measuring lactate dehydrogenase released into the culture medium and by crystal violet staining of surviving cells. Activation of the caspase-dependent apoptotic pathway was evaluated by monitoring cleavage of cytokeratin 18 by caspases using enzyme-liked immunosorbent assay (ELISA). To estimate the cytotoxic signaling pathways responsible for epithelial injury, agents with antiinflammatory or antioxidative properties were extensively screened for cytoprotective effects in the inflammation-associated epithelial injury model. The present study revealed that inflammatory cytokines exerted cytotoxicity in A549 cells. A mixture of interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), designated as cytomix, augmented cytotoxicity compared with each individual cytokine. Treatment with glucocorticoid (dexamethasone), tetracycline-derived antiinflammatory antibiotics (minocycline or doxycycline), angiotensin II receptor blockers (losartan or telmisartan), or antioxidants (dimethyl sulfoxide, catalase) attenuated cytomix-induced cytotoxicity, including caspase activation. These results implied that inflammatory cytokines alone could cause alveolar epithelial injury in the pathophysiology of septic ALI. Caspase-dependent apoptosis was speculated to be one mechanism responsible for the cytokine-induced cytotoxicity. Agents with antiinflammatory or antioxidative properties such as glucocorticoid, tetracycline-derived antibiotics, angiotensin II receptor blockers, or direct antioxidants showed substantial effect in attenuating cytokine-induced cytotoxicity and may be candidates for treatment options.

Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance.

Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects of statins, although direct evidence is lacking. Major features of sepsis-induced immune suppression include T-cell dysfunction, which is characterized by apoptosis of splenic T cells, increased CD4(+)Foxp3(+) regulatory T cells (Tregs), and suppression of type 1 helper T-cell response [e.g., interferon-γ (IFN-γ) secretion] in mice. Here, we show that the induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in farnesyltransferase activity and farnesylated proteins in the spleen relative to sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in farnesylated proteins and improved survival and bacterial clearance of septic mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and thymus, increased splenic CD4(+)Foxp3(+) Tregs, and suppressed IFN-γ secretion and proliferation of splenocytes in response to anti-CD3+CD28 antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity in septic mice. These results indicate that elevation in protein farnesylation plays a role in derangements in immune function and mortality of septic mice. These findings suggest that prevention of immune dysfunction might contribute to FTI-277-induced improvement in survival of septic mice. These data highlight protein farnesyltransferase as a novel potential molecular target to reduce the mortality of patients with sepsis.

[Intraoperative coronary spasm during caesarean section under spinal anesthesia].

A 37-year-old woman without history of ischemic heart disease or any coronary risk factors was scheduled for caesarean section. Under spinal anesthesia, the patient's blood pressure (BP) decreased to 93/72 mmHg. Although 6 mg of ephedrine was administered intravenously, BP continued to decrease to 75/40 mmHg and she complained of nausea. In addition to additional ephedrine (12 mg), phenylephrine (0.1 mg) and atropine (0.5 mg) were administered. BP increased to 170/100 mmHg, but electrocardiogram (ECG) showed ST elevation in I and aV(L), ST depression in II, III, aV(F), and frequent premature ventricular beats, and the patient complained of chest discomfort. Coronary dilators and lidocaine promptly reversed the ST elevation, premature ventricular beats and discomfort. The operation was started promptly and was uneventful. Although BP decreased again to 75/45 mmHg at the beginning of the operation, we did not use vasopressors to avoid the relapse of myocardial ischemia. The anesthetic course was uneventful thereafter. This cardiac event seemed to be derived from coronary spasm caused by acute sympathetic stimulation. The observations in this case suggest that the possibility of intraoperative coronary spasm should be considered even in a healthy patient.

Nitrosative stress and pathogenesis of insulin resistance.

Insulin resistance is a major causative factor for type 2 diabetes and is associated with increased risk of cardiovascular disease. Despite intense investigation for a number of years, molecular mechanisms underlying insulin resistance remain to be determined. Recently, chronic inflammation has been highlighted as a culprit for obesity-induced insulin resistance. Nonetheless, upstream regulators and downstream effectors of chronic inflammation in insulin resistance remain unclarified. Inducible nitric oxide synthase (iNOS), a mediator of inflammation, has emerged as an important player in insulin resistance. Obesity is associated with increased iNOS expression in insulin-sensitive tissues in rodents and humans. Inhibition of iNOS ameliorates obesity-induced insulin resistance. However, molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Protein S-nitrosylation, a covalent attachment of NO moiety to thiol sulfhydryls, has emerged as a major mediator of a broad array of NO actions. S-nitrosylation is elevated in patients with type 2 diabetes, and increased S-nitrosylation of insulin signaling molecules, including insulin receptor, insulin receptor substrate-1, and Akt/PKB, has been shown in skeletal muscle of obese, diabetic mice. Akt/PKB is reversibly inactivated by S-nitrosylation. Based on these findings, S-nitrosylation has recently been proposed to play an important role in the pathogenesis of insulin resistance.

[Retrospective analysis of critical perioperative myocardial infarction].

BACKGROUND: Myocardial infarction, a major complication of non-cardiac surgery, impacts on perioperative morbidity and mortality. METHODS: We retrospectively reviewed the intensive care unit records and anesthesia charts of non-cardiac surgical patients needing cardiac intensive care for myocardial infarction from April 1998 to December 2000 at the University of Tokyo Hospital and analyzed data obtained from these records. RESULTS: Four cases were detected. Three were vascular patients. The myocardial infarction occurred in two patients preoperatively, in one intraoperatively, and in another postoperatively. Hypovolemia was considered as an important contributing factor. All the patients developed shock abruptly and cardiac arrest followed in three. Three needed intra-aortic balloon counterpulsation, and one of these needed percutaneous cardiopulmonary support. Emergent percutaneous coronary intervention was performed in all cases and resuscitation was successful temporarily in all patients. However, the clinical outcome was poor; three died in our hospital and one transferred to another hospital became severely disabled. CONCLUSIONS: Surgical patients can be asymptomatic although they have significant coronary artery disease. Most of the events occurred abruptly without preexisting myocardial ischemia, suggesting the pathophysiology causing acute coronary syndrome. Thorough cardiac examination, including coronary angiography is recommended preoperatively in patients with strong coronary risks, especially in vascular patients.

[Anesthetic management of patients with hypertrophic obstructive cardiomyopathy undergoing non-cardiac surgery].

BACKGROUND: A considerable amount of data are available regarding cardiac risk in patients with coronary artery disease undergoing non-cardiac surgery, but few data are available regarding risk for patients with cardiomyopathy. METHODS: Reports on the anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing non-cardiac surgery were identified using Medline and the Igaku-Chuou-Zassi (Japana Centra Revuo Medicina) database (1981-2002). The data were analyzed in terms of patient characteristics, methods of intraoperative care, and clinical outcome. RESULTS: Sixty nine patients were included. The mean value of the left ventricular outflow tract pressure gradient (LVOTPG) was 63 mmHg. Twenty two cases were diagnosed as severe HOCM in terms of pressure gradient (LVOTPG > or = 50 mmHg) and clinical manifestations. Major complications, such as cardiac arrest and refractory shock, occurred in 10 cases. However, these perioperative risks were not correlated with severity of HOCM. CONCLUSIONS: Careful planning is inevitable in anesthesia for patients with HOCM. Although the rate of major perioperative complications is relatively low, they can occur unexpectedly and resemble the natural course of HOCM. In order to clearly elucidate risk factors for adverse perioperative outcomes, further analysis will be necessary as more cases are documented.

[Successful management of a patient for cardiac surgery with difficulty in weaning from cardiopulmonary bypass by using both isosorbide dinitrate and olprinone hydrochloride].

A 57-year-old man with mitral stenosis underwent mitral valve plasty under general anesthesia. He had a history of cerebral infarction. Although he was with atrial fibrillation, his left ventricular function was good. Preoperative coronary angiography revealed no significant coronary stenosis. Induction of anesthesia and the surgical procedure had been uneventful, but the patient had difficulty to wean the patient from cardiopulmonary bypass because of unexpected low cardiac output syndrome. O1-prinone hydrochloride, a newly developed phosphodiesterase III inhibitor, was initiated in addition to high doses of dopamine and dobutamine. This increased the amplitude of the electrocardiogram and caused ST elevation of the lead II. A full dose of isosorbide dinitrate was administered intravenously to differentiate coronary artery spasm from coronary air embolism. This drastically improved the ventricular function and mixed venous oxygen saturation, and weaning from CPB was finally accomplished. The heart showed hypercontraction and inotropes were tapered gradually without further cardiac events. Although there are various etiologies for low cardiac output syndrome after CPB, the possibility of myocardial ischemia must be the first consideration. Full pharmacological support must be tried before initiating a mechanical assist modality. Coronary dilators, nitrates in particular, and phosphodiesterase III inhibitors are promising agents in such cases.

[The successful anesthetic management of a patient with pheochromocytoma using prostaglandin E1 and a novel, short-acting beta-adrenergic blocker: landiolol hydrochloride].

A 48-year-old male with a history of hypertension was scheduled to undergo resection of a tumor in the upper region of the left kidney. However, his operation was postponed once because pheochromocytoma was suspected from the tumor location, sweating, and insomnia in addition to hypertension. The measurement of plasma catecholamines confirmed the presence of pheochromocytoma. Anesthesia was induced with thiopental and fentanyl, while ventilating with 5% sevoflurane in oxygen, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with 33% nitrous oxide and 0.6-3% sevoflurane in oxygen, in conjunction with fentanyl and 1% mepivacaine through an epidural catheter (T11-12). An arterial catheter and a pulmonary artery catheter were inserted. From the beginning of the operation, prostaglandin E1 and landiolol were administered continuously. Systolic blood pressure and heart rate were controlled between 90-140 mmHg and 80-105 beats x min(-1), respectively. Systemic vascular resistance was stable between 700-900 dyn x s x cm(-5) throughout the procedure. The operation was completed uneventfully. The patient was transferred to the general ward, extubated, and was in a stable condition. Various combinations of vasodilating and antihypertensive drugs have been used intraoperatively during the resection of pheochromocytoma. Of these, prostaglandin E1 and landiolol hydrochloride are very promising for maintaining stable hemodynamics.