Kyoko Kageyama

Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.

Background:  Orthopedic surgery, especially total knee and total hip arthroplasty, is considered a risk factor for peri‐operative venous thromboembolism.

Hypoxic gas therapy using nitrogen in the preoperative management of neonates with hypoplastic left heart syndrome.

Objective To evaluate the efficacy of hypoxic gas therapy using nitrogen, where the fraction of inspired oxygen (Fio2) was reduced to <0.21 in patients with univentricular parallel circulation. Design Case report. Setting A pediatric intensive care unit at a university hospital. Patients Two neonatal patients with hypoplastic left heart syndrome admitted to the pediatric intensive care unit preoperatively. Interventions Nitrogen insufflation by using continuous-flow respiratory support. Measurements and Main Results We reduced the Fio2 in these patients by giving additional nitrogen to relieve pulmonary overcirculation and systemic hypoperfusion suspected by transcutaneous arterial oxygen saturation >90%, systemic arterial hypotension, and low urine output in the preoperative course. The improvement of systemic hemodynamics concomitant with decreases in transcutaneous arterial oxygen saturation <85% was accomplished by controlling Fio2 between 0.14 and 0.18. These infants were able to undergo Norwood’s surgery after several days without complications relating to Fio2 reduction. Conclusion Hypoxic gas therapy with nitrogen was effective clinically in preventing pulmonary overcirculation in neonatal patients with univentricular and parallel circulation.

Lidocaine Inhibits Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor and Suppresses Proliferation of Corneal Epithelial Cells

Background: Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors’ previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation. Methods: To investigate the effect of lidocaine (4 μM–40 mM) on epidermal growth factor (EGF)–stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs. Results: Lidocaine (≥ 400 μM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (≥ 400 μM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR. Conclusion: Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.

Sevoflurane Does Not Inhibit Human Platelet Aggregation Induced by Thrombin

Background Sevoflurane reportedly inhibits adenosine diphosphate–induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation. Methods Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay. Results Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 ± 7%) to 71 ± 10% (1.0 mM) and 60 ± 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 ± 95 nM vs. 440 ± 124 nM [1.0 mM] or 410 ± 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 ± 48 nM vs. 142 ± 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. Conclusions Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.

Bioelectrical impedance analysis for assessment of severity of illness in pediatric patients after heart surgery

OBJECTIVE To investigate whether perioperative changes in bioelectrical impedance reflect the severity of illness in pediatric patients after heart surgery. DESIGN Prospective, controlled study. SETTING University-affiliated childrens hospital. PATIENTS A total of 107 patients admitted to a pediatric intensive care unit after congenital heart surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Single frequency (50 kHz) bioelectrical impedance was measured in the lower extremities before surgery and immediately, 16 hrs, and 40 hrs after admission (D0, D1, D2) to the pediatric intensive care unit. Postoperative changes in bioelectrical impedance were assessed by calculating values relative to the preoperative data (bioelectrical impedance ratio). These bioelectrical impedance ratios at D0 in both the nonsurviving and surviving patients were 0.84 +/- 0.06 and 0.85 +/- 0.01 (mean +/- SE), respectively, indicating that the initial decrease caused by surgical stress itself was not directly related to the prognosis. The bioelectrical impedance ratio showed an increase toward preoperative values in surviving patients (0.94 +/- 0.02) at D1, and they showed a sustained decrease (0.70 +/- 0.06) in nonsurviving patients. Patients with a bioelectrical impedance ratio at D1 of < 0.8 showed a higher mortality (25%) compared with those patients with a day-1 bioelectrical impedance ratio of > or = 1.0 (0%). The duration of the stay in the pediatric intensive care unit, mechanical ventilation, and inotropic support were all significantly longer in the patients with the lower bioelectrical impedance ratio. CONCLUSIONS Measurement of the relative changes in postoperative bioelectrical impedance, which reflects perioperative alterations in body composition, provides a quantitative estimation of the critical illness in pediatric patients after heart surgery.

The change of plasma endothelin‐1 levels before and after surgery with or without Down syndrome

Background:  The present study aimed to elucidate the pathophysiological roles of endothelin (ET)‐1 in patients with pulmonary hypertension and pulmonary vascular obstructive disease secondary to congenital heart disease and compare the plasma levels of ET‐1 between children with and without Down syndrome.

Phosphodiesterase 3 Inhibition Reduces Platelet Activation and Monocyte Tissue Factor Expression in Knee Arthroplasty Patients

Background:Tissue damage during surgery activates platelets and provokes a prothrombic state. The current study attempted to determine the impact of phosphodiesterase 3 inhibitors on platelet activation, platelet–leukocyte aggregate formation, and monocyte tissue factor expression during and after total knee arthroplasty. Methods:Thirty-four patients undergoing scheduled total knee arthroplasty were randomly assigned to receive either the phosphodiesterase 3 inhibitor milrinone or the same amount of saline perioperatively. The effects of milrinone on platelet and leukocyte function in vitro were then assessed in healthy volunteers. Results:Perioperative infusion of milrinone significantly attenuated platelet activation; phosphorylation of intraplatelet p38 mitogen-activated protein kinase, extracellular signal–regulated kinase 1/2, and Akt; and platelet–leukocyte aggregation. Furthermore, perioperative tissue factor expression on monocytes and fibrin monomer complex production were reduced by milrinone infusion in patients undergoing total knee arthroplasty. In vitro studies using adenosine diphosphate– and collagen–stimulated blood samples from healthy volunteers confirmed the antiplatelet effects and reduced monocyte tissue factor expression by milrinone. These studies further showed that platelet aggregation and integrin &agr;IIb&bgr;3 activation were modified by intraplatelet phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal–regulated kinase pathways, and that P-selectin expression on platelets and platelet–leukocyte aggregation were modulated by intraplatelet p38 mitogen-activated protein kinase pathway. Conclusion:Continuous milrinone infusion has the potential to reduce platelet activation and monocyte tissue factor expression during the perioperative period in total knee arthroplasty. These events may be mediated in part by the ability of milrinone to reduce activation of intraplatelet mitogen-activated protein kinases and phosphatidylinositol 3-kinase. The clinical impact of phosphodiesterase 3 inhibition on perioperative hemostasis remains to be elucidated.

Toborinone and olprinone, phosphodiesterase III inhibitors, inhibit human platelet aggregation due to the inhibition of both calcium release from intracellular stores and calcium entry.

PurposeWe investigated the inhibitory effects of toborinone and olprinone on human platelet aggregation and calcium mobilization.MethodsWashed human platelets were preincubated with toborinone or olprinone, then exposed to 0.015 U·ml−1 of thrombin. Aggregation curves were measured using an aggregometer. Effects of toborinone or olprinone on changes in intracellular calcium concentration ([Ca2+]i) were measured fluorometrically using fura-2 acetoxymethyl ester (fura-2). Levels of intracellular cyclic 3″,5″-adenosine monophosphate concentration ([cAMP]i) were also measured, using enzyme-linked immunosorbent assay (ELISA) techniques.ResultsThe concentrations required to cause 50% inhibition of aggregation (IC50) induced by thrombin were 9.7 ± 0.9 µM for toborinone and 3.6 ± 0.2 µM for olprinone. Both drugs at IC50 significantly elevated [cAMP]i levels and significantly inhibited Ca2+ release from intracellular stores. Release of [Ca2+]i induced by thrombin was 272.9 ± 87.1 nM, 153.3 ± 28.7 nM, and 138.9 ± 58.2 nM in the control, toborinone, and olprinone groups, respectively (P ≪ 0.02). Calcium influx through calcium channels in the plasma membrane was also suppressed by toborinone and olprinone.ConclusionToborinone (9.7 µM) and olprinone (3.6 µM) inhibit human platelet aggregation, though these concentrations are higher than their therapeutic plasma concentrations. The inhibitory effects of both drugs are related to the inhibition of both Ca2+ release and Ca2+ entry through [cAMP]i elevation.

A Fatal Hyperthermic Syndrome in a Patient with Myokymia

A fatal hyperthermic syndrome occurred in a patient with myokymia. The patient suffered acute circulatory collapse and severe rhabdomyolysis associated with hyperthermia. Although these symptoms, were similar to neuroleptic malignant syndrome or malignant hyperthermia, he did not have a history of antipsychotic medication or anesthesia. Continuous muscular contraction due to myokymia likely led to the development of hyperthermic syndrome.

The Peculiarity of an Anesthesia Accident

麻酔科領域には紛争, 訴訟に発展する数々の特殊な問題が潜んでいる. 第一に,「麻酔担当医と患者との人間関係, 信頼関係が十分に形成されない間に麻酔が実施される」, 第二に, 患者側の「麻酔の危険性」に対する認識不足, 第三に,「全身麻酔は患者の不可視の状態の下に行われ, 医療行為の過程が患者にはわからない」, 第四に「局所麻酔の場合, 患者にとって簡易な医療行為にみえるにもかかわらず発生した結果はきわめて重大・深刻である」ということである. これらの特殊性を理解したうえでの慎重な麻酔業務の遂行と, 不幸にして事故が発生した場合,「過失」に相当するか否か慎重に検討し, 事故の再発防止と当事者, 被害者両者の救済に努める必要がある.