The malcirculation caused by the vascular endothelial injury plays the important roles in the development of septic organ dysfunction. The natural anticoagulant, activated protein C (APC) is expected not only to regulate the hypercoagulability but also to modulate the leukocyte-endothelial interaction. [Purpose] The aim of this study is to examine the effects of APC on pro-inflammatory cytokine production and leukocyte-endothelial interaction in endotoxemia. [Methods] Rats were injected either 100, 000 U·kg^-1 of plasma derived APC (APC group, n=12) or 0.5% human albumin (control group, n=12), 30min prior to 2.5 mg·kg^-1 of endotoxin (LPS) injection. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), cytokine-induced neutrophil chemoattractant (CINC) and monocyte chemoattractant protein-1 (MCP-1) were measured at 1 and 3hr after LPS injection (n=5 in each group). In another series, the frequency of leukocyte rolling and sticking were measured at 1, 2 and 3hr after LPS injection under the intravital microscope (n=7 in each group). [Results] APC suppressed the elevated levels of TNF at 1 and 3hr (P<0.01, respectively) and IL-6 at 3hr (P<0.05) after LPS injection. CINC level was significantly suppressed at 3hr after LPS injection in APC group (P<0.05). On the other hand, MCP-1 level was not affected by APC. Significant decreases in leukocyte rolling and sticking were observed in APC group. In summary, APC suppresses the production of inflammatory cytokines such as TNF, IL-6 and CINC, and inhibits the leukocyte-endothelial interaction. These changes lead to the improvement of microcirculation during endotoxemia.

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Antipsychotic drugs prolong QT interval and cause ventricular arrhythmia in a dose-dependent manner, in which thioridazine has the most marked risk. Olanzapine, an atypical antipsychotic, is not associated with this fatal complication. We report herein a case of QT interval prolongation and ventricular arrhythmia caused by drug interaction of thioridazine and olanzapine. Plasma concentration of the two drugs is also presented. A 35-year-old woman ingested 200mg of thioridazine and 80mg of olanzapine in a suicide attempt. Electrocardiograph on admission revealed prolonged QT interval (corrected QT, 670 msec), and polymorphic ventricular tachycardia and ventricular fibrillation appeared several times which were treated successfully with electrical cardioversion. Plasma concentration of thioridazine on admission was extraordinarily high, despite the fact that 200mg of thioridazine is a therapeutic dose. We conclude that olanzapine overdose caused competitive inhibition of metabolic enzyme CYP2D6 and increased thioridazine concentration which resulted in QT prolongation and ventricular arrhythmia.

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We present a case of severe respiratory failure associated with toxic epidermal necrolysis (TEN). A 3-year-old girl was administered antibiotics (cefditoren pivoxil) and NSAID (acetaminophen) for acute upper airway infection. Two days later, erythema, erosion and bullae developed widely on her body. She was diagnosed as TEN probably caused by the antibiotics, and transferred to our hospital. Steroid pulse therapy and γ-globulin therapy were started. On the 6th day, she was admitted to our ICU because of severe acute respiratory failure. Although mechanical ventilation was started, hypoxemia and acidosis deteriorated. Nitric oxide inhalation was tried, which was not effective on her oxygenation. On the 9th day, extracorporeal lung assist (ECLA) was performed for the rest of the lungs. On the 20th day, ECLA was discontinued because of the complication of consumptive coagulopathy. Although the lung compliance appeared to be gradually improved, irreversible respiratory failure developed. She had bacterial pneumonia and recurrent pneumothorax. On the 24th day, she died of respiratory failure. The rate of pulmonary complications in TEN is about 25%. The complications may incidentally take a fatal course. Adequate respiratory care is required from the earlier stage of TEN.

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We reported a case of 72-year-old man who developed hyper-inflammatory state and multiple organ disorders without any apparent origin after off-pump coronary-artery bypass grafting (CABG), and who was treated with high-dose methylprednisolone successfully. Administration of high-dose corticosteroids for critically ill patients is not supported now, but this case showed prompt recovery after administration of steroid, so the treatment was thought to be effective. The patient was admitted to the emergent department in our hospital because of worsening angina pectoris. His past medical history showed hypertension and previous smoking, CABG, and Y-graft replacement of abdominal aortic aneurysm. He was diagnosed that left internal thoracic artery (LITA) and saphenous vein graft (SVG) were stenotic and scheduled to undergo off-pump CABG with left thoracotomy due to the history of mediastinitis following previous CABG. The procedure was performed successfully, but he developed high-grade fever and significant leukocytosis, hyper-bilirubinemia, and acute renal failure. He did not show any signs of local infection or allergy, and the microbiological tests such as sputum, blood, and cerebrospinal fluid cultures were negative. Infectious endocarditis was excluded by transesophageal echocardiography and mediastinitis was also excluded by computed tomography. We admimistered 500mg of methylprednisolone for three days from the 12th postoperative day, and observed prompt resolution of high-grade fever, inflammation and multiple organ disorder. Since then steroid administration was tailored for 25 days in total, and he discharged from ICU on 42nd day. We speculated the administration of methylprednisolone was effective because of the prompt recovery and its dependence on steroid dose.

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A woman in her sixties presented with dyspnea and was diagnosed with upper airway obstruction due to a giant vocal cord polyp. An electrocardiogram demonstrated T wave inversion in leads I, aVL, and V_3-6. An echocardiogram revealed severe hypokinesis of the apical, septal, and anterior walls of the left ventricle. Since upper airway obstruction deteriorated in a short duration, an emergent tracheostomy was performed. After the operation, she developed severe hypoxemia. A chest radiograph showed pulmonary edema, mediastinal emphysema, and subcutaneous emphysema of the neck and chest wall. Emergent coronary angiography demonstrated 75% stenosis of the first diagonal branch, and left ventriculogram demonstrated Takotsubo-like left ventricular dysfunction. She was transferred to the ICU and was maintained on mechanical ventilation. On day 3, the peak CPK value was 131IU·l^-1. On day 5 of admission, she was discharged from the ICU. The coronary angiography performed on day 7 showed improvement of the left ventricular function. The spasm provocation test with acetylcholine demonstrated diffuse multivessel coronary spasm. On day 22, laryngeal microsurgery was performed, and the impacted, giant vocal cord polyp was removed. This patient showed Takotsubo-like left ventricular dysfunction without significant organic coronary artery disease. Multivessel coronary spasm and significant stress due to asphyxia may contribute to the onset of this condition. We assumed that negative pressure pulmonary edema developed following upper airway obstruction because of the rapid onset and resolution of the edema.

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Rhabdomyolysis is caused by a variety of mechanisms, such as drug intoxication, trauma, electrolytes abnormalites and neuro-muscular disorders. This article describes a 63-year-old male patient developed rhabdomyolysis due to hyponatremia after water intoxination and during its correction. Rhabdomyolysis due to water intoxication is rare, and the mechanism has not yet clearly elucidated. Some investigators suspect that serum electrolytes abnormalities according to sodium-calcium exchanger or changes in serum osmolarity may lead to cell membrane fragility. Our case highlights the clinical importance of serum electrolytes and osmolarity abnormalities as causes of rhabdomyolysis due to water intoxication.

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