A newly devised flow cytometric antibody binding assay helps evaluation of dithiothreitol treatment for the inactivation of CD38 on red blood cells.

BACKGROUND AND OBJECTIVES: Anti-CD38 monoclonal antibodies, including daratumumab and isatuximab, often interfere with pretransfusion testing. Dithiothreitol (DTT) treatment of red blood cells (RBCs) negates this interference. However, the optimum DTT concentration and treatment time have not been well defined. Here, we quantified CD38 on RBCs before and after DTT treatment using a flow cytometric antibody binding assay (FABA) to specify the optimum conditions for CD38 inactivation. MATERIALS AND METHODS: For FABA, untreated or DTT-treated RBCs were incubated with fluorescein isothiocyanate-labelled anti-CD38 antibody, in the presence or absence of 100-fold or more excess of unlabelled anti-CD38 antibody, and then analysed by flow cytometry (FCM). Dissociation of CD38-positive and control histograms was determined from the D-value using the Kolmogorov-Smirnov test. The results from FABA were compared with those from conventional FCM, indirect antiglobulin test (IAT) and Western blotting. RESULTS: The results from FABA were more consistent than those from conventional FCM. The D-value was found to be reliable in the analysis of difference between CD38 before and after DTT treatment. Our data showed that 0·0075 mol/l DTT for 30 min is sufficient to inactivate CD38 on RBCs. These results were stable and consistent with the findings from IAT. CONCLUSION: Flow cytometric antibody binding assay is an objective way of evaluating the efficacy of DTT treatment for CD38 on RBCs. This approach allows the detection of a small number of cell surface antigens and will be useful for assessing the various chemical treatments to denature RBC antigens.

Interactions between bradykinin and plasmin in the endothelial Ca2+ response.

Plasmin is a fibrinolytic factor and a serine protease that activates protease-activated receptors (PARs) to produce endothelium-derived relaxing factors such as nitric oxide and prostacyclin. Nitric oxide and prostacyclin production is regulated, at least in part, by the intracellular Ca2+ concentration in various blood vessel types. Bradykinin and plasmin stimulate vascular endothelial cells and work simultaneously in pathophysiological conditions such as thrombosis and inflammation. Here, we explored the interactions between bradykinin and plasmin in the endothelial Ca2+ response using the fluorescent indicator, Fura-2/AM, in primary cultures of porcine aortic endothelial cells (PAECs). Plasmin (0.15-15 µg/ml) and bradykinin (0.1-10 nM) increased intracellular Ca2+ concentrations in PAECs in a dose-dependent manner, and the plasmin-induced endothelial Ca2+ response occurred only once. Bradykinin (0.1-10 nM) inhibited the plasmin-induced endothelial Ca2+ response in a dose-dependent manner, however, plasmin did not affect the bradykinin-induced endothelial Ca2+ response. Pretreatment with gabexate mesilate (GM, 100 µM), a serine protease inhibitor, that blocks plasmin's proteolytic activity, fully suppressed the plasmin-induced Ca2+ response. After washout of GM and the first plasmin, the second administration of plasmin caused Ca2+ increases. However, when the first plasmin-induced Ca2+ response was blocked by pretreatment with bradykinin, the second plasmin (15 µg/ml) application did not cause any Ca2+ response, even 30 min after the washout of the first plasmin and bradykinin. Our data suggested that bradykinin regulated the plasmin-induced endothelial Ca2+ response by inhibiting the pathway downstream of the PARs' N-terminus cleavage.

[The Effectiveness of Two Anesthesia Machines in the Water Generation of the Anesthesia Circuit during the Prolonged Low Flow Desflurane Anesthesia].

BACKGROUND: Water is generated by a reaction of carbon dioxide and a carbon dioxide absorbent We evaluated the effectiveness of the anesthesia machines about the water generation which occurs to an anes- thetic circuit during the prolonged low flow anesthesia. METHODS: Fifteen patients were divided into three groups; group HHS (n=5) in which a hot heater system was equipped inside anesthesia machine, group WCD (n=5) in which a water catchment device was connected with anesthesia machine, and control group N(n=5)in which normal anesthesia machine was used without special device, and studies were performed with FGF 11 - min- low flow desflurane anesthesia for more than 6 hours. The water situation in an anesthe- sia circuit was observed during the operation and was compared after the operation between these groups. RESULTS: In an anesthesia circuit of the anesthesia machines inside there was no water in group HHS and WCD, but more water in group N. In an anesthesia circuit of the anesthesia machines outside there was little water in group WCD, but more water in group HHS and N. CONCLUSIONS: Two anesthesia machines, group HHS and WCD, were effective about reduction of water generation in an anesthesia circuit of the anesthesia machines inside during FGF 11 - min-I prolonged low flow desflurane anesthesia.

Radial artery cannulation decreases the distal arterial blood flow measured by power Doppler ultrasound.

Radial arterial cannulation is a popular technique for continuous hemodynamic monitoring in an area of anesthesia and intensive care. Although the risk for invasive monitoring is considerable, there is scarce information about the change in blood flow of cannulated vessel after the catheterization. In the current investigation, we evaluated the change in the cannulated arterial blood flow. Six volunteers (study 1) and eight post-surgical patients (study 2) were enrolled into the studies. In the study 1, the both side of diameter of radial artery (RA), ulnar artery (UA) and dorsal branch of radial artery (DBRA) of participants were measured using power Doppler ultrasound (PDU) with or without proximal oppression. In the study 2, the diameter of RA, UA and DBRA of the both intact and cannulated side were compared. Study 1: The diameter of RA was 3.4 (0.52) [mean (SD)] mm and the proximal oppression significantly decreased the diameter to 1.8 (0.59) mm. The diameter of DBRA measured by PDU also decreased 2.0 (0.60)-1.3 (0.59) mm. Study 2: There was no difference between the diameters of right and left RA, however, the UA was larger [3.4 (0.60) vs. 2.8 (0.83) mm] and the DBRA was narrower [1.4 (0.43) vs. 2.0 (0.47) mm] in the cannulated side. The diameters of DBRA were different between the intact and cannulated side in the patients. Although there is no information of relationships between cause of severe complication and decreased flow, significant reduction of blood flow should be concerned.

Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α2 adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3 µg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15 min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.

Rhabdomyolysis in a Long-Term Statin User Without Traditional Risk Factors: A Case Report.

We report a rare case of rhabdomyolysis in a 64-year-old man who had been receiving long-term statin therapy for hyperlipidemia. The patient initially presented with symptoms of acute appendicitis, which later progressed to acute renal failure and rhabdomyolysis. No commonly identified risk factors for rhabdomyolysis, including drug interactions and statin doses, were observed. The patient was urgently admitted to the intensive care unit where the relevant medications were discontinued in a timely manner and infusion resuscitation was performed. Renal function and serum creatine kinase levels gradually stabilized without the need for hemodialysis. After four days, the patient was transferred to a general ward and was fully discharged from the hospital 13 days after admission. This case highlights the importance of considering rhabdomyolysis as a possible complication among patients receiving statin therapy, even in the absence of traditional risk factors.

Postoperative norepinephrine versus dopamine in patients undergoing noncardiac surgery: a propensity-matched analysis using a nationwide intensive care database.

BACKGROUND: Choosing catecholamines, such as norepinephrine and dopamine, for perioperative blood pressure control is essential for anesthesiologists and intensivists. However, studies specific to noncardiac surgery are limited. Therefore, we aimed to evaluate the effects of postoperative norepinephrine and dopamine on clinical outcomes in adult noncardiac surgery patients by analyzing a nationwide intensive care patient database. METHODS: The Japanese Intensive care PAtient Database (JIPAD) was used for this multicenter retrospective study. Adult patients in the JIPAD who received norepinephrine or dopamine within 24 h after noncardiac surgery in 2018-2020 were included. We compared the norepinephrine and dopamine groups using a one-to-one propensity score matching analysis. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, hospital length of stay, and ICU length of stay. RESULTS: A total of 6,236 eligible patients from 69 ICUs were allocated to the norepinephrine (n = 4,652) or dopamine (n = 1,584) group. Propensity score matching was used to create a matched cohort of 1,230 pairs. No differences in the in-hospital mortality was found between the two propensity score matched groups (risk difference: 0.41%, 95% CI [-1.15, 1.96], P = 0.608). Among the secondary outcomes, only the ICU length of stay was significantly shorter in the norepinephrine group than in the dopamine group (median length: 3 vs. 4 days, respectively; P < 0.001). CONCLUSIONS: In adult patients after noncardiac surgery, norepinephrine was not associated with decreased mortality but was associated with a shorter ICU length of stay than dopamine.

Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice.

PURPOSE: Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an α(2)-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice. METHODS: Male adult mice were intravenously administered either dexmedetomidine (30 µg/kg) or hydroxyzine (5 mg/kg) with propofol (3.75-10 mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300 µg/kg), or hydroxyzine (50 mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED(50)) for LRR was calculated, and the duration of LRR was determined. RESULTS: The hypnotic dose of propofol was 9.95 ± 1.04 mg/kg (ED(50) ± SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED(50) of propofol to 5.32 ± 0.57 and 5.63 ± 0.57 mg/kg, respectively. Coadministration of dexmedetomidine significantly extended LRR duration compared with propofol alone, whereas hydroxyzine significantly shortened LRR duration. A maximal dose of dexmedetomidine or hydroxyzine alone did not induce hypnosis. CONCLUSIONS: Dexmedetomidine and hydroxyzine demonstrated no hypnotic action alone; however, their coadministration potentiated the hypnotic activity of propofol. Although reduction in the dose of propofol was similar, only dexmedetomidine prolonged the duration of hypnosis.

[Sudden increases and decreases in bispectral index values more than 30 within 1 minute during general anesthesia].

We described, in a 40-year-old man, sudden and unexpected increases in bispectral index values during the general anesthesia with total intravenous anesthesia using propofol in a dental surgery. The patient was administered continuous infusion of propofol and remifentanil, and intermittent supplementation of fentanyl. Immediately after the beginning of surgery, the bispectral index value increased abruptly to 90; whereas, heart rate and non-invasive blood pressure were unchanged and no physiological finding was observed. Approximately 25 min later, the value decreased to below 40 without any modification of anesthesia. The extent of unanticipated increase might be compatible with the duration of surgical procedure using dental air turbine. Therefore, the noise from surgical device might induce unpredictable change in bispectral index values.

[Pycnodysostosis: a case report].

A 53-year-old man suffered maxillar osteomyelitis and removal of sequester was scheduled under general anesthesia. Pycnodysostosis had been diagnosed in childhood and body height and weight were 148 cm and 40 kg, respectively. He presented facial dysmorphia, hypomobile mandible and narrow oral cavity. At the pre-anesthetic visit, we planned awake fiberscopic intubation before the induction of general anesthesia. On the day of surgery, however, face-mask ventilation was easily established with 100-microg dose of fentanyl. Thus, 70 mg of propofol was administered to achieve hypnosis and naso-tracheal intubation using fibrescope was accomplished. The patient's trachea was easily intubated without a decrease of pulse oximetry values and marked changes in cardiovascular parameters. Pycnodysostosis is a rare clinical entity; however, the airway difficulty was mild in the present case.

Treatment-resistant venous thrombosis and pulmonary embolism in a patient with granulomatosis with polyangiitis: a case report.

BACKGROUND: We herein present a case of venous thrombosis that developed more than 20 years after diagnosis of granulomatosis with polyangiitis (GPA), although many reports of GPA have described venous thrombosis within 1 year of diagnosis. CASE PRESENTATION: A 73-year-old man with GPA was admitted for lower extremity swelling and diagnosed with venous thrombosis and pulmonary embolism. On the second day, catheter-based thrombolysis was unsuccessful, and inferior vena cava filter insertion and anticoagulation were performed. On the third day, respiratory disturbance and loss of consciousness appeared and progressed. The patient died on the fifth day. The autopsy revealed a large thrombus in the inferior vena cava filter, and death of progressive venous thrombosis was suspected. CONCLUSIONS: We experienced a case of venous thrombosis that developed 20 years after diagnosis of GPA, although GPA is frequently associated with venous thrombosis immediately after diagnosis. The thrombosis progressed rapidly and was resistant to treatment.

[Successful extubation in a patient with alacepril-induced tongue angioedema].

We describe a case of marked swelling of the tongue in a patient after a long prone position neurosurgery, who was treated for hypertension with alacepril. The tongue was not congestive and history of taking an angiotensin-converting enzyme inhibitor suggested an alacepril-induced angioedema. The day after surgery, the patient's tongue was still swollen; however, fibrescopic observation of the larynx and pharynx through the nasal cavity revealed that the edema was limited to anterior tongue, and the oral cavity and oropharynx were not involved. Although, tongue angioedema was observed, we introduced a 3-mm tube exchanger to the patient's trachea and removed the endotracheal tube. The ventilation and oxygenation were maintained, and 30 min later, the exchanger was detached. On the second postoperative day, the angioedema disappeared completely and the patient was transferred to a ward without any complication.

Nafamostat prevents hypothermia and improves survival time after administration of lipopolysaccharide in a mouse surgical model.

Lipopolysaccharide (LPS) is an endotoxin known to induce disseminated intravascular coagulation and multiple organ failure followed by septic shock in animals. Nafamostat is a synthetic protease inhibitor with anticoagulant effects. This study investigated the effect of systemic administration of nafamostat on thermogenic homeostasis and survival time in a mouse surgical model. Male C57Bl/6 mice were anesthetized with sevoflurane and implanted with intraabdominal telemetry transmitters. Following the surgery, three groups of animals were administered Escherichia coli LPS (0127: B8) subcutaneously at doses of 0.3, 1.0, or 3.0 mg kg(-1), and one group received saline without LPS. Three other groups received 3 mg.kg(-1) LPS with 1, 3, or 10 mg kg(-1) of nafamostat. In another group 10 mg kg(-1)1 of nafamostat only was administered. The times to the onset of hypothermia (body temperature < 30 degrees C) and death were determined. L LPS significantly shortened the duration of both normothermia and survival, and nafamostat prolonged the normothermic periods that were reduced b 3 mg.kg(-1) LPS. Survival time was significantly correlated with the duration of normothermia (n = 48; r (2) = 0.779; P < 0.000001). The results demonstrated the effect of systemic administration of nafamostat against LPS-induced hypothermia. Nafamostat prevented hypothermia, and the consequent normal thermoregulation may have prolonged the survival period.

[Serotonin syndrome caused by an overdose of dextromethorphan, Medicon].

We report the first case of serotonin syndrome caused by overdose of dextromethorphan in Japan. A 34-year-old woman with schizophrenia received a dextromethorphan (Medicon) for a catarrhal symptom from two individual departments of the university hospital by chance. The daily amount of dextromethorphan was up to 180 mg for several days in addition to other regular antipsychotic drugs including risperidone, amitriptyline and levomepromazine. Finally, she was found in deep comatose state (GCS coma scale: E1V1M1) and the trachea was intubated in the emergency room. After admission to intensive care unit, the consciousness gradually improved; however, she was confused and agitated. The situation was normalized within next 24 hours and she was weaned from the mechanical ventilation next day. Serotonin syndrome demonstrates various signs and might be overlooked in an emergency room. Dextromethorphan is considered as a safe antitussive drug; however, the unexpected interaction should be suspected during chronic medical treatment.

[Apnea and severe respiratory depression induced by dexmedetomidine after general anesthesia in intensive care unit].

Dexmedetomidine (DEX) is widely used in intensive care unit for perioperative sedation. The one advantage of DEX administration for sedation is the lack of significant respiratory depression. However, DEX shows significant interaction with anesthetics and narcotics, and we present a case in which post-anesthetic administration of DEX induced apnea and severe respiratory depression after extubation. A 74-year-old, 38.3 kg, 148 cm woman was scheduled to undergo implantation of internal cardiac defibrillator. General anesthesia was maintained by sevoflurane, remifentanil and intermittent administration of fentanyl. After the surgery, she was transferred to intensive care unit with intubation, and DEX administration was commenced. After 3.5 hr from the end of anesthesia, the patient's trachea was extubated under continuous infusion of DEX (0.26 microg x kg(-1) x hr(-1)). Ninety min later, she showed apnea and severe respiratory depression. The interaction of DEX and residual narcotics might have induced life-threatening respiratory complication.

[Multiple difficulties for central venous access required the distal femoral vein catheterization: a case report].

The low femoral approach for catheterization of the central venous line is a difficult procedure because the surface landmark technique is not helpful. We report a case of patient who required the distal femoral cannulation. Re-catheter cannulation was planned for the patient after the major cardiovascular surgery. The right internal jugular vein showed the venous thrombus attributed to the previous catheter placement for the operation. The left internal, jugular vein had anatomical anomaly at the level of cricoid cartilage and the last approach for cannulation was not feasible. The right subclavian and right femoral regions were scarred with the surgical procedure. Finally, we performed the distal femoral cannulation using real time ultrasound guidance. When multiple difficulties for venous access are present, ultrasound-guided low approach of femoral vein might be one of the solutions.

Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study.

Between April 2004 and December 2010, we conducted a prospective randomized controlled study comparing tamibarotene with all-trans retinoic acid (ATRA) in the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL), and here report the final results of this study with a median follow-up of 7.3 years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%) achieved complete remission (CR). After completion of three courses of consolidation chemotherapy, 269 patients in molecular remission underwent maintenance randomization, 135 to ATRA (45 mg/m2 daily), and 134 to tamibarotene (6 mg/m2 daily) for 14 days every 3 months for 2 years. The primary endpoint was relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in the tamibarotene arm (p = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference was prominent in high-risk patients with initial leukocytes ≥ 10.0 × 109/L (62% vs. 89%; p = 0.034). Tamibarotene was significantly superior to ATRA by decreasing relapse in high-risk patients. Overall survival after randomization did not differ (96% vs. 97%; p = 0.520). Secondary hematopoietic disorders developed in nine patients, secondary malignancies in 11, and grade 3 or more late cardiac comorbidities in three. These late complications did not differ between the two arms.

[Two cases of anesthesia mumps in the upper parotid gland after general anesthesia in the lateral position].

We describe two cases of acute transient swelling of the upper side of parotid glands of the patients after general anesthesia in the lateral position. The serum amylase levels in the patients were not increased and the enlargement of the parotid gland was diagnosed as anesthesia mumps. Previous reports suggested that mechanical compression might produce the swelling of the secreting organ, but our patients showed temporal parotid enlargement in the upper free side. Although, pre-medication with atropine might become a cause of parotid gland swelling, we anesthetized these patients without anti-cholinergic drugs. Procedures of oro-tracheal intubation and stimuli of endotracheal tube may induce impairment of the normal flow of saliva and lead to enlargement of the parotid gland.

[Bispectral index decreased to "10" during propofol anesthesia despite the appropriate serum concentration of propofol].

We report a case showing a bispectral index (BIS) value "10" during anesthesia maintained with propofol. Vital signs of the patient including blood pressure and heart rate were stable and the depth of anesthesia was considered as adequate. The serum concentration of propofol measured later was 2.5 and 2.2 microg ml(-1) when BIS indicated 10 and 35, respectively. The age of patient was 81 and the BIS values in elderly might decrease in accordance with the reduction of brain function.

[Patient awakening from anesthesia was re-sedated by administration of flumazenil].

An 83-year-old female patient was managed in intensive care unit postoperatively with artificial ventilation and propofol-based sedation. On the second postoperative day, we tried to remove an endotracheal tube. Naloxone was administered to the patient for reversing the sedative effect of fentanyl infused intraoperatively. Her consciousness level was improved; however, subsequent administration of flumazenil induced hypnosis. Benzodiazepine-like partial agonistic effect of flumazenil might have enhanced residual hypnotic effect of propofol. Administration of flumazenil to the patient infused with propofol should be done cautiously for awakening the patient from anesthesia.