[Case Report : Monitored Anesthesia Care (MAC) with Dexmedetomidine.]

Dexmedetomidine (DEX) is a sedative used for monitored anesthesia care (MAC). DEX has been used frequently for MAC because of its less respiratory depressant effect We used DEX in four patients with severe complications who needed surgery under MAC. We started MAC with continuous infusion of 0.5-0.9 µtg - kg(-1) . hr(-1) of DEX, without initial loading dose, combined with regional anesthesia, and gradually either increased or decreased continuous infusion according to Ramsay sedation scale (RSS). The simulated plasma concentrations of DEX were calculated by AnestAs- sistTM PK . PD(-1). All patients were well sedated and operations were completed safely, although simulated plasma concentrations of DEX were low. Remarkable cardiovascular responses and respiratory depression were not observed. Our study indicated that the usage of DEX without initial loading dose combined with regional anesthesia could be an option for patients with severe complications undergoing MAC.

[Survey of patients at the preoperative evaluation clinic (PAC)].

Anesthesia requires informed consent because it is an invasive procedure with high risks. We carried out a questionnaire study in 1,050 patients who were seen at the preoperative evaluation clinic (PAC). Patients who heard about PAC for the first time accounted for 77.9% in spite of having experienced anesthesia. Many patients were provided with the information about anesthesia the day before surgery and medication control and additional checking were difficult to carry out. Some patients (34.2%) were told about anesthesia with no attendant. In particular, about complications of anesthesia, many patients did not remember what the specific explanation had been offered in the past. We thought that it is necessary to explain the complications of anesthesia even if it is the second anesthesia for patients.

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 alpha(IIb)beta(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.

Effect of synthetic cell-penetrating peptides on TrkA activity in PC12 cells.

As TrkA, a high-affinity receptor of nerve growth factor (NGF), is a potential target for relieving uncontrolled inflammatory pain, an effective inhibitor of TrkA has been required for pain management. To identify a specific inhibitor of TrkA activity, we designed cell-penetrating peptides combined with amino-acid sequences in the activation loop of TrkA to antagonize tyrosine kinase activity. To select a peptide inhibiting TrkA activity, we examined the effect of cell-penetrating peptides on tyrosine kinase activity of recombinant TrkA in vitro and studied their effects on NGF-stimulated neurite outgrowth and protein phosphorylation in PC12 cells. Thereafter we investigated the effect of the selected peptide on NGF-stimulated TrkA activity and the expression of transient receptor potential channel 1 in PC12 cells. The selected peptide inhibited TrkA activity, but did not inhibit tyrosine kinase activities of other receptor-type tyrosine kinases in vitro. It also suppressed NGF-stimulated responses in PC12 cells. The selected synthetic cell-penetrating peptide antagonizing TrkA function would be a candidate for inflammatory pain therapy.

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. METHODS: Subjects comprised 32 children with congenital heart disease aged 0.5-14 months. Patients were classified into two groups: those with Down syndrome (Group D, n = 16); and those with nonDown syndrome (Group ND, n = 16). Heparinized blood samples were taken from a radial arterial line and plasma ET-1 levels were measured preoperatively, during cardiopulmonary bypass (CPB), a few minutes after termination of CPB, and 2, 6 and 24 h after discontinuation of CPB. RESULTS: Plasma ET-1 levels were significantly higher in Group D than in Group ND at all times except for a few minutes after termination of CPB. In both groups, peak ET-1 values were obtained at 6 h after CPB. At 24 h after CPB, ET-1 concentrations returned to baseline levels before CPB in Group ND, but not in Group D. A correlation was identified between preoperative pulmonary to systemic pressure ratio and ET-1 concentration before and after CPB in both groups. CONCLUSIONS: Pre- and postoperative plasma ET-1 concentrations reflect pre- and postoperative pulmonary artery conditions in both groups. Specific features in Down syndrome could be associated with ET injury and might cause persistent increases in ET concentration and prolong artificial respiration.

[Perioperative management of a neonate with a retroperitoneal giant teratoma who underwent its extirpation under general anesthesia: a case report].

We gave anesthesia to a neonate with a retroperitoneal giant teratoma who underwent its extirpation. Even if patients have a prenatal diagnosis of teratoma like this case, there are many patients, especially infants, with severe general condition. We report the difficulty for management during anesthesia because of severe respiratory acidosis due to pressure from diaphragmatic pleura by tumor, severe circulatory disorder due to massive bleeding during operation and severe hyperkalemia due to renal failure.

Factors contributing to successful discontinuation from inhaled nitric oxide therapy in pediatric patients after congenital cardiac surgery.

OBJECTIVE: To investigate variables that contribute to successful discontinuation from inhaled nitric oxide (iNO) therapy in children after surgical repair of congenital heart disease. DESIGN: Analysis of retrospectively collected data. SETTING: The pediatric intensive care unit of a university hospital. PATIENTS: A total of 65 pediatric patients receiving iNO therapy for the purpose of pulmonary circulation control after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into two groups: those successfully weaned from iNO therapy on the initial attempt (group A, n = 45) and those for whom the initial attempt at weaning failed (group B, n = 20). Variables including intraoperative findings, postoperative hemodynamic and ventilatory variables, medication profiles, and dose and duration of iNO therapy were compared between groups. Using a multivariate logistic regression model, iNO therapy of >72 hrs (odds ratio, 5.6) and NO dose at discontinuation of <2 ppm (odds ratio, 4.1) were found to be significantly associated with successful weaning. Those results could be emphasized in a subgroup of left-to-right shunt cardiac anomaly. CONCLUSIONS: Longer continuation (>72 hrs) and lower final concentration (<2 ppm) represent factors contributing to successful discontinuation of iNO therapy in pediatric patients after cardiac surgery, specifically for children with left-to-right shunt correction.

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

PURPOSE: We investigated the inhibitory effects of toborinone and olprinone on human platelet aggregation and calcium mobilization.Abstract Copyright: METHODS: Washed 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. RESULTS: The concentrations required to cause 50% inhibition of aggregation (IC50) induced by thrombin were 9.7 +/- 0.9 micro M for toborinone and 3.6 +/- 0.2 micro M 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. CONCLUSION: Toborinone (9.7 micro M) and olprinone (3.6 micro M) 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.

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 microM-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 (> or =400 microM) 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 (> or = 400 microM) 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.

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 children's 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.