Katsuya Mikawa

Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature.

Background There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard. Methods Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by &OV0422; value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval. Results Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34–0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups. Conclusion The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.

Efficacy of Oral Clonidine Premedication in Children

BackgroundClonidine, an α2-adrenoceptor agonist, has been shown to be effective as a preanesthetic medication in adults. The current study was designed to investigate the efficacy of two doses of oral clonidine as a premedicant preceding oral atropine in children. MethodsIn a prospective, randomized, double-blind, controlled clinical trial, 105 children, aged 4–12 yr, undergoing elective ophthalmologic surgery received 0.4 mg/kg diazepam, 2 μg/kg clonidine, or 4 μg/kg clonidine orally. These agents mixed with apple juice were administered 105 min before the estimated time of induction of anesthesia, and were followed by treatment with 0.03 mg/kg oral atropine 60 min before anesthesia. A blinded observer noted the childrens level of sedation, quality of separation from parents, and degree of acceptance of mask application during inhalation of nitrous oxide used for establishment of venous access. Anesthesia was induced with 5 mg/kg thiamylal, and tracheal intubation was facilitated with 0.2 mg/kg vecuronium. Hemodynamic changes after tracheal intubation were compared among the three groups. ResultsClonidine produced significant sedation, and the effect was dose related. Clonidine, 4 μg/kg, provided better quality of separation and acceptance of mask than the two other regimens. This dose of clonidine attenuated the increases in blood pressure and heart rate after tracheal intubation. No clinically significant perioperative hypotension or bradycardia was observed. ConclusionsThese data indicate that, even in pediatric surgery, the combination of 4 μg/kg and 0.03 mg/kg oral clonidine is an effective premedication. However, the safety and optimal dose of clonidine in this setting remain to be determined.

Oral clonidine premedication reduces postoperative pain in children.

Clonidine is an effective preanesthetic medication in children, providing a preoperative sedative effect.The analgesic properties of the drug have been well documented in adults. The current study was designed to investigate the effect of oral clonidine given preoperatively on postoperative pain in children undergoing minor surgery. In a prospective, randomized, controlled clinical trial, 90 children aged 5-12 yr undergoing elective ophthalmic, urologic, and otologic surgery received placebo (control), clonidine 2 micro gram/kg, or clonidine 4 micro gram/kg. These drugs were administered 105 min before the estimated time of induction of anesthesia and followed by treatment with oral atropine 0.03 mg/kg 60 min before anesthesia. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). Clonidine 4 micro gram/kg provided lower OPS (highest) scores during 12 h after surgery and reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. These data suggest that oral clonidine premedication (4 micro gram/kg) is a possible approach to facilitating postoperative analgesia in children undergoing minor surgery. (Anesth Analg 1996;82:225-30)

Clonidine in paediatric anaesthesia

Introduction anaesthesia was available. A prospective study on oral clonidine premedication in children dates from Clonidine, an a2-adrenoceptor agonist, was first 1993 (11). Recently, the number of publications introduced into adult clinical practice as antiindicating effectiveness of clonidine in paediatric hypertensive medication in the late 1960s (1). The anaesthesia has increased and several articles are first application of clonidine to children dates back published annually in anaesthesia journals worldto 1973 (2): an eleven-year-old child received the wide (Figure 1). In this article, we review the drug for migraine. This treatment, which is not present state of clonidine application to paediatric currently used, was based on continuous low doses anaesthesia by focusing on recent investigations, of clonidine reducing the responsiveness of vascular mainly a series of our studies on premedication with smooth muscle to sympathetic nerve activity. Thereafter, clonidine has been used as a provocative test of growth hormone (GH) or treatment for neuropsychiatric disorder (see later section) and in adult patients with migraine or hypertension. However, its use was limited because of adverse side effects including sedation and antisialogogue action, but it is these properties which have been partially responsible for a new enthusiasm for clonidine in anaesthesia. In 1979, clonidine was used experimentally to reduce the dose requirement for anaesthetic and analgesic drugs (3). Not until the late 1980s did several studies demonstrate that clonidine is an effective premedicant in adult patients, providing preoperative sedation (4–7), perioperative haemodynamic stability (8,9), and reduction in the volatile 1997 30

Effect of Lidocaine Pretreatment on Endotoxin-induced Lung Injury in Rabbits

Background:It is well known that endotoxin causes acute lung injury resulting in adult respiratory distress syndrome. Numerous cellular and humoral factors such as macrophages, neutrophils, platelets, and inflammatory mediators (e.g., activated complements, cytokines, and arachidonic acid metabolites) are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury. Furthermore, pulmonary edema in acute lung injury is associated with an increase in vascular permeability that may arise from a perturbation of the endothelial cell surface membrane. Lidocaine has been shown to inhibit function of these cells and stabilize cell membranes. The aim of the current study was to determine whether pretreatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits. Methods:Twenty-seven anesthetized male rabbits were randomly assigned to receive one of three treatments (n=9 for each group); infusion of saline (as a control), infusion of Escbericbia coli endotoxin (30 µg kg-1 over a 60–min period) without treatment with lidocaine, and infusion of endotoxin with treatment with lidocaine. A single dose of intravenous lidocaine 2 mg·kg-1 was administered 10 min before infusion of endotoxin and thereafter infused at a rate of 2 mg·kg-1· h-1 until 6 h after the start of endotoxin administration, when the animals were killed. The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocytes counts, and arterial oxygen tension were recorded during the ventilation period. After the observation, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolites concentrations in BALF were measured and analyzed. The lung wet- to dry-weight ratio and albumin concentrations in BALF were analyzed as an indices of pulmonary edema. The cypridina luciferin analog-dependent chemiluminescence (representing superoxide production) by neutrophils isolated from the pulmonary artery and light microscopic findings were compared among the three groups. Results:Endotoxin caused decreases in peripheral leukocyte counts, lung compliance, and arterial oxygen tension, and increases in the lung wet- to dry-weight ratio, polymorphonuclear cell counts in BALF, and albumin, C3a, C5a, tumor necrosis factor α, interleukin-1β2, and thromboxane B2 concentrations in BALF. Lidocaine pretreatment attenuated these changes. The cypridina luciferin analog—dependent chemiluminescence was greater in rabbits receiving endotoxin than in the control. Lidocaine pretreatment attenuated the increase in chemiluminescence. Endotoxin caused extensive morphologic lung damage, which was lessened by lidocaine. Conclusions:These results suggest that intravenous lidocaine pretreatment has a prophylactic effect on endotoxin-induced lung injury in rabbits. However, further studies are required to investigate the therapeutic (as an early posttreatment) effect of the drug given after lung injury because rabbits in the current study received lidocaine before endotoxemia.

Lidocaine attenuates hyperoxic lung injury in rabbits

Background: High concentrations of oxygen acute lung injury. Neutrophils are thought to play a pivotal role in the pathogenesis of this lung injury through the release of oxygen radicals, neutral proteases, and lysosomal enzymes. Lidocaine has been shown to inhibit neutrophil function. We examined whether intravenous pretreatment with lidocaine attenuated acute lung injury induced by hyperoxia.

Attenuation of acute lung injury with propofol in endotoxemia.

Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg · kg−1 · h−1) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.

Protein kinase C during differentiation of human promyelocytic leukemia cell line, HL-60

Protein kinase C (PKC) from human promyelocytic leukemia HL‐60 cells can be resolved into three fractions (peak a, b and c) by hydroxyapatite column chromatography. Peak a and c enzymes are indistinguishable from the brain type II PKC having β (βI and βII)‐sequence and type III having α‐sequence, respectively. Peak b enzyme is a previously unidentified PKC subspecies that has enzymological properties subtly different from type I (having γ‐sequence), type II and type III PKC. Upon treatment of HL‐60 cells with 1 μM retinoic add, this peak b enzyme is decreased dramatically within 24 h, whilst peak a enzyme (β‐PKC) is increased, and peak c (α‐PKC) enzyme is slightly decreased within 48 h. The result implies that the PKC subspecies in HL‐60 cells have distinct functions during cell differentiation.

Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection.

ObjectiveWe attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DesignProspective animal study. SettingUniversity laboratory. SubjectsForty Japanese white rabbits. InterventionsThe rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL·kg−1·hr−1) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg·kg−1·hr−1) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. Measurements and Main Results Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as estimated by hypoxemia, decreased lung compliance, pulmonary edema, and vascular permeability. The therapeutic efficacy was similar to that found in our previous pretreatment study. The treatment after 1 hr dramatically inhibited OA-induced surfactant degradation in the bronchoalveolar lavage fluid (BALF), without affecting the concentrations of thromboxane A2, leukotriene B4, and interleukin-8 in BALF. The degree of surfactant degradation in BALF paralleled well with the severity of the lung injury. Furthermore, recombinant human sPLA2-IIA reproduced the similar hydrolysis pattern of isolated surfactant in vitro, which was inhibited by S-5920/LY315920Na. ConclusionsOur results indicate that therapeutic blockade of sPLA2-IIA ameliorated lung dysfunction via protection of surfactant degradation in an animal model of acute lung injury, and they suggest a new strategy in treating clinical acute lung injury.

Effects of Exogenous Intravenous Glucose on Plasma Glucose and Lipid Homeostasis in Anesthetized Children

Whether or not intravenous glucose administration during pediatric anesthesia is necessary remains a controversial issue. The current study was designed to investigate the effect of glucose infusion on concentrations of plasma glucose, nonesterified fatty acids (NEFA), triglycerides, ketone bodies, and insulin and to determine whether the use of solutions containing less than 5% glucose would maintain physiologic plasma glucose concentrations during tympanoplasty lasting about 6 h. Forty-five children aged between 1.5 and 9 yr were divided randomly into three groups of 15 patients each to receive the following intravenous solutions: LR groups, lactated Ringers solution (LR) alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. All fluids were infused at a rate of 6 ml.kg-1.h-1 until 1 h after anesthesia. In the LR group, the plasma glucose concentrations remained unchanged perioperatively compared with basal values, whereas in the D2LR group they showed a gradual increase during surgery but remained normoglycemic. On the other hand, in the D5LR group, the plasma glucose concentrations increased markedly both during and after the operation. Furthermore, 3 of 15 patients showed hyperglycemia of more than 300 mg.dl-1 during anesthesia. There was no evidence of lipid mobilization or impaired secretion of insulin, since plasma NEFA, triglycerides, ketone bodies, and insulin remained within normal concentration ranges throughout the sample period in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)