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Biomedical subjects

N Maekawa

Publications and source records attributed to N Maekawa.

At least 19 recordsLinked to original sources
PubMed1997

Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery.

PURPOSE: Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting. METHODS: In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups. RESULTS: Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting. CONCLUSION: These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery.

Analgesics↗
PubMed1997

ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.

Endotoxin causes acute lung injury resembling acute respiratory distress syndrome. Elastase, as well as reactive oxygen species released from activated neutrophils, are thought to play pivotal roles in the pathogenesis of this lung injury. This study investigated whether ONO-5046, a specific elastase inhibitor, can attenuate acute lung injury induced by endotoxin in rabbits. Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline without ONO-5046 treatment (Group S-S), infusion of saline with ONO-5046 (Group S-O), infusion of Escherichia coli endotoxin (100 micrograms/kg over 60 min) without ONO-5046 (Group E-S), and infusion of endotoxin with ONO-5046 (Group E-O). Fifteen minutes before the infusion of endotoxin (Groups E-O and E-S) or saline (Groups S-S and S-O), the animals received a bolus injection of ONO-5046 (10 mg/kg) followed by continuous infusion (10 mg.kg-1.h-1: Groups S-O and E-O) or saline (Groups S-S and E-S). The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocyte and platelet counts, and PaO2 were recorded during the ventilation period (6 h). Lung mechanics, cell fraction of the bronchoalveolar lavage fluid (BALF), activated complement, cytokines, and arachidonic acid metabolite concentrations in the BALF were measured at 6 h. The wet- to dry (W/D)-weight ratio of the lung and albumin concentrations in BALF were analyzed as indices of pulmonary edema. Endotoxin decreased lung compliance and PaO2, and increased the W/D weight ratio, neutrophil counts, and albumin concentration in the BALF. Concentrations of activated complement C5a, interleukin-6, interleukin-8, and thromboxane B2 in the BALF were increased by the infusion of endotoxin. ONO-5046 treatment attenuated these changes. Endotoxin caused extensive morphologic lung damage, which was lessened by ONO-5046. In conclusion, intravenous ONO-5046 pretreatment attenuated endotoxin-induced lung injury in rabbits. This beneficial effect of ONO-5046 may be due, in part, to a reduction in the levels of mediators that activate neutrophils, in addition to the direct inhibitory effect on elastase.

Airway Resistance↗
PubMed1997

Optimal dose of granisetron for prophylaxis against postoperative emesis after gynecological surgery.

UNLABELLED: We previously reported that 20 and 40 microg/kg of granisetron given during anesthesia prevented postoperative emesis with no severe complications. The aim of the current study was to determine the optimal dose of granisetron for the prevention of postoperative nausea and vomiting (PONV) after gynecological surgery. Two hundred female patients (ASA physical status I) were randomly allocated to one of five groups (n = 40 for each): saline (as a control), granisetron 2 microg/kg, granisetron 5 microg/kg, granisetron 10 microg/kg, and granisetron 20 microg/kg. Saline or granisetron was given intravenously immediately after induction of anesthesia. PONV was assessed 24 h after surgery. The percentage of emesis-free patients was significantly greater in the 5- to 20-microg/kg granisetron groups than in the control and 2-microg/kg granisetron groups (18%, 23%, 68%, 78%, and 75% of patients receiving saline or granisetron 2 microg/kg, 5 microg/kg, 10 microg/kg, and 20 microg/kg, respectively). Granisetron doses of 5 microg/kg or larger were also superior to the saline and 2-microg/kg granisetron treatment for the prevention of nausea over the 24-h study period (nausea visual analog scales 24 h after surgery: 49, 41, 18, 16, and 14 mm in the control and granisetron 2 microg/kg, 5 microg/kg, 10 microg/kg, and 20 microg/kg groups, respectively). A smaller proportion of patients received "rescue" antiemetic in the 5-microg/kg or larger granisetron groups than in the control and 2-microg/kg granisetron groups (48%, 40%, 18%, 13%, and 10% of patients in the control and granisetron 2 microg/kg, 5 microg/kg, 10 microg/kg, and 20 microg/kg groups, respectively). The antiemetic effect of granisetron was similar among the groups who received 5-microg/kg or larger doses. In conclusion, we suggest that the optimal dose of granisetron is 5 microg/kg for the prevention of PONV after gynecological surgery. IMPLICATIONS: Nausea and vomiting postoperatively after gynecologic surgery is a significant problem. The authors found that granisetron, a selective antagonist of serotonin, markedly decreases the incidence of postoperative nausea and vomiting at doses of 5 microg/kg or larger.

Adult↗
PubMed1997

Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils.

BACKGROUND: Reactive oxygen species (ROS) generated from neutrophils accumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto-injury. Lidocaine has been shown to reduce the injury. We investigated the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS production by neutrophils using an in vitro system. METHODS: We measured the production of superoxide (ferricytochrome c method), hydrogen peroxide (H2O2: scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas method) by neutrophils isolated from human adult volunteers in the absence and presence of lidocaine (2-200 micrograms/mL), mepivacaine (3-300 micrograms/mL), and bupivacaine (3-300 micrograms/mL). We also measured the ROS generation in a cell-free (xanthine-xanthine oxidase) system. RESULTS: Lidocaine and mepivacaine at higher levels significantly decreased the production of ROS by neutrophils. However, these local anaesthetics at clinically relevant blood concentrations had no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to reduce ROS generated by the cell-free system. Bupivacaine did not decrease ROS generation by either generating system. CONCLUSION: In conclusion, in the present in vitro system, only concentrations of lidocaine and mepivacaine 100-fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically relevant blood concentrations had no suppressive effect. Further studies using in vivo systems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings.

Adult↗
PubMed1996

Evaluation of left atrial appendage stasis in patients with atrial fibrillation using transesophageal echocardiography with an intravenous albumin-contrast agent.

To assess stasis in the left atrial appendage in patients with atrial fibrillation and to identify patients at increased risk for thromboembolism, we performed transesophageal echocardiography with an intravenous albumin contrast agent (Albunex) in 25 patients with atrial fibrillation and in 22 patients in sinus rhythm. We demonstrated that the absence of opacification in the left atrial appendage after Albunex administration implies a high risk of left atrial thrombus and cardiogenic thromboembolism.

Adult↗
PubMed1996

Detection of lysyl oxidase gene expression in rat skin during wound healing.

Lysyl oxidase (LOX) initiates the crosslinking of the lysine-derived aldehyde and plays an essential role in maturation of collagen, for example in wound healing. Although the activity of this enzyme has been examined in various disorders, and a further intriguing aspect of the relationship between LOX and tumorigenesis has recently emerged, its gene expression pattern in tissues is still unknown. We examined LOX gene expression during wound healing in rat skin. In addition, type III collagen gene expression was studied to determine the formation of fibrils. The LOX mRNA level reached a peak by day 3 after injury, which was earlier than that of type III collagen, and continued at a high level until day 22. The type III collagen mRNA level began to rise from day 3 and had increased intensely by day 22. In situ hybridization revealed grains corresponding to LOX mRNA in the fibroblasts of the granulomatous tissue. These results suggest that LOX is produced before collagen synthesis in preparation for crosslinking in the early phase of wound healing.

Animals↗
PubMed1996

Prostaglandin E1 attenuates the hypertensive response to tracheal extubation.

PURPOSE: Tracheal extubation causes hypertension and tachycardia, which may cause imbalance between myocardial oxygen demand and supply in patients at risk of coronary artery disease. We conducted a randomized, controlled study to evaluate the effects of 0.05 or 0.1 microgram.kg-1.min-1 prostaglandin E1 (PGE1) iv on haemodynamic variables occurring during tracheal extubation and emergence from anaesthesia and compared them in patients receiving either lidocaine or saline. METHODS: Eighty ASA physical status 1 patients undergoing elective surgery were enrolled in the current study. Anaesthesia was maintained with sevoflurane 1.0%-2.5% (ET concentration) and nitrous oxide 60% in oxygen. Muscle relaxation was achieved with vecuronium. The patients were randomly assigned to receive one of four treatments (n = 20 each): saline (control), 0.05 microgram.kg-1.min-1 PGE1, 0.1 microgram.kg-1.min-1 PGE1, or 1 mg.kg-1 lidocaine. PGE1 was infused from completion of surgery until five minutes after tracheal extubation. Changes in heart rate (HR) and blood pressure (BP) were measured during and after tracheal extubation. RESULTS: In the control group, the HR, systolic BP, and diastolic BP increased during tracheal extubation. Administration of 0.1 microgram.kg-1.min-1 PGE1 and 1 mg.kg-1 lidocaine attenuated the increases in BP although 0.05 microgram.kg-1.min-1 PGE1 failed to do so. The inhibitory effect of the 0.1 microgram.kg-1.min-1 PGE1 on BP was similar to that of lidocaine 1 mg.kg-1 iv. The increase in HR was attenuated by lidocaine but not by PGE1. CONCLUSION: The intravenous infusion of 0.1 microgram.kg-1.min-1 PGE1 given during emergence from anaesthesia and tracheal extubation is a useful method for attenuating the hypertension associated with noxious stimuli during this period.

Adult↗
PubMed1996

Comparison of nicardipine, diltiazem and verapamil for controlling the cardiovascular responses to tracheal intubation.

We have compared the efficacy of three calcium channel blockers, nicardipine, diltiazem and verapamil, in attenuating the cardiovascular responses to laryngoscopy and intubation in 60 normotensive patients (ASA I) undergoing rapid sequence induction of anaesthesia with thiopentone and fentanyl. We also examined whether or not these blockers inhibited catecholamine release induced by intubation. The patients were allocated to one of four groups (n = 15 for each): saline (control), nicardipine 30 micrograms kg-1, diltiazem 0.2 mg kg-1 or verapamil 0.1 mg kg-1. Verapamil and the three other drugs were administered 45 s and 60 s before the start of direct laryngoscopy, respectively, in a double-dummy design. Anaesthesia was induced with thiopentone 4 mg kg-1 i.v. and fentanyl 2 micrograms kg-1 i.v. Tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. During anaesthesia, ventilation was assisted or controlled with 1% isoflurane and 50% nitrous oxide in oxygen. Laryngoscopy lasting 30 s was attempted 2 min after administration of thiopentone and vecuronium. Patients receiving saline exhibited significant increases in systolic and diastolic arterial pressures (AP), heart rate (HR) and plasma concentrations of catecholamines associated with tracheal intubation. The increase in AP was attenuated in patients treated with any calcium channel blocker. The greatest effect was elicited by verapamil, which attenuated the increase in HR, although nicardipine seemed to enhance tachycardia. All three drugs failed to suppress the increase in plasma catecholamine concentrations in response to tracheal intubation. These findings suggest that bolus injection of verapamil 0.1 mg kg-1 was a more effective method of controlling hypertension and tachycardia associated with intubation than diltiazem 0.2 mg kg-1 or nicardipine 30 micrograms kg-1, and that these prophylactic effects were not caused by inhibition of the catecholamine response.

Adult↗
PubMed1996

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 micrograms/kg, or clonidine 4 micrograms/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 micrograms/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 micrograms/kg) is a possible approach to facilitating postoperative analgesia in children undergoing minor surgery.

Administration, Oral↗
PubMed1996

A comparison of lansoprazole, omeprazole, and ranitidine for reducing preoperative gastric secretion in adult patients undergoing elective surgery.

Acid aspiration syndrome of induction of anesthesia is a life-threatening complication whose severity is affected by both pH and volume of the aspirated gastric juice. We compared the effects of two proton pump inhibitors (PPIs), lansoprazole and omeprazole, and an H2 blocker, ranitidine, on gastric secretion in a prospective, randomized, double-blind fashion in 200 adult patients of ASA physical status I undergoing elective surgery. The patients were divided into eight groups (n = 25 each) according to their premedication. The patients received lansoprazole-lansoprazole (Group L-L), lansoprazole-placebo (Group L-P), placebo-lansoprazole (Group P-L), omeprazole-omeprazole (Group O-O), omeprazole-placebo (Group O-P), placebo-omeprazole (Group P-O), placebo-ranitidine (Group P-R), or placebo-placebo (Group P-P), as the first and second medications. The dose of the study drug was 30 mg for lansoprazole, 150 mg for ranitidine, and 80 mg for omeprazole. The first medication was administered orally at 9:00 PM on the night before surgery and the second at 5:30 AM in the morning on the day of the surgery. Each patient fasted overnight and took the drug with 20 mL of water. After tracheal intubation, gastric fluid was aspirated via an orogastric tube and the volume and pH of the aspirate were measured. The pH of the aspirated gastric fluid was higher in Groups P-R, L-L, P-L, O-O, and O-P than in Group P-P (P < 0.05). The volume of the gastric contents was similar in Groups P-0 and P-P, and the other groups had smaller gastric volume than Group P-P (P < 0.05). Gastric fluid from patients in Group P-R was the least acidic (pH 6.1 +/- 1.2) and had the least volume (0.09 +/- 0.06 mL/kg). Group L-L was comparable with Group P-R in both pH and volume, whereas Groups P-L and O-O were similar to Group P-R only in volume. The proportion of patients at risk according to the traditional criteria (pH < 2.5 and volume 0.4 mL/kg) was significantly lower in Groups L-L (0%), P-L (4%), O-O (4%), and P-R (0%) than in Group P-P (48%) (P < 0.05). We concluded that two consecutive doses of lansoprazole or a morning dose of ranitidine seemed to be the most effective preanesthetic medication for reducing gastric acidity and volume.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Attenuation of cardiovascular responses to tracheal extubation: verapamil versus diltiazem.

We studied the effect of intravenous injection of verapamil (0.05 mg/kg or 0.1 mg/kg) on cardiovascular changes during tracheal extubation and emergence from anesthesia and compared the efficacy of the drug with that of diltiazem (0.2 mg/kg). Eighty patients (ASA physical status I) who were to undergo elective gynecological surgery were randomly assigned to one of four groups (n = 20 each): saline (control), 0.05 mg/kg and 0.1 mg/kg verapamil, and 0.2 mg/kg diltiazem. These medications were given 2 min before tracheal extubation. Anesthesia was maintained with 0.5%-1.8% isoflurane and 60% nitrous oxide in oxygen. Muscle relaxation was achieved with vecuronium. Changes in heart rate (HR) and arterial blood pressure (AP) were measured during and after tracheal extubation. In the control group, the HR and systolic and diastolic AP increased significantly during tracheal extubation. Both calcium channel blockers attenuated the increases in these variables. The inhibitory effect was greatest with verapamil 0.1 mg/kg, while the alleviative effect of verapamil 0.05 mg/kg was inferior to that of diltiazem 0.2 mg/kg. These findings suggest that a bolus injection of verapamil 0.1 mg/kg given 2 min before tracheal extubation is a more effective prophylactic for attenuating the cardiovascular changes associated with extubation than is diltiazem 0.2 mg/kg.

Adult↗
PubMed1996

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. METHOD: Twenty-seven anaesthetized male rabbits were allocated to receive one of three treatments (n = 9 for each group): ventilation with 100% oxygen for 36 h with and without lidocaine treatment, and ventilation with air for 36 h without lidocaine. In the lidocaine-treated group, a single intravenous lidocaine 2 mg/kg was administered immediately after the initiation of exposure to 100% oxygen; thereafter, the lidocaine was infused at a rate of 2 mg.kg(-1).h(-1) for 36 h until the animals were sacrificed. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure, the lung mechanics and cell fraction in bronchoalveolar lavage fluid (BALF) were measured and analyzed, as was the concentration of activated complements, and cytokines in BALF. The lung wet-to dry- (W/D) weight ratio and albumin concentrations in BALF were analyzed as an index of pulmonary oedema. We also compared the chemiluminescence of neutrophils isolated from the pulmonary artery, and light microscopic findings, in the three groups. RESULTS: Pure oxygen for 36 h caused no significant changes in haemodynamics, lung mechanics, or PaO2/FiO2 ratio. However, hyperoxia significantly increased the lung W/D weight ratio, the influx of neutrophils into the lung, and BALF concentrations of C3a, C5a, TNF-alpha, IL-1 beta, and albumin. Lidocaine attenuated these increases (W/D ratio: 5.7 vs 5.1, %PMN: 19.2% vs 1.6%, C3a: 62 ng/dl vs 14 ng/dl, C5a: 7.9 ng/dl vs 4.1 nd/dl, TNF-alpha: 25 fmol/ml vs 2.8 fmol/ml, IL-1 beta: 36 fmol/ml vs 2.2 fmol/ml, and albumin: 9.5 mg/dl vs 2.8 mg/dl, all: P < 0.05). The chemiluminescence was increased in hyperoxic compared with in normoxic rabbits and lidocaine treatment attenuated the increase (opsonized zymosan stiluated: 3.7 x 10(6) cpm vs 2.3 x 10(6) cpm, P < 0.05). Exposure to 100% oxygen caused extensive morphologic lung damage which was lessened by lidocaine (lung injury score (mean): 3 vs 4, P < 0.05). CONCLUSION: These findings suggest that intravenous lidocaine has a prophylactic effect on initial hyperoxic lung injury (pulmonary vascular permeability, histopathological, and biochemical BALF changes) in rabbits. The effects of lidocaine on more severe lung injury (decreased oxygenation) caused by hyperoxia for 72 h deserve further study.

Albumins↗
PubMed1996

The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children.

BACKGROUND: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children. METHODS: In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5-11 yr, received placebo (control), 2 micrograms kg-1 clonidine, or 4 micrograms kg-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed. RESULTS: Higher inspired concentrations of halothane (%) were required in the control and 2 micrograms kg-1 clonidine-treated groups (mean SD: 1.1 +/- 0.2 and 1.0 +/- 0.2, respectively) than in the 4 micrograms kg-1 clonidine-treated group (0.6 +/- 0.1) for haemodynamic stability (P < 0.05). Clonidine, 4 micrograms kg-1, significantly reduced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens. CONCLUSION: Oral clonidine premedication at a dose of 4 micrograms kg-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.

Administration, Oral↗
PubMed1996

[Nitric oxide and the lung].

Many studies on nitric oxide (NO) as a messenger for biosignal transduction have recently been published. Endogenous NO is thought to play a pivotal role in homeostasis of the respiratory system and pulmonary circulation. As exhaled NO levels increase in patients with asthma or bronchiectasia, NO seems to be related to some pathological states in the respiratory organ. NO inhalation has been shown to be effective in attenuating pulmonary hypertension and desaturation in acute respiratory failure. Recent findings concerning NO in the lung were described in this review article.

Acute Disease↗