Biomedical subjects

H Obara

Publications and source records attributed to H Obara.

At least 19 recordsLinked to original sources

PubMed1998

Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter.

We examined the effects of interferon-alpha and -gamma, which are known to have psychiatric side effects including depression, on the transcriptional regulation of the serotonin transporter and the uptake activity of the serotonin transporter in order to clarify the involvement of the serotonin transporter in the pathogenesis of interferon-induced depression. In human placental choriocarcinoma cells (BeWo cells), both messenger RNA (mRNA) for the serotonin transporter and the imipramine-sensitive uptake of serotonin were detected. The levels of serotonin transporter mRNA were increased by treatment with interferon-alpha and -gamma for 3 h. The increase in serotonin transporter mRNA elicited by the interferons was inhibited by treatment with actinomycin D, an inhibitor of transcription. Treatment with interferon-alpha or -gamma for 3-6 h, but not for 30 min, increased the uptake activity of the serotonin transporter. Treatment with dibutyryl cAMP (Dib-cAMP) which was reported to up-regulate the transcription of the serotonin transporter, also increased the mRNA levels and the activity of serotonin transporter in BeWo cells. The levels of serotonin transporter mRNA gradually increased after treatment with Dib-cAMP over 24 h, while the maximal increase in serotonin transporter mRNA elicited by the interferons was detected 3 h after the treatment. The level of serotonin transporter mRNA was increased both in the midbrain and adrenal glands of mice which were treated with interferons for 3 h. These results suggest that the interferon-induced psychiatric side effects arise through regulation of serotonin transporter transcription and that the transcriptional regulation of the serotonin transporter is a possible neurochemical mechanism of affective disorders.

Animals↗

PubMed1998

Comparison of pirenzepine, ranitidine, and pirenzepine-ranitidine combination for reducing preoperative gastric fluid acidity and volume in children.

We conducted a two-part controlled study to evaluate the efficacy of preoperative oral pirenzepine (muscarinic receptor antagonist known to inhibit gastric secretion), ranitidine, and the combination pirenzepine-ranitidine in controlling gastric fluid pH and volume in 210 ASA I children, aged 2-14 yr, undergoing elective surgery. In the first part of the study (n = 90), the proportion of children considered at risk for aspiration pneumonitis was reduced with pirenzepine 25 mg (P < 0.05) but not with 12.5 mg. In the second part of the study, the other 120 children were allocated randomly to one of four groups: pirenzepine 25 mg with placebo; ranitidine 75 mg with placebo; pirenzepine 25 mg with ranitidine 75 mg; and placebo and placebo. These medications were administered 1 h before anaesthesia. After tracheal intubation, volume and pH of the gastric fluid aspiration via a multiorifice orogastric tube were measured. Pirenzepine 25 mg decreased gastric fluid volume (P < 0.05) but failed to increase gastric pH. Ranitidine 75 mg increased gastric pH (P < 0.05) but failed to decrease fluid volume. The pirenzepine-ranitidine combination reduced gastric fluid acidity and volume (P < 0.05).

Adolescent↗

PubMed1998

The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.

UNLABELLED: We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. IMPLICATIONS: Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.

Anesthetics↗

PubMed1998

The effect of halothane and sevoflurane on fatigue-induced changes in hamster diaphragmatic contractility.

UNLABELLED: The purpose of this study was to examine the effect of halothane and sevoflurane on fatigue-induced changes in diaphragmatic contractility. Forty-two hamster diaphragm strips were randomly allocated according to anesthetics (no anesthesia control, 1%-3% halothane, 2%-6% sevoflurane) and stimulated directly in an organ bath. Under the influence of the anesthetics, muscle fatigue was induced by repetitive tetanic contraction, and diaphragmatic contractilities (i.e., peak twitch and tetanic tension, twitch contraction time, and half-relaxation time) were measured before and after fatigue. Neither halothane nor sevoflurane changed tension generation before or after fatigue, but each anesthetic significantly enhanced fatigue-induced prolongations of the contraction time and half-relaxation time after fatigue. Specifically, the half-relaxation times after fatigue in the 3% halothane, 4% sevoflurane, and 6% sevoflurane groups (225.6 +/- 37.6, 236.0 +/- 76.5, and 287.3 +/- 55.5 ms, respectively) were more than twice as long as those of the control group (104.7 +/- 19.7 ms, P < 0.05). We conclude that halothane and sevoflurane augment fatigue-induced prolongations of the contraction and relaxation times. Diaphragmatic function may deteriorate when there is a fatiguing task during the clinical administration of halothane or sevoflurane anesthesia. IMPLICATIONS: This study implicates diaphragmatic fatigue during anesthesia. An in vitro hamster diaphragm muscle preparation was used to study the effect of halothane and sevoflurane on fatigue-induced change in contractility. Our findings suggest that increased load on the diaphragm during volatile anesthesia may lead to impaired diaphragmatic contractility.

Anesthetics, Inhalation↗

PubMed1998

Effects of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion in children.

BACKGROUND: Oral clonidine may influence plasma glucose and lipid homeostasis by modulating endocrinologic responses to surgical stress. The effect of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion were investigated in children undergoing minor surgery. METHODS: Otherwise healthy children (n, 120; aged 3-13 yr) were assigned randomly to six groups according to the glucose concentration of the intravenous solution (0%, 2%, or 5%, at a rate of 6 ml kg(-1) x h(-1)) and the preoperative medications (4 microg/kg clonidine or placebo given 100 min before anesthesia) they were to receive. The plasma concentrations of glucose, nonesterified fatty acid, ketone bodies, epinephrine, norepinephrine, and cortisol were determined. RESULTS: Infusion of 5% glucose caused hyperglycemia (mean glucose concentration >200 mg/dl) in six children receiving placebo and two receiving clonidine. Although the mean plasma glucose concentration increased in three placebo groups, it was unchanged and the plasma concentrations of total ketone bodies and nonesterified fatty acid were increased in children receiving clonidine and glucose-free solution. The plasma epinephrine, norepinephrine, and cortisol levels in children receiving placebo increased in response to surgery. Clonidine attenuated the increase in catecholamines and cortisol. CONCLUSIONS: Oral clonidine premedication attenuated the hyperglycemic response, probably by inhibiting the surgical stress-induced release of catecholamines and cortisol. Infusion of 2% of glucose maintained plasma glucose concentrations within physiologic ranges in children receiving clonidine.

Administration, Oral↗

PubMed1998

Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits.

BACKGROUND: Neutrophils play a crucial role in the pathogenesis of acid-induced acute lung injury. Lidocaine inhibits the function of neutrophils. This study aimed to determine whether lidocaine attenuates acute lung injury induced by hydrochloric acid (HCl) instillation. METHODS: In study 1, rabbits were divided into four groups (n = 7 each). Lung injury was induced by intratracheal HCl (0.1 N, 3 ml/kg) in two groups. The other two groups received saline intratracheally. Lidocaine given intravenously (2 mg/ g bolus + 2 mg x kg(-1) x h(-1) infusion) was started 10 min before intratracheal instillation in one HCl and one saline group, and saline was given intravenously in the other two groups. In study 2, rabbits (four groups of seven animals each) received HCl (0.1 N, 3 ml/kg) intratracheally. Treatment with intravenous lidocaine was started 10 min before, 10 min after, or 30 min after acid instillation, or saline was given intravenously 10 min before instillation. RESULTS: In study 1, HCl caused deterioration of the partial pressure of oxygen (PaO2), lung leukosequestration, decreased lung compliance, and increased the lung wet-to-dry weight ratio and albumin, interleukin-6 (IL-6), and IL-8 levels in bronchoalveolar lavage fluid. Lidocaine pretreatment attenuated these changes. Hydrochloric acid increased superoxide anion production by neutrophils and caused morphologic lung damage, both of which were lessened by lidocaine. In study 2, lidocaine given 10 min after acid instillation was as effective as pretreatment in PaO2, lung mechanics, and histologic examination. However, PaO2 changes in lidocaine 30 min after injury were similar to those in saline given intravenously. CONCLUSIONS: Intravenous lidocaine started before and immediately after acid instillation attenuated the acute lung injury, in part by inhibiting the sequestration and activation of neutrophils.

Anesthetics, Local↗

PubMed1998

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Adult↗

PubMed1998

Aminoguanidine attenuates endotoxin-induced acute lung injury in rabbits.

OBJECTIVE: To assess the effect of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, on endotoxin-induced acute lung injury in rabbits. DESIGN: Prospective, blinded, controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Twenty-eight male rabbits. INTERVENTIONS: The animals were randomly assigned to receive one of four treatments (n = 7 for each group): infusion of saline only (S-S group), infusion of saline and aminoguanidine (S-AG group), infusion of Escherichia coli endotoxin (5 mg/kg over 60 mins) (E-S group), and infusion of endotoxin and aminoguanidine (E-AG group). Fifteen minutes before infusion of endotoxin (E-S and E-AG groups) or saline (S-S and S-AG groups), the animals received an intravenous injection of 1 mg/kg of aminoguanidine (S-AG and E-AG groups) or saline (S-S and E-S groups). The same dose of aminoguanidine or saline was given 1 hr after the end of endotoxin or saline infusion. The lungs of the rabbits were ventilated with 40% oxygen. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, peripheral leukocyte counts, and PaO2 were recorded during the ventilation period (6 hrs). After these observations were made, lung mechanics, cell fraction of bronchoalveolar lavage fluid, and concentrations of thromboxane A2 and prostacyclin metabolites in bronchoalveolar lavage fluid were determined. The wet weight/dry weight ratio of the lung and albumin concentrations in bronchoalveolar lavage fluid were analyzed as indices of pulmonary edema. Endotoxin decreased the lung compliance and PaO2 and increased the wet weight/dry weight ratio, neutrophil counts, and albumin concentrations in bronchoalveolar lavage fluid. The bronchoalveolar lavage fluid concentrations of thromboxane B2 in bronchoalveolar lavage fluid were increased by infusion of endotoxin. Aminoguanidine attenuated these changes. Endotoxin caused extensive morphologic lung damage, which was lessened by aminoguanidine. CONCLUSIONS: Aminoguanidine given intravenously before and after endotoxin attenuated endotoxin-induced lung injury in rabbits. These findings suggest that inducible nitric oxide synthase inhibition may be useful in the treatment of endotoxin-induced lung injury. However, further studies are required to determine the optimal dosage of aminoguanidine, when the inhibitor is given alone as therapy after lung injury.

Animals↗

PubMed1998

Vaginal birth after cesarean delivery: results in 310 pregnancies.

OBJECTIVE: To assess and compare the risk associated with a trial of vaginal birth after cesarean section (VBAC) with the risk of an elective repeat cesarean section. METHODS: A retrospective review of the records of 310 consecutive women who, at the Jichi Medical School Hospital in the 6-year period of 1990 through 1995, had previously undergone a primary cesarean section and gave birth to a singleton infant weighing > or = 2,000 g at > or = 36 weeks of gestation in a subsequent pregnancy. RESULTS: Elective cesarean sections were performed on 96 (31%) of 310 women, and VBACs were attempted by 214 women (69%). Vaginal deliveries were successful in 132 (43%) of the 310 pregnancies. No maternal death or perinatal deaths occurred in either group. A uterine rupture occurred in 2 (0.9%) of the 214 women who attempted a VBAC, and 5 women (2.3%) gave birth to neonates with a 1-minute Apgar score < or = 6. None of the 96 women who underwent an elective cesarean section had such complications, although the difference in these complication rates did not reach a significant level. CONCLUSIONS: A trial of a VBAC significantly reduced the rate of cesarean sections. Although the rates of uterine rupture and neonatal asphyxia were slightly higher in women who attempted a VBAC than in women who underwent an elective cesarean section, obstetricians should offer the option of a trial of labor, because more than one-half of the women with a previous cesarean delivery might have successful vaginal deliveries, and the VBAC-related maternal mortality rate does not reportedly differ between women undergoing a trial of labor and women undergoing an elective repeat cesarean section.

Adult↗

PubMed1997

Prostaglandin E1, lidocaine, and prostaglandin E1-lidocaine combination for attenuating cardiovascular responses to extubation.

PURPOSE: Tracheal extubation produces haemodynamic changes that may cause myocardial ischaemia in patients with coronary arterial disease. Intravenous infusion of prostaglandin E1 (PGE1) attenuated the hypertensive response to tracheal extubation but failed to blunt the tachycardia, which was attenuated by intravenous lidocaine. Thus, we investigated whether a combination of PGE1 and lidocaine can overcome the drawbacks of treatment with PGE1 alone. METHODS: One hundred adult patients (ASA 1) undergoing elective minor surgery were randomly assigned to receive one of four treatments: saline (as a control), 1 mg-kg-1 lidocaine, infusion of 0.1 microgram-1.kg-1.min-1 PGE1, or infusion of 0.1 microgram-1.kg-1.min-1 PGE1 plus injection of 1 mg-1.kg-1 lidocaine. Lidocaine was injected two minutes before tracheal extubation. The PGE1 was infused from completion of surgery until five minutes after tracheal extubation. Anaesthesia was maintained with sevoflurane 1.0%-2.5% and nitrous oxide 60%. Heart rate (HR) and blood pressure (BP) were measured before and after tracheal extubation. RESULTS: Lidocaine alone and PGE1-lidocaine combination attenuated the increases in BP and HR observed in the control group: PGE1 alone was effective in attenuating hypertensive response but ineffective for tachycardia. The suppressive effect of the PGE1-lidocaine combination on BP increase was superior to that of each drug alone, and the combined effect on HR increase was similar to that of lidocaine alone. CONCLUSION: The combination of PGE1 infusion and lidocaine is a more effective method of attenuating hypertension and tachycardia associated with tracheal extubation than either drug alone.

Adult↗

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

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Aged↗

PubMed1997

Temporal brain imaging by a rapid scan ESR-CT system in rats receiving intraperitoneal injection of a methyl ester nitroxide radical.

We performed in vivo ESR-CT (electron spin resonance-computed tomography) on rats' heads, in which the blood-brain barrier-permeable nitroxide radical, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM) was injected intraperitoneally, using a rapid scan ESR-CT system operating at 700 MHz. In a spatiotemporal study we found that different regions of the brain showed differences in the rate of decay of the radical. Repeated injection of PCAM gave clear ESR-CT images of the brain. We think that the present method is useful for evaluating the capacity to eliminate exogenous free radicals in some parts of the brain.

Animals↗

PubMed1997

The relaxing effect of ketamine on isolated rabbit lower esophageal sphincter.

We used ketamine to investigate the effects and intracellular mechanisms of several anesthetics on strips of lower esophageal sphincter (LES) from rabbits. Ketamine induced dose-dependent relaxation of LES preparations. It increased the content of 3',5'-cyclic adenosine monophosphate (cAMP) dose-dependently, but decreased that of 3',5'-cyclic guanosine monophosphate (cGMP). Pretreatment with nicotinic acid, an inhibitor of adenylate cyclase, along with atropine to block neurogenic effects, antagonized ketamine-induced relaxation. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89), a selective antagonist for cAMP-dependent protein kinase, similarly antagonized the relaxant effect of ketamine. Cholera toxin and dibutyryl cAMP induced LES relaxation. However, dibutyryl cGMP induced little LES relaxation, and pretreatment with NG-nitro-L-arginine or methylene blue did not alter the relaxant effect. Atropine, propranolol, phentolamine, vasoactive intestinal peptide (VIP) antagonist, and tetrodotoxin did not affect the ketamine-induced relaxation. This response, however, was potentiated in the presence of indomethacin or diphenhydramine. Ketamine-induced relaxation was inhibited in the presence of verapamil. These findings suggest that ketamine induces relaxation of LES, in part, by modulating the activity of adenylate cyclase and in part by inhibiting transmembrane influx of Ca2+.

Adenylyl Cyclases↗

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

Attenuation of cardiovascular responses to tracheal extubation: comparison of verapamil, lidocaine, and verapamil-lidocaine combination.

UNLABELLED: We recently showed that verapamil attenuated hemodynamic responses to tracheal extubation. The aim of the current study was to compare the efficacy of a combination of intravenous (I.V.) verapamil (0.1 mg/kg) and I.V. lidocaine (1 mg/kg) with that of each drug alone in suppressing the cardiovascular changes during tracheal extubation and emergence from anesthesia. One hundred adult patients (ASA physical status I) who were to undergo elective minor surgery were randomly assigned to one of four groups (n = 25 each): Group S = saline plus saline (control), Group V = verapamil 0.1 mg/kg I.V. plus saline, Group L = lidocaine 1 mg/kg I.V. plus saline, and Group V-L = verapamil 0.1 mg/kg I.V. plus lidocaine 1 mg/kg I.V. These medications were given 2 min before tracheal extubation. Anesthesia was maintained with 1.0%-2.0% sevoflurane and 60% nitrous oxide (N2O) in oxygen. Muscle relaxation was achieved with vecuronium, and a residual neuromuscular blockade was reversed with neostigmine 0.05 mg/kg (combined with atropine 0.02 mg/kg). 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. Verapamil, lidocaine, and their combination attenuated the increases in these variables. The beneficial effect was the greatest with the combination of verapamil and lidocaine. These findings suggest that verapamil 0.1 mg/kg and lidocaine 1 mg/kg given I.V. concomitantly 2 min before tracheal extubation is a simple and more effective prophylaxis than verapamil or lidocaine alone for attenuating the cardiovascular changes associated with tracheal extubation. IMPLICATIONS: Tachycardia and hypertension associated with tracheal extubation, which may lead to myocardial ischemia, represent a potential risk for patients with coronary arterial disease. To seek effective pharmacological prophylaxis against these complications, we compared the attenuation of hemodynamic changes among verapamil, lidocaine, and a verapamil/lidocaine combination using ASA physical status I patients and found the combination to be effective.

Adult↗

PubMed1997

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for tracheal intubation in children.

BACKGROUND: Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MAC(TI)) of sevoflurane was assessed with and without N2O and clonidine premedication. METHODS: Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 microg/kg oral clonidine or 4 microg/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial RESULTS: The MAC(TI) of sevoflurane in the absence of N2O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MAC(TI) of sevoflurane by 26%, 24%, and 27% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups. CONCLUSIONS: Oral clonidine premedication decreased the MAC(TI) of sevoflurane. Nitrous oxide also decreased the MAC(TI). The combination of clonidine and N2O lessened the MAC(TI) of sevoflurane more than did either drug alone.

Administration, Oral↗