Improvement of the accuracy of references in the Journal of Cardiothoracic and Vascular Anesthesia.
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Bibliometrics↗
Biomedical subjects
K Nishina
Publications and source records attributed to K Nishina.
A comparison of rabeprazole, lansoprazole, and ranitidine for improving preoperative gastric fluid property in adults undergoing elective surgery.
UNLABELLED: Acid aspiration syndrome at the induction of anesthesia is still a potentially life-threatening complication. Its severity is affected by both pH and volume of the gastric juice that is aspirated. We compared the effects of rabeprazole (a new proton pump inhibitor), lansoprazole, and ranitidine on gastric fluid properties in a prospective, randomized, double-blinded fashion in 180 adult patients undergoing elective surgery. Patients were divided into six groups (n = 30 in each) according to their premedication. Patients in each group received placebo-rabeprazole (PLA-RAB), rabeprazole-placebo (RAB-PLA), rabeprazole-rabeprazole (RAB-RAB), lansoprazole-lansoprazole (LAN-LAN), placebo-ranitidine (PLA-RAN), or placebo-placebo (PLA-PLA) for the first-second medication. Each dose of the study drug was 20 mg for rabeprazole, 30 mg for lansoprazole, and 150 mg for ranitidine. The first medication was given orally at 9:00 PM on the day before surgery and the second at 5:30 AM on the day of 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 was measured. Preoperative gastric fluid acidity and volume were improved by the study drugs in the following order: PLA-RAN (pH 5.3, volume 0.10 mL/kg), RAB-RAB, LAN-LAN, PLA-RAB, and RAB-PLA (pH 3.8, volume 0.22 mL/kg). The proportion of patients at risk of acid aspiration syndrome according to the traditional criteria (pH < 2.5 and volume > 0.4 mL/kg) was minimized in Groups RAB-RAB and PLA-RAN (0%). We concluded that a single morning dose of ranitidine rather than two doses (bedtime and morning) of rabeprazole was the most effective premedicant to control gastric fluid properties and to minimize the risk of aspiration pneumonitis. IMPLICATIONS: Acid aspiration syndrome at the induction of anesthesia is rare but still a potentially life-threatening complication. We compared rabeprazole, lansoprazole, and ranitidine for reduction of preoperative gastric fluid acidity and volume in elective surgery and found that a combination of bedtime and morning doses of rabeprazole, or a morning dose of ranitidine, similarly minimized the variables. In adult patients who are at risk of aspirating gastric contents, improvement of gastric fluid environment by rabeprazole can reasonably be anticipated to provide protection against pneumonitis should regurgitation and aspiration of gastric contents occur.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Oral clonidine premedication does not change efficacy of simulated epidural test dose in sevoflurane-anesthetized children.
BACKGROUND: Caudal epidural anesthesia is often used as an adjunct to general anesthesia and for postoperative pain relief in children. In anesthetized children, epinephrine and isoproterenol are reliable indicators to detect accidental intravascular injection of a test dose. Oral clonidine, a useful premedicant in pediatric anesthesia, modifies hemodynamic responses to sympathomimetics, including catecholamines. The aim of the current study was to determine whether oral clonidine premedication alters the efficacy of a simulated intravascular test dose containing epinephrine or isoproterenol in sevoflurane-anesthetized children. METHODS: One hundred twenty children (aged 1-7 yr) were randomly divided into six groups; control-saline, control-epinephrine, control-isoproterenol, clonidine-saline, clonidine-epinephrine, and clonidine-isoproterenol. The three clonidine groups received oral clonidine 4 microg/kg [DOSAGE ERROR CORRECTED] as premedication, whereas the three control groups did not receive any premedication. Anesthesia was maintained with sevoflurane at a level of 1.2 minimum alveolar concentration. After hemodynamics were stable, 0.1 ml/kg of 1% lidocaine containing epinephrine 0.5 mg/kg or isoproterenol 75 ng/kg was intravenously given to the two epinephrine or isoproterenol groups, respectively, to simulate intravascular injection of a test dose. The saline groups received saline alone instead of the test dose. Heart rate, blood pressure, and T-wave amplitude of electrocardiogram were recorded before and after administration of study drugs for subsequent analysis. RESULTS: Test solution containing epinephrine increased heart rate, systolic blood pressure, and T-wave amplitude. Oral clonidine had no effect on elevation of these variables in response to epinephrine. The isoproterenol-containing test dose produced a prominent increase in heart rate and a less pronounced increase in systolic blood pressure and T-wave amplitude. Oral clonidine also failed to modify isoproterenol-induced hemodynamic and T-wave changes. Calculated sensitivity and specificity of epinephrine or isoproterenol were all 100% based on a new heart rate criterion (positive if >/= 10 beats/min) and were unaltered by oral clonidine premedication. CONCLUSIONS: Epinephrine or isoproterenol is a reliable marker to detect accidental intravascular injection of a test dose with 100% sensitivity and specificity based on a new heart rate criterion in sevoflurane-anesthetized children. These data suggest that oral clonidine premedication does not alter the efficacy of a simulated epidural test dose containing epinephrine or isoproterenol.
Administration, Oral↗
Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin.
OBJECTIVE: Acute severe pancreatitis is often associated with acute lung injury, including acute respiratory distress syndrome. Acute lung injury induced by phospholipase A2 (PLA2) or trypsin, a pancreatic enzyme, is an experimental model resembling acute respiratory distress syndrome. Neutrophils and platelets are thought to play a pivotal role in the pathogenesis of acute respiratory failure. Lidocaine inhibits some aspects of neutrophil and platelet functions. We conducted the current study to assess the effects of pretreatment with lidocaine on acute lung injury induced by a combination of PLA2 and trypsin. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one adult male Japanese White rabbits (weight range, 2.0-2.4 kg). INTERVENTIONS: The animals were mechanically ventilated with a tidal volume of 10 mL/kg and an Fio2 of 0.4, and thereafter, they were randomly assigned to three groups. Acute lung injury was induced by a combination of PLA2 (1000 units/kg/hr) and trypsin (5000 units/kg/hr) infused intravenously for 4 hrs. Immediately before induction of the acute lung injury, the lidocaine treatment group received intravenous lidocaine (2 mg/kg bolus followed by 2 mg/kg/hr) until they were killed. In the nontreatment group, saline was given instead of lidocaine. Rabbits in the nonlung-injury group received saline infusion instead of the pancreatic enzymes. MEASUREMENTS AND MAIN RESULTS: During the experimental period (4 hrs), arterial blood gases, lung mechanics, and peripheral neutrophil and platelet counts were measured. Immediately after killing, the wet weight/dry weight ratio of the lung was recorded. Light microscopic findings (lung injury score and number of neutrophils) were compared between the three groups. The combination of PLA2 and trypsin decreased Pao2, lung compliance, and peripheral counts of neutrophils and platelets and increased alveolar/arterial oxygen tension difference, lung resistance, wet weight/dry weight ratio, and the number of neutrophils in the lung. Lidocaine treatment attenuated these changes. The two pancreatic enzymes caused extensive morphologic lung damage, which was lessened by lidocaine. CONCLUSIONS: We conclude that pretreatment with intravenous lidocaine attenuated the lung injury induced by the pancreatic enzymes. However, further studies are required to determine whether this drug has a therapeutic effect once the lung injury has developed.
Animals↗
The effect of phosphodiesterase III inhibitors on human neutrophil function.
OBJECTIVES: Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions. DESIGN: Prospective in vitro study. SETTING: Academic research laboratory. SUBJECTS: Neutrophils isolated from 12 healthy adult volunteers. INTERVENTIONS: We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system MEASUREMENTS AND MAIN RESULTS: None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients.
3',5'-Cyclic-AMP Phosphodiesterases↗
Attenuation of hyperoxia-induced diaphragmatic dysfunction with lidocaine in hamsters.
OBJECTIVE: Toxic free radicals cause dysfunction of respiratory muscles, probably leading to respiratory distress. Exposure to high concentrations of oxygen generates plenty of free radicals. Lidocaine scavenges the reactive molecules. The purposes of the current study were first to examine whether hyperoxia impairs diaphragmatic function, and second, to assess the effects of lidocaine on hyperoxia-induced diaphragmatic dysfunction, if developed. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Forty and 48 adult male Golden-Syrian hamsters (110-150 g) in parts I and II studies, respectively. INTERVENTION: In the part I study, hyperoxia for 5 and 6 days reduced diaphragmatic contractility and enhanced fatigue. In the part II study, hamsters were randomly allocated to one of six groups (n = 8 each): exposure to air for 6 days with saline (group A-S) or lidocaine infusion (group A-L), exposure to 100% oxygen for 5 days with saline (group 05-S) or lidocaine (group 05-L), and exposure to 100% oxygen for 6 days with saline (group 06-S) or lidocaine (group 06-L). Saline or lidocaine (2 mg/kg/hr) was subcutaneously given immediately before exposure to air or oxygen. Diaphragmatic contractility and fatigability were assessed in vitro using muscle strips excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free radical-mediated lipid peroxidation, were measured. These variables were compared between groups. MEASUREMENTS AND MAIN RESULTS: Twitch and tetanic tensions in groups 05-S and 06-S were reduced compared with group A-S. Tensions generated during fatigue trials were also decreased in groups 05-S and 06-S. MDA levels were elevated in diaphragms from these groups. In groups 05-L and 06-L, contractile dysfunction, deterioration of fatigability, and MDA formation in the diaphragm were attenuated. CONCLUSIONS: Lidocaine attenuated hyperoxia-induced diaphragmatic dysfunction assessed by contractile profiles and fatigability in hamsters. This beneficial effect may be attributable, in part, to inhibition of lipid peroxidation.
Animals↗
Lidocaine attenuates sepsis-induced diaphragmatic dysfunction in hamsters.
OBJECTIVES: Sepsis or endotoxemia causes diaphragmatic dysfunction, which may contribute to respiratory distress. Toxic free radicals are partly responsible for the pathogenesis. Lidocaine scavenges the reactive molecules. The purpose of the current study was to examine whether lidocaine prevents the diaphragmatic dysfunction of sepsis. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: A total of 40 male Golden-Syrian hamsters. INTERVENTIONS: The animals were randomly allocated to one of five groups (n = 8 each): hamsters undergoing sham laparotomy alone and receiving saline infusion (Sham group), those undergoing cecal ligation with puncture (CLP) and receiving an infusion of saline (Sepsis group), those undergoing sham laparotomy and receiving infusion of lidocaine, 2 mg/kg/hr (Sham-LID group), those undergoing CLP and receiving infusion of lidocaine, 1 mg/kg/hr (Sepsis-LID 1 group), and those undergoing CLP and receiving infusion of lidocaine, 2 mg/kg/hr (Sepsis-LID 2 group). Subcutaneous infusion of saline or lidocaine was started 6 hrs before surgery and continued until 24 hrs after the operation when all hamsters were killed. MEASUREMENTS AND MAIN RESULTS: Diaphragmatic contractility and fatigability were assessed in vitro by using muscle strips excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free radicals-mediated lipid peroxidation, were also measured. Twitch and tetanic tensions in the Sepsis group were reduced compared with the Sham group. Tensions generated during fatigue trials were decreased, and MDA levels were elevated in diaphragms from the Sepsis group. An infusion of 2 mg/kg/hr lidocaine attenuated contractile dysfunction, aggravation of fatigability, and the increase in MDA formation. In contrast, 1 mg/kg/hr lidocaine failed to do so. Electrophysiologic diaphragmatic characteristics in the Sham-LID group were similar to those in the Sham group. CONCLUSIONS: Pretreatment with 2 mg/kg/hr but not 1 mg/kg/hr lidocaine attenuated sepsis-induced diaphragmatic dysfunction in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of lidocaine may be attributable, in part, to inhibition of lipid peroxidation in the diaphragm.
Anesthetics, Local↗
Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgery.
We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given 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 a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.
Administration, Oral↗
Identification and analysis of the polyhydroxyalkanoate-specific beta-ketothiolase and acetoacetyl coenzyme A reductase genes in the cyanobacterium Synechocystis sp. strain PCC6803.
Synechocystis sp. strain PCC6803 possesses a polyhydroxyalkanoate (PHA)-specific beta-ketothiolase encoded by phaA(Syn) and an acetoacetyl-coenzyme A (CoA) reductase encoded by phaB(Syn). A similarity search of the entire Synechocystis genome sequence identified a cluster of two putative open reading frames (ORFs) for these genes, slr1993 and slr1994. Sequence analysis showed that the ORFs encode proteins having 409 and 240 amino acids, respectively. The two ORFs are colinear and most probably coexpressed, as revealed by sequence analysis of the promoter regions. Heterologous transformation of Escherichia coli with the two genes and the PHA synthase of Synechocystis resulted in accumulation of PHAs that accounted for up to 12.3% of the cell dry weight under high-glucose growth conditions. Targeted disruption of the above gene cluster in Synechocystis eliminated the accumulation of PHAs. ORFs slr1993 and slr1994 thus encode the PHA-specific beta-ketothiolase and acetoacetyl-CoA reductase of Synechocystis and, together with the recently characterized PHA synthase genes in this organism (S. Hein, H. Tran, and A. Steinbüchel, Arch. Microbiol. 170:162-170, 1998), form the first complete PHA biosynthesis pathway known in cyanobacteria. Sequence alignment of all known short-chain-length PHA-specific acetoacetyl-CoA reductases also suggests an extended signature sequence, VTGXXXGIG, for this group of proteins. Phylogenetic analysis further places the origin of phaA(Syn) and phaB(Syn) in the gamma subdivision of the division Proteobacteria.
Acetyl-CoA C-Acyltransferase↗
The effects of clonidine and dexmedetomidine on human neutrophil functions.
UNLABELLED: Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2-agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils. IMPLICATIONS: Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation.
Adjuvants, Anesthesia↗
The effects of cimetidine, ranitidine, and famotidine on human neutrophil functions.
UNLABELLED: Neutrophil functions, which play an important role in the antibacterial host defense system, are inhibited by various anesthetics and surgical procedures. Histamine H2-receptor antagonists are perioperatively used as a prophylaxis against acid aspiration syndrome or stress ulceration. We examined the effect of cimetidine, ranitidine, and famotidine, at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil function using an in vitro system. The three H2-receptor antagonists did not impair neutrophils' chemotaxis or phagocytosis. Cimetidine and famotidine inhibited superoxide (O2-) and hydrogen peroxide (H2O2) production of the neutrophils in a dose-dependent manner, although the inhibitory effects were minimal. In contrast, ranitidine failed to change O2- or H2O2 production of neutrophils. The three H2-receptor antagonists did not scavenge these reactive oxygen species generated by the xanthine-xanthine oxidase system. The increase in intracellular calcium concentrations in neutrophils by a stimulant were dose-dependently attenuated with cimetidine or famotidine. This decreasing effect of the drugs on [Ca2+]i in neutrophils may represent one of mechanisms responsible for inhibition of reactive oxygen species generation. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that cimetidine and famotidine slightly reduced the O2- or H2O2 production of neutrophils in a dose-dependent manner, although ranitidine failed to do so. At least ranitidine does not seem to have any deleterious effect on neutrophil function, which is clearly an important consideration in its use in severely ill patients.
Calcium↗
Effects of exogenous surfactant on acute lung injury induced by intratracheal instillation of infant formula or human breast milk in rabbits.
BACKGROUND: An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. METHODS: The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. RESULTS: The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. CONCLUSION: Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.
Animals↗
Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits.
Group IIA secretory phospholipase A(2) (sPLA(2)) has been implicated in a variety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA(2) in this disorder remains unclear. The aim of the present investigation was to examine the role of this enzyme in a model of ALI induced by oleic acid (OA) in rabbits by testing human group IIA phospholipase A(2) (PLA(2)) inhibitor, S-5920/LY315920Na. Experimental groups consisted of a saline control group (n = 8), an OA control group (n = 10) infused intravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA + S-5920/LY315920Na (three different doses, n = 8, respectively). Infusion of OA provoked pulmonary hemorrhage and edema formation, protein leakage, and massive neutrophil infiltration, resulting in severe hypoxemia and impaired lung compliance. PLA(2) activity was detected in the bronchoalveolar lavage fluid (BALF), but not plasma, which correlated well with severity of lung injury in this model. Pretreatment with S-5920/LY315920Na diminished the OA-induced PLA(2) activity in the BALF and dose-dependently attenuated the previously described lung injury induced by OA, accompanied by protection against lung surfactant degradation and production of thromboxane A(2) (TXA(2)) and leukotriene B(4) (LTB(4)). S-5920/LY315920Na also inhibited the OA-induced production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA(2) appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA(2) inhibitor may be a promising agent for patients with acute respiratory distress syndrome (ARDS).
Acetates↗
Clonidine in paediatric anaesthesia.
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Adjuvants, Anesthesia↗
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↗
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↗
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↗
Propofol inhibits human neutrophil functions.
UNLABELLED: Neutrophils play important roles in the antibacterial host defense mechanism and in the pathogenesis of tissue injury. Propofol has been reported to impair the production of reactive oxygen species from neutrophils. We examined the effect of propofol (2,6-diisopropylphenol), at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil functions using an in vitro system. Propofol significantly inhibited chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, propofol suppressed these neutrophil functions, but it did not decrease ROS generation by the cell-free (xanthine-xanthine oxidase) system. Increase in intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine was dose-dependently attenuated by propofol. This decreasing effect on [Ca2+]i in neutrophils may represent one of the mechanisms responsible for the inhibition of neutrophil functions by propofol. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that at clinically relevant concentrations, propofol impaired neutrophil functions. Further studies may determine whether this impairment, observed in vitro, leads to clinical immunological suppression.
Anesthetics, General↗