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Biomedical subjects

Fumio Goto

Publications and source records attributed to Fumio Goto.

At least 55 records · Page 3Linked to original sources
PubMed2005

Cannabinoid antagonist AM 281 reduces mortality rate and neurologic dysfunction after cecal ligation and puncture in rats.

OBJECTIVES: The purpose of this study was to examine whether anandamide, an endogenous cannabinoid receptor ligand, is involved in the pathogenesis of septic encephalopathy. DESIGN: Prospective, controlled study. SUBJECTS: Male Wistar rats (7 wks old) were randomly divided into four groups as follows: group 1, control (0.5 mL of saline injected subcutaneously); group 2, sham (surgical abdominal incision and suturing were performed, but ligation and puncture of the cecum were omitted); group 3, cecal ligation and puncture (CLP); group 4, CLP + AM 281 ([N-morpholin-4-yl]-5-[2,4-yl]-5-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3-carboxamide) as the cannabinoid receptor antagonist (1 mg/kg intraperitoneally). INTERVENTIONS: Sepsis was induced by CLP under pentobarbital anesthesia (10 mg/kg intraperitoneally) with 1% isoflurane. A 2-Fr high-fidelity micromanometer catheter was inserted into the left ventricle via the right carotid artery to assess hemodynamics. Each of the rats was neurologically assessed at 30 mins and 12, 24, and 48 hrs after the treatment. The cytoplasmic levels of caspase-3 in the hippocampi were assayed before surgery and at 30 mins and 24 and 48 hrs after surgery using Western blotting techniques. To examine the effects of AM 281 on neurologic function and mortality rate, we set another control group treated solely with AM 281. Selective inducible nitric oxide synthase inhibitor, L-N6-(1-iminoethyl)-lysine (4 mg/kg), was injected intraperitoneally immediately after CLP to produce the CLP + L-N6-(1-iminoethyl)-lysine group to exclude the influence of depressed hemodynamics on neurologic impairment. MEASUREMENTS AND MAIN RESULTS: It was found that administration of AM 281 could prevent the hemodynamic changes induced by sepsis. Reflex responses, including the pinna, corneal, paw or tail flexion, and righting reflexes, and the escape response significantly decreased in the CLP and CLP + L-N6-(1-iminoethyl)-lysine groups at 48 hrs after the surgery. In contrast, no changes in these reflex responses were found between the CLP + AM 281 and control and sham groups. In addition, no effects of the administration of AM 281 on neurologic function and mortality rate in the control group were found. Tissue caspase-3 levels were elevated at 48 hrs after CLP in the CLP alone group (means +/- sd: control, 3.9 +/- 0.4; sham, 4.2 +/- 0.4; CLP, 7.1 +/- 1.0 [p < .01]; CLP + AM 281, 4.0 +/- 0.5 densitometric units). In addition, administration of AM 281 also decreased the mortality rate (p < .05). CONCLUSIONS: Administration of AM 281 prevented the hemodynamic changes and development of neurologic dysfunction occurring in association with septic shock, and could decrease the mortality rate in experimentally induced septic shock in rats. Although further studies are necessary to determine whether endogenous cannabinoids cause septic encephalopathy in rats directly or via their effects on systemic hemodynamics, the beneficial effects of AM 281 on these rats might have significant therapeutic implications in cases of septic encephalopathy.

Animals↗
PubMed2005

Influence of landiolol on the dose requirement of propofol for induction of anesthesia.

It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short-acting beta-1-adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control and landiolol group. Induction of anesthesia commenced 10 min after the infusion of 0.9% saline or landiolol, using a Diprifusor set to achieve propofol plasma concentration of 6.0 microg/mL. Induction of anesthesia was defined as the first lack of response to command. Propofol dose was 2.22+/- 0.21 mg/kg for the control group and 1.79+/- 0.28 mg/kg for the landiolol group (P<0.0001). The quantity of propofol required for the induction of anesthesia was reduced by the administration of landiolol.

Adult↗
PubMed2005

The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.

Antidepressants are often used to treat neuropathic pain. In the present study, we determined the antiallodynic effects of selective monoamine reuptake inhibitors in the spinal cord in a rat model of neuropathic pain. Mechanical allodynia was produced by tight ligation of the left L5 and L6 spinal nerves and determined by applying von Frey filaments to the left hindpaw. A serotonin noradrenaline reuptake inhibitor, milnacipran, a selective serotonin reuptake inhibitor, paroxetine, or a selective noradrenaline reuptake inhibitor, maprotiline, was administered intrathecally via a chronically implanted catheter. Milnacipran produced dose-dependent antiallodynic effects at doses between 3 microg and 100 microg. The effect lasted for 7 h after injection of 100 microg (P < 0.05). The antiallodynic effect of 30 microg of milnacipran was attenuated by intrathecal coadministration of 30 microg of yohimbine, an alpha(2)-adrenoceptor antagonist, 30 microg of methysergide, a serotonin receptor antagonist, or 30 microg of atropine, a muscarinic receptor antagonist (P < 0.01, respectively). Intraperitoneal administration of milnacipran had no antiallodynic effects at doses of 3 to 30 mg/kg. Antiallodynic effects were not produced by intrathecal administration of paroxetine (10 to 100 microg) or maprotiline (10 to 100 microg). These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain.

Adrenergic Uptake Inhibitors↗
PubMed2005

[Successful management of a man with fulminant myocarditis using percutaneous cardiopulmonary support].

Fulminant myocarditis is a fetal disease characterized by a distinct viral prodrome, sudden onset of severe hemodynamic compromise, and marked myocardial inflammation. One possible therapy to improve the poor prognosis of such patients may be the implantation of circulatory support systems that allow myocardial recovery. We report here successful management of a patient with fulminant myocarditis using percutaneous cardiopulmonary support (PCPS), intra-aortic balloon pump (IABP), and continuous hemodiafiltration (CHDF). A 37-year-old Japanese man suddenly experienced cardiopulmonary dysfunction shortly after general fatigue, and was diagnosed as having fulminant myocarditis. PCPS was immediately initiated because catecholamine infusion and IABP were not enough to support circulation. Although severe dyskinesis was observed on his admission, cardiac function recovered twelve days after PCPS initiation with ejection fraction from 16% to 73%. Renal and hepatic failure also recovered with the improvement of cardiac function. We describe our clinical experiences in cardiogenic shock after acute fulminant myocarditis and discuss therapeutic guidelines for the use of PCPS, with its management and complications.

Adult↗
PubMed2005

[Preoperative evaluation of hemodynamics using indocyanine green clearance meter in patients with peritonitis from gastrointestinal perforation].

BACKGROUND: Since patients with perforated peritonitis often present hemodynamic instability, preoperative evaluation of hemodynamics is important for anesthesiologists. Indocyanine green (ICG) can be used to measure cardiac output (C.O.), blood volume (B.V.) and hepatic function. Previous studies have reported that the average elimination rate constant of ICG (KICG) might be reduced in critically ill patients. This study was therefore conducted to investigate the relationship between acute physiology and chronic health evaluation (APACHE) II score and KICG value, cardiac output, and blood volume in patients scheduled for emergency surgery. METHODS: After obtaining informed consent hemodynamics of thirteen patients undergoing emergency surgery for perforated peritonitis were measured by in vivo ICG clearance technique. After induction of anesthesia, ICG elimination rate was measured following intravenous administration of ICG (20 mg) with a DDG analyzer (DDG-2001) using a nose probe for pulse dye densitometry. All measurements were performed prior to surgery. The value of C.O./B.V. was used as an indicator of cardiac function. The severity of each patient's illness was also assessed using the APACHE II scoring system at the start of operation. RESULTS: There was a negative correlation between APACHE II score and KICG (KICG = 0.34 0.01 x APACHE II score, r = -0.56). In addition, there was a positive correlation between APACHE II score and C.O./B.V. (C.O./B.V. = 1.10 + 0.05 x APACHE II score, r = 0.79). CONCLUSIONS: Patients with high APACHE II score may show low hepatic blood flow and high cardiac output compared with blood volume. ICG clearance rate might be useful for preoperative evaluation of hemodynamics in patients with perforated peritonitis.

APACHE↗
PubMed2005

[Perioperative management of patients with Brugada syndrome].

In 1992, Brugada et al. first reported eight cases of ventricular fibrillation, in which ST-segment abnormalities in leads V1 through V3 along with T-wave inversion, and complete or incomplete right bundle branch block were observed on the standard 12-leads ECG. Since then, this syndrome has been widely recognized as one of important diseases that can produce sudden death in middle aged healthy males. The ECG morphology of Brugada syndrome is believed to be caused by either an accentuation of the notch in the early phase of the action potential or loss of the action potential dome in the epicardium. Mechanisms of ventricular fibrillation in this syndrome are still unclear, but thought to be phase II re-entry caused by dispersion of the action potentials. It has been shown that mutations of the human cardiac Na+ channel gene (SCN5A) underlie multiple cardiac diseases including Brugada syndrome. In fact, single amino acid substitution within the SCN5A coding region can evoke a cardiac rhythm behavior. In this review, we will focus on recent progress of basic and clinical research of Brugada syndrome and perioperative management of this syndrome.

Bundle-Branch Block↗
PubMed2004

Volatile anesthetics inhibit calcitonin gene-related peptide receptor-mediated responses in pithed rats and human neuroblastoma cells.

Calcitonin gene-related peptide (CGRP) has a potent vasodilatory effect that is mediated by specific receptors predominantly coupled to the activation of adenylate cyclase. The effects of volatile anesthetics on CGRP-induced vasodilation are unclear. We studied the effects of sevoflurane and isoflurane on CGRP-induced vasodilation in pithed rats and CGRP receptor-mediated responses in SK-N-MC cells, which are used as a model system to study the CGRP receptor and its downstream pathways. Male Wistar rats were pithed by inserting a stainless steel rod into the spinal cord. Mean arterial pressure (MAP) and cardiac output were maintained at approximately 100 mmHg and 50 ml.min(-1), respectively, with continuous infusion of noradrenaline. After 30 min of inhalation of anesthetics, CGRP (0.1, 0.3, 1.0, and 3.0 microg/kg) was administered intravenously. In SK-N-MC cells, CGRP-, forskolin-, or cholera toxin-induced cAMP production was measured with or without anesthetics using radioimmunoassays. CGRP receptor binding density and affinity for the agonist were determined with (2-[125I]iodohystidyl10) CGRP with or without the anesthetics. Sevoflurane (4%) and isoflurane (2%) significantly inhibited the decrease in MAP and systemic vascular resistance. Furthermore, both anesthetics significantly inhibited CGRP- but not forskolin-induced cAMP production. Sevoflurane (4%) and isoflurane (4%) significantly inhibited cholera toxin-induced cAMP production. Both anesthetics did not affect ligand binding. These data suggest that sevoflurane and isoflurane inhibit CGRP-induced vasodilation at the site between the CGRP receptor and adenylate cyclase activation. The inhibitory site of volatile anesthetics on the CGRP receptor-mediated response involves Gs protein.

Anesthetics, Inhalation↗
PubMed2004

Oral etodolac, a COX-2 inhibitor, reduces postoperative pain immediately after fast-track cardiac surgery.

PURPOSE: The present study was designed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor, etodolac, on postoperative pain after fast-track cardiac surgery, and to examine the changes in plasma etodolac concentration after oral administration. METHODS: Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomly assigned preoperatively in a double-blind fashion to receive either vehicle ( n = 15) or etodolac 400 mg ( n = 15) via a gastric tube at the end of the surgery. Standardized fast-track cardiac anesthesia was used. In both groups, postoperative pain was treated with buprenorphine suppository. Visual analogue pain scores (VASs) were recorded immediately after extubation and at 24 h after surgery. Plasma etodolac concentration was measured at 1, 2, and 6 h after administration ( n = 8). RESULTS: No difference was detected in time to extubation between the etodolac group (209 +/- 85 min, mean +/- SD) and the vehicle group (207 +/- 98 min). VASs were significantly lower in the etodolac (2.3 +/- 2.1) vs the vehicle group (5.8 +/- 2.0) immediately after extubation ( P = 0.009), but no difference was detected in pain scores at 24 h after surgery, or in the amount of buprenorphine administered in the intensive care unit (ICU), or in the incidence of side effects. Plasma etodolac concentration was within the pharmaceutically recommended range at 1 h, 2 h, and 6 h after administration. CONCLUSION: The oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects.

Administration, Oral↗
PubMed2004

Acute thrombus formation in the left atrium after the termination of warfarin.

We report a case of acute thrombosis formation in the left atrium 3 days after the discontinuation of warfarin therapy prior to mitral valve replacement in a patient with mitral stenosis and atrial fibrillation. A 58-year-old Asian female patient was scheduled for mitral valve replacement for mitral stenosis. She had received warfarin therapy every day for 2 years. Warfarin therapy was discontinued 3 days before surgery. Using transesophageal echocardiography (TEE), we confirmed that there was no thromboembolism at the left atrium 10 days before surgery. No replacement anticoagulant therapy, such as heparin, was given after the discontinuation of warfarin. After the induction of anesthesia, a TEE probe was inserted through the esophagus to monitor left ventricular function. We found two thrombi (35 mm and 40 mm in diameter) in the left atrium. This case shows that discontinuation of warfarin therapy within a few days before operation carries a risk of thromboembolism formation.

Acute Disease↗
PubMed2004

Jugular venous oxygen saturation during mild hypothermic versus normothermic cardiopulmonary bypass in elderly patients.

PURPOSE: Age is known to be a major risk factor for adverse postoperative cognitive dysfunction after cardiac surgery. We conducted this study to determine if jugular venous oxygen saturation (SjvO(2)) differed during mild hypothermic (32 degrees C) and normothermic cardiopulmonary bypass (CPB) in elderly patients. METHODS: Sixty patients aged over 70 years who underwent elective coronary artery bypass grafting were randomly divided into two groups. Group 1 ( n = 30) underwent normothermic CPB (>35 degrees C) and group 2 ( n = 30) underwent mild hypothermic CPB (32 degrees C). For the continuous monitoring of SjvO(2), a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb after the induction of anesthesia. Hemodynamic parameters, and arterial and jugular venous blood gases were measured at seven time points. RESULTS: The SjvO(2) in the normothermic group was lower at the onset of CPB and 20 min after the onset, than from the time of induction of anesthesia until the start of surgery (period 1), the respective SjvO(2) values being 50.3% +/- 1.0%, 50.1% +/- 1.6%, and 59.5% +/- 1.9% ( P < 0.05). However, in the mild hypothermic group there were no changes in the SjvO(2) value throughout the study. The cerebral desaturation time (when the SjvO(2) value was <50%) and the ratio of the cerebral desaturation time to the total CPB time in the normothermic group differed significantly from those in the hypothermic group, being 19 +/- 11 min and 17% +/- 10%, and 9 +/- 3 min and 8% +/- 4%, respectively ( P < 0.05). CONCLUSIONS: The SjvO(2) value was better during mild hypothermic CPB than during normothermic CPB in elderly patients.

Aged↗
PubMed2004

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding.

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.

Adult↗
PubMed2004

Cerebrovascular carbon dioxide reactivity with propofol anesthesia in patients with previous stroke.

STUDY OBJECTIVE: To examine whether patients with previous stroke have impaired cerebrovascular carbon dioxide (CO2) reactivity when receiving propofol anesthesia. DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENTS: 34 consecutive patients, 17 of whom had previous stroke and were scheduled for elective cardiac surgery, and 17 control age-matched patients without previous stroke who were also scheduled for cardiac surgery. INTERVENTIONS: Anesthesia was induced and a 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window. Mean blood flow velocity of the middle cerebral artery (Vmca) was measured continuously. MEASUREMENTS: After establishing baseline Vmca, arterial blood gases and cardiovascular hemodynamic values, partial pressure of end-tidal CO2 (PETCO2) was increased by changing the ventilatory frequency by 2 to 5 breaths/min. The measurements were repeated when PETCO2 increased and remained stable for 5 to 10 minutes. MAIN RESULTS: Values for absolute CO2 reactivity in the control patients and in those with previous stroke were 2.6 +/- 0.5 and 2.9 +/- 0.7 cm/sec/mmHg, respectively, a nonsignificant difference in these values. Values for relative CO2 reactivity in control patients and in patients with previous stroke were 6.4 +/- 1.4 and 6.1 +/- 1.4%/mmHg, respectively, with no significant difference noted. CONCLUSIONS: Cerebrovascular CO2 reactivity in patients with previous stroke is normal during propofol anesthesia.

Anesthetics, Intravenous↗
PubMed2004

Antiallodynic effects of intrathecally administered 5-HT(2C) receptor agonists in rats with nerve injury.

Intrathecal administration of serotonin type 2 (5-HT(2)) receptor agonists, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), produces antiallodynic effects in a rat model of neuropathic pain. In the present study, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT(2C) receptors. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and was measured by applying von Frey filaments to the left hindpaw. Administration of the 5-HT(2C) receptor agonist, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 3-100 microg), 1-(m-chlorophenyl)-piperazine (mCPP; 30-300 microg), or 1-(m-trifluoromethylphenyl)-piperazine (TFMPP; 30-300 microg), produced antiallodynic effects in a dose-dependent manner with no associated motor weakness. The ED(50) values of MK212, mCPP, and TFMPP were 39.2, 119.9, and 191.9 microg, respectively. Intrathecal pretreatment with the selective 5-HT(2C) receptor antagonist RS-102221 (30 microg) diminished the effects of the highest doses of 5-HT(2C) receptor agonists. The preferential 5-HT(2A) receptor antagonist ketanserin (30 microg) did not reverse the effects. In contrast to 5-HT(2C) receptor agonists, the antiallodynic effects of intrathecally administered alpha-m-5-HT (30 microg) and DOI (100 microg) were reversed by ketanserin, but not by RS-102221. These results indicate that 5-HT(2C) receptors have a role in spinal inhibition of neuropathic pain, and the effects produced by intrathecal administration of 5-HT(2C) receptor agonists are mediated by a mechanism different from that of alpha-m-5-HT or DOI, which seem to produce their effects through 5-HT(2A) receptors.

Amphetamines↗
PubMed2004

Intracellular calcium increases in growth cones exposed to tetracaine.

UNLABELLED: Neurotoxicity of local anesthetics has been reported for both matured and growing neurons. In the present study, we examined if tetracaine increases Ca(2+) concentration during growth cone collapse. Intracellular Ca(2+) concentration was measured by fura 2/AM after exposure to tetracaine. Tetracaine (1-2 mM) induced increases in intra-growth cone Ca(2+) concentration (P < 0.01). The Ca(2+) hot spot was expanded into the neurite from the periphery towards the cell body. When tetracaine was applied to growth cones in Ca(2+) free media, the increase was minor. However, tetracaine induced growth cone collapse even in the culture media, which did not contain Ca(2+). Ni(2+) (100 microM; a general Ca(2+) channel inhibitor) and BAPTA-AM (5 microM; intracellular Ca(2+) chelator) could not inhibit growth cone collapse induced by 1-2 mM tetracaine. Tetracaine (>1 mM) induces collapse and Ca(2+) increase at growth cones simultaneously; however, these two phenomena might be provoked independently. IMPLICATIONS: Tetracaine induced intracellular Ca(2+) increases and growth cone collapse in dorsal root ganglion neurons. The Ca(2+) hot spot in the growth cone expanded into the neurite from periphery towards the cell body.

Anesthetics, Local↗
PubMed2004

Selective inducible nitric oxide inhibition can restore hemodynamics, but does not improve neurological dysfunction in experimentally-induced septic shock in rats.

In this study, we evaluated the time course of changes in inducible nitric oxide synthase (iNOS) in the brain by using the rat model of sepsis induced by cecal ligation and puncture (CLP) and examined whether selective iNOS inhibition can prevent the hemodynamic and neurological changes induced by sepsis. Male Wistar rats were randomly divided into four groups: control, sham, CLP, and CLP + the selective iNOS inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL). Septic shock was induced in the rats by CLP under pentobarbital anesthesia, and then we measured hemodynamic variables, neurological indicators, blood gases, plasma levels of nitrate/nitrite (an indicator of the biosynthesis of NO), and brain iNOS activity and nitrotyrosine levels after 1, 6, 12, and 24 h. Plasma nitrite was increased at 12 and 24 h in the CLP group. The activity of iNOS in the brain was increased at 12 and 24 h after CLP (at 12 h: control, 0.3 +/- 0.05; sham, 0.3 +/- 0.1; CLP, 1.3 +/- 0.08*; CLP + L-NIL, 0.33 +/- 0.1 fmol x mg(-1) x min(-1); at 24 h: control, 0.27 +/- 0.08; sham, 0.31 +/- 0.1; CLP, 1.0 +/- 0.3*; CLP + L-NIL, 0.34 +/- 0.1 fmol x mg(-1) x min(-1); mean +/- SD; *P < 0.05). Brain nitrotyrosine was increased at 24 h after CLP (at 24 h: control, 6.7 +/- 0.4; sham, 6.7 +/- 0.5; CLP, 11.2 +/- 2.8*; CLP + L-NIL, 7.52 +/- 0.5 densitometric units; means +/- SD; *P < 0.01). In contrast, in both the CLP and CLP + L-NIL groups, the consciousness reflex was significantly decreased at 24 h after CLP. Selective iNOS inhibition restored the hemodynamic changes induced by sepsis but could not improve neurological dysfunction.

Animals↗
PubMed2004

Pilot study of the effects of ONO-5046 in patients with acute respiratory distress syndrome.

Evidence has linked neutrophil elastase to acute respiratory distress syndrome (ARDS), suggesting that inhibiting the activity of this enzyme could prevent the development and progression of ARDS. However, few clinical trials have examined this notion. We therefore examined the effects of ONO-5046 (sivelestat, a specific inhibitor of neutrophil elastase; sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylaminobenzoyl]amino-acetate tetrahydrate]) in a randomized, double-blinded trial in patients with ARDS. We randomly assigned 24 patients with ARDS to groups that received conventional therapy without or with sivelestat (0.2 mg. kg(-1). h(-1)) for 14 days. The variables of interest associated with clinical outcome were the duration of mechanical ventilation; changes in oxygenation from baseline; changes in cytokine levels from baseline; number of patients alive at 30 days who did not need mechanical ventilation; and mortality rate. The length of intensive care unit stay, number of ventilation days, and mortality rates did not statistically differ between groups. ARDS was more persistent in the control than in the sivelestat group (control, 19.5 +/- 7.4 days; sivelestat, 13.5 +/- 5.9 days; P = 0.039). Neutrophil elastase activity significantly differed between groups at 72 h after treatment. Levels of interleukin-6 were lower in the sivelestat group than in the controls at 24, 48, and 72 h after treatment. ONO-5046 apparently did not affect survival or the duration of mechanical ventilation.

Adult↗