Biomedical subjects

M Beste

Publications and source records attributed to M Beste.

11 recordsLinked to original sources

PubMed2000

Lidocaine inhalation for local anaesthesia and attenuation of bronchial hyper-reactivity with least airway irritation. Effect of three different dose regimens.

The inhalation of lidocaine attenuates bronchial hyper-reactivity but also causes airway irritation. However, how lidocaine dose and plasma concentration influence relationships are unknown. Accordingly, we evaluated the effects of three concentrations of lidocaine (1, 4, and 10%, total dose of 0.5, 2.0, and 5.0 mg kg-1, respectively) vs. placebo in 15 mild asthmatic patients, selected by their response to a histamine challenge (decrease in FEV1 > 20% to less than 18 mg mL-1 of histamine [PC20]). Baseline lung function, histamine-induced bronchoconstriction, topical anaesthesia, and lidocaine plasma concentrations were obtained. FEV1 following lidocaine inhalation showed the greatest decrease for the highest dose (from 3.79 +/- 0.15-3.60 +/- 0.15; P = 0.0012). Lidocaine inhalation increased baseline PC20 (6.1 +/- 1.3 mg mL-1) significantly (to 11.8 +/- 3.1, 16.1 +/- 3.3, and 18.3 +/- 4.5 mg mL-1, respectively) with no difference between the two highest doses. The duration of local anaesthesia was not significantly different between lidocaine concentrations of 4% and 10%. Thus, lidocaine inhalation, with increasing concentrations of the aerosolized solution, increases initial bronchoconstriction while significant attenuation of bronchial hyper-reactivity is not further enhanced with increasing concentrations from 4 to 10%. Plasma concentrations of lidocaine were always far below the toxic threshold. In conclusion, when local anaesthesia of the airways is required a lidocaine dose of 2.0 mg kg-1 as a 4% solution can be recommended for local anaesthesia and attenuation of bronchial hyper-reactivity with the least airway irritation.

Adult↗

PubMed2000

Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction.

BACKGROUND: Lidocaine inhalation, in subjects with bronchial hyperreactivity, attenuates evoked bronchoconstriction but also irritates airways. Whether salbutamol pretreatment can mitigate airway irritation and whether combined treatment offers more protection than treatment with either drug alone is unknown. Therefore, we evaluated the effects of the inhalation of lidocaine, salbutamol, lidocaine and salbutamol combined, and placebo on an inhalational histamine challenge. METHODS: Fifteen patients with mild asthma were selected by a screening procedure (ie, a provocative concentration of a substance [histamine aerosol of < 18 mg/mL] causing a 20% fall in FEV(1) [PC(20)]). On 4 different days after pretreatment with the inhalation of lidocaine (5 mg/kg), inhalation of salbutamol (1.5 mg), combined treatment, or placebo, the histamine challenge was repeated. RESULTS: The baseline FEV(1) after lidocaine inhalation but prior to the histamine challenge decreased by > 5% in 7 of 15 volunteers, with a mean (+/- SD) decrease from 3.82 +/- 0.90 to 3.54 +/- 0.86 L (p = 0.0054). The baseline PC(20) for histamine was 6.4 +/- 4.3 mg/mL. Both lidocaine and salbutamol inhalation significantly increased PC(20) more than twofold (14.9 +/- 13.7 and 16.8 +/- 10.9 mg/mL, respectively; p = 0, 0007) at a lidocaine plasma concentration of 0.7 +/- 0.3 microg/mL. Combined treatment quadrupled the PC(20) to 29.7 +/- 20.3 mg/mL (vs lidocaine, p = 0.002; vs salbutamol, p = 0.003). CONCLUSIONS: Thus, histamine-evoked bronchoconstriction, as a model of reflex bronchoconstriction, can be significantly attenuated by salbutamol or lidocaine inhalation. However, lidocaine inhalation causes significant initial bronchoconstriction. The combined inhalation of salbutamol and lidocaine prevents the initial bronchoconstriction observed with lidocaine alone and offers even more protection to a histamine challenge than either lidocaine or salbutamol alone. Therefore, the combined inhalation of lidocaine and salbutamol can be recommended to mitigate bronchoconstriction when airway instrumentation is required.

Administration, Inhalation↗

PubMed1999

Both intravenous and inhaled lidocaine attenuate reflex bronchoconstriction but at different plasma concentrations.

Intravenous lidocaine can attenuate bronchial hyperreactivity. However, lidocaine inhalation might yield the same or better results at higher airway and lower lidocaine plasma concentrations. Therefore, we tested in awake volunteers with bronchial hyperreactivity the effect of lidocaine on histamine-induced bronchoconstriction administered either intravenously or as an aerosol. After approval of the local ethics committee, 15 volunteers were enrolled in this placebo-controlled, double-blinded, randomized study. Volunteers were selected by showing a decrease in FEV1 greater than 20% of baseline (PC20) in response to histamine inhalation. On three different days the challenge was repeated after pretreatment with either intravenous lidocaine, inhaled lidocaine, or placebo. Blood samples for determination of lidocaine plasma concentration were drawn. Comparisons were made using the Friedman and Wilcoxon signed-rank tests. Baseline PC20 was 6.4 +/- 1.1 mg. ml-1. Both inhalation of lidocaine and intravenous administration significantly increased PC20 to 14.8 +/- 3.5 mg. ml-1 and 14.2 +/- 2. 5 mg. ml-1, respectively (p = 0.0007). Peak plasma lidocaine concentrations at the end of challenges were 0.7 +/- 0.1 microg. ml-1 (inhaled) and 2.2 +/- 0.1 microg. ml-1 (i.v.). However, 7 of 15 subjects showed an initial decrease of FEV1 greater than 5% following lidocaine inhalation. While both intravenous as well as inhaled lidocaine attenuate reflex bronchoconstriction significantly, lidocaine plasma concentrations are significantly lower after inhalation. However, the high incidence of initial bronchoconstriction to lidocaine inhalation may limit its use in patients with asthma and thus offers therapeutic advantages for intravenous lidocaine.

Administration, Inhalation↗

PubMed1998

Combined intravenous lidocaine and inhaled salbutamol protect against bronchial hyperreactivity more effectively than lidocaine or salbutamol alone.

BACKGROUND: Airway instrumentation in persons with asthma is linked to the risk of life-threatening bronchospasm. To attenuate the response to airway irritation, intravenous lidocaine is recommended (based on animal experiments) and mitigates the response to histamine inhalation in asthmatic volunteers. However, the effects of lidocaine have not been compared with standard prophylaxis with beta-sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol, combined treatment, and placebo control were tested in awake volunteers with bronchial hyperreactivity. METHODS: After approval from the local ethics committee, 15 persons, who were selected because they showed a decrease in forced expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a placebo-controlled, double-blind, and randomized study. The challenge was repeated on four different days and the volunteers were pretreated with either intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also measured. Statistical analyses included the Friedman test and Wilcoxon's rank sum. RESULTS: The baseline PC20 was 6.4 +/- 4.3 mg/ml. Intravenous lidocaine and salbutamol aerosol both significantly increased the histamine threshold to 14.2 +/- 9.5 mg/ml and 16.8 +/- 10.9 mg/ml, respectively (mean +/- SD). However, the combination of lidocaine and salbutamol significantly increased the PC20 even further to 30.7 +/- 15.7 mg/ml than did salbutamol or lidocaine alone. CONCLUSIONS: In volunteers with bronchial hyperreactivity, both lidocaine and salbutamol attenuate the response to an inhalational histamine challenge, and their combined administration has much greater effects than does either drug alone. Accordingly, pretreatment of patients with bronchial hyperreactivity with both beta-mimetic aerosol and intravenous lidocaine is recommended before airway irritation.

Administration, Inhalation↗

PubMed1997

Value of an extended monoethylglycinexylidide formation test and other dynamic liver function tests in liver transplant donors.

Measuring monoethylglycinexylidide (MEGX) formation after intravenous administration of lidocaine in potential organ donors (MEGX test) has been advocated as a useful test to select donor livers for transplantation, but some groups have demonstrated a low test efficacy. We, therefore, investigated the value of an extended MEGX formation test and the value of other dynamic liver function tests, in selecting suitable human donor livers. In 51 human multi-organ donors, we measured elimination of galactose, indocyanine green, and lidocaine, as well as formation of MEGX, at 15, 30, and 60 min after administration of the test substances. In the early postoperative period, the function of the transplanted liver was then classified as good or poor, as defined by a prothrombin time above or below 65% by day 4 and fibrinogen concentration above or below 300 mg/dl by day 7. Donor characteristics and preservation modalities were very similar between the two groups. Galactose, indocyanine green, and lidocaine metabolism failed to predict good or poor graft function in the early postoperative period. MEGX serum concentrations, however, were significantly higher in the group of donors whose organs functioned well in the recipients, as compared with donors whose organs functioned poorly in the recipients. This was true for MEGX concentrations at 15 min (117+/-9 vs. 90+/-9 ng/ml; P=0.03), 30 min (108+/-8 vs. 86+/-8 ng/ml; P=0.04), and 60 min (100+/-6 vs. 73+/-5 ng/ml; P=0.006). Extending the MEGX formation test from 15 to 60 min improved test efficacy. Maximal MEGX concentration in 9 or up to 12 consecutive blood samples, drawn between 3 and 120 min after lidocaine infusion, was also significantly higher in donors whose organs functioned well, than in donors whose organs functioned poorly (129+/-10 vs. 101+/-10 ng/ml; P=0.03). Although the groups with good and poor organ function differed significantly with respect to their MEGX serum concentrations, and although efficacy of the MEGX test was improved by extending the test from 15 to 60 min, the overlap in individual MEGX serum concentrations was still so wide that it is virtually impossible to predict early graft function only on the basis of the MEGX test in the donor. Therefore, the MEGX test, although of potential scientific interest, does not predict early graft function with an accuracy necessary for clinical use.

Adult↗

PubMed1997

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long-term follow-up.

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

Adult↗

PubMed1997

Serial quantitative liver function tests in patients with primary biliary cirrhosis: a prospective long-term study.

Primary biliary cirrhosis (PBC) is a rare chronic cholestatic disorder of unknown origin that can now be treated effectively with ursodeoxycholic acid (UDCA). The clinical course of PBC is very variable, but a significant proportion of patients eventually die or undergo liver transplantation. In this single-center prospective long-term study, we analyzed the effect of UDCA therapy (10 mg/kg b.w./day) on conventional liver function tests and we also investigated whether serial quantitative liver function tests are useful in the clinical management of patients with PBC. Fifteen patients, most of them in an early disease stage, were followed up for either 4 (n = 7) or 5 (n = 8) years. In addition to regular conventional liver function tests, every 12 months quantitative liver function tests were performed. Thus we measured galactose elimination capacity, indocyanine green half-life and lidocaine half-life. Quantitative liver function tests were also performed once in healthy volunteers. Treatment with UDCA significantly improved conventional liver function tests, and this effect was maintained for several years (values in U/l before therapy and 4 years after therapy: AP = 1,346 +/- 317 vs. 516 +/- 93; gammaGT 378 +/- 80 vs. 144 +/- 30; LAP 122 +/- 10 vs. 71 +/- 9; AST 61 +/- 19 vs. 34 +/- 12; ALT 90 +/- 19 vs. 68 +/- 35; GLDH 14.3 +/- 1.9 vs. 8.2 +/- 1.9). Quantitative liver function tests were not significantly different between healthy volunteers and patients (GEC 6.8 +/- 0.3 vs. 7.0 +/- 0.3 mg/kg x min; ICG half-life 4.2 +/- 0.4 vs. 3.7 +/- 0.3 min; lidocaine half-life 75 +/- 8 vs. 79 +/- 6 min). In the patients, results of quantitative liver function tests (GEC, ICG and lidocaine half-lives) were not affected by UDCA therapy and remained constant over time. In the 1 patient who was transplanted, serial quantitative liver function tests did not indicate deteriorating liver function earlier than the patient's progressive symptoms or conventional liver function tests. Thus UDCA therapy markedly improved conventional liver function tests in patients with PBC, and this effect was maintained for at least 4-5 years. Possibly due to the fact that most of the patients were in an early disease stage, serial quantitative liver function tests provided little additional information that was relevant for planning therapy in the individual patient.

Adult↗

PubMed1996

Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ).

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Adult↗

PubMed1996

[Primary sclerosing cholangitis: conventional and quantitative liver function tests during long-term therapy with ursodeoxycholic acid].

Primary sclerosing cholangitis, a chronic cholestatic liver disease, frequently leads to an impairment of liver function. In nine men and two women, aged 23 to 57 years, we prospectively studied for three to six years the effect of treatment with ursodeoxycholic acid (UDCA) on liver function. 10 mg UDCA/kg bw significantly reduced serum activities of AP, gamma GT, AST and ALT for several years. After three years of treatment, however, serum concentration of bilirubin was higher than before therapy in eight out of eleven patients (1.8 +/- 0.8 versus 0.9 +/- 0.1 mg/dl; p = 0.01). Likewise, serum concentration of bilirubin was higher in eight out of nine patients after four years of treatment (1.3 +/- 0.3 versus 0.9 +/- 0.1 mg/dl; p = 0.03). In most cases, however, the increase was discrete. Parameters of synthetic liver function (coagulation, serum protein concentration, serum activity of cholinesterase) remained constant in the observation time. Quantitative liver function tests (galactose elimination capacity and indocyanine green half-life) also showed little variation in the observation time. We conclude that UDCA treatment significantly improves serum activities of liver enzymes for several years. Nevertheless, serum bilirubin concentration, believed to be of prognostic value in patients with PSC, seems to rise slowly over time. Serial determinations of galactose elimination capacity and indocyanine green halflife are not superior to conventional liver function tests in the timing of liver transplantation in the individual patient.

Adult↗

PubMed1993

[Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis].

Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic-capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association.

Endothelins↗

PubMed1991

Influence of the calcium antagonist nitrendipine on the hepatotoxic effect of cyclosporine A.

Calcium antagonists have a protective effect on different forms of nephrotoxicity due to cyclosporine A (CsA). The objective of the present study was to examine the influence of a calcium antagonist on the liver function in CsA-treated patients after kidney transplants. Different quantitative liver function tests were performed in six patients before and 3 months after administration of the calcium antagonist nitrendipine. Indocyanine green clearance (ICG-Cl) as a marker for hepatic blood flow and excretion showed a significant increase under nitrendipine. In addition, there was an improvement of the galactose elimination capacity. Although nitrendipine and lidocaine are both metabolized by the cytochrome P system, there was no reduction in lidocaine clearance. These results suggest an improvement of liver function under nitrendipine. Whether these findings alone are the expression of an improved liver blood flow or whether there is an additional hepatoprotective characteristic of the calcium antagonist nitrendipine cannot be determined.

Cyclosporine↗