Comparison of terbutaline and atosiban as tocolytic agents in intrauterine repair of myelomeningocele: a retrospective cohort study.

BACKGROUND: Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as ß2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair. METHODS: Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery. RESULTS: Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL-1 vs. 13.06 ± 6.35 mg.dL-1, for atosiban, p = 0.001) levels. CONCLUSIONS: Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair.

Serotonin Syndrome Following Terbutaline Administration in a Heart Transplant Patient on Multiple Inotropic Agents: A Case Report.

The significance of serotonin syndrome due to drug-drug interactions has emerged as a prominent consideration when the effects of polypharmacy are reviewed. The emergence of the selective serotonin reuptake inhibitors has most likely fueled the increased reporting of serotonin syndrome in the literature, leading to increased awareness of this phenomenon. However, their presence is not necessarily inclusive to a case and the utilization of agents precipitating an occurrence may be unavoidable. We report a case of serotonin syndrome occurring in a heart transplant patient without the presence of any of the usual suspect agents involved. In the postoperative course, the patient developed cardiogenic shock with vasoplegia requiring continuation of inotropic therapy along with vasopressor support of epinephrine. Oral terbutaline was begun for hemodynamic improvement. The patient's tenuous mental status rapidly deteriorated after addition of the terbutaline, with symptoms consistent with serotonin syndrome. Administration of cyproheptadine, a known reversal agent for serotonin toxicity, rapidly alleviated the adverse symptoms.

ß2-Agonist Induces Net Leg Glucose Uptake and Free Fatty Acid Release at Rest but Not During Exercise in Young Men.

Objective: The role of selective ß2-adrenergic stimulation in regulation of leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in humans. The objective of this study was to investigate ß2-adrenergic effects on net leg glucose uptake and clearance, as well as FFA balance at rest and during exercise. Design: The study was a randomized, placebo-controlled crossover trial where 10 healthy men received either infusion of ß2-agonist terbutaline (0.2 to 0.4 mg) or placebo. Net leg glucose uptake and clearance and FFA balance were determined at rest and during 8 minutes of knee extensor exercise using Fick's principle. Vastus lateralis muscle biopsies were collected at rest and at cessation of exercise. The primary outcome measure was net leg glucose uptake. Results: At rest, net leg glucose uptake and clearance were 0.35 (±0.16) mmol/min and 41 (±17) mL/min (mean ± 95% CI) higher (P < 0.001) for terbutaline than placebo, corresponding to increases of 84% and 70%. During exercise, no treatment differences were observed in net leg glucose uptake, whereas clearance was 101 (±86) mL/min lower (P < 0.05) for terbutaline than placebo. At rest, terbutaline induced a net leg FFA release of 21 (±14) µmol/min, being different from placebo (P = 0.04). During exercise, net leg FFA uptake was not different between the treatments. Conclusions: These observations indicate that ß2-agonist alters net leg glucose uptake and clearance, as well as FFA balance in humans, which is associated with myocellular ß2-adrenergic and insulin-dependent signaling. Furthermore, the study shows that exercise confounds the ß2-adrenergic effect on net leg glucose uptake and FFA balance.

Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together.

Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.

Assessment of new-generation high-power electronic nicotine delivery system as thermal aerosol generation device for inhaled bronchodilators.

PURPOSE: A need remains for alternative devices for aerosol drug delivery that are low cost, convenient and easy to use for the patient, but also capable of producing small-sized aerosol particles. This study investigated the potential of recent high power electronic nicotine delivery systems (ENDS) as aerosol generation devices for inhaled bronchodilators. METHODS: The particle size distribution was measured using a cascade impactor. The delivery of terbutaline sulfate, a current bronchodilator used for asthma or COPD therapy by inhalation, was studied. This drug was quantified by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The particle size distribution in terms of mass frequency (in two ways, gravimetrically and quantitatively through drug assay on each stage) and the terbutaline sulfate concentration in the aerosol were elucidated. The mass median aerodynamic diameter (MMAD) and the drug delivery rose when the power level increased, to reach 5.6±0.4µg/puff with a MMAD of 0.78±0.03µm at 25W. CONCLUSION: New generation high-power ENDS are very efficient to generate carrier-droplets in the submicron range containing drug molecules with a constant drug concentration whatever the size-fractions. ENDS appear to be highly patient-adaptive.

Two-week inhalation of budesonide increases muscle Na,K ATPase content but not endurance in response to terbutaline in men.

While chronic systemic administration of glucocorticoids increases muscle Na+ ,K+ ATPase content, such effect is unexplored after therapeutic inhalation. We investigated the effect of therapeutic inhalation of the glucocorticoid budesonide on Na+ ,K+ ATPase content of skeletal muscle in men. Ten healthy trained subjects, aged 23 ± 4 years (mean ± 95% CI), participated in the study. Before and after 2 weeks of daily inhalation of budesonide (1.6 mg/day), a biopsy was taken from the vastus lateralis muscle for measurement of Na+ ,K+ ATPase content and blood samples were drawn for determination of plasma budesonide, cortisol, and K+ . Subjects' performance during cycling to fatigue at 90% of incremental peak power output (iPPO) was measured in response to 4 mg inhaled terbutaline to maximally stimulate Na+ ,K+ ATPase activity. Plasma concentrations of budesonide rose to 5.0 ± 1.6 nM with the intervention, whereas no changes were observed in plasma cortisol. Muscle Na+ ,K+ ATPase content increased (P ≤ 0.01) by 46 ± 34 pmol/(g wet wt) (17% increase) with the intervention. Cycling performance at 90% of iPPO did not change (P = 0.21) with the intervention (203 vs 214 s) in response to terbutaline. The present observations show that therapeutic inhalation of glucocorticoids increases muscle Na+ ,K+ ATPase content, but does not enhance high-intensity cycling endurance in response to terbutaline.

Altered sympathetic-to-immune cell signaling via ß2-adrenergic receptors in adjuvant arthritis.

Adjuvant-induced arthritic (AA) differentially affects norepinephrine concentrations in immune organs, and in vivo ß-adrenergic receptor (ß-AR) agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered ß-AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined ß2-AR expression in spleen and draining lymph nodes (DLNs) for the arthritic limbs using radioligand binding and western blots and splenocyte ß-AR-stimulated cAMP production using enzyme-linked immunoassay (EIA). During severe disease, ß-AR agonists failed to induce splenocyte cAMP production, and ß-AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte ß2-AR phosphorylation (pß2-AR) by protein kinase A (pß2-AR(PKA)) decreased in severe disease, and pß2-AR by G protein-coupled receptor kinases (pß2-AR(GRK)) increased in chronic disease. Conversely, in DLN cells, pß2-AR(PKA) rose during severe disease, but fell during chronic disease, and pß2-AR(GRK) increased during both disease stages. A similar pß2-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund's adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors) are important for DLN pß2-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in ß2-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis.

[Clinical effects of budesonide/formoterol combination drug in elder patients with asthma compared with budesonide plus tulobuterol patch combination treatment].

BACKGROUND AND AIMS: Tulobuterol patch (Tulo) is often used for treatment of elder patient with asthma in Japan. However, there is no evidence either ICS plus Tulo or ICS/LABA combination is better for elder patient. METHODS: Elder patients with asthma (aged≥ 70, n=17) who had treated with budesonide (BUD) 400 µg/day plus Tulo 2 mg/day, were randomly assigned either to change control medication to budesonide/formoterol combination (BUD/FM) 320/9 µg/day or to keep BUD plus Tulo treatment for 12 weeks. RESULTS: At week 4 and week 12, the BUD/FM group showed significant increase in lung function (FEV1, %FEV1) and mini AQLQ score compared with the BUD plus Tulo group. The BUD/FM group also showed decrease in Tumor Necrosis Factor-alpha level in exhaled breath condensate at week 12. No adverse event was observed in both groups. CONCLUSION: In elder patients with asthma, treatment with BUD/FM does not have any clinical disadvantage and may provide better efficacy in lung function, QOL, and possibly anti-inflammation compared with BUD plus Tulo treatment.

ß-Adrenergic agonists differentially regulate highly selective and nonselective epithelial sodium channels to promote alveolar fluid clearance in vivo.

ß-Adrenergic receptors (ß-AR) increase epithelial sodium channel (ENaC) activity to promote lung fluid clearance. However, the effect of selective ß-AR agonist on highly selective cation (HSC) channels or nonselective cation (NSC) channels in alveolar type 1 (T1) and type 2 (T2) cells is unknown. We hypothesized that stimulation with ß(1)-AR agonist (denopamine) or ß(2)-AR agonist (terbutaline) would increase HSC and/or NSC channel activity in alveolar epithelial cells. We performed single-channel measurements from T1 and T2 cells accessed from rat lung slices. Terbutaline (20 µM) increased HSC ENaC activity (open probability, NP(o)) in T1 (from 0.96 ± 0.61 to 1.25 ± 0.71, n = 5, P <0.05) and T2 cells (from 0.28 ± 0.14 to 1.0 ± 0.30, n = 8, P = 0.02). Denopamine (20 µM) increased NSC NP(o) in T1 cells (from 0.34 ± 0.09 to 0.63 ± 0.14, n = 7, P = 0.02) and in T2 cells (from 0.47 ± 0.09 to 0.68 ± 0.10, P = 0.004). In vivo X-ray imaging of lung fluid clearance and ICI 118,551 selective inhibition of ß(2)-ARs confirmed patch-clamp findings. cAMP concentrations increased following treatment with denopamine or terbutaline (n = 3, P < 0.002). The effects of systemic (intraperitoneal, IP) and local (intratracheal, IT) modes of delivery on lung fluid clearance were assessed. IT delivery of denopamine promoted alveolar flooding, whereas IP delivery promoted delayed fluid clearance. In summary, ß-AR agonists differentially regulate HSC and NSC in T1 and T2 cells to promote lung fluid clearance in vivo, and the mode of drug delivery is critical for maximizing ß-AR agonist efficacy.

Use of within-group designs to test anti-tussive drugs in conscious guinea-pigs.

INTRODUCTION: Cough is a common medical problem for which there are few effective drug treatments. A limited understanding of the mechanisms of induction and maintenance of cough and a paucity of suitable animal models frustrate drug discovery efforts to find novel anti-tussives. As in humans, guinea-pigs evoke a cough reflex upon exposure to tussive agents such as citric acid and capsaicin; both of which have been widely used to assess novel anti-tussive drugs. However, the potential for using within-group designs in drug development has received little attention and such designs may offer a way of assisting the drug discovery effort in the area of cough as well as other areas. METHODS: Cough can be monitored in conscious guinea-pigs by placing animals in a Perspex chamber, in which air is continually exchanged by use of negative pressure and drug delivery of aerosols to the chamber can be accurately timed. Cough in response to a tussive agent (e.g. 0.2-0.4M citric acid; 10-30 microM capsaicin) is detected by the simultaneous microphonic recording of audible signals characteristic of the cough response as well as by positive pressure changes in the chamber generated by a cough dependent rapid expiration of air from the lungs. Both the sound and pressure signals are recorded using an online analyzer, whilst the number of coughs can be analyzed off-line. The number of coughs over a 15 min period is used to quantitate tussive events. RESULTS: Reproducible cough can be detected in animals using cross-over designs that lend themselves to drug studies. Both the time and concentration dependence of anti-tussive drug action can be evaluated in the same animal. Furthermore, the effect of different anti-tussive drugs can be evaluated thereby reducing between group error and thereby improving the sensitivity of the test. DISCUSSION: Repeated measures design improves the precision with which to evaluate anti-tussive drugs in preclinical models and could be used to make the drug discovery process more efficient.

Increased cardiac index due to terbutaline treatment aggravates capillary-alveolar macromolecular leakage in oleic acid lung injury in dogs.

INTRODUCTION: We assessed the in vivo effects of terbutaline, a beta2-agonist assumed to reduce microvascular permeability in acute lung injury. METHODS: We used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung injured dogs. BAL was performed in a closed lung sampling site, using a bronchoscope fitted with an inflatable cuff. Fluorescein-labeled Dextran (FITC-D70) was continuously infused and its concentration measured in plasma and BAL fluid. A two-compartment model (blood and alveoli) was used to calculate KAB, the transport rate coefficient of FITC-D70 from blood to alveoli. KAB was estimated every 15 minutes over 4 hours. Terbutaline intra-venous perfusion was started 90 min. after the onset of the injury and then continuously infused until the end of the experiment. RESULTS: In the non-treated injured group, the capillary-alveolar leakage of FITC-D70 reached a peak within 30 minutes after the OA injury. Thereafter the FITC-D70 leakage decreased gradually until the end of the experiment. Terbutaline infusion, started 90 min after injury, interrupted the recovery with an aggravation in FITC-D70 leakage. CONCLUSIONS: As cardiac index increased with terbutaline infusion, we speculate that terbutaline recruits leaky capillaries and increases FITC-D70 leakage after OA injury. These findings suggest that therapies inducing an increase in cardiac output and a decrease in pulmonary vascular resistances have the potential to heighten the early increase in protein transport from plasma to alveoli within the acutely injured lung.

Modification of the effect of nifedipine in the pregnant rat myometrium: the influence of progesterone and terbutaline.

AIMS: The aims of the study were to investigate the effects of nifedipine on potassium chloride (KCl)-evoked rat uterine contractions on different days of pregnancy in vitro, and the alterations in the effects of nifedipine on combination with terbutaline or progesterone. MAIN METHODS: In rat myometrial rings taken on different days of pregnancy, rhythmic contractions were evoked with KCl in an isolated organ bath. KEY FINDINGS: The relaxing effect of nifedipine was most expressed in the 25 mM KCl-induced uterine contractions, reaching the maximum on the last day of pregnancy (day 22). This effect was decreased by progesterone pretreatment in vivo. Synergism was observed in the uterus-relaxing effect of nifedipine+terbutaline, though the extent of potentiation depended on the sequence of administration of the two compounds. When terbutaline was added first in a single dose, the maximal inhibitory effect of nifedipine was lower. This decrease in the inhibition was suspended by a Ca(2+)-poor buffer, indicating the role of Ca(2+) channel activating effect of terbutaline. SIGNIFICANCE: It is concluded that the uterus-relaxing effect of nifedipine is weakened by progesterone and may be enhanced by low concentrations of beta-mimetics. However, the administration of terbutaline cannot precede the administration of nifedipine.

Terbutaline in myasthenia gravis: a pilot study.

The objective of this study was to assess the short-term efficacy and safety of terbutaline, a beta2-adrenergic agonist, in patients with myasthenia gravis (MG) in a randomized, double-blind, placebo-controlled, crossover study. The primary endpoint for efficacy was a reduction of at least 3 points in the quantitative MG score (QMGS). Secondary endpoints included changes in the functional disability scale (FDS), forced vital capacity (FVC), grip strength, anti-acetylcholine receptor (AChR) antibody levels and decremental response. During the terbutaline phase, five of eight (63%) patients had an improvement in the QMGS of 3.0 or greater, while 3/8 (38%) patients had improvement in the FDS of one grade. No improvement was seen during the placebo period. Statistical analysis using Wilcoxon signed-rank test confirmed that terbutaline treatment resulted in a significant improvement in QMGS. There was no change in FVC, grip strength or anti-AChR antibody levels, but there was an improvement in the decremental response during terbutaline phase. Terbutaline was well-tolerated in all study subjects. We conclude that terbutaline may be an effective adjunct therapy in a subset of patients with myasthenia, although confirmation with larger trials will be required.

Characterization of monolithic matrix patch system containing tulobuterol.

The aim of this study was to investigate the effect of the functional groups in acrylic adhesive on tulobuterol uptake, release rate and permeation rate across rat dorsal skin. In addition, the relationship between these parameters was identified in order to formulate the monolithic matrix patch system. Seven acrylate pressure sensitive adhesives were used in this study with three different functional groups as follows: (1) no functionality (DT-4098), (2) hydroxyl group (DT-2287, DT-2510, DT-2525, DT-2516), and (3) carboxyl group (DT-2353, DT-2852). Tulobuterol-uptake in PSA was determined by the drug-uptake method. The amount of tulobuterol-uptake in acrylic polymers with a carboxyl group was higher than those in acrylate pressure sensitive adhesives with either a hydroxyl group or a nonfunctional group. The release rate of tulobuterol from the monolithic patches was evaluated and DT-2353 and DT-2852, which contained a carboxyl group, showed lower release rates of tulobuterol than the other acrylate pressure sensitive adhesives. The skin permeation of tulobuterol was investigated using excised rat dorsal skin and the permeation rate of tulobuterol from DT-2353 and DT-2852 was also lower than the other acrylate pressure sensitive adhesives. Taking into consideration the relationship between all the parameters, pressure sensitive adhesives can be categorized into two groups: those containing a carboxylic acid functional group and those containing a non-carboxylic group. These results indicate that there was an interaction between the secondary amino group of tulobuterol and the carboxyl group of the acrylate polymer. Therefore, we suggest that a drug's chemical structure and functional groups in pressure sensitive adhesives must be considered in order to formulate a transdermal patch system.

Comparison of physical and inhalation properties of spray-dried and micronized terbutaline sulphate.

Terbutaline sulphate particles, for use in dry powder inhaler formulations, were prepared by spray-drying, using a Büchi 190 mini spray dryer. Spray-drying conditions were chosen to allow the production of spray-dried terbutaline sulphate with a size similar to micronized terbutaline sulphate, that is to say about 2.9 microm of volume mean diameter. The physical properties and in vitro inhalation behaviour of micronized and spray-dried terbutaline sulphate were compared. X-ray diffraction, DSC, SEM and laser size analysis were investigated. Spray-dying produced spherically shaped particles with amorphous structure. After blending with different lactoses, adhesion and aerodynamic properties were investigated. Evaluation of adhesion was carried out with a mechanical sieve and an Alpine air-jet sieve. The adhesion of terbutaline sulphate on the lactoses tested was lower in the case of the spray-dried drug. Aerodynamic evaluation of fine particle dose and emitted dose was conducted using a twin stage impactor. The emitted doses and the fine particle doses were higher with the spray-dried terbutaline sulphate. The Alpine air-jet sieve assays showed that there was a correlation between drug separation from a carrier by sieving and that obtained from longer in vitro deposition studies. There was a linear relationship between the adhesion characteristics and the fine particle dose.

Formulation and characterization of formaldehyde cross-linked degradable starch microspheres containing terbutaline sulfate.

Preparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18-24 microm. Whatever the cross-linking time, it was seen that the release of the TBS was not complete during the release experiments. The influence of enzyme on the degradation of microspheres was moderate. Following intravenous administration, initial uptake of microspheres by the lung was higher than those of other organs.

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.

Modulation of the inflammatory response to histamine by terbutaline and sodium nitroprusside in guinea-pig skin.

We measured the microvascular response (vasodilatation and plasma exudation) to skin prick provocations with histamine, terbutaline, sodium nitroprusside (SNP) and the combinations of terbutaline and histamine as well as SNP and histamine in guinea-pig skin. The response was measured by external detection of beta radiation from transferrin labelled with (113m)In. Histamine induced a moderate microvascular response. Terbutaline alone induced a smaller response, probably reflecting vasodilatation. When added to histamine, terbutaline significantly reduced the microvascular response to histamine. The response to histamine, SNP and the combination of histamine and SNP were all similar. We conclude that the anti-inflammatory effect of terbutaline can be readily measured with this technique. We found no indication of a pro-inflammatory effect of SNP when combined with histamine. Rather, the lack of additive effect may suggest an anti-inflammatory effect of SNP on the response to histamine.

Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease.

BACKGROUND: This study aimed to assess and compare the effectiveness of lidocaine and bronchodilator inhalation treatments for rapid cough suppression in patients with chronic obstructive pulmonary disease (COPD). METHODS: Prospective comparison study carried out in a tertiary emergency department. Consecutive COPD patients presenting with intractable cough were randomly assigned to receive lidocaine or terbutaline inhalation treatments for cough suppression. Patients with dyspnoea, unstable vital signs, and pneumonia or neoplasm on chest x ray were excluded. A subjective, 10 point questionnaire based cough severity score was used for assessing the outcome. RESULTS: The final study sample included 127 patients (mean (SD) age, 69.2 (12.1) years; 33.1% women) of whom 62 received nebulised lidocaine and 65 nebulised bronchodilator. The cough severity score was significantly reduced one hour after inhalation treatment with both lidocaine and bronchodilator, with no significant difference in efficacy. Common but mild side effects in the lidocaine group included oropharyngeal numbness and bitter taste, and, in the bronchodilator group, tremor and palpitation. Dyspnoea, dizziness, and nausea and vomiting were equally uncommon in both groups. None of these problems caused any of the patients to discontinue their treatments and no allergic reactions were reported. CONCLUSIONS: Both lidocaine and bronchodilator inhalation treatments are equally effective for short term cough suppression in patients with COPD.