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H Groeben

Publications and source records attributed to H Groeben.

At least 19 recordsLinked to original sources
PubMed2005

["Highlights" in emergency medicine -- severe head trauma, polytrauma and cardiac arrest].

According to scientific publications focusing on emergency medicine and published in international journals in the past few months, new and clinically important results can be identified. In patients with severe head trauma (SHT), application of hypertonic solutions is possible; long term outcome, however, is not improved by this measure. Prehospital capnometry is important, because otherwise up to 40 % of all mechanically ventilated patients are hypoventilated. In a study in 200 patients with prehospital cardiac arrest and ventricular fibrillation as initial cardiac rhythm, subgroup analysis (alarm-response time > 5 min) showed an increase in survival rate (14 % vs. 2 %), if defibrillation was proceeded by 3 min of conventional cardiopulmonary resuscitation (CPR) for reperfusion. If ACD ("active compression decompression")-CPR is combined with a specific ventilatory valve ("inspiratory impedance threshold device", ITD) which does not allow passive inspiration, survival rate after cardiac arrest is increased for up to 24 h. Such a device facilitates an increase in venous return to the heart during decompression of the thorax. High-dose adrenalin for intrahospital CPR in children is not associated with better survival but with worse outcome. Comparison of an emergency medical service (EMS) system from U.K. with paramedics and a physician-staffed German EMS system demonstrated that survival rate following prehospital cardiac arrest is markedly increased with doctors on board. The European multicentre trial comparing vasopressin vs. adrenalin as first vasopressor during CPR in 1219 patients did not reveal any differences between both groups. In subgroup analyses of patients with asystoly and prolonged CPR, vasopressin was superior without being associated with a benefit on neurological outcome. Further subgroup analyses revealed beneficial effects of amiodarone and thrombolysis during CPR. Thrombolysis during CPR apears to be associated with an increased rate of haemodynamic stabilisation without increased risk of bleeding complications. In a very clear advisory statement, the "International Liaison Committee on Resuscitation" (ILCOR) has recommended mild therapeutic hypothermia (i. e., cooling of cardiac arrest victims to 32 - 34 degrees C central body temperature for 12 - 24 h following cardiac arrest of cardiac etiology) not only for unconciuous patients with ventricular fibrillation as initial prehospital rhythm, but also for all other adult patients (other rhythms, intrahospital CPR) following cardiac arrest. In randomised controlled clinical trials, this therapy has markedly improved survival rate and neurological outcome. Such therapeutic cooling can be initiated nearly everywhere and with simple methods - like the infusion of ice-cold cristalloid solutions.

Cardiopulmonary Resuscitation↗
PubMed2005

[Catecholamine-resistant hypotension -- an update].

Vasoplegia as catecholamine resistent hypotension occurs in severe hemorrhagic or septic shock and post cardiopulmonary bypass. The entire rational behind this phenomenon is still unclear. An ATP-shortage in the vascular musculature, disregulation of vasopressin release, and the activation of ATP-dependent potassium-channels are discussed. In the last years, attention is drawn towards the activation of ATP-dependent potassium-channels and the possible therapeutic inhibition by glibenclamid. However, inhibition of potassium-channels does not normalize blood pressure under all circumstances. In particular in septic shock other mechanisms have to be involved. Overall, the sometimes desperate clinical situation has led to a large number of case reports und uncontrolled series of retrospectively analysed cases, where vasopressin or methylenblue were discribed as successfully reversing catecholamine resistent hypotension. Nevertheless, in hemorrhagic and septic shock scientific evidence of the clinical effects and the right dose as well as placebo controlled studies comparing the agents and possible combinations of agents are desirable but hardly available yet. In the case of severe hypotension following surgery under cardiopulmonary bypass results of the first randomized and placebo controlled studies describe successful restoration of blood pressure and even a decrease in perioperative mortality. Concerning the side effects, vasopressin and methylenblue, like most vasopressors, can cause gastrointestinal ischemia, but with the small number of patients enrolled so far, further major side effects can not be ruled out. Accordingly, the identification of risk factors for the development of vasoplegia and the prediction of the extent of the response or the rate of non-responders to these treatments are widely unknown. However, although the administration of vasopressin and methylenblue can not be recommended as a standard treatment it provides an additional option in individual cases of life threatening vasoplegia.

ATP-Binding Cassette Transporters↗
PubMed2004

Influence of volatile anaesthetics on hypercapnoeic ventilatory responses in mice with blunted respiratory drive.

BACKGROUND: Subanaesthetic concentrations of volatile anaesthetics significantly affect the respiratory response to hypoxia and hypercapnoeia. Individuals with an inherited blunted respiratory drive are more affected than normal individuals. To test the hypothesis that subjects with blunted hypercapnoeic respiratory drive are diversely affected by different anaesthetics, we studied the effects of three volatile anaesthetics on the control of breathing in C3H/HeJ (C3) mice, characterized by a blunted hypercapnoeic respiratory response. METHODS: Using whole body plethysmography, we assessed respiratory rate (RR) and pressure amplitude in 11 male C3 mice at rest, during anaesthesia with isoflurane, sevoflurane or desflurane, and during recovery. To test respiratory drive, mice were exposed to 8% carbon dioxide. Data were analysed by two-way-analysis of variance with post hoc tests and Bonferroni correction. RESULTS: RR was unaffected during sevoflurane anaesthesia up to 1.0 MAC. Likewise, sevoflurane at 1.5 MAC affected RR less than either isoflurane (P=0.0014) or desflurane (P=0.0048). The increased RR to a carbon dioxide challenge was blocked by all three anaesthetics even at the lowest concentration, and remained depressed during recovery (P<0.0001). Tidal volume was unaffected by all three anaesthetics. CONCLUSIONS: In C3 mice, spontaneous ventilation was less affected during sevoflurane compared with either isoflurane or desflurane anaesthesia. However, the RR response to hypercapnoeia was abolished at 0.5 MAC for all the anaesthetic agents and remained depressed even at the end of recovery. Our data suggest that different volatile anaesthetics have varying effects on the control of breathing frequency but all block the respiratory response to carbon dioxide. Therefore, a genetic predisposition to a blunted carbon dioxide response represents a susceptibility factor that interacts with hypercapnoeic hypoventilation during maintenance of anaesthesia and in the emergence from anaesthesia, regardless of the agent used.

Anesthetics, Inhalation↗
PubMed2004

Strategies in the patient with compromised respiratory function.

Respiratory diseases are commonly divided into restrictive or obstructive lung diseases. For anaesthesiological considerations restrictive lung diseases appear as a static condition with minimal short-term development. Overall, restrictive lung diseases don't lead to acute exacerbations due to the choice of anaesthetic techniques or the choice of anaesthesia-specific agents. Compared to restrictive lung diseases, obstructive lung diseases such as asthma or chronic obstructive lung diseases have a high prevalence and are one of the four most frequent causes of death. Obstructive lung diseases can be significantly influenced by the choice of anaesthetic technique and anaesthetic agent. Basically, the severity of the chronic obstructive pulmonary disease (COPD) and the degree of bronchial hyperreactivity will determine the perioperative anaesthetic risk. This risk has to be assessed by a thorough preoperative evaluation and will provide the rationale on which to decide the adequate anaesthetic technique. In particular, airway instrumentation can cause severe reflex bronchoconstriction. The use of regional anaesthesia alone or in combination with general anaesthesia can help to avoid airway irritation and even leads to reduced postoperative complications. Prophylactic anti-obstructive treatment, volatile anaesthetics, propofol, opioids, and an adequate choice of muscle relaxants minimize the anaesthetic risk when general anaesthesia is required. If intraoperative bronchospasm occurs, despite all precautions, deepening of anaesthesia, repeated administration of beta2-adrenergic agents and parasympatholytics, and a single systemic dose of corticosteroids are the main treatment options.

Adrenal Cortex Hormones↗
PubMed2004

Predictive value of mechanomyography and accelerometry for pulmonary function in partially paralyzed volunteers.

BACKGROUND: Accelerometry (ACM) of adductor pollicis muscle has been used for monitoring of neuromuscular blockade but its validity compared with the gold standard, mechanomyography (MMG), has been questioned. During neuromuscular blockade we compared these methods and we assessed pulmonary function. METHODS: In awake partially paralyzed volunteers we spirometrically assessed pulmonary function every 5 min until recovery. Rocuronium (0.01 mg kg(-1) + 2-10 microg kg(-1) min(-1)) was administered to maintain train-of-four (TOF)-ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The TOF-ratio associated with 'acceptable' pulmonary recovery [forced vital capacity (FVC) and forced inspiratory volume in 1 s (FIV1) of > or =90% of baseline] was calculated using a linear regression model. During 5-min periods of repetitive nerve stimulation we compared the squared residuals of the FVC and FIV1 estimates from TOFACM vs. TOFMMG, and compared variance of values derived from ACM and MMG using Wilcoxon's test. RESULTS: Limits of agreement of TOF-ratio derived from ACM and MMG were wide [0.15+/-0.016 (SD)], and variability of TOFACM exceeded that of TOFMMG[variance: 77+/-105 vs. 51+/-55% (P<0.01)]. Calculated TOF(ACM) and TOFMMG ratios of 0.56 (0.22-0.71) [mean (95%CI) and 0.6 (0.28-0.74)], respectively, predict 'acceptable' (90%) recovery of FVC while FIV1 remains impaired until TOF-ratios of 0.91 (0.82-1.07) and 0.95 (0.82-1.18), respectively. In turn, TOFMMG (TOFACM) of unity predicted 'acceptable' recovery of FVC and FIV1 in 94 (93) % and 68 (73) % of measurements, respectively. CONCLUSIONS: Accelerometry predicts effects of relaxation on pulmonary function as valid as the gold standard mechanomyography. We recommend that recovery of TOF ratio to 0.9-1.0 should be used as an indication of sufficient neuromuscular recovery in daily practice.

Adult↗
PubMed2003

[Emergency medicine -- new concepts and therapies improve outcome from cardiac arrest].

According to scientific articles focusing on emergency medicine published in international journals in the past few months, early defibrillation by lay persons, thrombolysis during cardiopulmonary resuscitation (CPR) and treatment with mild therapeutic hypothermia have been identified as relevant, new and clinically important treatment options to improve outcome following cardiac arrest. Early defibrillation using automated external defibrillators by lay persons reduces the time interval between collapse and first attempts at defibrillation and thus improves outcome after prehospital cardiac arrest. Thrombolysis during CPR -- for which the results regarding safety and efficacy are available from nonrandomized trials -- can also be safely performed in case of pulseless electrical activity. Thrombolysis during cardiopulmonary resuscitation has, however, no significant effect in this subgroup of patients with pulseless electrical activity in whom outcome is poor if the drug is administered at the end of conventional CPR procedures. Mild therapeutic hypothermia, i. e., cooling of cardiac arrest victims to 32-34 degrees C central body temperature for 12-24 h following out-of-hospital cardiac arrest, markedly improves survival rate and neurological outcome. Since this has now been clearly documented in two randomized clinical trials, it can be assumed that this kind of intervention will be recommended and translated into clinical practice soon. In conclusion, new and clinically relevant methods to improve outcome following cardiac arrest are available and can now be widely used clinically.

Cardiopulmonary Resuscitation↗
PubMed2003

[Rationale and management of perioperative atrial fibrillation].

Atrial fibrillation is the most common clinically relevant arrhythmia. Anesthesiologists will be faced with atrial fibrillation of new or undetermined onset at their preoperative evaluation of patients as well as during intra- and post operative care. Because of fast electrophysical and structural remodeling, atrial fibrillation tends to persist and reoccur after successful conversion with increasing time of duration. Therefore, atrial fibrillation with an onset of less than 48 hours should be attempt to convert as soon as diagnostic work up has been made and possible causes have been corrected. New developments of electrophysiological and pharmacological treatment have improved the short term success rate of cardioversion. Further developments might give even more specific treatment options for the individual patient. In contrast, for treatment of chronic atrial fibrillation rate control therapy and thromboembolic prophylaxes seems to be more advisable with a lower risk of drug side effects and stroke. Anticoagulation should be initiated not later than 48 hours after the onset of atrial fibrillation. Finally, the development of implantable devices for the treatment of atrial fibrillation seem to be a promising therapeutic option for patients in end-stage heart diseases.

Atrial Fibrillation↗
PubMed2003

[New pathways and current concepts in intensive care medicine--a summary of important articles of the last month].

One of the most outstanding critical care concepts of the last month is the definition of 5 therapy strategies by the Society of Critical Care for treatment of patients in septic shock. These strategies are: Low tidal volume of 6 ml/kg(-1) body weight in patients with ARDS, early goal-directed therapy, activated protein C therapy, moderate-dose corticosteroids, and tight control of blood sugar. Following further review of the main critical care medicine related journals for strategies to reduce mortality, the non-invasive ventilation is worthwhile mentioning. Moreover, this review summarizes articles on the topics of: Low-dose dopamine does not prevent acute renal insufficiency, increase of mortality is not related to albumin infusion, subglottic suctioning prevents early onset of ventilator associated pneumonia, prone position in ARDS patients has no influence on mortality, the safest site for central venous catheterization, and pulmonary-artery catheter directed therapy has no influence on mortality of high-risk surgical patients.

English Abstract↗
PubMed2003

Heritable differences in respiratory drive and breathing pattern in mice during anaesthesia and emergence.

BACKGROUND: Postanaesthetic hypoxia and ischaemia can lead to postoperative morbidity and mortality. We studied the effect of isoflurane anaesthesia in two inbred mouse strains known for phenotypic differences in breathing pattern and respiratory drive during carbon dioxide challenge and their first-generation offspring (F(1)). METHODS: Using whole body plethysmography, we assessed respiratory rate (RR) and pressure amplitude (Amp) in male B6 (high responder to hypercapnia), C3 (low responder), and F(1) mice at rest, during anaesthesia with isoflurane, and during recovery from anaesthesia. At each time point, the magnitude and pattern of breathing were determined during hypercapnic challenge (FI(CO(2)) = 0.08). Data (mean (SD)) were analysed by generalized ANOVA with post hoc Bonferroni's correction (P<0.05). RESULTS: During isoflurane anaesthesia, strain differences between B6 and C3 mice in RR were obscured while differences in Amp persisted. In contrast to baseline RR responses to carbon dioxide were significantly reduced at 0.5 MAC (increase in RR: 175 (33) bpm, 147 (44) bpm, 127 (33) bpm, for B6, C3, and F(1) strains respectively) and completely blocked at 1.5 MAC (change in RR: -3 (10) bpm, -2 (1) bpm, -4 (5) bpm, for B6, C3, and F(1) strains, respectively). During recovery, B6 mice showed a significant increase in RR (77 (33) bpm; P<0.0001) as well as in Amp. This was not observed in either C3 (-22 (31) bpm) or F(1) mice (23 (51) bpm). CONCLUSION: Isoflurane anaesthesia abolished the strain differences in respiratory drive between B6, C3, and F(1) mice. However, during recovery from anaesthesia, significant strain variation in respiratory drive reappeared and was more pronounced compared with pre-anaesthetic levels. These results suggested, that genetic differences may have minimal contribution to decreased respiratory drive during anaesthesia, but may be a major risk factor for post-operative hypoventilation and the associated morbidity and mortality.

Anesthesia↗
PubMed2001

Human G protein beta3 subunit variant does not alter hypercarbic or hypoxic ventilatory response.

Hypercarbic respiratory drive is mainly determined by PCO(2) and pH with activity of the intracellular Na+/H+ exchanger (NHE) playing an important role in maintaining intracellular pH and respiratory drive. Because NHE activity varies with genetically different G-protein beta3 subunits (GNB3) (C/T polymorphism at nucleotide position 825) different genotypes might alter respiratory regulation. To test the hypothesis that short-term ventilatory responses vary with different GNB3 healthy volunteers with different genotypes (CC, TC, TT) were exposed to either hyperoxic hypercarbia (n=33) or to isocapnic hypoxia (n=31), respectively. There was no difference between CC, TC, and TT genotypes in hypercarbic and hypoxic respiratory drive when assessed as the ratio of minute ventilation over endexpiratory PCO(2) changes (DeltaV.E/DeltaPETCO(2)), maximal tolerable PETCO(2), and ratio of changes in ventilation over arterial haemoglobin desaturation (DeltaV.E/DeltaSO(2)), respectively. Thus, short-term hypercarbic and hypoxic ventilatory drive do not differ between individuals with genotypes encoding different GNB3. Whilst respiratory control may still be influenced by G-protein aberration, other mechanisms seem to have a more important role in controlling ventilation.

Genotype↗
PubMed2001

Airway anesthesia alone does not explain attenuation of histamine-induced bronchospasm by local anesthetics: a comparison of lidocaine, ropivacaine, and dyclonine.

BACKGROUND: Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity. METHODS: Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD. RESULTS: The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]). CONCLUSION: Both lidocaine and the new amide local anesthetic ropivacaine significantly attenuate histamine-induced bronchospasm. In contrast, dyclonine, despite its longer lasting and more intense local anesthesia, does not alter histamine-evoked bronchoconstriction and irritates the airways. Thus, airway anesthesia alone does not necessarily attenuate bronchial hyperreactivity. Other properties of inhaled local anesthetics may be responsible for attenuation of bronchial hyperreactivity.

Adult↗
PubMed2000

Effects of high thoracic epidural anesthesia and local anesthetics on bronchial hyperreactivity.

Bronchial hyperreactivity can cause life threatening bronchospasm after airway irritation. Therefore, endotracheal intubation is avoided in asthmatics when feasible. High thoracic epidural anesthesia can be used to avoid endotracheal intubation and offers less postoperative pulmonary complications when compared to systemic postoperative analgesia. However, there are concerns that it might also cause impaired ventilation by extended motor blockade, increased airway resistance, and increased bronchial reactivity because of pulmonary sympathicolysis. Nevertheless, high thoracic epidural anesthesia causes only a slight decrease in vital capacity and neither an increase in airway resistance nor increased bronchial reactivity. In fact, it causes a decrease in bronchial reactivity in patients with bronchial hyperreactivity mostly due to the systemic effect of the local anesthetic. The attenuation of bronchial hyperreactivity can be shown as a dose dependent effect of lidocaine and bupivacaine. The intravenous effect of lidocaine is comparable to the effect of a moderate dose of salbutamol and leads to an additive effect when both drugs are used in combination. Overall, high thoracic epidural anesthesia can be used safely in patients with bronchial hyperreactivity and intravenous administration of lidocaine (1.5-2.0 mg x kg(-1)) can be used as a prophylactic treatment prior to airway instrumentation.

Anesthesia, Epidural↗
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↗
PubMed1999

Is beta-adrenergic-mediated airway relaxation of salmeterol antagonized by its solvent xinafoic acid?

STUDY OBJECTIVE: Isolated case reports of asthmatic fatalities accompanied by the use of salmeterol have raised the question whether a paradoxical effect of salmeterol or its vehicle on the airways might contribute to these fatalities. We questioned whether salmeterol's solvent, xinafoic acid, has detrimental effects on the tone of airways or on beta-adrenoceptor binding. MATERIALS AND METHODS: Basenji-greyhound dogs were anesthetized and their peripheral airways challenged with xinafoic acid via a wedged bronchoscope technique. Radioligand binding assays were performed in lung membranes prepared from these dogs. RESULTS: In contrast to a methacholine control, xinafoic acid (0.001 to 1.0 mg/mL) aerosolized into the peripheral airways of anesthetized dogs did not increase airway resistance. Xinafoate alone had no significant effect on the specific binding of 125I-cyanopindolol to lung membranes and did not affect the affinity of salmeterol for the beta-adrenoceptor in the absence or presence of xinafoate, respectively (-log concentration that inhibits 50% [IC50] of the high-affinity site, 7.7+/-0.15 and 7.9+/-0.27; -log IC50 of the low-affinity site = 5.6+/-0.44 and 5.3+/-0.28 [n = 4]). CONCLUSION: These findings suggest that xinafoic acid, the solvent for salmeterol, does not have direct airway irritant effects, does not bind to beta-adrenoceptors, and does not impair the binding of salmeterol to beta-adrenoceptors. Thus, xinafoate is unlikely to contribute to the worsening of airway symptoms in asthmatics using salmeterol xinafoate.

Administration, Inhalation↗
PubMed1998

[The importance of bronchial hyperreactivity in anesthesiology].

Airways of patients with bronchial hyperreactivity (BHR) are characterised by exaggerated bronchoconstriction in response to a variety of stimuli; bronchospasm may be elicited during induction and maintenance of anaesthesia. The prevalence of BHR in normal populations is approximately 10%. BHR is an important feature of clinical asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis, atopy, upper respiratory tract infections and smoking. This review will outline some important aspects of the pathophysiological basis of BHR, i.e., neural and inflammatory mechanisms. Furthermore, it should assist in identifying patients at risk and update perioperative anaesthetic considerations. Prophylaxis of airway reflex activation and an appropriate anaesthetic plan should prevent airway constriction. Since tracheal intubation is the major risk factor to induce bronchospasm intubation should be avoided whenever possible and regional anaesthesia preferred. If tracheal intubation is unavoidable, propofol and ketamine can be recommended as induction agents. Prophylaxis of intraoperative bronchospasm and initial therapy, such as deepening of anaesthesia, inhalational administration of sympathomimetics and anticholinergics, and i.v. use of local anaesthetics and corticosteroids are outlined. Despite its popularity theophylline offers little benefit during anaesthesia. Adequate preoperative evaluation and preparation of the patient with BHR will contribute to optimising anaesthetic management of patients with BHR.

Anesthesia↗