Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome.

Patients with moderate to severe acute respiratory distress syndrome (ARDS) benefit from prone positioning. Although the accuracy of esophageal pressure (Pes) to estimate regional pleural pressure (Ppl) has previously been assessed in the supine position, such data are not available in the prone position in ARDS. In six anesthetized, paralyzed, and mechanically ventilated female pigs, we measured Pes and Ppl into dorsal and ventral parts of the right pleural cavity. Airway pressure (Paw) and flow were measured at the airway opening. Severe ARDS [arterial partial pressure of oxygen ([Formula: see text])/fraction of inspired oxygen ([Formula: see text]) < 100 mmHg at positive end-expiratory pressure (PEEP) of 5 cmH2O] was induced by surfactant depletion. In supine and prone positions assigned in a random order, PEEP was set to 20, 15, 10, and 5 cmH2O and static end-expiratory chest wall pressures were measured from Pes (PEEPtot,es) and dorsal (PEEPtot,PplD) and ventral (PEEPtot,PplV) Ppl. The magnitude of the difference between PEEPtot,es and PEEPtot,PplD was similar in each position [-3.6 cmH2O in supine vs. -3.8 cmH2O in prone at PEEP 20 cmH2O (PEEP 20)]. The difference between PEEPtot,es and PEEPtot,PplV became narrower in the prone position (-8.3 cmH2O supine vs. -3.0 cmH2O prone at PEEP 20). PEEPtot,PplV was overestimated by Pes in the prone position at higher pressures. The median (1st-3rd quartiles) dorsal-to-ventral Ppl gradient was 4.4 (2.4-6.8) cmH2O in the supine position and -1.5 (-3.5 to +1.1) cmH2O in the prone position (P < 0.0001) and marginally influenced by PEEP (P = 0.058). Prone position narrowed end-expiratory dorsal-to-ventral Ppl vertical gradient, likely because of a more even distribution of mechanical forces over the chest wall.NEW & NOTEWORTHY In a porcine model of acute respiratory distress syndrome, we found that static end-expiratory esophageal pressure did not change significantly in prone position compared with supine position at any positive end-expiratory pressure (PEEP) tested between 5 and 20 cmH2O. Prone position was associated with an increased ventral pleural pressure and reduced end-expiratory dorsal-to-ventral pleural pressure (Ppl) vertical gradient, likely due to a more even distribution of mechanical forces over the chest wall.

Comparison between neurally-assisted, controlled, and physiologically variable ventilation in healthy rabbits.

BACKGROUND: Various ventilation strategies have been proposed to reduce ventilation-induced lung injury that occurs even in individuals with healthy lungs. We compared new modalities based on an individualised physiological variable ventilation model to a conventional pressure-controlled mode. METHODS: Rabbits were anaesthetised and ventilated for up to 7 h using pressure-controlled ventilation with (Group PCS, n=10), and without (Group PC, n=10) regular sighs. Variable ventilation in the other two groups was achieved via a pre-recorded spontaneous breathing pattern [Group physiologically variable ventilation (PVV), n=10] or triggered by the electrical activity of the diaphragm [Group neurally adjusted ventilation assist (NAVA), n=9]. Respiratory elastance, haemodynamic profile, and gas exchange were assessed throughout the ventilation period. Cellular profile, cytokine content of bronchoalveolar lavage fluid, and wet-to-dry lung weight ratio (W/D) were determined after protocol completion. Lung injury scores were obtained from histological analysis. RESULTS: Marked deteriorations in elastance were observed (median and 95% confidence interval) in Group PC [48.6 (22)% increase from baseline], while no changes were detected in Groups PCS [3.6 (8.1)%], PVV [18.7 (13.2)%], and NAVA [-1.4 (12.2)%]. In comparison with Group PC, Group PVV had a lower lung injury score [0.29 (0.02) compared with 0.36 (0.05), P<0.05] and W/D ratio [5.6 (0.1) compared with 6.2 (0.3), P<0.05]. There was no difference in blood gas, haemodynamic, or inflammatory parameters between the groups. CONCLUSIONS: Individualised PVV based on a pre-recorded spontaneous breathing pattern provides adequate gas exchange and promotes a level of lung protection. This ventilation modality could be of benefit during prolonged anaesthesia, in which assisted ventilation is not possible because of the absence of a respiratory drive.

Airway management in paediatric anaesthesia in Europe-insights from APRICOT (Anaesthesia Practice In Children Observational Trial): a prospective multicentre observational study in 261 hospitals in Europe.

BACKGROUND: Critical respiratory events are common in children in the peri-anaesthetic period and are caused by airway and ventilation management difficulties. We aimed to analyse current European paediatric airway management practices and identify the incidence and potential consequences of difficult airway management. METHODS: We performed a secondary analysis of airway and ventilation management details of the European multicentre observational trial (Anaesthesia PRactice in Children Observational Trial, APRICOT) of children from birth to 15 yr of age. The primary endpoint was the incidence of difficult airway management. Secondary endpoints were the associations between difficult airway management, known pre-existing respiratory risk factors, and the occurrence of critical respiratory events. RESULTS: Details for 31 024 anaesthetic procedures were available for analysis. Three or more tracheal intubation attempts were necessary in 120 children (0.9%) and in 40 children (0.4%) for supraglottic airways insertions. The incidence (95% confidence interval) for failed tracheal intubation and failed supraglottic airway insertions was 8/10 000 (0.08%; 0.03-0.13%) and 8.2/10 000 (0.08%; 0.03-0.14%) children, respectively. Difficulties in securing the airway increased the risk for a critical respiratory event for tracheal tube (2.1; 1.3-3.4) and supraglottic airway (4.3; 1.9-9.9) placement. History of pre-existing respiratory risk factors was significantly associated with critical respiratory events independently of the airway device used. CONCLUSIONS: Airway management practices vary widely across Europe. Multiple airway device insertion attempts and pre-existing respiratory risk factors increase the likelihood of critical respiratory events in children and require further stratification during preoperative assessment and planning. This study highlights areas where education, research, and training may improve perioperative care. CLINICAL TRIAL REGISTRATION: NCT01878760.

Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

The farming environment protects mice from allergen-induced skin contact hypersensitivity.

BACKGROUND: Being born and raised in a farm provides a long-lasting protection for allergies. The microbial environment provided by farm animals is crucial to induce this protective effect, although underlying immune mechanisms remain elusive. OBJECTIVE: To establish a mouse model of global exposure to the farming environment and to study immunologic changes linked to protection of allergy. METHODS: Mice colonies were bred in parallel in a farm cowshed and the university animal facility (AF). Mice from both locations were subjected to a skin contact allergy model. Peripheral blood cells and cell cytokine production were assessed in both populations. In addition, the gut microbiome at various ages was characterized. RESULTS: Mice born in the farm were less prone to develop allergy than mice bred in the AF. Mice transfers between the AF and the farm showed a better protection when mice were moved to the farm early in life. As compared to AF-bred mice, farm mice displayed early immune activation with higher CD4+ T cell population, in particular CD4+ CD25+ FoxP3- (activated cells). The cytokine profile of mice from the farm was skewed towards an IL-17 and IL-22 secreting cell profile accompanied by increased IL-10 secretion. These differences were mostly seen within a specific age window between birth and 8 weeks of age. Microbiome analysis showed differences between 4 and 20 weeks old mice and between farm and AF mice with an increased number of Murine mastadenovirus B in young farm mice exclusively. CONCLUSION: The farming environment provides a strong, allergy protective IL-22 stimulus and generates activated CD4+ T cells. Exposure to the farm environment early in their life may also provide a better protection for contact skin allergy. Whether a viral trigger might decisively influence protection for allergies remains to be determined.

Peri-operative adverse respiratory events in children.

Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse respiratory event should rely on clinical, rather than immunological, assessment.

Perioperative use of oxygen: variabilities across age.

Enormous interest has emerged in the perioperative use of high concentrations of inspired oxygen in an attempt to increase tissue oxygenation and thereby improve postoperative outcome. An extensive debate has arisen regarding the risk/benefit ratio of oxygen therapy, with some researchers advocating the benefits of perioperative hyperoxia, particularly with regard to surgical site infection, whereas others emphasize its detrimental consequences on multiple organs, particularly the lungs and the brain. As one aspect of this debate, there is increased awareness of effects of reactive oxygen metabolites, a feature that contributes to the complexity of achieving consensus regarding optimum oxygen concentration in the perioperative period. Many reviews have discussed the pros and cons in the use of perioperative oxygen supplementation, but the potential importance of age-related factors in hyperoxia has not been addressed. The present narrative review provides a comprehensive overview of the physiological mechanisms and clinical outcomes across the age range from neonates to the elderly. Risks greatly outweigh the benefits of hyperoxia both in the very young, where growth and development are the hallmarks, and in the elderly, where ageing increases sensitivity to oxidative stress. Conversely, in middle age, benefits of short-term administration of perioperative oxygen therapy exceed potential adverse change effects, and thus, oxygen supplementation can be considered an important therapy to improve anaesthesia management.

Awareness in children: a secondary analysis of five cohort studies.

Five recent cohort studies have shown a frequency of awareness in paediatric anaesthesia of between 0.2% and 1.2%, but they were not individually large enough to identify risk factors. This study pooled raw data from these five studies to identify factors associated with awareness in children. The outcome of awareness was taken as the cases judged to be most likely awareness cases in each study. Logistic regression was used to identify awareness-associated factors. A combined sample of 4486 anaesthetics revealed 33 cases of awareness. Unadjusted analysis demonstrated weak evidence that nitrous oxide used as an anaesthetic maintenance adjunct was associated with awareness (OR 2.04 (95% CI 0.97-4.33), p=0.06), and some evidence that use of a tracheal tube was associated with awareness (OR 2.78 (95% CI 1.11-6.94), p=0.03). Multivariable regression analysis revealed that nitrous oxide maintenance and use of a tracheal tube were independently associated with awareness (nitrous oxide, OR 2.4 (95% CI 1.08-5.32), p=0.03; tracheal tube, OR 3.0 (95% CI 1.20-7.56), p=0.02).

Does implicit memory during anaesthesia persist in children?

BACKGROUND: Recent studies suggest that implicit memory (especially perceptual implicit memory) persists during adequate general anaesthesia in adults. Studies in children, however, have failed to demonstrate implicit memory during general anaesthesia, possibly because of differences in methodological design. We therefore designed a prospective study with the aim of evaluating implicit memory in children undergoing general anaesthesia, using a perceptual memory test based on the mere exposure effect, previously tested in a control group. METHODS: Twelve infrequent neutral words were played 12 times in a random sequence via headphones to 36 children aged 8-12 yr during elective or emergency surgery. The children were not premedicated, and general anaesthesia was maintained with isoflurane. The word presentation started immediately after the surgical incision. Within 36 h after the stimulus presentation, the memory was assessed by using a forced-choice preference judgement task. Time constraint and word deterioration with a low-pass filter were used to prevent the subjects from utilizing intentional retrieval. The implicit memory score was obtained by calculating the proportion of target words preferred, which was compared with the chance level (0.5). RESULTS: The percentage of correct responses given by the children was comparable with the chance level. The memory score was mean (sd) 0.48 (0.16) (95% CI 0.43-0.53). CONCLUSIONS: The use of a perceptual implicit memory test based on the mere exposure procedure in children failed to reveal any evidence of implicit memory under general anaesthesia.

Intra-operative awareness in children and post-traumatic stress disorder.

Adults who experience intra-operative awareness can develop disturbing long-lasting after-effects, such as daytime anxiety, sleep disturbances, nightmares, flashbacks and, in the worst case, a post-traumatic stress disorder (PTSD). It is unknown whether intra-operative awareness has a similar psychological impact in children. We designed the present study in order to evaluate the incidence of psychological symptoms in children who had either confirmed or possible intra-operative awareness. Attempts were made to locate 11 children who had been identified in a previous study, approximately 1 year following their experience. A PTSD questionnaire was administered to the children and their parents in order to detect any long-term or short-term psychological symptoms (the 1-month postoperative data were evaluated retrospectively). Factors believed to be associated with PTSD, such as intra-operative perceptions, the children's temperament and cognitive strategies, and the parents' coping strategies, were also analysed. Seven children were successfully located and interviewed and no short or long-term psychological symptoms were identified. None of them offered negative appraisals of the traumatic event and none had displayed dysfunctional behaviour or cognitive strategies. Thus, none of them had developed a PTSD syndrome. In contrast with what has been reported in adults, these children claimed not to have experienced major pain, terror or helplessness during their surgery. Despite the small sample size, the results of the present study suggest that children suffer less psychological sequelae than adults following intra-operative awareness. This may be due to the fact that the children reported less frightening intra-operative sensations as compared with the adults, and had less understanding of the anaesthesia procedure, and this may have influenced their appraisal of their awareness and protected them from the full impact of this potentially traumatic experience.

Intra-operative awareness in children: the value of an interview adapted to their cognitive abilities.

Intra-operative awareness in paediatric patients has been little studied for many years because of the difficulties in relying on children's testimony. Earlier questionnaires used to detect this complication were not adapted to children's language and memory capacities. By using a qualitative method, a semi-structured in-depth interview adapted to their cognitive abilities, we have now conducted a prospective evaluation of the incidence and risk factors for intra-operative awareness in children undergoing general anaesthesia. Data were obtained from interviews with 410 children (aged 6-16 years) which were conducted within 36 h of general anaesthesia for elective or emergency surgery. One month after surgery, 293 of these patients were interviewed again. Three independent adjudicators classified each potential case of awareness. We considered awareness to include both the 'confirmed awareness' and the 'possible awareness' cases. The accuracy of the children's recall was calculated. The relationship between their awareness and the anaesthesia management was examined. There were five cases of confirmed awareness, and six cases of possible awareness. The incidence of confirmed awareness was 1.2%, but when the possible cases were also considered, the overall incidence of this complication was as high as 2.7% (95% confidence interval, 1.4-5.0%). The only predictive factor identified was the multiple manoeuvres with which the airways were secured (odds ratio, 8.4; 95% confidence interval, 2.4-29.07%). The present study confirms the existence of intra-operative awareness in the paediatric population. The application of a semi-structured in-depth interview adapted to the cognitive capacities of the children appears to enhance the detection of awareness in this population.

Influence of anesthesia on immune responses and its effect on vaccination in children: review of evidence.

Anesthesia and surgery exert immunomodulatory effects and some authors argue that they may exert additive or synergistic influences on vaccine efficacy and safety. Alternatively, inflammatory responses and fever elicited by vaccines may interfere with the postoperative course. There is a lack of consensus approach among anesthesiologists to the theoretical risk of anesthesia and vaccination. Few studies have assessed the influence of anesthesia and surgery on pediatric vaccine responses. We have undertaken an extensive review of articles published in English between 1970 and 2006 meeting the criteria: measurement of immune parameters following general anesthesia in children. By searching the major medical databases (OVID Medline, PubMed, ISI Web of Science) and references cited in the articles themselves, among 277 articles obtained none examined directly the influence of anesthesia/surgery on vaccine responses. Only 16 original reports assessed the influence of several anesthetic agents on various markers of immunity including lymphocyte numbers and functions. These results are reinterpreted here in view of our current understanding of the immune mechanisms underlying vaccine efficacy and adverse events. We conclude that the immunomodulatory influence of anesthesia during elective surgery is both minor and transient (around 48 h) and that the current evidence does not provide any contraindication to the immunization of healthy children scheduled for elective surgery. However, respecting a minimal delay of 2 days (inactivated vaccines) or 14-21 days (live attenuated viral vaccines) between immunization and anesthesia may be useful to avoid the risk of misinterpretation of vaccine-driven adverse events as postoperative complications.

[Pharmacokinetics of tramadol in children]. / Particularités pharmacologiques du tramadol chez l'enfant.

The recent studies focusing on the pharmacokinetics of tramadol in children contributed to the increase popularity of tramadol as an analgesic alternative in clinical practice. Tramadol is a racemic mixture of 2 enantiomers that have comparable pharmacokinetic profile and this lack of difference is also observed with their main active metabolite, O-demethyl tramadol (M1). The serum concentrations of this metabolite depend largely on the activity of the cytochrome P450 and particularly of the enzyme CYP2D6 which reaches its maturity in the newborn. Nevertheless, the interindividual variability observed in the pharmacokinetics of tramadol and consequently in the pharmacodynamic profile is mainly due to the genetic polymorphism of cytochrome P450.

Impact of Trendelenburg positioning on functional residual capacity and ventilation homogeneity in anaesthetised children.

Trendelenburg positioning, a head-down tilt, is routinely used in anaesthesia when inserting a central venous catheter to increase the calibre of the jugular or subclavian veins and to prevent an air embolism. We investigated the impact of Trendelenburg positioning on functional residual capacity and ventilation homogeneity as well as the potential reversibility of these changes by repositioning and/or a recruitment manoeuvre in children with congenital heart disease. Functional residual capacity and ventilation homogeneity were assessed in 20 anaesthetised children between the ages of 3 months and 8 years who required central venous catheterisation before undergoing cardiac surgery. Functional residual capacity was measured (1) in the supine position, (2) in the Trendelenburg position, (3) after repositioning supine and (4) after a recruitment manoeuvre to total lung capacity which was performed by manually elevating the airway pressure to 40 cmH(2)O for ten consecutive breaths. Adopting the Trendelenburg position led to a significant decrease in functional residual capacity (median [range]- 12 (6-21)%) and increase in lung clearance index (12 (2-19)%). Baseline values were not reached after repositioning supine in any patient until after a standardised recruitment manoeuvre was performed.

Multimodality imaging for focus localization in pediatric pharmacoresistant epilepsy.

UNLABELLED: Multiple structural and functional imaging modalities are available to localize the epileptogenic focus. In pre-surgical evaluation of children with pharmacoresistant epilepsy, investigations with the maximum yield should be considered in order to reduce the complexity of the workup. OBJECTIVE: To determine the extent to which PET, ictal/interictal SPECT and its co-registration with the patient's MRI contributes to correct localization of the epileptogenic focus, surgical intervention and to the post surgical outcome in paediatric patients. METHODS: The study population included children and adolescents with pharmacoresistant epilepsy (n = 50) who underwent preoperative evaluation, surgery and had postoperative follow-up for at least 12 months. Outcome was measured by postoperative seizure frequency using Engel's classification. RESULTS: Thirty-nine patients (78%) became completely seizure free after surgical intervention. The likelihood to benefit from surgical treatment was significantly higher if localization with more imaging modalities (MRI, PET, SPECT) were concordant with respect to the resected brain area (p < 0.01). Preoperative PET examination provided better localizing information in patients with extratemporal epilepsy and/or dysplastic lesions, whereas SPECT was found to be superior to PET in patients with temporal lobe epilepsy and/or tumors (p < 0.05). No significant difference was noted in the surgical outcome in younger or older age group, in children with or without special education needs. CONCLUSION: In paediatric epilepsy pre-surgical evaluation, the combined use of multiple functional imaging modalities for a precise localisation of the epileptogenic focus is worthwhile for both extratemporal and temporal lobe epilepsy, also when EEG and MRI alone are non-contributive, given the potential benefit of complete postoperative seizure control.

Value of eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid for predicting lung function impairment in anaesthetised, asthmatic children.

Bronchial hyperactivity, a key feature of active asthma in children, is a risk factor for respiratory adverse events in the peri-operative period. The presence of activated eosinophils in the lungs and mast cell degranulation can contribute to bronchial hyperreactivity. Eosinophil cationic protein is released by activated eosinophils and tryptase reflects mast cell degranulation. This study focused on the relationship of respiratory mechanics, eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid in asthmatic and healthy children under general anaesthesia. We measured eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid from 21 asthmatic and 21 healthy children following induction of general anaesthesia. Respiratory system resistance and dynamic compliance were measured during mechanical ventilation. Eosinophil cationic protein was more common in bronchoalveolar lavage fluid from asthmatics (12/21) than from controls (4/21, p = 0.01) and was present at higher levels (p = 0.002). Tryptase was also more common in the asthmatics (8/21 vs 1/21, p = 0.01). Respiratory resistance was significantly higher in asthmatic children with detectable eosinophil cationic protein levels than in those with undetectable eosinophil cationic protein levels (p = 0.019). Furthermore, 50% of the asthmatics with detectable eosinophil cationic protein exhibited bronchospasm after sampling their bronchoalveolar lavage fluid. These findings suggested that high levels of eosinophil cationic protein in the bronchoalveolar lavage fluid are associated with irritable airways, presumably secondary to airway inflammation, and this might be a useful marker for respiratory adverse events in the peri-operative period.

Protective effects of volatile agents against acetylcholine-induced bronchoconstriction in isolated perfused rat lungs.

BACKGROUND: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. METHODS: Low-frequency pulmonary impedance data (ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal (n = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance (Raw) and parenchymal damping and elastance were estimated from the Z(L) data by model fitting. RESULTS: Under baseline conditions, the basic value of Raw was significantly decreased by Des (- 31.2 +/- 3.8%) and Sev (- 18.0 +/- 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (- 3.3 +/- 5.1% and - 8.6 +/- 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between - 14.3 +/- 11.4% for Hal and - 37.5 +/- 10.9% for Sev. CONCLUSIONS: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction.