Anaesthesia management of patients with airway susceptibilities: what have we learnt from animal models?

Anaesthesia management of patients with airway susceptibility remains a challenge in daily clinical practice due to the increased risk of perioperative bronchospasm. Therefore, understanding the mechanisms participating in the interaction between anaesthetic drugs and the lungs is essential in providing the optimal care for patients with chronic lung diseases. Experimental studies performed on various animal models mimicking airway susceptibility have played a key role in understanding the pathogenesis of lung diseases and have characterised the different pathways involved in the altered airway and lung tissue responses to anaesthetic agents. This narrative review highlights the progress that has been achieved by investigations in animal models and discusses the potential translation of these experimental findings to the clinical setting. The application of animal models with normal and allergically sensitised airways demonstrated that volatile and intravenous anaesthetic agents, muscle relaxants, analgesics and local anaesthetics exert their pulmonary effects via different neurosensorial pathways and through activating various receptors in the lungs. Attention is drawn to the significant differences in the pulmonary effects of anaesthetic agents between lungs with normal and those with susceptible airways. Extrapolating clear-cut conclusions from animal research to clinical practices should be made with caution, particularly for muscle relaxants, opioids and local anaesthetics wherein complex pathophysiological mechanisms are responsible for the potential respiratory effects of these agents. Animal models are of great importance in evaluating the potential interaction between anaesthetic drugs and the lungs, in identifying the pathways involved and in targeting preventive or treatment strategies to the lung compartment primarily involved

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

Role of endogenous histamine in altered lung mechanics in rabbits

Unlike the effects of exogenous histamine, those of endogenous histamine on the lung mechanics have not yet been characterized. The site of endogenous histamine liberation by mivacurium was determined, as were the effects of this histamine on the airway and parenchymal mechanics in control rabbits (group C) and rabbits pretreated with H1 and H2 receptor blockers (group AH). The effectiveness of the receptor blockade was ensured by challenges with exogenous histamine

Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs

Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin

Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs

It was hypothesised that the recruitment of atelectatic lung areas is signified by changes in the airway and tissue mechanics, and by the appearance of crackle activity attributed to the sudden reopening of collapsed airways. The authors also assumed that the acoustic activity is an earlier indicator of lung recruitment than the change in the overall mechanical state of the lungs. Six thoracotomised and mechanically ventilated mini-pigs were studied. Low-frequency pulmonary impedance was measured at end-expiratory pauses at transpulmonary pressures of 4 and 1 hPa to estimate airway resistance (Raw) and the coefficient of lung tissue elastance (H), and tracheal sounds were recorded during subsequent slow inflations to 30 hPa, in the control state and following increasing doses of i.v. methacholine (Mch). Raw and H were higher at baseline and increased more in response to Mch at 1 hPa than at 4 hPa. The crackles detected during the subsequent inflations were concentrated around and associated with the development of the lower knee of the pressure-volume curve. The number of crackles increased faster following the Mch doses and reached statistical significance earlier than Raw and H. Crackle recording during mechanical ventilation can be employed as a simple method with which to monitor lung recruitment-derecruitment

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

<p>Abstract</p> <p>Background</p> <p>The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR) following a left ventricular dysfunction (LVD) induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension.</p> <p>Methods</p> <p>Airway resistance (Raw) was identified from the respiratory system input impedance (Zrs) in four groups of rats. End-expiratory lung volume (EELV) was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I), or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE), or a calcium channel blocker (diltiazem, Group ID). The equivalent dose of methacholine causing a 100% increase in Raw (ED₅₀) was determined in each group. Diastolic pulmonary arterial pressure (Pap_D) was assessed by introducing a catheter into the pulmonary artery.</p> <p>Results</p> <p>The sustained presence of a LVD increased Pap_D in all groups of rats, with variable but significant elevations in Groups I (p = 0.004), ID (p = 0.013) and IE (p = 0.006). A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED₅₀ from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p = 0.006). The BHR was completely abolished in both Groups ID and IE, with no changes in ED₅₀ (9.5 ± 3.6 vs. 10.7 ± 4.7, p = 0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p = 0.56, respectively).</p> <p>Conclusions</p> <p>These findings suggest that a LVD following coronary ischaemia consistently induces BHR. The more consistent efficacy of both treatment strategies in preventing BHR than in treating the adverse pulmonary vascular consequences suggests the benefit of both calcium channel blockade and ACE inhibition to counteract the airway susceptibility following a LVD.</p

Development of bronchoconstriction after administration of muscle relaxants in rabbits with normal or hyperreactive airways

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L, respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity