Multiple functions of the larynx are controlled by reflexes. Despite the clinical significance of these reflexes, information on anaesthetised humans is limited, not least related to the practical difficulty of assessing laryngeal function in vivo . Among the protective reflexes, laryngospasm occurs more frequently during the administration of anaesthesia to paediatric compared with adult patients . Although laryngospasm can be safely treated when experienced personnel trained in paediatric anaesthesia are at hand, it remains the most commonly reported respiratory-related cause of peri-operative cardiac arrest , rendering progress in the diagnosis, prevention and treatment of laryngospasm in children mandatory.
Well-designed clinical investigations have been scarce since Fink’s seminal description of human laryngospasm back in 1956 . Laryngospasm is defined as complete closure of the false and/or vocal cords leading to the complete cessation of airflow. A common limitation of clinical studies examining the effectiveness of measures to prevent laryngospasm is the analysis of combined outcomes such as stridor and/or the occurrence of hypoxaemia from whatever cause. In fact, it is often difficult or impossible during clinical practice to determine the exact location of upper airway obstruction, making the dichotomous outcome, presence or absence of laryngospasm, ambiguous based on clinical signs alone. Therefore, making firm conclusions is difficult.
Further limitations include the difficulty to control for several potentially confounding variables such as gas flow, airway pressure, depth of anaesthesia, controlled versus spontaneous ventilation, partial pressure of carbon dioxide in the blood, applied airway manoeuvres and the use of airway devices. As a result, most of these studies are underpowered concerning the relatively rare event of true laryngospasm. Furthermore, it is complex to compare the results of different studies or to perform systematic reviews, since known confounding factors (e.g. experience of the anaesthetist, presence of upper airway infections  and exposure to environmental tobacco smoke ) are often not reported or controlled for. With these premises, a well-designed, large, clinical (multicentre) controlled trial aiming to answer how to prevent or treat laryngospasm will be exceedingly difficult to perform.
Aiming to overcome the many difficulties for research in the field of laryngeal and respiratory reflex responses, a new approach using a laryngeal stimulation technique in adult patients has been developed and found to be useful [1,–7]. In this clinical model, a fibreoptic endoscope is inserted through the shaft of the laryngeal mask airway in anaesthetised patients. Analysis of synchronously recorded laryngeal video data with gas flow and airway pressure data permits a detailed description and ultimately a classification of laryngeal and respiratory reflex responses. Spraying the laryngeal mucosa with distilled water is the best method to stimulate laryngeal receptors and evoke specific laryngeal reflex responses . The behaviour of the larynx in anaesthetised children is undoubtedly different from adults . Developmental aspects are of further importance concerning the paediatric group. Accordingly, in order to gain new clinically valuable knowledge, this information must be generated in paediatric patients [9–11].
Apart from the reliability of a response to a given stimulus, the stability over time to repeated stimuli is an important issue in studies where an intervention’s effect is measured against a baseline response. Study designs where individuals serve as their own control are attractive, because it allows the measurement of an induced intra-individual change of the response, ultimately reducing the number of subjects that must be included in the study. The response to repeated stimuli induced by spraying small amounts of water on the laryngeal mucosa has been found to be steady in anaesthetised humans [7, 11], making this type of study design suitable for generating valid data and making subsequent conclusions.
Results of studies using this technique have yielded important clinical information: (i) laryngeal closure/spasm occurs with the same incidence irrespective of the depth of sevoflurane anaesthesia ; (ii) laryngospasm occurs more frequently when sevoflurane is used compared with propofol ; (iii) fentanyl does not reduce the incidence of laryngospasm in children anaesthetised with sevoflurane , and (iv) intravenous lidocaine reduces the incidence of laryngospasm temporarily .
We acknowledge that there are important scientific and ethical issues involved in the application and study of this model [13–15], and appreciate the opportunity to put forward our viewpoint. We believe that our clinical stimulation studies provide relevant information to improve the pathophysiological understanding of laryngeal and respiratory reflex responses in anaesthetised children, ultimately providing information for further clinical studies advancing beyond the experimental model of water stimulation, and hence improving the safety of anaesthesia in children.