Isocapnic hyperventilation in anaesthesia practice. Clinical and experimental studies

Background: Isocapnic hyperventilation (IHV) has been shown to shorten recovery time after volatile anaesthesia by accelerating elimination of inhalational agents by increasing minute ventilation while maintaining normal carbon dioxide (CO2) levels. It has also been shown that IHV reduces time spent in post-operative care units (PACUs). There are several principally different ways to maintain the CO2 level during hyperventilation but IHV methods currently in clinical use has unfortunately not reached wider clinical implementation. The original method of directly adding CO2 to the breathing circuit of the anaesthesia apparatus during hyperventilation was abandoned in the 1980s, partly due to development of short acting anaesthetic agents and partly due to the risk of hypercapnia associated with this procedure. Thus, this particular IHV method has not been studied to a great extent since then, although a considerable technical development of anaesthesia delivery systems and methods for monitoring airway gas concentrations have taken place in the last 30 years. Aims: The aims of the present thesis were: (1) to investigate if a method of adding CO2 directly into the breathing circuit using standard monitoring equipment and mechanical hyperventilation, provides effective and safe isocapnic hyperventilation, (2) to quantify the amount of delivered CO2 and to construct a nomogram for CO2 delivery during isocapnic hyperventilation at various physiological conditions, (3) to assess whether elimination of volatile anaesthetics can be accelerated using this IHV method, (4) to evaluate the clinical feasibility of this IHV method, (5) to compare the perioperative outcome for this IHV method to a routine wake-up method in a two-armed randomised study. Methods: Studies were performed in a mechanical lung model with simulated metabolism, in an experimental porcine model and in patients undergoing major head and neck surgery. A standard breathing circuit with a 450-ml CO2-mixing box connected to the inspiratory limb was used. A CO2 bottle was connected to the mixing box. CO2 flow was manually regulated by a high precision mechanical flow meter, dosed according to a nomogram during a standardised hyperventilation procedure using mechanical ventilation. The expired (FETCO2) and inspired (FICO2) fraction of CO2 values provided by the standard monitoring equipment, were used to monitor CO2 levels, also confirmed by arterial blood samples. Electric impedance tomography (EIT) was used in the porcine study for monitoring lung volume changes during hyperventilation. In the clinical studies, the end points were time to extubation, eye-opening and time to discharge from the operation room (OR) as well as post-operative measurements of pain, nausea and cognition according to the Postoperative Quality of Recovery Scale (PQRS). Results: In a bench study, we established a nomogram for CO2 delivery when base-line minute ventilation was doubled, to achieve IHV. In an animal experiment, the method proved to increase the elimination rate of anaesthetic gas without any relevant respiratory or circulatory side-effects. In a clinical pilot study, the nomogram was validated. In all studies a FICO2 level of about 3% produced stable isocapnia, provided that the study protocol was followed. In the randomised prospective study, a shortening of time to extubation