Respiratory drive assessment : an evaluation of the breath-by-breath occlusion pressure method in man

A simplified concept of respiratory drive is to consider it as the integrated "output" from the CNS to the respiratory "pump" muscles. This drive is a result of a complex central respiratory pattern generation, and can in abnormal situations, e.g. of pathological or pharmacological origin, be altered.

The aim of this thesis was to develop devices and methods for assessment of respiratory drive in man, and to evaluate the method in clinical and experimental studies.

A modified breath-by-breath Po.1 measurement technique based on occlusion pressure was designed. Three generations of dedicated devices for assessment of respiratory drive were built, and a ventilator was further adapted for the technique. Several methods for measuring ventilatory adjustment to disturbed breathing (chemical or mechanical stimulation) were evaluated, and the technique was also used to study pathologically and pharmacologically altered breathing. Comparisons between equipment, methods and medical conditions were performed as group comparisons between patients and healthy subjects.

The proposed technique to measure Po.1 breath-by-breath can be used without influencing the breathing pattern. As Po.1 shows a high temporal variability, this continuous breath-by-breath measurement should be preferred to intermittent measurement on single breaths. When breathing on a ventilator, Po.1 measurement can be compromised by mechanical loading of the equipment.

Breathing on a ventilator was shown to be compatible with all the tested methods for provocation of breathing. Transient response to short pulses Of C02 is a patient-friendly possibility to test chemosensitivity, in comparison with steady-state and rebreathing technique. A ventilator is especially suited for measurement of sensitivity to mechanical stimulation.

Clinical application of the technique was performed in three studies with the following results: 1) Ketamine reverses the depressive effect on ventilation of alfentanil. 2) COPD patients with nocturnal hypoxemia preserve their drive and chemosensitivity unaltered in at least one year without development of daytime hypoxemia. 3) Growth hormone profoundly improves the hypoventilation and chemosensitivity in Prader-Willi patients.

It is concluded that respiratory drive assessment can give added diagnostic or therapeutic value in several specific medical situations, and can be accomplished without a complicated or invasive technique.

List of scientific papers

I. Larsson H, Hellstrom LG, Linnarsson D (1993). Breath-by-breath determination of inspiratory occlusion pressure. Clin Physiol. 13(2): 133-42.
https://pubmed.ncbi.nlm.nih.gov/8453867

II. Hellstrom LG, Larsson H, Linnarsson D (1999). Implementation of a respiratory drive monitor on a servo ventilator. J Clin Monit and Comp. 15: 163-70.

III. Hellstrom LG, Persson J (2001). Respiratory sensitivity to small mechanical stimuli, assessed by spontaneously breathing on a ventilator. Proc 23rd Ann Int Conf IEEE Eng Med Biol Soc. [Manuscript]

IV. Hellstrom LG, Persson J (2002). Respiratory sensitivity to carbon dioxide assessed by spontaneously breathing on a ventilator. [Manuscript]

V. Persson J, Scheinin H, Hellstrom LG, Bjorkman S, Gotharson E, Gustafss LL (1999). Ketamine antagonizes alfentanil-induced hypoventilation in healthy male volunteers. Acta Anaesthesiol Scand. 43: 744-52.

VI. Sandek K, Andersson T, Bratel T, Hellstrom G, Lagerstrand L (1999). Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia. Respir Med. 93(2): 79-87.
https://pubmed.ncbi.nlm.nih.gov/10464857

VII. Lindgren AC, Hellstrom LG, Ritzen EM, Milerad J (1999). Growth hormone treatment increases CO(2) response, ventilation and central inspiratory drive in children with Prader-Willi syndrome. Eur J Pediatr. 158(11): 936-40.
https://pubmed.ncbi.nlm.nih.gov/10541953