Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing?

Supplementary oxygen is routinely administered to patients, even those with adequate oxygen saturations, in the belief that it increases oxygen delivery. But oxygen delivery depends not just on arterial oxygen content but also on perfusion. It is not widely recognized that hyperoxia causes vasoconstriction, either directly or through hyperoxia-induced hypocapnia. If perfusion decreases more than arterial oxygen content increases during hyperoxia, then regional oxygen delivery decreases. This mechanism, and not (just) that attributed to reactive oxygen species, is likely to contribute to the worse outcomes in patients given high-concentration oxygen in the treatment of myocardial infarction, in postcardiac arrest, in stroke, in neonatal resuscitation and in the critically ill. The mechanism may also contribute to the increased risk of mortality in acute exacerbations of chronic obstructive pulmonary disease, in which worsening respiratory failure plays a predominant role. To avoid these effects, hyperoxia and hypocapnia should be avoided, with oxygen administered only to patients with evidence of hypoxemia and at a dose that relieves hypoxemia without causing hyperoxia

Rapid elimination of CO through the lungs: coming full circle 100 years on

At the start of the 20th century, CO poisoning was treated by administering a combination of CO2 and O2 (carbogen) to stimulate ventilation. This treatment was reported to be highly effective, even reversing the deep coma of severe CO poisoning before patients arrived at the hospital. The efficacy of carbogen in treating CO poisoning was initially attributed to the absorption of CO2; however, it was eventually realized that the increase in pulmonary ventilation was the predominant factor accelerating clearance of CO from the blood. The inhaled CO2 in the carbogen stimulated ventilation but prevented hypocapnia and the resulting reductions in cerebral blood flow. By then, however, carbogen treatment for CO poisoning had been abandoned in favour of hyperbaric O2. Now, a half-century later, there is accumulating evidence that hyperbaric O2 is not efficacious, most probably because of delays in initiating treatment. We now also know that increases in pulmonary ventilation with O2-enriched gas can clear CO from the blood as fast, or very nearly as fast, as hyperbaric O2. Compared with hyperbaric O2, the technology for accelerating pulmonary clearance of CO with hyperoxic gas is not only portable and inexpensive, but also may be far more effective because treatment can be initiated sooner. In addition, the technology can be distributed more widely, especially in developing countries where the prevalence of CO poisoning is highest. Finally, early pulmonary CO clearance does not delay or preclude any other treatment, including subsequent treatment with hyperbaric O2

Phrenic motoneuron discharge during sustained inspiratory resistive loading

Iscoe, Steve. Phrenic motoneuron discharge during sustained inspiratory resistive loading. J. Appl. Physiol. 81(5): 2260–2266, 1996.—I determined whether prolonged inspiratory resistive loading (IRL) affects phrenic motoneuron discharge, independent of changes in chemical drive. In seven decerebrate spontaneously breathing cats, the discharge patterns of eight phrenic motoneurons from filaments of one phrenic nerve were monitored, along with the global activity of the contralateral phrenic nerve, transdiaphragmatic pressure, and fractional end-tidal CO2 levels. Discharge patterns during hyperoxic CO2 rebreathing and breathing against an IRL (2,500–4,000 cmH2O ⋅ l−1 ⋅ s) were compared. During IRL, transdiaphragmatic pressure increased and then either plateaued or decreased. At the highest fractional end-tidal CO2 common to both runs, instantaneous discharge frequencies in six motoneurons were greater during sustained IRL than during rebreathing, when compared at the same time after the onset of inspiration. These increased discharge frequencies suggest the presence of a load-induced nonchemical drive to phrenic motoneurons from unidentified source(s). </jats:p

Supraspinal and spinal control mechanisms in respiration.

In anaesthetized, paralyzed, ventilated and vagotomized cats, stimulation of somatic afferent nerves at fixed times in the respiratory cycle could delay or advance the onset of the next respiratory phase. Repetitive stimulation produced sustained increases in respiratory frequency, entrainment of the frequency of the respiratory oscillator to that of stimulation occurring in half of the cats. These observations demonstrate the existence of a reflex pathway which may account for the locking of respiratory frequency to the period of rhythmic muscular activity. In anaesthetized, non-vasotomized spontaneously breathing T1 spinal cats, the mouth pressure at which phrenic motoneurones were recruited was measured during airway occlusion. The threshold pressure of recruitment of a motoneurone was constant at a given end tidal CO2. No unit was recruited at a pressure greater than 70% of maximum. [...]Chez le chat anesthésié, vagotomisé, curarisé et ventilé par respirateur, la stimulation de nerfs somatiques afferents peut retarder ou avancer le debut de la prochaine phase respiratoire. Un stimulus répétitif augmente la fréquence respiratoire; chez la moitié des chats étudiés, il y'eut synchronisation entre la fréquence respiratoire et celle du stimulus. Ces observations démontrent l'existence d'une voie réflexe responsable de la synchronisation entre la fréquence respiratoire et celle de l'activité motrice. [...

Respiratory periodicity following stimulation of vagal afferents

The effects on respiratory periodicity of electrical stimulation of the cut central end of a vagus nerve were studied in anaesthetized, vagotomized, paralyzed, and ventilated rabbits. Electrical activity of a phrenic nerve was used to determine inspiratory and expiratory durations (Ti and Te). The central cut end of one vagus nerve was electrically stimulated during the entire inspiratory phase of every 10th respiratory cycle and Ti and Te of that respiratory cycle and the following 8 were measured. When only the fastest conducting afferents (pulmonary stretch receptor afferents) were stimulated, reductions in Ti and Te were restricted to the stimulated cycle. When stimulus intensity was increased, activating higher threshold, more slowly conducting afferents (including those of irritant receptors), Te but not necessarily Ti decreased, increasing the frequency of phrenic bursts (respiratory frequency). The recovery of Te following stimulation was exponential, with a time constant of 3–7 s which varied inversely with control respiratory frequency. The effects on Ti and Te on higher intensity stimulation suggest either that coupling between inspiratory and expiratory neurones in the brainstem respiratory oscillator can be "looser" than currently hypothesized or a separate population of expiratory neurones, with a short-term memory (three time constants or [Formula: see text]), mediates the observed effects. </jats:p

Regional intercostal activity during coughing and vomiting in decerebrate cats

Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours.Key words: diaphragm, abdominal muscles, intercostal muscles. </jats:p