Cystic Fibrosis Adult Care: Consensus Conference Report

The shortage of available donor hearts continues to limit cardiac transplantation. For this reason, strict criteria have limited the number of patients placed on the US waiting list to approximately 6000 to 8000 per year. Because the number of available donor hearts has not increased beyond approximately 2500 per year, the transplant waiting list mortality rate remains substantial. Suboptimal and variable utilization of donor hearts has compounded the problem in the United States. In 1999, the average donor yield from 55 US regions was 39%, ranging from 19% to 62%. This report provides the detailed cardiac recommendations from the conference on "Maximizing Use of Organs Recovered From the Cadaver Donor" held March 28 to 29, 2001, in Crystal City, Va. The specific objective of the report is to provide recommendations to improve the evaluation and successful utilization of potential cardiac donors. The report describes the accuracy of current techniques such as echocardiography in the assessment of donor heart function before recovery and the impact of these data on donor yield. The rationale for and specific details of a donor-management pathway that uses pulmonary artery catheterization and hormonal resuscitation are provided. Administrative recommendations such as enhanced communication strategies among transplant centers and organ-procurement organizations, financial incentives for organ recovery, and expansion of donor database fields for research are also described.

Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28-29, 2001, Crystal City, Va.

Respiratory volumes and timing have been measured in 19 healthy adults during wakefulness and sleep. Minute ventilation was significantly less (p less than 0.05) in all stages of sleep than when the subject was awake (7.66 +/- 0.34(SEM) 1/min), the level in rapid-eye-movement (REM) sleep (6.46 +/- 0.29 1/min) being significantly lower than in non-REM sleep (7.18 +/- 0.39 1/min). The breathing pattern during all stages of sleep was significantly more rapid and shallow than during wakefulness, tidal volume in REM sleep being reduced to 73% of the level during wakefulness. Mean inspiratory flow rate (VT/Ti), an index of inspiratory drive, was significantly lower in REM sleep than during wakefulness or non-REM sleep. Thus ventilation falls during sleep, the greatest reduction occurring during REM sleep, when there is a parallel reduction in inspiratory drive. Similar changes in ventilation may contribute to the REM-associated hypoxaemia observed in normal subjects and in patients with chronic obstructive pulmonary disease.

https://thorax.bmj.com/content/thoraxjnl/37/11/840.full.pdf

Respiration during sleep in normal man.

Sleep in chronic obstructive lung disease.

Ventilation was studied during wakefulness and sleep in six healthy humans in normoxia (mean barometric pressure (PB) = 740 torr), and in hypobaric hypoxia (PB = 455 torr). Hypoxia caused hyperventilation and hypocapnic alkalosis (delta Pa,CO2 = -7 torr) during wakefulness and in all sleep states. Periodic breathing was the predominant pattern of breathing in all stages of non-rapid eye movement (non-r.e.m.) sleep in hypoxia, but was rarely observed during wakefulness or r.e.m. sleep. Periodic breathing was composed of repetitive oscillations of reproducible cycle length characterized by clusters of breaths with augmented inspiratory effort (VT/TI) and highly variable distribution of breath-to-breath minute ventilation (VE) and tidal volume (VT), which alternated regularly with prolongations of the expiratory pause of the last breath of each cluster (apnea duration = 5-18 sec). Hypoxia-induced periodic breathing was eliminated by: (a) acute restoration of normoxia coincident with a 3-6 torr increase in Pa,CO2; and (b) augmented FI,CO2 (at constant arterial oxygen saturation) which rapidly and reversibly eliminated apneas and stabilized breathing pattern with a less than 2 torr increase in Pa,CO2. If hypocapnia was prevented (by augmented FI,CO2) during acute induction of hypoxia in non-r.e.m. sleep, periodic breathing was also prevented. We propose that the genesis of hypoxia-induced periodic breathing requires the combination of hypoxia and hypocapnia. Periodicity results from oscillations in CO2 about a CO2-apnea threshold whose functional expression is critically linked to sleep state.

Mechanisms of hypoxia-induced periodic breathing during sleep in humans.

Ventilation and oxygenation changes during sleep in cystic fibrosis.

Three normal subjects and 5 patients with chronic obstructive pulmonary disease and chronic CO2 retention were studied to determine the effect of chronic ventilatory stimulation with medroxyprogesterone acetate (MPA) on ventilatory control and pulmonary gas exchange during sleep. All patients had lowered PaCO2 after treatment with MPA while awake. Using a randomized application of treatment and placebo conditions, 4 wk of MPA therapy in the normal subjects caused a reduction in PaCO2 while awake (delta PaCO2 -4 to -7 mmHg) and during non-REM sleep (delta PaCO2 -5 to -7 mmHg). The response consisted of an increased minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI) awake and during non-REM sleep. In the patient group, 4 wk of MPA therapy caused significant reductions in PaCO2 while awake (from 54 +/- 2 to 47 +/- 2 mmHg) and during non-REM sleep (from 57 +/- 2 to 49 +/- 2 mmHg). Minute ventilation tidal volume, and mean inspiratory flow increased to a similar extent while awake and during all sleep stages. Improvement in SaO2 during sleep induced by treatment was attributable to an increase in alveolar ventilation rather than a decrease in alveolar-arterial oxygen partial pressure difference. Medroxyprogesterone acetate elicited chronic increases in inspiratory effect, tidal volume, and alveolar ventilation while awake and during all sleep stages in selected patients with chronic CO2 retention despite severe mechanical impairment and maldistribution ventilation:perfusion. The drug drives ventilation by a mechanism of action that is independent of many other peripheral and "central" ventilatory stimuli and/or inhibitors, including higher central nervous system influenced on ventilatory control that are dependent on the state of wakefulness.

Correction of CO2 retention during sleep in patients with chronic obstructive pulmonary diseases.

peridic breathing during sleep in healthy persons at high altitudes was first documented in the 1890s (16) Although additional studies in humans (la, 22, 29–31) have demonstrated periodic breathing at high altitudes, the mechanism of hypoxia-induced periodic breathing and its relationship to sleep remain unclear In 1909 Douglas and Haldane (7) induced periodic breathing in normal humans after periods of acute voluntary hyperventilation and suggested the importance of both hypoxia and hypocapnia on its occurrence Recent studies based on computer modeling and anesthetized-animal experiments propose that periodic breathing reflects instability in the chemical feedback control of ventilation (3–6, 13, 17, 18) In the series of studies described in this chapter, we combined sleep and hypoxia in normal humans to test for possible mechanisms involved in the genesis of periodic breathing (for more detailed information, see ref 1) Under these conditions the ventilatory control system may be altered by the following: 1) neurophysiological changes in the higher central nervous system associated with individual changes in sleep state; 2) hypoxia itself, which enhances peripheral feedback, and the attendant hyperventilation and hypocapnic alkalosis, which decrease central chemoreceptor feedback; and 3) a direct effect of hypoxia on the brain (ie, cerebral hypoxic depression and cerebral alkalosis) (11, 25) or a direct effect of hypoxia or hypocapnia on upper airway resistance (8) Our purpose was to both quantitatively describe the nature of hypoxia-induced periodic breathing on a breath-to-breath basis and investigate how the sleep state, hypoxia per se, and hypocapnic alkalosis secondary to hypoxia may contribute to hypoxia-induced ventilatory instability and periodic breathing

Jerome A. Dempsey

Papers

Ventilation and oxygenation changes during sleep in cystic fibrosis.

Correction of CO2 retention during sleep in patients with chronic obstructive pulmonary diseases.

Hypoxic Versus Hypocapnic Effects on Periodic Breathing During Sleep

termination of obstructive apneas Peripheral vascular resistance increases after

airway resistance in sleeping humans An induced blood pressure rise does not alter upper