Apnea Threshold in Pediatric Brain Death: A Case with Variable Results Across Serial Examinations

Consensus guidelines currently exist for the evaluation of pediatric patients with suspected brain death. The guidelines include the requirement for two consistent examinations separated by an observation period and a threshold of 60 mm Hg for PaCO2 during apnea testing. We present a patient who met all prerequisites to perform brain death examination but had variability in examinations during apnea testing. We discuss our strategy in managing these unexpected findings, including the importance of open and ongoing communication with the family, and the implications for current guidelines for the determination of brain death in pediatric patients.

Influence of cerebral blood flow on breathing stability

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H+ and Pco2 at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO2 would narrow the difference between the eupneic PaCO2 and the apneic threshold PaCO2 (ΔPaCO2), known as the CO2 reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO2 by ∼25% below control. The CO2 reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce PaCO2 until apnea occurred. results: Indo significantly reduced the CO2 reserve required to produce apnea from 6.3 ± 0.5 to 4.4 ± 0.7 mmHg ( P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs. Indo: 1.06 ± 0.10 vs. 1.61 ± 0.27 l·min−1·mmHg−1, P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.

Abstract 2405: Acute Increase In Left Ventricular Filling Pressure Leads To Hyperventilation In Heart Failure Patients With Central But Not Obstructive Sleep Apnea Or Without Sleep Disordered Breathing

The pathohysiology of Cheyne-Stokes-respiration (CSR) in congestive heart failure (CHF) is not fully understood. Increase in pulmonary capillary wedge pressure (PCWP) may lead to stimulation of pulmonary J-receptors and consecutive hyperventilation. The present study investigates the influence of an acute increase in PCWP in CHF pts without sleep disordered breathing (SDB) compared to pts with central (CSR) and obstructive sleep apnea (OSA). Simultaneous left and right heart catheterizations were performed in 29 CHF pts (NYHA ≥ II, LVEF ≤ 40%). PCWP and arterial pCO 2 were measured under standardized settings at baseline and after left ventricular angio- and/or aortography resulting in an acute increase in intravascular volumes. Type and severity of SDB were determined by cardiorespiratory polygraphy the night before or thereafter. NT-proBNP concentration was measured and central CO 2 - receptor sensitivity determined by testing hypercapnic-hyperoxic-ventilatory response (HCVR) according to Read. CSR was diagnosed in 15 pts (apnea-hypopnoea-index [AHI] 32 ± 19/h; 59 ± 11 years; LVEF 32 ± 6%), OSA in 9 pts (AHI 27 ± 29/h; 64 ± 13 years; LVEF 33 ± 5%); 5 pts had no SDB (AHI 1 ± 2/h; 48 ± 13 years; LVEF 32 ± 7%). HCVR and NT-proBNP concentrations were significantly higher in CSR (5.6 ± 6.5l/min/mmHg and 5237 ± 6268pg/ml) compared to OSA (2.2 ± 0.6l/min/mmHg and 1127 ± 874pg/ml) or pts without SDB (1.6 ± 0.6l/min/mmHg and 197 ± 146pg/ml; p < 0.05). PCWP were elevated at baseline and increased significantly after angiography in all groups (CSR: 20.3 ± 6.6 mmHg to 22.9 ± 7.9 mmHg; OSA 22.8 ± 10 to 25.4 ± 11 mmHg; noSDB: 14.2 ± 10 to 17.4 ± 9mmHg; all p < 0.05). Arterial pCO 2 at baseline tended to be lower in pts with CSR. Only in CSR, not in OSA or pts without SDB increase in PCWP was accompanied by a further decrease in pCO 2 (CSR: 36.1 ± 5mmHg to 33.3 ± 5mmHg, p = 0.05; OSA: 38.7 ± 4mmHg to 40.1 ± 6mmHg, p = ns; noSDB: 39.6 ± 6mmHg to 39.7 ± 6mmHg, p = ns). In CHF pts with CSR but not in those without SDB or OSA, acute increase in PCWP stimulates ventilation, together with other factors like an increased central CO 2 - receptor sensitivity this may lead to hyperventilation and a consecutive decrease in pCO 2 below the apnea threshold. Moreover, the present data may explain why CSR in some pts reflects CHF severity.

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

Xie, Ailiang, Fiona Rankin, Ruth Rutherford, and T. Douglas Bradley. Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea. J. Appl. Physiol. 82(3): 918–926, 1997.—We hypothesized that reductions in arterial [Formula: see text]([Formula: see text]) below the apnea threshold play a key role in the pathogenesis of idiopathic central sleep apnea syndrome (ICSAS). If so, we reasoned that raising[Formula: see text] would abolish apneas in these patients. Accordingly, patients with ICSAS were studied overnight on four occasions during which the fraction of end-tidal CO2 and transcutaneous[Formula: see text] were measured: during room air breathing ( N1), alternating room air and CO2 breathing ( N2), CO2 breathing all night ( N3), and addition of dead space via a face mask all night ( N4). Central apneas were invariably preceded by reductions in fraction of end-tidal CO2. Both administration of a CO2-enriched gas mixture and addition of dead space induced 1- to 3-Torr increases in transcutaneous [Formula: see text], which virtually eliminated apneas and hypopneas; they decreased from 43.7 ± 7.3 apneas and hypopneas/h on N1 to 5.8 ± 0.9 apneas and hypopneas/h during N3( P < 0.005), from 43.8 ± 6.9 apneas and hypopneas/h during room air breathing to 5.9 ± 2.5 apneas and hypopneas/h of sleep during CO2 inhalation during N2 ( P< 0.01), and to 11.6% of the room air level while the patients were breathing through added dead space during N4 ( P< 0.005). Because raising[Formula: see text] through two different means virtually eliminated central sleep apneas, we conclude that central apneas during sleep in ICSA are due to reductions in[Formula: see text] below the apnea threshold.

Apnea threshold and breathing rhythmicity in newborn lambs

This study was designed to determine the effect of the removal of chemical stimuli on breathing rhythmicity in awake newborn lambs; it was also designed to define the chemical threshold below which breathing would stop [arterial PCO2 (PaCO2) apnea threshold]. We used a technique of graded extracorporeal CO2 removal with apneic oxygenation in three groups of animals according to age and carotid body (CB) integrity: < 2 days, CB intact (n = 5); 12 days, CB intact (n = 7); and 12 days, CB denervated (CBD; n = 5). In all animals, whatever their age and CB status, suppression of the chemical drive resulted in sustained apnea. The study, performed at four constant levels of oxygenation (hyperoxia, normoxia, moderate hypoxia, and severe hypoxia), allowed precise determination of the PaCO2 apnea threshold. We found that this PaCO2 apnea threshold depended on the degree of postnatal maturation (it was higher in the younger lambs), the level of arterial oxygenation (it was lowered by hypoxia), and CB status (it was higher in CBD animals). Moreover, we found that the 12-day-old CBD lambs breathe at a level of PaCO2 set close to the point of apnea.(ABSTRACT TRUNCATED AT 250 WORDS)