Alexandra Mardimae

Prospective targeting and control of end-tidal CO2 and O2 concentrations

Current methods of forcing end‐tidal PCO2 (PETCO2) and PO2 (PETO2) rely on breath‐by‐breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo‐control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath‐by‐breath basis. In this paper, we introduce a low gas flow method to prospectively target and control PETCO2 and PETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change PETCO2 from control (40 mmHg for PETCO2 and 100 mmHg for PETO2) to two target PETCO2 values (45 and 50 mmHg) at iso‐oxia (100 mmHg), PETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and PETCO2 with PETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, PETCO2 and PETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for PETCO2 was ± 1 mmHg, and for PETO2 was ± 4 mmHg. PETCO2 varied by ± 1 mmHg and PETO2 by ± 5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min−1). We conclude that targeted end‐tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed‐forward, low gas flow system.

Non-invasive prospective targeting of arterial P(CO2) in subjects at rest.

Accurate measurements of arterial P  CO 2 (P  a,CO 2 ) currently require blood sampling because the end‐tidal P  CO 2 (P  ET,CO 2 ) of the expired gas often does not accurately reflect the mean alveolar P  CO 2 and P  a,CO 2. Differences between P  ET,CO 2 and P  a,CO 2 result from regional inhomogeneities in perfusion and gas exchange. We hypothesized that breathing via a sequential gas delivery circuit would reduce these inhomogeneities sufficiently to allow accurate prediction of P  a,CO 2 from P  ET,CO 2. We tested this hypothesis in five healthy middle‐aged men by comparing their P  ET,CO 2 values with P  a,CO 2 values at various combinations of P  ET,CO 2 (between 35 and 50 mmHg), P  O 2 (between 70 and 300 mmHg), and breathing frequencies (f; between 6 and 24 breaths min−1). Once each individual was in a steady state, P  a,CO 2 was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P  ET,CO 2 and average P  a,CO 2 was 0.5 ± 1.7 mmHg (P= 0.53; 95% CI −2.8, 3.8 mmHg) whereas the mean difference between the two measurements of P  a,CO 2 was −0.1 ± 1.6 mmHg (95% CI −3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P  ET,CO 2 and P  a,CO 2 over the ranges of P  O 2, f and target P  ET,CO 2. We conclude that when breathing via a sequential gas delivery circuit, P  ET,CO 2 provides as accurate a measurement of P  a,CO 2 as the actual analysis of arterial blood.

Comparison of the effects of independently-controlled end-tidal PCO2 and PO2 on blood oxygen level–dependent (BOLD) MRI

To assess the effect of changes in end‐tidal partial pressure of O2 (PETO2) on cerebrovascular reactivity (CVR) estimated from changes in blood oxygen level–dependent (BOLD) signal during cyclic changes in end‐tidal partial pressure of CO2 (PETCO2).

BOLD-MRI cerebrovascular reactivity findings in cocaine-induced cerebral vasculitis

Background An 18-year-old woman presented to a regional stroke center with dysphasia and right hemiparesis 2 days after consuming alcohol and inhaling cannabis and—for the first time—cocaine.Investigations Physical examination, blood tests for inflammatory markers, vasculitis and toxicology screen, echocardiography, electrocardiography, CT scanning, brain MRI, magnetic resonance angiography, magnetic resonance vessel wall imaging, catheter angiography, and correlation of blood oxygen level-dependent (BOLD)-MRI signal intensity with changes in end-tidal partial pressure of carbon dioxide.Diagnosis Cocaine-induced cerebral vasculitis.Management No specific therapy was initiated. The patients vital signs and neurological status were monitored during her admission. Follow-up medical imaging was performed after the patients discharge from hospital.

Measurement of Cerebrovascular Reactivity in Pediatric Patients With Cerebral Vasculopathy Using Blood Oxygen Level-Dependent MRI

Background and Purpose— Cerebrovascular reactivity (CVR) is an indicator of cerebral hemodynamics. In adults with cerebrovascular disease, impaired CVR has been shown to be associated with an increased risk of stroke. In children, however, CVR studies are not common. This may be due to the difficulties and risks associated with current CVR study methodologies. We have previously described the application of precise control of end-tidal carbon dioxide partial pressure for CVR studies in adults. Our aim is to report initial observations of CVR studies that were performed as part of a larger observational study regarding investigations in pediatric patients with cerebral vascular disease. Methods— Thirteen patients between the ages of 10 and 16 years (10 with a diagnosis of Moyamoya vasculopathy and 3 with confirmed, or suspected, intracranial vascular stenosis) underwent angiography, MRI, and functional blood oxygen level-dependent MRI mapping of CVR to hypercapnia. The results of the CVR study were then related to both the structural imaging and clinical status. Results— Sixteen blood oxygen level-dependent MRI CVR studies were performed successfully in 13 consecutive patients. Twelve of the 13 patients with angiographic abnormalities also had CVR deficits in the corresponding downstream vascular territories. CVR deficits were also seen in 8 of 9 symptomatic patients and 2 of the asymptomatic patients. Noteably, in patients with abnormalities on angiography, the reductions in CVR extended beyond the ischemic lesions identified with MR structural imaging into normal-appearing brain parenchyma. Conclusions— This is the first case series reporting blood oxygen level-dependent MRI CVR in children with cerebrovascular disease. CVR studies performed so far provide information regarding hemodynamic compromise, which complements traditional clinical assessment and structural imaging.

The interaction of carbon dioxide and hypoxia in the control of cerebral blood flow.

Both hypoxia and carbon dioxide increase cerebral blood flow (CBF), and their effective interaction is currently thought to be additive. Our objective was to test this hypothesis. Eight healthy subjects breathed a series of progressively hypoxic gases at three levels of carbon dioxide. Middle cerebral artery velocity, as an index of CBF; partial pressures of carbon dioxide and oxygen and concentration of oxygen in arterial blood; and mean arterial blood pressure were monitored. The product of middle cerebral artery velocity and arterial concentration of oxygen was used as an index of cerebral oxygen delivery. Two-way repeated measures analyses of variance (rmANOVA) found a significant interaction of carbon dioxide and hypoxia factors for both CBF and cerebral oxygen delivery. Regression models using sigmoidal dependence on carbon dioxide and a rectangular hyperbolic dependence on hypoxia were fitted to the data to illustrate this interaction. We concluded that carbon dioxide and hypoxia act synergistically in their control of CBF so that the delivery of oxygen to the brain is enhanced during hypoxic hypercapnia and, although reduced during normoxic hypocapnia, can be restored to normal levels with progressive hypoxia.

Cardiovascular response to functional electrical stimulation and dynamic tilt table therapy to improve orthostatic tolerance

Orthostatic hypotension is a common condition for individuals with stroke or spinal cord injury. The inability to regulate the central nervous system will result in pooling of blood in the lower extremities leading to orthostatic intolerance. This study compared the use of functional electrical stimulation (FES) and passive leg movements to improve orthostatic tolerance during head-up tilt. Four trial conditions were assessed during head-up tilt: (1) rest, (2) isometric FES of the hamstring, gastrocnemius and quadriceps muscle group, (3) passive mobilization using the Erigo dynamic tilt table; and (4) dynamic FES (combined 2 and 3). Ten healthy male subjects experienced 70 degrees head-up tilt for 15 min under each trial condition. Heart rate, blood pressure and abdominal echograms of the inferior vena cava were recorded for each trial. Passive mobilization and dynamic FES resulted in an increase in intravascular blood volume, while isometric FES only resulted in elevating heart rate. No significant differences in blood pressure were observed under each condition. We conclude that FES combined with passive stepping movements may be an effective modality to increase circulating blood volume and thereby tolerance to postural hypotension in healthy subjects.

Differences in the control of breathing between Andean highlanders and lowlanders after 10 days acclimatization at 3850 m

We used Duffins isoxic hyperoxic ( mmHg) and hypoxic ( mmHg) rebreathing tests to compare the control of breathing in eight (7 male) Andean highlanders and six (4 male) acclimatizing Caucasian lowlanders after 10 days at 3850 m. Compared to lowlanders, highlanders had an increased non‐chemoreflex drive to breathe, characterized by higher basal ventilation at both hyperoxia (10.5 ± 0.7 vs. 4.9 ± 0.5 l min−1, P= 0.002) and hypoxia (13.8 ± 1.4 vs. 5.7 ± 0.9 l min−1, P < 0.001). Highlanders had a single ventilatory sensitivity to CO2 that was lower than that of the lowlanders (P < 0.001), whose response was characterized by two ventilatory sensitivities (VeS1 and VeS2) separated by a patterning threshold. There was no difference in ventilatory recruitment thresholds (VRTs) between populations (P= 0.209). Hypoxia decreased VRT within both populations (highlanders: 36.4 ± 1.3 to 31.7 ± 0.7 mmHg, P < 0.001; lowlanders: 35.3 ± 1.3 to 28.8 ± 0.9 mmHg, P < 0.001), but it had no effect on basal ventilation (P= 0.12) or on ventilatory sensitivities in either population (P= 0.684). Within lowlanders, VeS2 was substantially greater than VeS1 at both isoxic tensions (hyperoxic: 9.9 ± 1.7 vs. 2.8 ± 0.2, P= 0.005; hypoxic: 13.2 ± 1.9 vs. 2.8 ± 0.5, P < 0.001), although hypoxia had no effect on either of the sensitivities (P= 0.192). We conclude that the control of breathing in Andean highlanders is different from that in acclimatizing lowlanders, although there are some similarities. Specifically, acclimatizing lowlanders have relatively lower non‐chemoreflex drives to breathe, increased ventilatory sensitivities to CO2, and an altered pattern of ventilatory response to CO2 with two ventilatory sensitivities separated by a patterning threshold. Similar to highlanders and unlike lowlanders at sea‐level, acclimatizing lowlanders respond to hypobaric hypoxia by decreasing their VRT instead of changing their ventilatory sensitivity to CO2.

Retinal Arteriolar and Middle Cerebral Artery Responses to Combined Hypercarbic/Hyperoxic Stimuli

PURPOSE The relative effect of simultaneously administered oxygen and carbon dioxide on the retinal and cerebral vessels is still controversial. The purpose of this study was to quantify and compare the superior-temporal retinal arteriole (RA) and middle cerebral artery (MCA) responses to hypercarbic and combined hypercarbic/hyperoxic stimuli. METHODS Twelve young, healthy volunteers participated in the study. End-tidal pressure of carbon dioxide was raised and maintained at 22% from baseline (hypercarbia), while end-tidal pressures of oxygen (P(ET)O(2)) of 100 (normoxia), 500, and 300 mm Hg (hyperoxia) were instituted. RA diameter and blood velocity were measured with laser Doppler velocimetry and simultaneous vessel densitometry; MCA blood velocity was measured with transcranial Doppler ultrasound. RESULTS Normoxic hypercarbia increased RA blood velocity by +17% and calculated flow by +21%. Hypercarbia/hyperoxia-500 mm Hg decreased RA diameter by -8%, velocity by -16% and calculated flow by -29%. MCA blood velocity increased by +45% in response to normoxic hypercarbia, significantly greater than RA blood velocity (P < 0.001). Increase in P(ET)O(2) did not affect the hypercarbia-induced increase in MCA blood velocity. CONCLUSIONS Hyperoxia reversed hypercarbia-induced vasodilation in RA in a concentration-dependent manner. Hypercarbia induced greater vasodilation in the MCA than in the RA but MCA blood velocity was unaffected by increases in P(ET)O(2).

Modified N95 Mask Delivers High Inspired Oxygen Concentrations While Effectively Filtering Aerosolized Microparticles

Study objective In a pandemic, hypoxic patients will require an effective oxygen (O2) delivery mask that protects them from inhaling aerosolized particles produced by others, as well as protecting the health care provider from exposure from the patient. We modified an existing N95 mask to optimize O2 supplementation while maintaining respiratory isolation. Methods An N95 mask was modified to deliver O2 by inserting a plastic manifold consisting of a 1-way inspiratory valve, an O2 inlet and a gas reservoir. In a prospective repeated-measures study, we studied 10 healthy volunteers in each of 3 phases, investigating (1) the fractional inspiratory concentrations of O2 (FIO2) delivered by the N95 O2 mask, the Hi-Ox80 O2 mask, and the nonrebreathing mask during resting ventilation and hyperventilation, each at 3 O2 flow rates; (2) the ability of the N95 mask, the N95 O2 mask, and the nonrebreathing mask to filter microparticles from ambient air; and (3) to contain microparticles generated inside the mask. Results The FIO2s (median [range]) delivered by the Hi-Ox80 O2 mask, the N95 O2 mask, and the nonrebreathing mask during resting ventilation, at 8 L/minute O2 flow, were 0.90 (0.79 to 0.96), 0.68 (0.60 to 0.85), and 0.59 (0.52 to 0.68), respectively. During hyperventilation, the FiO2s of all 3 masks were clinically equivalent. The N95 O2 mask, but not the nonrebreathing mask, provided the same efficiency of filtration of internal and external particles as the original N95, regardless of O2 flow into the mask. Conclusion An N95 mask can be modified to administer a clinically equivalent FiO2 to a nonrebreathing mask while maintaining its filtration and isolation capabilities.