Endovascular repair of arteriovenous fistula after microendoscopic discectomy and lamino-foraminotomy.

The last two decades have seen increasing adoption of minimally invasive approaches to lumbar disc herniation management. As with many new advances in surgery, the risk profile of these contemporary approaches has yet to be well defined. We present the case of a 32-year-old man who presented with decreasing exercise tolerance over a 6-month period after microendoscopic lumbar discectomy and lamino-foraminotomy. Subsequent work-up revealed a large fistula between his right common iliac artery and inferior vena cava, resulting in high-output cardiac failure. This was managed well with an endovascular approach. This case highlights the importance of complication cognizance for patients who undergo minimally invasive lumbar disc surgery, as serious consequences can occur.

Private expenditures on brand name prescription drugs after generic entry.

BACKGROUND: Generic drugs offer a less expensive and therapeutically equivalent alternative to brand name drugs. Nevertheless, many Canadian private drug plans continue to pay for brand name drugs even after generics become available. OBJECTIVE: The objective of this study was to quantify the excess spending resulting from this practice. METHODS: We used the IMS Brogan PharmaStat database to study private-plan drug spending in Ontario from 2000 to 2009. We focused on three widely used drug classes: proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), and angiotensin-converting enzyme (ACE) inhibitors. For each specific molecule, we determined the difference between what private plans spent on the brand name version and what would have been spent if an available generic version of the same molecule had been purchased instead. RESULTS: We found that prescriptions paid for by private drug plans were often filled with brand name drugs after generics became available. This led to excess private spending of more than Can$107.8 million for these three drug classes over our study period: Can$54.4 million for PPIs, Can$32.4 million for SSRIs and Can$21.0 million for ACE inhibitors. INTERPRETATION: Brand name drugs continue to be reimbursed by Canadian private drug plans at higher prices even after less expensive generic alternatives are available. By mandating generic substitution, substantial cost savings on benefit plans could be achieved.

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude.

Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P50). In contrast to findings from in-vitro studies, we found a pH-related reduction in P50 in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude.

Human skin hypoxia modulates cerebrovascular and autonomic functions.

Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.

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.

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

We used Duffin's 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 CO(2) 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 CO(2), and an altered pattern of ventilatory response to CO(2) 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 CO(2).

A simple and portable breathing circuit designed for ventilatory muscle endurance training (VMET).

BACKGROUND: Ventilatory muscle endurance training (VMET) involves increasing minute ventilation (V (E)) against a low flow resistance at rest to simulate the hyperpnea of exercise. Ideally, VMET must maintain normocapnia over a wide range of V (E). This can be achieved by providing a constant fresh gas flow to a sequential rebreathing circuit. The challenge to make VMET suitable for home use is to provide a source of constant fresh gas flow to the circuit without resorting to compressed gas. METHODS: Our VMET circuit was based on a commercial sequential gas delivery breathing circuit (Pulmanex Hi-Ox, Viasys Healthcare, Yorba Linda, CA USA). Airflow was provided either by a small battery-driven aquarium air pump or by the entrainment of air down a pressure gradient created by the recoil of a hanging bellows that was charged during each inhalation. In each case, fresh gas flow was adjusted to be just less than resting V (E). Eight subjects then breathed from the circuit for three 10min periods consisting of relaxed breathing, breathing at 20 and then at 40L/min. We monitored V (E), end-tidal PCO2 (PetCO2) and hemoglobin O2 saturation (SpO2). RESULTS: During hyperpnea at 20 and 40L/min, PetCO2 did not differ significantly from resting levels with either method of supplying fresh gas. SpO2 remained greater than 96% during all tests. CONCLUSION: Isocapnic VMET can be reliably accomplished with a simple self-regulating, sequential rebreathing circuit without the use of compressed gas.