Recruitment of non-perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m.

KEY POINTS: A physiological response to increase microcirculatory oxygen extraction capacity at high altitude is to recruit capillaries. In the present study, we report that high altitude-induced sublingual capillary recruitment is an intrinsic mechanism of the sublingual microcirculation that is independent of changes in cardiac output, arterial blood pressure or systemic vascular hindrance. Using a topical nitroglycerin challenge to the sublingual microcirculation, we show that high altitude-related capillary recruitment is a functional response of the sublingual microcirculation as opposed to an anatomical response associated with angiogenesis. The concurrent presence of a low capillary density and high microvascular reactivity to topical nitroglycerin at sea level was found to be associated with a failure to reach the summit, whereas the presence of a high baseline capillary density with the ability to further increase maximum recruitable capillary density upon ascent to an extreme altitude was associated with summit success. ABSTRACT: A high altitude (HA) stay is associated with an increase in sublingual capillary total vessel density (TVD), suggesting microvascular recruitment. We hypothesized that microvascular recruitment occurs independent of cardiac output changes, that it relies on haemodynamic changes within the microcirculation as opposed to structural changes and that microcirculatory function is related to individual performance at HA. In 41 healthy subjects, sublingual handheld vital microscopy and echocardiography were performed at sea level (SL), as well as at 6022 m (C2) and 7042 m (C3), during ascent to 7126 m within 21 days. Sublingual topical nitroglycerin was applied to measure microvascular reactivity and maximum recruitable TVD (TVDNG ). HA exposure decreased resting cardiac output, whereas TVD (mean ± SD) increased from 18.81 ± 3.92 to 20.92 ± 3.66 and 21.25 ± 2.27 mm mm-2 (P < 0.01). The difference between TVD and TVDNG was 2.28 ± 4.59 mm mm-2 at SL (P < 0.01) but remained undetectable at HA. Maximal TVDNG was observed at C3. Those who reached the summit (n = 15) demonstrated higher TVD at SL (P < 0.01), comparable to TVDNG in non-summiters (n = 21) at SL and in both groups at C2. Recruitment of sublingual capillary TVD to increase microcirculatory oxygen extraction capacity at HA was found to be an intrinsic mechanism of the microcirculation independent of cardiac output changes. Microvascular reactivity to topical nitroglycerin demonstrated that HA-related capillary recruitment is a functional response as opposed to a structural change. The performance of the vascular microcirculation needed to reach the summit was found to be associated with a higher TVD at SL and the ability to further increase TVDNG upon ascent to extreme altitude.

Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study.

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.

Assessment of endothelial cell function and physiological microcirculatory reserve by video microscopy using a topical acetylcholine and nitroglycerin challenge.

BACKGROUND: Assessment of the microcirculation is a promising target for the hemodynamic management of critically ill patients. However, just as the sole reliance on macrocirculatory parameters, single static parameters of the microcirculation may not represent a sufficient guide. Our hypothesis was that by serial topical application of acetylcholine (ACH) and nitroglycerin (NG), the sublingual microcirculation can be challenged to determine its endothelial cell-dependent and smooth muscle-dependent physiological reserve capacity. METHODS: In 41 healthy subjects, sublingual capillary microscopy was performed before and after topical application of ACH and NG. Total vessel density (TVD) was assessed in parallel using manual computer-assisted image analysis as well as a fully automated analysis pathway utilizing a newly developed computer algorithm. Flow velocity was assessed using space-time diagrams of the venules as well as the algorithm-based calculation of an average perfused speed indicator (APSI). RESULTS: No change in all measured parameters was detected after sublingual topical application of ACH. Sublingual topical application of NG however led to an increase in TVD, space-time diagram-derived venular flow velocity and APSI. No difference was detected in heart rate, blood pressure, and cardiac output as measured by echocardiography, as well as in plasma nitric oxide metabolite content before and after the topical application of ACH and NG. CONCLUSIONS: In healthy subjects, the sublingual microcirculatory physiological reserve can be assessed non-invasively by topical application of nitroglycerin without affecting systemic circulation.

Morphological Brain Changes after Climbing to Extreme Altitudes--A Prospective Cohort Study.

BACKGROUND: Findings of cerebral cortical atrophy, white matter lesions and microhemorrhages have been reported in high-altitude climbers. The aim of this study was to evaluate structural cerebral changes in a large cohort of climbers after an ascent to extreme altitudes and to correlate these findings with the severity of hypoxia and neurological signs during the climb. METHODS: Magnetic resonance imaging (MRI) studies were performed in 38 mountaineers before and after participating in a high altitude (7126 m) climbing expedition. The imaging studies were assessed for occurrence of new WM hyperintensities and microhemorrhages. Changes of partial volume estimates of cerebrospinal fluid, grey matter, and white matter were evaluated by voxel-based morphometry. Arterial oxygen saturation and acute mountain sickness scores were recorded daily during the climb. RESULTS: On post-expedition imaging no new white matter hyperintensities were observed. Compared to baseline testing, we observed a significant cerebrospinal fluid fraction increase (0.34% [95% CI 0.10-0.58], p = 0.006) and a white matter fraction reduction (-0.18% [95% CI -0.32--0.04], p = 0.012), whereas the grey matter fraction remained stable (0.16% [95% CI -0.46-0.13], p = 0.278). Post-expedition imaging revealed new microhemorrhages in 3 of 15 climbers reaching an altitude of over 7000 m. Affected climbers had significantly lower oxygen saturation values but not higher acute mountain sickness scores than climbers without microhemorrhages. CONCLUSIONS: A single sojourn to extreme altitudes is not associated with development of focal white matter hyperintensities and grey matter atrophy but leads to a decrease in brain white matter fraction. Microhemorrhages indicative of substantial blood-brain barrier disruption occur in a significant number of climbers attaining extreme altitudes.

Intensive care without walls - introduction of a Medical Emergency Team system in a Swiss tertiary care centre.

QUESTIONS UNDER STUDY: To improve the response of deteriorating patients during their hospital stay, the University Hospital Bern has introduced a Medical Emergency Team (MET). Aim of this retrospective cohort study is to review the preceding factors, patient characteristics, process parameters and their correlation to patient outcomes of MET calls since the introduction of the team. METHODS: Data on patient characteristics, parameters related to MET activation and intervention and patient outcomes were evaluated. A Vital Sign Score (VSS), which is defined as the sum of the occurrence of each vital sign abnormalities, was calculated for all physiological parameters pre MET event, during event and correlation with hospital outcomes. RESULTS: A total of 1,628 MET calls in 1,317 patients occurred; 262 (19.9%) of patients with MET calls during their hospital stay died. The VSS pre MET event (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.50-2.13; AUROC 0.63; all p <0.0001) and during the MET call (OR 1.60, 95% CI 1.41-1.83; AUROC 0.62; all p <0.0001) were significantly correlated to patient outcomes. A significant increase in MET calls from 5.2 to 16.5 per 1000 hospital admissions (p <0.0001) and a decrease in cardiac arrest calls in the MET perimeter from 1.6 in 2008 to 0.8 per 1000 admissions was observed during the study period (p = 0.014). CONCLUSIONS: The VSS is a significant predictor of mortality in patients assessed by the MET. Increasing MET utilisation coincided with a decrease in cardiac arrest calls in the MET perimeter.

New insights into changes in corneal thickness in healthy mountaineers during a very-high-altitude climb to Mount Muztagh Ata.

OBJECTIVE: To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT). METHODS: Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m. RESULTS: Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2 increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2) paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO(2) and age. CONCLUSIONS: Corneal swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness-related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.