Mark Edsell

Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study

Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n = 24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2 = 12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n = 7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.

Cerebral venous system and anatomical predisposition to high-altitude headache

As inspired oxygen availability falls with ascent to altitude, some individuals develop high‐altitude headache (HAH). We postulated that HAH results when hypoxia‐associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies.

Changes in pupil dynamics at high altitude--an observational study using a handheld pupillometer.

Gross pupil dynamics are used as an indirect measure of brain function. Changes in hypoxia and intracranial pressure are thought to alter pupil responses to light. This study assessed a portable handheld pupil measuring device (pupillometer) in the field investigating the changes in pupil size, speed of reaction, and rate of constriction/dilatation with hypoxia induced by changes in altitude. A correlation between pupil dynamics and acute mountain sickness was sought. Seventeen volunteers were studied following acute exposure to 3450 m and then during a trek to 4770 m in Ladakh, India. The pupillometer was used to record maximum and minimum pupil diameter in response to a standard light source with calculation of latency, constriction and dilatation velocities. Acute mountain sickness (AMS) was recorded using Lake Louise self completed questionnaires both in the morning and afternoon on each day. Acute altitude exposure resulted in a significant reduction of percentage change in pupil size (36.5% to 24.1% p=<0.001), significant delay in pupillary contraction (latency; 0.208 to 0.223 seconds p=0.015) and a significant slowing of the rate of contraction (constriction velocity; -2.77 mm/s to -1.75 mm/s p=0.012). These changes reverted to normal during a period of acclimatization. A significant diurnal variation in pupil size was also observed. There was no significant difference between subjects with and without AMS. The handheld pupillometer is a suitable robust tool for monitoring changes in pupil dynamics in the field. With acute exposure to hypobaric hypoxia associated with an ascent to a moderate altitude, there is a general slowing of pupil function which reverts to normal within a few days of acclimatization. There appears to be a marked diurnal variation in pupil size. The measurements clearly demonstrated an effect of hypoxia on cerebral function, but these changes did not relate to moderate AMS.

Predictors of Failure in Fast-Track Cardiac Surgery

OBJECTIVES Fast-track (FT) management of cardiac surgery patients is associated with early extubation and reduced length of intensive care unit (ICU) stay, with potential benefit of reduced hospital costs. The authors examined perioperative factors and their influence on failure of FT and what implications this failure had. DESIGN Prospective data collection from all adult cardiac surgeries between 2011 and 2013. SETTING Single-institution study. PARTICIPANTS The study included 2,770 consecutive adult cardiac surgery patients. INTERVENTIONS All participants underwent adult cardiac surgeries. Of those, 451 (16.3%) patients were selected to undergo FT management. MEASUREMENTS AND MAIN RESULTS Failure of FT was defined as early (admission to ICU on day of surgery) or late (patients later admitted to the ICU from the ward). Univariate and multivariate regression analyses were used to identify which variables predicted FT failure. Of the 451 patients included in this study, 138 (30.6%) failed the FT, with 115 (83.3%) early failures and 23 (16.7%) late failures. Predictors of failure were reduced renal function, hypertension, age, EuroSCORE, cardiopulmonary bypass time, first lactate or base deficit after surgery (all p<0.01), and cross-clamp time (p<0.05). Multivariate analysis showed that the strongest predictor of failure was glomerular filtration rate (GFR)<65 mL/min/BSA (sensitivity, 54%; specificity, 61%; likelihood ratio, 1.39; area under receiver operating characteristics curve, 0.59; 95% confidence interval, 0.53-0.64). Median length of hospital stay was longer for the failed group (5 v 7 days, p<0.001). There were no mortalities in any of the patients selected for FT. CONCLUSIONS A number of perioperative factors are associated with failure to FT, the strongest predictor being GFR. Failure to FT can lead to significantly longer hospital stay.

Exercise limitation of acetazolamide at altitude (3459 m)

OBJECTIVE To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.

Systemic oxygen extraction during exercise at high altitude

Background Classic teaching suggests that diminished availability of oxygen leads to increased tissue oxygen extraction yet evidence to support this notion in the context of hypoxaemia, as opposed to anaemia or cardiac failure, is limited. Methods At 75 m above sea level, and after 7–8 days of acclimatization to 4559 m, systemic oxygen extraction [C(a−v)O2] was calculated in five participants at rest and at peak exercise. Absolute [C(a−v)O2] was calculated by subtracting central venous oxygen content (CcvO2) from arterial oxygen content (CaO2) in blood sampled from central venous and peripheral arterial catheters, respectively. Oxygen uptake (V˙O2) was determined from expired gas analysis during exercise. Results Ascent to altitude resulted in significant hypoxaemia; median (range) SpO2 87.1 (82.5–90.7)% and PaO2 6.6 (5.7–6.8) kPa. While absolute C(a−v)O2 was reduced at maximum exercise at 4559 m [83.9 (67.5–120.9) ml litre−1 vs 99.6 (88.0–151.3) ml litre−1 at 75 m, P=0.043], there was no change in oxygen extraction ratio (OER) [C(a−v)O2/CaO2] between the two altitudes [0.52 (0.48–0.71) at 4559 m and 0.53 (0.49–0.73) at 75 m, P=0.500]. Comparison of C(a−v)O2 at peak V˙O2 at 4559 m and the equivalent V˙O2 at sea level for each participant also revealed no significant difference [83.9 (67.5–120.9) ml litre1 vs 81.2 (73.0–120.7) ml litre−1, respectively, P=0.225]. Conclusion In acclimatized individuals at 4559 m, there was a decline in maximum absolute C(a−v)O2 during exercise but no alteration in OER calculated using central venous oxygen measurements. This suggests that oxygen extraction may have become limited after exposure to 7–8 days of hypoxaemia.

Using ultrasound lung comets in the diagnosis of high altitude pulmonary edema: fact or fiction?

High altitude pulmonary edema is a life-threatening condition that remains a concern for climbers and clinicians alike. Within the last decade, studies have shown ultrasonography to be valuable in the accurate diagnosis of a variety of lung pathologies, including cardiogenic pulmonary edema, pleural effusion, pneumothorax, and lung consolidation. Recently, studies conducted in remote areas have demonstrated that ultrasound lung comets can be used as a measure of subacute pulmonary edema and high altitude pulmonary edema in climbers ascending to altitude. This clinical review article provides an overview of lung ultrasonography and its relevance as a diagnostic aid to respiratory pathology. In addition, we describe a standardized technique for identifying ultrasound lung comets and its utility in recognizing the presence of extravascular lung water, as well as the results of studies that have used this approach at sea level and high altitude.

Simulation-based learning of transesophageal echocardiography in cardiothoracic surgical trainees: A prospective, randomized study.

OBJECTIVES The Intercollegiate Surgical Curriculum now recommends that cardiac surgical trainees should be able to understand and interpret transesophageal echocardiography images. However, cardiac surgical trainees receive limited formal transesophageal echocardiography training. The objective of this study was to assess the impact of simulation-based teaching versus more traditional operating room teaching on transesophageal echocardiography knowledge in cardiac surgical trainees. METHODS A total of 25 cardiac surgical trainees with no formal transesophageal echocardiography learning experience were randomly assigned by computer to a study group receiving simulation-based transesophageal echocardiography teaching via the Heartworks (Inventive Medical, London, UK) simulator (n = 12) or a control group receiving transesophageal echocardiography teaching during elective cardiac surgery (n = 13). Each subject undertook a video-based test composed of 20 multiple choice questions on standard transesophageal echocardiography views before and after teaching. RESULTS There was no significant difference in the pretest scores between the 2 groups (P = .89). After transesophageal echocardiography teaching, subjects within each group demonstrated a statistically significant improvement in transesophageal echocardiography knowledge. Although the subjects within the simulation group outperformed their counterparts in the operating room teaching group in the post-test scores, this difference was not significant (P = .14). CONCLUSIONS Despite the familiarity with transesophageal echocardiography images during surgery, subjects in the simulation group performed at least as well as those in the operating room group. Surgical trainees will benefit from formal transesophageal echocardiography teaching incorporated into their training via either learning method.

High-intensity intermittent exercise increases pulmonary interstitial edema at altitude but not at simulated altitude.

OBJECTIVE Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders. METHODS Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines. RESULTS After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours. CONCLUSIONS HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema.

Improving Sleep at Altitude: A Comparison of Therapies

OBJECTIVE This study aimed to compare 3 treatment modalities during sleep at an altitude of 5300 m to identify strategies for reducing the incidence of periodic breathing at high altitude. METHODS Fifteen trekkers, with identical ascent profiles and no signs or symptoms of altitude illness, served as subjects. All study participants arrived at 5300 m after a gradual ascent from 1300 m. On their second night at 5300 m, subjects were randomly assigned (with a computer-based random assignment procedure) to 1 of 4 different treatment groups: control (n = 4); 1 L/min O(2) via a demand system during sleep (n = 3); 1 L/min O(2)/CO(2) mix (1.5% CO(2)) via a demand system during sleep (n = 4); or 125 mg acetazolamide 30 minutes before bedtime (n = 4). Heart rate, respiration rate, blood oxygen saturation, tidal volume, minute volume, and apnea hypopnea index were measured. RESULTS Upon comparing the 4 groups, there were no statistically significant differences between the variables. One-way analysis of variance indicated a trend toward statistical significance for SaO(2) between groups (F = 2.9, P = .08), and Tukey Honestly Significant Difference (HSD) post hoc tests indicated a trend in the SaO(2) difference between the 1 L/min oxygen and control groups (P = .07). While 1-way analysis of variance suggested no difference for respiratory rate between groups (F = 2.5, P = .1), Tukey HSD indicated a trend in statistical difference of the respiratory rate between 1 L/min O(2) and 1 L/min O(2)/CO(2) mixture (P = .08). CONCLUSIONS These statistical trends found between control and treatment groups indicate that further study is warranted.