Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation.

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT <40% of predicted peak VO2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT ≥40% (P<0.001). Regarding the cohort with AT <40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

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.

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.

Kite skier's toe: an unusual case of frostbite.

Frostbite is a well-known occurrence in outdoor winter activity and exploration. We report the first documented case of frostbite associated with kite skiing. Kite skiing is an emerging sport that uses a kite to harness wind power for recreation and to travel long distances on skis. Certain characteristics of this sport may predispose athletes to frostbite injury. The stance required to resist and redirect the force created by the wind and kite puts constant pressure and repetitive trauma on the downwind great toe. This can compromise blood flow and increase risk of cold injury. Future kite skier expeditions should focus on specific prevention methods including properly fitting boots, adequate boot insulation, and frequent rest periods to inspect and warm toes.

Peripheral arterial desaturation is further exacerbated by exercise in adolescents with acute mountain sickness.

OBJECTIVE: Rapid ascent to altitude can result in the development of high altitude illnesses such as acute mountain sickness (AMS). This study aimed to investigate AMS symptoms in adolescents and study basic cardiopulmonary measurements at altitude. METHODS: Thirty-eight adolescents aged 16 to 19 years flew to 3500 m from 215 m and continued over a 23-day period to ascend to a maximum altitude of 5200 m. Each member of the expedition completed a Lake Louise Self-Assessment Questionnaire (LLSAQ) on a daily basis, and AMS was defined as a score of ≥ 3, with an associated headache. Physiology measurements included a step test, and both before and after exercise pulse oximetry, blood pressure, and pulse rate. RESULTS: Oxygen saturation inversely correlated with altitude (P = .001). Mean pulse rate increased from 70 beats/min (± 6.5) at 215 m to 83 beats/min (± 2.2) at 3500 m (P = .01), and a rise in blood pressure with ascent was highlighted (P = .004). The majority of subjects (84%) had an LLSAQ of 3 or more on at least 1 occasion, and they tended to record higher pulse rates (P = .005) and lower oxygen saturations (P = .001). Exercise-induced drops in oxygen saturation and raised pulse rates were more prolonged in subjects with severe AMS compared with subjects not having AMS (P = .046 and P = .005, respectively). CONCLUSIONS: The LLSAQ scoring system appeared to be a simple and effective technique to aid the diagnosis of adolescents who have AMS, and it may help improve the safety of large groups traveling to altitude. The AMS subjects tended to have low oxygen saturations and high pulse rates, highlighting potential areas for further research.

High altitude ataxia--its assessment and relevance.

Ataxia at altitude is reviewed in relation to acute mountain sickness (AMS). The cause of ataxia occurring at altitude is unknown but may be hypoxia affecting basal ganglia and hindbrain activity. Ataxia is an important sign of high altitude cerebral edema (HACE) but is less well-established as a clinical feature of AMS. Assessment of ataxia is part of the Environmental Systems and the Lake Louise questionnaires, together with a heel-to-toe measurement. More precise measures of ataxia include the Sharpened Romberg Test (SRT) and the use of unstable platforms. Isolated ataxia at altitude may not be related to AMS or HACE. Age affects ataxia and careful baseline measurements are essential in older subjects before results at high altitude can be interpreted. Testing for ataxia needs to be standardized with sufficient learning time. Ataxia should be distinguished from weakness or fatigue occurring at altitude. Specialized tests have not been shown to be clinically important. Our results above 5000 m showed that an abnormal SRT may be specific for AMS but with relatively poor sensitivity. Wobble board results have not correlated with AMS scores consistently. Other authors using an unstable platform in a chamber and static posturography during 3 days of exposure to 4559 m also found no relationship with AMS scores. Ataxia is a common and important clinical feature of HACE but is unhelpful in the assessment of mild or even moderate AMS in the absence of an altered mental state. The simple heel-to-toe test remains a useful part of the assessment of more severe AMS bordering on HACE.

Effect of losartan on performance and physiological responses to exercise at high altitude (5035 m).

OBJECTIVE: Altitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude. METHODS: Twenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count). RESULTS: At altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2 (70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44). CONCLUSION: Losartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m.

Perioperative Quality Initiative (POQI) consensus statement on fundamental concepts in perioperative fluid management: fluid responsiveness and venous capacitance.

BACKGROUND: Optimal fluid therapy in the perioperative and critical care settings depends on understanding the underlying cardiovascular physiology and individualizing assessment of the dynamic patient state. METHODS: The Perioperative Quality Initiative (POQI-5) consensus conference brought together an international team of multidisciplinary experts to survey and evaluate the literature on the physiology of volume responsiveness and perioperative fluid management. The group used a modified Delphi method to develop consensus statements applicable to the physiologically based management of intravenous fluid therapy in the perioperative setting. DISCUSSION: We discussed the clinical and physiological evidence underlying fluid responsiveness and venous capacitance as relevant factors in fluid management and developed consensus statements with clinical implications for a broad group of clinicians involved in intravenous fluid therapy. Two key concepts emerged as follows: (1) The ultimate goal of fluid therapy and hemodynamic management is to support the conditions that enable normal cellular metabolic function in order to produce optimal patient outcomes, and (2) optimal fluid and hemodynamic management is dependent on an understanding of the relationship between pressure, volume, and flow in a dynamic system which is distensible with variable elastance and capacitance properties.

The cerebral effects of ascent to high altitudes.

Cellular hypoxia is the common final pathway of brain injury that occurs not just after asphyxia, but also when cerebral perfusion is impaired directly (eg, embolic stroke) or indirectly (eg, raised intracranial pressure after head injury). We Review recent advances in the understanding of neurological clinical syndromes that occur on exposure to high altitudes, including high altitude headache (HAH), acute mountain sickness (AMS), and high altitude cerebral oedema (HACE), and the genetics, molecular mechanisms, and physiology that underpin them. We also present the vasogenic and cytotoxic bases for HACE and explore venous hypertension as a possible contributory factor. Although the factors that control susceptibility to HACE are poorly understood, the effects of exposure to altitude (and thus hypobaric hypoxia) might provide a reproducible model for the study of cerebral cellular hypoxia in healthy individuals. The effects of hypobaric hypoxia might also provide new insights into the understanding of hypoxia in the clinical setting.

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation.

BACKGROUND: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. METHODS: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. RESULTS: There were 70 participants (age 41.7±14.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27-0.68; p<0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12-0.59; p = 0.001). The area under the receiver-operating-characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. CONCLUSIONS: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients.

Visual analogue self-assessment of acute mountain sickness in adolescents: experience from two Himalayan expeditions.

OBJECTIVE: Recent studies have investigated visual analogue scales (VAS) as an alternative to the Lake Louise AMS Self-Report Score (LLS) for the self-assessment of acute mountain sickness (AMS). We investigated their use in adolescents. METHODS: The study was conducted during the 2009 and 2010 British Schools Exploring Society 35-day expeditions to Ladakh. Comparable ascent profiles were followed, reaching a maximum altitude of 6000 m. LLS and VAS AMS scores were recorded each morning. VAS comprised 100 mm lines for each LLS symptom; VAS scores were summed to give a composite daily total (VAS(c), expressed as a percentage). In 2010, an additional line was used to score overall "altitude sickness' (VAS(o)). RESULTS: 42 individuals participated in 2009 (83% compliance; mean age 17.4 years); 28 in 2010 (82% compliance; 17.5 years). 759 data points were recorded in 2009; 529 in 2010. There was a significant correlation between LLS and VAS(c) on both expeditions (rho=0.80, p<0.001 in 2009; rho=0.65, p<0.001 in 2010). These significant correlations remained when cases of AMS were analyzed separately. However, in all cases, the relationship between LLS and VAS was distorted, with a tendency for VAS to underscore symptoms of AMS when LLS<5. A VAS(c) value of 5.5% had an 82% specificity and sensitivity for all cases of AMS; VAS(c) of 9.5% had a 90% specificity and sensitivity for moderate and severe AMS. CONCLUSIONS: Whilst adolescents are capable of self-monitoring for AMS using VAS, the relationship with LLS is distorted. The LLS, despite its limitations, therefore remains the preferred method for the self-assessment of AMS in adolescents.

Intrapulmonary and intracardiac shunting with exercise at altitude.

Recent studies in normal participants have shown that right to left shunt blood vessels in the lung open up during exercise. We describe the first field study to investigate this phenomenon at altitude. This study aimed to assess the effect of altitude and partial acclimatization on inducible right to left shunting at rest and with exercise. A contrast-enhanced transcranial Doppler imaging technique to detect microbubbles after injection of blood and saline agitated with air was used to measure right to left shunting in 10 normal participants at rest and immediately after exercising to maximum oxygen consumption (VO(2max)) at 80 m, on acute exposure to 3450 m, and finally after a week above 3450 m. At 80 m, exercising resulted in right to left shunting via patent foramen ovale in 2 participants, but there was no evidence of shunting in the remaining 8 participants. Cerebral microbubbles were detected at rest in the 2 participants with patent foramen ovale on acute exposure to 3450 m, and the shunting increased on exercise (P = .04). In 5 of the remaining 8 participants without patent foramen ovale, cerebral microbubbles were detected on exercise (P = .04) but not at rest. Partial acclimatization had minimal effect on the prevalence or magnitude of the intrapulmonary or intracardiac shunts. Oxygenation was similar in those with shunts compared with those without shunts. Intrapulmonary shunting occurs on exercise at altitude, but the clinical and physiologic significances have yet to be determined. Despite the occurrence of shunting in most participants, our results suggest that this phenomenon is not a significant factor in altitude and exercise-induced hypoxia.