Alveolar PCO2 oscillations and ventilation at sea level and at high altitude.

This study examines the potential for a ventilatory drive, independent of mean PCO2, but depending instead on changes in PCO2 that occur during the respiratory cycle. This responsiveness is referred to here as "dynamic ventilatory sensitivity." The normal, spontaneous, respiratory oscillations in alveolar PCO2 have been modified with inspiratory pulses approximating alveolar PCO2 concentrations, both at sea level and at high altitude (5,000 m, 16,400 ft.). All tests were conducted with subjects exercising on a cycle ergometer at 60 W. The pulses last about half the inspiratory duration and are timed to arrive in the alveoli during early or late inspiration. Differences in ventilation, which then occur in the face of similar end-tidal PCO2 values, are taken to result from dynamic ventilatory sensitivity. Highly significant ventilatory responses (early pulse response greater than late) occurred in hypoxia and normoxia at sea level and after more than 4 days at 5,000 m. The response at high altitude was eliminated by normalizing PO2 and was reduced or eliminated with acetazolamide. No response was present soon after arrival (<4 days) at base camp, 5,000 m, on either of two high-altitude expeditions (BMEME, 1994, and Kanchenjunga, 1998). The largest responses at 5,000 m were obtained in subjects returning from very high altitude (7,100-8,848 m). The present study confirms and extends previous investigations that suggest that alveolar PCO2 oscillations provide a feedback signal for respiratory control, independent of changes in mean PCO2, suggesting that natural PCO2 oscillations drive breathing in exercise.

Acute mountain sickness: pulmonary and cerebral oedema of high altitude.

Acute mountain sickness is a condition affecting otherwise healthy individuals on going rapidly to altitude. It is caused by sub-acute hypoxia in susceptible subjects. Its study may provide lessons for the more complicated situation of hypoxia in patients undergoing intensive care. This paper reviews the incidence and aetiology of acute mountain sickness, pulmonary and cerebral oedema of high altitude and possible mechanisms are discussed. Prophylaxis depends on an awareness of the condition in all those venturing to high altitude and guidelines are suggested. The treatment of the established condition is reviewed.

Serum erythropoietin in humans at high altitude and its relation to plasma renin.

Serum immunoreactive erythropoietin (siEp) was estimated in samples collected from members of two scientific and mountaineering expeditions, to Mount Kongur in Western China and to Mount Everest in Nepal. SiEp was increased above sea-level control values 1 and 2 days after arrival at 3,500 m and remained high on ascent to 4,500 m. Thereafter, while subjects remained at or above 4,500 m, siEp declined, and by 22 days after the ascent to 4,500 m was at control values but increased on ascent to higher altitude. Thus siEp was at a normal level during the maintenance of secondary polycythemia from high-altitude exposure. On descent, with removal of altitude hypoxia, siEp decreased, but despite secondary polycythemia levels remained measurable and in the range found in subjects normally resident at sea level. On Mount Everest, siEp was significantly (P less than 0.01) elevated above preexpedition sea-level controls after 2-4 wk at or above 6,300 m. There was no correlation between estimates of siEp and plasma renin activity in samples collected before and during both expeditions.

Nocturnal periodic breathing at altitudes of 6,300 and 8,050 m.

Nocturnal periodic breathing was studied in eight well-acclimatized subjects living at an altitude of 6,300 m [barometric pressure (PB) 350-352 Torr] for 3-5 wk and in four subjects during one night at 8,050 m altitude (PB 281-285 Torr). The measurements at 6,300 m included tidal volume by inductance plethysmography, arterial O2 saturation by ear oximetry (calibrated by arterial blood samples), electrocardiogram (ECG), and electrooculogram. At 8,050 m, periodic breathing was inferred from the cyclical variation in heart rate obtained from a night-long ECG record. All subjects at 6,300 m altitude showed well-marked periodic breathing with apneic periods. Cycle length averaged 20.5 s with 7.9 s apnea. Minimal arterial O2 saturation averaged 63.4% corresponding to a PO2 of approximately 33 Torr, i.e., approximately 6 Torr lower than the normal value at rest during daytime. This was probably the most severe hypoxemia of the 24-h period. At 8,050 m altitude, the cycle length averaged 15.4 s, much longer than predicted by a theoretical model. Cyclical variations in heart rate caused by periodic breathing occurred in all subjects, but abnormal cardiac rhythms such as ventricular premature contractions were uncommon. The severe arterial hypoxemia caused by periodic breathing may be an important determinant of tolerance to these great altitudes.

Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness.

The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P < 0.05). A marked increase in resting plasma CCK was observed on the morning of the second day at BC relative to sea-level control values (62.9 +/- 42.2 pmol/L(-1) vs. SL1: 4.3 +/- 8.3 pmol/L(-1), P < 0.05 vs. SL2: 26.5 +/- 25.2 pmol/L(-1), P < 0.05). Maximal exercise increased CCK by 78.5 +/- 24.8 pmol/L(-1), (P < 0.05 vs. resting value) during the SL1 test and increased the plasma concentration of non-esterified fatty acids and glycerol at BC (P < 0.05 vs. SL1/SL2). The CCK response was not different in five subjects who presented with anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.

Serial changes in spirometry during an ascent to 5,300 m in the Nepalese Himalayas.

The aims of the present study were to determine the changes in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and peak expiratory flow (PEF), during an ascent to 5,300 m in the Nepalese Himalayas, and to correlate the changes with arterial oxygen saturation measured by pulse oximetry (SpO2) and symptoms of acute mountain sickness (AMS). Forty-six subjects were studied twice daily during an ascent from 2,800 m (mean barometric pressure 550.6 mmHg) to 5,300 m (mean barometric pressure 404.3 mmHg) during a period of between 10 and 16 days. Measurements of FVC, FEV1, PEF, SpO2, and AMS were recorded. AMS was assessed using a standardized scoring system. FVC fell with altitude, by a mean of 4% from sea level values [95% confidence intervals (CI) 0.9% to 7.4%] at 2,800 m, and 8.6% (95% CI 5.8 to 11.4%) at 5,300 m. FEV1 did not change with increasing altitude. PEF increased with altitude by a mean of 8.9% (95% CI 2.7 to 15.1%) at 2,800 m, and 16% (95% CI 9 to 23%) at 5,300 m. These changes were not significantly related to SpO2 or AMS scores. These results confirm a progressive fall in FVC and increase in PEF with increasing hypobaric hypoxia while FEV1 remains unchanged. The increase in PEF is less than would be predicted from the change in gas density. The fall in FVC may be due to reduced inspiratory force producing a reduction in total lung capacity; subclinical pulmonary edema; an increase in pulmonary blood volume, or changes in airway closure. The absence of a correlation between the spirometric changes and SpO2 or AMS may simply reflect that these measurements of pulmonary function are not sufficiently sensitive indicators of altitude-related disease. Further studies are required to clarify the effects of hypobaric hypoxia on lung volumes and flows in an attempt to obtain a unifying explanation for these changes.

High altitude headache: treatment with ibuprofen.

Up to half of those who ascend rapidly to altitudes of over 3,000 m may experience symptoms of acute mountain sickness (AMS) and of these some 95% may suffer from high altitude headache. We report the first controlled trial specifically to assess an oral drug therapy for this common symptom. Subjects were 21 members of mountaineering expeditions to similar altitudes in the Bolivian Andes and the Himalayas in Nepal. The study was of a randomized, placebo-controlled, double-blind, within-patient crossover design. Ibuprofen was significantly superior to placebo both in reducing headache severity and in speed of relief (a mean difference of 94 min in time to no/minimal headache). Only 14% of subjects who initially took ibuprofen felt the need for further medication compared to 83% of those who took placebo first (p = 0.02). Of the 11 subjects completing both phases of the crossover, 8 (73%) favored ibuprofen while the remainder had no preference (p = 0.004). No attributable adverse effects occurred. The results suggest that ibuprofen is a safe and effective treatment for high altitude headache.

Acid-base changes associated with respiratory acclimatization to altitude.

The respiratory changes associated with chronic hypoxia are described. The possible biochemical mechanisms which are responsible for the changes in control of ventilation are discussed and relevant experimental evidence assessed.

Arterial oxygen desaturation and intestinal absorption of xylose.

Small-bowel absorption was studied using the xylose absorption test in 16 patients with varying degrees of arterial oxygen desaturation due to either congenital heart disease or chronic lung disease. Xylose absorption was decreased in the cases with more severe desaturation. The correlation of xylose absorption with arterial saturation was significant. In nine cases hypoxia was relieved by either oxygen administration or surgery. Repeat testing showed an increase in xylose absorption in every case, the mean increase being 11.7%, which was statistically significant.

The ventilatory response to hypoxia: how much is good for a mountaineer?

Methods for measuring the ventilatory response to hypoxia (HVR) are reviewed. The criteria for success as a high altitude mountaineer are defined as freedom from acute mountain sickness (AMS) and ability to perform well at extreme altitude. The evidence for a brisk HVR being protective against AMS and associated with successful high altitude performance is reviewed. The contrary evidence of blunted HVR in high altitude residence and some elite climbers is discussed. The effect of a brisk HVR in producing periodic breathing when asleep at altitude is noted. It seems that there is an optimum HVR for different circumstances and peoples. A brisk HVR is a benefit in lowlanders going to altitude for the first time whereas a blunted HVR is appropriate for high altitude residents and possibly for very experienced elite climbers.

Therapeutic fibreoptic bronchoscopy in intensive care.

Experience with therapeutic bronchoscopy using the fibreoptic bronchoscope in intensive care has shown it to be a useful procedure. The Nosworthy connection has also been modified to allow intermittent positive-pressure ventilation to be maintained during bronchoscopy. This procedure is valuable in those cases where sputum or blood are retained in the airways despite adequate physiotherapy and endotracheal suction. Fibreoptic bronchoscopy should be available as a routine service in intensive therapy units.

Salt and water control at altitude.

The physiological effect of altitude hypoxia, in the absence of exercise, is a sodium and water diuresis with decrease in plasma and extra-cellular volumes. Plasma aldosterone concentrations (PAC) are reduced but plasma atrial natriuretic peptide (ANP) levels are modestly increased. Day-long exercise at low altitude has almost opposite effects on fluid balance. There is an anti-diuresis, sodium retention, expansion of the plasma and extra-cellular compartments, elevation of PAC and ANP. Subjects who develop acute mountain sickness (AMS) show a pathological response to hypoxia even before the development of symptoms. There is an anti-diuresis, sodium retention, increased plasma and extra-cellular volumes and increased PAC compared with subjects resistant to AMS. Plasma ANP tends to be elevated compared with sea level values but the relation of ANP levels to AMS is variable. In general therefore, the pathological response to altitude hypoxia parallels that of exercise at low altitude and is opposite to the physiological response. Both exercise and the pathological response predispose the subject to edema and are probably important in the genesis of AMS.

Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease.

Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre.

Renin, aldosterone, and converting enzyme during exercise and acute hypoxia in humans.

The possibility that hypoxia might inhibit the secretion of angiotension-converting enzyme (ACE) would explain the low concentrations of aldosterone reported in humans at high altitude. To observe the effect of such a reduction in ACE concentration on the plasma aldosterone concentration (PAC) four subjects performed mild exercise throughout a 2-h study so as to elevate their plasma renin activity (PRA). After the first 60 min breathing air they were switched to breathing 12.8% O2 (4,000 an altitude equivalent). Venous samples were taken at intervals for hormone analysis. Results showed the expected rise of PRA and PAC both tending toward a plateau after about 45 min. There was no significant change in ACE activity (F = 0.065). Hypoxia produced a further 50% rise in PRA but a fall in PAC and a 30% reduction in ACE activity. Angiotensin I concentrations closely followed PRA throughout (r = 0.984). These results indicate that during exercise acute hypoxia changes the usual close relationship between PAC and PRA by reducing ACE activity.

Angiotensin converting enzyme response to hypoxia in man: its role in altitude acclimatization.

The response of serum angiotensin converting enzyme (ACE) activity to three grades of hypoxia was studied in two groups of human subjects. Hypoxic gas mixtures having oxygen concentrations of 14, 12.6 and 10.4% were breathed successively for a period of 10 min at each concentration. Venous blood was sampled at the end of each of the three periods and arterial oxygen saturation was recorded throughout the experiment. The subjects were selected as being 'good' or 'poor' acclimatizers according to their history of acute mountain sickness. There were five subjects in each group. Hypoxia resulted in a reduction in ACE activity in both groups, the reduction being linear with respect to arterial oxygen saturation. The reduction in ACE activity was greater in the good acclimatizer group as shown by a significantly greater slope of the response line of ACE activity to arterial oxygen saturation. The significance of this finding in relation to the mechanism underlying acute mountain sickness is discussed.