Gustavo R. Zubieta-Calleja, M.D., Gustavo Zubieta-Castillo, M.D., Luis A. Zubieta-Calleja, M.D., Rosayda Bersatti, M.D.

High Altitude Pathology Clinic (IPPA), P.O. Box 2852. La Paz, Bolivia.

All support for this paper by Instituto de Patologia de la Altura * Clinica IPPA.

ABSTRACT

On ascent to high altitude, with a lowered partial inspiratory oxygen tension, the normal compensatory mechanism is hyperventilation, an attempt to increase the arterial oxygen partial pressure (PaO₂ in mmHg). We report 2 cases of hypoventilation, witnessed on ascent by airplane from sea level to the city of La Paz (3600 m, PB = 495 mmHg). The first, a physician who arrived in La Paz and spent a restless night with increasing headache, not relieved by aspirin or acetaminophen. He described having had a slight flu before his arrival. His PaO₂ was 38 mmHg and ventilation (VE BTPS) 2715 cc/min/m2. (Normal for newcomers to this altitude is 60 and 6300 respectively). The second, a tourist who upon arrival in transit to the La Paz airport, felt extremely drowsy and sleepy. His PaO₂ was 41 mmHg and VE 2513 cc/min/m2. What strikes one the most was their low PaO₂ and low minute ventilation without evidence of pulmonary shunts, as subsequent hyperoxic tests gave normal PaO_2's .
When given 100 % oxygen by Hans Rudolph valves, both increased their ventilation (3327 and 6501 respectively) along with their PaO₂ (215,205) and their symptoms subsided. Two weeks later the physician returned to La Paz for two days and had absolutely no problems. It is possible that a transitory viral disorder of the respiratory center was responsible for the paradoxical hypoventilation on exposure to high altitude. The respiratory center responded with hyperventilation when given 100 % oxygen to breathe.

Key words: hypoxia, hypoventilation, oxygen, hypoxic ventilatory response, high altitude, hyperoxia.

It is well known that on ascent to high altitude, the human body has several compensating mechanisms. Hyperventilation is the means by which the organism compensates for a low inspired partial oxygen tension, a consequence of lowered barometric pressure.

Some authors (1,2,3,8) suspect that a poor hypoxic ventilatory response (HVR) may be related to the presentation of Acute Mountain Sickness (AMS).

We have observed, however that some people with acute mountain sickness, have low ventilation (hypoventilate), and hence low partial oxygen tension in the arterial blood (PaO₂), on arrival to 3600 m. Here we present two cases that have some variation of symptoms but have in common hypoventilation and in which we performed basic pulmonary testing including hyperoxia.

CASE REPORTS

Case 1

A 47 years old, white male Chilean physician on a trip to Sucre (2500 m. above sea level) for a Medical conference, remained in La Paz (3600 m.) for a couple of days. A few hours after his arrival at the airport, located at 4000 m, he began to have a headache, that gradually increased, and was unrelieved by acetaminophen or aspirin. He described that he had a slight flu before his trip. He was unable to sleep because of the intense headache but had no vomiting despite nausea, and loss of appetite. He had never smoked and had not ingested any alcohol prior to or after his arrival. He usually drank 2 cups of coffee per day. He had mild chronic constipation. He described an episode of cerebral insufficiency some years ago, that left no sequelae. He had had a tonsillectomy. His father had died from a neoplasm of the pancreas, his wife and 3 children were all healthy. He described a normal life in his country.

On physical examination, his vital signs were: weight: 68 K. Height: 1.80 m BP: 136/97 mmHg Temp: 36.7 ºC Pulse: 75/min Resp: 18/min, the pharynx was normal, no heart murmurs, nor abnormal chest sounds were heard. The electrocardiogram was normal. In blood tests: RBC count: 4.7 million/mm3, Htc = 42%, Hgb = 14 gm%, WBC count: 8200 with a differential of 80 % neutrophils, 18 % lymphocytes and 2 % monocytes. His chest X-Ray was normal.

The day after arrival, his blood gases breathing ambient air and during 100 % oxygen by Hans Rudolph mouthvalves are shown in table 1. Ventilation was measured using a mouthpiece attached to a Hans-Rudolph valve and recollected in a Tissot. The ventilation (ATPS) was measured through an AnalogDigital converter hooked to an Apple II+ computer, during five minutes, where all volumes were calculated. Capillary blood, alveolar (recollected by the Haldane-Priestley method) and expired air were measured in a PHM71 Mk2 Acid-Base Analyzer from Radiometer, calibrated according to the constructors manual. For the Hyperoxic tests a Douglas bag was filled with pure oxygen and later connected to the input respiratory valve. and ventilation measurements were repeated. Cheyne-Stokes ventilation was not present at any moment.

Case 2

A 27 year old Japanese male tourist arrived in the La Paz airport transiting from Miami to Santiago, Chile. After a one hour wait he began to get sleepy, very tired, and confused. He could hardly keep his eyes open, but responded to questions with difficulty and fell back asleep. The airport physician transferred him to our Clinic for evaluation. He complained of a headache.

He did not speak Spanish and very little English, which made communication difficult. He was a non smoker and had not ingested alcohol recently. He denied a previous history of drug or medication usage. A complete examination found the following:

Vital signs: weight: 67.7 K. height: 1.75 m BP: 140/81 mmHg Temp: 36.5 ºC Pulse: 60/min Resp: 8/min. The electrocardiogram was normal. CBC: WBC count: 11400 with a differential of 2 %, Band 72 % neutrophils, 2% eosinophils and 24 % lymphocytes. Hgb:17 gm% Hct: 51 % and RBC count: 5.71 million/mm3. Urine analysis was normal. His blood gases, during arrival, breathing ambient air and during 100 % oxygen by Hans Rudolph mouthvalves and ventilation measurements are shown in table 1. These ventilation measurements were made at the bedside, because he was drowsy, by adapting the Hans-Rudolph valves to a Wright respirometer, with recollection of gases in a Douglas Bag. Cheyne-Stokes respiration was not present at any moment.

Cholesterol, glucose, urea nitrogen, creatinine, SGOT, SGPT and bilirubin all were normal. Sodium was 135 mEq/l, Potassium 4.0 mEq/l and Chloride 102 mEq/l. Echography of the liver and gall bladder was normal, and was performed because the chest X-Ray showed an elevation of the right hemidiafragm, but was otherwise normal, with no signs of HAPE.

He was treated at the Clinic for two days with continuous oxygen by nasal prongs at 3 liters/minute. He received penicillin IM daily, Normal Ringer solution 500 cc plus 1 amp of potassium, and non-narcotic Ketorolaco 15 mg, IM. Blood gases were checked daily with and without oxygen and the second day breathing ambient air his PaO₂ was 55 mmHg, pH was 7.32, PaCO₂ was 29, which approached the normal for this altitude. His WBC count returned to normal 7500. He resumed his flight the third day, feeling much better and alert.

DISCUSSION:

Recent studies (9) show that at moderate altitudes (up to 3000 m) 25% of visitors suffer from

acute mountain sickness. This was associated with poor physical conditioning or underlying pulmonary problems. Although some studies have shown that people with the highest ventilatory response to hypoxia have the least symptoms of AMS (10,2,8), others fail to show a correlation (11,12) which makes the subject a controversial matter.

It is apparent from the evaluation of these two cases that hypoventilation is common to both and is an opposite response to the expected hyperventilation at lower barometric pressures and secondary lower partial inspired oxygen tensions (PIO₂). It is also evident that when given oxygen there is an increase in alveolar ventilation more significant in case # 2. This may be related to the paradoxical hyperventilation of some normal persons when given oxygen to breathe at altitude (4). As we previously showed (5), Chronic Mountain Sickness (CMS) patients demonstrate this type of response with a higher incidence than normal inhabitants of high altitude. Kryger et. al. (6) show hyperventilation on oxygen administration to be present only in CMS patients. It is significant that when given 100 % oxygen no intra-pulmonary shunt abnormalities were observed. Furthermore, the maximum PIO₂ achieved at 3600 m from a 98% oxygen cannula corresponds to approximately 430 mmHg, and with this mixture a normal person achieves a PaO₂ of at least 200 mmHg (7).

In an interesting comparison of ventilation (VE) in South American Indians, Sherpas of Nepal, inhabitants of the Tibetian Plateau and persons living in Leadville, Colorado, Hackett et. al.(4) show that South American natives have lower pulmonary ventilation, compared to lowlanders recently acclimatized to high altitudes. This was interpreted to be a energy saving mechanism for the work of breathing is reduced.

The patients described here, presented with a sensation of compression of the head, headaches, typical of AMS. They were not relieved by the common analgesics, aspirin or tylenol. One of the patients was a physician and therefore became acutely aware of this. The headache was relieved with oxygen.

The physician, while travelling to Sucre (2500 m), for a Medical meeting located at 2500 m, was examined at 3600 m. for the intense headache,. He felt very well in Sucre and one week later returned to La Paz, for two days but had no symptoms whatsoever. From this, we make the supposition that the hypoventilatory response was transitory. Unfortunately we were unable to measure his ventilation and blood gases a second time. Clinical normality with no headache suggested a normal physiological response. He had blood gases measured at sea level in his home town and said that they were completely normal. This implies that either the brain "learned" the appropriate reaction to hypoxia or that a reversible infection (perhaps viral) temporarily diminished his CNS ventilatory response. We don't know, however if the paradoxic hyperventilation on oxygen administration is a permanent event in these patients.

Occasionally, newcomers have died overnight in the city of La Paz. We are told that they went to bed and never woke up. It is not clear if they had any symptoms. No autopsies, to our knowledge, have been made and some cases were diplomats whose bodies were rapidly returned to their countries of origin. A possible explanation for these sudden deaths at altitude, could be progressive hypoventilation, that evolves to respiratory arrest and death. This needs to be explored further.

Todate no tests are known that can absolutely predict who will suffer from high altitude illness (1,2). Low hypoxic ventilatory response (HVR) has been suggested. However it is not known whether other factors such as fatigue, loss of sleep, diet or other external influences, may be involved. (1).

The low hypoxic ventilatory response may be explained partly by the fact that the hypoventilation could be time specific. Although a person may have a normal response to hypoxia before the ascent, some mechanism such as viral or bacterial disease may temporarily alter their respiratory center, thereby producing a limited hypoxic ventilatory response. The first case described here may be an example of this phenomenon.

Temporary hypoventilation on ascent to altitude may be an explanation for some cases of maladaptation to high altitude. These patients when given 100 % oxygen, may hyperventilate.

 

	Breathing ambient air					Breathing 100 % Oxygen by Hans Rudolph Valve
	Hct	PaO2	PaCO2	pH	VA(BTPS)	PaO2	VA(BTPS)
	%	mmHg	mmHg		Ml/min/m2	mmHg	ml/min/m2
NORMAL	55	60	30	7.40	4100	195	3910
CASE 1	42	38	33	7.36	1297	215	1467
CASE 2	51	41	28	7.43	2384	205	5151

 

Table 1. Acid-base status and ventilation of normal subjects (13,7) and both cases breathing ambient air and during hyperoxia. VE=Ventilation in ml/min/m2, Hct=Hematocrit, PaO₂=Partial pressure of oxygen in arterial blood. PaCO₂= partial pressure of carbon dioxide in arterial blood.
 

REFERENCES

1. Houston C.S. Research in altitude illness. Medicine Sport Sci 1985; 19: 170-179.

2. West J.B. Acclimatization and tolerance to extreme altitude. Journal of Wilderness Medicine 1993; 4: 17-26.

3. Hackett P.H. Hazards of high-altitude travel International Travel Med Proceedings 1991; 256-262.

4. Hackett P.H., Reeves J.T., Grover R.F., Weil J.V. Ventilation in human populations native to high altitude. In: High Altitude and Man. Waberly Press Inc Am Physiol Soc 1984; 179-191.

5. Zubieta-Castillo G, Zubieta-Calleja GR. Las enfermedades pulmonares y el mal de montana cronico. Revista de la Academia Nacional de Ciencias de Bolivia 1986; 5: 47-54.

6. Kryger M, McCullough R, Doekel R, Collins D, Weill JV, and Grover RF. Excessive polycythemia of high altitude: Role of ventilatory drive and lung disease. Am Rev Respir Dis 1987; 118: 659-666.

7. Zubieta-Calleja G.R., Zubieta G. In: High Altitude Pathology at 12000 ft. IPPA. Casilla 2852, La Paz, Bolivia. 1989; .

8. Schoene R.B. Hypoxic ventilatory response and exercise ventilation at sea level and high altitude. In: High Altitude and Man. Waberly Press Inc. Am Physiol Soc 1984; .

9. Honigman B., Theis M.K., Koziol M.J., Roach R., Yip R., Houston C., Moore L.G. Acute mountain sickness in a general tourist population at moderate altitudes. Annals of Internal Medicine 1993; 118: 587-592.

10. Hackett P.H., Rennie D., Hofmeister S.E., Grover R.F. Grover E.B. Reeves J.T. Fluid retention and relative hypoventilation in acute mountain sickness. Respiration 1982; 43: 3211-9.

11. Milledge J.S., Thomas P.S., Beeley J.M., English J.S.C. Hypoxic ventilatory response and acute mountain sickness. Eur Respir J 1988; 1: 948-951.

12. Milledge J.S., Beeley J.M., Broome J., Luff N., Pelling M., Smith D. Acute mountain sickness: susceptibility, fitness and hypoxic ventilatory response Eur Respir J 1991; 4: 1000-1003.

13. Cudkowicz L, Spielvogel H. and Zubieta G. Respiratory studies in women at high altitude. Respiration 1972; 29: 393-426. 14. Consolazio C.F., Johnson R.E, Pecora L.J. In: Physiological Measurements of Metabolic Functions in Man. 1963; McGraw-Hill Book Company.