ORIGINAL CONTRIBUTION acute mountain sickness, treatment
Treatment of Acute Mountain Sickness: Hyperbaric Versus Oxygen Therapy Study objectives: To compare the benefits of simulated descent in a hyperbaric chamber with those of supplementary oxygen for the treatment of acute m o u n t a i n sickness. Design: A prospective study. Setting: The Snake River Health Clinic in Keystone, Colorado, which has an altitude of 2,850 m (9,300 it). Type of participants: Twenty-four patients w h o presented with acute m o u n t a i n sickness. Interventions: A simulated descent of 1,432 m (4,600 it) was attained by placing the patients in a fabric hyperbaric chamber and pressurizing the chamber to 120 m m Hg (2.3 PSI) above ambient pressure. Patients were randomly assigned to either the hyperbaric treatment or treatment with 4 L of oxygen given by facemask; both treatments lasted for two hours. Measurements and main results: Mean arterial oxygen saturation (Sao2) increased 7% (84 +- 2% to 91 +_ 1%) with pressurization and 14% (83 +_ 4% to 96 ± 1%) with oxygen during treatment over pretreatment levels. S y m p t o m s of acute m o u n t a i n sickness decreased as rapidly with pressurization as with oxygen treatment, despite significantly higher Sao 2 in the oxygen-treated group during treatment, S y m p t o m a t i c i m p r o v e m e n t was retained in both groups at least one hour after treatment. Conclusion: Simulated descent in a fabric hyperbaric chamber is as effective as oxygen therapy for the i m m e d i a t e relief of acute m o u n t a i n sickness. [Kasic JF, Yaron M, Nicholas RA, Lickteig JA, Roach R: Treatment of acute m o u n t a i n sickness: Hyperbaric versus oxygen therapy. A n n Emerg Med October 1991;20:1109-1112.] INTRODUCTION
High-altitude illnesses are caused by the hypobaric hypoxia experienced by visitors to a high altitude. These are classified as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). Although AMS is usually mild and self-limited, it often is associated with or may progress to the potentially fatal forms of HAPE or HACE. AMS is effectively treated with descent, oxygen, or medication. Simulated descent has recently become a practical treatment option because of the development of lightweight, portable hyperbaric chambers. 1 Mountaineers have reported several cases of dramatic improvement with this treatment while they were high on a mountain where neither descent nor oxygen was immediately available. 2 Takei and associates were the first to report the use of hyperbaric therapy for the treatment of altitude illness. 3 They found that the majority of their 14 patients had complete relief of their symptoms. No control group was used in this initial study. Taber evaluated hyperbaric treatment in patients with AMS, HAPE, and HACE. 4 Hyperbaria was found to be effective, although no control group was included, and many patients had either oxygen or dexamethasone treatment concurrent with hyperbaria. 4 Hackett and colleagues evaluated the effectiveness of hyperbaria versus equal oxygen therapy in the treatment of moderate-to-severe HAPE. s They concluded that oxygen and hyperbaric therapy were equally effective in the resolution of symptoms. To date, no controlled comparison of hyperbaria
80/1109
Annals of Emergency Medicine
James F Kasic* Boulder, Colorado Michael Yaron, MD, FACEPt Denver, Colorado Richard A Nicholas, MD¢ Keystone, Colorado Julie Ann Lickteig, MS, RD§ Milwaukee, Wisconsin Robert Roach, MD rl Albuquerque, New Mexico From the Department of Chemical Engineering, University of Colorado, Boulder;* Section of Emergency Medicine and Trauma, University of Cdorado Health Sciences Center, Denver;t University of Colorado Health Sciences Center, Snake River Health Clinic, Keystone;¢ Cardinal Stritch College, Milwaukee, Wisconsin;§ and Lovelace Medical Foundation, Albuquerque, New Mexico. II Received for publication December 4, 1990. Revision received April 11, 1991. Accepted for publication May 6, 1991. This study was funded in part by a grant from DuPont de Nemours and Company, Inc, and the University of Colorado Department of Chemical Engineering. Address for reprints: James Kasic, Department of Engineering, Campus Box 424, University of Colorado, Boulder, Colorado 80309-0424.
20:10 October 1991
ACUTE M O U N T A I N S I C K N E S S Kasic et al
11°1
TABLE. Comparison of entry characteristics Diagnosis
Treatment
AMS
Pressure Oxygen
Gender Male Female
Hyperbaria
Age (Yr)
Height (cm)
Weight (kg)
7 5
3 3
46 + 4 37 + 3
173 ± 5 179 + 4
74 + 5 76 + 7
Pressure 3 2 Oxygen NOsignibcant differences betweentrealmenl groups.
0 1
30 _+ 8 36 ± 3
180 + 3 174 _+ 1
78 + 7 82 ± 5
AMS and HAPE
Travel Time (hr) 11 + 3
loo
~
I _ T
"r l i t
Oxygen
9o
11 ± 2 14 ± 3 8 ± 1
8o
85
with o x y g e n for t h e t r e a t m e n t of AMS has been reported. Therefore, we c o m p a r e d the efficacy of s i m u lated d e s c e n t w i t h t h a t of o x y g e n therapy in p a t i e n t s w i t h A M S and AMS associated w i t h m i l d HAPE. MATERIALS AND METHODS Study patients were recruited from those entering the Snake River Health Clinic in Keystone, Colorado (altitude, 2,950 m; b a r o m e t r i c pressure, 544 _+ 7 m m Hg), for medical treatment of altitude illness. Patients who received a clinical diagnosis of AMS were evaluated for the presence and severity of headache and nausea. A m i l d h e a d a c h e was assigned one point, and two points were given for a severe headache. N a u s e a was given one point. P a t i e n t s w i t h n a u s e a or headache who had arrived to altitude within 72 hours were considered to have A M S and q u a l i f i e d for e n t r y into the study. AMS p a t i e n t s w i t h mild HAPE as diagnosed by chest radiography and c l i n i c a l e x a m i n a t i o n also were recruited into the study. 6-a E x c l u s i o n criteria i n c l u d e d severe altitude illness (requiring prompt evacuation to a lower-altitude treatm e n t facility); p r e v i o u s t r e a t m e n t with oxygen, acetazolamide, or dexamethasone; acute or chronic heart or lung disease (not i n c l u d i n g HAPE); less than 18 years of age; pregnancy or n u r s i n g m o t h e r ; or e v i d e n c e of acute upper respiratory infection. On acceptance into the study, the m e t h o d s a n d r a t i o n a l e w e r e explained. Patients agreeing to particip a t e s i g n e d i n f o r m e d c o n s e n t and then were r a n d o m l y assigned to oxygen or h y p e r b a r i c t r e a t m e n t p r o t o cols. The study was approved by the H u m a n Subjects Review C o m m i t t e e of the U n i v e r s i t y of Colorado. Physiologic parameters and sympt o m responses were recorded by one of t h e i n v e s t i g a t o r s . B a s e l i n e m e a surements of pulse rate, blood pressure, and arterial oxygen s a t u r a t i o n (Saoz) were recorded. Supine blood 20:10 October 1991
F I G U R E 1. M e a n b l o o d pressure, heart rate, and arterial oxygen saturation versus time. ~P < .05 between treatments. F I G U R E 2. C o m b i n e d s y m p t o m scores of headache and nausea. Significant improvement occurred with both therapies by the end of treatment. P < .05.
75
65
CS
; ' '3~' 'do' ' ~o' '~o' '6o' '~o ~ p r e s s u r e and h e a r t r a t e ( m e a s u r e d w i t h a P h y s i o - C o n t r o l VSM3 m o n i tor, Physio-Control Corp, Redmond, Washington), Sao2 (measured w i t h an Ohmeda 4700 pulse oximeter [Ohmeda Monitoring Systems, Louisville, Colorado] by finger probe), and s y m p t o m s of headache and nausea were m o n i t o r e d at 15-minute intervals for the first hour and at 30m i n u t e i n t e r v a l s for an a d d i t i o n a l hour of t r e a t m e n t and for one hour after treatment. Symptom scores were m o n i t o r e d using the same point s y s t e m that was used for entry of pat i e n t s i n t o t h e study. Sao 2 v a l u e s w e r e c a l c u l a t e d by a v e r a g i n g m e a s u r e m e n t s stored at six-second intervals over a t h r e e - m i n u t e p e r i o d at each 15-minute interval. Normal values for Sao z at the clinic altitude were obtained by pulse o x i m e t r y in 47 n o r m a l , h e a l t h y , a c c l i m a t i z e d volunteers. A 5.5-kg, 0 . 8 1 - m - d i a m e t e r by 2.1m - l o n g c y l i n d r i c a l fabric h y p e r b a r i c c h a m b e r (Gamow Medical Tent, Port a b l e H y p e r b a r i c s Inc, I l i o n , N e w York) w i t h an internal support frame was used as the pressure chamber. The chamber is large enough to easily accommodate a supine patient, and plastic w i n d o w s p e r m i t observation of the c h a m b e r i n t e r i o r b y the c l i n i c i a n . T h e c h a m b e r was p r e s surized (over three to four minutes) w i t h a 4-1b b e l l o w s - t y p e foot p u m p to 100 m m Hg above a m b i e n t atmospheric pressure. O n c e pressurized, an o i l - f r e e d i a p h r a g m c o m p r e s s o r ( m o d e l 607CE, T h o m a s I n d u s t r i e s Annals of Emergency Medicine
Time(rain)
1 2.0 ~
~ ~
~
Hyperbaria
1.6 1.4 12 1.0 OB O6 02
2
0
30
60 90 Time (rain)
120
150 180
Inc, S h e b o y g a n , W i s c o n s i n ) c i r c u lated air through the c h a m b e r at 1.5 ft3/min and increased the pressure to 120 m m Hg (2.3 PSI) above a m b i e n t atmospheric pressure (equal to a des c e n t of a p p r o x i m a t e l y 1,432 m [4,600 ft] at the Keystone location). In earlier studies w i t h the chamber, this v o l u m e was found adequate to keep the s t e a d y - s t a t e oxygen and carbon d i o x i d e c o n c e n t r a t i o n s a b o v e 20% and below 1%, respectively. 9 T h e o x y g e n - t r e a t e d p a t i e n t s were given oxygen through a rebreather f a c e m a s k at a flow rate of 4 L / m i n ( f r a c t i o n of i n s p i r e d o x y g e n , FIo2, 30% to 35%). This oxygen-flow rate r e p r e s e n t e d the standard of care for A M S t h e r a p y at t h e S n a k e R i v e r Health Clinic. Therapy lasted two hours in each t r e a t m e n t modality. Differences between treatment g r o u p s for h e a r t rate, Saoz, b l o o d p r e s s u r e , age, h e i g h t , w e i g h t , and travel t i m e to Keystone were evaluated using a two-sample Student's t test. Symptom responses between groups and genders were c o m p a r e d 1110/81
ACUTE MOUNTAIN SICKNESS Kasic et al
using the Mann-Whitney U test. The l o g - r a n k s u r v i v a l c o m p a r i s o n was used to evaluate time to resolution of symptoms between the groups. Data presented are given as mean -+ SEM, with P < .05 considered significant.
hours of treatment and one hour after treatment (Figure 2). Analysis of the data for AMS and HAPE patients alone revealed results s i m i l a r to t h o s e of the A M S - o n l y patients.
RESULTS
DISCUSSION
T w e n t y - n i n e p a t i e n t s were randomized into the study. Because of m e c h a n i c a l and t e c h n i c a l errors, complete data were available in only 24 of the subjects, and the remainder was e x c l u d e d f r o m data analysis. These errors occurred in the monitoring equipment, not with the hyperbaric chamber. Missing data were distributed between the two groups (two in hyperbaric and three in oxygen). Of the 24 with complete data, 18 were diagnosed with AMS alone, and six had mild HAPE in addition to AMS. Ten AMS p a t i e n t s r e c e i v e d hyperbaric treatment, and eight received oxygen treatment. Three AMS and HAPE patients received hyperbaric treatment, and three received oxygen treatment. Treatment groups were similar w i t h regard to gender, age, height, weight, travel time to Keystone, and s y m p t o m severity at presentation (Table). Oxygen saturation on room air was m e a s u r e d in n o r m a l a c c l i m a t i z e d volunteers; m e a n value was 94 -+ 2%. Before t r e a t m e n t , b o t h treatment groups in the present study had Sao2 values significantly below this normal control value (P < .05). Pretreatment values for Sao2, heart rate, and blood pressure were similar bet w e e n groups. D u r i n g t r e a t m e n t , Sao 2 was significantly higher in the oxygen-treated group (83 -+ 4% to 96 _+ 1%) than in the hyperbaric treatm e n t group (84 ± 2% to 91 -+ 1%). This represents a 14% increase over pretreatment values for the oxygentreated group and a 7% increase for the hyperbaric t r e a t m e n t group. At one h o u r after t r e a t m e n t , Sao 2 in each treatment group returned to pretreatment values. Heart rate and mean arterial blood pressure decreased significantly in both groups during treatment com-pared with pretreatment values, with no significant differences b e t w e e n the groups (Figure 1). Both treatments significantly improved symptoms by the end of treatment (P < .05). Symptom responses and speed of s y m p t o m resolution did not differ significantly between the groups throughout two
This study demonstrated that hyperbaric therapy was as effective as oxygen therapy for the i m m e d i a t e t r e a t m e n t of AMS. Both m e t h o d s were successful in resolving or improving the symptoms of AMS in the majority of patients. The long-term effects of our treatments are u n k n o w n because our patients were monitored for only one hour after treatment. Two patients (one in each group) were unresponsive to treatment. Both of these patients m a y have been misdiagnosed initially. One patient (oxygen treatment) m a y have had a migraine headache, and one p a t i e n t (hyperbaric treatment) was t h o u g h t to have a viral syndrome. No complications occurred as a res u l t of h y p e r b a r i c t h e r a p y . T h e chamber offered sufficient room for the patients to stretch out and rest. No patient had to be released from the c h a m b e r b e c a u s e of claustrophobia. Although the pressure change in the chamber can cause a p r e s s u r e g r a d i e n t across the t y m panic membrane, no patients had difficulty clearing their ears w h e n the chamber was pressurized slowly. No other complaints were made by the hyperbaric patients except that the chamber tended to get w a r m as a result of pressurization and the presence of monitoring equipment. Bartseh and associates recently reported i m p r o v e m e n t in AMS symptoms in persons breathing r o o m air only, suggesting that a significant placebo effect exists in the treatment of AMS. 1° In our study, the aim was to compare two treatments as they are used in the clinical setting. We did not a t t e m p t to blind either the oxygen or the hyperbaric therapy. AMS is a clinical syndrome consisting of headache, nausea, vomiting, shortness of breath, dizziness, and malaise. Symptoms and severity of AMS vary in different persons. AMS is generally more severe with rapid ascent to altitude. H e a d a c h e and nausea are the cardinal symptoms of AMS (and thus were chosen for the monitoring parameters in this
82/1111
Annals of Emergency Medicine
study).7,8,11 HAPE is characterized by increasing dyspnea, a dry cough progressing to a productive one, prostration, and, if untreated, death.7, s As more people travel to high altitudes, AMS has become more common. A recent unpublished study by the Colorado Altitude Research Institute has shown that as m a n y as 24% of the 10 to 15 million visitors to the Rocky Mountain high country (altitude, 8,000 to 10,000 ft) experience some form of AMS (Ben Honigman, MD, personal communication, 1990). It is estimated that the high-altitude resort industry m a y lose $50 to $75 million a year because of altitude illness among visitors. 12 In mild cases of AMS, rest, frequent small meals, avoidance of alcohol, and over-thec o u n t e r m e d i c a t i o n s for h e a d a c h e m a y be all that is needed for treatm e n t . In our clinical experience, m o s t people recover in a few days and are able to gradually resume normal activity. However, in more severe cases of high-altitude illness, descent is the treatment of choice and m a y indeed be life saving. D r a m a t i c improvem e n t often accompanies a modest, 300-m r e d u c t i o n in altitude. ~3 Descent reverses hypobaric hypoxia by increasing the partial pressure of inspired oxygen (P~02). Oxygen therapy reverses hypoxia by raising the fraction of oxygen in the inspired gas (FI02). Dexamethasone and acetazolamide have been used to treat AMS patients effectively,~4,15 but neither medication works all the time, each can have unpleasant side effects, and both have a significant delay of onset of action. 16 In rough mountainous terrain, during bad weather conditions, and with very ill patients, descent m a y not be feasible, and s u p p l e m e n t a l oxygen m a y not be available. Simulated descent in a hyperbaric chamber m a y be the t r e a t m e n t of c h o i c e u n d e r these conditions. In contrast to bottled oxygen, which is heavy to carry and limited in supply, fabric hyperbaric chambers are lightweight, and the duration of treatment is not limited. Although the role of hypoxia in the pathophysiology of altitude illness is of primary importance, it is unclear w h e t h e r h y p o b a r i a plays an additional role. Decompression-induced platelet aggregation, ~7 intravascular microbubble formation,18 and alter20:10 October 1991
ACUTE MOUNTAIN SICKNESS Kasic et al
ation of the forces governing transvascular fluid fluxes across the pulmonary vasculature 19 have been suggested as mechanisms. In our study, the Sao 2 values in the
oxygen group were s i g n i f i c a n t l y higher throughout the two hours of treatment compared with those of the hyperbaric group. This reflects the increased PIo 2 in the oxygen group (Pio2, 149 to 173 m m Hg w i t h
oxygen vs 123 m m Hg with hyperbaria). We note with interest that increased oxygen saturation associated with oxygen therapy did not result in better s y m p t o m resolution than hyperbaric treatment. This finding sug-
gests the possibility that a threshold exists beyond w h i c h further improvement in oxygenation is of no additional benefit. It remains unclear exactly what roles oxygen and elevation of barometric pressure play or interplay in the treatment of AMS. CONCLUSION Oxygen and simulated descent resulting from pressurization in a hyperbaric chamber arc equally effective in the immediate treatment of AMS. Two hours of simulated descent of more than 1,400 m is as effective as breathing 4 L/min of supplemental oxygen for the relief of the symptoms of AMS. Two hours of treatment resulted in a greater Sao z with oxygen therapy; however, AMS symptoms decreased as rapidly with
20:10 October 1991
pressurization as with oxygen therapy. Further studies are needed to help elucidate the role of hyperbaria and its synergistic effects with oxygen in the treatment of AMS. The authors are grateful to the Colorado Altitude Research Institute and the staff of the Snake River Health Services, Inc, for their patience and assistance and to the University of Colorado Graduate School and DuPont de Nemours and Co, Inc, for their generous financial support. They thank Patricia Pearce for her invaluable help and support. The University of Colorado Emergency Medicine Clinical Research Center and Ben Honigman, MD, provided assistance with the manuscript and data analysis. The chamber was donated to the institute by Hyperbaric Mountain Technologies Inc. Professor Igor Gamow provided inspiration for this study, for which the authors are grateful.
REFERENCES 1. Gamow RI, Geer BD, Kasic JF, et ah Methods of gasbalance control to be used with a portable hyperbaric chamber in the treatment of high altitude illness. J Wilderness Med 1990;1:165-180. 2. King SJ, Greenlee R: Successful use of the Gamow hyperbaric bag in the treatment of altitude illness at Mount Everest. J Wilderness Med 1990;1:193-202. 3. Takei S, Kamio S, Uehara A, et ah Treatment of acute mountain sickness using a compression chamber, in Ueda G, Kusama S, Voekel N {eds}: High Ahitnde Medical Science. Matsumom, Japan, Shinsu University Press, 1988, p 284-288.
G, Remmers ]E (eds): Hypoxia: The Adaptatdons. Philadelphia, BC Dekker, 1990, p 291. 6. Huhgren HN: High altitude pulmonary edema, in Staub NC led): Lung Water and Solute Exchange. New York, Marcel Dekker, 1978, p 437-469. 7. Singh L, Khanna PK, Srivastava MC, et ah Acute mountain sickness. N Engi J Med 1969;280:175-184. 8. Hackett PH, Rennie D, Levine HD: The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976;2:1149-1154. 9. Geer CA, Gamow RI: A portable hyperbaric chamber for the treatment of high altitude illness )abstract), in Sutton JR, Coates G, Remmers JE (eds): Hypoxia: The Adaptations. Philadelphia, BC Dekker, 1990, p 291. 10. Bartsch P, Baumgarmer RF, Waber U, et ah Compar ison of carbon dioxide enriched, oxygen enriched, and normal air in treatment of acute mountain sickness. Lancet 1990;1:772-775. 11. Larson EB, Roach RC, Schoene RB, et ah Acute mountain sickness and acetazolamide~ Clinical efficacy and effect on ventilation. JAMA 1982~288:328-332. 12. Houston CS: Incidence of acute mountain sickness: A study of winter visitors to six Colorado resorts. Am
Alpine I 1985;27:162 165. 13. Hackett PH: Acute mountain sickness - The clini cal approach. Adv Cardiol 1980;27:6-10. 14. Ferrazzini G, Maggiorini M, Kriemler S, et ah Successful treatment of acute m o u n t a i n sickness with dexamethasone. Br Med J 1987;294:1380-1382. 15. Grissom CK, Roach RC, Sarnqnist FH, et ah Acetazolamide in the treatment of acute mountain sickness: Clinical efficacy and effect on gas exchange. Yale J Biol Med 1990;63:222. 16. Shlim DR: Treatment of acute mountain sickness.
N Engl [ Med 1985;313:891. 17. Murayama M: AMS (acute mountain sicknessl: A vascular occlusive disease. Med Hypotheses 1990;31: 189-195.
4. Taber RL: Protocols for the use of a portable hyperbaric chamber for the treatment of high altitude disorders. [ Wilderness Med 1990;1:181-192.
18. Grover RF, Tucker A, Reeves JT: Hypobaria: An eti ologic factor in acute mountain sickness?, in Loeppky JA, Riedesel MI {eds}: Oxygen Transport t o Human Tissues. New York, Elsevier/North Holland, 1982, p 223-230.
5. Hackett PH, Roach RC, Goldberg S, et ah A portable, fabric hyperbaric chamber for the treatment of high altitude pulmonary edema (abstract), in Sutton IR, Coates
19. Levine BD, Kubo K, Knbayashi T, et ah Role of barometric pressure in pulmonary fluid balance and oxygen transport. J Appl Physiol 1988;64:419-428.
Annals of Emergency Medicine
1112/83
Treatment of Acute Mountain Sickness: Hyperbaric Versus Oxygen Therapy Study objectives: To compare the benefits of simulated descent in a hyperbaric chamber with those of supplementary oxygen for the treatment of acute m o u n t a i n sickness. Design: A prospective study. Setting: The Snake River Health Clinic in Keystone, Colorado, which has an altitude of 2,850 m (9,300 it). Type of participants: Twenty-four patients w h o presented with acute m o u n t a i n sickness. Interventions: A simulated descent of 1,432 m (4,600 it) was attained by placing the patients in a fabric hyperbaric chamber and pressurizing the chamber to 120 m m Hg (2.3 PSI) above ambient pressure. Patients were randomly assigned to either the hyperbaric treatment or treatment with 4 L of oxygen given by facemask; both treatments lasted for two hours. Measurements and main results: Mean arterial oxygen saturation (Sao2) increased 7% (84 +- 2% to 91 +_ 1%) with pressurization and 14% (83 +_ 4% to 96 ± 1%) with oxygen during treatment over pretreatment levels. S y m p t o m s of acute m o u n t a i n sickness decreased as rapidly with pressurization as with oxygen treatment, despite significantly higher Sao 2 in the oxygen-treated group during treatment, S y m p t o m a t i c i m p r o v e m e n t was retained in both groups at least one hour after treatment. Conclusion: Simulated descent in a fabric hyperbaric chamber is as effective as oxygen therapy for the i m m e d i a t e relief of acute m o u n t a i n sickness. [Kasic JF, Yaron M, Nicholas RA, Lickteig JA, Roach R: Treatment of acute m o u n t a i n sickness: Hyperbaric versus oxygen therapy. A n n Emerg Med October 1991;20:1109-1112.] INTRODUCTION
High-altitude illnesses are caused by the hypobaric hypoxia experienced by visitors to a high altitude. These are classified as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). Although AMS is usually mild and self-limited, it often is associated with or may progress to the potentially fatal forms of HAPE or HACE. AMS is effectively treated with descent, oxygen, or medication. Simulated descent has recently become a practical treatment option because of the development of lightweight, portable hyperbaric chambers. 1 Mountaineers have reported several cases of dramatic improvement with this treatment while they were high on a mountain where neither descent nor oxygen was immediately available. 2 Takei and associates were the first to report the use of hyperbaric therapy for the treatment of altitude illness. 3 They found that the majority of their 14 patients had complete relief of their symptoms. No control group was used in this initial study. Taber evaluated hyperbaric treatment in patients with AMS, HAPE, and HACE. 4 Hyperbaria was found to be effective, although no control group was included, and many patients had either oxygen or dexamethasone treatment concurrent with hyperbaria. 4 Hackett and colleagues evaluated the effectiveness of hyperbaria versus equal oxygen therapy in the treatment of moderate-to-severe HAPE. s They concluded that oxygen and hyperbaric therapy were equally effective in the resolution of symptoms. To date, no controlled comparison of hyperbaria
80/1109
Annals of Emergency Medicine
James F Kasic* Boulder, Colorado Michael Yaron, MD, FACEPt Denver, Colorado Richard A Nicholas, MD¢ Keystone, Colorado Julie Ann Lickteig, MS, RD§ Milwaukee, Wisconsin Robert Roach, MD rl Albuquerque, New Mexico From the Department of Chemical Engineering, University of Colorado, Boulder;* Section of Emergency Medicine and Trauma, University of Cdorado Health Sciences Center, Denver;t University of Colorado Health Sciences Center, Snake River Health Clinic, Keystone;¢ Cardinal Stritch College, Milwaukee, Wisconsin;§ and Lovelace Medical Foundation, Albuquerque, New Mexico. II Received for publication December 4, 1990. Revision received April 11, 1991. Accepted for publication May 6, 1991. This study was funded in part by a grant from DuPont de Nemours and Company, Inc, and the University of Colorado Department of Chemical Engineering. Address for reprints: James Kasic, Department of Engineering, Campus Box 424, University of Colorado, Boulder, Colorado 80309-0424.
20:10 October 1991
ACUTE M O U N T A I N S I C K N E S S Kasic et al
11°1
TABLE. Comparison of entry characteristics Diagnosis
Treatment
AMS
Pressure Oxygen
Gender Male Female
Hyperbaria
Age (Yr)
Height (cm)
Weight (kg)
7 5
3 3
46 + 4 37 + 3
173 ± 5 179 + 4
74 + 5 76 + 7
Pressure 3 2 Oxygen NOsignibcant differences betweentrealmenl groups.
0 1
30 _+ 8 36 ± 3
180 + 3 174 _+ 1
78 + 7 82 ± 5
AMS and HAPE
Travel Time (hr) 11 + 3
loo
~
I _ T
"r l i t
Oxygen
9o
11 ± 2 14 ± 3 8 ± 1
8o
85
with o x y g e n for t h e t r e a t m e n t of AMS has been reported. Therefore, we c o m p a r e d the efficacy of s i m u lated d e s c e n t w i t h t h a t of o x y g e n therapy in p a t i e n t s w i t h A M S and AMS associated w i t h m i l d HAPE. MATERIALS AND METHODS Study patients were recruited from those entering the Snake River Health Clinic in Keystone, Colorado (altitude, 2,950 m; b a r o m e t r i c pressure, 544 _+ 7 m m Hg), for medical treatment of altitude illness. Patients who received a clinical diagnosis of AMS were evaluated for the presence and severity of headache and nausea. A m i l d h e a d a c h e was assigned one point, and two points were given for a severe headache. N a u s e a was given one point. P a t i e n t s w i t h n a u s e a or headache who had arrived to altitude within 72 hours were considered to have A M S and q u a l i f i e d for e n t r y into the study. AMS p a t i e n t s w i t h mild HAPE as diagnosed by chest radiography and c l i n i c a l e x a m i n a t i o n also were recruited into the study. 6-a E x c l u s i o n criteria i n c l u d e d severe altitude illness (requiring prompt evacuation to a lower-altitude treatm e n t facility); p r e v i o u s t r e a t m e n t with oxygen, acetazolamide, or dexamethasone; acute or chronic heart or lung disease (not i n c l u d i n g HAPE); less than 18 years of age; pregnancy or n u r s i n g m o t h e r ; or e v i d e n c e of acute upper respiratory infection. On acceptance into the study, the m e t h o d s a n d r a t i o n a l e w e r e explained. Patients agreeing to particip a t e s i g n e d i n f o r m e d c o n s e n t and then were r a n d o m l y assigned to oxygen or h y p e r b a r i c t r e a t m e n t p r o t o cols. The study was approved by the H u m a n Subjects Review C o m m i t t e e of the U n i v e r s i t y of Colorado. Physiologic parameters and sympt o m responses were recorded by one of t h e i n v e s t i g a t o r s . B a s e l i n e m e a surements of pulse rate, blood pressure, and arterial oxygen s a t u r a t i o n (Saoz) were recorded. Supine blood 20:10 October 1991
F I G U R E 1. M e a n b l o o d pressure, heart rate, and arterial oxygen saturation versus time. ~P < .05 between treatments. F I G U R E 2. C o m b i n e d s y m p t o m scores of headache and nausea. Significant improvement occurred with both therapies by the end of treatment. P < .05.
75
65
CS
; ' '3~' 'do' ' ~o' '~o' '6o' '~o ~ p r e s s u r e and h e a r t r a t e ( m e a s u r e d w i t h a P h y s i o - C o n t r o l VSM3 m o n i tor, Physio-Control Corp, Redmond, Washington), Sao2 (measured w i t h an Ohmeda 4700 pulse oximeter [Ohmeda Monitoring Systems, Louisville, Colorado] by finger probe), and s y m p t o m s of headache and nausea were m o n i t o r e d at 15-minute intervals for the first hour and at 30m i n u t e i n t e r v a l s for an a d d i t i o n a l hour of t r e a t m e n t and for one hour after treatment. Symptom scores were m o n i t o r e d using the same point s y s t e m that was used for entry of pat i e n t s i n t o t h e study. Sao 2 v a l u e s w e r e c a l c u l a t e d by a v e r a g i n g m e a s u r e m e n t s stored at six-second intervals over a t h r e e - m i n u t e p e r i o d at each 15-minute interval. Normal values for Sao z at the clinic altitude were obtained by pulse o x i m e t r y in 47 n o r m a l , h e a l t h y , a c c l i m a t i z e d volunteers. A 5.5-kg, 0 . 8 1 - m - d i a m e t e r by 2.1m - l o n g c y l i n d r i c a l fabric h y p e r b a r i c c h a m b e r (Gamow Medical Tent, Port a b l e H y p e r b a r i c s Inc, I l i o n , N e w York) w i t h an internal support frame was used as the pressure chamber. The chamber is large enough to easily accommodate a supine patient, and plastic w i n d o w s p e r m i t observation of the c h a m b e r i n t e r i o r b y the c l i n i c i a n . T h e c h a m b e r was p r e s surized (over three to four minutes) w i t h a 4-1b b e l l o w s - t y p e foot p u m p to 100 m m Hg above a m b i e n t atmospheric pressure. O n c e pressurized, an o i l - f r e e d i a p h r a g m c o m p r e s s o r ( m o d e l 607CE, T h o m a s I n d u s t r i e s Annals of Emergency Medicine
Time(rain)
1 2.0 ~
~ ~
~
Hyperbaria
1.6 1.4 12 1.0 OB O6 02
2
0
30
60 90 Time (rain)
120
150 180
Inc, S h e b o y g a n , W i s c o n s i n ) c i r c u lated air through the c h a m b e r at 1.5 ft3/min and increased the pressure to 120 m m Hg (2.3 PSI) above a m b i e n t atmospheric pressure (equal to a des c e n t of a p p r o x i m a t e l y 1,432 m [4,600 ft] at the Keystone location). In earlier studies w i t h the chamber, this v o l u m e was found adequate to keep the s t e a d y - s t a t e oxygen and carbon d i o x i d e c o n c e n t r a t i o n s a b o v e 20% and below 1%, respectively. 9 T h e o x y g e n - t r e a t e d p a t i e n t s were given oxygen through a rebreather f a c e m a s k at a flow rate of 4 L / m i n ( f r a c t i o n of i n s p i r e d o x y g e n , FIo2, 30% to 35%). This oxygen-flow rate r e p r e s e n t e d the standard of care for A M S t h e r a p y at t h e S n a k e R i v e r Health Clinic. Therapy lasted two hours in each t r e a t m e n t modality. Differences between treatment g r o u p s for h e a r t rate, Saoz, b l o o d p r e s s u r e , age, h e i g h t , w e i g h t , and travel t i m e to Keystone were evaluated using a two-sample Student's t test. Symptom responses between groups and genders were c o m p a r e d 1110/81
ACUTE MOUNTAIN SICKNESS Kasic et al
using the Mann-Whitney U test. The l o g - r a n k s u r v i v a l c o m p a r i s o n was used to evaluate time to resolution of symptoms between the groups. Data presented are given as mean -+ SEM, with P < .05 considered significant.
hours of treatment and one hour after treatment (Figure 2). Analysis of the data for AMS and HAPE patients alone revealed results s i m i l a r to t h o s e of the A M S - o n l y patients.
RESULTS
DISCUSSION
T w e n t y - n i n e p a t i e n t s were randomized into the study. Because of m e c h a n i c a l and t e c h n i c a l errors, complete data were available in only 24 of the subjects, and the remainder was e x c l u d e d f r o m data analysis. These errors occurred in the monitoring equipment, not with the hyperbaric chamber. Missing data were distributed between the two groups (two in hyperbaric and three in oxygen). Of the 24 with complete data, 18 were diagnosed with AMS alone, and six had mild HAPE in addition to AMS. Ten AMS p a t i e n t s r e c e i v e d hyperbaric treatment, and eight received oxygen treatment. Three AMS and HAPE patients received hyperbaric treatment, and three received oxygen treatment. Treatment groups were similar w i t h regard to gender, age, height, weight, travel time to Keystone, and s y m p t o m severity at presentation (Table). Oxygen saturation on room air was m e a s u r e d in n o r m a l a c c l i m a t i z e d volunteers; m e a n value was 94 -+ 2%. Before t r e a t m e n t , b o t h treatment groups in the present study had Sao2 values significantly below this normal control value (P < .05). Pretreatment values for Sao2, heart rate, and blood pressure were similar bet w e e n groups. D u r i n g t r e a t m e n t , Sao 2 was significantly higher in the oxygen-treated group (83 -+ 4% to 96 _+ 1%) than in the hyperbaric treatm e n t group (84 ± 2% to 91 -+ 1%). This represents a 14% increase over pretreatment values for the oxygentreated group and a 7% increase for the hyperbaric t r e a t m e n t group. At one h o u r after t r e a t m e n t , Sao 2 in each treatment group returned to pretreatment values. Heart rate and mean arterial blood pressure decreased significantly in both groups during treatment com-pared with pretreatment values, with no significant differences b e t w e e n the groups (Figure 1). Both treatments significantly improved symptoms by the end of treatment (P < .05). Symptom responses and speed of s y m p t o m resolution did not differ significantly between the groups throughout two
This study demonstrated that hyperbaric therapy was as effective as oxygen therapy for the i m m e d i a t e t r e a t m e n t of AMS. Both m e t h o d s were successful in resolving or improving the symptoms of AMS in the majority of patients. The long-term effects of our treatments are u n k n o w n because our patients were monitored for only one hour after treatment. Two patients (one in each group) were unresponsive to treatment. Both of these patients m a y have been misdiagnosed initially. One patient (oxygen treatment) m a y have had a migraine headache, and one p a t i e n t (hyperbaric treatment) was t h o u g h t to have a viral syndrome. No complications occurred as a res u l t of h y p e r b a r i c t h e r a p y . T h e chamber offered sufficient room for the patients to stretch out and rest. No patient had to be released from the c h a m b e r b e c a u s e of claustrophobia. Although the pressure change in the chamber can cause a p r e s s u r e g r a d i e n t across the t y m panic membrane, no patients had difficulty clearing their ears w h e n the chamber was pressurized slowly. No other complaints were made by the hyperbaric patients except that the chamber tended to get w a r m as a result of pressurization and the presence of monitoring equipment. Bartseh and associates recently reported i m p r o v e m e n t in AMS symptoms in persons breathing r o o m air only, suggesting that a significant placebo effect exists in the treatment of AMS. 1° In our study, the aim was to compare two treatments as they are used in the clinical setting. We did not a t t e m p t to blind either the oxygen or the hyperbaric therapy. AMS is a clinical syndrome consisting of headache, nausea, vomiting, shortness of breath, dizziness, and malaise. Symptoms and severity of AMS vary in different persons. AMS is generally more severe with rapid ascent to altitude. H e a d a c h e and nausea are the cardinal symptoms of AMS (and thus were chosen for the monitoring parameters in this
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Annals of Emergency Medicine
study).7,8,11 HAPE is characterized by increasing dyspnea, a dry cough progressing to a productive one, prostration, and, if untreated, death.7, s As more people travel to high altitudes, AMS has become more common. A recent unpublished study by the Colorado Altitude Research Institute has shown that as m a n y as 24% of the 10 to 15 million visitors to the Rocky Mountain high country (altitude, 8,000 to 10,000 ft) experience some form of AMS (Ben Honigman, MD, personal communication, 1990). It is estimated that the high-altitude resort industry m a y lose $50 to $75 million a year because of altitude illness among visitors. 12 In mild cases of AMS, rest, frequent small meals, avoidance of alcohol, and over-thec o u n t e r m e d i c a t i o n s for h e a d a c h e m a y be all that is needed for treatm e n t . In our clinical experience, m o s t people recover in a few days and are able to gradually resume normal activity. However, in more severe cases of high-altitude illness, descent is the treatment of choice and m a y indeed be life saving. D r a m a t i c improvem e n t often accompanies a modest, 300-m r e d u c t i o n in altitude. ~3 Descent reverses hypobaric hypoxia by increasing the partial pressure of inspired oxygen (P~02). Oxygen therapy reverses hypoxia by raising the fraction of oxygen in the inspired gas (FI02). Dexamethasone and acetazolamide have been used to treat AMS patients effectively,~4,15 but neither medication works all the time, each can have unpleasant side effects, and both have a significant delay of onset of action. 16 In rough mountainous terrain, during bad weather conditions, and with very ill patients, descent m a y not be feasible, and s u p p l e m e n t a l oxygen m a y not be available. Simulated descent in a hyperbaric chamber m a y be the t r e a t m e n t of c h o i c e u n d e r these conditions. In contrast to bottled oxygen, which is heavy to carry and limited in supply, fabric hyperbaric chambers are lightweight, and the duration of treatment is not limited. Although the role of hypoxia in the pathophysiology of altitude illness is of primary importance, it is unclear w h e t h e r h y p o b a r i a plays an additional role. Decompression-induced platelet aggregation, ~7 intravascular microbubble formation,18 and alter20:10 October 1991
ACUTE MOUNTAIN SICKNESS Kasic et al
ation of the forces governing transvascular fluid fluxes across the pulmonary vasculature 19 have been suggested as mechanisms. In our study, the Sao 2 values in the
oxygen group were s i g n i f i c a n t l y higher throughout the two hours of treatment compared with those of the hyperbaric group. This reflects the increased PIo 2 in the oxygen group (Pio2, 149 to 173 m m Hg w i t h
oxygen vs 123 m m Hg with hyperbaria). We note with interest that increased oxygen saturation associated with oxygen therapy did not result in better s y m p t o m resolution than hyperbaric treatment. This finding sug-
gests the possibility that a threshold exists beyond w h i c h further improvement in oxygenation is of no additional benefit. It remains unclear exactly what roles oxygen and elevation of barometric pressure play or interplay in the treatment of AMS. CONCLUSION Oxygen and simulated descent resulting from pressurization in a hyperbaric chamber arc equally effective in the immediate treatment of AMS. Two hours of simulated descent of more than 1,400 m is as effective as breathing 4 L/min of supplemental oxygen for the relief of the symptoms of AMS. Two hours of treatment resulted in a greater Sao z with oxygen therapy; however, AMS symptoms decreased as rapidly with
20:10 October 1991
pressurization as with oxygen therapy. Further studies are needed to help elucidate the role of hyperbaria and its synergistic effects with oxygen in the treatment of AMS. The authors are grateful to the Colorado Altitude Research Institute and the staff of the Snake River Health Services, Inc, for their patience and assistance and to the University of Colorado Graduate School and DuPont de Nemours and Co, Inc, for their generous financial support. They thank Patricia Pearce for her invaluable help and support. The University of Colorado Emergency Medicine Clinical Research Center and Ben Honigman, MD, provided assistance with the manuscript and data analysis. The chamber was donated to the institute by Hyperbaric Mountain Technologies Inc. Professor Igor Gamow provided inspiration for this study, for which the authors are grateful.
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G, Remmers ]E (eds): Hypoxia: The Adaptatdons. Philadelphia, BC Dekker, 1990, p 291. 6. Huhgren HN: High altitude pulmonary edema, in Staub NC led): Lung Water and Solute Exchange. New York, Marcel Dekker, 1978, p 437-469. 7. Singh L, Khanna PK, Srivastava MC, et ah Acute mountain sickness. N Engi J Med 1969;280:175-184. 8. Hackett PH, Rennie D, Levine HD: The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976;2:1149-1154. 9. Geer CA, Gamow RI: A portable hyperbaric chamber for the treatment of high altitude illness )abstract), in Sutton JR, Coates G, Remmers JE (eds): Hypoxia: The Adaptations. Philadelphia, BC Dekker, 1990, p 291. 10. Bartsch P, Baumgarmer RF, Waber U, et ah Compar ison of carbon dioxide enriched, oxygen enriched, and normal air in treatment of acute mountain sickness. Lancet 1990;1:772-775. 11. Larson EB, Roach RC, Schoene RB, et ah Acute mountain sickness and acetazolamide~ Clinical efficacy and effect on ventilation. JAMA 1982~288:328-332. 12. Houston CS: Incidence of acute mountain sickness: A study of winter visitors to six Colorado resorts. Am
Alpine I 1985;27:162 165. 13. Hackett PH: Acute mountain sickness - The clini cal approach. Adv Cardiol 1980;27:6-10. 14. Ferrazzini G, Maggiorini M, Kriemler S, et ah Successful treatment of acute m o u n t a i n sickness with dexamethasone. Br Med J 1987;294:1380-1382. 15. Grissom CK, Roach RC, Sarnqnist FH, et ah Acetazolamide in the treatment of acute mountain sickness: Clinical efficacy and effect on gas exchange. Yale J Biol Med 1990;63:222. 16. Shlim DR: Treatment of acute mountain sickness.
N Engl [ Med 1985;313:891. 17. Murayama M: AMS (acute mountain sicknessl: A vascular occlusive disease. Med Hypotheses 1990;31: 189-195.
4. Taber RL: Protocols for the use of a portable hyperbaric chamber for the treatment of high altitude disorders. [ Wilderness Med 1990;1:181-192.
18. Grover RF, Tucker A, Reeves JT: Hypobaria: An eti ologic factor in acute mountain sickness?, in Loeppky JA, Riedesel MI {eds}: Oxygen Transport t o Human Tissues. New York, Elsevier/North Holland, 1982, p 223-230.
5. Hackett PH, Roach RC, Goldberg S, et ah A portable, fabric hyperbaric chamber for the treatment of high altitude pulmonary edema (abstract), in Sutton IR, Coates
19. Levine BD, Kubo K, Knbayashi T, et ah Role of barometric pressure in pulmonary fluid balance and oxygen transport. J Appl Physiol 1988;64:419-428.
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