Incidence and risk factors associated with acute mountain sickness in children trekking on Jade Mountain, Taiwan. Vascular endothelial growth factor and acute mountain sickness Ginkgo biloba Does—and Does Not—Prevent Acute Mountain Sickness Reproducibility of Acute Mountain Sickness in Children and Adults: A Prospective Study Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial. Efficacy of low-dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial. Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes. Acetazolamide and dexamethasone in the prevention of acute mountain sickness. Reliability and utility of a visual analog scale for the assessment of acute mountain sickness. Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. Prevention of Acute Mountain Sickness by Acetazolamide in Nepali Porters: A Double-Blind Controlled Trial Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level. Spironolactone does not prevent acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial by SPACE Trial Group (spironolactone and acetazolamide trial in the prevention of acute mountain sickness group). Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial. Efficacy of Dexamethasone in Preventing Acute Mountain Sickness in COPD Patients: Randomized Trial Prophylactic Effect of Erythropoietin Injection to Prevent Acute Mountain Sickness: An Open-Label Randomized Controlled Trial Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m). Prophylactic Acetaminophen or Ibuprofen Results in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial. Remote ischemic preconditioning does not prevent acute mountain sickness after rapid ascent to 3,450 m. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial. Autonomic cardiovascular regulation in subjects with acute mountain sickness. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure.
BACKGROUND Acute mountain sickness ( AMS ) is a pathophysiological symptom complex that occurs in high-altitude areas . The incidence of AMS on Jade Mountain , the highest peak in Taiwan ( 3952 m ) , has been reported to be ∼36 % . There is a lack of data in children trekking at altitude in Taiwan . The purpose of this study was to determine the incidence , risk factors and symptoms of AMS in children trekking on Jade Mountain , Taiwan . METHODS This prospect i ve cohort study included a total of 96 healthy non-acclimatized children aged 11 - 12 years who trekked from an elevation of 2600 - 3952 m in 3 days .  The Lake Louise AMS score  was used to record symptoms associated with AMS . RESULTS AMS were reported in 59 % of children trekking on Jade Mountain over a 3 day period . AMS incidence increased significantly with increasing altitude . The most common AMS symptom was headache , followed by fatigue or weakness , difficulty sleeping , dizziness or lightheadedness and gastrointestinal symptoms . Children who had experienced upper respiratory infection ( URI ) within the 7 days before their trek tended to have a greater risk for development of AMS . AMS incidence did not significantly differ according to gender , recent acute gastroenteritis , menstruation and body mass index . CONCLUSIONS The incidence of AMS in children trekking on Jade Mountain is greater than that observed in adults , and was associated with altitude and recent URI Study Objective : Despite causing significant morbidity throughout the mountainous regions of the world , the pathophysiology of acute mountain sickness ( AMS ) remains poorly understood . This study aims to improve the underst and ing of altitude illness by determining if vascular endothelial growth factor ( VEGF ) plays a role in the development of AMS . The purpose of this study was to determine if elevated plasma VEGF correlates with increased symptoms of AMS at high altitude . Patients and Methods : This is a prospect i ve study of a cohort of healthy climbers on Denali ( Mount McKinley ) in Alaska at 14 , 200 feet . Baseline demographics , medications , rates of ascent , and AMS scores were recorded .  Pulse oximetry measurements and venous blood sample s were obtained . Comparisons were made between mountaineers with and without AMS . Results : Seventy-two climbers were approached for participation in the study ; 21 ( 29 % ) refused . Of the 51 climbers participating in the study , 14 subjects ( 27.5 % ) had symptoms of AMS and 37 subjects ( 72.5 % ) were free of symptoms of AMS . Plasma VEGF levels were 79.14 pg/dl ( SD : 121.44 ) and 57.57pg/dl ( SD : 102.71 ) in the AMS and non-AMS groups , respectively . These results were nonsignificant . Similarly , comparison of sex , age , rate of ascent , pulse oximetry values , or history of altitude illness did not reveal significant differences between the AMS and non-AMS groups . Conclusion : This study does not provide evidence in support of the theory that plasma VEGF correlates with symptoms of AMS Abstract Objective .—To determine the efficacy of 2 different sources of Ginkgo biloba extract ( GBE ) in reducing the incidence and severity of acute mountain sickness ( AMS ) following rapid ascent to high altitude . Methods .—Two r and omized , double-blind , placebo-controlled cohort studies were conducted in which participants were treated with GBE ( 240 mg·d−1 ) or placebo prior to and including the day of ascent from 1600 m to 4300 m ( ascent in 2 hours by car ) . Acute mountain sickness was diagnosed if the Environmental Symptom Question naire III acute mountain sickness – cerebral ( AMS-C ) score was ≥0.7 and the Lake Louise Symptom ( LLS ) score was ≥3 and the participant reported a headache . Symptom severity was also determined by these scores . Results .— Results were conflicting : Ginkgo biloba  reduced the incidence and severity of AMS compared to placebo in the first but not the second study . In the first study , GBE reduced AMS incidence ( 7/21 ) vs placebo ( 13/19 ) ( P = .027 , number needed to treat = 3 ) , and it also reduced severity ( AMS-C = 0.77 ± 0.26 vs 1.59 ± 0.27 , P = .029 ) . In the second study , GBE did not reduce incidence or severity of AMS ( GBE 4/15 vs placebo 10/22 , P = .247 ; AMS-C = 0.48 ± 0.13 vs 0.58 ± 0.11 , P = .272 ) . The primary difference between the 2 studies was the source of GBE . Conclusions .—The source and composition of GBE products may determine the effectiveness of GBE for prophylaxis of AMS OBJECTIVE : Although a history of previous acute mountain sickness ( AMS ) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure , the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospect i ve controlled study . METHODS : In 27 nonacclimatized children and 29 adults ,  AMS  was assessed during the first 48 hours after rapid ascent to 3450 m on 2 consecutive occasions 9 to 12 months apart . RESULTS : During the first exposure , 18 adults ( 62 % ) and 6 children ( 22 % ) suffered from AMS ; during the second exposure , 14 adults ( 48 % ) and 4 children ( 15 % ) suffered from this problem ( adults versus children , P ≤ .01 ) . Most importantly , the intraindividual reproducibility of AMS  was very different ( P < .001 ) between children and adults . None of the 6 children having suffered from AMS during the first exposure suffered from AMS during the second exposure , but 4 children with no AMS during the first exposure did experience this problem during the second exposure . In contrast , 14 of the 18 adults who suffered from AMS on the first occasion also presented with this problem during the second exposure , and no new case developed in those who had not experienced AMS on the first occasion . CONCLUSIONS : In adults , a history of AMS is highly predictable of the disease on subsequent exposure , whereas in children it has no predictive value . A history of AMS should not prompt practitioners to advise against reexposure to high altitude or to prescribe drugs for its prophylaxis in children BACKGROUND Acute mountain sickness ( AMS ) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m.  Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis ; however , there is conflicting evidence regarding the efficacy of Ginkgo biloba use . We performed a r and omized , placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis . METHODS We r and omized unacclimatized adults to receive acetazolamide , Ginkgo biloba , or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours . We grade d AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System ( LLS ) and compared the incidence of AMS ( defined as LLS score > or =3 and headache ) . RESULTS Fifty-seven subjects completed the trial ( 20 received acetazolamide ; 17 , Ginkgo biloba , and 20 , placebo ) . The LLS scores were significantly different between groups ; the median score of the acetazolamide group was significantly lower than that of the placebo group ( P=.01 ; effect size , 2 ; and 95 % confidence interval [ CI ] , 0 to 3 ) , unlike that of the Ginkgo biloba group ( P=.89 ; effect size , 0 ; and 95 % CI , -2 to 2 ) . Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group ( effect size , 30 % ; 95 % CI , 61 % to -15 % ) , and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group ( effect size , -5 % ; 95 % CI , -37 % to 28 % ) . CONCLUSIONS In this study , prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence . We found no evidence of similar efficacy for Ginkgo biloba The objective of this study was to determine the efficacy of low-dose acetazolamide ( 125 mg twice daily ) for the prevention of acute mountain sickness ( AMS ) . The design was a prospect i ve , double-blind , r and omized , placebo-controlled trial in the Mt. Everest region of Nepal between Pheriche ( 4243 m ) , the study enrollment site , and Lobuje ( 4937 m ) , the study endpoint . The participants were 197 healthy male and female trekkers of diverse background , and they were evaluated with the Lake Louise Acute Mountain Sickness Scoring System  and  pulse oximetry .  The main outcome measures were incidence and severity of AMS as judged by the Lake Louise Question naire score at Lobuje . Of the 197 participants enrolled , 155 returned their data sheets at Lobuje . In the treatment group there was a statistically significant reduction in incidence of AMS ( placebo group , 24.7 % , 20 out of 81 subjects ; acetazolamide group , 12.2 % , 9 out of 74 subjects ) . Prophylaxis with acetazolamide conferred a 50.6 % relative risk reduction , and the number needed to treat in order to prevent one instance of AMS was 8 . Of those with AMS , 30 % in the placebo group ( 6 of 20 ) versus 0 % in the acetazolamide group ( 0 of 9 ) experienced a more severe degree of AMS as defined by a Lake Louise Question naire score of 5 or greater ( p = 0.14 ) . Secondary outcome measures associated with statistically significant findings favoring the treatment group included decrease in headache and a greater increase in final oxygen saturation at Lobuje . We concluded that acetazolamide 125 mg twice daily was effective in decreasing the incidence of AMS in this Himalayan trekking population To test the value of dexamethasone acetate for ameliorating acute mountain sickness ( AMS ) , we conducted a double-blind , r and omized study that compared the effects of 4 mg of dexamethasone acetate or a placebo ( given every six hours for six doses beginning at the time of exposure ) at 2700 and 2050 m. Study subjects , who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains , were classified as having AMS when they reported three or more of the five usual symptoms ( headache , insomnia , dyspnea , anorexia , and /or fatigue ) on a single day . All symptoms with an intensity of at least grade 2 ( moderate ) out of 5 were analyzed . At 2700 m , there was a 50 % decrease in the mean AMS symptom score in the dexamethasone group ( 0.94 + /- 1.11 vs 1.84 + /- 1.44 [ mean + /- SD ] ) and the incidence of AMS was 20 % of that in the control group ( 3/38 vs 14/35 ) . At 2050 m , there was no difference between dexamethasone and a placebo in the mean AMS symptom score ( 1.52 + /- 1.50 vs 1.24 + /- 1.33 ) and the incidence of AMS ( 5/25 vs 4/25 ) . Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 We r and omly assigned 32 healthy backpackers to receive placebo , acetazolamide ( 250 mg twice a day ) , dexamethasone acetate ( 4 mg four times a day ) , or both drugs in combination to determine the drug efficacy in preventing  acute mountain sickness ( AMS ) at altitudes of 3,650 to 4,050 m ( 12,000 to 13,300 ft ) . The incidence of AMS was high but symptoms were generally mild . Combined drug therapy was superior to both placebo and single drug therapy in risk reduction . Using acetazolamide alone was moderately beneficial in preventing the occurrence of AMS , although minor side effects were frequent . The use of dexamethasone alone did not significantly reduce the AMS incidence , and discontinuing its use result ed in symptoms suggestive of adrenal insufficiency . For recreational backpackers , routine drug prophylaxis is not recommended , in view of the mild nature of this illness and the adverse effects of medications . The efficacy of combined acetazolamide-dexamethasone therapy warrants further investigation at higher altitudes , where AMS is more severe , and the dexamethasone should be withdrawn gradually to avoid a possible adrenal crisis Acute mountain sickness ( AMS ) is a common condition that affects people that ascend too rapidly to high altitude . It is typically assessed with the Lake Louise AMS Self-report Score ( LLSelf ) that uses a categorical numeric rating scale to answer five questions addressing AMS-related symptoms , such as headache . A 100-mm visual analog scale ( VAS ) is commonly used to assess subjective phenomena such as pain , but this scale has never been used for the self- assessment of AMS . The purpose of this study was to compare a  VAS score  to the total LLSelf and to evaluate the test-retest and interrater reliability of the VAS when used as an assessment of AMS .  Participants ( N = 356 ) completed both the LLSelf and the VAS on the summit of Mt. Whitney ( 4419 m ) . There was a significant relationship ( r = 0.65 , p < 0.01 ) between the LLSelf ( 2.8 + /- 2.0 , mean + /- SD ) and the VAS ( 14.4 + /- 14.1 mm ) . Fifty-seven participants were r and omly selected for reliability testing of the VAS . Both test-retest reliability ( ICC = 0.996 , 95 % CI = 0.992 to 0.998 ) and interrater reliability ( ICC = 1.000 , 95 % CI = 0.999 to 1.000 ) were high . The mean difference in the VAS score between tests was < 1 mm , as was the difference between raters . These results demonstrate excellent reliability for the VAS as an assessment of AMS 750 mg per day of acetazolamide in the prevention of  acute mountain sickness ( AMS  ) , as recommended in the meta- analysis published in 2000 in the British Medical Journal , may be excessive and is controversial . To determine if the efficacy of low-dose acetazolamide 125 mg bd ( 250 mg ) , as currently used in the Himalayas , is significantly different from 375 mg bd ( 750 mg ) of acetazolamide in the prevention of AMS , we design ed a prospect i ve , double-blind , r and omized , placebo-controlled trial . The participants were sample d from a diverse population of ( non-Nepali ) trekkers at Namche Bazaar ( 3440 m ) in Nepal on the Everest trekking route as they ascended to study midpoints ( 4280 m/4358 m ) and the endpoint , Lobuje ( 4928 m ) , where data were collected . Participants were r and omly assigned to receive 375 mg bd of  acetazolamide ( 82 participants ) , 125 mg bd of acetazolamide ( 74 participants ) , or a placebo ( 66 participants ) , beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd ( 24 % vs. 21 % , 95 % confidence interval , -12.6 % , 19.8 % ) , in contrast to significantly greater AMS ( 51 % ) observed in the placebo group ( 95 % confidence interval for differences : 8 % , 46 % ; 12 % , 49 % for low and high comparisons , respectively ) . Both doses of acetazolamide  improved oxygenation equally ( 82.9 % for 250 mg daily and 82.8 % for 750 mg daily ) , while placebo endpoint oxygen saturation was significantly less at 80.7 % ( 95 % confidence interval for differences : 0.5 % , 3.9 % and 0.4 % , 3.7 % for low and high comparisons , respectively ) . There was also more paresthesia in the 375-mg bd group ( p < 0.02 ) . We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS ; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 Abstract Objective .—This study aim ed to determine the efficacy , tolerability , and practicality of acetazolamide for the prevention of acute mountain sickness ( AMS ) in Nepali trekking porters early in the trekking season . Methods .—This study was a r and omized , double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal , trekking from Namche Bazaar ( 3440 m ) to Lobuche ( 4930 m ) , the study endpoint . Participants were r and omized to receive 250 mg acetazolamide daily or placebo , and AMS symptom scores ( Lake Louise ) were compared in highl and ers vs lowl and ers . Results .—Only 109 ( 27.2 % ) of the 400 porters completed the trial ( 28 highl and ers , 81 lowl and ers ) . The rest either dropped out ( 275/400 porters , 68.8 % ) or were excluded ( 16/400 porters , 4 % ) . Acute mountain sickness occurred in 13 ( 11.9 % ) of 109 porters ; all were lowl and ers ; 7 were taking acetazolamide , 6 taking placebo .  Birthplace , acclimatization in the week before the trial , ascent rate , and rest days were the most important variables affecting the incidence of AMS . No highl and ers , but 13 ( 16.1 % ) of 81 lowl and ers had AMS ( P = .016 ) . Acclimatization in the pretrial week reduced AMS incidence ( P = .013 ) , as did a slower ascent rate ( P = .0126 ) , but rest days were the most potent prophylactic variable ( P = .0001 ) . Side effects were more frequent in porters taking acetazolamide than in the placebo group ( P = .0001 ) , but there were no serious side effects . Conclusions .—Acetazolamide was tolerable , but impractical for the routine prevention of AMS in Nepali porters . A good trekking schedule and adequate acclimatization remain the most effective preventive measures . This study identified lowl and porters as a high-risk group for developing AMS Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness ( AMS ) . Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS . To determine whether lower , less frequent doses were effective in preventing AMS , 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber  on two occasions while taking one of three doses of dexamethasone ( 4 mg , 1 mg , or .25 mg every 12 h ) or a placebo in a double-blind , crossover design . The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels . Dexamethasone did not alter fluid balance or plasma volume changes , but treatment with 1 mg and 4 mg suppressed cortisol secretion . There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment . The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS , while lower doses are relatively ineffective OBJECTIVES Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness ( AMS )  , but to date there have been no large r and omized trials investigating the efficacy of spironolactone in prevention of AMS . Hence , a prospect i ve , double-blind , r and omized , placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS . METHODS Participants were sample d from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach ( Nepal side ) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled , and 251 completed the trial from October to November 2007 . Participants were r and omly assigned to receive at least 3 doses of spironolactone 50 mg BID , acetazolamide 250 mg BID , or visually matched placebo . A Lake Louise AMS Score of 3 or more , together with the presence of headache and 1 other symptom , was used to evaluate the incidence and severity of AMS . Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache ( HAH ) . RESULTS Acetazolamide was more effective than spironolactone in preventing AMS ( OR = 0.28 , 95 % CI 0.12 - 0.60 , p < 0.01 ) . Spironolactone was not significantly different from placebo in the prevention of AMS . AMS incidence for placebo was 20.3 % , acetazolamide 10.5 % , and spironolactone 29.4 % . Oxygen saturation was also significantly increased in the acetazolamide group ( 83 % ± 0.04 ) vs spironolactone group ( 80 % ± 0.05 , p < 0.01 ) . CONCLUSIONS Spironolactone ( 50 mg BID ) was ineffective in comparison to acetazolamide ( 250 mg BID ) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya BACKGROUND Acute mountain sickness may be caused by cerebrovascular fluid leakage due to oxidative damage to the endothelium . This may be reduced by oral antioxidant supplementation . AIM To assess the effectiveness of antioxidant supplementation for the prevention of acute mountain sickness ( AMS ) . DESIGN A parallel-group double blind , r and omized placebo-controlled trial . METHODS The study was conducted in a university clinical research facility and a high altitude research laboratory . Eighty-three healthy lowl and volunteers ascended to 5200 m on the Apex 2 high altitude research expedition . The treatment group received a daily dose of 1 g l-ascorbic acid , 400 IU of alpha-tocopherol acetate and 600 mg of alpha-lipoic acid ( Cultech Ltd. , Wales , UK ) in four divided doses . Prevalence of AMS was measured using the Lake Louise Consensus score sheet ( LLS ) . Secondary outcomes were AMS severity measured using a novel visual analogue scale , arterial oxygen saturation and pulmonary artery systolic pressure ( PASP ) . RESULTS Forty-one subjects were allocated to the antioxidant group , and 42 to the placebo group . There was no difference in AMS incidence or severity between the antioxidant and placebo groups using the LLS at any time at high altitude . At the pre-determined comparison point at Day 2 at 5200 m , 69 % of the antioxidant group ( 25/36 ) and 66 % of the placebo group ( 23/35 ) had AMS using the LLS criteria ( P = 0.74 ) . No differences were observed between the groups for PASP , oxygen saturation , presence of a pericardial effusion or AMS assessed by VAS . CONCLUSION This trial found no evidence of benefit from antioxidant supplementation at high altitude . TRIAL REGISTRATION NUMBER NCT00664001 Background Patients with COPD may experience acute mountain sickness ( AMS ) and other altitude‐related adverse health effects ( ARAHE ) when traveling to high altitudes . This study evaluated whether dexamethasone , a drug used for the prevention of AMS in healthy individuals , would prevent AMS/ARAHE in patients with COPD . Methods This placebo‐controlled , double‐blind , parallel‐ design trial included patients with COPD and Global Initiative for Obstructive Lung Disease grade 1 to 2 who were living below 800 m. Patients were r and omized to receive dexamethasone ( 8 mg/d ) or placebo starting on the day before ascent and while staying in a high‐altitude clinic at 3,100 m for 2 days . The primary outcome assessed during the altitude sojourn was the combined incidence of AMS/ARAHE , defined as an Environmental Symptoms Question naire cerebral score evaluating AMS ≥ 0.7 or ARAHE requiring descent or an intervention . Results In 60 patients r and omized to receive dexamethasone ( median [ quartiles ] age : 57 years [ 50 ; 60 ] , FEV1 86 % predicted [ 70 ; 104 ] ; PaO2 at 760 m : 9.6 kPa [ 9.2 ; 10.0 ] ) , the incidence of AMS/ARAHE was 22 % ( 13 of 60 ) . In 58 patients r and omized to receive placebo ( age : 60 y [ 53 ; 64 ] ; FEV1 94 % predicted [ 76 ; 103 ] ; PaO2 : 10.0 kPa [ 9.1 ; 10.5 ] ) , the incidence of AMS/ARAHE was 24 % ( 14 of 58 ) ( χ2 statistic vs dexamethasone , P = .749 ) . Dexamethasone  mitigated the altitude‐induced PaO2 reduction compared with placebo ( mean between‐group difference [ 95 % CI ] , 0.4 kPa [ 0.0‐0.8 ] ; P = .028 ) . Conclusions In lowl and ers with mild to moderate COPD , the incidence of AMS/ARAHE at 3,100 m was moderate and not reduced by dexamethasone treatment . Based on these findings , dexamethasone can not be recommended for the prevention of AMS/ARAHE in patients with COPD undertaking high‐altitude travel , although the drug mitigated the altitude‐induced hypoxemia . Trial Registry Clinical Trials.gov ; No. : NCT02450968 ; URL : www . clinical trials.gov This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections  prevents acute mountain sickness ( AMS ) . This open-label , r and omized , controlled trial involved 39 healthy volunteers with hemoglobin ≤15.5 g/dL who were divided r and omly into  erythropoietin ( n=20 ) and control ( n=19 ) groups .  Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks . On day 1 , and 7 days after the last injection ( day 29 ) , oxygen saturation ( SaO2 ) , and hemoglobin were measured . The subjects departed Seoul on day 30 and arrived at Annapurna base camp ( ABC , 4,130 m ) on day 34 . AMS was diagnosed when headache and Lake Louise score ( LLS ) of ≥3 were present . Immediate descent criteria followed US Army recommendations . Two groups differ in hemoglobin levels on day 29 ( 15.4±1.1 vs 14.2±1.0 g/dL , P=0.001 ) . At ABC , erythropoietin group had a significantly lower mean LLS , AMS incidence , and number of subjects who met immediate descent criteria . Multiple logistic regression analysis showed that SaO2<87 % and control group , but not hemoglobin<15.0 g/dL , independently predicted satisfaction of immediate descent criteria . Erythropoietin-related adverse effects were not observed . In conclusion , erythropoietin may be an effective prophylaxis for AMS . ( Clinical Trial Registry Number ; NCT 01665781 ) . Graphical In a previous controlled study , dexamethasone ( DEX ) was shown to prevent acute mountain sickness ( AMS ) during exposure to simulated high altitude . To determine the effect of DEX during actual altitude exposure , 16 young men were treated with either DEX ( 4 mg every 6 h ) or placebo for 48 h prior to and 48 h after being rapidly transported from sea level to the summit of Pikes Peak , CO ( 4,300 m ) . Symptoms of AMS were evaluated twice daily at Pikes Peak using the Environmental Symptoms Question naire and a clinical assessment . During treatment the mean symptom scores were higher for subjects taking placebo in 18 out of 20 comparisons . On an individual basis , 60 % of the subjects receiving placebo met the criteria for being " sick " compared to 31 % of subjects receiving DEX . Beginning 24 h after cessation of treatment , DEX subjects experienced a progressive increase in symptom scores which lasted through the end of the altitude sojourn ( day 6 ) . The results indicate that DEX is an effective prophylactic treatment for AMS in an actual mountain environment , but that AMS symptoms can occur if the drug is stopped abruptly OBJECTIVE Recent trials have demonstrated the usefulness of ibuprofen in the prevention of  acute mountain sickness ( AMS )  , yet the proposed anti-inflammatory mechanism remains unconfirmed . Acetaminophen and ibuprofen were tested for AMS prevention . We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen 's mechanism of possible symptom reduction by predominantly mediating nociception in the brain . METHODS A double-blind , r and omized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS .  A total of 332 non-Nepali participants were recruited at Pheriche ( 4371 m ) and Dingboche ( 4410 m ) on the Everest Base Camp trek . The participants were r and omized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche ( 4940 m ) , where they were reassessed . The primary outcome was AMS incidence measured by the Lake Louise Question naire score . RESULTS Data from 225 participants who met inclusion criteria were analyzed . Twenty-five participants ( 22.1 % ) in the acetaminophen group and 18 ( 16.1 % ) in the ibuprofen group developed AMS ( P = .235 ) . The combined AMS incidence was 19.1 % ( 43 participants ) , 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location , suggesting that both interventions reduced the incidence of AMS . CONCLUSIONS We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence . This suggests that AMS prevention may be multifactorial , affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception . Additional study is needed Remote ischemic preconditioning ( RIPC ) has been shown to protect remote organs , such as the brain and the lung , from damage induced by subsequent hypoxia or ischemia . Acute mountain sickness ( AMS ) is a syndrome of nonspecific neurologic symptoms and in high-altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction ( HPV ) plays a pivotal role . We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3,450 m. Forty nonacclimatized volunteers were r and omized into two groups . At low altitude ( 750 m ) the RIPC group ( n = 20 ) underwent 4 × 5 min of lower-limb ischemia ( induced by inflation of bilateral thigh cuffs to 200 mmHg ) followed by 5 min of reperfusion . The control group ( n = 20 ) underwent a sham protocol ( 4 × 5 min of bilateral thigh cuff inflation to 20 mmHg ) . Thereafter , participants ascended to 3,450 m by train over 2 h and stayed there for 48 h. AMS was evaluated by the Lake Louise score ( LLS ) and the AMS-C score . Systolic pulmonary artery pressure ( SPAP ) was assessed by transthoracic Doppler echocardiography . RIPC had no effect on the overall incidence ( RIPC : 35 % , control : 35 % , P = 1.0 ) and severity ( RIPC vs. CONTROL P = 0.496 for LLS ; P = 0.320 for AMS-C score ) of AMS . RIPC also had no significant effect on SPAP [ maximum after 10 h at high altitude ; RIPC : 33 ( SD 8) mmHg ; controls : 37 ( SD 7 ) mmHg ; P = 0.19 ] . This study indicates that RIPC , performed immediately before passive ascent to 3,450 m , does not attenuate AMS and the magnitude of high-altitude pulmonary hypertension . NEW & NOTEWORTHY Remote ischemic preconditioning ( RIPC ) has been reported to improve neurologic and pulmonary outcome following an acute ischemic or hypoxic insult , yet the effect of RIPC for protecting from high-altitude diseases remains to be determined . The present study shows that RIPC , performed immediately before passive ascent to 3,450 m , does not attenuate acute mountain sickness and the degree of high-altitude pulmonary hypertension . Therefore , RIPC can not be recommended for prevention of high-altitude diseases Acute mountain sickness ( AMS ) is a common and disabling condition that occurs in healthy individuals ascending to high altitude . Based on the ability of iron to influence cellular oxygen sensing pathways , we hypothesized that iron supplementation would protect against AMS . To examine this hypothesis , 24 healthy sea-level residents were r and omized to receive either intravenous iron(III)-hydroxide sucrose ( 200 mg ) or saline placebo , before ascending rapidly to Cerro de Pasco , Peru ( 4340 m ) . The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude . No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude . However , the mean increase in AMS score was 65 % smaller in the iron group than in the saline group ( p<0.05 ) , and the change in AMS score correlated negatively with the change in ferritin ( R=-0.43 ; p<0.05 ) . Hematocrit and arterial oxygen saturation were unaffected by iron . In conclusion , this preliminary r and omized , double-blinded , placebo-controlled trial suggests that intravenous iron supplementation may protect against the symptoms of AMS in healthy volunteers The aims of this study were 1 ) to evaluate whether subjects suffering from acute mountain sickness ( AMS ) during exposure to high altitude have signs of autonomic dysfunction and 2 ) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS . Forty-one mountaineers were studied at 4,559-m altitude . AMS was diagnosed using the Lake Louise score , and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure ( BP ) variability on 10-min resting recordings . Seventeen subjects ( 41 % ) had AMS . Subjects with AMS were older than those without AMS ( P < 0.01 ) . At high altitude , the low-frequency ( LF ) component of systolic BP variability ( LF(SBP ) ) was higher ( P = 0.02 ) and the LF component of R-R variability in normalized units ( LF(RR)NU ) was lower ( P = 0.001 ) in subjects with AMS . After 3 mo , 21 subjects ( 43 % with AMS ) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture . LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude ( P < 0.001 ) and did not change between low and high altitude in subjects with AMS . Conversely , LF(SBP ) increased significantly during short-term hypoxia only in subjects with AMS , who also had higher resting BP ( P < 0.05 ) than those without AMS . Autonomic cardiovascular dysfunction accompanies AMS . Marked LF(SBP ) response to short-term hypoxia identifies AMS-prone subjects , supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS Bloch , Konrad E. , Alex and er J. Turk , Marco Maggiorini , Thomas Hess , Tobias Merz , Martina M. Bosch , Daniel Barthelmes , Urs Hefti , Jacqueline Pichler , Oliver Senn , and Otto D. Schoch . Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata , 7546 m. High Alt . Med . Biol . 10:25 - 32 , 2009.- Data on acclimatization during expedition-style climbing to > 5000 m are scant . We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness ( AMS ) symptoms and mountaineering success in climbers to Muztagh Ata ( 7546 m ) , Western China . We performed a r and omized , controlled trial during a high altitude medical research expedition to Muztagh Ata . Thirty-four healthy mountaineers ( mean age 45 yr , 7 women ) were r and omized to follow one of two protocol s , ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m , respectively . The main outcome measures , AMS symptom scores and the number of proceeding climbers , were assessed daily . Mean + /- SD AMS-C scores of 16 climbers r and omized to slow ascent were 0.06 + /- 0.18 , 0.26 + /- 0.08 , 0.41 + /- 0.45 , 0.53 + /- 0.77 at camps I ( 5533 m ) , II ( 6265 m ) , III ( 6865 m ) , and the summit ( 7546 m ) , respectively . Corresponding values in 18 climbers r and omized to fast ascent were significantly higher : 0.17 + /- 0.23 , 0.43 + /- 0.75 , 0.49 + /- 0.36 , and 0.69 + /- 0.54 ( p < 0.008 , vs. slow ascent in regression analysis accounting for weather-related protocol deviation ) . Climbers r and omized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers r and omized to fast ascent ( p = 0.04 , Kaplan-Meier analysis ) . More climbers r and omized to slow ascent were successful in reaching the highest camp at 6865 m without AMS ( odds ratio 9.5 ; 95 % confidence interval 1.02 to 89 ) . In climbers ascending to very high altitudes , differences of a few days in acclimatization have a significant impact on symptom severity , the prevalence of AMS , and mountaineering success . Clinical Trials.gov Identifier NCT00603122 METHOD We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract ( EGb 761 )  on acute mountain sickness ( AMS ) and vasomotor changes of the extremities during a Himalayan expedition . After giving their written informed consent , the subjects were r and omized to two groups . One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo . Assessment was based on the course of the Environmental Symptom Question naire ( ESQ ) score and the cold gradient measured by photoplethysmography . RESULTS The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study . In terms of factor 1 ( AMS-Cerebral ) , no subject in the EGb 761 group developed acute mountain sickness versus 40.9 % of subjects in the placebo group ; this difference was very significant ( p < or = 1.4 x 10(-3 ) ) . In terms of factor 2 ( AMS-Respiratory ) , 3 subjects ( 13.6 % ) in the EGb 761 group developed acute mountain sickness versus 18 ( 81.8 % ) in the placebo group ; this difference was very significant ( p = 1.2 x 10(-5 ) ) . CONCLUSION Due to its multiple pharmacological actions , EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude ( 5400 m ) with gradual exposure . It also decreased vasomotor disorders of the extremities , as demonstrated by plethysmography ( p < 10(-8 ) ) and a specific question naire ( p < 10(-9 ) )
Ensuring that the characteristics of the history and future ascents are similar may improve the clinical utility of AMS history
PURPOSE The goal of this meta- analysis was to determine the clinical utility of  acute mountain sickness ( AMS ) history to predict future incidents of AMS .