1. Acute Altitude Illness Susie Hunter, MS4 Andrew Bridgforth, MS4 University of Nevada School of Medicine

2. Definition  Potentially serious conditions related to altitude ascent in otherwise healthy individuals, including :  Acute mountain sickness  High altitude cerebral edema (HACE)  High altitude pulmonary edema (HAPE) (noncardiogenic form of pulmonary edema)

3. Epidemiology  Men and women equally affected  Symptoms of acute altitude illness occur in approximately  25% of visitors to Colorado ski areas  50% of visitors to Himalayas  85% of visitors who travel directly to Mt. Everest region  Approximately 0.1%-4% incidence of high altitude cerebral and pulmonary edema

4. Causes  Ascent to altitude, related to  absolute altitude change  failure to acclimatize  genetic/physiologic susceptibility (such as failure to adequately increase ventilation)

5. Pathogenesis  Exact pathogenesis unknown  Acute mountain sickness and high altitude cerebral edema probably represent points on same spectrum  Hypoxia may lead to  Acute rise in hemoglobin concentration, indicating initial increase in vascular permeability followed by shift of fluid out of intravascular space which results in tissue edema  Altered permeability of blood brain barrier which predisposes brain to vasogenic form of cerebral edema  Inadequate ventilatory response (causing more severe hypoxia) coupled with fluid retention (causing volume expansion) may exacerbate both increased flow and increased pressure in brain

6. Pathogenesis cont.Pathogenesis cont. - High altitude pulmonary edema may be due to exaggerated hypoxic pulmonary vasoconstriction resulting in increased pulmonary capillary pressure  Elevated capillary pressure leads to mechanical disruption of pulmonary capillaries followed by extravasation of fluid into interstitial space and alveolar spaces in absence of inflammation  Limited availability of nitric oxide may increase pulmonary arterial pressure  Impaired sodium and water transportation within lung may also play a role

7. Risk FactorsRisk Factors  Likely risk factors:  Rapid ascent  Higher altitude (sleeping elevation)  History of altitude sickness (predictive or recurrence in adults, but not children)  Strenuous exertion  Cold temperature  Recent upper respiratory tract infection  Young age  Resident of low altitude  Patent foramen ovale associated with increased susceptibility to high altitude pulmonary edema, based on case-control study  Possible risk factors:  Obesity might increase risk of acute mountain sickness based on small cohort of 9 obese and 10 non- obese men spending 24 hours in hypobaric environmental chamber, symptoms consistent with acute mountain sickness in 78% obese vs. 40% non-obese men

8. Why it’s an issue.Why it’s an issue.  Complications:  Death  Coma  Profound hypoxemia  Altered mental status  *Coma or death may occur within 24hrs of high altitude cerebral edema!

9. History of Present IllnesssHistory of Present Illnesss  High altitude headache developing within 24 hours of ascent and worsening at night and with exertion  Additional symptoms- usually appear within 6-12hrs after arrival at altitude and resolve in 1-3 days:  nausea/vomiting or reduced appetite  fatigue  dizziness  debilitating tiredness and/or difficulty sleeping  decreased urine output independent of fluid intake  hallucinations  dry cough progressing to productive cough with frothy, and eventually blood-stained, sputum  greater reduction in exercise tolerance than expected for altitude  dyspnea  chest tightness or congestion

10. HPI cont.HPI cont.  Symptoms of high altitude cerebral edema may develop in persons with unresolved acute mountain sickness  Symptoms of high altitude pulmonary edema usually develop 1-4 days after arrival at altitude > 2,500 meters (8,200 feet) in person with or without symptoms of acute mountain sickness  Ask about alcohol or drug use (to rule out symptoms of intoxication which may mimic acute altitude illness)

11. Physical signsPhysical signs  Signs of acute altitude illnesses include:  Debilitating tiredness and fatigue  Vomiting  Dry cough progressing to productive cough with frothy, and eventually blood-stained, sputum  Altered mental status (such as impaired mental capacity, hallucinations, stupor, ataxia)  Signs of high altitude pulmonary edema may include  Central cyanosis  Tachypnea  Tachycardia

12. Physical signs cont.Physical signs cont.  Lungs:  Crackles may be present on chest auscultation in person with high altitude pulmonary edema  Assess for wheezing, tachypnea, rales  Neuro:  Assess for altered mental status such as:  impaired mental capacity  stupor  ataxia  hallucinations

13. Diagnosis  Acute mountain sickness: requires recent ascent to altitude + headache + additional symptom and absence of fever  High altitude cerebral edema: change in mental status or ataxia with acute mountain sickness OR change in mental status and ataxia without acute mountain sickness  High altitude pulmonary edema: requires two signs and symptoms

14. Case #1Case #1  30 year old adventurer from San Francisco travels to Ecuador and decides to ascend Mt. Cotopaxi (5897 m or 19,347 ft) on his second day in country. That night at base camp (4572 m or 15,000 ft), the guide notices the man becomes confused and is having trouble breathing.

15. Case #2Case #2  30 y/o male from the Central Valley in California decides he wants to climb Mt. Whitney in day

16. Treatment  Stop ascent, consider descent in all cases

17. Treatment: AMSTreatment: AMS  Mild acute mountain sickness (score 2-4):  Analgesics (ibuprofen or acetaminophen) and antiemetics for symptomatic control  Acetazolamide 250mg twice daily can be used (good evidence, speeds acclimatization but better in prevention than treatment)

18. Treatment: AMSTreatment: AMS  Moderate to severe acute mountain illness (score 5-15):  Dexamethasone 8mg IV followed by 4mg every 6 hrs until symptoms resolve +/- acetazolamide twice daily  Dexamethasone does NOT facilitate acclimatization however  Possible other treatment options: oxygen (low quality evidence), hyperbaric chamber, descent if severe

19. Treatment: HACETreatment: HACE  High altitude cerebral edema (HACE):  Assisted descent (usually > 1000ft)  Fluids  Dexamethasone 8mg once followed by 4mg q6hrs until symptoms resolve  Oxygen and hyperbaric chamber when descent is not possible

20. Treatment: HAPETreatment: HAPE  High altitude pulmonary edema (HAPE):  Assisted descent (> 1000ft)  Oxygen and hyperbaric chamber if descent not possible  Nifedipine sustained release 30mg q6hrs  Other possible treatments with poor evidence currently: sildenafil/taladafil, beta agonists (salmeterol), CPAP, diuretics

21. Prophylaxis & PreventionProphylaxis & Prevention  Low risk: no hx of altitude illness and ascending to 2 days to reach 2500-3000m with no more than 500m gain per day  No medications required  If >3000m, max sleeping elevation increase of 500m/day with rest day every 3-4 days (sleep elevation more important than altitude reached during waking hours)

22. Prophylaxis & Prevention Cont’d  Moderate risk: hx of altitude illness and ascending to 2500-2800m in a day OR no hx of altitude illness but ascending to >2800m in a day OR daily elevation gain >500m at above 3000m  Acetazolamide 125mg BID started at least one day before ascent and continued until start of descent  Alternative: Dexamethasone 2mg q6hrs or 4mg q12hrs started the day of the ascent; cannot be used >10 days

23. Prophylaxis & Prevention Cont’d  High risk: hx of altitude illness and ascending to > 2800m in a day OR hx of HACE or HAPE OR ascending > 3500m in a day OR daily elevation gain >500m at above 3500m OR very rapid ascents  Same as moderate with following exceptions  Hx of HAPE: add nifedipine sustained release 60mg daily starting one day prior to ascent and continuing until descent +/- salmeterol 125mcg twice daily

24. References  Fiore DC, Hall S, Shoja P. “Altitude Illness: Risk Factors, Prevention, Presentation, and Treatment.” American Family Physician. 82.9 (2010): 1103-1110. Print  Gallagher SA, Hackett PH. “High Altitude Illness.” Emergency Medicine Clinics of North America. 22 (2004): 329-355. Print  Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH. “Wilderness Medical Society Concensus Guidelines for the Prevention and Treatment of Acute Altitude Illness.” Wilderness & Environmental Medicine. 21 (2010): 146-155. Print  DynaMed [Internet]. Ipswich (MA): EBSCO Publishing. 1995 – present. Acute Altitude Illness; [updated 2011 Aug 2].Available from http://0- web.ebscohost.com.innopac.library.unr.edu/dynamed/detail?vid=3&hid=19&sid=6612 8086-325e-4b1a-aadf- d03db27fb679%40sessionmgr10&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPX NpdGU%3d#db=dme&AN=116210&anchor=Patient-Information. Registration and login required.