ALTITUDE MEDICINE Shawn Dowling Sept 2008 Shawn Dowling Sept 2008

Objectives Discuss basic altitude physiology Discuss basic altitude physiology How to recognize altitude disorders How to recognize altitude disorders Management Management Prevention Prevention Discuss basic altitude physiology Discuss basic altitude physiology How to recognize altitude disorders How to recognize altitude disorders Management Management Prevention Prevention Will not discuss: Subacute/Chronic Altitude Illnesses Cold-related illnesses Altitude-exacerbated illnesses

High Altitude Illnesses Definition Definition Cerebral (AMS  HACE spectrum) and pulmonary (HAPE) syndromes which develop in un- or underacclimatized persons after ascent to high altitude Cerebral (AMS  HACE spectrum) and pulmonary (HAPE) syndromes which develop in un- or underacclimatized persons after ascent to high altitude Are often PREVENTABLE and can usually be managed if S/Sx are recognized early and Tx are implemented in a timely fashion Are often PREVENTABLE and can usually be managed if S/Sx are recognized early and Tx are implemented in a timely fashion Definition Definition Cerebral (AMS  HACE spectrum) and pulmonary (HAPE) syndromes which develop in un- or underacclimatized persons after ascent to high altitude Cerebral (AMS  HACE spectrum) and pulmonary (HAPE) syndromes which develop in un- or underacclimatized persons after ascent to high altitude Are often PREVENTABLE and can usually be managed if S/Sx are recognized early and Tx are implemented in a timely fashion Are often PREVENTABLE and can usually be managed if S/Sx are recognized early and Tx are implemented in a timely fashion

Moderate Altitude m (8,000-10,000ft)- i.e. Lake Louise/Sunshine Valley m (8,000-10,000ft)- i.e. Lake Louise/Sunshine Valley Minor impairment of arterial oxygen transport (S a O 2 >90%), P A O 2 >60 torr Minor impairment of arterial oxygen transport (S a O 2 >90%), P A O 2 >60 torr Usually not clinically important unless significant underlying medical disorder Usually not clinically important unless significant underlying medical disorder AMS common with rapid ascent above 2500 meters AMS common with rapid ascent above 2500 meters m (8,000-10,000ft)- i.e. Lake Louise/Sunshine Valley m (8,000-10,000ft)- i.e. Lake Louise/Sunshine Valley Minor impairment of arterial oxygen transport (S a O 2 >90%), P A O 2 >60 torr Minor impairment of arterial oxygen transport (S a O 2 >90%), P A O 2 >60 torr Usually not clinically important unless significant underlying medical disorder Usually not clinically important unless significant underlying medical disorder AMS common with rapid ascent above 2500 meters AMS common with rapid ascent above 2500 meters

High Altitude m (10,000-18,000ft) m (10,000-18,000ft) i.e. Mount Columbia (12, 365ft – highest point in Alberta) i.e. Mount Columbia (12, 365ft – highest point in Alberta) Maximum arterial saturation < 90%; P A O 2 <60 torr Maximum arterial saturation < 90%; P A O 2 <60 torr Most common range for serious altitude illness Most common range for serious altitude illness m (10,000-18,000ft) m (10,000-18,000ft) i.e. Mount Columbia (12, 365ft – highest point in Alberta) i.e. Mount Columbia (12, 365ft – highest point in Alberta) Maximum arterial saturation < 90%; P A O 2 <60 torr Maximum arterial saturation < 90%; P A O 2 <60 torr Most common range for serious altitude illness Most common range for serious altitude illness

Extreme Altitude m (18,000-29,035ft) from Mount Logan (19550ft) to Mount Everest (29035ft) m (18,000-29,035ft) from Mount Logan (19550ft) to Mount Everest (29035ft) Marked hypoxemia and hypocapnia Marked hypoxemia and hypocapnia Maximum arterial saturation 50-75%; P A O torr Maximum arterial saturation 50-75%; P A O torr Deterioration eventually outstrips acclimatization, complete acclimatization not possible Deterioration eventually outstrips acclimatization, complete acclimatization not possible m (18,000-29,035ft) from Mount Logan (19550ft) to Mount Everest (29035ft) m (18,000-29,035ft) from Mount Logan (19550ft) to Mount Everest (29035ft) Marked hypoxemia and hypocapnia Marked hypoxemia and hypocapnia Maximum arterial saturation 50-75%; P A O torr Maximum arterial saturation 50-75%; P A O torr Deterioration eventually outstrips acclimatization, complete acclimatization not possible Deterioration eventually outstrips acclimatization, complete acclimatization not possible

Epidemiology Study Group# at Risk per Year Sleeping Altitude % AMS (# affected) % HAPE or HACE Western USA Visitors 40 Million meters 15 (6 million).01(4000?) Mt. Everest Trekkers 6, meters 35 (2100)1.0 (60?) Mt. McKinley Climbers 1, meters 30 (300)2-3 (25-35) Mt. Rainier Climbers 9, meters 67 (6000)?

Holy Crap!!

More About Gas! At sea level we are underneath an ocean of air At sea level we are underneath an ocean of air % O 2 is always 21% % O 2 is always 21% But as you climb higher, the P atm drops and thus your PO 2 drops But as you climb higher, the P atm drops and thus your PO 2 drops Pi O2 = 0.21(P B -47) Pi O2 = 0.21(P B -47) P B =barometric pressure P B =barometric pressure At sea level At sea level Pi O2 = 160 mm Hg Pi O2 = 160 mm Hg At 2500m At 2500m Pi O2 = 119 mm Hg  Pi O2 = 119 mm Hg  Aconquilcha,Chile 5340m Aconquilcha,Chile 5340m Pi O2 = 82 mm Hg Pi O2 = 82 mm Hg On top of Everest (8848m) On top of Everest (8848m) Pi O2 = 43 mm Hg  Pi O2 = 43 mm Hg  Thanks Rigby

Acclimatization Complex adaptation by essentially every system to minimize hypoxia and maintain cellular functions despite decreased PiO2 Complex adaptation by essentially every system to minimize hypoxia and maintain cellular functions despite decreased PiO2 Given sufficient time most people can acclimatize to 5500m/18150ft, beyond that progressive deterioration occurs Given sufficient time most people can acclimatize to 5500m/18150ft, beyond that progressive deterioration occurs Complex adaptation by essentially every system to minimize hypoxia and maintain cellular functions despite decreased PiO2 Complex adaptation by essentially every system to minimize hypoxia and maintain cellular functions despite decreased PiO2 Given sufficient time most people can acclimatize to 5500m/18150ft, beyond that progressive deterioration occurs Given sufficient time most people can acclimatize to 5500m/18150ft, beyond that progressive deterioration occurs

So WHAT IS the problem with Altitude? HYPOXIA HYPOXIA WHAT ARE THE PHYSIOLOGIC COMPENSATIONS? WHAT ARE THE PHYSIOLOGIC COMPENSATIONS? Essentially all the physiologic changes are attempting to improve arterial and therefore cellular oxygenation Essentially all the physiologic changes are attempting to improve arterial and therefore cellular oxygenation HYPOXIA HYPOXIA WHAT ARE THE PHYSIOLOGIC COMPENSATIONS? WHAT ARE THE PHYSIOLOGIC COMPENSATIONS? Essentially all the physiologic changes are attempting to improve arterial and therefore cellular oxygenation Essentially all the physiologic changes are attempting to improve arterial and therefore cellular oxygenation

Pulmonary Response to PiO2 Hypoxemic Ventilatory Response Hypoxemic Ventilatory Response Begins w/i minutes of ascent above 1500m Begins w/i minutes of ascent above 1500m Hypoxia - pulmonary vasoconstrictor Hypoxia - pulmonary vasoconstrictor Allows for selective shunting away from areas of hypoxia w/preferential areas of vasodilation Allows for selective shunting away from areas of hypoxia w/preferential areas of vasodilation pulmonary vascular resistance pulmonary vascular resistance pulmonary artery pressure (cold and exercise PAP while descent, O2 and certain Rx PAP) pulmonary artery pressure (cold and exercise PAP while descent, O2 and certain Rx PAP) diffusion capacity and lung volume diffusion capacity and lung volume Hypoxemic Ventilatory Response Hypoxemic Ventilatory Response Begins w/i minutes of ascent above 1500m Begins w/i minutes of ascent above 1500m Hypoxia - pulmonary vasoconstrictor Hypoxia - pulmonary vasoconstrictor Allows for selective shunting away from areas of hypoxia w/preferential areas of vasodilation Allows for selective shunting away from areas of hypoxia w/preferential areas of vasodilation pulmonary vascular resistance pulmonary vascular resistance pulmonary artery pressure (cold and exercise PAP while descent, O2 and certain Rx PAP) pulmonary artery pressure (cold and exercise PAP while descent, O2 and certain Rx PAP) diffusion capacity and lung volume diffusion capacity and lung volume

Hypoxemic Ventilatory Response Ventilation increases proportionally to the degree of hypoxia detected at the chemoreceptors Ventilation increases proportionally to the degree of hypoxia detected at the chemoreceptors Lower PaCO2 = higher P A O2 Lower PaCO2 = higher P A O2 remember … P A O2 = PiO2 - PaCO2/R remember … P A O2 = PiO2 - PaCO2/R As PCO2 drops a respiratory alkalosis occurs (what does this do to the medulla?) As PCO2 drops a respiratory alkalosis occurs (what does this do to the medulla?) kidneys compensate by excreting bicarb(over 6- 8/7) kidneys compensate by excreting bicarb(over 6- 8/7) Vigourous HVR helps acclimatization whereas a poor HVR may lead to altitude- illness Vigourous HVR helps acclimatization whereas a poor HVR may lead to altitude- illness Ventilation increases proportionally to the degree of hypoxia detected at the chemoreceptors Ventilation increases proportionally to the degree of hypoxia detected at the chemoreceptors Lower PaCO2 = higher P A O2 Lower PaCO2 = higher P A O2 remember … P A O2 = PiO2 - PaCO2/R remember … P A O2 = PiO2 - PaCO2/R As PCO2 drops a respiratory alkalosis occurs (what does this do to the medulla?) As PCO2 drops a respiratory alkalosis occurs (what does this do to the medulla?) kidneys compensate by excreting bicarb(over 6- 8/7) kidneys compensate by excreting bicarb(over 6- 8/7) Vigourous HVR helps acclimatization whereas a poor HVR may lead to altitude- illness Vigourous HVR helps acclimatization whereas a poor HVR may lead to altitude- illness

HVR Carotid bodiesO2O2 Aortic bodies

Cerebral Circulation Hypoxemia = increases cerebral blood flow Hypoxemia = increases cerebral blood flow Hypocapnea = decreases cerebral blood flow Hypocapnea = decreases cerebral blood flow Net result is an increase (modest) in cerebral blood flow at PaO2 12,500 feet) Net result is an increase (modest) in cerebral blood flow at PaO2 12,500 feet) Contributes to pathophysiology of AMS and HACE Contributes to pathophysiology of AMS and HACE Hypoxemia = increases cerebral blood flow Hypoxemia = increases cerebral blood flow Hypocapnea = decreases cerebral blood flow Hypocapnea = decreases cerebral blood flow Net result is an increase (modest) in cerebral blood flow at PaO2 12,500 feet) Net result is an increase (modest) in cerebral blood flow at PaO2 12,500 feet) Contributes to pathophysiology of AMS and HACE Contributes to pathophysiology of AMS and HACE

CVS Response Catecholamine release: Epi and Norepi Catecholamine release: Epi and Norepi Sympathetic Tone: Sympathetic Tone: CO= HR x SV CO= HR x SV BP= CO x PVR BP= CO x PVR This responses allows for better tissue perfusion (but, also decreases exercise performance) – over time epi/norepi levels drop and CO/HR/PVR return to normal This responses allows for better tissue perfusion (but, also decreases exercise performance) – over time epi/norepi levels drop and CO/HR/PVR return to normal Catecholamine release: Epi and Norepi Catecholamine release: Epi and Norepi Sympathetic Tone: Sympathetic Tone: CO= HR x SV CO= HR x SV BP= CO x PVR BP= CO x PVR This responses allows for better tissue perfusion (but, also decreases exercise performance) – over time epi/norepi levels drop and CO/HR/PVR return to normal This responses allows for better tissue perfusion (but, also decreases exercise performance) – over time epi/norepi levels drop and CO/HR/PVR return to normal

Hematologic Blood volume increases immediately: Blood volume increases immediately: Primarily due to hemo[ ] from diuresis Primarily due to hemo[ ] from diuresis Hypoxia stimulates renal EPO production Hypoxia stimulates renal EPO production Takes weeks for it to effect Red Cell Mass Takes weeks for it to effect Red Cell Mass Oxygen Dissociation curve – combination of inc 2,3 DPG (rightward shift) and alkalosis (leftward shift) leads to minimal net effect Oxygen Dissociation curve – combination of inc 2,3 DPG (rightward shift) and alkalosis (leftward shift) leads to minimal net effect Blood volume increases immediately: Blood volume increases immediately: Primarily due to hemo[ ] from diuresis Primarily due to hemo[ ] from diuresis Hypoxia stimulates renal EPO production Hypoxia stimulates renal EPO production Takes weeks for it to effect Red Cell Mass Takes weeks for it to effect Red Cell Mass Oxygen Dissociation curve – combination of inc 2,3 DPG (rightward shift) and alkalosis (leftward shift) leads to minimal net effect Oxygen Dissociation curve – combination of inc 2,3 DPG (rightward shift) and alkalosis (leftward shift) leads to minimal net effect

Acclimatization AcuteChronic Ventilation, O2 Diffusion capacity Ventilation Heart Rate Red Cell Mass (from EPO release) Cerebral Blood Flow Metabolism (tissue changes) Diuresis, Hct (from volume contraction)

Gotta know it. It’ll be on the exam!

High Altitude Illness What are RF? What are RF? What are positive predictors? What are positive predictors? What worsens altitude illnesses? What worsens altitude illnesses? What does not effect altitude illnesses? What does not effect altitude illnesses? What are RF? What are RF? What are positive predictors? What are positive predictors? What worsens altitude illnesses? What worsens altitude illnesses? What does not effect altitude illnesses? What does not effect altitude illnesses?

High Altitude Illness What are Risk Factors? What are Risk Factors? Rate of ascent/Starting altitude Rate of ascent/Starting altitude Altitude reached Altitude reached Sleeping at altitude Sleeping at altitude Individual physiology/Genetics? Individual physiology/Genetics? What are Positive Predictors? What are Positive Predictors? Hx of prior ascent w/o Sx Hx of prior ascent w/o Sx Elderly (less AMS/HACE), Women (less HAPE) Elderly (less AMS/HACE), Women (less HAPE) What are Risk Factors? What are Risk Factors? Rate of ascent/Starting altitude Rate of ascent/Starting altitude Altitude reached Altitude reached Sleeping at altitude Sleeping at altitude Individual physiology/Genetics? Individual physiology/Genetics? What are Positive Predictors? What are Positive Predictors? Hx of prior ascent w/o Sx Hx of prior ascent w/o Sx Elderly (less AMS/HACE), Women (less HAPE) Elderly (less AMS/HACE), Women (less HAPE)

What worsens altitude-illnesses? What worsens altitude-illnesses? Respiratory depressants/Alcohol Respiratory depressants/Alcohol Pre-existing Medical Illnesses (very few): Pre-existing Medical Illnesses (very few): i.e. Pulm HTN, certain CHD, Exertion Exertion Hypothermia Hypothermia What does not affect risk? What does not affect risk? Physical fitness Physical fitness CAD/HTN CAD/HTN Mild COPD Mild COPD Pregnancy Pregnancy DM DM What worsens altitude-illnesses? What worsens altitude-illnesses? Respiratory depressants/Alcohol Respiratory depressants/Alcohol Pre-existing Medical Illnesses (very few): Pre-existing Medical Illnesses (very few): i.e. Pulm HTN, certain CHD, Exertion Exertion Hypothermia Hypothermia What does not affect risk? What does not affect risk? Physical fitness Physical fitness CAD/HTN CAD/HTN Mild COPD Mild COPD Pregnancy Pregnancy DM DM

Case #1 You’ve decided to hike to Machu Picchu and have flown directly from Lima (sea level) into Cuzco (3515m/11,600ft). That day you start the hike up and notice you develop a nasty HA, and nausea. You’ve decided to hike to Machu Picchu and have flown directly from Lima (sea level) into Cuzco (3515m/11,600ft). That day you start the hike up and notice you develop a nasty HA, and nausea.

What’s your Diagnosis? 1. Acute Mountain Syndrome 2. High Altitude Cerebral Edema 3. High Altitude Pulmonary Edema 4. Other Medical Illness 1. Acute Mountain Syndrome 2. High Altitude Cerebral Edema 3. High Altitude Pulmonary Edema 4. Other Medical Illness

Pearl Any illness at altitude is altitude illness until proven otherwise. Any illness at altitude is altitude illness until proven otherwise.

Lake Louise Criteria for AMS Presence of a HA in an un-acclimatized person who has arrived at an altitude >2000m (usu >2500m) Presence of a HA in an un-acclimatized person who has arrived at an altitude >2000m (usu >2500m) + 1 of + 1 of GI (anorexia, N,V) GI (anorexia, N,V) Fatigue Fatigue Insomnia Insomnia Dizziness/lightheaded Dizziness/lightheaded Sx usually begin between 6-10 hrs but may be as early as 1 hour Sx usually begin between 6-10 hrs but may be as early as 1 hour Presence of a HA in an un-acclimatized person who has arrived at an altitude >2000m (usu >2500m) Presence of a HA in an un-acclimatized person who has arrived at an altitude >2000m (usu >2500m) + 1 of + 1 of GI (anorexia, N,V) GI (anorexia, N,V) Fatigue Fatigue Insomnia Insomnia Dizziness/lightheaded Dizziness/lightheaded Sx usually begin between 6-10 hrs but may be as early as 1 hour Sx usually begin between 6-10 hrs but may be as early as 1 hour

Pearls Never ascend with symptoms of AMS Never ascend with symptoms of AMS Never leave someone with AMS alone Never leave someone with AMS alone -Letting someone with AMS hike alone is the equilavent of going for a hike in the Kananaski’s alone the night of Party at the retreat. Never ascend with symptoms of AMS Never ascend with symptoms of AMS Never leave someone with AMS alone Never leave someone with AMS alone -Letting someone with AMS hike alone is the equilavent of going for a hike in the Kananaski’s alone the night of Party at the retreat.

AMS Pathophysiology

Treatment? Any or Combination Any or Combination Stop, Rest and Continue once Sx resolve Stop, Rest and Continue once Sx resolve Acetazolimide (alone or in combination) Acetazolimide (alone or in combination) Dexamethasone Dexamethasone O2, immediate descent O2, immediate descent Nifedipine Nifedipine + Symptomatic Treatment + Symptomatic Treatment Any or Combination Any or Combination Stop, Rest and Continue once Sx resolve Stop, Rest and Continue once Sx resolve Acetazolimide (alone or in combination) Acetazolimide (alone or in combination) Dexamethasone Dexamethasone O2, immediate descent O2, immediate descent Nifedipine Nifedipine + Symptomatic Treatment + Symptomatic Treatment

Treatment? Any or Combination Any or Combination 1. Stop, Rest and Continue once Sx resolve 2. Acetazolamide (alone or in combination) 3. Dexamethasone (if severe) 4. O2, rapid/immediate descent 5. Nifedipine 6. + Symptomatic Treatment Any or Combination Any or Combination 1. Stop, Rest and Continue once Sx resolve 2. Acetazolamide (alone or in combination) 3. Dexamethasone (if severe) 4. O2, rapid/immediate descent 5. Nifedipine 6. + Symptomatic Treatment

Treatment Options of AMS Stop and rest at altitude that Sx 1 st develop +/- Acetazolamide -> May proceed once Sx abate Stop and rest at altitude that Sx 1 st develop +/- Acetazolamide -> May proceed once Sx abate + Tx Sx + Tx Sx Nausea: Prochlorperazine 10mg po/im (stimulates HVR) Nausea: Prochlorperazine 10mg po/im (stimulates HVR) HA: Tylenol/NSAID’s HA: Tylenol/NSAID’s Insomnia: acetazolamide 125mg PO QHS Insomnia: acetazolamide 125mg PO QHS Stop and rest at altitude that Sx 1 st develop +/- Acetazolamide -> May proceed once Sx abate Stop and rest at altitude that Sx 1 st develop +/- Acetazolamide -> May proceed once Sx abate + Tx Sx + Tx Sx Nausea: Prochlorperazine 10mg po/im (stimulates HVR) Nausea: Prochlorperazine 10mg po/im (stimulates HVR) HA: Tylenol/NSAID’s HA: Tylenol/NSAID’s Insomnia: acetazolamide 125mg PO QHS Insomnia: acetazolamide 125mg PO QHS

Treatment of AMS Mild Symptoms Mild Symptoms Does not need descent if mild Sx and constant supervision Does not need descent if mild Sx and constant supervision Stop ascent until better Stop ascent until better Acetazolamide (250 BID) Acetazolamide (250 BID) Tylenol/ASA for Sx Tylenol/ASA for Sx Anti-emetic PRN Anti-emetic PRN Consider O 2 at 1-2 LPM Consider O 2 at 1-2 LPM Moderate or Unresolving AMS Moderate or Unresolving AMS Descent 500 m Descent 500 m Consider: Consider: O 2 at 1-2 LPM O 2 at 1-2 LPM Hyperbaric therapy Hyperbaric therapy Dexamethasone 4mg PO q6h until able to descend Dexamethasone 4mg PO q6h until able to descend May ascend after symptoms resolve May ascend after symptoms resolve

If someone is getting worse, go down at once If someone is getting worse, go down at once If Sx of HACE are present DESCEND IMMEDIATELY If Sx of HACE are present DESCEND IMMEDIATELY If someone is getting worse, go down at once If someone is getting worse, go down at once If Sx of HACE are present DESCEND IMMEDIATELY If Sx of HACE are present DESCEND IMMEDIATELY

Quick word about Acetazolamide What’s the MOA? What’s the MOA?

Quick word about Acetazolamide What’s the MOA? What’s the MOA? Causes a bicarb diuresis by inhibiting Carbonic Anhydrase at the kidney Causes a bicarb diuresis by inhibiting Carbonic Anhydrase at the kidney This leads to a metabolic acidosis which counteracts the alkalosis from hyperventilation This leads to a metabolic acidosis which counteracts the alkalosis from hyperventilation Allowing an individual to have a better HVR and therefore acclimatize better Allowing an individual to have a better HVR and therefore acclimatize better Which allergy must you ask about? Which allergy must you ask about? What’s the MOA? What’s the MOA? Causes a bicarb diuresis by inhibiting Carbonic Anhydrase at the kidney Causes a bicarb diuresis by inhibiting Carbonic Anhydrase at the kidney This leads to a metabolic acidosis which counteracts the alkalosis from hyperventilation This leads to a metabolic acidosis which counteracts the alkalosis from hyperventilation Allowing an individual to have a better HVR and therefore acclimatize better Allowing an individual to have a better HVR and therefore acclimatize better Which allergy must you ask about? Which allergy must you ask about?

Pt adamant that the HA is from dehydration Pt adamant that the HA is from dehydration Can give Dx/Tx of 1L of fluid + advil or tylenol – if this completely resolves HA, not likely to be AMS Can give Dx/Tx of 1L of fluid + advil or tylenol – if this completely resolves HA, not likely to be AMS Pt adamant that the HA is from dehydration Pt adamant that the HA is from dehydration Can give Dx/Tx of 1L of fluid + advil or tylenol – if this completely resolves HA, not likely to be AMS Can give Dx/Tx of 1L of fluid + advil or tylenol – if this completely resolves HA, not likely to be AMS

Case #2 Despite the advice to refrain from continuing to ascend, you continue up and begin to feel disoriented and noticed you seem to be walking with a drunken’ sort of gait Despite the advice to refrain from continuing to ascend, you continue up and begin to feel disoriented and noticed you seem to be walking with a drunken’ sort of gait Dx? Dx? Despite the advice to refrain from continuing to ascend, you continue up and begin to feel disoriented and noticed you seem to be walking with a drunken’ sort of gait Despite the advice to refrain from continuing to ascend, you continue up and begin to feel disoriented and noticed you seem to be walking with a drunken’ sort of gait Dx? Dx?

High Altitude Cerebral Edema (HACE) Least common but most lethal altitude illness Least common but most lethal altitude illness Usually occurs above 3600m(12,000 feet) Usually occurs above 3600m(12,000 feet) Symptoms usually develop over 1-3 days Symptoms usually develop over 1-3 days reported range 12 hours to 9 days reported range 12 hours to 9 days Usually also have symptoms of AMS / HAPE Usually also have symptoms of AMS / HAPE Least common but most lethal altitude illness Least common but most lethal altitude illness Usually occurs above 3600m(12,000 feet) Usually occurs above 3600m(12,000 feet) Symptoms usually develop over 1-3 days Symptoms usually develop over 1-3 days reported range 12 hours to 9 days reported range 12 hours to 9 days Usually also have symptoms of AMS / HAPE Usually also have symptoms of AMS / HAPE

HACE Dx Presence of a change in mental status and/or ataxia in a person with AMSPresence of a change in mental status and/or ataxia in a person with AMSOr Presence of both mental status changes and ataxia in a person without AMSPresence of both mental status changes and ataxia in a person without AMS Presence of a change in mental status and/or ataxia in a person with AMSPresence of a change in mental status and/or ataxia in a person with AMSOr Presence of both mental status changes and ataxia in a person without AMSPresence of both mental status changes and ataxia in a person without AMS

HACE S & Sx Think of the effect of hypoxia and ICP Think of the effect of hypoxia and ICP Global encephalopathy Global encephalopathy Ataxia Ataxia Altered mentation Altered mentation Seizures Seizures Occasional CN palsies (secondary to increased ICP) Occasional CN palsies (secondary to increased ICP) Papilledema Papilledema Retinal hemorrhage Retinal hemorrhage Coma Coma Death is due to brain herniation Death is due to brain herniation Think of the effect of hypoxia and ICP Think of the effect of hypoxia and ICP Global encephalopathy Global encephalopathy Ataxia Ataxia Altered mentation Altered mentation Seizures Seizures Occasional CN palsies (secondary to increased ICP) Occasional CN palsies (secondary to increased ICP) Papilledema Papilledema Retinal hemorrhage Retinal hemorrhage Coma Coma Death is due to brain herniation Death is due to brain herniation

HACE Pathophys

Management? Management?

Tx of HACE DESCENT (until pt improves) DESCENT (until pt improves) O2 O2 DXM 8mg PO/IM/IV initially then 4mg Q6H DXM 8mg PO/IM/IV initially then 4mg Q6H +/- acetazolamide 250mg PO BID +/- acetazolamide 250mg PO BID What if the weather does not allow for a safe descent and you happen to be part of a well equipped expedition? What if the weather does not allow for a safe descent and you happen to be part of a well equipped expedition? DESCENT (until pt improves) DESCENT (until pt improves) O2 O2 DXM 8mg PO/IM/IV initially then 4mg Q6H DXM 8mg PO/IM/IV initially then 4mg Q6H +/- acetazolamide 250mg PO BID +/- acetazolamide 250mg PO BID What if the weather does not allow for a safe descent and you happen to be part of a well equipped expedition? What if the weather does not allow for a safe descent and you happen to be part of a well equipped expedition?

Protective Inflatable Toboggan?

Gamow Bag Hyperbaric Chambers Hyperbaric Chambers Lightweight (14.9 lb) Lightweight (14.9 lb) Manually pressurized Manually pressurized Generate 103mm Hg (2 psi) above ambient pressure Generate 103mm Hg (2 psi) above ambient pressure Simulates descent of feet at moderate altitudes Simulates descent of feet at moderate altitudes Simulates descent of 9000 feet at top of Mt. Everest Simulates descent of 9000 feet at top of Mt. Everest After short course of treatment patient often able to descend on their own After short course of treatment patient often able to descend on their own This is primarily a temporizing measure - Not an alternate to descending This is primarily a temporizing measure - Not an alternate to descending Hyperbaric Chambers Hyperbaric Chambers Lightweight (14.9 lb) Lightweight (14.9 lb) Manually pressurized Manually pressurized Generate 103mm Hg (2 psi) above ambient pressure Generate 103mm Hg (2 psi) above ambient pressure Simulates descent of feet at moderate altitudes Simulates descent of feet at moderate altitudes Simulates descent of 9000 feet at top of Mt. Everest Simulates descent of 9000 feet at top of Mt. Everest After short course of treatment patient often able to descend on their own After short course of treatment patient often able to descend on their own This is primarily a temporizing measure - Not an alternate to descending This is primarily a temporizing measure - Not an alternate to descending

Case #3 During a visit to Nepal, Mr. Hackalung, decides to organize a hike to Everest Base camp (5430m/18000ft). During a visit to Nepal, Mr. Hackalung, decides to organize a hike to Everest Base camp (5430m/18000ft). On day 3 you notice you notice he develops a dry cough and during the lunch break he’s quite SOB On day 3 you notice you notice he develops a dry cough and during the lunch break he’s quite SOB You’re the group doc You’re the group doc What’s the most likely Dx? What’s the most likely Dx? During a visit to Nepal, Mr. Hackalung, decides to organize a hike to Everest Base camp (5430m/18000ft). During a visit to Nepal, Mr. Hackalung, decides to organize a hike to Everest Base camp (5430m/18000ft). On day 3 you notice you notice he develops a dry cough and during the lunch break he’s quite SOB On day 3 you notice you notice he develops a dry cough and during the lunch break he’s quite SOB You’re the group doc You’re the group doc What’s the most likely Dx? What’s the most likely Dx?

Case #3 Fortunately for you, you realize that you develop X-ray vision at altitude – convenient skill – except that you’re on an all guy expedition but…- here is what you see.

Responsible for most high altitude deaths Responsible for most high altitude deaths Relatively Abrupt Onset Relatively Abrupt Onset Usually occurs on 2 nd night at altitude, Rare after 4 days Usually occurs on 2 nd night at altitude, Rare after 4 days Women less susceptible than men Women less susceptible than men Presence of HAPE increases likelihood of cerebral illnesses – by worsening hypoxemia: 50% have AMS & 14% have HACE Presence of HAPE increases likelihood of cerebral illnesses – by worsening hypoxemia: 50% have AMS & 14% have HACE Responsible for most high altitude deaths Responsible for most high altitude deaths Relatively Abrupt Onset Relatively Abrupt Onset Usually occurs on 2 nd night at altitude, Rare after 4 days Usually occurs on 2 nd night at altitude, Rare after 4 days Women less susceptible than men Women less susceptible than men Presence of HAPE increases likelihood of cerebral illnesses – by worsening hypoxemia: 50% have AMS & 14% have HACE Presence of HAPE increases likelihood of cerebral illnesses – by worsening hypoxemia: 50% have AMS & 14% have HACE High Altitude Pulmonary Edema (HAPE)

HAPE Diagnosis At least two of the following Sx: At least two of the following Sx: Dyspnea at rest Dyspnea at rest Cough Cough Weakness or decreased exercise performance Weakness or decreased exercise performance Chest tightness or congestion Chest tightness or congestion At least two of the following Sx: At least two of the following Sx: Dyspnea at rest Dyspnea at rest Cough Cough Weakness or decreased exercise performance Weakness or decreased exercise performance Chest tightness or congestion Chest tightness or congestion At least two of the following signs: Central cyanosis Audible crackles or wheezing in at least one lung field Tachypnea tachycardia

HAPE Pathophys Increase CWP & PAP

Doc, how do you want to treat him? Doc, how do you want to treat him? You have access to most drugs, but no monitoring equipment. You have access to most drugs, but no monitoring equipment. Doc, how do you want to treat him? Doc, how do you want to treat him? You have access to most drugs, but no monitoring equipment. You have access to most drugs, but no monitoring equipment.

HAPE Tx – Increase PiO2 Definitive Tx Definitive Tx Descent or Simulated descent (if unable to Descend) Descent or Simulated descent (if unable to Descend) Supplemental O2 (SaO2>90%) Supplemental O2 (SaO2>90%) May be a role for observant management (bed rest/O2) if mild case and experienced and well- equipped physician present May be a role for observant management (bed rest/O2) if mild case and experienced and well- equipped physician present Definitive Tx Definitive Tx Descent or Simulated descent (if unable to Descend) Descent or Simulated descent (if unable to Descend) Supplemental O2 (SaO2>90%) Supplemental O2 (SaO2>90%) May be a role for observant management (bed rest/O2) if mild case and experienced and well- equipped physician present May be a role for observant management (bed rest/O2) if mild case and experienced and well- equipped physician present Temporizing Measures Nifedipine 10mg PO Ventolin Diamox PEEP Viagra – currently being studied DXM – no benefit

Prevention Rational Ascent (MOST IMPORTANT) Rational Ascent (MOST IMPORTANT) First night not higher than 2400m (8000 feet) First night not higher than 2400m (8000 feet) CLIMB HIGH, SLEEP LOW. At altitudes above 3000 meters (10,000 feet), your sleeping elevation should not increase more than 300 meters (1000 feet) per night, daytime increase of 600m. CLIMB HIGH, SLEEP LOW. At altitudes above 3000 meters (10,000 feet), your sleeping elevation should not increase more than 300 meters (1000 feet) per night, daytime increase of 600m. Every 1000 meters (3300 feet) of sleeping elevation gain you should spend a second night. Every 1000 meters (3300 feet) of sleeping elevation gain you should spend a second night. Ginko biloba Ginko biloba Limited studies have been performed, but the results look very promising for prophylaxis of AMS. 120 mg po BID starting 5 days before ascent, and continuing at altitude. Limited studies have been performed, but the results look very promising for prophylaxis of AMS. 120 mg po BID starting 5 days before ascent, and continuing at altitude. Rational Ascent (MOST IMPORTANT) Rational Ascent (MOST IMPORTANT) First night not higher than 2400m (8000 feet) First night not higher than 2400m (8000 feet) CLIMB HIGH, SLEEP LOW. At altitudes above 3000 meters (10,000 feet), your sleeping elevation should not increase more than 300 meters (1000 feet) per night, daytime increase of 600m. CLIMB HIGH, SLEEP LOW. At altitudes above 3000 meters (10,000 feet), your sleeping elevation should not increase more than 300 meters (1000 feet) per night, daytime increase of 600m. Every 1000 meters (3300 feet) of sleeping elevation gain you should spend a second night. Every 1000 meters (3300 feet) of sleeping elevation gain you should spend a second night. Ginko biloba Ginko biloba Limited studies have been performed, but the results look very promising for prophylaxis of AMS. 120 mg po BID starting 5 days before ascent, and continuing at altitude. Limited studies have been performed, but the results look very promising for prophylaxis of AMS. 120 mg po BID starting 5 days before ascent, and continuing at altitude.

Acetazolamide Acetazolamide Not routinely indicated but use consider if; Not routinely indicated but use consider if; Forced rapid ascent (1 day) to altitudes over 3000m. Forced rapid ascent (1 day) to altitudes over 3000m. A rapid gain in sleeping elevation - for example gaining 1000 m in one day. A rapid gain in sleeping elevation - for example gaining 1000 m in one day. A history of recurrent AMS. A history of recurrent AMS. Dose: 125 mg BID, 24 hrs before ascent + 2-3/7 after ascent Dose: 125 mg BID, 24 hrs before ascent + 2-3/7 after ascent Acetazolamide Acetazolamide Not routinely indicated but use consider if; Not routinely indicated but use consider if; Forced rapid ascent (1 day) to altitudes over 3000m. Forced rapid ascent (1 day) to altitudes over 3000m. A rapid gain in sleeping elevation - for example gaining 1000 m in one day. A rapid gain in sleeping elevation - for example gaining 1000 m in one day. A history of recurrent AMS. A history of recurrent AMS. Dose: 125 mg BID, 24 hrs before ascent + 2-3/7 after ascent Dose: 125 mg BID, 24 hrs before ascent + 2-3/7 after ascent

DXM DXM Indication – Hx of AMS, but diamox probably preferred Indication – Hx of AMS, but diamox probably preferred Dose: 2mg PO Q6H, start day before ascent and continue until at max altitude x 48 hrs Dose: 2mg PO Q6H, start day before ascent and continue until at max altitude x 48 hrs Nifedipine ER Nifedipine ER Indication – Hx of HAPE Indication – Hx of HAPE 20-30mg PO BID, start day before ascent and continue until at max altitude x 48 hrs 20-30mg PO BID, start day before ascent and continue until at max altitude x 48 hrs DXM DXM Indication – Hx of AMS, but diamox probably preferred Indication – Hx of AMS, but diamox probably preferred Dose: 2mg PO Q6H, start day before ascent and continue until at max altitude x 48 hrs Dose: 2mg PO Q6H, start day before ascent and continue until at max altitude x 48 hrs Nifedipine ER Nifedipine ER Indication – Hx of HAPE Indication – Hx of HAPE 20-30mg PO BID, start day before ascent and continue until at max altitude x 48 hrs 20-30mg PO BID, start day before ascent and continue until at max altitude x 48 hrs

Avoid Avoid Alcohol Alcohol Sleeping Pills (diamox is the Rx of choice) Sleeping Pills (diamox is the Rx of choice) Narcotics (other than at moderate doses) Narcotics (other than at moderate doses) Avoid overexertion Avoid overexertion Stay warm Stay warm Avoid Avoid Alcohol Alcohol Sleeping Pills (diamox is the Rx of choice) Sleeping Pills (diamox is the Rx of choice) Narcotics (other than at moderate doses) Narcotics (other than at moderate doses) Avoid overexertion Avoid overexertion Stay warm Stay warm

Pearls SUMMARY: DESCEND IF UNSURE SUMMARY: DESCEND IF UNSURE All other Tx are only temporizing for life- threatening illnesses SUMMARY: DESCEND IF UNSURE SUMMARY: DESCEND IF UNSURE All other Tx are only temporizing for life- threatening illnesses

What Should make you think of Other diagnoses? Onset of Sx >3/7 after ascent to a given altitude Onset of Sx >3/7 after ascent to a given altitude Lack of a HA Lack of a HA Rapid response to rest/stopping ascent Rapid response to rest/stopping ascent Lack of response to descent, O2, or dexamethasone(unless HAPE) Lack of response to descent, O2, or dexamethasone(unless HAPE) Onset of Sx >3/7 after ascent to a given altitude Onset of Sx >3/7 after ascent to a given altitude Lack of a HA Lack of a HA Rapid response to rest/stopping ascent Rapid response to rest/stopping ascent Lack of response to descent, O2, or dexamethasone(unless HAPE) Lack of response to descent, O2, or dexamethasone(unless HAPE)

Summary Early recognition is important Early recognition is important AMS AMS stop ascent, rest, +/- diamox, Tx Sx stop ascent, rest, +/- diamox, Tx Sx HACE HACE DESCENT +/- DXM, diamox DESCENT +/- DXM, diamox HAPE HAPE DESCENT +/- nifedipine, ventolin DESCENT +/- nifedipine, ventolin Early recognition is important Early recognition is important AMS AMS stop ascent, rest, +/- diamox, Tx Sx stop ascent, rest, +/- diamox, Tx Sx HACE HACE DESCENT +/- DXM, diamox DESCENT +/- DXM, diamox HAPE HAPE DESCENT +/- nifedipine, ventolin DESCENT +/- nifedipine, ventolin

References High-Altitude Illness. Emerg M Clinics of N America, High-Altitude Illness. Emerg M Clinics of N America, High-Altitude Illness. NEJM, July High-Altitude Illness. NEJM, July Rosen’s. Rosen’s. Guyton. Textbook of Medical Physiology Guyton. Textbook of Medical Physiology Aric’s Rounds 2003 Aric’s Rounds 2003 Rigby’s NRC lecture Rigby’s NRC lecture High-Altitude Illness. Emerg M Clinics of N America, High-Altitude Illness. Emerg M Clinics of N America, High-Altitude Illness. NEJM, July High-Altitude Illness. NEJM, July Rosen’s. Rosen’s. Guyton. Textbook of Medical Physiology Guyton. Textbook of Medical Physiology Aric’s Rounds 2003 Aric’s Rounds 2003 Rigby’s NRC lecture Rigby’s NRC lecture

So what’s UP with Altitude? Barometric pressure decreases as altitude rises (hypobaria) and with higher latitudes Barometric pressure decreases as altitude rises (hypobaria) and with higher latitudes Hypobaria decreases the partial pressure of O2: x Atm Pressure = PiO2, note- [02] remains at 21% Hypobaria decreases the partial pressure of O2: x Atm Pressure = PiO2, note- [02] remains at 21% Changes in weather (eg: low pressure front) can change relative altitude (up to feet) Changes in weather (eg: low pressure front) can change relative altitude (up to feet) Barometric pressure decreases as altitude rises (hypobaria) and with higher latitudes Barometric pressure decreases as altitude rises (hypobaria) and with higher latitudes Hypobaria decreases the partial pressure of O2: x Atm Pressure = PiO2, note- [02] remains at 21% Hypobaria decreases the partial pressure of O2: x Atm Pressure = PiO2, note- [02] remains at 21% Changes in weather (eg: low pressure front) can change relative altitude (up to feet) Changes in weather (eg: low pressure front) can change relative altitude (up to feet)