Altitude Illness INTRODUCTION Background: Altitude illness refers to a constellation of syndromes that result from hypoxic injury alone or in combination with various maladaptive physiological changes. Cerebral syndromes usually develop at altitudes above 8000 ft (2500 m). Everyone travelling to altitude is at risk, regardless of the level of physical fitness or previous altitude experience. The cerebral form of altitude illness includes a spectrum of severity from mild (Acute Mountain Sickness, AMS) to severe (High Altitude Cerebral Edema, HACE). AMS is felt to represent a subacute form of the frank brain edema seen in HACE, and differentiating between these two differently named syndromes can be difficult. Pathophysiology: Rapid ascent to high altitude outstrips the body's ability to tolerate the decreasing availability of oxygen. The cerebral forms of altitude illness appear to be due to hypoxic-induced changes in blood-brain barrier permeability, which result in a vasogenic brain edema. Frequency: In the U.S.: The true incidence of AMS is unknown, although it is estimated to occur in approximately 25% of lowland visitors to moderate-elevation ski areas in Utah and Colorado. Internationally: AMS frequency is proportional to the maximum altitude attained. From 24-50% of those who sojourn to altitudes over 4000 m will suffer at least moderate AMS. HACE is estimated to occur in about 1% of those persons who are at risk. Mortality/Morbidity: AMS is a self-limiting disease, and will generally resolve in 1-5 days. HACE may be fatal within 1-2 days unless treated by immediate descent. Recovery is usually complete, although a small percentage of patients will die even with proper treatment. Age: Age has a small effect in adults: younger adults are slightly more susceptible than those who are older. Children have similar rates of altitude cerebral syndromes as adults. CLINICAL History: Patients will often have a history of rapid ascent to an altitude greater than about 8000 ft (2500 m). An additional risk factor is an increase in the sleeping elevation by more than 300 m /1000 ft per night when above 10,000 ft (3000 m). At-risk patients frequently lack the spontaneous diuresis normally seen at altitude. Normal symptoms at altitude include the following: Exertional dyspnea Spontaneous diuresis Nocturnal periodic breathing (Cheyne-Stokes respirations) Frequent awakening at night Weird or vivid dreams Diagnosis of AMS is implied by headache plus at least one of the following symptoms: Gastrointestinal symptoms such as anorexia, nausea and vomiting Light-headedness or dizziness Weakness or fatigue Insomnia Diagnosis of HACE is implied by the following: Ascent with symptoms of AMS is the most common history. May evolve after a very rapid ascent despite the absence of AMS. Commonly occurs after the onset of severe high altitude pulmonary edema (HAPE) Confusion, lassitude and other mental status changes, by history Gait ataxia, by history Physical: AMS Patients appear ill, but otherwise have no specific physical findings. Neurologic examination (especially mental status and gait) is normal. Cardiac rate does not correlate with either acclimatization or AMS. Pulmonary rales may be present in some patients. Fever is absent. HACE Suspect the diagnosis in a patient with symptoms of AMS who develops either gait ataxia (cannot walk heel-toe in a straight line) or mental status changes. Regardless of AMS symptoms, a combination of ataxia and mental status changes suggests HACE. Usually, neurologic examination is otherwise normal. Focal neurologic signs (such as third and sixth cranial nerve palsies) may be seen in end-stage HACE, but are more suggestive of other causes of focal deficits at altitude such as a CVA, TIA, migraine or brain neoplasm. Causes: Rapid ascent Higher altitudes are more risky. Continued ascent despite AMS is the major risk factor for developing HACE. HACE is frequently seen secondary to HAPE, presumably due to rapidly worsening hypoxia (equivalent to continued ascent). DIFFERENTIALS Anxiety Encephalitis Gastroenteritis Guillain-Barre Syndrome Headache, Cluster Headache, Migraine Headache, Tension Hypothermia Meningitis Neoplasms, Brain Pediatrics, Dehydration Pediatrics, Headache Pediatrics, Meningitis and Encephalitis Sinusitis Stroke, Hemorrhagic Stroke, Ischemic Subarachnoid Hemorrhage Subdural Hematoma Transient Ischemic Attack Other Problems to be Considered: Carbon monoxide poisoning Imaging Studies: Head CT Useful in patients with either focal neurologic findings or atypical cases of suspected HACE. The CT scan can help diagnose a CVA, subdural hematoma, subarachnoid hemorrhage or cerebral neoplasm that becomes symptomatic at altitude. Head MRI Useful in demonstrating changes specific to HACE as indicated by an increased T2 signal in the white matter of the corpus callosum. The MRI may be helpful in evaluating causes of focal neurologic deficits. Procedures: Portable hyperbaric treatment Portable hyperbaric chambers (Gamow Bag, Certec Bag, Portable Altitude Chamber) are in wide use among adventure travel and trekking groups and climbing expeditions. These are all lightweight coated fabric bags about 2 m long and 0.7 m diameter. The patient is placed completely within the bag, which is sealed shut and inflated with a manually operated pump, pressurizing the inside to 105-220 mmHg above ambient atmospheric pressure. Depending on the elevation during usage, a physiologic (simulated) descent of up to 600 ft (2000 m) may be achieved within minutes. Continuous pumping is necessary to flush CO2 out of the system, unless a chemical scrubber system is used. Patients are typically treated in one-hour increments and then re-evaluated. TREATMENT Prehospital Care: AMS Rest, hydration and mild analgesics are generally sufficient. The patient should ascend no further until completely asymptomatic. Acetazolamide and/or dexamethasone can be given. Oxygen, if available, should be administered at 4 L/min by mask or nasal cannula. Hyperbaric treatment can be given in 1-hour increments for 2-4 hours. Improvement will generally occur in 12-24 hours with acetazolamide, in 2-6 hours with dexamethasone and rapidly with descent, oxygen or hyperbaric treatment. HACE The classic treatment aphorism is that there are three primary treatments: descent, descent, and descent. Dexamethasone should be given early. Oxygen, if available, should be administered at 4 L/min by mask or nasal cannula. Hyperbaric treatment in 1-hour increments for 2-6 hours may awaken a comatose patient and improve ataxia sufficiently to greatly reduce the difficulty of evacuating the patient to a lower altitude. Emergency Department Care: All of the symptoms of AMS improve dramatically with descent, and by the time a patient reaches the ED further treatment is rarely indicated. Oxygen administered at 4 L/min or to keep SaO2 above 90% should be used in patients who continue to be acutely ill with either severe AMS or HACE after descent. Dexamethasone should be continued in symptomatic HACE patients. Consultations: Consult a neurologist for focal neurologic deficits or if there are unusual or persistent symptoms of HACE. MEDICATION Mild analgesics such as aspirin, acetaminophen or ibuprofen are indicated for symptomatic treatment of headache. Drug Category: Diuretics - Acetazolamide has been shown to be useful for the cerebral altitude syndromes due to its respiratory-stimulant properties. Drug Name Acetazolamide (Diamox) - Acetazolamide, a carbonic anhydrase inhibitor, is used for its respiratory-stimulant effect. It accelerates acclimatization to altitude. It is used to treat AMS and to help prevent AMS in a forced rapid ascent or in patients with a history of repeated AMS. It will help ameliorate periodic breathing at altitude. This agent is not indicated for general prophylaxis of AMS; rather, patients should be educated about slower ascents. Adult Dose 125 mg po bid for AMS until well; 125 mg po hs for periodic breathing until below the threshold altitude at which troublesome periodic breathing began. Pediatric 5 mg/kg/d po divided bid for AMS Contraindications Allergy to sulfonamides or medication Interactions Cyclosporin, primidone, diflunisal Pregnancy C - Safety for use during pregnancy has not been established Drug Category: Corticosteroids - Used for their potent anti-inflammatory activity in brain edema. Drug Name Dexamethasone (Decadron) - May improve AMS and HACE by treating vasogenic cerebral edema and possibly by improving endothelial integrity. Dexamethasone prevents AMS, but does not improve acclimatization, and rebound AMS may occur if the drug is discontinued at altitude. Adult Dose 8 mg po/im stat, then 4 mg po/im q6h for HACE 4 mg po/im q4h x 2 doses for AMS Pediatric 0.5 mg/kg po/im stat, then 0.2 mg/kg po/im q6h for HACE Contraindications Systemic fungal infections Pregnancy C - Safety for use during pregnancy has not been established Precautions Diabetes mellitus Drug Category: Antiemetics - Used for symptomatic treatment of nausea in AMS. Drug Name Prochlorperazine (Compazine) - In addition to its antiemetic effect, has the advantage of augmenting the hypoxic ventilatory response, acting as a respiratory stimulant at altitude. Adult Dose 5-10 mg IM q 4h prn nausea Pediatric 0.132 mg/kg IM Pregnancy C - Safety for use during pregnancy has not been established FOLLOWUP Further Inpatient Care: Further inpatient care is not indicated for AMS. For HACE, hospitalization may be indicated depending on the severity. Care is supportive. Further Outpatient Care: After descent, further outpatient care is not indicated for AMS. Mild HACE should be seen in follow-up in 2-3 days to check for clearance of symptoms. In/Out Patient Meds: Symptomatic treatment of residual headache or nausea in AMS Continue dexamethasone for 1-2 days after descent in uncomplicated HACE or until the mental status clears in severe HACE requiring hospitalization. Deterrence: Staged ascent Patients planning travel to high altitude in the future should be encouraged to stage their ascent and pay careful attention to symptoms. Avoid abrupt ascents to sleeping elevations over 10,000 ft (3000 m), and spend at least two nights between 2500-3000 m before further ascent. Above 3000 m, sleeping elevations should not increase by more than 300-400 m per night, with a second night at the same elevation every 1000 m. Day hikes to higher elevations, with return to a lower sleeping elevation, improve acclimatization. Acetazolamide prophylaxis indications Unavoidable rapid ascent, such as flying in to a high city (e.g. Lhasa, Tibet) Past history of recurrent AMS Complications: Symptoms of HACE, particularly ataxia, commonly persist for days to weeks after descent. Rarely, patients may have long-term neurologic deficits after severe or prolonged HACE. Prognosis: Excellent for AMS and for survivors of HACE. Re-ascent with caution is acceptable after complete recovery. Patient Education: Patients should be educated on staged ascents (see Deterrence, above). The Golden Rules of Altitude Illness If you feel unwell at altitude, it is altitude illness until proven otherwise. If you have symptoms of AMS, go no higher. If your symptoms are worsening (or, with HACE or HAPE), you must go down immediately. MISCELLANEOUS Medical/Legal Pitfalls: Suddenly symptomatic brain tumors misdiagnosed as HACE Guillain-Barré Syndrome misdiagnosed as HACE Cortical blindness and other TIA-like conditions misdiagnosed as HACE Special Concerns: Focal neurologic deficits May occur in end-stage HACE, otherwise should be a tip-off to consider another diagnosis. Cerebrovascular accidents occasionally occur at high altitude in persons with no obvious risk factors. Transient ischemic attacks and migraine headaches may also be causes of focal neurologic deficits at high altitude. Transient aphasia and cortical blindness that resolve with descent or oxygen therapy have been reported. Previously unknown brain tumors that become suddenly symptomatic at altitude should also be considered in patients with focal deficits or whose symptoms fail to clear with descent and time. High altitude retinal hemorrhage Relatively common Usually asymptomatic, unless it happens to occur over macula (rare) No specific treatment, but descent prevents further hemorrhages. Prognosis is good.