Ibuprofen vs Acetaminophen for AMS Prevention

Overview

AMS (acute mountain sickness) affects those who ascend too high (\>2000m) too fast. Acetazolamide is an effective drug for the prevention of AMS where proper acclimatization with gradual ascent may not be an option. AMS presents with headache and other non-specific symptoms such as nausea, tiredness, and dizziness. Because of the side effects of acetazolamide such as a tingling sensation, other drugs have been investigated to see if they will prevent AMS. Ibuprofen has recently been shown to prevent AMS. In this present study the investigators want to see if acetaminophen can also prevent AMS as acetaminophen unlike ibuprofen does not have gastric side effects. Second, because acetaminophen has much less anti-inflammatory component than ibuprofen, it may also provide some insight into the pathophysiology of AMS if acetaminophen were found to be effective in the prevention of AMS.

Acute mountain sickness (AMS) is a well-known disorder in sojourners to high altitude (\>2000m) characterized by headache, nausea and tiredness, akin to hangover-like symptoms. The Lake Louise criteria for AMS was primarily developed to allow uniformity in comparing the prevalence of AMS in different high altitude regions. Proper acclimatization by gradual ascent to high altitude is the best means of prevention of AMS. However there may be instances when rapid ascents may be necessary. Acetazolamide is the best known drug for the prevention of AMS. Because of its well-known side effects like tingling sensation in the fingers and toes and its potential sulpha allergy (acetazolamide is a sulpha-based drug) problems, alternative drugs in the prevention of AMS have been sought. Recently two randomized controlled trials have shown the usefulness of ibuprofen 600 mg tid orally in the prevention of AMS. The exact mechanism causing AMS is unknown although evidence points to a process in the central nervous system. The mechanism of headache, the main feature in most AMS patients, is probably multifactorial with various chemical and mechanical factors activating a final common pathway, the trigeminovascular system. Triggering factors associated with high altitude hypoxia leading to AMS may include arachidonic acid metabolites amongst others such as serotonin, histamine, and nitric oxide. The response in AMS prevention to non-steroidal anti-inflammatory drugs (NSAIDs) and steroids provides indirect evidence of arachidonic acid pathway and inflammation in the genesis of AMS. But in contrast, the role of drugs such as acetaminophen which primarily provide analgesia by blunting the meningovascular receptors known to mediate nociception is unknown in the prevention of AMS. Crucially if acetaminophen can prevent AMS the gastric irritation and possible gastrointestinal bleeding which are well known side effects of ibuprofen would not be encountered. In addition acetaminophen like ibuprofen and (unlike acetazolamide) is easily available over the counter. Therefore, the investigators hypothesize that acetaminophen in adequate dosage ( 1 g tid) will be as effective as ibuprofen ( 600 mg tid) in the prevention of AMS. Western trekkers will be randomly administered either acetaminophen or ibuprofen in a double blind fashion at 4300m where the investigators will enroll the participants. Then, at 5000 m at Lobuje after 48 to 96 hours the investigators will re-examine with the Lake Louise Questionnaire (LLQ) to see their AMS status. The investigators will also check the pulse oximeter. Sample Size: With a variable alpha 5%, power 80%, control 34% (based on previous studies) and experimental group 18%, the sample size arrived at (using http://www.sealedenvelope.com/power/binary-superiority/ ) was 115 per arm, a total of 230 participants. With a 20 % drop out the final number the investigators require is 288 participants.