Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m
Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, p...
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| creator | Berger, Marc Moritz Sareban, Mahdi Schiefer, Lisa Maria Swenson, Kai E Treff, Franziska Schäfer, Larissa Schmidt, Peter Schimke, Magdalena M Paar, Michael Niebauer, Josef Cogo, Annalisa Kriemler, Susi Schwery, Stefan Pickerodt, Philipp A Mayer, Benjamin Bärtsch, Peter Swenson, Erik R |
| description | Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended ( |
| doi_str_mv | 10.1152/japplphysiol.00806.2021 |
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= 7, 250 mg 3 times/day; placebo:
= 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo,
= 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (
< 0.001) without a group difference (
= 0.68). Arterial Po
fell to 36 ± 9 mmHg (
< 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (
= 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both
< 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.
This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.</description><identifier>ISSN: 8750-7587</identifier><identifier>EISSN: 1522-1601</identifier><identifier>DOI: 10.1152/japplphysiol.00806.2021</identifier><identifier>PMID: 35511718</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Acetazolamide ; Altitude ; Ascent ; Carbonic anhydrase ; Carbonic anhydrases ; Dexamethasone ; Echocardiography ; Edema ; Heart ; High altitude ; High-altitude environments ; Hypoxia ; Mountains ; Nifedipine ; Oxygenation ; Placebos ; Pressure ; Prevention ; Pulmonary arteries ; Pulmonary artery ; Radiography ; Statistical analysis ; Vasoconstriction ; Veins & arteries ; Ventricle</subject><ispartof>Journal of applied physiology (1985), 2022-06, Vol.132 (6), p.1361-1369</ispartof><rights>Copyright American Physiological Society Jun 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c256t-e63ffb53ad266d8cef87d762a73cae81f08a3c5265504af1b26c475adc612d5f3</citedby><cites>FETCH-LOGICAL-c256t-e63ffb53ad266d8cef87d762a73cae81f08a3c5265504af1b26c475adc612d5f3</cites><orcidid>0000-0001-5875-8250 ; 0000-0001-6771-3193 ; 0000-0002-2811-9041 ; 0000-0002-4117-6198</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35511718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berger, Marc Moritz</creatorcontrib><creatorcontrib>Sareban, Mahdi</creatorcontrib><creatorcontrib>Schiefer, Lisa Maria</creatorcontrib><creatorcontrib>Swenson, Kai E</creatorcontrib><creatorcontrib>Treff, Franziska</creatorcontrib><creatorcontrib>Schäfer, Larissa</creatorcontrib><creatorcontrib>Schmidt, Peter</creatorcontrib><creatorcontrib>Schimke, Magdalena M</creatorcontrib><creatorcontrib>Paar, Michael</creatorcontrib><creatorcontrib>Niebauer, Josef</creatorcontrib><creatorcontrib>Cogo, Annalisa</creatorcontrib><creatorcontrib>Kriemler, Susi</creatorcontrib><creatorcontrib>Schwery, Stefan</creatorcontrib><creatorcontrib>Pickerodt, Philipp A</creatorcontrib><creatorcontrib>Mayer, Benjamin</creatorcontrib><creatorcontrib>Bärtsch, Peter</creatorcontrib><creatorcontrib>Swenson, Erik R</creatorcontrib><title>Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m</title><title>Journal of applied physiology (1985)</title><addtitle>J Appl Physiol (1985)</addtitle><description>Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide:
= 7, 250 mg 3 times/day; placebo:
= 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo,
= 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (
< 0.001) without a group difference (
= 0.68). Arterial Po
fell to 36 ± 9 mmHg (
< 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (
= 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both
< 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.
This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.</description><subject>Acetazolamide</subject><subject>Altitude</subject><subject>Ascent</subject><subject>Carbonic anhydrase</subject><subject>Carbonic anhydrases</subject><subject>Dexamethasone</subject><subject>Echocardiography</subject><subject>Edema</subject><subject>Heart</subject><subject>High altitude</subject><subject>High-altitude environments</subject><subject>Hypoxia</subject><subject>Mountains</subject><subject>Nifedipine</subject><subject>Oxygenation</subject><subject>Placebos</subject><subject>Pressure</subject><subject>Prevention</subject><subject>Pulmonary arteries</subject><subject>Pulmonary artery</subject><subject>Radiography</subject><subject>Statistical analysis</subject><subject>Vasoconstriction</subject><subject>Veins & arteries</subject><subject>Ventricle</subject><issn>8750-7587</issn><issn>1522-1601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpdkc1O3DAURq2qqExpX6G11E0XzdR24h-WCNEWCYkNXUd37OuOR0kcbAcJHoGnxlNoQayuLJ_z-VofIZ85W3MuxfcdzPMwb29ziMOaMcPUWjDB35BVvRUNV4y_JSujJWu0NPqQvM95xxjvOsnfkcNWSs41Nytyf-Y92pJp9BQsFriLA4zBIY0TnZdhjBOkWwqpYB1zwpyXhBQmtz_c4FRCBau8DX-2DQwllKXKzyY6HIGCrz5NMAdXnynhpkZkW21aIu2-SXlMxw_kwMOQ8ePTPCK_f5xdnf5qLi5_np-eXDRWSFUaVK33G9mCE0o5Y9Eb7bQSoFsLaLhnBlorhZKSdeD5RijbaQnOKi6c9O0R-fqYO6d4vWAu_RjqLsMAE8Yl9zWWccakURX98grdxSVNdbtKaamOldZ7Sj9SNsWcE_p-TmGsn-856_d19S_r6v_W1e_rquanp_xlM6L77_3rp30A2o-Wyg</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Berger, Marc Moritz</creator><creator>Sareban, Mahdi</creator><creator>Schiefer, Lisa Maria</creator><creator>Swenson, Kai E</creator><creator>Treff, Franziska</creator><creator>Schäfer, Larissa</creator><creator>Schmidt, Peter</creator><creator>Schimke, Magdalena M</creator><creator>Paar, Michael</creator><creator>Niebauer, Josef</creator><creator>Cogo, Annalisa</creator><creator>Kriemler, Susi</creator><creator>Schwery, Stefan</creator><creator>Pickerodt, Philipp A</creator><creator>Mayer, Benjamin</creator><creator>Bärtsch, Peter</creator><creator>Swenson, Erik R</creator><general>American Physiological Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5875-8250</orcidid><orcidid>https://orcid.org/0000-0001-6771-3193</orcidid><orcidid>https://orcid.org/0000-0002-2811-9041</orcidid><orcidid>https://orcid.org/0000-0002-4117-6198</orcidid></search><sort><creationdate>20220601</creationdate><title>Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m</title><author>Berger, Marc Moritz ; Sareban, Mahdi ; Schiefer, Lisa Maria ; Swenson, Kai E ; Treff, Franziska ; Schäfer, Larissa ; Schmidt, Peter ; Schimke, Magdalena M ; Paar, Michael ; Niebauer, Josef ; Cogo, Annalisa ; Kriemler, Susi ; Schwery, Stefan ; Pickerodt, Philipp A ; Mayer, Benjamin ; Bärtsch, Peter ; Swenson, Erik R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-e63ffb53ad266d8cef87d762a73cae81f08a3c5265504af1b26c475adc612d5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acetazolamide</topic><topic>Altitude</topic><topic>Ascent</topic><topic>Carbonic anhydrase</topic><topic>Carbonic anhydrases</topic><topic>Dexamethasone</topic><topic>Echocardiography</topic><topic>Edema</topic><topic>Heart</topic><topic>High altitude</topic><topic>High-altitude environments</topic><topic>Hypoxia</topic><topic>Mountains</topic><topic>Nifedipine</topic><topic>Oxygenation</topic><topic>Placebos</topic><topic>Pressure</topic><topic>Prevention</topic><topic>Pulmonary arteries</topic><topic>Pulmonary artery</topic><topic>Radiography</topic><topic>Statistical analysis</topic><topic>Vasoconstriction</topic><topic>Veins & arteries</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berger, Marc Moritz</creatorcontrib><creatorcontrib>Sareban, Mahdi</creatorcontrib><creatorcontrib>Schiefer, Lisa Maria</creatorcontrib><creatorcontrib>Swenson, Kai E</creatorcontrib><creatorcontrib>Treff, Franziska</creatorcontrib><creatorcontrib>Schäfer, Larissa</creatorcontrib><creatorcontrib>Schmidt, Peter</creatorcontrib><creatorcontrib>Schimke, Magdalena M</creatorcontrib><creatorcontrib>Paar, Michael</creatorcontrib><creatorcontrib>Niebauer, Josef</creatorcontrib><creatorcontrib>Cogo, Annalisa</creatorcontrib><creatorcontrib>Kriemler, Susi</creatorcontrib><creatorcontrib>Schwery, Stefan</creatorcontrib><creatorcontrib>Pickerodt, Philipp A</creatorcontrib><creatorcontrib>Mayer, Benjamin</creatorcontrib><creatorcontrib>Bärtsch, Peter</creatorcontrib><creatorcontrib>Swenson, Erik R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of applied physiology (1985)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berger, Marc Moritz</au><au>Sareban, Mahdi</au><au>Schiefer, Lisa Maria</au><au>Swenson, Kai E</au><au>Treff, Franziska</au><au>Schäfer, Larissa</au><au>Schmidt, Peter</au><au>Schimke, Magdalena M</au><au>Paar, Michael</au><au>Niebauer, Josef</au><au>Cogo, Annalisa</au><au>Kriemler, Susi</au><au>Schwery, Stefan</au><au>Pickerodt, Philipp A</au><au>Mayer, Benjamin</au><au>Bärtsch, Peter</au><au>Swenson, Erik R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m</atitle><jtitle>Journal of applied physiology (1985)</jtitle><addtitle>J Appl Physiol (1985)</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>132</volume><issue>6</issue><spage>1361</spage><epage>1369</epage><pages>1361-1369</pages><issn>8750-7587</issn><eissn>1522-1601</eissn><abstract>Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide:
= 7, 250 mg 3 times/day; placebo:
= 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo,
= 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (
< 0.001) without a group difference (
= 0.68). Arterial Po
fell to 36 ± 9 mmHg (
< 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (
= 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both
< 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.
This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>35511718</pmid><doi>10.1152/japplphysiol.00806.2021</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5875-8250</orcidid><orcidid>https://orcid.org/0000-0001-6771-3193</orcidid><orcidid>https://orcid.org/0000-0002-2811-9041</orcidid><orcidid>https://orcid.org/0000-0002-4117-6198</orcidid></addata></record> |
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| source | American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acetazolamide Altitude Ascent Carbonic anhydrase Carbonic anhydrases Dexamethasone Echocardiography Edema Heart High altitude High-altitude environments Hypoxia Mountains Nifedipine Oxygenation Placebos Pressure Prevention Pulmonary arteries Pulmonary artery Radiography Statistical analysis Vasoconstriction Veins & arteries Ventricle |
| title | Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m |
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