Adrenergic storm: Difference between revisions

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Added the use of antipsychotics as accepted standard treatment for adrenergic toxicity and a selection of 11 new bibliographic sources in the form of 11 studies published in medical journals and 2 chapters from medical books; now the article I'm sure does not have any issues of insufficient citations, I hope my editions prove enough to consider those issues fixed; IMPORTANT: I fixed the disambiguation issues as well in this new edition
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An '''adrenergic storm''' is a sudden and dramatic increase in [[serum (blood)|serum]] levels of the [[catecholamines]] [[adrenaline]] and [[noradrenaline]] (also known as [[epinephrine]] and [[norepinephrine]] respectively), with a less significant increase in [[dopamine]] transmission. It is a life-threatening condition because of extreme [[tachycardia]] and [[hypertension]], and is especially dire for those with prior heart problems. If treatment is prompt, [[prognosis]] is good; typically large amounts of [[diazepam]] or other [[benzodiazepine]]s are administered alongside [[beta blockers]]. Beta blockers are [[contraindicate]]d in some patients, so other [[anti-hypertensive]] medication such as [[clonidine]] may be used.<ref name="King">{{cite journal |last1=King |first1=Andrew |first2=Mirjana |last2=Dimovska |first3=Luke |last3=Bisoski |date=24 February 2018 |access-date=28 July 2021 |url=https://link.springer.com/article/10.1007/s11906-018-0807-9 |doi=10.1007/s11906-018-0807-9 |editor1-first=Suzanne |editor1-last=Oparil |issn=1522-6417 |title=Sympathomimetic toxidromes and other pharmacological causes of acute hypertension |journal=Current hypertension reports |volume=20 |issue=1 |pages=1-13 |oclc=46464855 |publisher=[[Springer Nature]] |publication-place=[[Basingstoke]], [[United Kingdom of Great Britain]] }}</ref> It is usually caused by overdose of [[stimulant]]s, especially [[cocaine]] or [[methamphetamine]], or eating foods high in [[tyramine]] while taking [[MAOI|monoamine oxidase inhibitors]].<ref name=":0" /> A [[subarachnoid hemorrhage]] can also cause an adrenergic storm.<ref name=":0" /> A catecholamine storm is part of the normal course of [[rabies]] infection, and is responsible for the severe feelings of agitation, terror, and [[dysautonomia]] present in the pre-coma stage of the disease.<ref name="Holstege">{{cite journal |last1=Holstege |first1=Christopher P. |first2=Heather A. |last2=Borek |title=Toxidromes |journal=[[Critical Care Clinics]] |volume=28 |issue=4 |url=https://www.criticalcare.theclinics.com/article/S0749-0704(12)00060-7 |access-date=28 July 2021 |date=29 August 2012 |doi=10.1016/j.ccc.2012.07.008 |pages=479-498 |editor1-first=John A. |editor1-last=Kellum |publisher=[[Elsevier]] |issn=07490704 |lccn=85643425 |oclc=11078407 |publication-place=[[Amsterdam]], [[Netherlands]] }}</ref>
An '''adrenergic storm''' is a sudden and dramatic increase in [[serum (blood)|serum]] levels of the [[catecholamines]] [[adrenaline]] and [[noradrenaline]] (also known as [[epinephrine]] and [[norepinephrine]] respectively), with a less significant increase in [[dopamine]] transmission. It is a life-threatening condition because of extreme [[tachycardia]] and [[hypertension]], and is especially dire for those with prior heart problems. If treatment is prompt, [[prognosis]] is good; typically large amounts of [[diazepam]] or other [[benzodiazepine]]s are administered alongside [[beta blockers]]. Beta blockers are [[contraindicate]]d in some patients, so other [[anti-hypertensive]] medication such as [[clonidine]] may be used.<ref name="King">{{cite journal |last1=King |first1=Andrew |first2=Mirjana |last2=Dimovska |first3=Luke |last3=Bisoski |date=24 February 2018 |access-date=28 July 2021 |url=https://link.springer.com/article/10.1007/s11906-018-0807-9 |doi=10.1007/s11906-018-0807-9 |editor1-first=Suzanne |editor1-last=Oparil |issn=1522-6417 |title=Sympathomimetic toxidromes and other pharmacological causes of acute hypertension |journal=Current hypertension reports |volume=20 |issue=1 |pages=1-13 |oclc=46464855 |publisher=[[Springer Nature]] |publication-place=[[Basingstoke]], [[United Kingdom of Great Britain]] }}</ref>
[[Antipsychotic|Antipsychotics]] are also used to treat the most severe psychiatric reactions such as psychosis, [[paranoia]] or terror, after their use was formerly discouraged because of their potential to [[Long QT Syndrome|prolong]] the [[QT interval]]; however, more recent research performed since 2019 has revealed that this and other severe side effects are rare and their occurrence does not warrant banning antipsychotics from the treatment of adrenergic for the treatment in which they can be extremely useful.<ref name="Malashock" /><ref name="Connors" /><ref name="Richards">{{cite journal |url=https://www.sciencedirect.com/science/article/abs/pii/S0735675719303079 |journal=The American Journal of Emergency Medicine |pages=1880-1890 |issn=0735-6757 |via=[[ScienceDirect]] |editor1-first=J. Douglas |editor1-last=White |editor2-first=William J. |editor2-last=Brady |oclc=08996781 |publisher=[[Elsevier]] |publication-place=[[Amsterdam]], [[Netherlands]] |title=Another dogma dispelled? Antipsychotic treatment of sympathomimetic toxicity |doi=10.1016/j.ajem.2019.05.013 |pmid=31088749 |date=10 December 2019 |volume=37 |issue=12 |pages=2256-2257 |first1=John R. |last1=Richards |first2=Robert W. |last2=Derlet |language=English |access-date=28 July 2021 }}</ref><ref>{{cite book |date=1 January 2020 |first1=Scott |last1=Goldstein |first2=John R. |last2=Richards |publisher=StatPearls Publishing |publication-place=[[Treasure Island, Florida]], United States of America |pmid=28613508 |title=Sympathomimetic Toxicity |url=https://www.ncbi.nlm.nih.gov/books/NBK430757 |editor1-first=John R. |editor1-last=Richards |via=[[National Center for Biotechnology Information|NCBI (National Center for Biotechnology Information)]]/[[United States National Library of Medicine|NLM (United States National Library of Medicine)]] |access-date=28 July 2021 }}</ref><ref name="Connors19">{{cite journal |title=Evidence over dogma and anecdotes |volume=37 |issue=12 |page=2257 |date=1 December 2019 |first1=Nicholas J. |last1=Connors |first2=Ahmed |last2=Alsakha |first3=Alexandre |last3=Larocque |first4=Robert S. |last4=Hoffman |first5=Tara |last5=Landry |first6=Sophie |last6=Gosselin |doi=10.1016/j.ajem.2019.05.014 |url=https://www.ajemjournal.com/article/S0735-6757(19)30308-0 |access-date=28 July 2021 |issn=0735-6757 |editor1-first=J. Douglas |editor1-last=White |editor2-first=William J. |editor2-last=Brady |oclc=08996781 |publisher=[[Elsevier]] |publication-place=[[Amsterdam]], [[Netherlands]] }}</ref><ref>{{cite book |first1=Vivian |last1=Lam |first2=Robert W. |last2=Shaffer |chapter=8. Management of Sympathomimetic Overdose Including Designer Drugs |title=Evidence-Based Critical Care: A Case Study Approach |doi=10.1007/978-3-030-26710-0 |publisher=[[Springer Nature]] |publication-place=[[Cham, Switzerland|Cham]], [[Switzerland]] |isbn=978-3030267094 |orig-year=2017 |page=65 |chapter-url=https://books.google.com/books?&id=cc7YDwAAQBAJ&pg=PA63 |via=[[Google Books]] |edition=2nd |editor1-first=Robert C. |editor1-last=Hyzy |editor2-first=Jakob |editor2-last=McSparron |url=https://books.google.com/books?&id=cc7YDwAAQBAJ }}</ref><ref>{{cite journal |date=1 January 2016 |access-date=28 July 2021 |volume=38 |issue=1 |pages=10-12 |doi=10.1097/01.EEM.0000476273.56614.28 |journal=Emergency Medicine News |title=InFocus: Treating Sympathomimetic Toxicity |first=James R. |last=Roberts |publisher=[[Wolters Kluwer|Wolters Kluwer Health, Inc.]] ([[Lippincott Williams & Wilkins]]) |editor1-first=James R. |editor1-last=Roberts |editor2-first=Lisa |editor2-last=Hoffman |editor3-first=Lynn |editor3-last=Nace |editor4-first=Grace |editor4-last=Gibson |url=https://journals.lww.com/em-news/Fulltext/2016/01000/InFocus__Treating_Sympathomimetic_Toxicity.24.aspx |archive-date=10 January 2016 |archive-url=https://web.archive.org/web/20160110210712/https://journals.lww.com/em-news/Fulltext/2016/01000/InFocus__Treating_Sympathomimetic_Toxicity.24.aspx }}</ref>

Adreneric storms are usually caused by overdoses of [[stimulant]]s, especially [[cocaine]] or [[methamphetamine]], or eating foods high in [[tyramine]] while taking [[MAOI|monoamine oxidase inhibitors]].<ref name=":0" /> A [[subarachnoid hemorrhage]] can also cause an adrenergic storm.<ref name=":0" /> A catecholamine storm is part of the normal course of [[rabies]] infection, and is responsible for the severe feelings of agitation, terror, and [[dysautonomia]] present in the pre-coma stage of the disease.<ref name="Holstege">{{cite journal |last1=Holstege |first1=Christopher P. |first2=Heather A. |last2=Borek |title=Toxidromes |journal=[[Critical Care Clinics]] |volume=28 |issue=4 |url=https://www.criticalcare.theclinics.com/article/S0749-0704(12)00060-7 |access-date=28 July 2021 |date=29 August 2012 |doi=10.1016/j.ccc.2012.07.008 |pages=479-498 |editor1-first=John A. |editor1-last=Kellum |publisher=[[Elsevier]] |issn=07490704 |lccn=85643425 |oclc=11078407 |publication-place=[[Amsterdam]], [[Netherlands]] }}</ref>


== Signs and symptoms ==
== Signs and symptoms ==
The behavioral symptoms are similar to those of an [[amphetamine]], [[cocaine]] or [[caffeine]] overdose. Overstimulation of the [[central nervous system]] results in a state of [[hyperkinetic]] movement and unpredictable mental status including mania, rage and suicidal behavior; [[hyperthermia]] is also prominently present.<ref>{{cite journal |first=Jeffrey R. |last=Suchard |title=Recovery from Severe Hyperthermia (45°C) and Rhabdomyolysis Induced by Methamphetamine Body-Stuffing |pmc=2672216 |pmid=19561691 |volume=8 |issue=3 |pages=93-95 |date=1 August 2007 |access-date=28 July 2021 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672216/pdf/0080093.pdf |format=PDF |via=[[PubMed]] |journal=[[Western Journal of Emergency Medicine]] |issn=1936-900X |editor1-first=Mark I. |editor1-last=Langdorf |language=English |publisher=[[eScholarship]]/[[University of California, Irvine School of Medicine]] |publication-place=[[Irvine, California|Irvine]], [[California]], United States of California |editor2-first=Shadi |editor2-last=Lahham |archive-date=21 February 2017 |archive-url=https://web.archive.org/web/20170221022527/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672216/pdf/0080093.pdf }}</ref> [[Delirium]] can also be present but rarely.<ref>{{cite journal |first1=Ammrei |last1=von Braun |first2=Annette |last2=Bühler |first3=Bernd |last3=Yuen |doi=10.1007/s11739-011-0572-0 |volume=7 |issue=Supplement 1 |pages=S27-S28 |journal=Internal and Emergency Medicine |title=Severe thyrotoxicosis: a rare cause of acute delirium |date=31 March 2011 |publisher=Italian Society of Internal Medicine (Società Italiana di Medicina Interna)/[[Springer]] |editor1-first=Domenico |editor1-last=Prisco |publication-place=[[Rome]], [[Italy]] |issn=1828-0447 |oclc=889552819 |language=English |url=https://boris.unibe.ch/3460/1/11739_2011_Article_572.pdf |format=PDF }}</ref>
The behavioral symptoms are similar to those of an [[amphetamine]], [[cocaine]] or [[caffeine]] overdose. Overstimulation of the [[central nervous system]] results in a state of [[hyperkinetic]] movement and unpredictable mental status including mania, rage and suicidal behavior; [[hyperthermia]] is also prominently present.<ref>{{cite journal |first=Jeffrey R. |last=Suchard |title=Recovery from Severe Hyperthermia (45°C) and Rhabdomyolysis Induced by Methamphetamine Body-Stuffing |pmc=2672216 |pmid=19561691 |volume=8 |issue=3 |pages=93-95 |date=1 August 2007 |access-date=28 July 2021 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672216/pdf/0080093.pdf |format=PDF |via=[[PubMed]] |journal=[[Western Journal of Emergency Medicine]] |issn=1936-900X |editor1-first=Mark I. |editor1-last=Langdorf |language=English |publisher=[[eScholarship]]/[[University of California, Irvine School of Medicine]] |publication-place=[[Irvine, California]], United States of California |editor2-first=Shadi |editor2-last=Lahham |archive-date=21 February 2017 |archive-url=https://web.archive.org/web/20170221022527/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672216/pdf/0080093.pdf }}</ref> [[Delirium]] can also be present but rarely.<ref>{{cite journal |first1=Ammrei |last1=von Braun |first2=Annette |last2=Bühler |first3=Bernd |last3=Yuen |doi=10.1007/s11739-011-0572-0 |volume=7 |issue=Supplement 1 |pages=S27-S28 |journal=Internal and Emergency Medicine |title=Severe thyrotoxicosis: a rare cause of acute delirium |date=31 March 2011 |publisher=Italian Society of Internal Medicine (Società Italiana di Medicina Interna)/[[Springer]] |editor1-first=Domenico |editor1-last=Prisco |publication-place=[[Rome]], [[Italy]] |issn=1828-0447 |oclc=889552819 |language=English |url=https://boris.unibe.ch/3460/1/11739_2011_Article_572.pdf |format=PDF }}</ref>


Physical symptoms are more serious and include heart [[Heart arrhythmia|arrhythmia]]s as well as outright [[Coronary infarction|heart attack]] or [[stroke]] in people who are at risk of [[coronary disease]]. Breathing is rapid and shallow while both pulse and blood pressure are dangerously elevated.<ref>{{Cite journal |last1=Mayersohn |first1=Michael |last2=Guentert |first2=Theodor W.|date=1 November 1995 |title=Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide |journal=Clinical Pharmacokinetics |volume=29 |issue=5 |pages=292–332 |doi=10.2165/00003088-199529050-00002|issn=0312-5963|pmid=8582117 |s2cid=25628650 |url=https://link.springer.com/article/10.2165%2F00003088-199529050-00002 |publisher=[[Springer]] |publication-place=[[Amsterdam]], [[Netherlands]]
Physical symptoms are more serious and include heart [[Heart arrhythmia|arrhythmia]]s as well as outright [[Coronary infarction|heart attack]] or [[stroke]] in people who are at risk of [[coronary disease]]. Breathing is rapid and shallow while both pulse and blood pressure are dangerously elevated.<ref>{{Cite journal |last1=Mayersohn |first1=Michael |last2=Guentert |first2=Theodor W.|date=1 November 1995 |title=Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide |journal=Clinical Pharmacokinetics |volume=29 |issue=5 |pages=292–332 |doi=10.2165/00003088-199529050-00002|issn=0312-5963|pmid=8582117 |s2cid=25628650 |url=https://link.springer.com/article/10.2165%2F00003088-199529050-00002 |publisher=[[Springer]] |publication-place=[[Amsterdam]], [[Netherlands]]
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Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the [[Central nervous system|CNS]], it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various [[entheogen]]s to attain a stronger [[psychedelic experience]], both from adrenergic storms and [[serotonin syndrome]]. Combining drugs like [[MDMA]], [[2C-B]], [[mescaline]], [[2C-T-7]], etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.
Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the [[Central nervous system|CNS]], it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various [[entheogen]]s to attain a stronger [[psychedelic experience]], both from adrenergic storms and [[serotonin syndrome]]. Combining drugs like [[MDMA]], [[2C-B]], [[mescaline]], [[2C-T-7]], etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.


[[Subarachnoid hemorrhage]] is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the [[intracranial pressure]] increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space.<ref>{{Cite book |chapter=CHAPTER 2: Clinical Presentation |url=https://books.google.com/books?id=uzdr1wLtIgAC |via=[[Google Books]] |volume=15 |chapter-url=https://books.google.com/books?id=uzdr1wLtIgAC&pg=PA21 |publisher=AANS Publications Committee ([[American Association of Neurological Surgeons|American Association of Neurological Surgeons (AANS)]]) |title=Cuerrent Management of Cerebral Aneurysms |first1=Karen A. |last1=Rodman |first2=Issam A. |last2=Awad |editor1-first=Isam A. |editor1-last=Awad |editor2-first=Daniel L. |editor2-last=Barrow |editor3-first=Linda S. |editor3-last=Miller |series=Neurosurgical Topics |year=1993 |publication-place=[[Rolling Meadows]], [[Illinois]], United States of America |pages=21-43 }}</ref> An alternative explanation that has been proposed is that this increase in intracranial pressure transduces through the brain parenchyma through to the blood vessels producing a loss in effective cerebral perfusion. This triggers the sympathetic nervous system to secrete more norepinepherine and epinepherine increasing blood pressure and heart rate to dangerous levels to maintain cerebral perfusion.<ref>{{cite journal |title=“Toxidrome” A Review |journal=Saudi Journal of Medical and Pharmaceutical Sciences |issn=2413-4929 |first1=J. John |last1=Kirubakaran |first2=Magharla Dasaratha |last2=Dharanaju |doi=10.21276/sjumps.2019.5.3.7 |date=30 March 2019 |access-date=28 July 2021 |url=https://www.researchgate.net/profile/John-Kirubakaran/publication/335055710_Toxidrome_A_Review/links/5d4c4d2d92851cd046ad2055/Toxidrome-A-Review.pdf |format=PDF |language=English |pages=206-212 |publisher=Scholars Middle East Publishers |publication-place=[[Dubai]], [[United Arab Emirates]] |editor1-first=Mohammed Habibur |editor1-last=Rahman }}</ref>
[[Subarachnoid hemorrhage]] is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the [[intracranial pressure]] increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space.<ref>{{Cite book |chapter=CHAPTER 2: Clinical Presentation |url=https://books.google.com/books?id=uzdr1wLtIgAC |via=[[Google Books]] |volume=15 |chapter-url=https://books.google.com/books?id=uzdr1wLtIgAC&pg=PA21 |publisher=AANS Publications Committee ([[American Association of Neurological Surgeons|American Association of Neurological Surgeons (AANS)]]) |title=Cuerrent Management of Cerebral Aneurysms |first1=Karen A. |last1=Rodman |first2=Issam A. |last2=Awad |editor1-first=Isam A. |editor1-last=Awad |editor2-first=Daniel L. |editor2-last=Barrow |editor3-first=Linda S. |editor3-last=Miller |series=Neurosurgical Topics |year=1993 |publication-place=[[Rolling Meadows, Illinois]], United States of America |pages=21-43 }}</ref> An alternative explanation that has been proposed is that this increase in intracranial pressure transduces through the brain parenchyma through to the blood vessels producing a loss in effective cerebral perfusion. This triggers the sympathetic nervous system to secrete more norepinepherine and epinepherine increasing blood pressure and heart rate to dangerous levels to maintain cerebral perfusion.<ref>{{cite journal |title=“Toxidrome” A Review |journal=Saudi Journal of Medical and Pharmaceutical Sciences |issn=2413-4929 |first1=J. John |last1=Kirubakaran |first2=Magharla Dasaratha |last2=Dharanaju |doi=10.21276/sjumps.2019.5.3.7 |date=30 March 2019 |access-date=28 July 2021 |url=https://www.researchgate.net/profile/John-Kirubakaran/publication/335055710_Toxidrome_A_Review/links/5d4c4d2d92851cd046ad2055/Toxidrome-A-Review.pdf |format=PDF |language=English |pages=206-212 |publisher=Scholars Middle East Publishers |publication-place=[[Dubai]], [[United Arab Emirates]] |editor1-first=Mohammed Habibur |editor1-last=Rahman }}</ref>


===Rare causes===
===Rare causes===
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The first line treatments are [[diazepam]] and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, [[alprazolam]] and [[propranolol]];<ref name="Holstege" /> alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition.<ref name="ASCP" />
The first line treatments are [[diazepam]] and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, [[alprazolam]] and [[propranolol]];<ref name="Holstege" /> alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition.<ref name="ASCP" />


[[Antipsychotics|Antipsychotics]] can also used to treat the psychiatric symptoms such as aggression, agitation, [[psychosis]], [[paranoia]] or [[anxiety]]; originally, the use of antipsychotics was discouraged because of their potential [[Long QT syndrome|to prolong]] the [[QT interval]];<ref name="Connors" /> however, newer research has revealed that their careful use does not carry the potential for any significative side effects and their judicious use is encouraged.<ref name="Connors">{{cite journal |first1=Nicholas J. |last1=Connors |first2=Ahmed |last2=Alsakha |first3=Alexandre |last3=Larocque |first4=Robert S. |last4=Hoffman |first5=Tara |last5=Landry |first6=Sophie |last6=Gosselin |title=Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review |journal=The American Journal of Emergency Medicine |volume=37 |issue=10 |date=1 October 2019 |pages=1880-1890 |issn=0735-6757 |via=[[ScienceDirect]] |url=https://www.sciencedirect.com/science/article/abs/pii/S0735675719300014 |editor1-first=J. Douglas |editor1-last=White |editor2-first=William J. |editor2-last=Brady |oclc=08996781 |publisher=[[Elsevier]] |publication-place=[[Amsterdam]], [[Netherlands]] }}</ref><ref>{{cite journal |title=Pediatric Methamphetamine Toxicity: Clinical Manifestations and Therapeutic Use of Antipsychotics—One Institution’s Experience |first1=Hannah R. |last1=Malashock |first2=Claudia |last2=Yeung |first3=Alexa R. |last3=Roberts |first4=Jerry W. |last4=Snow |first5=Richard D. |last5=Gerkin |first6=Ayrn D. |last6=O'Connor |date=13 January 2021 |access-date=28 July 2021 |journal=Journal of Medical Toxicity |page=168-175 |publisher=[[American College of Medical Toxicology|American College of Medical Toxicology (ACMT)]]/[[Springer]] |publication-place=[[Phoenix, Arizona]], United States of America |editor1-first=Mark B. |editor1-last=Mycyk |issn=1556-9039 |oclc=163567183 |doi=10.1007/s13181-020-00821-4 |volume=17 |editor2-first=Peter |editor2-last=Chai |issue=2 |archive-date=24 January 2021 |archive-url=https://web.archive.org/web/20210124011526/https://link.springer.com/article/10.1007/s13181-020-00821-4 |via=[[Springer Science+Business Media|Springer Link]] |url=https://link.springer.com/article/10.1007/s13181-020-00821-4 }}</ref>
[[Antipsychotics|Antipsychotics]] are also used to treat the psychiatric symptoms such as aggression, agitation, [[psychosis]], [[paranoia]] or [[anxiety]]. Originally, the use of antipsychotics was discouraged because of their potential [[Long QT syndrome|to prolong]] the [[QT interval]];<ref name="Connors" /> however, newer research has revealed that their careful use does not carry the potential for any significative side effects and their judicious use is encouraged.<ref name="Connors">{{cite journal |first1=Nicholas J. |last1=Connors |first2=Ahmed |last2=Alsakha |first3=Alexandre |last3=Larocque |first4=Robert S. |last4=Hoffman |first5=Tara |last5=Landry |first6=Sophie |last6=Gosselin |title=Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review |journal=The American Journal of Emergency Medicine |volume=37 |issue=10 |date=1 October 2019 |pages=1880-1890 |issn=0735-6757 |via=[[ScienceDirect]] |url=https://www.sciencedirect.com/science/article/abs/pii/S0735675719300014 |editor1-first=J. Douglas |editor1-last=White |editor2-first=William J. |editor2-last=Brady |oclc=08996781 |publisher=[[Elsevier]] |publication-place=[[Amsterdam]], [[Netherlands]] }}</ref><ref name="Malashock">{{cite journal |title=Pediatric Methamphetamine Toxicity: Clinical Manifestations and Therapeutic Use of Antipsychotics—One Institution’s Experience |first1=Hannah R. |last1=Malashock |first2=Claudia |last2=Yeung |first3=Alexa R. |last3=Roberts |first4=Jerry W. |last4=Snow |first5=Richard D. |last5=Gerkin |first6=Ayrn D. |last6=O'Connor |date=13 January 2021 |access-date=28 July 2021 |journal=Journal of Medical Toxicity |page=168-175 |publisher=[[American College of Medical Toxicology|American College of Medical Toxicology (ACMT)]]/[[Springer]] |publication-place=[[Phoenix, Arizona]], United States of America |editor1-first=Mark B. |editor1-last=Mycyk |issn=1556-9039 |oclc=163567183 |doi=10.1007/s13181-020-00821-4 |volume=17 |editor2-first=Peter |editor2-last=Chai |issue=2 |archive-date=24 January 2021 |archive-url=https://web.archive.org/web/20210124011526/https://link.springer.com/article/10.1007/s13181-020-00821-4 |via=[[Springer Science+Business Media|Springer Link]] |url=https://link.springer.com/article/10.1007/s13181-020-00821-4 }}</ref><ref name="Richards">{{cite journal |url=https://www.sciencedirect.com/science/article/abs/pii/S0735675719303079 |journal=The American Journal of Emergency Medicine |pages=1880-1890 |issn=0735-6757 |via=[[ScienceDirect]] |editor1-first=J. Douglas |editor1-last=White |editor2-first=William J. |editor2-last=Brady |oclc=08996781 |publisher=[[Elsevier]] |publication-place=[[Amsterdam]], [[Netherlands]] |title=Another dogma dispelled? Antipsychotic treatment of sympathomimetic toxicity |doi=10.1016/j.ajem.2019.05.013 |pmid=31088749 |date=10 December 2019 |volume=37 |issue=12 |pages=2256-2257 |first1=John R. |last1=Richards |first2=Robert W. |last2=Derlet |language=English |access-date=28 July 2021 }}</ref><ref>{{cite journal |title=The emerging ‘incense’ and ‘bath salt’ phenomenon |first1=Jason |last1=Jerry |first2=Gregory |last2=Collins |first3=David |last3=Streem |doi=10.3949/ccjm.79a.11147 |journal=[[Cleveland Clinic Journal of Medicine]] |volume=79 |issue=4 |date=10 April 2012 |pages=258-264 |pmid=22473725 |publisher=[[Cleveland Clinic|The Cleveland Clinic Foundation]] |publication-place=[[Lyndhurst, Ohio]], United States of America |url=https://www.ccjm.org/content/ccjom/79/4/258.full.pdf |format=PDF |editor1-first=Brian F. |editor1-last=Mandell |editor2-first=Pelin |editor2-last=Batur |editor3-first=Craig |editor3-last=Nielsen |editor4-first=Peter G. |editor4-last=Studer |editor5-first=Mary T. |editor5-last=Cusick |archive-date=21 January 2021 |archive-url=https://web.archive.org/web/20210421112022/https://www.ccjm.org/content/ccjom/79/4/258.full.pdf |issn=0891-1150 |lccn=87640278 |oclc=14576751 }}</ref>


Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down.<ref name="King" />
Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down.<ref name="King" />

Revision as of 06:50, 29 July 2021

Adrenergic storm
Other namesSympathomimetic toxicity
Sympathomimetic toxidrome
ComplicationsTachycardia, hypertension
CausesCocaine, stimulant abuse, subarachnoid hemorrhage, methamphetamine, foods high in tyramine, rabies
Treatmentdiazepam, benzodiazepines, beta blockers, anti-hypertensives

An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenaline and noradrenaline (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It is a life-threatening condition because of extreme tachycardia and hypertension, and is especially dire for those with prior heart problems. If treatment is prompt, prognosis is good; typically large amounts of diazepam or other benzodiazepines are administered alongside beta blockers. Beta blockers are contraindicated in some patients, so other anti-hypertensive medication such as clonidine may be used.[1] Antipsychotics are also used to treat the most severe psychiatric reactions such as psychosis, paranoia or terror, after their use was formerly discouraged because of their potential to prolong the QT interval; however, more recent research performed since 2019 has revealed that this and other severe side effects are rare and their occurrence does not warrant banning antipsychotics from the treatment of adrenergic for the treatment in which they can be extremely useful.[2][3][4][5][6][7][8]

Adreneric storms are usually caused by overdoses of stimulants, especially cocaine or methamphetamine, or eating foods high in tyramine while taking monoamine oxidase inhibitors.[9] A subarachnoid hemorrhage can also cause an adrenergic storm.[9] A catecholamine storm is part of the normal course of rabies infection, and is responsible for the severe feelings of agitation, terror, and dysautonomia present in the pre-coma stage of the disease.[10]

Signs and symptoms

The behavioral symptoms are similar to those of an amphetamine, cocaine or caffeine overdose. Overstimulation of the central nervous system results in a state of hyperkinetic movement and unpredictable mental status including mania, rage and suicidal behavior; hyperthermia is also prominently present.[11] Delirium can also be present but rarely.[12]

Physical symptoms are more serious and include heart arrhythmias as well as outright heart attack or stroke in people who are at risk of coronary disease. Breathing is rapid and shallow while both pulse and blood pressure are dangerously elevated.[13]

Other complications would include rhabdomyolysis, a breakdown of the voluntary muscles because of the excessive physical movement, causing the components of the muscle, most notably myoglobin, to be released into the bloodstream and then clog the kidneys, causing renal failure.[14] In all, rhabomyolysis is especially common in adrenergic storms caused by the use of stimulant drugs, most notably those of the phenetylamine such as cathinones or amphetamines.[15]

Causes

There are several known causes of adrenergic storms; in the United States, cocaine overdose is the leading cause.[16] Any stimulant drug has the capacity to cause this syndrome if taken in sufficient doses, but even non-psychotropic drugs can very rarely provoke a reaction.[17]

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the enzyme monoamine oxidase. This enzyme is responsible for breaking down many compounds; basically, anything with a primary amine moiety is likely to be oxidized by monoamine oxidase. An important substrate of the enzyme MAO is tyramine. MAOIs inhibit the enzyme either reversibly, in which MAO is inhibited only until the drug is cleared from the system, or irreversibly, in which the substrate binds permanently to the enzyme, rendering it inactive and effectively destroying it. Irreversible MAOIs are potentially more dangerous, because the body takes about two weeks to regenerate MAO enzymes to functional levels.[18] Two subtypes of MAO exist: MAO-A and MAO-B; this is relevant to adrenergic storms, as there are significant differences between the two types, such as their differential expression throughout the body, and range of substrates. While both MAO-A and MAO-B metabolize tyramine, only MAO-A is present in the gastrointestinal tract and singularly metabolizes the majority of consumed tyramine.[9] (The small portion normally passing into circulation is mostly degraded in the liver where both MAO types act.[9]) Consequently, MAOIs that irreversibly inhibit MAO-A will permit high levels of circulating tyramine able to cause tyramine-induced hypertensive crisis. Aged cheese, beer, red wine, some mushrooms, and fermented products such as pickles are foods containing high levels of tyramine that passed into circulation can cause such a hypertensive crisis.

Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the CNS, it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various entheogens to attain a stronger psychedelic experience, both from adrenergic storms and serotonin syndrome. Combining drugs like MDMA, 2C-B, mescaline, 2C-T-7, etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.

Subarachnoid hemorrhage is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the intracranial pressure increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space.[19] An alternative explanation that has been proposed is that this increase in intracranial pressure transduces through the brain parenchyma through to the blood vessels producing a loss in effective cerebral perfusion. This triggers the sympathetic nervous system to secrete more norepinepherine and epinepherine increasing blood pressure and heart rate to dangerous levels to maintain cerebral perfusion.[20]

Rare causes

Rarely, a pheochromocytoma (tumor of the medullar tissue of the adrenal glands, which are located anterior to the kidney), may result in an adrenergic storm.[21] This type of tumor is not common to begin with, and furthermore, the subtype that can cause massive adrenaline release is rarer still. Patients with pheochromocytoma can unexpectedly fly into a rage or sink into trembling fear, possibly dangerous to themselves and others as their judgment is impaired, their senses and pain threshold are heightened, and the level of the adrenalin in their bloodstream is more than most people ever experience; pheochromocytoma can, very rarely, kill by internal adrenaline overdose.[22] But overall, adrenergic storm is an uncommon but certainly not rare phenomenon associated with the also uncommon condition of pheochromocytoma.[23]

Diagnosis

Differential diagnosis

Because the adrenergic storm overlaps with so many other similar conditions, such as hypertensive crises, stimulant intoxication or overdose, or even panic attack, and because the treatments for these overlapping conditions are largely alike, it is not necessary to obtain a differential and definitive diagnosis before initiating treatment. However, analysis of the patient's medical history, checked against the possible causes of the adrenergic storm such as those above, should be done, because some adrenergic storms can be caused by serious underlying conditions.[10] If a patient has an adrenergic storm and all or most of the other factors are ruled out, the adrenergic storm could lead to the discovery of a pheochromocytoma, which can become malignant. However, not all cases of adrenergic storm have an identifiable cause. Like a seizure, sometimes a patient has a single one, or perhaps a few, and then does not for the rest of their life.[24] The mechanisms of idiopathic adrenergic storm are very poorly understood.

Serotonin syndrome, in which an excess of serotonin in the synapses causes a similar crisis of hypertension and mental confusion, could be confused with an adrenergic storm. Serotonin, being a tryptamine (non-catecholamine) involved in higher brain functions, can cause dangerous hypertension and tachycardia from its effects on the sympathetic nervous system.[24] Symptoms caused by excessive adrenergic signalling can occur alongside those of serotonergic signalling. One example would be: overdose of drug(s) influencing multiple targets including serotonin, and adrenergic systems, with concurrent MAOI use). Abnormal echocardiograms, or chest pain are indicative of adrenergic crisis.[24] On the other hand, uncontrollable slow, rhythmic, and/or jerky movements, contractions and tension-often in every part of the body, dangerously high fever, eye rolling, and bruxism are more indicative of serotonin syndrome.[10][25]

Treatment

If there is evidence of overdose or it is suspected, the patient should be given gastric lavage, activated charcoal, or both; this could make the difference between life and death in a close situation.[26] It can however aggravate the patient which should be taken into account.[10]

The first line treatments are diazepam and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, alprazolam and propranolol;[10] alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition.[24]

Antipsychotics are also used to treat the psychiatric symptoms such as aggression, agitation, psychosis, paranoia or anxiety. Originally, the use of antipsychotics was discouraged because of their potential to prolong the QT interval;[3] however, newer research has revealed that their careful use does not carry the potential for any significative side effects and their judicious use is encouraged.[3][2][4][27]

Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down.[1]

See also

References

  1. ^ a b King, Andrew; Dimovska, Mirjana; Bisoski, Luke (24 February 2018). Oparil, Suzanne (ed.). "Sympathomimetic toxidromes and other pharmacological causes of acute hypertension". Current hypertension reports. 20 (1). Basingstoke, United Kingdom of Great Britain: Springer Nature: 1–13. doi:10.1007/s11906-018-0807-9. ISSN 1522-6417. OCLC 46464855. Retrieved 28 July 2021.
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  27. ^ Jerry, Jason; Collins, Gregory; Streem, David (10 April 2012). Mandell, Brian F.; Batur, Pelin; Nielsen, Craig; Studer, Peter G.; Cusick, Mary T. (eds.). "The emerging 'incense' and 'bath salt' phenomenon" (PDF). Cleveland Clinic Journal of Medicine. 79 (4). Lyndhurst, Ohio, United States of America: The Cleveland Clinic Foundation: 258–264. doi:10.3949/ccjm.79a.11147. ISSN 0891-1150. LCCN 87640278. OCLC 14576751. PMID 22473725. Archived from the original (PDF) on 21 January 2021. {{cite journal}}: |archive-date= / |archive-url= timestamp mismatch; 21 April 2021 suggested (help)