Heat stroke differential diagnosis: Difference between revisions

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Latest revision as of 14:40, 5 June 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2],Usama Talib, BSc, MD [3]

Overview

Heat stroke must be differentiated from other disease that may cause alteration in mental status and hyperthermia including: Neuroleptic malignant syndrome, Malignant hyperthermia, Serotonin syndrome, cocaine use and sepsis.^[1]^[2]^[3]^[4]^[5]^[6]

Differentiating Heat stroke from other Diseases

Differentiation between 2 types of heat stroke (Classic vs Exertional) is based on history, clinical findings, and laboratory findings.^[7]^[8] The following table summarizes their differentiating feature.

Characteristic		Exertional Heat Stroke	Classic Heat Stroke
Age		Adults	Early childhood or elderly
Health status		Healthy and athlete	Ill and debilitate
Weather condition		Temperate or hot	Heat wave
Activity		Sustained or heavy exertion	Sedentary
Medications or drug use		Ergogenic aids, ecstasy, cocaine	Diuretics, β-blockers, antihistamines, antidepressants
Sweating		Present	Abscent
Laboratory findings	Acid-base disturbance	Metabolic acidosis	Mixed metabolic and respiratory acidosis
	Calcium	↓	Nl
	Potassium	↓ or ↑	Nl
	Phosphate	↑	↓
	Blood glucose	↓	↑
	Creatine kinase (CK)	↑↑↑	↑
	AST, ALT	↑↑↑	↑
Complications	Rhabdomyolysis	Severe	Mild
Complications	Acute renal failure	Common (∼25%)	Uncommon (∼5%)

Differentiating Heat stroke from other Diseases that may cause hyperthermia and altered mental status

Heat stroke must be differentiated from other conditions that may cause hyperthermia and altered mental status.^[1]^[2]^[3]^[4]^[5]^[6]

Disease	Symptoms and signs	Labs	Other findings
Heat stroke	CNS dysfunction (disorientation, headache, irrational behavior, irritability, emotional instability, confusion, coma, or seizure) Hypotension and tachycardia Hyperventilation Weakness, nausea and vomiting, profuse sweating, dehydration.	Electrolyte disturbances, increased CK, AST, and ALT	Relevant history of excessive exercise and lack of water access
Sepsis	Altered mental status (confusion, altered consciousness, coma, or seizure) Respiratory rate ≥22/minute Systolic blood pressure ≤100 mmHg	Thrombocytopenia, leukocytosis, leukopenia, elevated Cr
Malignant hyperthermia	Masseter muscle rigidity (early) Generalized muscle rigidity Sinus tachycardia Arrhythmia	Hypercarbia (PaCO2) >65 mmHg, hyperkalemia	History of receiving anaesthetic agent
Neuroleptic malignant syndrome	Change in mental status Muscle rigidity Autonomic instability (labile BP, tachypnea, profuse sweating)	Electrolyte disturbances, increased CK, LDH, ALP, AST, and ALT, leukocytosis, myoglobinuria.	Relevant history of recent use of anti-psychotics
Serotonin syndrome	Mental status changes (anxiety, agitated delirium, restlessness, and disorientation) Autonomic instability (diaphoresis, tachycardia,, hypertension, vomiting, and diarrhea) Neuromuscular hyperactivity (tremor, myoclonus, hyperreflexia, and bilateral Babinski sign)	Elevated CK, LDH, ALP, AST, and ALT	History of recent use of SSRIs, SNRIs , or MAOIs.

References

↑ ^1.0 ^1.1 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016). "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 801–10. doi:10.1001/jama.2016.0287. PMC 4968574. PMID 26903338.
↑ ^2.0 ^2.1 Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC (2016). "Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 762–74. doi:10.1001/jama.2016.0288. PMC 5433435. PMID 26903335.
↑ ^3.0 ^3.1 Carbone JR (2000). "The neuroleptic malignant and serotonin syndromes". Emerg. Med. Clin. North Am. 18 (2): 317–25, x. PMID 10767887.
↑ ^4.0 ^4.1 Bodner RA, Lynch T, Lewis L, Kahn D (1995). "Serotonin syndrome". Neurology. 45 (2): 219–23. PMID 7854515.
↑ ^5.0 ^5.1 Ener RA, Meglathery SB, Van Decker WA, Gallagher RM (2003). "Serotonin syndrome and other serotonergic disorders". Pain Med. 4 (1): 63–74. PMID 12873279.
↑ ^6.0 ^6.1 Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB (2010). "Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006". Anesth. Analg. 110 (2): 498–507. doi:10.1213/ANE.0b013e3181c6b9b2. PMID 20081135.
↑ Bouchama A, Knochel JP (2002). "Heat stroke". N. Engl. J. Med. 346 (25): 1978–88. doi:10.1056/NEJMra011089. PMID 12075060.
↑ O'Connor FG, Casa DJ, Bergeron MF, Carter R, Deuster P, Heled Y, Kark J, Leon L, McDermott B, O'Brien K, Roberts WO, Sawka M (2010). "American College of Sports Medicine Roundtable on exertional heat stroke--return to duty/return to play: conference proceedings". Curr Sports Med Rep. 9 (5): 314–21. doi:10.1249/JSR.0b013e3181f1d183. PMID 20827100.

|}

[pmid26903338-1] 1.0 ^1.1 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016). "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 801–10. doi:10.1001/jama.2016.0287. PMC 4968574. PMID 26903338.

[pmid26903335-2] 2.0 ^2.1 Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC (2016). "Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 762–74. doi:10.1001/jama.2016.0288. PMC 5433435. PMID 26903335.

[pmid10767887-3] 3.0 ^3.1 Carbone JR (2000). "The neuroleptic malignant and serotonin syndromes". Emerg. Med. Clin. North Am. 18 (2): 317–25, x. PMID 10767887.

[pmid7854515-4] 4.0 ^4.1 Bodner RA, Lynch T, Lewis L, Kahn D (1995). "Serotonin syndrome". Neurology. 45 (2): 219–23. PMID 7854515.

[pmid12873279-5] 5.0 ^5.1 Ener RA, Meglathery SB, Van Decker WA, Gallagher RM (2003). "Serotonin syndrome and other serotonergic disorders". Pain Med. 4 (1): 63–74. PMID 12873279.

[pmid20081135-6] 6.0 ^6.1 Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB (2010). "Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006". Anesth. Analg. 110 (2): 498–507. doi:10.1213/ANE.0b013e3181c6b9b2. PMID 20081135.

[pmid12075060-7] Bouchama A, Knochel JP (2002). "Heat stroke". N. Engl. J. Med. 346 (25): 1978–88. doi:10.1056/NEJMra011089. PMID 12075060.

[pmid20827100-8] O'Connor FG, Casa DJ, Bergeron MF, Carter R, Deuster P, Heled Y, Kark J, Leon L, McDermott B, O'Brien K, Roberts WO, Sawka M (2010). "American College of Sports Medicine Roundtable on exertional heat stroke--return to duty/return to play: conference proceedings". Curr Sports Med Rep. 9 (5): 314–21. doi:10.1249/JSR.0b013e3181f1d183. PMID 20827100.

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@@ Line 3: / Line 3: @@
 {{CMG}};{{AE}}{{SMP}},{{USAMA}}
 ==Overview==
-Heat stroke must be differentiated from other disease that may cause alteration in mental status and hyperthermia including: [[Neuroleptic malignant syndrome]], [[Malignant hyperthermia]], [[Serotonin syndrome]], and [[sepsis]].<ref name="pmid26903338">{{cite journal |vauthors=Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC |title=The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=801–10 |year=2016 |pmid=26903338 |pmc=4968574 |doi=10.1001/jama.2016.0287 |url=}}</ref><ref name="pmid26903335">{{cite journal |vauthors=Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC |title=Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=762–74 |year=2016 |pmid=26903335 |pmc=5433435 |doi=10.1001/jama.2016.0288 |url=}}</ref><ref name="pmid10767887">{{cite journal |vauthors=Carbone JR |title=The neuroleptic malignant and serotonin syndromes |journal=Emerg. Med. Clin. North Am. |volume=18 |issue=2 |pages=317–25, x |year=2000 |pmid=10767887 |doi= |url=}}</ref><ref name="pmid7854515">{{cite journal |vauthors=Bodner RA, Lynch T, Lewis L, Kahn D |title=Serotonin syndrome |journal=Neurology |volume=45 |issue=2 |pages=219–23 |year=1995 |pmid=7854515 |doi= |url=}}</ref><ref name="pmid12873279">{{cite journal |vauthors=Ener RA, Meglathery SB, Van Decker WA, Gallagher RM |title=Serotonin syndrome and other serotonergic disorders |journal=Pain Med |volume=4 |issue=1 |pages=63–74 |year=2003 |pmid=12873279 |doi= |url=}}</ref><ref name="pmid20081135">{{cite journal |vauthors=Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB |title=Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006 |journal=Anesth. Analg. |volume=110 |issue=2 |pages=498–507 |year=2010 |pmid=20081135 |doi=10.1213/ANE.0b013e3181c6b9b2 |url=}}</ref>
+Heat stroke must be differentiated from other disease that may cause alteration in mental status and hyperthermia including: [[Neuroleptic malignant syndrome]], [[Malignant hyperthermia]], [[Serotonin syndrome]], [[cocaine use]] and [[sepsis]].<ref name="pmid26903338">{{cite journal |vauthors=Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC |title=The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=801–10 |year=2016 |pmid=26903338 |pmc=4968574 |doi=10.1001/jama.2016.0287 |url=}}</ref><ref name="pmid26903335">{{cite journal |vauthors=Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC |title=Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=762–74 |year=2016 |pmid=26903335 |pmc=5433435 |doi=10.1001/jama.2016.0288 |url=}}</ref><ref name="pmid10767887">{{cite journal |vauthors=Carbone JR |title=The neuroleptic malignant and serotonin syndromes |journal=Emerg. Med. Clin. North Am. |volume=18 |issue=2 |pages=317–25, x |year=2000 |pmid=10767887 |doi= |url=}}</ref><ref name="pmid7854515">{{cite journal |vauthors=Bodner RA, Lynch T, Lewis L, Kahn D |title=Serotonin syndrome |journal=Neurology |volume=45 |issue=2 |pages=219–23 |year=1995 |pmid=7854515 |doi= |url=}}</ref><ref name="pmid12873279">{{cite journal |vauthors=Ener RA, Meglathery SB, Van Decker WA, Gallagher RM |title=Serotonin syndrome and other serotonergic disorders |journal=Pain Med |volume=4 |issue=1 |pages=63–74 |year=2003 |pmid=12873279 |doi= |url=}}</ref><ref name="pmid20081135">{{cite journal |vauthors=Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB |title=Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006 |journal=Anesth. Analg. |volume=110 |issue=2 |pages=498–507 |year=2010 |pmid=20081135 |doi=10.1213/ANE.0b013e3181c6b9b2 |url=}}</ref>
 ==Differentiating Heat stroke from other Diseases==
@@ Line 81: / Line 81: @@
 |}
 |}
-<br>Heat stroke must be differentiated from other conditions that may cause hyperthermia.<ref name="pmid26903338">{{cite journal |vauthors=Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC |title=The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=801–10 |year=2016 |pmid=26903338 |pmc=4968574 |doi=10.1001/jama.2016.0287 |url=}}</ref><ref name="pmid26903335">{{cite journal |vauthors=Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC |title=Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=762–74 |year=2016 |pmid=26903335 |pmc=5433435 |doi=10.1001/jama.2016.0288 |url=}}</ref><ref name="pmid10767887">{{cite journal |vauthors=Carbone JR |title=The neuroleptic malignant and serotonin syndromes |journal=Emerg. Med. Clin. North Am. |volume=18 |issue=2 |pages=317–25, x |year=2000 |pmid=10767887 |doi= |url=}}</ref><ref name="pmid7854515">{{cite journal |vauthors=Bodner RA, Lynch T, Lewis L, Kahn D |title=Serotonin syndrome |journal=Neurology |volume=45 |issue=2 |pages=219–23 |year=1995 |pmid=7854515 |doi= |url=}}</ref><ref name="pmid12873279">{{cite journal |vauthors=Ener RA, Meglathery SB, Van Decker WA, Gallagher RM |title=Serotonin syndrome and other serotonergic disorders |journal=Pain Med |volume=4 |issue=1 |pages=63–74 |year=2003 |pmid=12873279 |doi= |url=}}</ref><ref name="pmid20081135">{{cite journal |vauthors=Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB |title=Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006 |journal=Anesth. Analg. |volume=110 |issue=2 |pages=498–507 |year=2010 |pmid=20081135 |doi=10.1213/ANE.0b013e3181c6b9b2 |url=}}</ref>
+== Differentiating Heat stroke from other Diseases that may cause hyperthermia and altered mental status ==
+Heat stroke must be differentiated from other conditions that may cause hyperthermia and altered mental status.<ref name="pmid26903338">{{cite journal |vauthors=Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC |title=The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=801–10 |year=2016 |pmid=26903338 |pmc=4968574 |doi=10.1001/jama.2016.0287 |url=}}</ref><ref name="pmid26903335">{{cite journal |vauthors=Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC |title=Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) |journal=JAMA |volume=315 |issue=8 |pages=762–74 |year=2016 |pmid=26903335 |pmc=5433435 |doi=10.1001/jama.2016.0288 |url=}}</ref><ref name="pmid10767887">{{cite journal |vauthors=Carbone JR |title=The neuroleptic malignant and serotonin syndromes |journal=Emerg. Med. Clin. North Am. |volume=18 |issue=2 |pages=317–25, x |year=2000 |pmid=10767887 |doi= |url=}}</ref><ref name="pmid7854515">{{cite journal |vauthors=Bodner RA, Lynch T, Lewis L, Kahn D |title=Serotonin syndrome |journal=Neurology |volume=45 |issue=2 |pages=219–23 |year=1995 |pmid=7854515 |doi= |url=}}</ref><ref name="pmid12873279">{{cite journal |vauthors=Ener RA, Meglathery SB, Van Decker WA, Gallagher RM |title=Serotonin syndrome and other serotonergic disorders |journal=Pain Med |volume=4 |issue=1 |pages=63–74 |year=2003 |pmid=12873279 |doi= |url=}}</ref><ref name="pmid20081135">{{cite journal |vauthors=Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB |title=Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006 |journal=Anesth. Analg. |volume=110 |issue=2 |pages=498–507 |year=2010 |pmid=20081135 |doi=10.1213/ANE.0b013e3181c6b9b2 |url=}}</ref>
 <br>
-{| align=center
+{| align="center"
 |-
 |
@@ Line 100: / Line 102: @@
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |Electrolyte disturbances, increased [[Creatine kinase|CK]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]]
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |Relevant history of excessive exercise and lack of water access
+|-
+| align="center" style="background:#DCDCDC;" |[[Sepsis]]
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
+* Altered mental status ([[confusion]], altered consciousness, [[coma]], or [[seizure]])
+* Respiratory rate ≥22/minute
+* Systolic blood pressure ≤100 mmHg
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Thrombocytopenia]], [[leukocytosis]], [[leukopenia]], elevated [[Creatinine|Cr]]
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
+|-
+| align="center" style="background:#DCDCDC;" |[[Malignant hyperthermia]]
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
+* [[Masseter muscle|Masseter]] [[muscle rigidity]] (early)
+* Generalized muscle rigidity
+* [[Sinus tachycardia]]
+* [[Arrhythmias|Arrhythmia]]
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Hypercarbia]] (PaCO2) >65 mmHg, [[hyperkalemia]]
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |History of receiving anaesthetic agent
 |-
 |align="center" style="background:#DCDCDC;"|[[Neuroleptic malignant syndrome]]
@@ Line 108: / Line 127: @@
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |Electrolyte disturbances, increased [[Creatine kinase|CK]], [[Lactate dehydrogenase|LDH]], [[ALP]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]], [[leukocytosis]], [[myoglobinuria]].
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |Relevant history of recent use of anti-psychotics
-|-
-|align="center" style="background:#DCDCDC;"|[[Malignant hyperthermia]]
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |
-* [[Masseter muscle|Masseter]] [[muscle rigidity]] (early)
-* Generalized muscle rigidity
-* [[Sinus tachycardia]]
-* [[Arrhythmias|Arrhythmia]]
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Hypercarbia]] (PaCO2) >65 mmHg, [[hyperkalemia]]
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |History of receiving anaesthetic agent
 |-
 |align="center" style="background:#DCDCDC;"|[[Serotonin syndrome]]
@@ Line 125: / Line 135: @@
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |Elevated [[Creatine kinase|CK]], [[Lactate dehydrogenase|LDH]], [[Alkaline phosphatase|ALP]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]]
 |style="padding: 5px 5px; background: #F5F5F5;" align="left" |History of recent use of [[Selective serotonin reuptake inhibitor|SSRIs]], [[Serotonin-norepinephrine reuptake inhibitor|SNRIs]] , or [[Monoamine oxidase inhibitor|MAOIs]].
-|-
-|align="center" style="background:#DCDCDC;"|[[Sepsis]]
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |
-* Altered mental status ([[confusion]], altered consciousness, [[coma]], or [[seizure]])
-* Respiratory rate ≥22/minute
-* Systolic blood pressure ≤100 mmHg
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Thrombocytopenia]], [[leukocytosis]], [[leukopenia]], elevated [[Creatinine|Cr]]
-|style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 |}
 ==References==
-{{reflist|2}}
+{{reflist|2}}|}