{{Use dmy dates|date=October 2021}} {{Infobox medical condition (new) | name = Hyperosmolar hyperglycemic state | synonyms = Hyperosmolar hyperglycemic nonketotic coma (HHNC), hyperosmolar non-ketotic coma (HONK), nonketotic hyperosmolar coma, hyperosmolar hyperglycemic nonketotic syndrome (HHNS)<ref>{{cite web |url=http://www.diabetes.org/living-with-diabetes/complications/hyperosmolar-hyperglycemic.html |title=Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS) |website=American Diabetes Association |access-date=6 July 2012 |archive-url=https://web.archive.org/web/20120702221724/http://www.diabetes.org/living-with-diabetes/complications/hyperosmolar-hyperglycemic.html |archive-date=2 July 2012 }}</ref> | field = Endocrinology, critical care medicine | image = Hyperosmolar hyperglycemic state by hariadhi.svg | caption = Video describing diabetes and its complications, including HHS. | symptoms = Signs of dehydration, altered level of consciousness<ref name=AFP2005/> | complications = Disseminated intravascular coagulopathy, mesenteric artery occlusion, rhabdomyolysis<ref name=AFP2005/> | onset = Days to weeks<ref name=Fra2016/> | duration = Few days<ref name=Fra2016/> | types = | causes = | risks = Infections, stroke, trauma, certain medications, heart attacks<ref name=Pas2014/> | diagnosis = Blood tests<ref name=AFP2005/> | differential = Diabetic ketoacidosis<ref name=AFP2005/> | prevention = | treatment = Intravenous fluids, insulin, low molecular weight heparin, antibiotics<ref name=Fra2016/> | medication = | prognosis = ~15% risk of death<ref name=Pas2014/> | frequency = Relatively common<ref name=AFP2005/> | deaths = }} <!-- Definition and symptoms -->

'''Hyperosmolar hyperglycemic state''' ('''HHS'''), also known as '''hyperosmolar non-ketotic state''' ('''HONK'''), is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis.<ref name=Pas2014/><ref name="PageSkinner2008">{{cite book |last1=Page |first1=Piers |last2=Skinner |first2=Greg |title=Emergencies in Clinical Medicine |date=17 January 2008 |publisher=OUP Oxford |isbn=978-0-19-920252-2 |pages=224–225 |language=en}}</ref> Symptoms include signs of dehydration, weakness, leg cramps, vision problems, and an altered level of consciousness.<ref name=AFP2005/> Onset is typically over days to weeks.<ref name=Fra2016/> Complications may include seizures, disseminated intravascular coagulopathy, mesenteric artery occlusion, or rhabdomyolysis.<ref name=AFP2005>{{cite journal|last1=Stoner|first1=GD|title=Hyperosmolar hyperglycemic state.|journal=American Family Physician|date=1 May 2005|volume=71|issue=9|pages=1723–30|pmid=15887451}}</ref>

<!-- Cause and diagnosis --> The main risk factor is a history of diabetes mellitus type 2.<ref name=Pas2014/> Occasionally it may occur in those without a prior history of diabetes or those with diabetes mellitus type 1.<ref name=Fra2016>{{cite journal|last1=Frank|first1=LA|last2=Solomon|first2=A|title=Hyperglycaemic hyperosmolar state.|journal=British Journal of Hospital Medicine|date=2 September 2016|volume=77|issue=9|pages=C130-3|doi=10.12968/hmed.2016.77.9.C130|pmid=27640667}}</ref><ref name=Pas2014/> Triggers include infections, stroke, trauma, certain medications, and heart attacks.<ref name=Pas2014/> Diagnosis is based on blood tests finding a blood sugar greater than 30&nbsp;mmol/L (600&nbsp;mg/dL), osmolarity greater than 320 mOsm/kg, and a pH above 7.3.<ref name=AFP2005/><ref name=Fra2016/>

<!-- Treatment --> Initial treatment generally consists of intravenous fluids to manage dehydration, intravenous insulin in those with significant ketones, low molecular weight heparin to decrease the risk of blood clotting, and antibiotics among those in whom there are concerns of infection.<ref name=Fra2016/> The goal is a slow decline in blood sugar levels.<ref name=Fra2016/> Potassium replacement is often required as the metabolic problems are corrected.<ref name=Fra2016/> Efforts to prevent diabetic foot ulcers are also important.<ref name=Fra2016/> It typically takes a few days for the person to return to baseline.<ref name=Fra2016/>

<!-- Epidemiology and history --> While the exact frequency of the condition is unknown, it is relatively common.<ref name=AFP2005/><ref name=Pas2014/> Older people are most commonly affected.<ref name=Pas2014/> The risk of death among those affected is about 15%.<ref name=Pas2014/> It was first described in the 1880s.<ref name=Pas2014>{{cite journal|last1=Pasquel|first1=FJ|last2=Umpierrez|first2=GE|title=Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment.|journal=Diabetes Care|date=November 2014|volume=37|issue=11|pages=3124–31|doi=10.2337/dc14-0984|pmid=25342831|pmc=4207202}}</ref>

==Signs and symptoms== Symptoms of high blood sugar including increased thirst (polydipsia), increased volume of urination (polyuria), and increased hunger (polyphagia).<ref name=Hen2016>{{cite book|last1=Henry|first1=McMichael|title=ATI RN Adult Medical Surgical Nursing 10.0|date=2016|publisher=Assessments Technology Institutes|isbn=978-1-56533-565-3|pages=537–538}}</ref>

Symptoms of HHS include: * Altered level of consciousness * Neurologic signs including: blurred vision, headaches, focal seizures, myoclonic jerking, reversible paralysis<ref name=Hen2016 /> * Motor abnormalities including flaccidity, depressed reflexes, tremors or fasciculations * Hyperviscosity and increased risk of blood clot formation * Dehydration<ref name=Hen2016 /> * Weight loss<ref name=Hen2016 /> * Nausea, vomiting, and abdominal pain<ref name=Hen2016 /> * Weakness<ref name=Hen2016 /> * Low blood pressure with standing<ref name=Hen2016 />

==Cause== The main risk factor is a history of diabetes mellitus type 2.<ref name=Pas2014/> Occasionally it may occur in those without a prior history of diabetes or those with diabetes mellitus type 1.<ref name=Fra2016/><ref name=Pas2014/> Triggers include infections, stroke, trauma, certain medications, and heart attacks.<ref name=Pas2014/>

Other risk factors: * Lack of sufficient insulin (but enough to prevent ketosis)<ref name=Hen2016 /> * Poor kidney function<ref name=Hen2016 /> * Poor fluid intake (dehydration)<ref name=Hen2016 /> * Older age (50–70 years)<ref name=Hen2016 /> * Certain medical conditions (cerebral vascular injury, myocardial infarction, sepsis)<ref name=Hen2016 /> * Certain medications (glucocorticoids, beta-blockers, thiazide diuretics, calcium channel blockers, and phenytoin)<ref name=Hen2016 />

==Pathophysiology== HHS is usually precipitated by an infection,<ref name="Stoner">{{cite journal | last=Stoner | first=GD | title=Hyperosmolar hyperglycemic state | journal=American Family Physician | volume=71 | issue=9 | pages=1723–30 | date=May 2005 | url=http://www.aafp.org/afp/20050501/1723.html | pmid=15887451 | url-status=live | archive-url=https://web.archive.org/web/20080724204133/http://www.aafp.org/afp/20050501/1723.html | archive-date=24 July 2008 }}</ref> myocardial infarction, stroke or another acute illness. A relative insulin deficiency leads to a serum glucose that is usually higher than 33&nbsp;mmol/L (600&nbsp;mg/dL), and a resulting serum osmolarity that is greater than 320 mOsm. This leads to excessive urination (more specifically an osmotic diuresis), which, in turn, leads to volume depletion and hemoconcentration that causes a further increase in blood glucose level. Ketosis is absent because the presence of some insulin inhibits hormone-sensitive lipase-mediated fat tissue breakdown.{{citation needed|date=September 2022}}

==Diagnosis== ===Criteria=== According to the American Diabetes Association, diagnostic features include:<ref name="RowlandPedley2010">{{cite book|author1=Lewis P. Rowland|author2=Timothy A. Pedley|title=Merritt's Neurology|url=https://books.google.com/books?id=si1Bm6bJhhQC&pg=PA145|year=2010|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-9186-1|pages=369–370|url-status=live|archive-url=https://web.archive.org/web/20170324004314/https://books.google.com/books?id=si1Bm6bJhhQC&pg=PA145|archive-date=24 March 2017}}</ref><ref name="pmid11219236">{{cite journal|vauthors=Magee MF, Bhatt BA | title=Management of decompensated diabetes. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. | journal=Crit Care Clin | year= 2001 | volume= 17 | issue= 1 | pages= 75–106 | pmid=11219236 | doi= 10.1016/s0749-0704(05)70153-6}}</ref> * Plasma glucose level >30&nbsp;mmol/L (>600&nbsp;mg/dL) * Serum osmolality >320 mOsm/kg * Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia)) * Serum pH >7.30<ref name="pmid11219236"/> * Bicarbonate >15 mEq/L * Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3&nbsp;mmol/L) * Some alteration in consciousness * BUN > 30&nbsp;mg/dL (increased)<ref name=Hen2016 /> * Creatinine > 1.5&nbsp;mg/dL (increased)<ref name=Hen2016 />

===Imaging=== Cranial imaging is not used for diagnosis of this condition. However, if an MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.<ref>''Neuroradiology'' 2007 Apr;49(4):299-305.</ref>

===Differential diagnosis=== The major differential diagnosis is diabetic ketoacidosis (DKA). In contrast to DKA, serum glucose levels in HHS are extremely high, usually greater than 40-50&nbsp;mmol/L (600&nbsp;mg/dL).<ref name=Hen2016 /> Metabolic acidosis is absent or mild.<ref name=Hen2016 /> A temporary state of confusion (delirium) is also more common in HHS than DKA. HHS also tends to affect older people more. DKA may have fruity breath, and rapid and deep breathing.<ref name=Hen2016 />

DKA often has serum glucose level greater than 300&nbsp;mg/dL (HHS is >600&nbsp;mg/dL).<ref name=Hen2016 /> DKA usually occurs in type 1 diabetics whereas HHS is more common in type 2 diabetics.<ref name=Hen2016 /> DKA is characterized by a rapid onset, and HHS occurs gradually over a few days.<ref name=Hen2016 /> DKA also is characterized by ketosis due to the breakdown of fat for energy.<ref name=Hen2016 />

Both DKA and HHS may show symptoms of dehydration, increased thirst, increased urination, increased hunger, weight loss, nausea, vomiting, abdominal pain, blurred vision, headaches, weakness, and low blood pressure with standing.<ref name=Hen2016 />

==Management==

=== Phases and timelines === The [https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group JBDS] HHS care pathway<ref name=":0">{{Cite journal |last1=Mustafa |first1=Omar G. |last2=Haq |first2=Masud |last3=Dashora |first3=Umesh |last4=Castro |first4=Erwin |last5=Dhatariya |first5=Ketan K. |last6=the Joint British Diabetes Societies (JBDS) for Inpatient Care Group |date=March 2023 |title=Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group |journal=Diabetic Medicine |language=en |volume=40 |issue=3 |article-number=e15005 |doi=10.1111/dme.15005 |pmid=36370077 |issn=0742-3071|pmc=10107355 }}</ref> comprises 3 main themes to consider when managing a patient with HHS:

* clinical assessment and monitoring * interventions * assessments and prevention of harm

To streamline management, there are 5 phases of therapy from the time of recognition of the condition to resolution:

# 0–60 min # 1–6 hours # 6–12 hours # 12–24 hours # 24–72 hours<ref name=":0" />

===Intravenous fluids=== Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12&nbsp;liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1&nbsp;L/h for the first few hours or until the condition stabilizes.<ref>{{cite book |first1=Judith E. |last1=Tintinalli |first2=Gabor D. |last2=Kelen |first3=J. Stephan |last3=Stapczynski |title=Emergency Medicine: A Comprehensive Study Guide |url=https://books.google.com/books?id=GQoDewvXQ74C |edition=6th |year=2004 |publisher=McGraw-Hill Prof Med/Tech |isbn=978-0-07-138875-7 |page=1309 |url-status=live |archive-url=https://web.archive.org/web/20170324012313/https://books.google.com/books?id=GQoDewvXQ74C |archive-date=24 March 2017 }}</ref>

===Electrolyte replacement=== Potassium replacement is often required as the metabolic problems are corrected.<ref name=Fra2016/> It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output.<ref>{{harvnb|Tintinalli|Kelen|Stapczynski|2004|p=1320}}</ref>

===Insulin===

Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/L, then an insulin infusion of 0.1 units/kg/hr is started.<ref>{{harvnb|Tintinalli|Kelen|Stapczynski|2004|p=1310}}</ref> The goal for resolution is a blood glucose of less than 200&nbsp;mg/dL.<ref name=Hen2016 />

==References== {{reflist}}

==External links== {{Medical resources | DiseasesDB = 29213 | ICD10 = {{ICD10|E10-E14}} | ICD9 = {{ICD9|250.2}} | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = emerg | eMedicineTopic = 264 | MeshID = D006944 }} {{Diabetes}}

Category:Medical emergencies Category:Complications of diabetes Category:Wikipedia medicine articles ready to translate Category:Wikipedia emergency medicine articles ready to translate