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==Historical Perspective==
==Historical Perspective==
The notable events regarding the history of hyperosmolar hyperglycemic state include:<ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid4065612">{{cite journal |vauthors=Fisher JN, Shahshahani MN, Kitabchi AE |title=Diabetic ketoacidosis: low-dose insulin therapy by various routes |journal=N. Engl. J. Med. |volume=297 |issue=5 |pages=238–41 |year=1977 |pmid=406561 |doi=10.1056/NEJM197708042970502 |url=}}</ref><ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid25342831">{{cite journal| author=Pasquel FJ, Umpierrez GE| title=Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. | journal=Diabetes Care | year= 2014 | volume= 37 | issue= 11 | pages= 3124-31 | pmid=25342831 | doi=10.2337/dc14-0984 | pmc=4207202 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25342831  }} </ref><ref name="pmid16144505">{{cite journal| author=Milionis HJ, Elisaf MS| title=Therapeutic management of hyperglycaemic hyperosmolar syndrome. | journal=Expert Opin Pharmacother | year= 2005 | volume= 6 | issue= 11 | pages= 1841-9 | pmid=16144505 | doi=10.1517/14656566.6.11.1841 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16144505  }} </ref><ref name="pmid21752485">{{cite journal| author=Fadini GP, de Kreutzenberg SV, Rigato M, Brocco S, Marchesan M, Tiengo A et al.| title=Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. | journal=Diabetes Res Clin Pract | year= 2011 | volume= 94 | issue= 2 | pages= 172-9 | pmid=21752485 | doi=10.1016/j.diabres.2011.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21752485  }} </ref><ref name="pmid16694999">{{cite journal| author=Martin HE, Wick AN| title=QUANTITATIVE RELATIONSHIPS BETWEEN BLOOD AND URINE KETONE LEVELS IN DIABETIC KETOSIS. | journal=J Clin Invest | year= 1943 | volume= 22 | issue= 2 | pages= 235-41 | pmid=16694999 | doi=10.1172/JCI101388 | pmc=435232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16694999  }} </ref><ref name="pmid14693938">{{cite journal |vauthors=Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM |title=Hyperglycemic crises in diabetes |journal=Diabetes Care |volume=27 Suppl 1 |issue= |pages=S94–102 |year=2004 |pmid=14693938 |doi= |url=}}</ref><ref name="pmid20751675">{{cite journal |vauthors=Dreschfeld J |title=The Bradshawe Lecture on Diabetic Coma |journal=Br Med J |volume=2 |issue=1338 |pages=358–63 |year=1886 |pmid=20751675 |pmc=2256374 |doi= |url=}}</ref><ref name="pmid8325282">{{cite journal |vauthors=Fleckman AM |title=Diabetic ketoacidosis |journal=Endocrinol. Metab. Clin. North Am. |volume=22 |issue=2 |pages=181–207 |year=1993 |pmid=8325282 |doi= |url=}}</ref>
The notable events regarding the history of hyperosmolar hyperglycemic state include:<ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid4065612">{{cite journal |vauthors=Fisher JN, Shahshahani MN, Kitabchi AE |title=Diabetic ketoacidosis: low-dose insulin therapy by various routes |journal=N. Engl. J. Med. |volume=297 |issue=5 |pages=238–41 |year=1977 |pmid=406561 |doi=10.1056/NEJM197708042970502 |url=}}</ref><ref name="pmid25342831">{{cite journal| author=Pasquel FJ, Umpierrez GE| title=Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. | journal=Diabetes Care | year= 2014 | volume= 37 | issue= 11 | pages= 3124-31 | pmid=25342831 | doi=10.2337/dc14-0984 | pmc=4207202 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25342831  }} </ref><ref name="pmid16144505">{{cite journal| author=Milionis HJ, Elisaf MS| title=Therapeutic management of hyperglycaemic hyperosmolar syndrome. | journal=Expert Opin Pharmacother | year= 2005 | volume= 6 | issue= 11 | pages= 1841-9 | pmid=16144505 | doi=10.1517/14656566.6.11.1841 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16144505  }} </ref><ref name="pmid21752485">{{cite journal| author=Fadini GP, de Kreutzenberg SV, Rigato M, Brocco S, Marchesan M, Tiengo A et al.| title=Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. | journal=Diabetes Res Clin Pract | year= 2011 | volume= 94 | issue= 2 | pages= 172-9 | pmid=21752485 | doi=10.1016/j.diabres.2011.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21752485  }} </ref><ref name="pmid16694999">{{cite journal| author=Martin HE, Wick AN| title=QUANTITATIVE RELATIONSHIPS BETWEEN BLOOD AND URINE KETONE LEVELS IN DIABETIC KETOSIS. | journal=J Clin Invest | year= 1943 | volume= 22 | issue= 2 | pages= 235-41 | pmid=16694999 | doi=10.1172/JCI101388 | pmc=435232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16694999  }} </ref><ref name="pmid14693938">{{cite journal |vauthors=Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM |title=Hyperglycemic crises in diabetes |journal=Diabetes Care |volume=27 Suppl 1 |issue= |pages=S94–102 |year=2004 |pmid=14693938 |doi= |url=}}</ref><ref name="pmid20751675">{{cite journal |vauthors=Dreschfeld J |title=The Bradshawe Lecture on Diabetic Coma |journal=Br Med J |volume=2 |issue=1338 |pages=358–63 |year=1886 |pmid=20751675 |pmc=2256374 |doi= |url=}}</ref><ref name="pmid8325282">{{cite journal |vauthors=Fleckman AM |title=Diabetic ketoacidosis |journal=Endocrinol. Metab. Clin. North Am. |volume=22 |issue=2 |pages=181–207 |year=1993 |pmid=8325282 |doi= |url=}}</ref>
* The known history of [[diabetes]] dates back to the Egyptian era and the first documented evidence was found in an Egyptian papyrus dating back to 1552 BC.
* The known history of [[diabetes]] dates back to the Egyptian era and the first documented evidence was found in an Egyptian papyrus dating back to 1552 BC.
* In 1828, Von Stosch for the first time described [[diabetic coma]] in detail.
* In 1828, Von Stosch for the first time described [[diabetic coma]] in detail.
Line 27: Line 27:
* In 2004–2009, [[American Diabetes Association]] published the guidelines for the management of the hyperosmolar hyperglycemic state in adults.
* In 2004–2009, [[American Diabetes Association]] published the guidelines for the management of the hyperosmolar hyperglycemic state in adults.
* In 2011, Pediatric Endocrine Society guidelines for treatment of HHS in children were published.
* In 2011, Pediatric Endocrine Society guidelines for treatment of HHS in children were published.
==Landmark Events in the Development of Treatment Strategies==
==Landmark Events in the Development of Treatment Strategies==
The landmark events in the treatment of hyperosmolar hyperglycemic state are:<ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid4065612">{{cite journal |vauthors=Fisher JN, Shahshahani MN, Kitabchi AE |title=Diabetic ketoacidosis: low-dose insulin therapy by various routes |journal=N. Engl. J. Med. |volume=297 |issue=5 |pages=238–41 |year=1977 |pmid=406561 |doi=10.1056/NEJM197708042970502 |url=}}</ref><ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid25342831">{{cite journal| author=Pasquel FJ, Umpierrez GE| title=Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. | journal=Diabetes Care | year= 2014 | volume= 37 | issue= 11 | pages= 3124-31 | pmid=25342831 | doi=10.2337/dc14-0984 | pmc=4207202 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25342831  }} </ref><ref name="pmid16144505">{{cite journal| author=Milionis HJ, Elisaf MS| title=Therapeutic management of hyperglycaemic hyperosmolar syndrome. | journal=Expert Opin Pharmacother | year= 2005 | volume= 6 | issue= 11 | pages= 1841-9 | pmid=16144505 | doi=10.1517/14656566.6.11.1841 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16144505  }} </ref><ref name="pmid21752485">{{cite journal| author=Fadini GP, de Kreutzenberg SV, Rigato M, Brocco S, Marchesan M, Tiengo A et al.| title=Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. | journal=Diabetes Res Clin Pract | year= 2011 | volume= 94 | issue= 2 | pages= 172-9 | pmid=21752485 | doi=10.1016/j.diabres.2011.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21752485  }} </ref><ref name="pmid16694999">{{cite journal| author=Martin HE, Wick AN| title=QUANTITATIVE RELATIONSHIPS BETWEEN BLOOD AND URINE KETONE LEVELS IN DIABETIC KETOSIS. | journal=J Clin Invest | year= 1943 | volume= 22 | issue= 2 | pages= 235-41 | pmid=16694999 | doi=10.1172/JCI101388 | pmc=435232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16694999  }} </ref><ref name="pmid14693938">{{cite journal |vauthors=Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM |title=Hyperglycemic crises in diabetes |journal=Diabetes Care |volume=27 Suppl 1 |issue= |pages=S94–102 |year=2004 |pmid=14693938 |doi= |url=}}</ref>
The landmark events in the treatment of hyperosmolar hyperglycemic state are:<ref name="pmid820228">{{cite journal |vauthors=Kitabchi AE, Ayyagari V, Guerra SM |title=The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis |journal=Ann. Intern. Med. |volume=84 |issue=6 |pages=633–8 |year=1976 |pmid=820228 |doi= |url=}}</ref><ref name="pmid4065612">{{cite journal |vauthors=Fisher JN, Shahshahani MN, Kitabchi AE |title=Diabetic ketoacidosis: low-dose insulin therapy by various routes |journal=N. Engl. J. Med. |volume=297 |issue=5 |pages=238–41 |year=1977 |pmid=406561 |doi=10.1056/NEJM197708042970502 |url=}}</ref><ref name="pmid25342831">{{cite journal| author=Pasquel FJ, Umpierrez GE| title=Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. | journal=Diabetes Care | year= 2014 | volume= 37 | issue= 11 | pages= 3124-31 | pmid=25342831 | doi=10.2337/dc14-0984 | pmc=4207202 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25342831  }} </ref><ref name="pmid16144505">{{cite journal| author=Milionis HJ, Elisaf MS| title=Therapeutic management of hyperglycaemic hyperosmolar syndrome. | journal=Expert Opin Pharmacother | year= 2005 | volume= 6 | issue= 11 | pages= 1841-9 | pmid=16144505 | doi=10.1517/14656566.6.11.1841 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16144505  }} </ref><ref name="pmid21752485">{{cite journal| author=Fadini GP, de Kreutzenberg SV, Rigato M, Brocco S, Marchesan M, Tiengo A et al.| title=Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. | journal=Diabetes Res Clin Pract | year= 2011 | volume= 94 | issue= 2 | pages= 172-9 | pmid=21752485 | doi=10.1016/j.diabres.2011.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21752485  }} </ref><ref name="pmid16694999">{{cite journal| author=Martin HE, Wick AN| title=QUANTITATIVE RELATIONSHIPS BETWEEN BLOOD AND URINE KETONE LEVELS IN DIABETIC KETOSIS. | journal=J Clin Invest | year= 1943 | volume= 22 | issue= 2 | pages= 235-41 | pmid=16694999 | doi=10.1172/JCI101388 | pmc=435232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16694999  }} </ref><ref name="pmid14693938">{{cite journal |vauthors=Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM |title=Hyperglycemic crises in diabetes |journal=Diabetes Care |volume=27 Suppl 1 |issue= |pages=S94–102 |year=2004 |pmid=14693938 |doi= |url=}}</ref>
{{Family tree/start}}
{{Family tree/start}}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01='''''Preinsulin era'''''<br> •The treatment modalities used for diabetic coma include blood transfusion, castor oil with potassium citrate, and saline solutions with sodium carbonate among other therapies.
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01='''''Preinsulin era'''''<br> •The treatment modalities used for [[diabetic coma]] include [[blood transfusion]], castor oil with potassium citrate, and saline solutions with sodium carbonate among other therapies.
| boxstyle_B02= text-align: Center;  
| boxstyle_B02= text-align: Center;  
| boxstyle_B03= text-align: left;  
| boxstyle_B03= text-align: left;  
}}
}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1930–1950'''''<br> •The usual practice was to use insulin in 20–100 units i.v. or s.c. bolus followed by 20 units s.c. every 30–60 min depending on glucosuria.
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1930–1950'''''<br> •The usual practice was to use [[insulin]] in 20–100 units i.v. or s.c. bolus followed by 20 units s.c. every 30–60 min depending on [[glucosuria]].
| boxstyle_B02= text-align: Center;  
| boxstyle_B02= text-align: Center;  
| boxstyle_B03= text-align: left;  
| boxstyle_B03= text-align: left;  
}}
}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1950–1970s'''''<br> • In that period, the insulin was given as 2 units/kg bolus of crystalline insulin; up to 920 units in the first 7 h.
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1950–1970s'''''<br> • In that period, the [[insulin]] was given as 2 units/kg bolus of crystalline [[insulin]]; up to 920 units in the first 7 h.
| boxstyle_B02= text-align: Center;  
| boxstyle_B02= text-align: Center;  
| boxstyle_B03= text-align: left;  
| boxstyle_B03= text-align: left;  
}}
}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''Early 1970s'''''<br> • Insulin was given as low-dose insulin regimens with Regular insulin 0.1 units/kg i.v. followed by 0.1–0.3 units/h i.v., s.c., or i.m.
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''Early 1970s'''''<br> • [[Insulin]] was given as low-dose [[insulin]] regimens with regular [[insulin]] 0.1 units/kg i.v. followed by 0.1–0.3 units/h i.v., s.c., or i.m.
}}
}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1990s'''''<br> • Insulin was administered as 0.1 units/kg i.v. bolus, then 0.1 units/kg/h as continuous infusion until glucose level <13.8 mmol/L (250 mg/dL)
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''1990s'''''<br> • [[Insulin]] was administered as 0.1 units/kg i.v. bolus, then 0.1 units/kg/h as continuous infusion until glucose level <13.8 mmol/L (250 mg/dL)
}}
}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''2004–2009'''''<br> • ADA consensus for treatment of DKA and HHS in adult patients according to which Initial bolus (0.1 units/kg i.v.), followed by 0.1 units/kg/h until glucose <250 mg/dL, then reduce insulin by 50%
{{familytree | boxstyle= text-align: Center; | | | |B01| | | | |B01= '''''2004–2009'''''<br> • ADA consensus for treatment of [[DKA]] and [[HHS]] in adult patients according to which initial bolus (0.1 units/kg i.v.), followed by 0.1 units/kg/h until [[glucose]] <250 mg/dL, then reduce [[insulin]] by 50%
}}
}}


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Latest revision as of 14:45, 17 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Overview

The first cases of the hyperosmolar hyperglycemic state (HHS) were described by Von Frerichs and Dreschfeld in the 1880s in some patients with unusual diabetic coma. In 1971, Aerieff and Carroll proposed the diagnostic criteria for patients presenting with diabetic coma and named it as a hyperosmolar hyperglycemic nonketotic state. In the recent times, the term has been changed to the hyperosmolar hyperglycemic state as most of the patients present without coma and with minimal ketosis. Before the discovery of insulin in 1922, it was rare for the patient of diabetes with an episode of diabetic coma to survive for more than a few months. With the discovery of insulin, the development of diabetic coma in patients with diabetes became less frequent. The management of hyperosmolar hyperglycemic state has evolved over the years with the use of insulin and adjustment of doses of insulin to achieve optimum control of the disease.

Historical Perspective

The notable events regarding the history of hyperosmolar hyperglycemic state include:[1][2][3][4][5][6][7][8][9]

  • The known history of diabetes dates back to the Egyptian era and the first documented evidence was found in an Egyptian papyrus dating back to 1552 BC.
  • In 1828, Von Stosch for the first time described diabetic coma in detail.
  • In 1857, Petters discovered acetone in the urine of patients with diabetes.
  • In 1865, Gerhardt discovered acetoacetic acid in the urine of patients with diabetes.
  • In 1874, Kussmaul also described diabetic coma in detail.
  • In 1878, Foster described some cases of diabetic coma and ketonemia.
  • In 1883–1884, Stadelmann, Külz, Minkowski found out that in addition to acetone patients with diabetic coma also have β-hydroxybutyric acid.
  • In 1884–1886, Von Frerichs and Dreschfeld described some cases of patients with diabetic coma but without kussmaul breathing or ketones.
  • In 1922, insulin was discovered and isolated by Banting and Best.
  • In 1909–1923, Lépine, Revillet, McCaskey and Bock et al also described some cases of patients with diabetic coma without ketonuria.
  • In 1930–1935, Lawrence and Joslin described the management of diabetic coma.
  • In 1957, Sament, Schwartz, Graeff, and Lips also described some case reports of diabetic coma without ketones and hyperosmolality.
  • In 1962, Singer et al explained the relationship of hyperglycemia and osmolality.
  • In 1971, Arieff, Carroll and Gerich et al described the modern definition and initial diagnostic criteria of the hyperosmolar hyperglycemic state which they termed as hyperosmolar hyperglycemic non-ketotic state.
  • In 1973, Arieff and Kleeman explained the mechanism of cerebral edema occurring during the treatment of hyperosmolar hyperglycemic state.
  • In 1976–1977, Alberti, Hockaday and Kitabchi et al described the low-dose insulin protocols for the treatment of HHS.
  • In 2004–2009, American Diabetes Association published the guidelines for the management of the hyperosmolar hyperglycemic state in adults.
  • In 2011, Pediatric Endocrine Society guidelines for treatment of HHS in children were published.

Landmark Events in the Development of Treatment Strategies

The landmark events in the treatment of hyperosmolar hyperglycemic state are:[1][2][3][4][5][6][7]

 
 
 
Preinsulin era
•The treatment modalities used for diabetic coma include blood transfusion, castor oil with potassium citrate, and saline solutions with sodium carbonate among other therapies.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1930–1950
•The usual practice was to use insulin in 20–100 units i.v. or s.c. bolus followed by 20 units s.c. every 30–60 min depending on glucosuria.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1950–1970s
• In that period, the insulin was given as 2 units/kg bolus of crystalline insulin; up to 920 units in the first 7 h.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early 1970s
Insulin was given as low-dose insulin regimens with regular insulin 0.1 units/kg i.v. followed by 0.1–0.3 units/h i.v., s.c., or i.m.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1990s
Insulin was administered as 0.1 units/kg i.v. bolus, then 0.1 units/kg/h as continuous infusion until glucose level <13.8 mmol/L (250 mg/dL)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2004–2009
• ADA consensus for treatment of DKA and HHS in adult patients according to which initial bolus (0.1 units/kg i.v.), followed by 0.1 units/kg/h until glucose <250 mg/dL, then reduce insulin by 50%
 
 
 
 

References

  1. 1.0 1.1 Kitabchi AE, Ayyagari V, Guerra SM (1976). "The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis". Ann. Intern. Med. 84 (6): 633–8. PMID 820228.
  2. 2.0 2.1 Fisher JN, Shahshahani MN, Kitabchi AE (1977). "Diabetic ketoacidosis: low-dose insulin therapy by various routes". N. Engl. J. Med. 297 (5): 238–41. doi:10.1056/NEJM197708042970502. PMID 406561.
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