* Case presentation: hyperosmolar hyperglycemic state (HHS) Mortality attributed to hyperosmolar hyperglycemic state (HHS) is considerably higher than that attributed to DKA, with recent mortality rates of 5–20%. * Agenda: Historical perspectives and diagnosis. Pathophysiology. Treatment issues. Rhabdomyolysis: an overlooked complication. Final bottom line and take home message.

1. Usama Ragab Yousif
MSc. Internal Medicine
Diabetes of stout people
Monday, 20/2/2017

2. Quiz

3. 52-year old male patient, Z.A., businessman, married and has 2 offspring the youngest is 7 years old,
born in Egypt, lives in KSA, no special habits of medical importance.
Chief complaint: he was brought to ER, drowsiness, with acute abdominal pain, vomiting,
constipation 2 days duration.
Medical History: Diabetic, since 1995, initially on OHD, then on insulin, Basal (30 U glargine) boluses
(10 U regular insulin) regimen + metformine 500 mg bid. It's complicated with retinopathy; managed
by PRPC therapy, nephropathy on conservative measures and neuropathy.
HTN diagnosed 9 months ago on aldomet 500 mg t.d.s., hydralazine 25 mg t.d.s., bisoprolol 10 m
g od, nitrates 60 mg tab, lercadipine 10 mg tab od. He is controlled on these medication.
History

4. Condition started five days before, with vomiting, diarrhea, he was not able to eat, discontinue medical
treatment, didn’t follow sick day guidance given to him by his doctors. Two days later he started to
experience abdominal pain, diffuse, not radiating, on-off in character. Diarrhea stopped, vomiting
increased in frequency. He sought medical advice, admitted to ER.
Vitiligo diagnosed since 1997.
Intracranial hematoma in 2012 managed by tapping.
Vitamin D deficiency.
Surgery for tendinits on right foot 2008
Hx of admission to hospital due to dyspnea, admitted to chest department, CT chest done revealed air
trapping, bronchiectasis changes in right upper lobes, bilateral pleural effusion, received antibiotic
course, diuretics and then discharged
History (cont.)

5. •Patient is drowsy GCS E3 V4 M6, sluggish response.
•Vital Signs (on admission):
•Blood Pressure: 90/60
•Pulse: 120, regular, equal on both sided.
•Temperature: 37.8ᵒc
•Respiratory rate: 18
•Decubitus: lies flat on bed.
•HEENT: vitiligo
•BMI: 105 kg/(1.9)2 = 29.2 kg/m2
•Extremities:
•Upper limbs: no clubbing, no pigmentations, no pallor, normal muscles and nerves.
•Lower limbs: bilateral lower limb edema above knees, no visible veins, scar of previous operatio
n was noticed on dorsum of right foot.
Examination

6. •Cardiac examination: Normal
•Chest examination: there is decrease air entry bilaterally more on right side, harsh vesicular breathing, mediu
m sized crackles scattered bilaterally.
•Abdomen: mildely distended, no tenderness, no audible intestinal sound, no shifting dullness (few physical si
gns)
Examination (cont.)

7. Work up
Laboratory
On admission:
POC capillary BG was high confirmed by venous sample in lab was 41.6 mmol/
L (750 mg/dL).
VBG was withdrawn: PH: 7.32, HCO3: 20 PCO2: 40 K: 5 Na: 150 mEq/L
SO2: 94% PO2: 80
Serum creatinine: 182 umol/L (2.06 mg/dL)
BUN: 89 mg/dL
Phosphorus: 5.14 mg/dL (2.5-4.5 mg/dL)
Mg: 1.5 mg/dL (1.7-2.4 mg/dL)
Ca: 8.6 mg/dL (8.5-10 mg/dL) corrected Ca = 9.4 mg/dL
Cl: 110 mEq/L
Albumin: 3 gm/dL

8. Work up
Laboratory
Anion gap= Na – (Cl + HCO3) = 15
Effective calculated osmolality = 2 Na + Glucose/18 = 341 mosmol/L
Ketons in urine: negative

9. Work up
Radiologically
PAUS was done; reveled dilated bowel loops, sluggish movement, mild IPFF. Pl
ain X-ray erect for abdomen was done reveled fluid level.
CT abdomen with CTA reveled atherosclerotic changes in SMA with stenosis r
anging 50-60%, as well as SMA branches heavily calcified with no complete oc
clusion. Extensive atherosclerotic changes in inferior MA as well.
MVO was diagnosed

10. •52-year old male patient, complicated diabetes presentation (acute , chronic), occlusive event,
hyperglycemia, hyperosmolality, hypernatremia.
Hyperosmolar hyperglycemic state
Salient features

11. Mortality attributed to HHS is considerably higher
than that attributed to DKA, with recent mortality
rates of 5–20%
Diabetes Care 2009 Jul; 32(7): 1335-1343.

12. Agenda
Historical perspectives and diagnosis.
Pathophysiology.
Treatment issues
An overlooked complication.
Answer of the quiz??
Final bottom line and take home message

13. What is the most important features that distinguish
HHS from DKA?
A. Age of the patient.
B. Type of diabetes
C. Absence of ketosis and acidosis.
D. Excess hyperglycemia and increased osmolality.
E. C and D

14. Diabetes Care 2014 Nov; 37(11): 3124-3131.

15. Metabolism 1971;20:529–538 Diabetes Care 2014;37:3124–3131
HHS 1970s criteria
Arieff and Carroll’s diagnostic criteria:
It included a blood glucose level >600 mg/dL, a total serum osmola
rity level >350 mOsm/L, and a serum acetone reaction from 0 to 2
pluses when the serum was diluted 1:1 with water

16. Diabetes Care 2009 Jul; 32(7): 1335-1343.

17. Diabetic Hyperglycemic Crises
Diabetic Ketoacidosis
(DKA)
Hyperglycemic Hyperosmolar State
(HHS)
Younger, type 1 diabetes Older, type 2 diabetes
No hyperosmolality Hyperosmolality
Volume depletion Volume depletion
Electrolyte disturbances Electrolyte disturbances
Acidosis No acidosis
Diabetes Care 2009 Jul; 32(7): 1335-1343.

18. Insulin deficiency?
A. Absolute
B. Relative

19. Diabetes Care 2014 Nov; 37(11): 3124-3131.

20. 1- Diabetes 1973 Apr; 22(4): 264-271.
2- Kitabchi AE, Fisher JN, Murphy MB, et al. Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. In: Kahn CR, Weir GC (ed), Joslin’s Diabetes Mellitus, 13
th edn, Philadelphia, USA: Lea & Febiger, 1994:738–70.

21. Serum sodium is 150 mEq/L? Is this significant?
A. Yes
B. No
C. In such presentation, Yes…

22. J of Pediatrics 2011;158(1):9-14.
Fluid and electrolyte status

23. Fluid and electrolyte status (cont.)
J of Pediatrics 2011;158(1):9-14.
Na = Measured Sodium + 0.016 * (Glucose - 100)

24. Diabetes Care 2014 Nov; 37(11): 3124-3131.
Typical fluid and electrolyte losses in HHS
Total osmolarity: 2 Na + glucose/18 + BUN/2.8
Effective osmolality: 2 Na + glucose/18

25. What is the most precipitating factor for HHS and DKA?
A. ACS
B. CVA
C. Infection
D. First presentation

26. Precipitating causes in patients with DKA and HHS
The most common precipitating factor in the development of HHS i
s infection in 30-60% : pneumonia and UTI.
Omission of antidiabetic medication.
First presentation in 3-13%
Underlying medical illness, such as stroke, myocardial infarction, an
d trauma
Nat Rev Endocrinol. 2016 Apr;12(4):222-32

27. From your point of view what is the main contributing fa
ctor for development of mental abnormalities in HHS?
A. Hyperglycemia
B. Dehydration
C. Osmolality

28. J Clin Endocrinol Metab, May 2008, 93(5):1541–1552
Diabetes Rev, 1994, 2: 115-126

29. Metabolism 1971;20:529–538 Diabetes Care 2014;37:3124–3131
HHS treatment Evolution

30. HHS Treatment goals
The goals of treatment of HHS are to treat the underlying cause and to gra
dually and safely:
• Normalise the osmolality
• Replace fluid and electrolyte losses
• Normalise blood glucose
Other goals include prevention of:
• Arterial or venous thrombosis
• Other potential complications e.g. cerebral oedema/ rhabdomyolysis
• Foot ulceration: underlying neuropathy, vasculopathy, diabetic foot.
Joint British Diabetes Societies Inpatient Care Group, 2012

31. Choice of fluid
Joint British Diabetes Societies Inpatient Care Group, 2012
Diabetes Care 2009 Jul; 32(7): 1335-1343.

32. HHS treatment
Joint British Diabetes Societies Inpatient Care Group, 2012

33. HHS treatment
Diabetes 28.6 (1979): 577-584.

34. Insulin
• If significant ketonaemia is not
present (3β-hydroxy butyrate is l
ess than 1 mmol/L) do NOT start
insulin.
Insulin treatment prior to adequa
te fluid replacement may result i
n cardiovascular collapse as wate
r moves out of the intravascular
space, with a resulting decline in
intravascular volume
Joint British Diabetes Societies Inpatient Care Group, 2012
Diabetes Care 2009 Jul; 32(7): 1335-1343.

35. Treatment
J of Pediatrics 2011;158(1):9-14.

36. Is a Priming Dose of Insulin Necessary?
A. Yes.
B. No.

37. Diabetes Care 31:2081–2085, 2008

38. Diabetes Care 31:2081–2085, 2008

39. What about the route?

40. Am J Med. 2004;117:291–296.
Route of Insulin

41. Diabetes Care 27:1873–1878, 2004
Route of Insulin

42. J Clin Endocrinol Metab, May 2008, 93(5):1541–1552

43. Nat Rev Endocrinol. 2016 Apr;12(4):222-32
Route of Insulin

44. Potassium replacement
Diabetes Care 2009 Jul; 32(7): 1335-1343.

45. J of Thrombosis and Haemostasis 2007;5(6):1185-90
Prophylactic anticoagulation
All patients should receive prophylactic low molecular weight hep
arin (LMWH) for the full duration of admission unless contraindica
ted; e.g. 1 mg/kg/24h. Or 40 mg/24h.
Full anticoagulation should only be considered in patients with su
spected thrombosis or acute coronary syndrome.

46. The next day lab reveled elevated serum creatinine kinas
e (990 IU/L), negative tropinine, no dynamic ECG change
s, what to consider?

47. Rhabdomyolysis (cont.)
Am J Med. 1990 Jan;88(1):9-12.

48. NICE CG10 2004 Putting Feet First. http://www.diabetes.org.uk/Get_involved/Campaigning/Putting-feet-first/ 2012.
Foot protection
Re-examine the feet daily

49. Diabetes Care 2009 Jul; 32(7): 1335-1343.
Recovery phase

50. https://en.wikipedia.org/wiki/Theresa_May https://www.diabetes.org.uk/About_us/News/Balance-interview-with-Theresa-May/
Theresa May

51. Is HHS a Monopoly for elderly?
A. Yes
B. No

52. Look for risk factor

53. There is no magic number

54. The same for HHS and DKA
DKA HHS

55. Image is inverted
HHS??

56. Journal of Paediatrics and Child Health 52 (2016) 80–84

57. Journal of Paediatrics and Child Health 52 (2016) 80–84

58. Journal of Paediatrics and Child Health 52 (2016) 80–84

59. Journal of Paediatrics and Child Health 52 (2016) 80–84

60. Final Bottom line
Prevention is the best therapy
HHS is a life-threatening emergency
Management involves
Attention to precipitating cause
Fluid and electrolyte management
Insulin therapy
Patient monitoring
Prevention of metabolic complications during recovery
Transition to long-term therapy
Patient education and discharge planning should aim at prevention of re
currence