Crises in DIabetes Sumba 2018

Hyperglycemic and Hypoglycemic
Crisis in Adult Patient with

Diabetes
Ervita Ritonga
ROAD SHOW PERKENI
ENDONESIA UNTUK INDONESIA
ENDONESIA UNTUK INDONESIA 2018
INTRODUCTION
The most serious Acute Metabolic

Complications of Diabetes:
• Diabetic Ketoacidosis
• Hyperosmolar Hyperglycemic State
• Hypoglycemia
Adapted from : International Working Group on the Diabetic Foot Practical guidelines on the management and prevention of the diabetic foot 2011
Diabetes Metab Res Rev 2012; 28(S1): 225-31

Hyperglycemic Crisis
• Potentially life-threathening complications

of Diabetes
• Considered as two manifestations of the

same underlying mechanism : INSULIN
DEFICIENCY

Hyperglycemic Crisis
• Mortality rate :
DKA : < 5%
HHS : ~ 11%

PATOPHYSIOLOGY
DIAGNOSIS
• HISTORY :
– DKA and HHS : Polyuria, polydipsia,

weight loss, vomiting, dehydration,
weakness, mental status change.
– HHS : The process usually evolves over
several days to weeks.
– DKA : The evolution of DKA episode in
type 1 or type 2 diabetes tends to be much
shorter (< 24 h).

Diabetic Ketoacidosis
(DKA)
• TRIAD :
* Uncontrolled Hyperglycemia
* Metabolic Acidosis
* Increased total body Ketone
concentration

Diabetic Ketoacidosis
(DKA)
• Blood Glucose ≥ 250 mg/dl

• Arterial pH < 7,3
• Bicarbonate < 15 mEq/l
• Moderate ketonuria or ketonemia

Hyperosmolar
Hyperglycemic State
(HHS)
• Characterized by :
• Severe Hyperglycemia
• Hyperosmolality
• Dehydration
• Absence of significant ketoacidosis

Diagnostic Criteria of HHS
• Serum glucose > 600 mg/dl

• Arterial pH > 7,3
• Serum bicarbonate > 15 mEq/l
• Minimal ketonuria and ketonemia
• Serum Osmolality > 320 mOsm/kg

PHYSICAL FINDINGS
• Poor skin turgor
• Kussmaul respiration (in DKA)
• Tachycardia, hypotension
• Mental status : from full normal alertness to
profound lethargy or coma
• HHS : Focal neurologic signs (hemiparesis) and
seizures (focal or generalized)
• Normothermic/ Hypothermic
• DKA : Nausea, vomiting, diffuse abdominal pain
seizures

DKA HHS
Mild Moderate Severe Plasma
(plasma (plasma glucose (plasma glucose glucose > 600
glucose > 250 > 250 mg/dl) > 250 mg/dl) mg/dl
mg/dl)
Arterial pH 7.25-7.30 7.00 to <7.24 < 7.00 > 7.30
Serum bicarbonate
15 – 18 10 to <15 10 >18
(mEq/L)
Urine ketone Positive Positive Positive Small

Serum ketone Positive Positive Positive Small
Effective serum Variable Variable Variable >320
osmolarity mOsm/k
g
Anion gap > 10 > 12 > 12 Variable
Mental status Alert Alert/drowsy Stupor/coma Stupor/com
a
Precipitating Factors
• Infection
• Discontinuation of or inadequate insulin therapy
• Pancreatitis
• Myocardial infarction
• Cerebrovascular accident
• Drugs : corticosteroids, thiazides, sympathomimetic
agents, pentamidine, antipsychotics

Precipitating Factors Mostly
in Type 1 Diabetes
• New onset type 1 Diabetes
• Discontinuation of insulin in established type 1 diabetes
• Psychological problems complicated by eating disorders
• Insulin ommision because of fear of weight gain
• Fear of Hypoglycemia
• Rebellion against authority
• Stress of chronic disease

ENDONESIA UNTUK INDONESIA HHS
• Underlying medical illness that provokes the release of
counterregulatory hormones or compromises the access
to water --> severe dehydration and HHS.
• Restricted water intake due to the patient being
bedridden and exacerbated by the altered thirst
response of the elderly.
• 20% of these patients have no history of diabetes -->
delayed recognition of hyperglycemic symptoms -->
severe dehydration.

MANAGEMENT

Assessing the Severity
of Na and Water Deficit
• Corrected Na :
Add 1,6 mg/dl to the measured serum Na
for each 100 mg/dl of glucose above
100 mg/dl.

Plasma Osmolality
(Na+) – [(Cl- + HCO3- (mEq/l) ]

Complete initial evaluation. Check capillary glucose and serum/urine ketones to confirm hyperglycemia and
Ketonemia/ketonuria. Obtain blood for metabolic profile. Start IV fluids : 1.0 L of 0.9% NaCl per hour.
IV Fluids Bicarbonate Insulin : Regular Potassium
pH ≥ 6.9 pH < 6.9
IV Route IV Route Establish adequate
(DKA and HHS) (DKA and HHS) renal function (urine
Determine hydration status No 100mmol in output ~ 50 ml/hr)
HCO2 400ml H2O
+ 20mEq 0.1 U/kg/B.Wt.
Severe Cardiogenic KCL. Infuse as IV bolus
Hypovolemia
Mild shock for 2 hours 0.14 U/kg/B.Wt/hr
dehydration as IV continuous
insulin infusion K+ < 3.3 mEq/L K+ > 5.2 mEq/L
0.1 U/kg/hr IV
Administer 0.9% Hemodynamic Repeat
NaCl (1.0 L/hr) Monitoring/
continuous
Every insulin infusion
pressors 2 hours Hold insulin and give Do not give K+
Evaluate corrected until pH ≥ 7. 20-30 mEq/hr but check serum K+
Serum Na++ Monitor If serum glucose does not fall by at every 2 hrs
serum K+ Until K+ > 3.3 mEq/L
least 10% in first hour. Give 0.14
every 2 hrs U/kg as IV bolus, then continue
Privious Rx
Serum Na+ Serum Na+ Serum Na+
high normal low
K+ = 3.3-5.2 mEq/L
When serum glucose
reaches 200 mg/dl, reduce
0.45% NaCl 0.9% NaCl regular insulin infusion to
(250-500 ml/hr) (250-500 ml/hr) 0.02 – 0.05 U/kg/hr IV. Or give
Give 20 – 30 mEq K+ in each
depending on depending on Rapid-acting insulin at 0.1
liter of IV fluid to keep serum
hydration state U/kg SC every 2 hrs. Keep
hydration state K+ between 4 – 5 mEq/L
serum glucose between 150
and 200 mg/dl until resolution
of DKA
When serum glucose reaches
200 mg/dl (DKA) Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until stable
change to 5% dextrose after resolution of DKA or HHS and when patient is able to eat, initiate SC multidose
with 0.45% NaCl at 150-250 ml/hr insulin regimen. To transfer from IV to SC, continue IV insulin infusion for 1 – 2 hr
after SC insulin begun to ensure adequate plasma insulin levels. In insulin naïve
DKA
patients, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust insulin as needed.
Look for precipitating cause(s).
Diabetes Care, volume 32, number 7, July 2009

Figure 1. Protokol for management of adult patients with DKA. DKA diagnostic criteria : blood glucose 250 mg/dl, arterial pH 7.3,
bicarbonate 15 mEq/L, and moderate ketonuria or ketonemia.
Management of Adult Patient with DKA & HHS
Complete initial evaluation, start iv fluids: 1 L of 0,9%NaCl perhour (15-20 mL/kg/h)
iv Fluids insulin potassium Assess need for bicarbonate

Determine hydration status
Hypovolemic shock Mild Hypotension Cardiogenic shock
Administer Evaluate corrected serum Na Hemodynamic

0,9% NaCl Monitoring
(1L/hr) &or
Plasma Serum Na Serum Na Serum Na
expander high normal low
0,45% NaCl 0,9% NaCl

(4-14ml/kg/h) (4-14ml/kg/h)
Depending on hydration state Depending on hydration state
iv route sc/im route

Insulin: 0,15 units/kg Insulin: 0,4 units/kg
as iv bolus ½ iv bolus, ½ im or sc
0,1 units/kg/h iv 0,1 units/kg/h regular

Insulin infusion Insulin sc or im
If serum glucose does not fall by 50-70 mg/dL in first hour
Double insulin infusion Give hourly iv insulin bolus

hourly until glucose falls (10 units) until glucose falls
by 50-70 mg/dL by 50-70 mg/dL
If initial serum K is < 3,3 mEq/L

Hold insulin and give 40 mEq K per h
(2/3 KCL &1/3 KPO4) until K > 3,3 mEq/L
If initial serum K is > 5,0 mEq/L

Do not give K but check K
every 2 h
If initial serum K is > 3,3 mEq/L but < 5,0 mEq/L

give 20-30 mEq K in each liter of iv fluid
(2/3 KCL &1/3 KPO4) to keep serum K at 4-5 mEq/L
pH < 6,9 pH 6,9-7,0 pH > 7,0
NaHCO3 (100 mmol) NaHCO3 (50 mmol) No HCO3

Dilute in 400 mL H2O Dilute in 200 mL H2O
Infuse at 200mL/h Infuse at 200mL/h
Repeat HCO3 administration

Every 2 h until pH > 7,0
Monitor serum K
When serum glucose reaches 250 mg/dL
Change to 5% dextrose with 0,45% NaCl at 150-250 ml/h with adequate insulin
(0,05-0,1 unit/kg/h iv infusion or 5-10 units SC every 2 h) to keep the serum
glucose between 150 and 200 mg/dL until metabolic control is achieved
Check electrolytes, BUN, creatinine and glucose every 2-4 h until stable.
After resolution of DKA, if the patient is NPO, continue IV insulin and supplement
with SC reguler insulin as needed. When the patient can eat, initiate a multidose
insulin regimen and adjust as needed. Continue IV insulin infusion for 1-2 h after
SC insulin is begun to ensure adequate plasma insulin levels.
Continue to look for precipitating factor(s).
Resolution of DKA
Glucose level < 200 mg/dl

Serum bicarbonate > 18 mEq/l
Venous pH > 7,3
Resolution of HHS is
associated with :
• Normal osmolality
• Regain of normal mental status

Complications of
Treatment
• Hypoglycemia
• Hypokalemia
• Cerebral edema
• Iatrogenic fluid overload

Signs of
Cerebral Edema
• Mental status changes
• Vomiting
• Headache
• Lethargy
• Elevated diastolic pressure
• Decorticate or decerebrate posturing
• Cranial nerve palsies
• Cheyne-Stokes respiration

Hipoglikemia
• dipertimbangan apabila kadar glukosa darah

kurang dari 60 mg/dl.
• Gejala yang muncul : gangguan status mental

dan atau stimulasi system syaraf simpatis.

Hipoglikemia
• Kadar glukosa darah normal dipertahankan

antara sekitar 65–140 mg/dl,
• Kurang dari 50 mg/dl tanpa gejala hipoglikemia

yang jelas
• Kurang dari 60 mg/dl dengan gejala hipoglikemia

Hipoglikemia
• Bukan hanya sebagai suatu kasus yang segera

perlu penanganan segera saja tetapi juga harus
dicari penyebab dasar.

Hipoglikemia
Kriteria modifikasi Whipple’s Triad tdd :

1. Gejala SSP seperti :
Bingung, perubahan perilaku, koma
2. Kadar gula darah kurang dari 60 mg/dL.
3. Perbaikan klinis setelah pemberian
glukosa

Etiologi
Obat-obatan
• Insulin
• Gangguan ekskresi obat (gagal ginjal, gagal hati)
• Perubahan regulasi hormon counter insulin
• Sulfonilurea
• Salisilat, beta blockers, quinine, quinolones

Etiologi
Kegagalan Fungsi Ginjal

• Organ kedua glukoneogenesis
• Penurunan ekskresi obat dan metabolitnya
(insulin, glibenclamide)
Kegagalan fungsi Hati
• Penurunan glikogenolisis
• Penurunan glukoneogenesis
• Tempat metabolisme tolbutamide, glibenclamide,
glipizide

Etiologi
Endokrinopati
• Insufisiensi adrenal (glukokortikoid)
• Defisiensi hormon pertumbuhan (GH)
• Defisiensi Glukagon

Etiologi
Poisoning / Keracunan
(Ethanol, Propanolol, Salicylates)
• Etanol menginhibisi glukoneogenesis

• Ethanol-induced hypoglycemia terjadi pada 12-
72 jam setelah minum etanol

Etiologi
Neoplasm
• Insulinoma
• Non–islet-cell tumors
• hepatocellular carcinoma,
• adrenocortical tumors,
• carcinoid tumors,
• leukemia, and lymphomas

Gejala
Gejala hipoglikemia :
• Sistem syaraf pusat (otak)
• Sistem syaraf otonom simpatis
Neuroglikopenia
lemah, pusing bingung, hilang konsentrasi, irritabiliats,
hallusinasi, pandangan kabur hemiplegia bahkan koma
atau kematian
Neurogenik
berkeringan yang berlebihan, palpitasi, tremor, cemas,
dan rasa lapar yang hebat.

Tingkatan Hipoglikemia
RINGAN
Gejala otonom yang jelas ditemukan
penderita bisa makan dan menolong dirinya sendiri
SEDANG
Gejala oronom dan neuroglikopenik jelas ditemukan
penderita masih bisa makan dan menolong dirinya sendiri
BERAT
memerlukan bantuan orang lain
Terjadi penurunan kesadaran
GD biasa nya < 2. mmol/L atau < 50 mg/dl

Tatalaksana
1. Inisial terapi yang segera dalam upaya meningkatkan

kadar gula darah
2. Terapi penyakit dasar yang menyebabkan hipoglikemi

dalam upaya pencegahan hipoglikemia yang berulang.

Hipoglikemia Ringan - Sedang
• Minum larutan gula murni 20-30 gr

• Minum gula gula
• Obat obat diabetes di berhentikan
• Pantau kadar glukosa darah tiap 1 -2 jam
• Pertahankan kadar glukosa darah berkisar 200 mg/dl
• Kemudian cari penyebab

Hipoglikemia Berat
1. 50 cc Dektrose 40% bolus ( atau glukagon 0.5 – 1

mg IV/IM)
2. Pemasang infus Dektrose 10 % 500 cc dalam 6
jam
3. Kadar glukosa darah diperiksa setiap ½ jam
4. Langkah ini dilakukan sampai penderita
kesadarannya membaik.

Hipoglikemia Berat
5. Apabila belum sadar dan kadar GD masih < 100 mg/dl

ulangi 50 ml dektrose 40%
6. Apabila belum sadar juga dan GD 200 mg/dl, berikan
hidrokortison 100 mg/dl tiap 4 jam selama 12 jam atau
Deksametasone 10 mg setiap 6-8 jam
7. Kemudian cari penyebab

Conclusions
• Hyperglycemic and hypoglycemic crises are

both life-threathening disorders, that carry
significant risk of morbidity and mortality.
• It is important to be familiar with the

pathophysiology, presentation, treatment,
complications and prevention

ENDONESIA UNTUK
INDONESIA
ROADSHOW PERKENI , SUMBA 2018
THANK YOU
Guidelines for Insulin Management
in DKA and HHS (1)
• Reg.Insulin 10 U iv stat or 0,15 U/kg iv.stat.

• Start Reg Insulin infusion 0,1 U/kg per hour
or 5 U per hour.
• Increase insulin by 1 U per hour every 1-2 hr if
less than10% decrease in glucose or no
improvement in acid-base status
• Decrease insulin by 1-2 U per hour
(0,05-0,1 U/kg per hour) when glucose
≤ 250 mg/dl and/or progressive improvement
in clinical status with decrease in glucose
of > 75 mg/dl per hour. Wyckoff J et al. Diabetic Ketoacidosis and hyperosmolar
Hyperglycemic state.In:Kahn CR,et al(Eds) Joslin’s
Diabetes Mellitus.14th ed Lippincot Williams&Wilkins
Baltimore , 2005. Pg887-899.
Guidelines for Insulin Management
in DKA and HHS (2)
•• Do not decrease insulin infusion to < 1 U

Maintain
per hour.
glucose between 140-180 mg/dl.
• If blood sugar decreases to < 80 mg/dl.
stop insulin infusion for no more than
I hr and restart infusion.
• If glucose drops consistently to < 100 mg/dl
change I.v fluids to D 10 to maintain blood
glucose between 140 and 180 mg/dl.
• Once patient is able to eat, consider change
to s.c. insulin
Wyckoff J et al. Diabetic Ketoacidosis and hyperosmolar

Hyperglycemic state.In:Kahn CR,et al(Eds) Joslin’s
Diabetes Mellitus.14th ed Lippincot Williams&Wilkins
Baltimore , 2005. Pg887-899.
IV Fluids Bicarbonate Insulin : Regular Potassium

pH ≥ 6.9 pH < 6.9
HCO2 400ml H2O
Hypovolemia
Mild shock for 2 hours 0.1 U/kg/B.Wt/hr
dehydration as IV continuous
insulin infusion K+ < 3.3 mEq/L K+ > 5.2 mEq/L
0.1 U/kg/hr IV
continuous
Serum Na++ Monitor If serum glucose does not fall by at every 2 hrs
least 10% in first hour. Give 0.14
every 2 hrs U/kg as IV bolus, then continue
Privious Rx
Serum Na+ Serum Na+ Serum Na+
high normal low DKA HHS
K+ = 3.3-5.2 mEq/L
When serum glucose When serum glucose
reaches 200 mg/dl, reduce reaches 300 mg/dl, reduce
0.45% NaCl 0.9% NaCl regular insulin infusion to regular insulin infusion to
(250-500 ml/hr) (250-500 ml/hr) 0.02 – 0.05 U/kg/hr IV. Or give 0.02 – 0.05 U/kg/hr IV. Or give
Rapid-acting insulin at 0.1 Rapid-acting insulin at 0.1 Give 20 – 30 mEq K+ in each
depending on depending on liter of IV fluid to keep serum
U/kg SC every 2 hrs. Keep U/kg SC every 2 hrs. Keep
hydration state hydration state serum glucose between 200 K+ between 4 – 5 mEq/L
and 200 mg/dl until resolution and 300 mg/dl until patient is
of DKA mentally alert

200 mg/dl (DKA) or 300 mg/dl
Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until stable
(HHS) change to 5% dextrose
after resolution of DKA or HHS and when patient is able to eat, initiate SC multidose
with 0.45% NaCl at 150-250 ml/hr
insulin regimen. To transfer from IV to SC, continue IV insulin infusion for 1 – 2 hr
patients, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust insulin as needed.

IVFluids Bicarbonat Insulin : Regular Potassium

e
pH ≥ 6.9 pH < 6.9
HCO2 400ml H2O
Hypovolemia
Mild shock for 2 hours 0.1
dehydration U/kg/B.Wt/hr
as IV K+ < 3.3 mEq/L K+ > 5.2 mEq/L
0.1 U/kg/hr IV continuous
continuous insulin infusion
Serum Na++ Monitor If serum glucose does not fall by every 2 hrs
at
every 2 hrs least 10% in first hour. Give 0.14
U/kg as IV bolus, then continue
+
Serum Na+ Serum Na+ Serum Na Privious Rx
high normal low DKA HHS
K+ = 3.3-5.2 mEq/L
When serum glucose When serum glucose
reaches 200 mg/dl, reduce reaches 300 mg/dl, reduce
0.45% NaCl 0.9% NaCl regular insulin infusion to regular insulin infusion to
(250-500 ml/hr) (250-500 ml/hr) 0.02 – 0.05 U/kg/hr IV. Or give 0.02 – 0.05 U/kg/hr IV. Or give
Rapid-acting insulin at 0.1 Rapid-acting insulin at 0.1 Give 20 – 30 mEq K+ in each
depending on depending on liter of IV fluid to keep serum
U/kg SC every 2 hrs. Keep U/kg SC every 2 hrs. Keep
hydration state hydration state serum glucose between 200 K+ between 4 – 5 mEq/L
and 200 mg/dl until resolution and 300 mg/dl until patient is
of DKA mentally alert

200 mg/dl (DKA) or 300 mg/dl
Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until
(HHS) change to 5% dextrose
stable
with 0.45% NaCl at 150-250 ml/hr
after resolution of DKA or HHS and when patient is able to eat, initiate SC
multidose
insulin regimen. To transfer from IV to SC, continue IV insulin infusion for 1 – 2 hr
patients, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust insulin as
needed.

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Hyperglycemic and Hypoglycemic

Crisis in Adult Patient with

The most serious Acute Metabolic

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• Potentially life-threathening complications

• Considered as two manifestations of the

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

– DKA and HHS : Polyuria, polydipsia,

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• Blood Glucose ≥ 250 mg/dl

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• Serum glucose > 600 mg/dl

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Arterial pH 7.25-7.30 7.00 to <7.24 < 7.00 > 7.30

Urine ketone Positive Positive Positive Small

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

(Na+) – [(Cl- + HCO3- (mEq/l) ]

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Care, volume 32, number 7, July 2009

iv Fluids insulin potassium Assess need for bicarbonate

iv Fluids insulin potassium Assess need for bicarbonate

Determine hydration status

Hypovolemic shock Mild Hypotension Cardiogenic shock

Administer Evaluate corrected serum Na Hemodynamic

0,45% NaCl 0,9% NaCl

iv Fluids insulin potassium Assess need for bicarbonate

iv route sc/im route

0,1 units/kg/h iv 0,1 units/kg/h regular

If serum glucose does not fall by 50-70 mg/dL in first hour

Double insulin infusion Give hourly iv insulin bolus

iv Fluids insulin potassium Assess need for bicarbonate

If initial serum K is < 3,3 mEq/L

If initial serum K is > 5,0 mEq/L

If initial serum K is > 3,3 mEq/L but < 5,0 mEq/L

iv Fluids insulin potassium Assess need for bicarbonate

pH < 6,9 pH 6,9-7,0 pH > 7,0

NaHCO3 (100 mmol) NaHCO3 (50 mmol) No HCO3

Repeat HCO3 administration

When serum glucose reaches 250 mg/dL

Glucose level < 200 mg/dl

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• dipertimbangan apabila kadar glukosa darah

• Gejala yang muncul : gangguan status mental

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• Kadar glukosa darah normal dipertahankan

• Kurang dari 50 mg/dl tanpa gejala hipoglikemia

• Kurang dari 60 mg/dl dengan gejala hipoglikemia

Diabetes Metab Res Rev 2012; 28(S1): 225-31

• Bukan hanya sebagai suatu kasus yang segera

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Kriteria modifikasi Whipple’s Triad tdd :

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Diabetes Metab Res Rev 2012; 28(S1): 225-31

Kegagalan Fungsi Ginjal