KETOASIDOSIS DIABETIKUM DAN STATUS

HIPERGLIKEMIK HIPEROSMOLAR

Dr. Wismandari Wisnu SpPD-KEMD

Divisi Metabolik Endokrin
Departemen Ilmu Penyakit Dalam
FKUI / RSCM
2018
Data Pribadi
§ Nama lengkap : dr. Wismandari Wisnu, SpPD, KEMD, FINASIM
§ Tempat/tgl lahir : Jakarta, 12 Februari 1972
§ Alamat : Jl. Karyawan no 14B, Jakarta 12310

Riwayat Pendidikan
§ S1, Sp-1 dan Sp-2 di Fakultas Kedokteran Universitas Kedokteran

Riwayat Pekerjaan
§ Humas Divisi Metabolik Endokrin, Departemen Ilmu Penyakit Dalam FKUI/RSCM (2009-sekarang)
§ Koordinator Kelas Internasional Mahasiswa S1 FKUI (2018-sekarang)
§ Koordinator Kelas Reguler Mahasiswa S1 FKUI (2017)
§ Koordinator tingkat 5 mahasiswa S1 FKUI (2012-2017)
§ Wakil Koordinator mahasiswa Departemen IPD (2010-sekarang)
§ Dokter PTT di Puskesmas Kecamatan Cilandak, Jakarta Selatan (2000-2003)

Organisasi/Kepanitiaan
Anggota IDI cabang Jakarta Selatan Bendahara Perkeni Jaya
Bidang Humas PB PAPDI Bendahara PAPDI Jaya
Bidang Organisasi PB Perkeni Anggota Internasional : AOTA, ISE, AFES
 TOPIK
• Definisi KAD dan HHS
• Patogenesis KAD dan HHS
• Tatalaksana KAD dan HHS
• Pencegahan
4 Komplikasi Akut DM
• Hipoglikemia

• Hiperglikemia
- KAD (Keto Asidosis Diabetikum)
- HHS (Hyperosmolar hyperglycemic state)
 Slide 5

WHAT IS DIABETIC KETOACIDOSIS ?

Ê Acute decompensated metabolic state due to
§ severe insulin deficiency
§ over-activity of glucagon & other counter-regulatory
hormone

Ê Common in Type 1; Rare in Type 2

Ê Potentially life-threatening

Ê High mortality

Ê Incidence : 5-8 /1000 diabetic persons/yr

Ê Mortality rates 9-14 % - Has improved with insulin useà 2%

Watkins et al. In: Diabetes and its Management 2003

 FAKTOR PRESIPITASI / PREDISPOSISI
KETOASIDOSIS DIABETIKUM

• Riwayat pemberian insulin

• Obat
inadekuat
• Klozapin / olanzapine
• Diabetes onset baru (20 – • Kokain
25%) • Lithium
• Penyakit akut • Penghambat SGLT-2
• Infeksi (30 – 40%) • Terbutaline
• Penyakit serebrovaskular • Tidak diketahui
• Infark miokar
• Pankreatitis akut

Kitabchi et al, Diab Care 2001;24(1):131–53.

 FAKTOR PRESIPITASI / PREDISPOSISI
STATUS HIPEROSMOTIK HIPERGLIKEMIA
• Gagal ginjal
• Riwayat pemberian insulin inadekuat (21 – 41%) • Heat stroke
• Diabetes kasus baru • Hipothermi
• Penyakit akut • Hematom subdural
• Infeksi (32 – 60%) • Luka bakar berat
• Pneumonia • Endokrin
• Infeksi saluran kemih • Akromegali
• Sepsis • Tirotoksikosis
• Penyakit serebrovaskular • Sindrom Cushing
• Infark miokard • Obat (Beta-adrenergic blockers, calcium-channel
• Pankreatitis akut blockers, klorpromazine, klortalidon, cimetidine,
• Emboli paru akut klozepin, diazoxid, asam ethakrinik, obat
• Obstruksi gastrointestinal imunosupresif, L-asparaginase, loksapin,
• Dialisis, peritoneal olanzapine, fenitoin, propranolol, steroid, diuretic
• Thrombosis mesenteric tiazid, total parenteral nutrition)

Kitabchi et al, Diab Care 2001;24(1):131–53.

8
PATHOGENESIS OF DKA AND HHS
Absolute Insulin ↑ Counterregulatory Relative Insulin
Deficiency Hormones Deficiency

↑ Lipolysis ↓Protein Synthesis ↑ Proteolysis Absent or Minimal

↑ Gluconeogenic Subrates Ketoacidosis
↑FFA to Liver
↑ Ketogenesis ↑Glucose ↑Gluconeogenesis ↑Glucogenolysis
Utilization
↓ Alkali Reserve
Hyperglycemia
↑ Ketoacidosis Glyucosuria ( Osmotic diuresis)

Loss of water and electrolytes

Triacylglycerol
Decreased fluid intake
Dehydration Hyperosmolarity
Hyperlipidemia Impaired renal function
HHS
DKA
 Ketoasidosis Diabetikum

Characterized by the triad of

• uncontrolled hyperglycemia,
• Metabolic acidosis
• increased total body ketone
concentration

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 Metabolic Acidosis states
Hyperglycemia states •Lactic acidosis
•DM •Hyperchloremic acidosis
•NKHC •Salicylism
•IGT •Uremic acidosis
•Stress Hyper- •Drug-induced acidosis

glycemia Acidosis
DKA

Ketotic states Ketosis

•Ketotic hypoglycemia
•Alkaholic ketotis
•Starvation ketosis

Kitabchi and Wall

 Mekanisme ketoasidosis diabetes
Absolute insulin ↑ Counter regulatory
deficiency hormones

↓ Protein
Lipolisis ↑ Proteolysis
synthesis

↑ FFA to liver ↑ Gluconeogenic

substances

↑ Ketogenesis ↓ Glucose
↑ Gluconeogenesis ↑ Glycogenolysis
utilization

↓ Alkali reserve Hyperglycemia

↑ Ketoacidosis Glycosuria
(osmotic diuresis)

↑ Triglyserides Loss of water and

electrolytes
↑ Hyperlipidemia
Dehydration

Impaired renal
Kitabchi et al, Diab Care 2001;24(1):131–53. function
Hyperosmolar Hyperglycemic Syndrome (HHS)

Characterized by:
• severe hyperglycemia
• Hyperosmolality
• dehydration
• In the absence of significant ketoacidosis

These metabolic derangements result from the combination

of absolute or relative insulin deficiency and an increase in
counterregulatory hormones (glucagon, catecholamines,
cortisol, and growth hormone).

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 Mekanisme HHS
↑ Counter regulatory Relative insulin
hormones deficiency

↓ Protein Absent to minimal

↑ Proteolysis ketogenesis
synthesis

↑ Gluconeogenic
substances
↓ Glucose
↑ Gluconeogenesis ↑ Glycogenolysis
utilization

Hyperglycemia

Glycosuria
(osmotic diuresis)

Loss of water and

electrolytes
Decreased fluid intake
Dehydration Hyperosmolarity

Impaired renal
Kitabchi et al, Diab Care 2001;24(1):131–53. function
 Slide 14

Diagnosis Ketoasidosis Diabetes

Tanda Gejala
Ê Penurunan nafsu makan Ê Takiardia

Ê Mual Ê Hipotensi

Ê Muntah Ê Hipotermia

Ê Rasa haus
Ê Penuruanan kesadaran
Ê Poliuria
Ê Kulit kering dan hangat
Ê Lemas
Ê Napas Kussmaul
Ê Nyeri perut
Ê Bau napas aseton
Ê Berat badan turun
 ANAMNESIS
KETOASIDOSIS STATUS HIPERGLIKEMIA
DIABETIKUM HIPEROSMOLAR (SHH)
• Mual/ muntah • Riwayat polyuria
• Haus/polyuria • Berat badan turun
• Nyeri perut • Berkurangnya asupan oral yang
• Sesak nafas terjadi dalam beberapa minggu

• Gejala berkembang dalam waktu • Akhir: Letargi / Koma

<24 jam

PIN PAPDI. Panduan Praktik Klinis Ilmu Penyakit Dalam. 2015

 PEMERIKSAAN FISIK – KDA DAN SHH
•Dehidrasi
•Hipotensi
•Takikardia
•Perubahan status mental

PIN PAPDI. Panduan Praktik Klinis Ilmu Penyakit Dalam. 2015

Pemeriksaan Penunjang Awal
Evaluasi metabolik Evaluasi penyakit menulara Lainnyaa
Glukosa Darah perifer lengkap dengan Elektrokardiografi
hitung banding
Keton serum X-ray dada Toksikologi urin
Elektrolit Na+, K+, Cl-, HCO3-, Ca2+, Kultur urin Uji kehamilan
Po43-, Mg2+
Osmolalitas serum Kultur darah
Blood Urea Nitrogen (BUN) dan Nasal swab viral
kreatinin
Analisa gas darah
Fungsi hepar
Amilase dan lipase
Hemoglobin A1c
Urinalysis
a Jika ada indikasi klinis
 Kriteria Diagnostik
KAD SHH
Ringan (kadar GD Sedang (Kadar GD Berat (Kadar GD Kadar GD >600
>250 mg/dL) >250 mg/dL) >250 mg/dL) mg/Dl)
pH arteri 7. 25 – 7.30 7.00 – 7.24 <7.00 >7.30
Bikarbonat serum 15 - 18 10 - 15 <10 >18
Keton urin Positif Positif Positif Kecil
Keton serum Positif Positif Positif Kecil
Osmolalitas serum Bervariasi Bervariasi Bervariasi > 320 mOsm/kg
efektif
Anion gap > 10 > 12 > 12 Bervariasi
Status mental Sadar Sadar/ mengantuk Stupor/ Koma Stupor / Koma
GD: Glukosa darah, Osmolalitas serum efektif = 2x [Na+ ukur (mEq/L)] + glukosa (mg/dL)/18.
Anion gap = (Na+)-[(Cl- + HCO3- (mEq/L)]
Kitabchi et al, Diab Care 2001;24(1):131–53.
 TATALAKSANA

Pemberikan Terapi Koreksi Koreksi

Monitor
cairan insulin Kalium asidosis

H
+
PIN PAPDI. Panduan Praktik Klinis Ilmu Penyakit Dalam. 2015
 PRIMARY MANAGEMENT OF DKA/HHS
20 IV Fluids Bicarbonate Insulin: Reguler Potassium

pH ˂ 6,9 pH ˂ 6,9 IV Route IV Route

(DKA and HHS) (DKA and HHS) Establish adequate
Determine hydration status 100mmol in Renal function (urine
No
400ml H20 Output – 50 ml/hr)
HCO3- 0.1 U/kg/B.Wt
+20mEq
Severe Cardiogenic as IV bolus
KCL, infuse
Hypovelemia shock 0.1 U/kg Bwt/hr
Mild for 2 hours
As IV Continous K+ <3.3 K+ > 5.2
dehydration
Insulin infusion mEq/L mEq/L
Hemodynamic Repeat 0.1 U/kg/hr IV
Administer 0,9%
Monitoring/ every Continous
NaCL ( 1.0 L/hr
Pressor 2 hours Insulin infusion Do not give K+,
Evaluated corrected Hold insulin and give
Until pH ≥ 7 But check serum
Serum Na+ 20 – 30 mEq/hr
Monitor If serum glucose does not fall by at K+
Until K+> 3.3 mEg/L
Serum K+ Leatst 10% in first hour , give 0.14 Every 2hrs
every 2 hrs U/kg as IV bolus , then continue
Previous Rx
Serum Na + Serum Na+ Serum Na+ K+ = 3.3 – 5.2
High Low When serum glucose mEq/L
Normal
Reaches 200 mg/dl, reduce When serum glucose
Reguler insulin infusion to reaches 300 mg/dl, reduce
0,45% NaCL 0,9% NaCL 0.02 – 0.05 U/kg/hr IV, or give reguler insulin infusion to
Rapid-acting insulin at 0.1 0.02 – 0.05 U/kg/hr . Keep Give 20-30 mEq K+ in each
(250-500 ml/Hr) (250-500 ml/Hr)
U/kg SC every 2 hrs. Keep serum glucose between 200 Liter of IV fluid to keep serum
depending on depending on
Serum glucose between 150 and 300 mg/dl until patient K+ between 4 - 5 mEg/L
hydration state hydration state
And 200 mg/dl until resolution Is mentally alert
of DKA
When serum glucose reaches
200 mg/dl (DKA) or 300 mg/dl Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hr until stable.
After resolution of DKA or HHS and when patient is able to eat , initiate SC multidose
(HHS), change to 5% dextrose
Insulin regimen . To transfer from IV to SC , continue IV insulin infusion for 1- 2 hrs
With 0.45% NaCL at 150-250 ml/hr
After SC insulin begun to ensure adequate plasma insulin levels . In Insulin native
Patiients, 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 2001 Jan; 24(1): 131-153

PRIMARY MANAGEMENT OF DKA/HHS– REFERRAL PREPARATION
21 IV Fluids

Determine hydration status

Severe Cardiogenic
Hypovelemia shock
Mild
dehydration
Administer 0,9% Hemodynamic
NaCl (10 L/hr) Monitoring/Pressor

Evaluated corrected
Serum Na+
Serum Na + Serum Na +
High Normal
0,45% NaCL (250-500 ml/Hr)
depending on hydration state
0,9% NaCl (250-500 ml/Hr)
depending on hydration state
Serum Na +
Low
When serum glucose reaches
200 mg/dl (DKA) or 300 mg/dl
(HHS), change to 5% dextrose
With 0.45% NaCL at 150-250 ml/hr
Diabetes Care 2001 Jan; 24(1): 131-1
PRIMARY MANAGEMENT OF DKA/HHS– REFERRAL PREPARATION
22
Bicarbonate

pH ≥ 6,9 pH ˂ 6,9

No 100mmol in
HCO3- 400ml H20
+20mEq
KCL, infuse for 2 hours

Repeat every
2 hours
Until pH ≥ 7
Monitor
Serum K+
every 2 hrs

Diabetes Care 2001 Jan; 24(1): 131-1

PRIMARY MANAGEMENT OF DKA/HHS– REFERRAL PREPARATION
23 Insulin :
Reguler

IV Route IV Route
(DKA and HHS) (DKA and HHS)

0.1 U/kg/B.Wt 0.1 U/kg Bwt/hr

as IV bolus As IV Continous
Insulin infusion

0.1 U/kg/hr IV
Continous
Insulin infusion

If serum glucose does not fall by at

Least 10% in first hour , give 0.14
U/kg as IV bolus , then continue
Previous Rx

Diabetes Care 2001 Jan; 24(1): 131-1

 EVALUASI TERAPI INSULIN
• Periksa elektrolit, pH vena, kreatinin
• GD tiap 2 – 4 jam sampai pasien stabil
• Setelah resolusi KAD atau SHH dan mampu makan
berikan regimen insulin subkutan
• Mengganti insulin IV ke subkutan: lanjutkan infus insulin IV
selama 1 – 2 jam setelah insulin subkutan dimulai untuk
mencapai kadar insulin plasma yang adekuat
• Pada pasien insulin-naïve, mulai dengan 0.5 U//hari – 0.8
U/KgBB /hari dan sesuaikan sesuai kebutuhan

PIN PAPDI. Panduan Praktik Klinis Ilmu Penyakit Dalam.

PRIMARY MANAGEMENT OF DKA/HHS– REFERRAL PREPARATION
25
Potassium

Establish adequate
Renal function (urine
Output – 50 ml/hr)

K+ <3.3 mEq/L K+ > 5.2 mEq/L

Hold insulin and give Do not give K+,

20 – 30 mEq/hr But check serum K+
Until K+> 3.3 mEg/L Every 2hrs

K+ = 3.3 – 5.2 mEq/L

Give 20-30 mEq K+ in each

Liter of IV fluid to keep serum
K+ between 4 - 5 mEg/L Diabetes Care 2001 Jan; 24(1): 131-1
 PEMANTAUAN

Pantau tekanan darah, nadi, napas,

status mental, asupan cairan dan urin
tiap 1 – 4 jam

PIN PAPDI. Panduan Praktik Klinis Ilmu Penyakit Dalam.

KOMPLIKASI
• Renjatan hipovolemik Komplikasi pengobatan
• Trombosis vena • Hipoglikemia
• Pendarahan saluran cerna • Hipokalemia
atas • Overload edema serebral
• Sindrom distres pernapasan
akut
PROGNOSIS

• Mortalitas KAD : 2% untuk usia <65 tahun dan

22% untuk usia > 65 tahun.
• Mortalitas SHH 20 – 30%
PREVENTION (1)
• Better access to medical care
• Intensive patients education
• Effective communication à acute illness
• Review sick-day management
• Insulin treatment
• Blood glucose goal
• Treat fever and infection
• Start easy digestible liquid diet
• Do not stop insulin or oral anti diabetes
PREVENTION (2)
• Increase BG monitoring during acute illness
• Check ketone bodies (either urine or blood) when BG >
300 mg/dl
• Hand held meter with BG and 3HB strips can be helpful
for avert DKA episode
 KESIMPULAN
• KAD dan HHS adalah kondisi kompikasi akut diabetes yang
mengancam nyawa
• Terdapat faktor predisposisi yang harus dihindari pada pasien
diabetes
• Tatalaksana KAD adalah rehidrasi, insulin, koreksi kalum, koreksi
asidosis dan monitor ketat
• Lakukan pencegahan terjadinya KAD dan HHS dengan cara
mentatalaksana kondisi akut dengan baik, tingkatkan monitor gula
darah dan jangan stop obat diabetes jika mengalami kondisi akut
 REFERENSI
1. Krisis hiperglikemia Dalam: Alwi I, Salim S, Hidayat R, Kurniawan J, Tahapary D. Penyunting.
Penatalaksanaan bidang ilmu penyakit dalam: panduan Praktik Klinis. Jakarta: Interna Publishing; 2015.
Hal 109 -14.
2. Soewondo Pradana. Ketoasidosis Diabetik. Dalam: Sudowo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiati
S. Penyunting. Buku ajar ilmu penyakit dalam. Edisi V. Jakarta: Interna Publishing; 2009. Hal 1906 – 1911.
3. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes.
Diabetes Care. 2009;32(7):1335 – 43.
4. Misra S, Oliver NS. Diabetic ketoacidosis in adults. BMJ. 2015; 351: 5660-7.
5. Lupsa BC, Inzucchi SE. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome Dalam: Loriaux
L. Endocrine Emergencies: Recognition and treatment. Springers; 2014. Hal 15 – 31.
6. Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab
2015; 100:2849.
7. Kitabchi AE, Razavi L.Hyperglycemic Crises: Diabetic Ketoacidosis (DKA), And Hyperglycemic
Hyperosmolar State (HHS). In: http://www.endotext.org/diabetes/diabetes24/diabetesframe24.htm
(Accessed on January 30, 2013).
Terima kasih atas
perhatiannya