PENGELOLAAN

KOMPLIKASI AKUT
PADA PENDERITA DIABETES MELLITUS

Octo Indradjaja
Divisi Endokrin Metabolisme Diabetes
FK. Uniba/ RSUD AL Ihsan Bandung
 Penyebab kematian terbanyak ke 4 atau
ke 5 pada negara berkembang
 Lebih dari 177 juta orang menderita
diabetes diseluruh dunia
 Insidensi diabetes meningkat
estimasi lebih dari 300 juta pada tahun
2025
Indonesia ??
2000 : 5.6 juta
2020 : 8.2 juta (prevalensi 4.6%)
 Prevalensi Diabetes di Dunia
2000 2030
Peringkat Negara Penderita Negara Penderita
diabetes diabetes
(Juta) (Juta)
1 India 31.7 India 79.4
2 China 20.8 China 42.3
3 Amerika 17.7 Amerika 30.3
4 Indonesia 8.4 Indonesia 21.3
5 Jepang 6.8 Pakistan 13.9
6 Pakistan 5.2 Brazil 11.3
7 Rusia 4.6 Banglades 11.1
8 Brazil 4.6 Jepang 8.9
9 Itali 4.3 Philippina 7.8
10 Banglades 3.2 Mesir 6.7
Dikutip dari : Wild S dkk. Diabetes Care 2004;27:1047-53
 Komplikasi Diabetes

Akut Kronis

Krisis Hiperglikemia : Retinopati

Ketoasidosis Diabetik Vasculopati
Hiperglikemi Hiperosmoler non Nephropati
ketosis Neuropati
Asidosis Laktat

Hipoglikemia Infeksi :
Gangrene Diabetik
KRISIS METABOLIK
KRISIS HIPERGLIKEMIK
Ketoasidosis Diabetik (KAD)
Diabetic ketoacidosis (DKA)
Keadaan Hiperglikemik Hiperosmoler
Hyperosmolar Hyperglicaemic State (HHS)

KRISIS HIPOGLIKEMIK
KRISIS HIPERGLIKEMIK
 BERKURANGNYA EFEKTIFITAS KERJA
INSULIN YG BEREDAR

+
Meningkatnya hormon
kontra - insulin
Glukagon, katekholamin Kortisol & GH

GLUKOSA HATI 
GLUKOSA GINJAL 
UTILISASI GLUKOSA 

Hiperglikemia
Osmolaritas extra sel 
DKA
“ DEFISIENSI “ Insulin + hormon kontra 

Lipolisis

Asam lemak Benda keton 

• Ketonemia
• Asidosis metabolik
HHS
KADAR INSULIN PLASMA RELATIF 

 Tidak cukup untuk memfasilitasi

utilisasi glukosa oleh jaringan

 Cukup untuk mencegah lipolisis

mencegah ketogenesis
DKA dan HHS
Hiperglikemia

Diuresis osmotic
 Glukosuria
 Kehilangan banyak
Na++, K++, dan Air
DKA HHS

+++ Ketosis +
+ Osmolalitas +++
FAKTOR PENCETUS
• Infeksi
• CVA / Stroke
• Alkoholisme
• Pankreatitis
• AMI
• Trauma fisik & Psi
• Obat-obat
• Penghentian insulin
(PD tipe I)
PADA PASIEN DM TIPE 1 MUDA

 Problem psikis Pola makan !

 Takut BB 
 Takut hipoglikemia
 Pemberontakan terhadap otoritas

Insulin distop

DKA
PEMERIKSAAN FISIK
 Turgor kulit kurang
 Takhikardia
 Hipotensi
 Syok
 Perubahan status mental
 Pernafasan Kussmaul (DKA)
 Koma
  Glukosa plasma
 BUN / Kreatinin
 Elektrolit
 Osmolalitas
 Urinalisis
 Keton – urin
 Keton serum
 BGA / AGD

(mEq/L)] + glukosa mg/dl

18
 Diagnostic Criteria for DKA and HHS
D
DKKAA
Mild
Mild Moderate
Moderate Severe
Severe HHS
HHS
Plasma
Plasma glucose
glucose (mg/dl)
(mg/dl) >> 250
250 >> 250
250 >> 250
250 >> 600
600
Arterial
Arterial pH
pH 7.25-7.30
7.25-7.30 7.00-7.24
7.00-7.24 << 7.00
7.00 << 7.30
7.30
Serum
Serum bicarbonate
bicarbonate (mEq/L)
(mEq/L) 15-18
15-18 10-<
10-< 15
15 << 10
10 << 15
15
Urine
Urine ketones
ketones ** Positive
Positive Positive
Positive Positive
Positive Small
Small
Serum
Serum ketones
ketones ** Positive
Positive Positive
Positive Positive
Positive Small
Small
Effective
Effective serum
serum osmolality
osmolality Variable
Variable Variable
Variable Variable
Variable >> 320
320
(( mOsm/kg)
mOsm/kg) 

Anion
Anion gap
gap ‡‡ >> 10
10 >> 12
12 >> 12
12 >> 12
12
Alteration
Alteration in
in sensorium
sensorium Alert
Alert Alert/drowsy
Alert/drowsy Stupor/coma
Stupor/coma Stupor/coma
Stupor/coma
or
or mental
mental obtundation
obtundation

** Nitroprusside
Nitroprusside reaction
reaction method
method ::   calculation
calculation :: 22 [measured
[measured Na
Na (mEq/L)]
(mEq/L)] ++ glucose
glucose
(mg/dl)/18;
(mg/dl)/18; ‡‡ calculation
calculation :: (Na
(Na )) –– (Cl
++
(Cl ++ HCO
HCO33)) (mEq/L),
(mEq/L), See
See text
text for
for details.
details.
 Typical Total Body Deficits of Water
and Electrolytes in DKA and HHS
DKA HHS
Total water (( litersliters )) 6 9
Water (( ml/kg
ml/kg )) ** 100 100 – 200
Na++ (( mEq/kg
mEq/kg )) 7 - 10 5 – 13
Cl-- (( mEq/dl
mEq/dl )) 3-5 5 – 15
K+ (( mEq
mEq // dldl )) 3-5 4–6
PO44 (( mmol/kg
mmol/kg )) 5-7 3–7
Mg2+ 2+ (( mEq/kg
mEq/kg )) 1-2 1-2
Ca2+ 2+ (( mEq/kg
mEq/kg )) 1-2 1-2

* Per kilogram of body weight

‡ From Ennis et al. 15
15 and Kreisberg 88
TERAPI DKA + HHS YANG BERHASIL, MELIPUTI :

• Koreksi
1. Dehidrasi
2. Hiperglikemia
3. Keseimbangan elektrolit
4. Faktor presipitasi

• Monitoring yang sering

TERAPI CAIRAN

• Ekspansi cairan intra &

extra seluler
• Perbaikan perfusi ginjal
 Initial DKA Treatment in Primary Care

1. Evaluate vital signs and urine volume

2. IV line, start the rehydration
3. Check the blood glucose periodically Prepare the patient
(per hour if possible) for Hospital

12:00
12:00 12:30
12:30 1:00
1:00 2:00
2:00
30 min. 30 min. 60 min.

• Start insulin with bolus IV 0.18 U/kgBW, and continue with insulin drip 0.09
U/hour/kgBW
• Check blood glucose per hour with glucometer on the way to hospital
I Na Cl 0,9% 1 jam I 1 – 1,5 L

II Na++ tinggi Na++ normal Na++ rendah

Na Cl 0,45% Na Cl 0,9%

Glukosa darah  250 mg/dl

III GANTI Dextrose 5% &

Na Cl 0,45%
(150 - 250 cc/jam)
Insulin (0,05 – 0,1) U / kg / jam
PERTAHANKAN GLUKOSA DARAH

DKA : 150 – 200 mg/dl

HHS : 250 – 300 mg/dl

Agar osmolalitas tak terlalu 

bahaya hipoglikemi <
INSULIN
Sesudah cairan 1 jam
Reguler 0,1 U/kg I.V. sebagai bolus

0,1 U/kg/ jam

Bila glukosa serum tidak turun

sebanyak 50-70 mg/dl dalam 1 jam

Lipat 2 x kan setiap jam

Sampai turun 50-70 mg/dl

Glukosa  250 mg/dl

Insulin
Insulin (0,05
(0,05 –– 0,1)
0,1) U
U // kg
kg // jam
jam
Dextrose
Dextrose 5%
5% & & Na
Na Cl
Cl 0,45%
0,45%
(150
(150 -- 250
250 cc/jam)
cc/jam)
SESUDAH FUNGSI GINJAL – O.K.
(dilihat dari diuresis)

Dipertimbangkan
pemberian K+
 Bila K+ serum < 3,3 mEq/L

Hentikan insulin
Berikan K+ 40 mEq
sampai K+ > 3,3 mEq/L

Bila K+ serum > 5,5 mEq/L

Jangan beri K+
pantau K+ setiap 2 jam

Bila K+ > 3,3 - < 5,5 mEq/L

Berikan 20-30 mEq K

dalam setiap liter cairan I.V

Pertahankan K+ antara 4-5 mEq/L

BIKARBONAT
Tentukan kebutuhan Bikarbonat

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

Larutkan Na HCO33 50 mmol Tak perlu

(100 mmol dalam Na HCO33 dalam Na HCO33
400 ml H22O) 200 ml H22O
200 ml/jam 200 ml/jam
Ulangi pemberian bikarbonat
tiap 2 jam sampai pH > 7,0,
lalu hentikan
SESUDAH DKA & HHS TERATASI

Bila pasien NPO

Teruskan insulin IV
+ suplemen S.C.

Bila pasien bisa makan

Teruskan insulin IV
atau S.C. multipel
KOMPLIKASI PENGOBATAN
PALING SERING
• HIPOGLIKEMI Insulin >>
• HIPOKALEMI Insulin >>
• HIPERGLIKEMI Penghentian insulin I.V
BERULANG tanpa pemb. S.C.
cukup
• EDEMA SEREBRAL (t.u. anak-anak)
 Osmolalitas terlalu cepat 
KRISIS HIPOGLIKEMIK
SEBAB
• Dosis obat berlebihan :
 Insulin
 Sekretagog insulin
(Sulfonil urea dst.)
• Makan terlambat atau kurang
• Aktifitas fisik yang berat
dan mendadak
HIPOGLIKEMI AKUT
Perubahan fungsi
kognitif yg transien

HIPOGLIKEMI BERULANG
Kelainan kognitif
terakumulasi

IQ 
Symptoms of Hypoglycemia
Neuroglycopenic
Neuroglycopenic symptoms
symptoms
Global
Global
Difficulty
Difficulty thinking
thinking Irritability
Irritability
Confusion
Confusion Nightmares
Nightmares
Poor
Poor coordination
coordination Abnormal
Headache Abnormal or or belligerent
belligerent behavior
behavior
Headache ** Somnolence
Hunger
Hunger ** Somnolence
Weakness
Weakness ** Seizures
Seizures
Dizziness
Dizziness Coma
Coma
Faintness
Faintness
Drowsiness
Drowsiness
Focal
Focal
Blurred
Blurred or
or double
double vision
vision
Slurred speech
Slurred speech
Paresthesias
Paresthesias **
Tinnitus
Tinnitus
Hemiplegia
Hemiplegia
Autonomic
Autonomic (adrenergic
(adrenergic or
or neurogenic)
neurogenic) symptoms
symptoms
Tremor
Tremor
Nervousness
Nervousness
Palpitations
Palpitations
Diaphoresis
Diaphoresis
Anxiety
Anxiety or
or apprehension
apprehension
Pallor
Pallor

** These
These symptoms
symptoms are
are sometimes
sometimes classified
classified as
as autonomic.
autonomic.
 80

70
Cathecolamine and Glucagon Secretion
Cortisol and Growth Hormone Secretion
Plasma 60
Autonomic Symptoms
Glucose
Neuroglycopenic Symptoms and Cognitive Dysfunction
(mg/dl) 50

40 Lethargy

30 Seizures and Coma

20

10

0
Relationships among signs, symptoms, and counterregulatory hormone responses to
progressive hypoglycemia
 Glucose Homeostatis
Studies in subjects without diabetes who are made hypoglycemic
in a research setting reveals that when

• PG approaches 80 mg/dl, endogenous insulin secretion decreases

• PG declines to 65-70 mg/dl, glucagon and epinephrine

secretion rises

• PG declines to 60-65 mg/dl, growth hormone secretion rises

• PG declines to < 60 mg/dl, cortisol secretion rises

PG = plasma glucose
 Hierarchy of Responses
to Decreases in PG Concentrations

90 –
80 – Counter-regulation
70 –
Autonomic symptoms
60 –
50 – Neuroglycopenic symptoms
40 –
30 – Coma
20 –
10 – Permanent
0 – damage
Death
PG = plasma glucose

Gerich JE et al. Endocr Rev 1991;12:356-71.

 Glycemic thresholds & related
symtomatology
Glucose (mM)
2.5 3.0 3.5 4.0

↑ Glucagon

↑ Epinephrine

↑ Growth hormone

↑ Cortisol

↓ Cognition
Symptoms

40 50 60 70
Glucose (mg/dL)
Arterialized (green) and venous (blue) glycemic (mean ±SE) threshold for symptoms of
hypoglycemia and impairment
Arterialized (green) and venousof(blue)
cognitive function
glycemic during
(mean decrements
±SE) in serum
threshold for glucose
symptoms of in
normal humansand
hypoglycemia from two independent
impairment studies
of cognitive function during decrements in serum glucose in
PENCEGAHAN
• Monitor yang ketat
• OHO gol sekretagog insulin

 Dosis !
 Jadwal pemberian
 OHO yang beredar di Indonesia
Dosis
Dosis Pemberian
Pemberian
Obat
Obat Ukuran
Ukuran tablet
tablet maksimal/hari
maksimal/hari sehari
sehari
Gol.
Gol. Sulfonilurea
Sulfonilurea
Glibenclamid
Glibenclamid 2,5
2,5 dan
dan 55 mg
mg 15
15 mg
mg 1-2
1-2 kali
kali
Gliklasid
Gliklasid 80
80 mg
mg 240
240 mg
mg 1-2
1-2 kali
kali
Glikuidon
Glikuidon 30
30 mg
mg 120
120 mg
mg 2-3
2-3 kali
kali
Glipizid
Glipizid 55 mg
mg 20
20 mg
mg 1-2
1-2 kali
kali
Glipisid
Glipisid GITS
GITS 55 dan
dan 10
10 mg
mg 20
20 mg
mg 11 kali
kali
Glimepirid
Glimepirid 11 mg,
mg, 22 mg
mg dan
dan 33 mg
mg 66 mg
mg 11 kali
kali
Klorpropamid
Klorpropamid 100
100 dan
dan 250
250 mg
mg 500
500 mg
mg 11 kali
kali
Gol. Biguanid
Biguanid
Metformin
Metformin 500
500 dan
dan 850
850 mg
mg 2.500
2.500 mg
mg 1-3
1-3 kali
kali
Gol.
Gol. Inhibitor
Inhibitor
glukosidase
glukosidase alfa
alfa
Acarbose
Acarbose 50
50 dan
dan 100
100 mg
mg 300
300 mg
mg 33 kali
kali
PENGOBATAN
HIPOGLIKEMI RINGAN
• Makan / minum
mengandung karbohidrat

15 gram sukrosa
dalam cairan atau tablet

• Glukosa : * gel
* juice

Respons glikemik
hanya pada 42%
 HIPOGLIKEMI BERAT
Gangguan
kesadaran

Terapi parenteral :
dextrose 50% 25 cc I.V.

Sadar sesudah < 30 menit

Dilanjutkan infus dextrose 5-10%

selama efek OHO / insulin
 Take Home Message
• Komplikasi akut diabetes :
krisis hiperglikemi dan hipoglikemi
• Pengenalan dini komplikasi akut diabetes
• Penatalaksanaan intensif dan adekuat
• Rujuk Ke RS dengan fasilitas memadai