Penatalaksanaan Terkini Kegawatdaruratan pada Diabetes
Sarwono Waspadji
Pusat Diabetes dan Lipid,
Divisi Metabolik-Endokrin, Departemen Ilmu Penyakit Dalam,
FKUI / RSUPN Cipto Mangunkusumo,
Jakarta
Diabetic ComplicationsDiabetic Complications
• Diabetic Ketoacidosis = DKA• Hyperosmolar Hyperglycemia Nonketoric Coma = HHNC
• Diabetic Ketoacidosis = DKA• Hyperosmolar Hyperglycemia Nonketoric Coma = HHNC
Retinopathy Nephropathy
Neuropathy
Retinopathy Nephropathy
Neuropathy
MacroangiopathyMacroangiopathy
Chronic :Chronic :Acute Acute
MicroangiopathyMicroangiopathy
CADPVD
Stroke
CADPVD
Stroke
• Hypoglycemia
• Metabolic Decompensation
Sebab Kesadaran Menurun pada Diabetes MelitusSebab Kesadaran Menurun pada Diabetes Melitus
Ketoasidosis DiabetikHiperosmolar non KetotikAsidosis Laktat
HipoglikemiaSebab Lain - Trauma
- Obat - Penyakit Lain :
Stroke Koma hepatik Uremik
Ketoasidosis DiabetikHiperosmolar non KetotikAsidosis Laktat
HipoglikemiaSebab Lain - Trauma
- Obat - Penyakit Lain :
Stroke Koma hepatik Uremik
Diagnosis Banding Koma Glukosa Keton Hipervent. Dehid. TD Kulit mg/d L
DKA >300 +s/d4+ ++ ++ N/ hngt
HONK >500 0 s/d+ 0 +++ N/ N
Hipoglik < 50 0 0 0 N lmb
Asidosis Laktat 20-200 trc s/d + +++ 0 Rnd hngt
Non N/ 0 s/d trc 0 s/d + 0 s/d + Variasi NMetab
HipoglikemiaSimtom:
Efek adrenergik alfa: sekresi insulin menurun, cerebral blood flow meningkatperipheral vasoconstriction
Efek adrenergik beta: glycogenolisis otot dan hatistimulasi release glukagonlipolisisuptake glukosa otot menurunincrease c.o.p, cerebral flow
Efek adrenomedullary discharge of Catecholamineaugmentasi efek adrenergik alfa dan beta
Gejala neuroglikopenik, gejala adrenergikHipoglikemia kronik berkepanjangan - demensia
Kadar Glukosa Darah dan Gejala Hipoglikemik Akut
g 72luk 54o sa 36
d a 18rah
................................................................. Neuroglikopenia Disfungsi Kognitif ringan
................................................................ Aktivasi gejala Keringat autonomik Gemetar ..................................... Berdebar ...... Neuroglikopenia berat Kejang ............................................................... Koma Waktu
Diagnosis Relatif mudah: pemeriksaan GDTrias Whipple:
Keluhan dan gejala hipoglikemia s/d kesadaran menurun, Kadar Glukosa < 45 mg/dL (pada wanita dapat < 30 mg/dL), Bangun kembali setelah diberikan glukosa
Perlu pemantauan yang lama jika pasien memakai obat long acting
Jika hipoglikemia berkelanjutan dapat menyebabkan kerusakan otak permanen, demensia
Respons Perubahan Hormonal pada Hipoglikemia:Penurunan sekresi insulinPeningkatan katekolamin dan epinefrinPeningkatan sekresi glukagonPeningkatan sekresi kortisolPeningkatan hormon pertumbuhan
Penatalaksanaan HipoglikemiaRingan: Berikan gula murni (bukan pemanis) yang
cukup sampai keluhan hilang Pastikan pemberian makanan / kalori cukup
untuk selanjutnya, terutama jika OAD long acting
Berat: Berikan glukosa 40 % IV sampai pasien sadar Berikan infus rumatan D10 6-8 jam perkolf cek glukosa darah setiap jam
jika < 100 mg/dL berikan kembali bolus D40Jika sudah 2 kali berturut-turut >100 mg/dL, setiap 2 jamJika sudah 2 kali berturut-turut > 100 md/dL, setiap 4 jam,dst sampai yakin bahwa kadar glukosa darah stabil aman
Perhatikan obat hipoglikemik yang dipakai:Obat kerja panjang, pemantauan dapat lama, berhari
Perhatikan pula fungsi ginjal dan hati dan usia pasien
Oral Antidiabetic Agents: side effects
TZDs
Met
form
in
Insu
lin
secr
etag
ogues
Risk of hypoglycaemia
Weight gain
–
–
–
–
Gastrointestinal side-effects
–
–
–
Adapted from DeFronzo RA. Ann Int Med. 1999; 131: 281–303.
-glu
cosi
dase
inhib
itors
*Observed in patients with renal impairment
Oedema
Lactic acidosis –
–
*
–
–
–
–
Anaemia – –
Principles in Selecting Antihyperglycemic Interventions
• Effectiveness in lowering blood glucose• Extraglycemic effect that may reduce
longterm complications• Safety profile• Tolerability• Ease of use• Cost
Nathan DM et al. Clinical Diabetes. 2009; 27 (1): 4-16
Diagnosis Type 2 DMDiagnosis Type 2 DM
Lifestyle changesLifestyle changes
A1C (%)* A1C (%)*
6.5-76.5-7 7-87-8 8-108-10
Oral CombinationOral# :•SU•Metformin•AGI•TZD•MeglitinidesSpecific condition:•Short/Rapid-acting Insulin analog•Pre-mixed Insulin analog
Oral CombinationOral# :•SU•Metformin•AGI•TZD•MeglitinidesSpecific condition:•Short/Rapid-acting Insulin analog•Pre-mixed Insulin analog
Monotherapy* :•Metformin•AGI•TZDSpecific Condition:•SU •Meglitinides•Short/Rapid-actingInsulin analog
Monotherapy* :•Metformin•AGI•TZDSpecific Condition:•SU •Meglitinides•Short/Rapid-actingInsulin analog
Combination Oral+Insulin :•Metformin•TZD•SU•Long-acting Insulin•Short/Rapid-acting Insulin analog•Pre-mixed Insulin analog•NPH•Other Combination
Combination Oral+Insulin :•Metformin•TZD•SU•Long-acting Insulin•Short/Rapid-acting Insulin analog•Pre-mixed Insulin analog•NPH•Other Combination
>10>10
Insulin Therapy:•Short/Rapid-acting Insulin analog•NPH or Long-acting Insulin•Pre-mixed Insulin analogIn selected Patients with A1C> 10% OHO Combination might be effective
Insulin Therapy:•Short/Rapid-acting Insulin analog•NPH or Long-acting Insulin•Pre-mixed Insulin analogIn selected Patients with A1C> 10% OHO Combination might be effectiveTarget
AchievedTarget
AchievedTarget
not Achieved
Targetnot
Achieved
TargetAchieved
TargetAchievedTarget
AchievedTarget
Achieved
TargetAchieved
TargetAchieved
Targetnot
Achieved
Targetnot
Achieved Targetnot
Achieeved
Targetnot
Achieeved
Targetnot
Achieved
Targetnot
AchievedIntensificationTherapy OR
IntensificationTherapy OR
ContinueTreatmentContinue
Treatment
ContinueTreatmentContinue
Treatment IntensificationTherapy OR
IntensificationTherapy OR Continue
TreatmentContinue
Treatment IntensificationTherapy OR
IntensificationTherapy OR
ContinueTreatmentContinue
Treatment
Intensification of Insulin Treatment
Basal+bolus
Intensification of Insulin Treatment
Basal+bolus
Algorithm for Management of Type 2 DM without Metabolic Decompensation Indonesian Society of Endocrinology 2007
ContinueContinue
<6.5<6.5
Blood Glucose Monitoring (FPG, PPG, Bed time)
*surrogate average blood glucosemight be used
Management of HyperglycemiaIn PatientsGeneral Principles:
Maximal blood glucose control, avoiding hypoglycemia Meticulous, Prudent, IndividualizedManagement of T2DM synchronized with other disease management
In critically ill patients, more over in metabolic decompensation, the blood glucose target should be more aggressive and achieved quicker
Sasaran Glukosa darah yang dianjurkan
Pasien Tidak Kritis : Senormal mungkin(110 – 180 mg/dL)Insulin mungkin diperlukanSedekat mungkin dengan 130 mg/dL
Pasien Kritis: Senormal mungkin (110 – 180 mg/dL)Umumnya memerlukan insulinSedekat mungkin dengan 110 mg/dL
* Beberapa Institusi mungkin menganggap nilai ini terlalu over agresif karena kepedulian akan risiko hipoglikemia
A D A Clinical Practice RecommendationDiabetes Care. 2007;3(suppl 1): S 32-33
The Nice-Sugar StudyICU setting 3 or more consecutive days
Intensive (81-108 mg/dL)Conventional (<180 mg/dL)Outcome mortality at 90 days
3054 intensive control vs. 3050 conventional Similar characteristic baselinePrimary outcome available for 3010 and 3012 respectively
829 (27.5 %) mortality in intensive control, OR 1.14751 (24.9%) mortality in conventional group
Severe hypoglycemia (< 40 mg/dL)206 (6.8%) in intensive control15 (0.5 %) in conventional group
The NICE Sugar study investigators. Intensive vs. conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283-97
Blood Glucose TargetCritically ill surgical patients: as normal as possible
(110 – 140 mg/dL)*Insulin is needed, IV protocolClose to 110 mg/dL (A)
Critically ill non surgical pts: as normal as possible (110 – 140 mg/dL)*Insulin is needed, IV protocolKeep BG < 140 mg/dL (C)
Non critically ill: as normal as possible, no specific goalsInsulin is preferredFBG <126 mg/dL, Random BG<180-200 mg/dL (E)
* Some institutions might considered this blood glucose target as over aggressive due to their cautious attitude toward hypoglycemia
A D A Clinical Practice RecommendationDiabetes Care. 2009;32(suppl 1): S 32-33
Pemantauan kadar glukosa darah harus cermat
Hyper-glycemia Acidosis
Ketosis
DKA
Kitabchi and Wall
Hyperglycemia states•DM•HHNC •IGT•Stress
Metabolic Acidosis states•Lactic acidosis•Hyperchloremic acidosis•Salicylism
•Uremic acidosis•Drug-induced acidosis
Ketotic states•Ketotic hypoglycemia•Alkaholic ketosis•Starvation ketosis
DKA Episode and Mortality Rate at Dr. Cipto Mangunkusumo Hospital,
Jakarta
Year Number of Cases Mortality rate %
1983-84 (9 months) 14 31,41984-88 (48 months) 55 401995 (12 months) 17 -1997 (6 months) 23 18,71998-99 (12 months) 37 512002 (5 months) 39 15
Pathogenesis of DKA and HHNC
HHNCDKA
Precipitating Factors of DKA & HHNC Infection Cerebro vascular accident Pancreatitis Myocardial infarction Trauma Medication Newly diagnosed type 1 diabetes Discontinuation of or inadequate insulin Substance abuse Not found
Clinical Features of DKA
• Abdominal pain• Leg cramps• Nausea and
vomiting• Confusion and
drowsiness• Coma
• Polyuria and nocturia
• Weight loss• Weakness• Blurred vision• Kussmaul
respiration
DKA HHNC
HHNC
HHNC
Principal Management of DKA and HHNC
Hour Hydration Insulin K+Correction HCO3- correction
0 guyur 50 mEq per If pH• guyur six hour <7 7-7.1
>7.1• guyur Start hour 2
iv bolus iv, Cont by infusion
dst dst dst
Hour Hydration Insulin K+Correction HCO3- correction
0 guyur 50 mEq per If pH• guyur six hour <7 7-7.1
>7.1• guyur Start hour 2
iv bolus iv, Cont by infusion
dst dst dst
Management of DKA at Cipto Mangunkusumo Hospital, Jakarta
Management of DKA at Cipto Mangunkusumo Hospital, Jakarta
A B C D EA B C D E
Penatalaksanaan Ketoasidosis Diabetik
* 1 jam 2 kolf, 1 jam 1 kolf, dst * Na Cl Fisiologis * 1/2 N, 2A - Kalau Na > 150 mek/l
1. Rehidrasi Cepat
2. Insulin
Bolus 10 U IV. G.D setiap jamDrip 5 U/jam sampai g.d. < 200 mg/dl - D5 %Drip 2,5 U/jam sampai g.d. stabil 200 - 300 mg/dlDrip 1 U/jam + sliding scale g.d. tiap 4 jam Dosis terbagi 3-4 kali sehari
3.Kalium < 3,5 mek/L -- 50 mek/L3,5 - 5 mek/L -- 25 mek/L>5 mek/L -- 0
4. Na HCO3 pH < 7 - 7,15. Faktor Presipitasi
***Dosis Kecil 5 U IM *** Pemantauan dengan Urin
Suhendro 2008Pengukuran asam laktat perlu pada pengelolaan KADSerum laktat > 4 mmol/L petanda prognostik burukJika disertai kesadaran menurun prognostik buruk
Perlu pengelolaan yang ketat sejak awalPasang CVP segeraHidrasi dicapai dengan lebih cepat
Prevention (1)• Better access to medical care
– Intensive patients education– Effective communication 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
Peran Dokter UmumPencegahan terjadinya Hiperglikemiadengan mengelola DM sebaik-baiknya
mencegah komplikasi kronik mencegah komplikasi akut DKAmenghindari komplikasi hipoglikemia
Jika menjumpai pasien tersangka komplikasi akut:Pastikan bukan hipoglikemia, kalau ragu,
jangan takut memberikan D40 Jika bukan hipoglikemia, tetapi KAD:
Infus NaCl dan segera kirim ke RSJikalau ada (misal di RS primer)
dapat diberikan insulin, kemudian rujukMemerlukan perawatan yang cermat, segera
di RS dengan peralatan yang memadai
Hibiscus rosasinensis
Hatur Nuhun