ACUTE COMPLICATIONS OF DIABETES MELLITUS PATIENTSdr. Rensa, Sp.PDDepartemen llmu Penyakit Dalam- FK UNIKA Atma Jaya

OUTLINESDiabetic Ketoacidosis (DKA)Hyperglicemic Hyperosmolar Syndrome (HHS)Hypoglicemia

DIABETIC KETOASIDOSIS(DKA)

KASUSPasien, Wanita, usia 42 tahun.Keluhan utama (chief complain) : panas, sesak (Kussmaul), lemah, kesadaran menurun.Menderita DM sejak usia 26 tahun, Terapi injeksi insulin, jenis: Novomix 10-0-10 units, Lab: Gula Darah Sewaktu : 480 mg/dl, WBC 24.000, analisis gas darah (AGD) : pH 6.98, K 3.6 meq/l, Keton urine (+), Thorax foto : paru/jantung : normal Kesimp : KAD, DM tipe1

Foto Pasien

DIABETIC KETOACIDOSISMortality : 5-10% (western), Indonesia 10-20% higher in elderlyAvoidableAffects : T1DM, can accur in T2DM during severe intercurrents illness as a precipitating factors

PRECIPITATING FACTORS

Infections 28%New cases of IDDM 10%Treatment errors 13%Miscellaneous 5%Myocardial infarction 1%No diagnosis established 43%

Source : John Pickup,Williams G, 39.0-39.23, 1997

KETOACIDOSIS (DEFINITION)Source : Alberty, 1974Severe uncontrolled diabetes requiring emergency treatment with insulin and intravenous fluids and with a blood ketone body (acetone, acetoacetate and 3-OH butyrate) concentration of > 5 mmol/l

KETOACIDOSIS (DEFINITION)Cardinal biochemical features : TRIAD hyperketonemia, metabolic acidosis and hyperglicaemia Metabolic acidosis : HCO3(-) concentration (arterial/cap) 15 mmol/l, Dehydration, defisit in fluid and electrolytes.significant ketosis (urine ketostix ++ or plasma ketostix + or more)Source : Diabetes Care 24(1),2001

PATHOGENESISIntercurrents illness raised concentration of catabolic counter regulatory hormone : glucagon, cathecolamines, cortisol, growth hormone

Relative deficiency of insulinHYPERGLICAEMIAKETOACIDOSISDEHYDRATIONELECTROLIT DISBALLANCE

Metabolic decompensation

METAB. DECOMPENSATION(HYPERGLICAEMIA, KETONEMIA)HYPERGLICEMIA Increased glucose production (hepatic glycogenolysis, gluconeognesis,renal gluconeognesis) Reduced glucose disposal (by periph. tissue : muscle, fat)

LIPOLYSIS FFA, NEFA keton bodies (OH butyrate, acetoacetate, acetone)

Ins deficiency (abs/rel) + stress hormone stimulates lipolysis acetyl CoA production : incr lipolysis Ac CoA keton bodies synthesis (adapt. QJ Med 2004,97:773-780)Fig : Pathofisiology Keton Bodies production

CLINICAL FEATURES OF DKAPoliuriaWeight lossWeaknessBlurred visionAcidotic (Kussmaull) respirationAbdominal pain (sp. in children)Leg crampsNausea and vomitingConfusion and drowsinessComa (10% of cases)

DIAGNOSISDKA : medical emergency !Hyperglicaemia glucose oxidase reagent stripUrine (ketones) : keton testing (acetest tab/ketostix dip sticks), plasma keton body concentration (ketostix or acetest)Venous blood : glucose, urea, electrolytes, full blood countBGA (blood gas analysis)

DIAGNOSTIC CRITERIA FOR DKA AND HHS DKA HHS Mild moderate severePG (mg/dl) > 250 >250 >250 >600Arterial pH 7.25-7.30 7.0-7.24 7.30HCO3(-) 15-18 10- 320Anin gap >10 >12 >12

LABORATORY TEST RESULTS AND DIFFERENTIAL DIAGNOSISLab test that would be routinely monitored in the setting of DKAHb, leucocyte, diff count.Glucose, electrolyte, BUN, creatinineChanges in Na,K,Cl,P,BUN,creatinineUraemic acidosisThe sine qua-none of DKA Acidosis (due to prod. and accum. of ketone), HCO3 < 10 meq/l anion gap > 14meq/L

ANION GAP

Most pts DKA: > 20 - < 40 mEq/L

Anion gap = sodium (chloride + bicarbonate)

TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS) FLUID AND ELECTROLYTES INSULIN OTHER MEASURES

FLUID AND ELECTROLYTESVolumes : usually 4-6 Litres /24 hFluids : isotonic salines, hypotonic (not more then 2-4 l) if Na >150mmol/l, D5 %if BG < 270 mg/dl (15 mmol/l) (simultane with saline if indicated), sodium bicarbonates if pH 5.5 mmol NO KCl*KCl to be added from 2nd litre onward TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS)

ASSESS NEED FOR BICARBONATE

pH < 6.9 NaHCO3, (100 mmol/l) in 400 cc H2O drips 200cc/hrs. Repeat adm every 2hrs until pH >7.0 and monitor K.pH 6.9-7.0 NaHCO3, (50 mmol/l) in 200 cc H2O drips 200cc/hrs. Repeat adm every 2hrs until pH >7.0 and monitor K.pH >7.0 NO HCO3- (bicarbonate)

Source : Diabetes Care 26(suppl1):S109,2003TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS)

POTASSIUMK /=3.3 meq/lK 5.0 meq/l : dont give K, but check every 2 hrsK 3.3 5.0 meq/l : give 20-30 meq/l / liter of IV fluid (2/3 KCl, 1/3 KPO4) keep serum K at 4.5 meq/l

Source : Diabetes Care 26(suppl1):S109,2003TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS)

FLUID AND ELECTROLYTESINSULINContinuous intravenous infusion.5-10 u/h (avrg 6 u/h) BG < 270 mg/dl (15 mmol/l) adjust rate (usually 1-4u/h) with D5 to maintain BG 90-180 mg/dl (5-10 mmol/l ) until pts eating again.Intramuscular injection20 u immediately IM, then 5-10 u/h untill BG fallen to 180-270 mg/dl (10-15 mmol/l), then change to 10 u/h SC untill pts eating again together with D5 infusionSource : Diabetes Care 26(suppl1):S109,2003TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS)

FLUID AND ELECTROLYTESINSULINOTHER MEASURESTight recordingSearch for and treat precipitating causeHypotension / dehidrationCVP monitoringNG tubeUrine cathetherECG monitoringCerebral edema : manitol, dexamethazone, brain imagingARDSThromboembolic complicationsConsider mechanical ventilation (to accelerate CO2 elimination)

TREATMENT (GUIDE TO INITIAL TREATMENT OF DKA IN ADULTS)

HYPOGLICEMIA

FREQUENCY OF HYPOGLYCEMIA

Type1 diabetesHypoglicemia is a fact of life for people with type1 diabetes.Many episodes of asymptomatic hypo.PG levels < 50-60 mg/dl, may be 10% of time 2 episode of symptomatic hypoglicemic per week.Severe hypo (at least temporary disabling) once a year.2-4% death due to hypoglicemia

Type2 diabetesDifficult to assess.During intensive therapy : 10-73 episode per 100 pts/years.Severe hypoglicemia about 10% of those in type 1 diabetes (even in aggressive ins th/).Major hypoglicemia in UKPDS : 2.4% metform groups, 3.3% SU and 11.2% insulin groups.DCCT : 65%

adapted : Cryer PE et al, Diabetes Care 2003, 26(6):1902, Cryer PE Diabetologia, 2002;45:937-48

HYPOGLYCAEMIC EPISODES IN ELDERLY DIABETIC PATS10/29 cases (34.48%)6 pats (20.68%) on OHA therapy, 4 (13.79%) on insulin therapy4 (13.79%) pats (half on insulin and half on OHA treatment) severe and need hospital admission.Astika N, et al. Geriatric div, Dept of Medicine, RSUP Denpasar 2007

HYPOGLYCEMIA(CLINICAL MANIFESTATION)Whipples triad Hypoglycemic symptom (+)Low PG (plasma glucose) concentrationSympt relief when PG raised

SYMPTOMS OF HYPOGLYCAEMIADivided into 2 categoriesNeurogenic (autonomic ) symptoms.Neuroglycopenic

SYMPTOMS OF HYPOGLYCEMIA(COMMON SYMPTS OF ACUTE HYPOGLYCEMIA IN DIABETIC PTS)Neurogenic / Autonomic cathecolamine release Sweating Pounding heart Shaking (tremor) Hunger Neuroglycopenic Confusion Drawsiness Speech dificulty Incoordination Atypical behaviourmalaise

SYMPTOMS OF HYPOGLYCAEMIANEUROGENIC / AUTONOMICAutonomic response due to : Falling BG and derangements of CNS functions.Neurogenic sympts : Catecholamine release : tachycardia, pallor, anxiety, tremulousness, sweating. Attenuated / absent in blocker th/, autonomic neuropathy and chr hypoglicemia,

SYMPTOMS OF HYPOGLYCAEMIANEUROGLICOPENIC SYMPTOMSNeuroglycopenic symptoms (neuro hypoglicemic sympts) due to CNS neuronal deprivation : confusion, lightheadedness, headache, aberrant behaviour, blurred vision, loss of consciousness, seizure

RISK FACTORS FOR SEVERE HYPOGLYCEMIAInsulin treatment regimen Intensified regimens and tight glycemic control High ins dosagesImpaired awareness of hypoglycemia Chronic (central autonomic failure) Acute (induced by proceeding hypoglycemia)Long duration of diabetesIncreasing age of ptsSleepExcessive alcohol consumption

TREATMENTPts conscious oral glucose (20-30 gr) or sucrosePts unconscious IV glucose 50% (30-50 ml), glucagon 1 ml/SC or IMCheck BG after 15-20 minConfirm recoveryNo recovery D5/D10 IVRecovery identify cause, re-educate, take measures to avoid hypoglycemia

GLUCAGON Dosis : 1mg, SC or IM or IV or intra nasal (spray)Act within minuts (IV > SC)Primary actions : hepatic glycogenolysis, stimulate insulin release (CI in SU induced hypoglycemia)SE : nausea, vomiting, head ache.

PREVENTIONPts educationFrequent SMBG (self monitoring blood glucose)Flexible insulin and other drug regimensIndividualized glycemic goalsProfessional guidance and support.

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