DDiabetic iabetic KKetoacidosisetoacidosis< DKA >< DKA >

HHyperglycemic yperglycemic HHyperosmolar yperosmolar NNonketotic onketotic SSyndromeyndrome

< HHNS >< HHNS >

By… Navinee VongsupathaiBy… Navinee Vongsupathai

&

DDiabetic iabetic KKetoacidosisetoacidosis< DKA >

BBy… Navinee Vongsupathaiy… Navinee Vongsupathai

Contents

DDefinition efinition EEtiologytiology PPathophysiologyathophysiology SSigns and igns and SSymptomsymptoms DDiagnosisiagnosis LLabab TTreatmentreatment CComplicationsomplications

DDefinitionefinition Diabetic ketoacidosis <DKA> is near complete deficiency of deficiency of

insulin and elevated levels of elevated levels of stress hormones Glucagon Cathecolamine Cortisol Growth hormone

DKA : acute metabolic complication of diabetes characterized by HyperglycemiaHyperglycemia HyperketonemiaHyperketonemia Metabolic acidosisMetabolic acidosis

DDefinitionefinition

DKA is a life-threatening complicationlife-threatening complication in Pt. with untreated DM (chronic high blood sugar or hyperglycemia).

DKA occurs mostly in type 1 DMtype 1 DM DKA is less common in type 2 DM, but it may occur in situations of

physiologic stress.

Pts. with new undiagnosed Type 1 DM frequently present to hospitals with DKA

EEtiologytiology

Precipitates DKAPrecipitates DKA -- > 5I’ s 5I’ s 1.1. Insulin deficiencyInsulin deficiency c relative or absolute increase in

glucagon<Inadequate insulin administration>

2.2. InfectionInfection or Inflammation < pneumonia, UTI, gastroenteritis, sepsis>

3.3. IschemiaIschemia or Infarction < cerebral, coronary, mesenteric, peripheral>

4.4. Intra-abdominal processIntra-abdominal process <pancreatitis, cholecystitis>

5.5. Iatrogenesis Iatrogenesis Drug < glucocorticoids,cocaine>

PPathophysiologyathophysiology

1. HyperglycemiaHyperglycemia : gluconeogenesis, glycogenolysis ,↓glucose uptake into cell <underutilization>

2. KetosisKetosis : lipolysis, ketogenesis , ↓ Peripheral tissue uptake ketone -- >ketonemia

3. HypertriglyceridemiaHypertriglyceridemia : ↑free fatty acid

4. Osmotic diuresisOsmotic diuresis : hyperglycemia -- > renal loss glucose, Na & K -- >electrolyte imbalance

5.. Volume depletionVolume depletion : hyperglycemia, glucosuria & osmotic diuresis -- >dehydration

SSigns and igns and SSymptomsymptoms

Initial symptoms of DKAInitial symptoms of DKA Anorexia, nausea, vomiting, abdominal pain Polyuria, polydipsia Dehydration -- > dry mucous membranes, tachycardia,

hypotension Alterated mental function-- > somnolence, stupor,coma Fever is not a sign of DKA -- >signifies underlying infection

Classic signs of DKAClassic signs of DKA Kussmaul ‘ s respirationsKussmaul ‘ s respirations <deep> to compensate for metabolic

acidosis with acetone odor on Pt. breath

LLabab

การตรวจทางห้องปฏิ�บั�ต�การเบั��องตน

1. Glucose & ketone in serum & urine

2. Serum electrolyte, BUN, Cr, Ca, PO4

3. Blood gas : capillary or arterial blood gas

4. EKG : hypo/ hyperkalemia5. CBC UA

การตรวจเพิ่��มเต�ม เม��อม�ข้อบั�งชี้��

1. Hemoculture

2. Urine culture

3. Throat swab culture

4. CSF culture

5. Chest x-ray

6. Omission of insulin

7. Physical or emotional stress ฯลฯ

DDiagnosisiagnosis

1.1. Serum glucose > 300 mg/dlSerum glucose > 300 mg/dl < euglycemic DKA-- > pregnancy, alcolhol drinking, stravation >

2.2. Acidosis : serum HCO3 < 15 mEq/ml or pH < 7.25Acidosis : serum HCO3 < 15 mEq/ml or pH < 7.25 < wide anion gap: >15 mEq/L> severity of DKA Mild : HCO3 > 15-18 mq/L & pH > 7.3 Moderate : HCO3 10-15 mq/L & pH 7.1-7.3 Severe : HCO3 < 10 mq/L &

pH < 7.1

3.3. Ketone : positive ketone in urine and / orKetone : positive ketone in urine and / or sermserm

TTreatmentreatment

Confirm Dx : ↑ BS, positive serum ketone, metabolic acidosis Admit Assess

Serum electrolyte : K, Na, Mg, Cl, HCO3, PO4 Acid-base status : pH, H CO3, Pco2 Renal function : creatinine, urine output

Replace fluid Administer regular insulin/ RI Assess patient

What precipitated the episode Initial appropriate work up

TTreatmentreatment

Measure capillary glucose every 1-2 hr/ E’lyte, anion gap every 4 hr for first 24 hr

Monitor BP, PR, respiration, mental status, fluid intake/output every 1-4 hr

Replace K

Continue above until Pt. stable

Administer intermediate or long – acting insulin as soon as Pt. eating

/ overlap in insulin infusion & subcutaneous injection.

Replace fluidReplace fluid

DKA : volume & Na depletion 0.9%NaCl or NSS0.9%NaCl or NSS -- > 1 L/hr in 1-3 hr <5-10 mL/kg/hr> then 0.45% NaCl or Nss/2-0.45% NaCl or Nss/2-- > 150-300 mL/hr

Pt. Na >150 mEq/L-- > NSS/2 Pt. euglycemic DKA -- > 5% D/NSS/2

Severe DKA volume depletion~ 5-6 L ,Na ~ 500 & Cl ~ 350 mEq

When BS < 300 -250 mg/dlBS < 300 -250 mg/dl change to 5%DN/2 5%DN/2 80-100 ml/hr

<Severe dehydration add NSS/2 >

Replace fluidReplace fluid

Adequate Fluid replace : ↑plasma volume ↑urine output ↑absorb/action insulin ↓release counter-regulatory hormone

Fluid replace : 50 % of volum in 6 hr & 50% in 24 hr Measure BP, PR, urine out put, E’ lyte, crepitation -- > pulmonary

edema

AAdminister dminister rregular egular iinsulinnsulin RI -- > ↓blood sugar , inhibit ketone production

low dose intramuscular insulin injection ( IMIII ) low dose continuous intravenous insulin infusion ( CIII )

AAdminister dminister rregular egular iinsulinnsulin low dose continuous intravenous insulin infusion low dose continuous intravenous insulin infusion

RI 10 U (0.1 U/kg) iv-- > RI 5-10 U/hr (0.1 U/kg/hr) -- > RI control BS decrease 75-100 mg/dl/hr

When BS 250-300 mg/dl change iv -- > 5% or 10% D/NSS/2 iv 80-100 ml/hr

ป้�องกั�นมิ�ให้�เกั�ด hypoglycemia & มิ�ให้�BSลดลงเร็�วและมิากัเกั�น -- > brain edemaโดยเฉพาะในเด�กั

RI in NSS conc. 1 u/ml กั�อน drip RI จะต้�องป้ล�อยRI ที่ !ผสมิแล�วที่�$งออกัไป้ต้ามิสายน&$าเกัล'อ

ป้ร็ะมิาณ 100 ml เพ'!อให้� RI จ�บกั�บผน�งสายน&$าเกัล'ออย�างเต้�มิที่ ! จะช่�วยให้�ได�ร็�บRI ในอ�ต้ร็าที่ !ต้�องกัาร็

AAdminister dminister rregular egular iinsulinnsulin

low dose continuous intravenous insulin infusion low dose continuous intravenous insulin infusion

BS decrease to 250-300 mg/dl in 4-6 hr

But acidosis improve ( HCO3 > 18 mEq/L ,pH > 7.3 ) in 8-12 hr

When BS 250-300 mg/dl -- > continue drip RI 3-4 hr + 5% or10% D/NSS/2 for control acidosis

HCO3 > 18 mEq/L-- >↓ RI 2-3 u/hr

AAdminister dminister rregular egular iinsulinnsulin

low dose continuous intravenous insulin infusionlow dose continuous intravenous insulin infusion

When can control BS, acidosis is resolve, Pt stable& eating -- > RI sc ac

Pt. should have continue RI ~24-48 hr until control BS ,

acidosis & improve precipitate DKA-- >change RI -- >intermediate-acting insulin ( NPH )

Rapid change RI to NPH -- >recurrence DKA

AAdminister dminister rregular egular iinsulinnsulin low dose intramuscular insulin injectionlow dose intramuscular insulin injection

RI 10 U iv & 5-10 U im -- >then RI 5-10 U im q 1 hr ↓BS 75-100 mg/dl/hr or ↓BS ~50 % in 4-6 hr

BS < 300 mg/dl -- > RI 5-10 U sc q 4-6 hr & 5% or10% D/NSS/2

ว�ธี น $เป้,นว�ธี ที่ !ได�ผลด สะดวกั และเห้มิาะส&าห้ร็�บกัาร็ร็�กัษาผ.�ป้/วยที่ !ร็ �บไว�ในห้อผ.�ป้/วยที่�!วไป้

ข้�อจ&ากั�ด คื'อ ผ.�ป้/วยที่ !มิ ภาวะคืวามิด�นเล'อดต้&!า ห้ร็'อกัาร็ไห้ลเว ยนล�มิเห้ลวจะมิ กัาร็ด.ดซึ4มิอ�นส5ล�นที่ !ฉ ดเข้�ากัล�ามิเน'$อไมิ�ด

PPotassium otassium SSupplementupplement

Moderate to severe DKA loss K~ 300-1,000 mEq or 3-5 mEq/kg

Rx :RI ,iv fluid -- > K shift in cell, loss K in urine-- > hypokalemia < cardiac arrhythmia ,muscle weakness >

K supplement -- >urine > 40 ml/hr , k< 5.5 mEq/L, EKG normal K < 3 : KCl 30 mEq/hr K < 3-4 : KCl 20 mEq/hr K < 4-5 : KCl 15 mEq/hr K < 5-6 : KCl 10 mEq/hr K > 6 : not corrected K

NaHCO3NaHCO3

NaHCO3 for Rx acidosis not recommence Randomized trail-- >NaHCO3 in Pt. DKA pH 6.9-7.1

not benefit for change biochemistry in plasma & CSF Because metabolic acidosis will improve when

appropiate replace fluid & RI

S/E NaHCO3 -- >metabolic alkalosis, hypernatremia, hypokalemia ,paradoxical CSF acidosis

NaHCO3NaHCO3

IndicationIndication pH < 7 mEq/L Shock Arrhythmia

DoseDose : 2 mEq/kg iv in 2 hr

MMonitoronitor

In first 6 hr BP, PR, RR, Mental status-- > q 15 min – 1 hr skin turgor, plasma ketone,BS– q 1 hr Urine output, urine glucose, urine ketone -- > q 1 hr E’lyte, BUN,Cr-- > q 4 hr

Long term F/U K supplement 7-10 day DM type 1 continue use insulin Advice control BS < 300 mg/dl

ข้อผิ�ดพิ่ลาดท��พิ่บับั�อยในการร�กษาข้อผิ�ดพิ่ลาดท��พิ่บับั�อยในการร�กษา DKADKA กัาร็ให้� iv fluid ไมิ�เพ ยงพอ -- > BS ลดลงช่�าห้ร็'อไมิ�ลดลง กัาร็ให้� insulin ไมิ�ต้�อเน'!อง เน'!องจากัร็อผลกัาร็ต้ร็วจ BS

ร็ายงานล�าช่�าห้ร็'อละเลยกัาร็ต้�ดต้ามิผล -- > BSลดลงช่�าและภาวะmetabolic acidosisย�งคืงมิ อย.�

ห้ย5ดกัาร็ให้� insulin อย�างต้�อเน'!อง -- > DKA ข้4$นซึ&$าได�อ กั

ไมิ�เป้ล !ยนเป้,น 5%DN/2 เมิ'!อ BS 250-300 mg/dl และย�งให้� insulin -- > hypoglycemia

ข้อผิ�ดพิ่ลาดท��พิ่บับั�อยในการร�กษาข้อผิ�ดพิ่ลาดท��พิ่บับั�อยในการร�กษา DKADKA ไมิ�ป้ร็�บ insulin เมิ'!อ BS < 250 mg/dl -- > hypoglycemia

ไมิ�ให้� K / ให้�ไมิ�เพ ยงพอ --- > hypokalemia, arrhythmia

กัาร็ให้� NaHCO3 โดยไมิ�จ&าเป้,นห้ร็'อมิากัเกั�นไป้ -- > เกั�ดภาวะแที่ร็กัซึ�อนซึ4!งที่&าให้�ผ.�ป้/วยมิ อากัาร็เลวลงได�

เป้ล !ยนจากั RI เป้,น NPH เร็�วเกั�นไป้ -- >DKA เกั�ดข้4$นซึ&$า

ไมิ�ได�ห้าและและร็�กัษาprecipitating cause-- > ผ.�ป้/วยไมิ�ต้อบสนองต้�อกัาร็ร็�กัษาเที่�าที่ !คืวร็ห้ร็'อที่&าให้�ผ.�ป้/วยมิ อากัาร็เลวลง

CComplicationomplication

Aspirate in Pt unconciouss-- > retain NG

Deep vein thrombosis จากัภาวะ hypercoagulability Disseminated intravascular clotting

Rhabdomyolysis-- > renal failure

Adult respiratory distress syndrome/ ARDS-- >pt < 50 yr Subclinical brain edema

HHyperglycemic yperglycemic HHyperosmolar yperosmolar NNonketotic onketotic SSyndromeyndrome

<HHNS><HHNS>

By… Navinee VongsupathaiBy… Navinee Vongsupathai

Hyperglycemic Hyperosmolar Hyperglycemic Hyperosmolar Nonketotic SyndromeNonketotic Syndrome Contents

DDefinition efinition EEtiologytiologyPPathophysiologyathophysiologySSigns and igns and SSymptomsymptomsDDiagnosisiagnosisLLababTTreatmentreatmentCComplicationsomplications

DDefinitionefinition

Extreme hyperglycemia < without ketoacidosis >

Hyperosmolality

Alteration of mental status

EEtiology & tiology & PPathophysiologyathophysiology

EtiologyEtiology Insulin deficiency + inadequate fluid intake

<dehydration> Precipitate same as DKA

PathophysiologyPathophysiology Occur in type 2 DM Hyperglycemia-- > osmotic diuresis-- >prerenal

azotemia-- >↑glucose

CClinical manifastationslinical manifastations

Polyuria, thirst Altered mental state <lethargy to coma>

The prototypical pt midly diabetic, elderly with a several week hx of poluria,

weight loss, deminished oral intake

DDiagnosisiagnosis

↑serum glucose > 600 mg/dl ↑serum osmolality > 350 mOsm/L No ketoacidosis ↑BUN ,Cr

Na ↑↓ depending on degree of hyperglycemia & dehydration

PseudohyponatremiaPseudohyponatremia : corrected Na -- > add 1.6 meq to measured Na for each 100 mg/dl rise in serum glucose

TTreatmentreatment Aggressive hydration

2-3 L of 0.9 NSS or 1/2NSS over first 1-3 hr Calculate free water deficit ~ 8-10 L should be resolved over the

next 1-2 day -- > 0.45NS initially then 5%DW

K repletion is usually necessary

BS may drop with hydration alone But Low-dose insulin is usually required RI 5-10 U iv -- >then 3-7 U/hr

RReferenceseferences

Harrison’s 15th Edition Pocket Medicine 2nd Edtion www.thaiendocrine.org/guidline www.chatlert.worldmedic.com

THE THE ENDEND

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