Diabetic EmergenciesDiabetic Emergencies

March 19, 2009March 19, 2009

Jennifer HughesJennifer Hughes

Mr. HMr. H 45 M with abdominal pain and feeling 45 M with abdominal pain and feeling

“unwell” x 10 days“unwell” x 10 days Presented to ED 1 week ago with Presented to ED 1 week ago with

abdominal pain, dx with Diabetes and abdominal pain, dx with Diabetes and started on Metformin.started on Metformin.

Pmhx: MI 1999 Pmhx: MI 1999 Labs at the time: 7.41/39/24Labs at the time: 7.41/39/24

– Na 122/K4.6/Cl 84/C02 18Na 122/K4.6/Cl 84/C02 18– Gluc 52Gluc 52– Urine ketonesUrine ketones

Progressively worse over the week, Progressively worse over the week, polydipsia, polyuric, increasing painpolydipsia, polyuric, increasing pain

ExaminationExamination

Thin, cacecticThin, cacectic Appears unwellAppears unwell Rapid breathingRapid breathing Decreased LOC/mild confusionDecreased LOC/mild confusion BP 130/75, P 120, sats 95%, afebrile, BP 130/75, P 120, sats 95%, afebrile,

RR 24. BG “high”RR 24. BG “high” Abdomen diffusely tender, Abdomen diffusely tender,

epigastrium ++, not peritonealepigastrium ++, not peritoneal

What do you do?What do you do?

LabsLabs

7.08/15/64/47.08/15/64/4 HB 188, WBC 15, platelets 169HB 188, WBC 15, platelets 169 BG 45BG 45 Na 135, K 3.0, Cl 99 Na 135, K 3.0, Cl 99 EKG – sinus tachEKG – sinus tach Cr 129Cr 129 ALP 127, ALT 69, bili 7, GGT 68ALP 127, ALT 69, bili 7, GGT 68 Lipase 2628Lipase 2628 Serum ketones smallSerum ketones small

VENOUS blood gasVENOUS blood gas Winter’s formulaWinter’s formula

– HC03 * 1.5 + 8 = pC02 (+/-2)HC03 * 1.5 + 8 = pC02 (+/-2)– Indicates adequate compensation in Indicates adequate compensation in

metabolic acidosismetabolic acidosis

D K AD K A

pH < 7.3pH < 7.3 Bicarb < 15 mmol/LBicarb < 15 mmol/L AG > 12AG > 12 Serum / urine ketonesSerum / urine ketones BG > 14 mmol/LBG > 14 mmol/L

Canadian Diabetic Association Guidelines 2008Canadian Diabetic Association Guidelines 2008

Are urine ketones good enough?Are urine ketones good enough?

Uses a nitroprusside reaction Good test for acetoacetate but NOT

betahydroxybutyrate DKA usually has a ratio

acetoacetate/betahyroxybutyrate of 1:3 but it can be 1:30

Rarely could have negative urine dip with very high ketonemia

Serum ketones = betahydroxybutyrate

How do you want to manage this How do you want to manage this patient?patient?

DKA ManagementDKA Management

ABCs but…ABCs but… Try not to intubate these patientsTry not to intubate these patients FluidsFluids PotassiumPotassium InsulinInsulin Look for underlying causeLook for underlying cause

FluidsFluids

Most important therapyMost important therapy Reduces glucose by dilution and Reduces glucose by dilution and

osmotic diuresisosmotic diuresis Can give PO fluidsCan give PO fluids 1-2 L NS at beginning1-2 L NS at beginning Once euvolemic and if Na is Once euvolemic and if Na is

normal/high – change to ½ NSnormal/high – change to ½ NS Once BG < 14 add D5W or D10W Once BG < 14 add D5W or D10W

Cerebral edemaCerebral edema Rare, 7/1000 episodes, 30% mortalityRare, 7/1000 episodes, 30% mortality Children under 5, new diagnosis DM with Children under 5, new diagnosis DM with

DKADKA Present with improving DKA and then Present with improving DKA and then

sudden deterioration sudden deterioration Pathophysiology Pathophysiology unknownunknown

– No clear link to fluids, ORNo clear link to fluids, OR– HypoxiaHypoxia– Volume depletionVolume depletion– Hyperosmolar stateHyperosmolar state– Initial glucoseInitial glucose– KetonesKetones

Cerebral EdemaCerebral Edema Case Control study in kids NEJM:Case Control study in kids NEJM: Negative trend in sodium (kids with Negative trend in sodium (kids with

cerebral edema often have lower Na)cerebral edema often have lower Na) Clinical associations with CEClinical associations with CE

Lower initial pCO2Lower initial pCO2 every decrease 7.8mm = RR 3.4 (1.9-6.3)every decrease 7.8mm = RR 3.4 (1.9-6.3)

Higher initial BUNHigher initial BUN every increase 3.2 = RR 1.7 (1.2-2.5) every increase 3.2 = RR 1.7 (1.2-2.5)

TherapeuticTherapeutic– Treated with HCO3 = RR 4.2 (1.5-12.1)Treated with HCO3 = RR 4.2 (1.5-12.1)

Glaser N. 2001, NEJMGlaser N. 2001, NEJM

TreatmentTreatment

– ABCABC– Elevate head of beadElevate head of bead– Hyperventilate (patient probably already Hyperventilate (patient probably already

doing this)doing this)– Mannitol: 0.2-1 g/kg over 30 minutesMannitol: 0.2-1 g/kg over 30 minutes– CT headCT head– Decrease IV rateDecrease IV rate– ICUICU

Best practiceBest practice

Reduce osmolality slowly (< 3 mmol/ Reduce osmolality slowly (< 3 mmol/ kg/ hr)kg/ hr)

Don’t allow plasma Na to fallDon’t allow plasma Na to fall No bicarbNo bicarb

PotassiumPotassium

Total body deficit of 3-5 meq/kgTotal body deficit of 3-5 meq/kg Every treatment for DKA will decr KEvery treatment for DKA will decr K

•K < 3.3 = NO INSULIN, give 40 K < 3.3 = NO INSULIN, give 40 meq/L, give po K. EKGmeq/L, give po K. EKG

•K 3.3-5.0 = 20-30 meq/L KCL K 3.3-5.0 = 20-30 meq/L KCL with NS and may start insulinwith NS and may start insulin

•K > 5.0 = EKG, start insulin, K > 5.0 = EKG, start insulin, recheck in 1 hourrecheck in 1 hour

InsulinInsulin

Treats the acidosis and ketosisTreats the acidosis and ketosis No benefit to bolusNo benefit to bolus Infusion Humulin R 0.1 mg/kg /hrInfusion Humulin R 0.1 mg/kg /hr Goal = drop glucose 3-4 mmol / hourGoal = drop glucose 3-4 mmol / hour

Double insulin rate if goal not achievedDouble insulin rate if goal not achievedCut insulin rate in half if decreasing too Cut insulin rate in half if decreasing too

quicklyquickly

BicarbonateBicarbonate

ConsiderConsider if ifpH < 7 (after 1 hour of hydration)pH < 7 (after 1 hour of hydration)hypotension, shock, comahypotension, shock, comasevere hyperkalemia with ECG changessevere hyperkalemia with ECG changes

Complications from Bicarb:Complications from Bicarb:Worsens CNS intracellular acidosisWorsens CNS intracellular acidosisshifts oxy-hemoglobin dissociation curve to shifts oxy-hemoglobin dissociation curve to

left – worsens oxygen release in tissuesleft – worsens oxygen release in tissuesdecreases serum Kdecreases serum Kmay produce alkalosis / dysrhythmiasmay produce alkalosis / dysrhythmias inhibits metabolism of ketonesinhibits metabolism of ketones? cerebral edema? cerebral edema

A final word on bicarbA final word on bicarb

Patients treated with bicarb do no Patients treated with bicarb do no better, and possibly worsebetter, and possibly worse

Even in severe DKA pH 6.9-7.1Even in severe DKA pH 6.9-7.1 It’s possible to manage DKA with It’s possible to manage DKA with

fluids and insulin alonefluids and insulin alone

Hyperglycemic Hyperosmolar Hyperglycemic Hyperosmolar Non-ketotic State Non-ketotic State

Hyperglycemia, hyperosmolarity, Hyperglycemia, hyperosmolarity, dehydration and decreased mental statusdehydration and decreased mental status

Spectrum of disease with DKASpectrum of disease with DKA Relative insulin resistance with poor renal Relative insulin resistance with poor renal

fxnfxn decreased renal clearance of glucosedecreased renal clearance of glucose Fluid shifts from ICF to ECFFluid shifts from ICF to ECF Fluid lost in osmotic diuresisFluid lost in osmotic diuresis Insufficient oral intake to compensate for Insufficient oral intake to compensate for

losseslosses

HHNKSHHNKS

Profound dehydration (8-12L)Profound dehydration (8-12L) Very high BG Very high BG BUN > 50BUN > 50 Serum osmoles > 350Serum osmoles > 350 No acidosis (bicarb > 15)No acidosis (bicarb > 15) No ketosisNo ketosis

Mr. MMr. M

45 M in code room at PLC restrained 45 M in code room at PLC restrained by 4 security guardsby 4 security guards

Extremely agitated, diaphoretic, Extremely agitated, diaphoretic, multiple contusions and laboured multiple contusions and laboured breathingbreathing

Family called EMS because he went Family called EMS because he went beserk and threw a chair across the beserk and threw a chair across the roomroom

CaseCase

After handcuffs were removed, pt After handcuffs were removed, pt had a focal seizure beginning in R had a focal seizure beginning in R hand and progressed to generalizedhand and progressed to generalized

Post-ictal: 120/80, 120, 24, 36.8Post-ictal: 120/80, 120, 24, 36.8 Lethargic, orientedLethargic, oriented R hemiparesis, R facial paralysis, R R hemiparesis, R facial paralysis, R

plantar extensionplantar extension BG 1.8 at time of seizureBG 1.8 at time of seizure

100cc D50W 100cc D50W 5 minutes later 5 minutes later patient’s neuro findings disappeared.patient’s neuro findings disappeared.

Hx: family physician placed him on a Hx: family physician placed him on a “diabetes” medication 2 weeks ago“diabetes” medication 2 weeks ago

Started on a drinking binge a few Started on a drinking binge a few days ago.days ago.

Manifestations of HypoglycemiaManifestations of Hypoglycemia

Catecholamine releaseCatecholamine release

TremorTremor TachycardiaTachycardia DiaphoresisDiaphoresis PiloerectionPiloerection AnxietyAnxiety HypertensionHypertension HAHA Dry mouthDry mouth HungerHunger NauseaNausea AnginaAngina

NeuroglycopeniaNeuroglycopenia

Blurred visionBlurred vision ParesthesiasParesthesias Loss of coordinationLoss of coordination Poor concentrationPoor concentration SomnolenceSomnolence Altered behaviourAltered behaviour HypothermiaHypothermia SeizuresSeizures HemiplegiaHemiplegia ComaComa DeathDeath

OHAsOHAs Sulfonylureas Sulfonylureas (insulin secretagogue)(insulin secretagogue)

– Glyburide (Diabeta), gliclazide (Diamicron)Glyburide (Diabeta), gliclazide (Diamicron)

Biguanides (inhibits gluconeogenesis)Biguanides (inhibits gluconeogenesis)– MetforminMetformin

Glitazones (Decreases insulin resistance by Glitazones (Decreases insulin resistance by increasing uptake into liver, adipose and skeletal increasing uptake into liver, adipose and skeletal muscle)muscle)– Rosiglitazone (avandia), pioglitazone (Actos)Rosiglitazone (avandia), pioglitazone (Actos)

Acarbose (Prandase)Acarbose (Prandase)– Prevents degradation of complex carbsPrevents degradation of complex carbs

Meglitinide (insulin segretagogue)Meglitinide (insulin segretagogue)– Repaglinide (Prandin)Repaglinide (Prandin)

SulfonylureasSulfonylureas

Main culprit in OHA hypoglycemiaMain culprit in OHA hypoglycemia T ½ 18-24 hoursT ½ 18-24 hours Requires 24 hours of monitoringRequires 24 hours of monitoring Often refractory to glucose Often refractory to glucose

administation – stimulates more administation – stimulates more insulin secretioninsulin secretion

Who gets hypoglycemia?Who gets hypoglycemia?

RF = overdose, elderly, renal disease, RF = overdose, elderly, renal disease, hepatic disease, multiple drugshepatic disease, multiple drugs

Precipitants in Diabetics:Precipitants in Diabetics:– EthanolEthanol– Propanolol (B-adrenergic antagonist)Propanolol (B-adrenergic antagonist)– SalicyclatesSalicyclates– Addison’sAddison’s– Malnutrition Malnutrition

Management of Mr. M Management of Mr. M

ABCsABCs Consider charcoalConsider charcoal FEED FEED IV D5*1/2NS at 150cc/hour to keep IV D5*1/2NS at 150cc/hour to keep

euglycemiceuglycemic With boluses of 2cc/kg of D50W (ie. 1 With boluses of 2cc/kg of D50W (ie. 1

amp)amp) Octreotide 50ug sc q6hOctreotide 50ug sc q6h

Dextrose, etcDextrose, etc

Po intake Po intake 1 amp D50W (25g glucose)1 amp D50W (25g glucose) Children: Children:

– D25W 0.5-1.0 g/kgD25W 0.5-1.0 g/kg– Neonates D10W Neonates D10W

Glucagon 1-2 mg IM/sc if no IV accessGlucagon 1-2 mg IM/sc if no IV access– 0.025-0.1 mg/kg children0.025-0.1 mg/kg children– Onset 10-20 minOnset 10-20 min– Duration 30-60 minDuration 30-60 min

OctreotideOctreotide

Synthetic somatostatinSynthetic somatostatin t ½ 72 mint ½ 72 min Inhibits B-cell insulin release stimulated by Inhibits B-cell insulin release stimulated by

glucoseglucose Fewer episodes recurrent hypoglycemiaFewer episodes recurrent hypoglycemia Lower dextrose requirements overallLower dextrose requirements overall 50 ug sc/IV q6h50 ug sc/IV q6h Few side effectsFew side effects

DispositionDisposition

Who needs admission?Who needs admission?

– Intermediate and long-acting insulinIntermediate and long-acting insulin– Persistent hypoglycemia with short Persistent hypoglycemia with short

actingacting– OHAs – sulfonyureas/meglitinideOHAs – sulfonyureas/meglitinide– Complicated Type 1 DM Complicated Type 1 DM – Overdoses/social factorsOverdoses/social factors– Hepatic/renal failureHepatic/renal failure

OHAs and IV contrastOHAs and IV contrast

55 yo F needs a CT Scan to diagnose 55 yo F needs a CT Scan to diagnose possible appendicitis. possible appendicitis.

On Metformin and Avandia for DMOn Metformin and Avandia for DM What do you do?What do you do?

– Risk of acute tubular necrosisRisk of acute tubular necrosis– Check renal functionCheck renal function– Hold Metformin 72 hours after until Cr Hold Metformin 72 hours after until Cr

checked againchecked again

Diagnosis and treatment of diabetic ketoacidosis and the Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Canadian Medical Assoication hyperglycemic hyperosmolar state. Canadian Medical Assoication Journal April 2003, vol 168(7). Journal April 2003, vol 168(7).

2008 Clinical Practice Guidelines. Canadian Journal of Diabetes 2008 Clinical Practice Guidelines. Canadian Journal of Diabetes 2008: Sept, vol 32 (1 Suppl).2008: Sept, vol 32 (1 Suppl).

American Diabetes Association Clinical Practice Guidelines. American Diabetes Association Clinical Practice Guidelines. Diabetes Care 2003; 26 (1 Suppl): S109-17Diabetes Care 2003; 26 (1 Suppl): S109-17

Glaser N. et al. Risk factors for cerebrel edema in children with diabetic ketoacidosis. NEJM 2001.

Viallon A. et al. Does bicarbonate therapy improve the management of severe DKA? Crit care med 1999: 27( 2690).

Boyle PJ et al. Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonyurea overdoses. J Clin Endocrin Metab 1993; 76: 752-756.