DKA

Diabetic KetoacidosisRamin Nazari, MD

Pediatric Critical Care Fellow

St. Christopher Hospital for Children

August 2012

Understand the pathophysiology of DKA Understand the management approach to

the patient with DKA Appreciate the complications that can occur

during treatment of DKA

Goals & Objectives

▶ DKA is a serious acute complications of Diabetes Mellitus.▶ Significant risk of death and/or morbidity especially with

delayed treatment.▶ The prognosis of DKA is worse in the extremes of age, with a

mortality rates of 5-10%. ▶ With the new advances of therapy, DKA mortality decreased

to < 2%. ▶ Before discovery and use of Insulin (1922) the mortality was

100%.

Introduction

DKA is characteristically associated with type 1 DM It also occurs in type 2 diabetes

Extreme stress Serious infection Trauma Cardiovascular Other emergencies

Epidemiology

Secondary to insulin deficiency, and the action of counter-regulatory hormones, blood glucose increases leading to hyperglycemia and glucosuria

Glucosuria osmotic diuresis water & Na loss

In the absence of insulin activity the body fails to utilize glucose as fuel and uses fats instead ketosis

Pathophysiology

‣ The excess of ketone bodies will cause metabolic acidosis, the later is also aggravated by Lactic acidosis caused by dehydration & poor tissue perfusion.

‣ Vomiting due to an ileus, plus increased insensible water losses due to tachypnea will worsen the state of dehydration.

‣ Electrolyte abnormalities are secondary to their loss in urine & trans-membrane alterations following acidosis & osmotic diuresis.

Pathophysiology

‣ Because of acidosis, K ions enter the circulation leading to hyperkalemia, this is aggravated by dehydration and renal failure.

‣ So, depending on the duration of DKA, serum K at diagnosis may be high, normal or low, but the intracellular K stores are always depleted.

‣ Phosphate depletion will also take place due to metabolic acidosis.

‣ Na loss occurs secondary to the hyperosmotic state & the osmotic diuresis

Pathophysiology

The dehydration can lead to decreased kidney perfusion and acute renal failure.

Accumulation of ketone bodies contributes to the abdominal pain and vomiting.

The increasing acidosis leads to acidotic breathing and acetone smell in the breath and eventually causes impaired consciousness and coma.

Pathophysiology

Signs and Symptoms Polyuria, polydipsia

Enuresis Deahydrtion

TachycardiaOrthostasis

Abdominal painNauseaVomiting

Fruity breathAcetone

Kussmaul breathing Mental status changes

CombativeDrunkComa

Risk factors Age <12 yrs

No first degree diabetic relative

Lower socioeconomic status

High dose glucocorticoids, atypical antipsychotics, diazoxide and some immunosuppresive drugs

Poor access to medical care

Uninsured

Hyperglycemia (> 200 mg/dL) ketones in the blood Blood pH below 7.3 Serum bicarbonate level below 15 mEq/L Venous pH <7.3 and/or bicarbonate <15 mmol/L

mild DKA pH <7.3 bicarbonate <15 moderate pH <7.2 bicarbonate <10 severe pH <7.1 bicarbonate < 5

Diagnosis

Diagnostic Studies in DKA Chemistry

Glucose > 200 Bicarbonate <15 Anion gap = (Na+) – (Cl- + HCO3

-) Frequently seen:

BUN/creatinine (dehydration) potassium sodium

Blood pH below 7.3 Serum acetones

Positive in DKA

Urinalysis Ketones (for DKA);

leukocyte esterase, WBC (for UTI)

CBC Leukocytosis (possible

infection) Amylase/Lipase

To evaluate for pancreatitis BUT, DKA by itself can also

increase them! EKG

Evaluate for possible MI

Laboratory Evaluation Blood glucose Electrolytes and osmolality Bicarbonate, lactate Calcium and ionized Ca, Mg, P BUN, creatinine Blood Gas CBC and hemoglobin A1c Blood beta hydroxybutyrate Urinalysis and urine for ketones If there is evidence of infection, culture:

blood, urine, throat, wound EKG for baseline evaluation of intracellular potassium status.

Treatment Monitoring Consider ICU admission for closer monitoring if:

Severe DKA (pH < 7.1 or < 7.2 in young child) Altered level of consciousness Under age of 5 years Increased risk for cerebral edema

Neurological status consider neuro checks q 1 hr How does the patient look TO YOU?

Goals of treatment of DKA intravascular volume expansion correction of deficits in fluids, electrolytes, and acid-base

status initiation of insulin therapy to correct catabolism,

acidosis Treatment is divided into 3 phases

treatment of ketoacidosis transition period continuing phase and guidance

Treatment

Fluid Therapy

Assume 10-15% dehydration Begin with a 10-20 ml/kg bolus of NS Replace calculated deficit evenly over 36 hours -

generally 1.5 x maintenance for the next several hours is appropriate

Do not exceed 40ml’s/kg in the initial 4 hours, or 4 L/m² in 24 hours

Double bag system NS at 1.5 x M until glucose below 300 mg/dl D10 NS to be mixed with NS to achieve desired

glucose concentration

Insulin Therapy

IV infusion with basal rate 0.1 U/kg/hr

No initial insulin bolus – it will decrease time to correction of the glucose, but does not alter the time to correction of acidosis

It may decrease the serum osmolality more rapidly than desirable

Ideal glucose decline is about 50-100 mg/hr

Continue insulin until urinary (blood) ketones are cleared

Potassium & Sodium Add potassium when K< 5 and with urination K >5.5 – no potassium in IVF K 4.5 – 5.5 – 20 meq/L K+ K <4.5 – 40 meq/L K+ K supplementation 20mEq/L K Acetate + 20mEq/L K Phosphate early replacement and frequent monitoring Pseudohyponatremia, add 1.6 mEq of Na to every 100mg/dL

of glucose above normal Expect that the Na+ level will rise during treatment If Na+ does not rise, true hyponatremia may be present (risk

of cerebral edema) and should be treated

Phosphate

Prevent depletion of RBC 2,3 DPG which will improve tissue oxygenation as acidosis is resolving

May be useful in patients with anemia, CHF, pneumonia, hypoxia

Ionized calcium is low, phosphorous should not be given

Bicarbonate

Bicarbonate should be used only when there is severe depression of the circulatory system or cellular metabolism

Not recommended unless pH <7.0, not even then, unless above true

Bicarbonate administration leads to increased cerebral acidosis HCO3

- + H+ = CO2 + H2O. Bicarbonate passes the BBB slowly CO2 diffuses freely exacerbating cerebral acidosis and cerebral depression

Infection Precipitates DKA Fever Leukocytosis can be secondary to acidosis

Shock If not improving with fluids r/o MI

Vascular thrombosis Severe dehydration Cerebral vessels Occurs hours to days after DKA

Pulmonary Edema Result of aggressive fluid resuscitation

Cerebral Edema First 24 hours

Complications

Major cause of death in childhood DKA 20% with cerebral edema die 20% with mild to severe neurologic outcomes

At risk: Younger age Initial pH < 7.1 Lower pCO2 New onset Longer duration of symptom Rapid rehydration (> 50cc/ kg in first 4 hrs) Hypernatremia/ persistent hyponatremia Increased BUN Use of bicarbonate Lack of an increase in the serum Na during Therapy

Cerebral Edema

The cause is not fully understood May be present before treatment has begun, but more

commonly occurs 4 to 12 hours after the initiation of therapy Numerous factors have been implicated in the

pathophysiology of DKA-related cerebral edema, but none has been proven Ischemic Vasogenic Osmotic Cytotoxic processes

Cerebral Edema-Pathophysiology

Ischemia/cytotoxic edema Decrease of N-acetylaspartate (NAA), a marker of

neuronal function or viability in several areas of the brain Increased lactate production in the basal ganglia

Vasogenic edema Primary damage to the cerebral vascular endothelium

results in increased BBB permeability or a disturbance in autoregulation, which permits abnormal diffusion of intravascular fluids into the cerebral tissues

Cerebral Edema-Pathophysiology

Osmotic edema as a consequence of fluid therapy During the hyperosmolar state of DKA, the brain produces

Idiogenic Osmoles as a compensatory measure to increase intracellular osmotic pressure and prevent cerebral dehydration

If the extracellular compartment is at a lower osmolarity than the intracellular compartment, osmotic pressure promotes water movement into the intracellular compartment.

During DKA, the combination of insulin and fluid repletion lowers the serum glucose and plasma osmolality, promoting osmotic water movement into the brain

Cerebral Edema-Pathophysiology

Usually develops several hours after the initiation of therapy Manifestations:

Headache Change of mental status Bradycardia and Hypertension Sudden onset/return of vomiting Unequal or fixed, dilated pupils

Treatment: Mannitol: 1 gram/ kg IV over 30 minutes Elevate the head of the bed Decrease IVF rate and insulin infusion rate ICU management Do not delay treatment until radiographic evidence

Cerebral Edema

A 10 y/o male (~30 kg) presents to the ED with a one-day history of emesis and lethargy.

Vitals show T 37C, HR 110, RR 25, BP 99/65. Patient is lethargic, but oriented x 3. Exam reveals the odor of acetone on the breath, dry lips, but otherwise unremarkable

Labs: pH 7.05, PaCO2 20, PaO2 100, BE -20, Na+ 133, K + 5.2, Cl 96, CO2 8, BS 600. Urine shows 4+ glucose and large ketones

Case Scenario #1

How much fluid would you administer as a bolus? Would you administer bicarbonate? What is the “true” serum sodium? How much insulin would you administer? What IVF would you start? At what rate?

Case Scenario #1

A 4 y/o female in the PICU is undergoing treatment for new onset IDDM and DKA. She is on an insulin infusion at 0.1 u/kg/hr, and fluids are running at 2400 cc/m2/day.

Over the last hour, she has been complaining about increasing headache. She is now found to be unresponsive with bilateral fixed and dilated pupils, HR is 50 with BP 150/100.

What is your next step in management?

Case Scenario #2

Case Scenario #3

12 year old admitted with: pH = 7.0 Na= 136, K=3.8, glucose 583mg/ dl She is oriented and conversant on admission, you follow

the DKA protocol, 2 hours later she becomes difficult to arouse and is

responsive only to deep pain. What do you do? Presume cerebral edema

Decrease fluid infusion Give mannitol: 1 gm/kg