kha-hhs pp

ELMIRA DARVISH PHARM.D. CANDIDATE OF 2016

SHENANDOAH UNIVERSITY

Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic

State

Objectives

To understand the precipitating factors, pathophysiology and diagnosis of DKA and HHS

To discuss treatment protocol based on the American Diabetes Association (ADA) guideline

Given a patient case, be able to differentiate HHS and DKA and initiate appropriate treatment plan

Introduction

DKA is commonly seen in T1DM patients < 65 years

DKA may be the initial symptoms leading to diagnosis of T1DM

HHS is more common in individuals with T2DM > 65 years

140,000 cases of DKA were reported in 2009 Rate of hospital admission for HHS is much

lower Mortality rate of hyperglycemic crisis has

declined

Precipitating Factors

New onset T1DMInsulin omission in

T1DMInfectionCerebrovascular

accident Alcohol abuseInfusion device

malfunction

Inadequate insulin intake

Psychosocial issues PancreatitisMITrauma Drugs

Pathophysiology

Ferenchick, Gary. Diabetic Ketoacidosis. Just in Time Medicine. Michigan State University. January 2014. Accessed on 07/22/15 http://www.justintimemedicine.com/CurriculumContent.aspx?NodeID=1473

Diagnosis

Symptoms: Polyuria, polydipsia,

polyphagia Weight lossAbdominal pain (DKA)Kussmaul breathing

(DKA)Hypotension Normothermic or

hypothermic

.

Accessed on 07/22/15 http://study.com/academy/lesson/what-is-ketosis-definition-symptoms.html

Diagnosis

Hyperglycemic Crisis in Diabetes. American Diabetes Association. Diabetes Care, Vol. 27, Supplement 1, 2004.

Differential Diagnosis

Alcoholic Ketoacidosis Mild glucose elevation or hypoglycemicStarvation ketoacidosisMild glucose elevation or hypoglycemicBicarbonate levels are ≥ 18 mEq/LDrug intoxication High anion-gap History of previous intoxications Measure blood lactate, salicylate and methanol

levels

Treatment

DKA

1) IV 1 L of 0.9% NS/hr 2) IV Fluids 3) Insulin 4) Potassium correction5) Bicarbonate 6) Treat precipitating

factor

HHS

1) IV 1 L of 0.9% NS/hr 2) IV Fluids 3) Insulin 4) Potassium correction 5) Treat precipitating

factor

Treatment of DKA


Treatment of DKA: IV Fluids All patients : IV 1 L of 0.9% NS/hr Determine hydration status

Hypovolemic shock IV 1 L of 0.9% NS/hr +/- plasma expanders

Cardiogenic shock hemodynamic monitoring

Mild hypotension Evaluate Na+ levels

Low: 0.9% NS (4-14 mL/kg/hr) Normal-high: ½ NS (4-14 mL/kg/hr)

Once serum glucose level is 250 mg/dl D5W + 1/2NS at 150-250 mL/hr with

adequate insulin Maintain glucose at 150-200 mg/dL

until metabolic control is achieved


Treatment of DKA


DO NOT initiate insulin unless K+≥3.3 mEq/L Mild DKA: SC/IM

Regular Insulin 0.4 units/kg ½ IV Bolus + ½ SC/IM Then, 0.1 units/kg/hr SC/IM IF glucose does not decrease 50-70 units in 1

hour: Give hourly 10 units IV bolus

Moderate-Severe: IV Regular Insulin 0.15 units/kg IV bolus Then, 0.1 units/kg/hr IV infusion IF glucose does not decrease 50-70 units in 1

hour: Double infusion rate

Once serum glucose level is 250 mg/dl 0.05-0.1 units/kg/hr IV insulin infusion or, 5-10 units

SC with adequate hydration Maintain glucose at 150-200 mg/dLuntil

metabolic control is achieved

Treatment of DKA: Insulin


Treatment of DKA


K+ < 3.3 mEq/L: Hold insulin Give 40 mEq K+/L/hr until ≥ 3.3

mEq/L

K+ 3.3-5 mEq/L: Give 20-30 mEq of k+ /L Maintain K+ levels 4-5 mEq/L

K+ ≥ 5 mEq/L: Do NOT give K+

Check levels every 2 hours

Treatment of DKA: Potassium


Treatment of DKA


pH <6.9 Give 100 mmol NaHCO3/ 400 mL

H2O Infuse at 200 mL/hr Repeat q2hr until pH > 7.0 Monitor serum K+

pH6.9-7.0 Give 50 mmol NaHCO3/200 mL H2O Infuse at 200 mL/hr Repeat q2hr until pH > 7.0 Monitor serum K+

pH > 7.0 No bicarbonate is needed

Treatment of DKA: Bicarbonate


Treatment of HHS


All patients : IV 1 L of 0.9% NS/hr Determine hydration status

Hypovolemic shock IV 1 L of 0.9% NS/hr +/- plasma expanders

Cardiogenic shock hemodynamic monitoring

Mild hypotension Evaluate Na+ levels

Low: 0.9% NS (4-14 mL/kg/hr) Normal-high: ½ NS (4-14 mL/kg/hr

Once serum glucose level is 300 mg/dl D5W + 1/2NS at 150-250 mL/hr with

adequate insulin Maintain glucose at 250-300 mg/dL

until osmolality is ≤315 mOsm/kg AND mentally alert

Treatment of HHS: IV Fluids


Treatment of HHS


Treatment of HHS: Insulin

DO NOT initiate insulin unless K+≥ 3.3 mEq/L

1. Regular Insulin 0.15 units/kg as IV bolus

2. 0.1 units/kg/hr insulin infusion 3. Check serum glucose hourly 4. IF glucose does not decrease

by 50 units in 1 hour: Double insulin dose hourly

Treatment of HHS: Insulin


Treatment of HHS


K+ < 3.3 mEq/L: Hold insulin Give 40 mEq K+/L/hr until ≥ 3.3

mEq/L

K+ 3.3-5 mEq/L: Give 20-30 mEq OF k+ /L Maintain K+ levels 4-5 mEq/L

K+ ≥ 5 mEq/L: Do NOT give K+

Check levels every 2 hours

Treatment of HHS: Potassium


General: Electrolytes:

Mental Status Temperature Vitals Serum glucose Urine ketones

Sodium PotassiumChlorine Bicarbonate Blood Urea NitrogenOsmolalityAnion Gap Mg 2+, Ca2+, Phosphate

Monitoring

Arterial Blood Gases: Others:

Venous and arterial pH

O2 saturationPaO2

PaCO2

Intake/Output of fluids

Insulin units and route

Precipitating factorAssess infection

Monitoring

Complications

Hypoglycemia/Hyperglycemia Excessive or inadequate insulin

Hypokalemia Fluid replacement therapy dilutes K+

Hyperchloremia Excessive fluid replacement with saline

Cerebral edema Common in newly diagnosed children Loss of consciousness, lethargy, headache, pupillary

changes Due to osmotic driven movement of water into CNS

In the Literature…Goyal N. et al. Kitabchi A. et al.

Study Design Non-concurrent, prospective observational cohort study

Prospective, Randomized, small

Number of Patients

157 37

Primary Outcome Hypoglycemia, length of hospital stay and decrease rate of serum glucose and anion gap

Changes in plasma free insulin, K+, glucose and recovery measures.

Results Administration of bolus dose does not have significant benefit to patient, but increases risk of hypoglycemia

Use of bolus dose is not necessary when adequate continuous insulin infusion is used. No significant difference between the groups

Clinical Application

In mild DKA cases, bolus dose may not be necessary

Rate of insulin infusion must be 0.14 units/kg/hr when no bolus dose is given

Comparison of protocols: DKAAmerican Diabetes Association

Guideline Reston Hospital Center Protocol

If initial K+ < 3.3 mEq/L, hold insulin and administer 40 mEq/L of K+/hr

Delay insulin therapy until K+ ≥ 3.3 mEq/L. Administer 40 mEq/L of K+/hr

Insulin: 0.15 units/kg IV Bolus + 0.1 units/kg/hr Infusion

Insulin drip: 0.14 units/kg/hr

If glucose level did not decrease by 50-70 mg/dl in one hour, double insulin infusion hourly

If glucose level did not decrease by ≥ 49 mg/dl in one hour, double insulin infusion rate

When serum glucose is 250 mg/dl: Reduce infusion rate to 0.05-0.1

units/kg/hr IV insulin infusion or 5-10 units SC

Maintain glucose levels at 150-200 mg/dl

When serum glucose is ≤200 mg/dl: Reduce infusion rate to 0.05

units/kg/hr and titrate based on the infusion chart


Comparison of protocols: HHS American Diabetes Association

Guideline Reston Hospital Center Protocol

If initial K+ < 3.3 mEq/L, hold insulin and administer 40 mEq/L of K+/hr

Delay insulin therapy until K+ ≥ 3.3 mEq/L. Administer 40 mEq/L of K+/hr

Insulin: 0.15 units/kg IV Bolus + 0.1 units/kg/hr Infusion

Insulin drip: 0.14 units/kg/hr

If glucose level did not decrease by 50-70 mg/dl in one hour, double insulin infusion hourly

If glucose level did not decrease by ≥ 49 mg/dl in one hour, double insulin infusion rate

When serum glucose is 300 mg/dl: Reduce infusion rate to 0.05-0.1

units/kg/hr IV insulin infusion or 5-10 units SC


When serum glucose is ≤300 mg/dl: Reduce infusion rate to 0.05

units/kg/hr and titrate based on the infusion chart


Summary

DKA and HHS are usually caused by a precipitating factor such as infection that must be adequately treated

Treatment of DKA includes fluid replacement, insulin, bicarbonate and potassium supplementation as necessary

Treatment of HHS include fluid and insulin replacement, and potassium supplementation as necessary

Case Study

Captain Frank Furillo is a cachectic 58 year old male presenting to ED with an abdominal pain, weakness labored breathing and tachycardia. His temp. is 102 0F and his BP is 88/56 mmHg. Upon further evaluation, his SBG is 460 mg/dl with an anion gap of 14, positive urine ketones, serum bicarbonate levels of 9 and K+< 3.3 mEq/l.

Q: What is the most appropriate initial therapy?A) Insulin bolus + infusion B) Evaluate K+ levels C) Evaluate Na+ levelsD) Start IV fluid with Normal Saline

Case Study

Captain Furillo is now started on insulin bolus + infusion. After one hour, his blood glucose level has decreased by 38 mg/dl.

Q: How would you modify his insulin treatment?

A) Give a bolus dose B) Repeat the serum glucose testC) Double the rate of infusion D) No modification is necessary

References

Ferenchick, Gary. Diabetic Ketoacidosis. Just in Time Medicine. Michigan State University. January 2014. Accessed on 07/22/15 http://www.justintimemedicine.com/CurriculumContent.aspx?NodeID=1473

Funk JL. Disorders of the Endocrine Pancreas. In: Hammer GD, McPhee SJ. eds. Pathophysiology of Disease: An Introduction to

Clinical Medicine, Seventh Edition. New York, NY: McGraw-Hill; 2013.http://accesspharmacy.mhmedical.com/content.aspx?bookid=961&Sectionid=53555699. Accessed July 23, 2015.

Goyal N., Miller J.B., Sankey S.S., and Mossallam U. Utility of Initial Bolus Insulin in the Treatement of Diabetic Ketoacidosis. The Journal of Emergency Medicine, Vol 38, No. 4, pp. 422-427, 2010. DOI: 10.1016/j.jemermed.2007.11.033

Haak, Danielle. What is ketosis? Human Anatomy and Physiology: Help and Review. Accessed on 07/22/15 http://study.com/academy/lesson/what-is-ketosis-definition-symptoms.html

Kitabchi A., Murphy M.B., and Spencer J. Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of

Diabetic Ketoacidosis? Diabetes Care 31: 2081-2085, 2008.

Kitabchi A.E., Nathan D.M., Hirsch B., and Emmett M. Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State in adults: Treatment. UpToDate 2015. http://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-treatment

Powers A.C., Diabetes Mellitus: Management and Therapies. Harrison’s Principles of Internal Medicine, 19e. New York, NY:McGraw-Hill; 2015. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130&Sectionid=79752952. Accessed July 23, 2015.

Reston Hospital Center. DKA/HHNK Treatment Protocol for Physicians. Accessed in 2015.


Triplitt CL, Repas T, Alvarez C. Chapter 57. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310509. Accessed July 23, 2015.

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