Case presentation

Christopher Betts PGY II

CC: increased urine output, nausea

HPI: 64 yo AAF with history of DM II, CAD, and cocaine abuse presented to the ER with four days of increased urinary frequency, abdominal pain, nausea, and vomiting. They were associated with intermittent headaches. She was concerned of daily glucose logs which have been progressively higher over the last few days. She was more alarmed upon finding her AM glucose prior to arrival being >500 mg/dl. In the ED she was initially given 1L NS bolus, then dilaudid 1mg, then 8U regular insulin, then NS infusion of 150cc/hr, then another regular insulin 8U, then another 1L NS bolus.

PMHxMigraine HADM type II (HbA1c > 15%, 09/12/14)DepressionHTNSickle cell diseaseHepatitis Ch/o Cocaine abuseIschemic CMCAD s/p bypass graftsLVSDh/o multiple hospitalizations for hyperglycemia

Allergies: (each causing rash/itching)PCNMetforminSulfaLatex

Rx:Lantus 10U qhsNeurontin 300mg bidLasix 40mg qdPravachol 40mg qhsASA 81mgRanexa 500mg bidSeroquel 50mg (1/2 tab AM, 1 tab PM)Citalopram 40mg

Rx (cont’d):Prilosec 20mgCoreg 6.25mg bidLisinopril 2.5mg Norco 5mg q6h prnClonidine 0.1mg bidProAir HFA prn Keppra 750mg bidPlavix 75mg Soma 8.6mg qhsMiralax 8.5g bidColace 100mg bidZofran 4mg bid prn

SHx:

• Quitted tobacco 2010• Denies EtOH history• History of cocaine abuse– Per patient stated quitted 2 years ago

• Lives alone

FMHx

HIVHeart diseaseAsthma Cancer (unspecified)DM

ROS

(+): fatigue, increased appetite & thirst, nausea/vomiting, abdominal pain, increased urine output, dizziness, weakness, constipation, chest pain, dyspnea

(-): no fever, chills, confusion, dysuria, hematuria, progressive weight loss, night sweats

VS: Temp 98.6, BP 107/67, HR 67, RR 18, Sat 98 on RAWeight: 70kg Exam:General – NAD, mildly anxiousHEENT – dry mucous membranes, PERRL (about 2mm in size), EOMINeck – supple, no LADSkin – no rashesHeart – RRR, III/VI SEM appreciated in left PSBLung – clear BS bilaterally in upper and lower fieldsGI – soft, non-tender, active BSMSK – 4/5 bilateral motor strength with no focal atrophyNeuro – no focal motor or sensory deficits, CN’s grossly intactGU & Breast – deferredPsyche – mildly anxious

What tests would you order?

[Discussion]

Studies done after arrival to ED:Na 133 corrected Na ____K 4.9Cl 96BUN 21CO2 21Cr 1.56 (baseline between 1.0-1.2)Ca 9.6AG 16 w/ corrected Na is ______Gluc 474Mg 2.3Phos 2.3Troponin 0.03Ketone 2.0

CBC: 5.5>14.6/42.5<139UDS: positive for cocaine

Tbili 0.5Dbili 0.2protein 7.6Alb 3.7AST 66ALT 56ALP 124

UA: 1.022, clear, >500 glucose, >20 ketones, negative nitrite, bilirubin, RBC, WBC, leukocyte esterase

ABG:7.39/37/91/22.6/96.5

CXR: no acute abnormalities

Differential Diagnoses

[Discussion]

Initial plan

[Discussion]

Which from this case favor DKA?

a) pH 7.39b) HCO3 22c) AG 16d) Gluc 474e) Ketone 2.0 & Ketouria >20f) c, d, eg) All of the above

Diagnostic factors of HHS and DKA

Plasma glucose (mg/dl)>250 in DKA>600 in HHS

Arterial pH>7.30 in HHS7.25 to 7.3 in mild DKA7.00 to <7.24 in moderate DKA<7.00 in severe DKA

Serum bicarbonate (mEq/L)>18 in HHS15-18 in mild DKA10-15 in moderate DKA<10 in severe DKA

Urine and serum ketones (serum ketones >0.42 mmol/L)Positive in DKASmall in HHSThe absence of ketonuria makes the diagnosis of DKA unlikely.

Diagnostic factors of HHS and DKA

Anion gap (mEq/L)>10 in mild DKA>12 in moderate and severe DKA<12 in HHS

Effective serum osmolality (mOsm/kg)Variable in DKA>320 in HHS

Mental status Alert in mild DKAAlert/drowsy in moderate DKAStupor/coma in severe DKA and HHS

PathophysiologyDKA: insulin deficiency leading to starved cells of glucose leading to elevation of counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Starved cells need to consider alternative energy sources: fat tissue. Ketones as byproduct of metabolized FFA. Endogenous glucose elevates from glycogenolysis, proteins, and gluconeogenesis. Hyperglycemia causes osmotic diuresis resulting in dehydration, metabolic acidosis, and a hyperosmolar state.

HHS: ambient insulin level effectively prevents lipolysis and subsequent ketogenesis yet is inadequate to facilitate peripheral glucose uptake and to prevent hepatic residual gluconeogenesis and glucose output.

What is the next most appropriate step?

a) IV insulin bolus (0.1 units/kg) b) IV fluid bolus 0.9% NS one literc) Give 20 mEq KCl per liter fluidd) Order BMP, Mg, and Phos every 3 hourse) Transfer to the ICUf) All of the above

DKA management: HYDRATE

FIRST, Stabilize and Hydrate the patient!• Bolus: Normal saline one liter over one hour• Continue aggressive fluid replacement of

15-20ml/kg/hr until patient is hemodynamically stable and making adequate urine output (at least 50ml/hr)

• The average total water deficit (TWD) for an adult can be 5 to 6 liters. Keep the TWD equation in mind.– The first half of TWD is given in the first 12-24 hrs; the

second half in the next 24 hrs.

DKA management: HYDRATE

• Maintenance hydration – Its only considered once patient is clinically stable– It also depends on patient’s corrected sodium– Rate: 4-14ml/kg/hr (or more simply 250-500ml/hr)– Low Na and/or severe dehydration: NS 0.9%– Normal/high Na and/or mild dehydration: NS 0.45%

• Closely monitor urine output (strict I’s & O’s), fluid status, blood pressure, and electrolytes.

• Note: maintenance will NOT fulfill deficit.

DKA management: POTASSIUM

Next, ensure adequate potassium levels• Manage potassium replacement based on

patient’s initial level on admission. If…• K < 3.3mEq/L – only IVF with 20-30 mEq KCl per

liter of fluid administered; NO INSULIN. • K is 3.3 to 5.2 mEq/L – same thing, plus insulin IV

can be initiated.• K is >5.2 mEq/L – continue IVF without added

potassium but monitor their levels every 2hrs.

DKA management: POTASSIUM

• Despite a significant reduction in total body potassium, the serum concentration is usually normal or high at presentation because of a shift into the extracellular compartment.

• The steepest decline of potassium occurs in the first few hours of treatment; many recommend that values are checked at least hourly during this phase.

• In any case, make sure patient has a urine output of at least 50cc/hr. Goal potassium level between 4-5mEq/L.

DKA management: PHOS, MAG

• K and phosphate may be both in normal or elevated range in the initial presentation of DKA.

• What is key is to watch closely their values decline during the first initial hours of insulin therapy!– Hence, why chemistries need frequent re-drawing

• Replacement is unnecessary unless…– Phosphate < 1.0 (20-30 mEq Kphos IV)– Mg < 1.2 and/or symptoms (paresthesias, tremor,

muscle spasm, seizures, ECG findings)

DKA management: INSULIN

Initiate after 1 hour of IV hydration AND initial potassium level is >3.3 mEq/ml. Bolus: 0.1U/kg of Regular insulinMaintenance: 0.1U/kg/hr of regular insulinOr….No bolus and initiate:Maintenance: 0.14U/kg/hr of regular insulin

DKA management: INSULINMonitor BG every hour.Goal is to decrease BG hourly by 50-70mg/dLIf BG is not decreasing by 10% (or at least 50mg/dL) Give another 0.14U/kg of IV insulin

Once glucose of 200mg/dL: change IV insulin infusion rate to 0.05 to 0.1 U/kg/hr AND add dextrose 5% to NS 0.45% at 150-250cc/hr

It is important to maintain a glucose of 150-200 mg/dL until DKA fully resolves.

DKA management: SQ INSULIN

• Uncomplicated DKA – immediate mgt:– Rapid acting insulin – 0.3U/kg bolus, then

0.1U/kg/hr or 0.2U/kg/2hr – This is doubled, if DBG <10% in first hour

• Once glucose of 200mg/dL: change to 0.05U/kg/hr AND add dextrose 5% to NS 0.45% at 150-250cc/hr

DKA management: BICARB

Bicarbonate replacement is only considered when the pH is less than 6.9.In addition to pH<6.9, added incentive to administer is if there is massive depletion of bicarb (HCO3 < 5) and/or life-threatening hyperkalemia (K>7.0)However, bicarbonate replacement remains controversial in management of DKA. This is mainly due to the increased risk of hypokalemia and tissue hypoxia with its use.

DKA management: BICARB

Bottom line:Current ADA guidelines continue to recommend bicarbonate replacement in persons with a pH < 6.9 using 100mEq of sodium bicarbonate in 400 ml of sterile water with 20 mEq of potassium chloride at a rate of 200ml/hr for two hours. This should be repeated every two hours until the pH is 6.9 or greater. Potassium levels must be closely watched as well.

DKA management: LABS – priority

• Basic metabolic profile – every 2-4 hours• Fingerstick Glucose – every hour• ABG’s repeated every hour – Arterial vs. venous: if hemodynamically stable– Venous pH increased by 0.02

• Serial Ketones?– Since the routine chemistry has anion gap, this

adequately assesses the progression of ketosis.

DKA management: LABS – others• Other labs that are less of priority but are notable to

follow, especially when assessing level of dehydration include– Mg, Phos (decreases with insulin therapy)– ECG (look for manifestations of K+ abnormalities)

– BUN, Cr (elevated)– CBC (WBC elevated solitary; infection unlikely)

– Amylase, lipase (possibly elevated)– Urinalysis (trend ketones)– Osmolality (variable, unlike in HHS)– Lactate (elevated)

DKA management: LABS – others

• Other tests important to order are those pertinent to the patient’s history. – CXR, Abd X-ray, CT head– Cultures, procalcitonin, CRP– Troponin, ECG, BNP– Urine drug screen, salicylates, Tylenol, alcohol – Liver profile, amylase, lipase– Etc…

DKA management: GOALS

Ideal-reversal of DKA would entail:• Glucose <200 mg/dL • Serum bicarbonate is >18 mEq/L• Venous pH is >7.3• Anion gap is <10• Patient can eat and/or tolerate fluids.

DKA management: GOALS

The ADA guidelines for DKA recommend that IV insulin infusion be tapered and SQ insulin schedule be started when the blood glucose is <200 mg/dL and two of the following are met:• Serum bicarbonate is >18 mEq/L• Venous pH is >7.3• Anion gap is <10

DKA management: IV to SQ INSULIN

• Transition from IV after DKA criteria resolved• Determine the average hourly rate of IV insulin over past 8 hours

– Multiply this average by 24 hours to determine daily IV insulin requirement

– Convert 2/3 of the daily IV insulin requirement to subcutaneous insulin • Give 50% as basal • Give 50% as rapid acting in divided doses

– Order sliding scale insulin• Discontinue IV insulin 1-2 hours after the first dose of

subcutaneous insulin is given. • Why is this important?? (half-life of circulating insulin is ____)

DKA management: IV to SQ INSULIN

• Transition from IV after DKA criteria resolved• Determine the average hourly rate of IV insulin over past 8

hours– Multiply this average by 24 hours to determine daily IV insulin

requirement (e.g. 1U/hr avg. = 24 units daily IV)– Convert 2/3 of the daily IV insulin requirement to subcutaneous

insulin (e.g. 24 units daily IV 16 units SQ)• Give 50% as basal (e.g. 8U every 24hrs)• Give 50% as rapid acting in divided doses (2U every 6 hours)

– Order sliding scale insulin• Discontinue IV insulin 1-2 hours after the first dose of

subcutaneous insulin is given.

DKA management: IV to SQ INSULIN

DKA management: COMPLICATIONS

• Cerebral edema• Cardiac arrest – Abnormally low/high potassium

References• D. Westerberg. Diabetic Ketoacidosis: Evaluation and Treatment. Am Fam Physician. 2013;87(5):337-

346.• v. Magaji, J.Johnston. Inpatient Management of Hyperglycemia and Diabetes. Clinical Diabetes Jan

2011 vol. 29 no. 1 3-9• C. Newton. Diabetic Ketoacidosis in Type 1 and Type 2 Diabetes Mellitus. Arch Intern Med.

2004;164(17):1925-1931• C.Clark PharmD. Management of Type 2 Diabetes: Injectable and Insulin Therapies. GHS Family

Medicine Afternoon Conference PowerPoint-Lecture, March 2014• R. Harden, N. Quinn. Emergency management of diabetic ketoacidosis in adults. Emerg Med J

2003;20:210–213Textbook sources: • Access Medicine

– Harrison’s Online (18th Edition)– Principles of Critical Care (3rd Edition)– Tintinalli’s Emergency Medicine (7th Ed.)

• Up To Date – DKA Management (last updated July 2014)• Epocrates Online• Washington Manual of Medical Therapeutics (34th Ed.)