INSULIN THERAPY IN HOSPITALIZED

Dr. Widyati, MClin Pharm, AptFarmasis Klinik RSAL dr Ramelan

Dosen MFK Ubaya

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PERSONAL DETAILS

• Sarjana Farmasi 1989 (UNPAD)

• Apoteker 1991 (UI)

• Observasi Hospital Pharmacy di 12 RS Australia(1995)

• MClin Pharm 1999(University of Queensland-Ausy)

• Dr: 2013 (Universitas Gajah Mada)

• Practising clinical pharmacy in hospital (Critical Care)

• Teach clinical pharmacy in UGM, Ubaya

• Org: Ketua Bidang Farklin HISFARSI, Tim Ahli ESO Badan POM

• Married, two children

• International Award: FIP International Travel Award (California,2003), ILAE Travel Award (Washington,2013)

Macam Insulin Regimen

SSI

ODI

MDIIIT

IV Insulin

Terapi Insulin Pada HOSPITALIZED

Acute IllnessChronic Illness

Critically Ill

PerioperativeDrug-induced hyperglycemi

a

Background

• Hyperglycemia frequently occurs with acute medical illness, and has been linked to increased morbidity and mortality in critically ill patients.

• Insulin therapy in hospitalized patients can be troublesome. The stress of the acute illness tends to raise blood glucose concentrations.

• Meanwhile on the other hand, the anorexia that often accompanies illness or the need for fasting before a procedure tends to do the opposite. Because the net effect of these countervailing forces is not easily predictable in a given patient, the target blood glucose concentration is usually higher than when the patient is stable.

DM in Acute Events

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SEPSIS

ACS

STROKE

Stress Hyperglycemia

• SH develops principally through a combination of (1) increased gluconeogenesis relative to glucose clearance and (2) development of insulin resistance affecting cellular uptake of glucose (Mechanick JI, 2006)

• Additionally, proinflammatory cytokines may directly inhibit insulin secretion by pancreatic β cells through stimulation of α-adrenergic receptors (Mizock BA,2001)

Penggunaan Insulin pada Pasien DM Rawat Inap

Acute Illness

• Severe Infection

• Acute Stroke

• ACS

• KAD

• HHS

Chronic Illness

• DM Hiperglikemia

• DM dengan infeksi

• DM dengan intercurrent illness

• DM dengan kehamilan

ACUTE CASES

o Decompensation due to an intercurrent event (eg, infection, acute injury, stress)

o Severe hyperglycemia with ketonemia or ketonuria (Komplikasi Akut)

o Acute events: Acute Coronary Syndrome (ACS), Stroke

o Upcoming surgery o Allergy or other serious reaction to oral agents

The importance of hyperglycemia

• Acute illness: A strong association between hyperglycemia and poor clinical outcome, such as mortality, morbidity, length of stay, infections, and overall complications.(Umpierrez et

al,2002)

• Non-Critical illness: Hyperglycemia is associated with poor hospital outcomes, including prolonged hospital stay, infections, disability after hospital discharge, and death.

Manajemen Inpatient Hyperglycemia

• Dipersulit dengan status nutrisi (ie, nothing by mouth, enteral tube feeding), drug-induced, perubahan kondisi klinis , dan lemahnya koordinasi antara coordination of BG testing with prandial insulin administration.

• ASHP guidelines for safe use of insulin in hospitals recommend a multidisciplinary team approach, institutions develop standardized procedures for BG management

• Subcutaneous insulin therapy should be comprised of 3 components: basal (daily or twice-daily injections of long-acting insulin), prandial or nutritional (injections of rapid-acting insulin before meals), and correction insulin

Dosis Insulin

TDD Estimation Patient Characteristics

0.3 units/kg body weight Underweight

• Older age

• Hemodialysis

0.4 units/kg body weight Normal weight

0.5 units/kg body weight Overweight

≥ 0.6 units/kg body weight Obese

• Insulin resistant

• Glucocorticoids

Perioperative

• Standards for perioperative care include the following:

• Target glucose range for the perioperative period should be 80–180 mg/dL (4.4–10.0 mmol/L).

• Preoperative risk assessment for patients at high risk for ischemic heart disease and those with autonomic neuropathy or renal failure.

• The morning of surgery or procedure, hold any oral hypoglycemic agents and give half of NPH dose or full doses of a long-acting analog or pump basal insulin.

• Monitor blood glucose every 4–6 h while NPO and dose with short-acting insulin as needed.

Insulin pada Non-Critically Ill

• A basal plus bolus correction insulin regimen is the preferred treatment for non-critically ill patients with poor oral intake or those who are taking nothing by mouth.

• An insulin regimen with basal, nutritional, and correction components is the preferred treatment for patients with good nutritional intake. A

• The sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.A

( Diabetes Care 2016)

Insulin Therapy in the Non–Critical Care Setting

• The practice of discontinuing oral diabetes medications and/or insulin therapy and starting sliding scale insulin (SSI) results in undesirable levels of hypoglycemia and hyperglycemia (Hirsch,2009)

Diabetes Care 2016

• Outside of critical care units, scheduled subcutaneous insulin injections should align with meals and bedtime or every 4–6 h if no meals or if continuous enteral/ parenteral therapy is used

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Critically Ill

• Insulin therapy should be initiated for treatment of persistent hyperglycemia ≥180 mg/dL (10 mmol/L).

• Target glucose range of 140 to 180 mg/dL (7.8 to 10 mmol/L) (A) ( ADA, 2011)

• Severe hypoglycemia (< 40 mg/dl) during critical illness should be avoided because it has been associated with increased mortality. (NICE-SUGAR, 2009)

KAD & HHD

• Insulin Therapy• Bolus of regular insulin at 0.15 units/kg body weight,

followed by a continuous infusion of regular insulin at a dose of 0.1 unit/kg/jam (5 to 7 units per hour in adults)

• If plasma glucose does not fall by 50 mg/dL from the initial value in the first hour, check hydration status; if acceptable, the insulin infusion may be doubled every hour until a steady glucose decline between 50 and 75 mg/hour

• Frequent laboratory and blood gas analyses are obtained to ensure ongoing resolution of metabolic acidosis

KAD

• “Maintenance” IV fluid at a rate of 2000 - 2400 cc/m2/day consists of 2/3 NS (0.66%) or NS– 5% Dextrose is added to IVF when blood glucose is ~ 300

mg/dL

– 10% Dextrose is added when blood glucose is ~ 200 mg/dL

• Insulin is used to treat acidosis, not hyperglycemia

– insulin should never be stopped if ongoing acidosis persists

• When the acidosis is corrected, the continuous insulin infusion may be discontinued and subcutaneous insulin initiated

• With this regimen, DKA is usually fully corrected in 36 to 48 hours

INSULIN USE IN CHRONIC CARE

INSULIN USE IN DM TYPE 2

• Indication: when glucose control can no longer be maintained with oral combination

• Insulin therapy overcome insulin resistance and provide adequate insulin even in the presence of islet beta-cell dysfunction

• Indications for insulin therapy of type 2 diabetes :

o Hyperglycemia despite maximum doses of oral agents

o Acute Cases

o Uncontrolled weight loss

o Pregnancy

o Renal disease

o A preference for insulin therapy by the patient or physician.

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Kombinasi OAD-Insulin

• Setelah kombinasi OAD gagal mengontrol gula

Kombinasi ↓FPG (mg/dl) ↓HbA1c (%)

SU+ insulin 60-80 0,5-1.8

Metformin+ins 60-80 1,7-2,5

Acarbose+ins 0-16 0,4-0,5

Glimepiride+ins 110 2,2

Pioglitazone+ins 35-49 0,7-1,0 24

PENETAPAN DOSIS INSULIN

Dosis Insulin

TDD Estimation Patient Characteristics

0.3 units/kg body weight Underweight

• Older age

• Hemodialysis

0.4 units/kg body weight Normal weight

0.5 units/kg body weight Overweight

≥ 0.6 units/kg body weight Obese

• Insulin resistant

• Glucocorticoids

Estimating Total Daily Insulin Requirement

Type 1 diabetes

Initial dose 0.3–0.5 unit/kg

Honeymoon phase 0.2–0.5 unit/kg

With ketosis, during illness, during growth 1.0–1.5 units/kg

Type 2 diabetes

With insulin resistance 0.7–1.5 units/kg

Estimating Basal Insulin Requirements

Basal requirements vary throughout the day,approximately 50% of total daily insulin needs. The basal requirement also is influenced by the presence of endogenous insulin, the degree of insulin resistance, and body weight.

Targets

• A1c ≤ 6,5 %

• FPG/SMBG ≤ 110mg/dl

• 2 hr PPG/SMBG ≤140-180 mg/dl

Treatment Naive

• Symptomatic

• FPG ≥260 mg/dl

• A1c ≥10%, ketoacidosis, recent rapid weight loss

• Pilihan:

• 1. Once-daily Insulin

• 2. Multi-dose insulin

• 3. Intensive insulin management

Oral Agent Failure

• 7,0 %> A1c < 8,5%

• Pilihan:

• 1. Once-daily Insulin

• 2. Multi-dose insulin

• 3. Intensive insulin management

Oral Agent Failure

• A1c > 8,5%

• Pilihan:

• 1. Multi-dose insulin

• 2. Intensive insulin management

• 3. Once –daily insulin

Once-Daily Insulin

• At bedtime : NPH or Long-acting insulin

• Before supper: short-acting insulin or premix 70/30

• Dosis awal : 0,1-0,25 U/kg or 6-10 U untukmanula kurus

• Naikkan dosis setiap 2-3 hari.

• Titration schedule: >180mg/dl – 6 unit

• 141-180mg/dl – 4 unit

• 121-140mg/dl -2 unit

Multi –Dose Insulin

• 2 x suntik : NPH + Short acting insulin

• Or premix 70/30

• 3 x suntik (if nocturnal hypoglycemia): Short acting insulin before breakfast and before supper sliding scale + NPH before breakfast and bedtime or Long acting insulin

• Starting dose: 0,3-0,5 unit/kg

Intensive Insulin Management

• 1:1 basal:bolus

• Basal :NPH before breakfast, before supper or bedtime x 2 or Long acting Insulin

• Bolus: Short acting insulin at each meal

• Starting dose: 0,3-0,5 U/kg

Drug-induced Hyperglycemia

Glucocorticoids

• Mechanism: primarily by inhibiting glucose uptake into muscle.

• Postprandial glucose levels are generally most affected

• Patients who are treated with a basal/bolus regimen will probably require a higher percentage of their TDD as bolus insulin while on glucocorticoids.

• It is important to reduce insulin doses as glucocorticoids are tapered to avoid hypoglycemia.

Combination Therapy

Kasus 1

• Tn HM 58th 160cm 85kg, MRS karena akanmenjalani ops katarak. Pada saat MRS hasilpemeriksaan gula puasa 216mg/dl, GD 2jamPP 234mg/dl. Menurut pengakuan Tn HM memang memiliki riwayat DM, namun tidakkontrol rutin, obatpun tidak rutin dan lebihsering meminum Glibenklamide.

Kasus 2

• Tn Y, 46th 167cm, 70kg, MRS dengan keluhanmual muntah. Pada pemeriksaan gula puasa di lab luar dijumpai GDP 253mg/dl; 2jPP 315 mg/dl. Pasien mengaku memiliki riwayat DM sudah lima tahunan dengan obatGlibenklamide 1-1-0 dan metformin 3x500mg.

• Bagaimana Pharm care untuk kasus ini?

Kasus 3

• Tn K 59th, 172cm 75kg, MRS dengan keluhankencing tidak lancar, disertai rasa panas dannyeri pada saat kencing. Pasien mengakumemiliki DM sudah 8tahun dan masih minumGliklazide 1-1-0 dan Metformin 3 x 850mg. Hasil lab: GDP 265mg/dl; 2JPP 168mg/dl; Leukosit (N), Leukosuria(+). Hasil observasiTTV TD 140/90; Temp (N). Bagaimana PharmCare pada kasus ini

Kasus 4

• Tn KP 62th, 161cm, 59kg MRS dengandiagnosa stroke infark di hemisphere kananyang luas. Hasil Lab GDP 154mg/dl sehinggadiberikan 3 x 4U s.c., namun 2 hari kemudianpasien kejang dan hasil GDP 189mg/dl. Pengakuan keluarga pasien hanya memakanmakanan RS. Bagaimana denganpenatalaksanaan DM?

Critically Ill

• Tn HO 64th, MRS dengan Stroke infark di hemisfer kiri yang luas. Hari kelima muncul problem medik baru yaitu pneumonia yang membuat pasien sangat sesak dan memerlukan ventilator (hari ke-9), sehingga dikirim ke ICU. GDA pada hari tersebut 346mg/dl, GCS 3-2-4. Bagaimana terapi insulin diberikan?

Online ResourcesAmerican Diabetes Association: www.ada.org

Diabetes UK:www.diabetes.org.uk.

National Diabetes Education Intiative: http://www.ndei.org