INSULIN THERAPY IN

HOSPITALIZED

Dr. Widyati, MClin Pharm, Apt

Farmasis Klinik RSAL dr Ramelan
Dosen MFK Ubaya
 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)
2
Macam Insulin Regimen

SSI

IV
Insulin ODI

IIT MDI
Terapi Insulin Pada HOSPITALIZED

Chronic
Acute Illness Critically Ill
Illness

Drug-induced
Perioperative 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

SEPSIS

ACS

STROKE

6
 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 Chronic Illness
• Severe Infection • DM Hiperglikemia
• Acute Stroke • DM dengan infeksi
• ACS • DM dengan
• KAD intercurrent illness
• HHS • 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 untuk
manula 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 akan
menjalani ops katarak. Pada saat MRS hasil
pemeriksaan gula puasa 216mg/dl, GD
2jamPP 234mg/dl. Menurut pengakuan Tn HM
memang memiliki riwayat DM, namun tidak
kontrol rutin, obatpun tidak rutin dan lebih
sering meminum Glibenklamide.
 Kasus 2
• Tn Y, 46th 167cm, 70kg, MRS dengan keluhan
mual 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 obat
Glibenklamide 1-1-0 dan metformin 3x500mg.
• Bagaimana Pharm care untuk kasus ini?
 Kasus 3
• Tn K 59th, 172cm 75kg, MRS dengan keluhan
kencing tidak lancar, disertai rasa panas dan
nyeri pada saat kencing. Pasien mengaku
memiliki DM sudah 8tahun dan masih minum
Gliklazide 1-1-0 dan Metformin 3 x 850mg.
Hasil lab: GDP 265mg/dl; 2JPP 168mg/dl;
Leukosit (N), Leukosuria(+). Hasil observasi
TTV TD 140/90; Temp (N). Bagaimana Pharm
Care pada kasus ini
 Kasus 4
• Tn KP 62th, 161cm, 59kg MRS dengan
diagnosa stroke infark di hemisphere kanan
yang luas. Hasil Lab GDP 154mg/dl sehingga
diberikan 3 x 4U s.c., namun 2 hari kemudian
pasien kejang dan hasil GDP 189mg/dl.
Pengakuan keluarga pasien hanya memakan
makanan RS. Bagaimana dengan
penatalaksanaan 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 Resources
American Diabetes Association: www.ada.org
Diabetes UK:www.diabetes.org.uk.
National Diabetes Education Intiative:
http://www.ndei.org