Glucose Management in Diabetes Inpatient Setting :

focus on Intravenous Insulin

MAT-ID-2100530 – V 1.0 (04/21)

 In-hospital hyperglycemia & Its Adverse Outcome

In-hospital hyperglycemia is defined as blood glucose (BG) levels > 140 mg/dL in hospitalized patients1

Possible Adverse Outcomes of In-hospital Hyperglycemia2

High infection rates Increased duration of hospital stay High mortality rates
~3X times more infection
Risk of complications Higher mortality rates in
rates in patients with
increased 3% for each 18 patients with BG > 200 mg/dl
BG > 220 mg/dl on first
mg/dl increase in admission vs. BG < 200 mg/dl
postoperative day vs.
glucose (5.0% vs. 1.8%, p < 0.001)
BG < 220 mg/dl

Reference: 1. ADA 2020 [Internet]. Available at https://care.diabetesjournals.org/content/43/Supplement_1. Accessed on 28 Nov, 2020. 2. Management of Diabetes and Hyperglycemia in Hospitalized Patients [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279093/.
Accessed on 09 Dec, 2020.
 Pathophysiology Of Hyperglycemia in Intensive Care Unit 

Perkeni, Perdici, Perdossi, Perki. Penatalaksanaan Hiperglikemia Di Unit Rawat Intensif. 2018. Jakarta
 Glycemic management of critically ill hospitalized patients
ADA 2021

• Continuous intravenous insulin infusion is the most effective method for

achieving glycemic targets.

• Intravenous insulin infusions should be administered based on validated written

or computerized protocols that allow for predefined adjustments in the infusion
rate, accounting for glycemic fluctuations and insulin dose

American Diabetes Association. Diabetes Care 2021;44(Suppl. 1):S211–S220

 Inpatient Glycemic Targets

Critically ill Non-critically ill

Preferred route Intravenous Subcutaneous

Glucose target (mg/dl) 140-180 mg/dl Premeal <140 mg/dl

(ADA 2020) (Selected patients* 110 -140 Random <180 mg/dl
mg/dl)

Not recommended Acceptable Recommended Not recommended

<110 110-140 140-180 >180

• Centers with extensive experience and appropriate nursing support, cardiac surgical patients, and patients with
stable glycemic control without hypoglycemia
Individualized glycemic goal; depends on patient’s clinical condition

ADA. Diabetes Care 2020;43(Suppl. 1):S193-S202

 Kebutuhan Insulin Pada Pasien Rawat Inap

PASIEN RAWAT INAP

KRITIS TIDAK KRITIS

KEGAWAT DARURATAN KEGAWAT DARURATAN JUMLAH ASUPAN NUTRISI GLUKOSA DARAH

DIABETES NON-DIABETES SUKAR/TIDAK TERKENDALI :

Ketoasisosis Metabolik Sepsis Pemakaian steroid

Infark miokard akut
Hipeosmolar Non Ketotik Stroke
Ketidakstabilan
hemodinamik
Perencanaan operasi segera
dengan glukosa darah tinggi
Operasi dengan kendali GD
TERATUR TIDAK TERATUR buruk / harus puasa lebih
dari 2x makan
Stroke yang membutuhkan
nutrisi parenteral total

Sub Kutan dosis

Sub Kutan terbagi tetap +
Infus IV kontinyu/ dosis terbagi dosis koreksional Infus IV kontinyu/
Infus IV kontinyu tetap
Sub Kutan Sub Kutan

Konsensus Insulin Perkeni 2019

 Common Indications for IV Insulin in Hospital
• Diabetic ketoacidosis and nonketotic hyperosmolar state
• Preoperative, intraoperative, and postoperative care
• Organ transplantation
• Myocardial infarction or cardiogenic shock
• Stroke
• Critically ill surgical patients on mechanical ventilation
• Hyperglycemia during high-dose glucocorticoid therapy
• NPO status in type 1 diabetes
• Dose-finding strategy prior to initiation of subcutaneous insulin therapy (type 1 or
type 2 diabetes)

NPO = nothing by mouth.

Clement S et al. Diabetes Care. 2004;27:553-591 .

 Protokol Insulin IV Kontinu (PERKENI, 2019)

Dosis awal 0,5-1 U/jam

Sasaran glukosa darah

< 100 mg/dL atau

klinis didapatkan 100-<140 mg/dL 140-180mg/dL >180mg/dL
hipoglikemia

Stop insulin Dosis diturunkan

sampai 50% dari Penurunan Penurunan
IV kontinyu
dosis terakhir glukosa darah glukosa darah <
> 60 mg/dL 60 mg/dL

Penurunan glukosa Penurunan glukosa Turunkan Naikan dosis

darah > 60 mg/dL darah < 60 mg/dL dosis 25% dari 25% dari
dosis terakhir dosis terakhir
Dosis diturunkan
Lanjutkan dosis
sampai 25% dari
sebelumnya
dosis terakhir
PERKENI. Pedoman Terapi Insulin pada Pasien Diabetes Melitus. 2019
 Penatalaksanaan Ketoasidosis Diabetik dan Sindroma
Hiperosmolar Hiperglikemia (PERKENI, 2019)
Jam Ke- Infus NaCI 0,9% Infus II (Insulin) Infus III (Koreksi K+) Infus IV (Koreksi
Bikarbonat HCO3))
0 } 2 kolf, ½ jam
1 kolf, ½ jam
1 } 2 kolf Pada jam ke-2 Bolus 180 50 mEq/6 jam (dalam infus)
Bila pH:
2 mU/kgBB dilanjutkan dengan Bila kadar K :
} 1 kolf
insulin IV kontinyu 90
• <7 : 100 mEq HCO3
3
} 1 kolf • <3 : 75 • 7 → 7,1 : 50 mEq HCO3
mU/jam/kgBB dalam NaCL
4 • 3 → 4,5 : 50 • >7,1 : 0
} ½ kolf 0,9%.
5 • 4,5 → 6 : 25
Bila GD < 200 mg/dL pada • >6 : 0 Analisa gas darah diperiksa
Bila GD < 200 mg/dL, ganti Dextrose 5%.
KAD atau GD < 300 mg/dL ulang tiap 6 jam sampai
Bila kadar Na > 145 mEq, infus NaCI 0,9% pada SHH, kecepatan insulin Kalium diperiksa ulang tiap stabil selama 24 jam.
diganti dengan NaCI 0,45 %. IV kontinyu dikurangi 6 jam sampai stabil selama
45mU/jam/kgBB. 24 jam
Pada pasien dengan gagal jantung dan gagal
ginjal direkomendasikan pemasangan CVC Bila GD stabil 200 → 300
(Central Venous Catheter) untuk memonitor mg/dLselama 12 jam dan
pemberian cairan. pasien dapat makan, dapat
dimulai pemberian insulin IV
Penanganan penyakit pencetus juga kontinyu 1 → 2 IU/jam disertai
merupakan prioritas yang harus segera dengan insulin koreksional
dilakukan (misalnya pemberian antibiotic yang ( sesuai Tabel IV,3,Bab IV).
adekuat pada kasus infeksi).

PERKENI. Pedoman Terapi Insulin pada Pasien Diabetes Melitus. 2019

Protokol Insulin IV RSUP Dr. Kariadi
 Requirement for Continuous Intravenous & Monitoring

Requirements for continuous IV insulin initiation

Monitoring Blood Glucose
1. As indicated
Continuous Insulin Infusion
2. It technically allows:
• Check BG every hour in the first
• available infrastructure (syringe pump, microdrip, independent 3 hours to evaluate for possible
blood glucose testing device / glucometer)
hypoglycemia
• skilled health personnel
• Intensive blood glucose checks can be done
• Furthermore, BG is monitored
according to the aggressiveness
3. K+ > 3mEq/L of insulin administration
4. Type of insulin used: short acting
5. Try an insulin concentration of 1 U / mL

PERKENI. Pedoman Terapi Insulin pada Pasien Diabetes Melitus. 2019

 Intravenous Insulin Infusion Preparation

 50 U of regular insulin or rapid acting analogue insulin is dissolved in 50 ml of 0.9% NaCl

in a 50 ml disposable syringe

 0.5-1 ml of fluid is flushed across the IV tube to prevent adhesion of the tube

 Other way if syringe pump not available : 50 – 100 U of regular insulin or rapid acting
analogue insulin is dissolved in 50 – 100 cc NaCl 0.9% using micro drip infusion set

PERKENI, PERDICI, PERDOSSI, PERKI. PENATALAKSANAAN HIPERGLIKEMIA DI UNIT RAWAT INTENSIF. 2018. Jakarta
S Restu, meta, Rahardjo, Sri, Mahmud. Jurnal Komplikasi Anestesi, 2015; 69-84
 Conversion to subcutaneous insulin
WHEN. ??

• Stable blood glucoses which are less than 180 mg/dL (7.7–10 mmol/L) for at least
4–6 h consecutively
• Normal anion gap and resolution of acidosis in DKA
• Stable clinical status; hemodynamic stability
• Not on vasopressors
• Stable nutrition plan or patient is eating
• Stable IV drip rates (low variability)

Because of short half-life of IV insulin, SC basal insulin should be administered at

least 1-2 hours prior to discontinuing the drip

Evans Kreider, K, F. Lien, Lilian. Curr Diab Rep (2015) 15: 23

 Transition From IV Insulin Infusion to SC Insulin Therapy

Example: Patient has received an average of 2 U/h IV during previous 6 h.

Recommended doses are as follows: SC TDD is 80% of 24-h insulin
requirement

2 Unit/h x 24 h = 80% x 48 Units =

48 Units 38 Units

Basal dose is 50% of SC TDD:

◦ 50% of 38 Units = 19 Units of long-acting insulin

Bolus total dose is 50% of SC TDD:

◦ 50% of 38 Units = 19 Units. Give as ~6 Units with each meal

Correction dose is actual BG minus target BG divided by the CF, and CF is

equal to 1700 divided by TDD: CF = 1700 ÷ 38 = ~40 mg/dL
Correction dose = (BG - 100) ÷ 40

BG, blood glucose; CF, correction factor; IV, intravenous; SC, subcutaneous; TDD, total daily dose.
Bode BW, et al. Endocr Pract. 2004;10(suppl 2):71-80.
Can rapid acting analog insulins be
administered intravenously?
Study of Continuous Insulin Infusion Protocols in the Medical
Intensive Care Unit by using Glulisine
Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n=77) or a standard
paper protocol (n=76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL.

• Both treatment
algorithms resulted in
significant improvement
in glycemic control in
critically ill patients in
the medical ICU.

Standard (n) 77 77 55 35 24 14 13 10 7 7 3
Glucommander (n) 76 76 50 37 31 32 18 17 15 11 8

Time on Infusion (Days)

Newton CA, et al. Journal of Hospital Medicine. 2010;5(8):432–7.

 Comparison Blood Glucose Control between Insulin
Infusion vs Subcutaneous in the Coronary Care Unit
Glucose levels over the course of
DESIGN AND METHODS the trial were significantly lower in the insulin arm.

Total 287 patients with an acute P-values standard therapy

1 NS
STEMI & a capillary glucose ≥ 8.0 2 <0.05
Insulin arm
mmol/L were randomized to insulin 3 <0.005

Glucose (mmol/L)
arm (insulin glulisine infusion in the 4 <0.0005

CCU, and insulin glargine once-

daily in ward) vs standard therapy
arm (physicians free to add insulin
therapy to treat high glucose level) for
30 days. The primary outcome was a
difference in mean glucose levels at
24 h.

Result: At 24 h, the mean glucose level was

1.41mmol/L (95%CI 0.69–2.13) lower in the
Insulin arm (6.53 vs. 7.94mmol/L).
Differences in glucose levels were
maintained at 72 h and 30 days Time
Nerenbergh et al., Diabetes Care 35:19–24, 2012
 Analogues vs Regular Insulin

68 Subjects
with DKA

Can Rapid IV Insulin Glulisine (n=34) IV Regular insulin (n=34)

Acting Analog
0.1 U/kg/hr until BD <250 mg/dl then 0.1 U/kg/hr until BD <250 mg/dl then
Insulins Be 0.05 u/kg/hr until resolution of DKA 0.05 u/kg/hr until resolution of DKA
Administered
Intravenously?
Transition to SC Transition to SC
Total daily dose 0.6 U/kg/day Total daily dose 0.6 U/kg/day

Given 1/2 as glargine OD, and 1/2 as Given 2/3 as NPH, and 1/3 as regular
glulisine before meals insulin twice daily

Umpierrez GE et al. Diabetes Care. 2009;32:1164–1169

 Analogues vs Regular Insulin

The rate of decline of blood

glucose concentration; duration
of treatment; amount of insulin;
and changes in acid base
parameters were not
significantly different between
patients treated with regular
insulin ( ) and glulisine ( ).

Umpierrez GE et al. Diabetes Care. 2009;32:1164–1169

 Conclusion

 Hyperglycemia is a common issue in critically ill patients

 Hyperglycemia can occur due to previous poor blood glucose control and / or acute metabolic
stress

 Hyperglycemia is associated with increased morbidity & mortality both in DM patient and non DM
 Control of hyperglycemia levels with a target of 140-180 mg / dl can decrease mortality and
morbidity

 The use of continuous intravenous insulin can control hyperglycemia in a relatively short time
 Insulin analog such as glulisine can be used for IV infusion.
 Tight monitoring of blood sugar levels can reduce the risk of hypoglycemia