Lessons learned from working with international injection technique guidelines

Lessons learned from working with international injection technique guidelines Anders Frid, MD, PhD Clinic of Endocrinology, Skåne University Hospital, Malmö Oslo 23rd March 2012

INJECTION TECHNIQUE IS IT IMPORTANT? Anders Frid, MD, PhD, T.I.T.AN Athens 11-12 sep 2009

TITAN 127 participants from Europe, Russia, USA, Canada, China, Taiwan, South Korea, Japan, Indonesia, The Philippines, India and Pakistan 10th - 13th September 2009

TITAN Worldwide Injection Technique Survey Athens, Thursday 11th, 2009 De Coninck C, Frid A et al, J Diabetes. 2010 Sep;2(3):168-79 10th - 13th September 2009

Introduction 2008-2009 Survey 4352 participants 171 centers 16 countries (Asia, North America, Eastern and Western Europe) One of largest studies of its kind in diabetes

Countries and Participants Number of participants Percentage of total responders USA 236 5.4 RUSSIA 239 5.5 NETHERLANDS 342 7.9 BELGIUM 563 12.9 FRANCE 134 3.1 SPAIN 220 5.1 ITALY 189 4.3 SWITZERLAND 15 0.3 UK & IRELAND 999 23.0 DENMARK 115 2.6 SWEDEN 67 1.5 GERMANY 269 6.2 CHINA 488 11.2 TURKEY 341 7.8 PORTUGAL 60 1.4 FINLAND 75 1.7 4352 100.0 Total

Key Educational Topics Topics Percent of Patients who DON T remember being trained in this subject Depth of injection 28% Length of needle 28% How long to hold a pinch up 32% How long to keep the needle in the skin 17% Not mixing site and time 36% Prevention of air bubbles 20% Mixing insulin in a syringe (for syringe users) 46% Re-suspension of cloudy insulin 27% Single use of syringe/needle 17% Safe disposal of sharps (needles, syringes) 28% Injection under 90 /45 20%

Key Educational Topics Topics Percent of Patients who DON T remember being trained in this subject Depth of injection 28% Length of needle 28% How long to hold a pinch up 32% How long to keep the needle in the skin 17% Not mixing site and time 36% Prevention of air bubbles 20% Mixing insulin in a syringe (for syringe users) 46% Re-suspension of cloudy insulin 27% Single use of syringe/needle 17% Safe disposal of sharps (needles, syringes) 28% Injection under 90 /45 20%

FOCUS!!

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

Christian Binder 1969: Soluble 131I-insulin (pig, U40) is absorbed faster from the abdomen compared to thigh with buttock in between. C. Binder: Absorption of injected insulin. Thesis, Copenhagen 1969

Absorption of Rapid-Acting Insulin Analogs No statistically significant difference between abdomen and thigh in time-topeak. Peak is somewhat lower and effect more protracted in thigh.

Absorption of regular insulin and insulin lispro2 Mean GIR versus time of all treatments (n = 12): Regular insulin (0.2 U/kg; A, insulin lispro (0.2 U/kg; B). Braak EW, et al. Diabetes Care. 1996;19(12):1437-1440.

Absorption of insulin 125I-Lantus after injection in arm, thigh and abdominal area Disappearance of radioactivity = arm = thigh --------- = abdomen Owens et al, Diabetes Care 23;6,June 2000

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

Effect of intramuscular injection, regular human insulin Diabetes Care. 1990 May;13(5):473-7

Absorption of Rapid-Acting Insulin Analogs No statistically significant difference in insulin absorption between fat and muscle tissue; however, only studied in resting muscle There is a 10-fold increase in blood flow in the working muscle! International consensus is still to recommend subcutaneous (sc), ie, intralipomatous injection

Insulin Levemir, sc and im injection Insulin Detemir Mean Profiles per Adm. Route Insulin Detemir (pmol/l) 4000 3500 3000 2500 2000 1500 1000 500 0 0 Novo Nordisk data on file 3 6 9 12 15 Elapsed Time (hours) i.m. i.v. Trial ID.: NN304-1320 Each mean profile based on data from 16 subjects Note that at least two measurements must be available to calculate a mean concentration of Insulin Detemir. Thus at time points where there is one or no valid measurements no markings occur on the figure e.g. at time points later than 240 minutes for the i.v. adm. route 18 21 24 s.c. Spadille ApS (08FEB02)

Diabetic Medicine 2005;22:1444-45

CT of thigh, normal-weight adult male

CT scan of abdomen, normal-weight male. White dots are contrast. 8 mm needle.

CT, abdominal area, female with DM2, BMI 28.0

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

Injection Depth and Insulin Absorption Frid et al., Intraregional Differences in the Absorption of Unmodified Insulin from the Abdominal Wall. Diabetic Medicine 1992; 9; 236-239

Injection Depth and Insulin Absorption 3mm A) 2mm B) I-labelled short acting insulin was injected ( 5 units each patient) Radioactivity decreased by insulin absorption (in %) One defined injection site was chosen for each abomen and thigh 2 injection depths, controlled by ultrasound: A) 3mm below the skin surface B) 2mm above the muscle facies 125 Injection Depth B) [from skin surface in mm]: Abdomen 9±2 / 15±3 Thigh 7±1 / 14±3 Frid et al., Intraregional Differences in the Absorption of Unmodified Insulin from the Abdominal Wall_Diabetic Medicine 1992; 9; 236-239

Injection Depth and Insulin Absorption 100 90 80 70 60 50 40 60 min 120 min 175 min Thigh - Deep Injection Thigh - Superficial Injection Abdomen - Deep Injection Abdomen - Superficial Injection No influence of the injection depth on the kinetics of insulin absorption has been shown in the study.

I n j e c t i o n Te c h n i q u e : Wh at Do We K n ow a n d Wh at Do We Wa n t t o K n ow? What about insulin absorption from different sites? Are modern insulin analogues different from human insulins regarding absorption? In what tissue do we want to deposit insulin? What technique do we use to achieve that? Does depth of injection influence absorption? How thick is the skin?

Gibney MA et al. Curr Med Res Opin. 2010 Jun;26(6):1519-30

Gibney MA et al. Curr Med Res Opin. 2010 Jun;26(6):1519-30

What Insulins at What Injection Site? All insulins should normally be given sc Soluble human insulins in the abdominal area NPH-insulins in the thigh or gluteal area Rapid-acting insulin analogs in the abdomen, may be given elsewere Insulin glargine in abdomen, thigh, or gluteal area (no studies), strictly sc Insulin detemir in the thigh (or gluteal area, no studies), strictly sc Premix insulins abdominal area in the morning; thigh or gluteal area in the afternoon/evening

Needle length 4, 5 and 6 mm needles may be used by any patient including obese ones; they will provide equivalent glycaemic control compared to 8 mm and 12.7 mm needles (9,63,110,112,113) A1 There is no evidence to date of significant leakage of insulin, increased pain, worsened diabetes management or other complications whrn using shorter (5-6 mm) needles. (9,63,110,114) A1

Directive 2010/32/EU

European Union Legislation In accordance with a new EU Directive and its transpositions into member-state legislation, all at-risk injections must be given with a safety-engineered device. A1 This obligation covers all diabetes injections in the hospital as well as those given in distributed institutional settings (nursing homes, home health settings, ambulatory clinics). A1 WISE, Brussels 14-15 Oct 2011

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