The pen-like injector for insulin is widely used by diabetic patients and improves their quality of life. However, an important disadvantage of this reusable injector is the possible contamination of biological materials (1). Macroscopic blood regurgitation into a cartridge is sometimes observed. In such a case, if the cartridges were to be used by another patient, this could result in the transmission of contagious diseases such as the hepatitis B virus. Therefore, we investigated the blood contamination in 146 cartridges used by diabetic patients by immunochromatography using anti-human hemoglobin antibody.

Hemoglobin was detected in 6 of 146 cartridges (4.1%). The quantity of the contaminated blood per cartridge was calculated to be over 0.3 μl. We carried out a simulative examination using three types of injectors. The injector punctured a rubber tube filled with dye solution. After 800 μl of insulin (2 U insulin serially 40 times for Novopen and 4 U insulin serially 20 times for Novopen III and Autopen) was injected without changing the needle under a hydrostatic pressure of 0 cm H2O, the dye content in the cartridge was measured fluorometrically. Dye regurgitation was detected in 13 of 19 cartridges with Novopen, in 3 of 19 cartridges with Novopen III, and in only 1 of 19 cartridges with Autopen. Novopen showed the highest incidence of dye regurgitation compared with Novopen III (x2 test; P = 0.001) and Autopen (P < 0.0001). The volume of regurgitated dye solution was 0.03–0.22 μl per cartridge. When the hydrostatic pressure in the rubber tube was elevated from 0 to 5, 10, 30, and 100 cm H2O by lifting the reservoir of dye solution from a flat level to 100 cm in height, dye regurgitation occurred at each hydrostatic pressure and was independent of the hydrostatic pressure. Such regurgitation appears to be dependent on the devices used and possibly on the frequency of pressing.

In addition, a questionnaire was administered to 193 outpatients using insulin cartridges at four outpatient clinics when collecting the patients’ used cartridges. Twenty of these patients reported noticing a reddened cartridge after insulin injection, and two patients reported sharing their insulin cartridges with other patients.

A study on viral transmission in chimpanzees reported that, if serum was positive for hepatitis B e antigen, injection of even 108 dilutions of the serum (105 μl) in chimpanzees could result in hepatitis B virus infection (2). Our findings indicate that the amount of blood or dye regurgitated into cartridges would be sufficient to transmit hepatitis B virus infection. In fact, previous reports suggested that hepatitis B infection might be developed by dental use of pen-like injectors for local anesthesia (3,4). Of course, insulin cartridges contain anti-microbial agents (i.e., phenol or cresol) (5,6). However, these agents are effective only for killing bacteria, not viruses (7). Therefore, it is imperative that attention should be called to the careful use of cartridges as well as needles (8). Shared use of insulin cartridges must be prohibited to prevent the transmission of viral infections.

Floch JPL, Lange F, Herbreteau C, Perlemuter L: Biologic material in needles and cartridges after insulin injection with a pen in diabetic patients.
Diabetes Care
Shikata T, Karasawa T, Abe K, Uzawa T, Suzuki H, Oda T, Imai M, Mayumi M, Moritsugu Y: Hepatitis B e antigen and infectivity of hepatitis B virus.
J Infect Dis
Levin M, Maddrey WC, Wands JR, Mendeloff AI: Hepatitis B transmission by dentists.
Ohkubo T, Shibata M, Haraga Y, Kaya H, Takahashi H: Blood reflux into cartridges for dental anesthesia: detection in residual solution.
Clin Prevent Dent
Schade DS, Eaton RP: Bactericidal properties of commercial U.S.P. formulated insulin.
Rathod M, Saravolatz L, Pohlod D, Whitehouse FJ, Goldman H: Evaluation of the sterility and stability of insulin from multidose vials used for prolonged periods.
Infect Control
Scioli D, Pizzella T, Vollaro L, Nardiello S, De Feo L: The action of VIRKON No Foam on the hepatitis B virus.
Eur J Epidemiol
World Health Organization: Expanded programme on immunization: changing needles but not the syringes: an unsafe practice.
Wkly Epidem Rec

Address correspondence to Kazuo Sonoki, MD, Department of Internal Medicine, Kyushu Dental College, Manazuru 2-6-1, Kokurakita-ku, Kitakyushu, 803-8580, Japan. E-mail: