Leakage Influenced by Injection Technique
Typical injection sites for a person with diabetes are the abdomen, thighs, buttocks, and upper arms, but only injections in the abdomen and thighs have been investigated for a relation with insulin leakage. Clinical trials provide contradicting conclusions, since some have found that leakage is more likely to occur after injections in the thighs than in the abdomen,3,8,10 whereas others found no relation between injection site and leakage.2,11 Our data show that when injecting in the subcutaneous tissue of the abdomen, both the frequency and the amount of leakage are lower than after injections in the thighs. It is unknown why less leakage is seen in the abdomen than in the thighs. However, a previous study described that making a skinfold in the abdomen is easier than in the thighs,12 which may indicate important differences in tissue density, internal tissue pressure, or other mechanical factors of the subcutaneous layer and the skin.
Whether the needle insertion angle influences leakage has been discussed previously with contradicting recommendations.13,14 In the present study, an angled needle insertion of 45° caused more leakage than after an injection with a perpendicular needle insertion. This may be explained by the fact that when using an angled insertion, the deposit of insulin is situated closer to the dense dermal layer. The difference may be that a deeper subcutaneous insulin deposition displaces the soft subcutaneous tissue without much resistance, while a deposition closer to the much more resistant dermal layer may cause higher pressure and more fluid to be forced out of the needle puncture. Thus, using an angled insertion might correspond to using a shorter needle. A number of studies conclude that a shorter needle causes less or equal amount of leakage than when using a longer needle.2,4,15-18 However, in these studies investigators tested not only needles of different length but also of different diameter, which could potentially influence the results. Two prior studies isolated needle length as the varying parameter and found that when only varying the length, shorter needles cause more leakage.9,11 Therefore, the increased leakage for 45° insertions in our study could potentially be explained by the closer deposition to the dermal layer. Leakage frequency has been reported to be higher with perpendicular than with angled injections (65% for perpendicular and 59% for angled, P < .001).3 In our study, there was no difference in frequency of leakage between perpendicular and angled injections.
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Larger injection volumes have been reported to cause more leakage in absolute terms.8,19-21 In 1 study, the volume of the injection did not affect the frequency of leakage.3 In accordance with most previous studies, we found that larger injection volumes cause larger absolute leakage.8 The relative amount of leakage did not differ for different injected volumes, which is also in line with a published study.21 The reason for the injection volume dependency could be an increased tissue pressure on the insulin deposition from the surrounding subcutaneous tissue. Thereby, a larger amount of leakage could be pushed out of the needle puncture. Although no difference in leakage volume was seen between 400, 800, and 1200 µL injections, the 1200 µL injections caused leakage more frequently.
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The effect of wait time on leakage has been investigated by several research groups, resulting in that the recommended wait time has decreased over the years; from 30-60 seconds in 1991,19 to 20 seconds in 2006,13 down to 10 seconds in publications between 2010 and 2012,14,21-23 and 6-10 seconds in a 2011 publication.24 A study from 2010 concluded that there was no relationship between wait time (more than/less than 10 seconds) and the volume of leakage from the injection site.25 To our knowledge wait times less than 6 seconds have not been investigated prior to our study. Our data show that immediate withdrawal of the needle caused more leakage than waiting as little as 3 seconds before withdrawal. No differences were observed between wait times of 3, 6, and 10 seconds. Thus, the subcutaneous tissue may not need more than 3 seconds to even out the applied pressure of an injection.
In several publications it is advised to inject slowly to avoid leakage,13,14,19,21 but in an experimental approach on porcine skin, no relation between injection speed and amount of leakage was found.9 Overall, speed did not influence leakage in our study, but higher speed caused the numerically largest absolute leakage, except for the injection volume of 1600 μL for which the leakage was negatively related to injection speed. It should, however, be noted that regardless of injection speed and dose, all needles were in the skin for a total of 15-20 seconds to blind the injection speed and volume combination.8 Thus, the 1600 µL dose at the fastest speed of 450 µL/s had a short injection time (3.5 seconds) followed by a long wait time (11.5-16.5 seconds), while the 1600 µL dose at lowest speed had a long injection time (10.7 seconds injection) and a short wait time (4.3-9.3 seconds). This could explain the negative relation between injection speed and leakage seen for 1600 µL injections. Although the findings regarding wait time revealed that waiting times between 3 and 10 seconds did not influence leakage, it should be noted that the doses used to test for wait time effect on leakage was 400 µL. For a dose 4 times as large, waiting time might play an important role, wherefore the combination of dose volume, speed and wait time should be assessed in future studies.
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