Abstract: For this update, we identified three new studies and therefore included in the Review four studies with a total of 459 participants who received subcutaneous injections of LMWH into the abdomen. Only one trial reported the injected drug volume (0.4 mL). Owing to the nature of the intervention, it was not possible to blind participants and care givers (personnel) in any included study. Two studies described blinding of outcome assessors; therefore overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds and the duration of the slow injection was 30 seconds in all included studies. Three studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection, and meta-analysis on 140 participants showed no clear difference in site pain intensity immediately post slow injection when compared to fast injection (low-quality evidence; P = 0.15). In contrast, meta-analysis of two studies with 59 participants showed that 48 hours after the heparin injection, slow injection was associated with less pain intensity compared to fast injection (low-quality evidence; P = 0.007). One study (40 participants) reported pain intensity at 60 and 72 hours after injection. This study described no clear difference in site pain intensity at 60 and 72 hours post slow injection compared to fast injection. All four included studies assessed bruise size at 48 hours after each injection. Meta-analysis on 459 participants showed no difference in bruise size after slow injection compared to fast injection (low-quality evidence; P = 0.07). None of the included studies measured the incidence of haematoma as an outcome. We found four RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity and bruise size. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 and 72 hours post injection. However, slow injection may reduce site pain intensity 48 hours after injection (low-quality evidence). We observed no clear difference in bruise size after slow injection compared to fast injection (low-quality evidence). We judged this evidence to be of low quality owing to imprecision and inconsistency.

Plain-language summary: We searched for studies that investigated the effects of speed of injection on the amount of pain and bruising where the injection is given (current to March 2017) and found four studies that fitted our review criteria. These studies took place in Turkey, Italy, and China. They enrolled a total of 459 people including 287 female and 172 male participants. All patients received LMWH, and none of the studies used UFH. Participants were treated in hospital, in neurology, orthopaedic, and cardiology units. Investigators injected heparin slow or fast into the abdomen (stomach) of participants. Participants could watch the injection being given and knew whether it was fast (10 seconds long) or slow (30 seconds long). Participants given injections said that pain was less with the slow injection after 48 hours. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 hours and 72 hours after injection. The bruise was not smaller with the slow injection. None of the included studies reported if participants had a swelling with blood inside (haematoma). We graded the quality of evidence as low because we found only a small number of published studies that reported on this question. These studies were small and had contradictory results. The fact that participants knew whether they received a fast or a slow injection may have affected the results.