Heparin is a drug used to help stop blood from clotting. It comes in two forms: unfractionated heparin (UFH) and low molecular weight heparin (LMWH). LMWH has a longer half-life (the time it takes for the concentration of a drug in the body to be reduced by 50%) and fewer side effects compared to UFH. Heparin is usually given by injection just underneath the skin, going into the layer of fat under the skin so that it is released slowly into the body. This type of injection can sometimes cause bruising and pain at the site where the needle is inserted. Bruising occurs when the small blood vessels and capillaries break and bleed under the skin and lead to discolouration of the skin. This bleeding can sometimes worsen and cause a swelling, known as a haematoma, that occurs when blood collects in the injury site. Several studies have been carried out to find out if the speed of injection affects the amount of pain and bruising at the site where the injection is given. Study investigators think that slow injection of heparin allows time for tissue under the skin to accommodate the injected volume, resulting in reduced pressure, capillary bleeding, and site pain intensity, thereby minimising the likelihood of bruising at the injection site. However, the results of studies differ, and study authors have not reached a clear final conclusion.
Study characteristics and key results
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 22 June 2020). Five studies met our inclusion criteria and were included in the review. The included studies took place in Thailand, Turkey, Italy, and China, and enrolled a total of 503 people (312 female and 191 male participants). All study participants received LMWH, whilst no study used UFH.
Study investigators injected heparin into the abdomen of participants. Participants could watch the injection being given and knew whether it was fast (10 seconds long) or slow (30 seconds long).
We found that pain may be slightly reduced 48 hours after slow injection compared with fast injection. Similarly, there may be smaller bruise sizes and fewer bruises with the slow injection 48 and 60 hours after the injection. None of the included studies measured the number or size of haematomas.
Certainty of the evidence
We graded the certainty of the evidence as low or very low because we found only a small number of published studies that reported on our review question, and the studies were small and had contradicting results. The fact that participants knew whether they had received a fast or a slow injection may also have affected the results because this knowledge may have led them to use different techniques (i.e. applying cold, heat, or massage) to relieve the pain and bruising based on the intervention received.
Administering medication safely and enhancing patient comfort are the main aims of clinical nurses. In this review, we identified five RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity, bruise size and incidence. We found that pain may be slightly reduced 48 hours after slow injection. Similarly, there may be a reduction in bruise size and incidence after slow injection compared to fast injection 48 and 60 hours postinjection. We downgraded the certainty of the evidence for all outcomes to low or very low due to risk of bias concerns, imprecision, and inconsistency. Accordingly, new trials with a more robust design, more participants, and a focus on different injection speeds will be useful in strengthening the certainty of the available evidence.
Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. Several studies have been carried out to determine if speed of injection affects the amount of pain and bruising where the injection is given; however, the results of these studies have differed, and study authors have not reached a clear final conclusion. This is the second update of a review first published in 2014.
To assess the effects of duration (speed) of subcutaneous heparin injection on pain and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). We also looked at haematoma at the injection site.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 June 2020. We undertook reference checking of included studies to identify additional studies.
We searched for randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site.
For this update, two review authors independently selected studies and extracted data via Covidence software and assessed methodological quality using Cochrane's risk of bias tool. The primary outcomes of interest were pain intensity at injection site and size and incidence of bruising. The secondary outcomes of interest were size and incidence of haematoma at injection site. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with corresponding 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria.
We identified one new study for this update, resulting in a total of five included studies with 503 participants who received subcutaneous injections of LMWH into the abdomen. Given the nature of the intervention, it was not possible to blind participants and caregivers (personnel) in any of the included studies. Two studies described blinding of outcome assessors. 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.
Four studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection; meta-analysis showed no evidence of a difference in site pain intensity immediately after slow injection when compared to fast injection (MD −1.52, 95% CI −3.56 to 0.53; 140 participants; low-certainty evidence). Meta-analysis of three studies indicated that site pain intensity may be slightly reduced 48 hours after the slow heparin injection compared to fast injection (MD −1.60, 95% CI −2.69 to −0.51; 103 participants; low-certainty evidence).
Five studies assessed bruise size at 48 hours, and two studies assessed bruise size at 60 hours. Meta-analysis showed there may be a reduction in bruise size 48 hours (SMD −0.54, 95% CI −1.05 to −0.02; 503 participants; 5 studies; very low-certainty evidence) and 60 hours (SMD −0.49, 95% CI −0.93 to −0.06; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. There was no evidence of a difference in bruise size 72 hours after slow injection compared to fast injection (SMD −0.27, 95% CI −0.61 to 0.06; 140 participants; 2 studies; low-certainty evidence).
Three studies evaluated incidence of bruising and showed there may be a reduction in bruise incidence 48 hours (OR 0.39, 95% CI 0.26 to 0.60; 444 participants; low-certainty evidence) and 60 hours (OR 0.25, 95% CI 0.10 to 0.65; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. We downgraded the certainty of the evidence due to risk of bias concerns, imprecision, and inconsistency.
None of the included studies measured size or incidence of haematoma.