Slow versus fast subcutaneous heparin injections for prevention of bruising and site‐pain intensity
Abstract
Background
Heparin is an anticoagulant medication that is normally 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.
Objectives
To assess the effects of the duration (speed) of subcutaneous heparin injection on pain, haematoma and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin or low molecular weight heparin.
Search methods
The Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 7). We searched MEDLINE, EMBASE, CINAHL and two Persian databases Iranmedex and SID (August 2013).
Selection criteria
We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injections of heparin on pain, bruising and haematoma at the injection site.
Data collection and analysis
Two review authors, working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by the Cochrane Handbook to assess the quality of included studies. The study outcomes were summarised using quantitative and qualitative methods.
Main results
One RCT was identified which met the inclusion criteria, involving 50 participants with a mean age of 55.25 (± 12.37) years. In this trial it was not possible to blind the participants and care givers. The method of sequence generation and allocation concealment was not described. The overall quality of the evidence was moderate due to the single small included study. Each participant had two injections, one in the left side and one in right side of the abdomen. One of these was injected slowly (intervention) and the other was injected fast (control). The second injection was 12 hours after the first injection. The duration of fast injection was 10 seconds and the duration of slow injection was 30 seconds. The study reported a significantly lower pain intensity for slow versus fast injection. The mean pain intensity was 13.9 ± 17.1 mm with the slow injection and 20.6 ± 22.3 mm with the fast injection (P < 0.001). In addition the bruising sizes were smaller with slow injections compared to fast injections at 48 hours follow‐up (mean bruising size 18.76 ± 9.32 mm2 with the slow injection and 109.2 ± 468.66 mm2 with the fast injection, P = 0.033) and 72 hours follow‐up (mean bruising size 21.72 ± 76.16 mm2 with the slow injection and 110.12 ± 472.86 mm2 with the fast injection, P = 0.025). The incidence of haematoma was not measured as an outcome.
Authors' conclusions
There is only limited evidence of any difference in pain intensity and bruising sizes following slow versus fast injections due to the inclusion of only one small unblinded trial. The single included study suggests that slow injection might have slightly lower pain intensity and bruising size at the heparin injection site, but the results should be considered with caution. Until more reliable evidence emerges, slow injection might be the preferred approach.
PICOs
Plain language summary
Does the speed of injection make a difference to the amount of pain and bruising in people having heparin injections?
Heparin is a drug used to help stop blood from clotting. It comes in two forms ‐ unfractionated heparin and low molecular weight heparin. These are usually given by injection just underneath the skin. The heparin goes 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 where the needle goes in. It can also sometimes cause a swelling that contains blood, called a haematoma.
There have been some studies to see if the speed of injection affects the amount of pain and bruising where the injection is given. We searched for these studies in August 2013 and found only one that fitted our review criteria. The study took place in Turkey. It looked at 50 people, male and female, whose average age was 55 years old. The participants were in hospital, in the neurology, orthopaedic and cardiology units. Each person was given either a slow or a fast injection in one side of their abdomen (stomach). Then 12 hours later they had the opposite injection in the other side of their abdomen. So, if they had a slow injection first, they would have a fast injection second, and if they had a fast injection first then they would have a slow injection second. The order of fast or slow injection first was chosen at random for each person. Since the people could watch the injection being given, they knew whether it was fast (10 seconds long) or slow (30 seconds long).
The people having the injections said that the pain was less with the slow injection. The size of the bruise was also smaller with the slow injection. In this study, they did not measure if there was a swelling with blood inside (haematoma). We rated the quality of the evidence as 'moderate'.
These results suggest that slow injections probably cause less pain and bruising than fast injections. However, we need to be careful because these results are from only one study and only 50 people were included. More studies need to be done before we can really know whether slow injections are less painful and cause less bruising than fast injections. Until more reliable evidence emerges, slow injection might be the preferred approach.
Authors' conclusions
Background
Description of the condition
Heparin is an anticoagulant medication that is used to prevent further development of an existing thrombus or new clot formation. Heparin is prescribed for the treatment or prevention of thromboembolic disorders. Different forms of heparin exist. Unfractionated heparin (UFH) may be administered either by subcutaneous (SC) or intravenous (IV) injection but low molecular weight heparin (LMWH) is a type of heparin that is only administered subcutaneously (Hodgson 2007).
Subcutaneous administration of heparin is frequently carried out as a nursing intervention (Wooldridge 1988). Subcutaneous injection is normally chosen when slow and continuous absorption of the drug is needed, e.g. insulin or heparin. The drug is injected into fat and connective tissue underlying the dermis, where there is less blood flow and as a result a slower absorption rate. Suitable sites for SC injections are often the umbilical region of the abdomen and the lateral sides of the arms and thighs (Hunter 2008). Administration and injection techniques that are used for subcutaneous heparin injection may cause adverse outcomes such as bruising, haematoma and pain at the injection site (Chan 2001; Kuzu 2001). The incidence of bruising at the injection site using 3 ml and 1 ml syringes has been reported as 69% and 79%, respectively (Hadley 1996). It is argued that slow versus fast injection of heparin might reduce pain, haematoma and bruising at the injection site. However, a systematic review has not been conducted to explore this theory.
Description of the intervention
Reducing patients' discomfort whenever and wherever possible is an important aim of nursing. Several studies have explored the effects of the temperature, syringe size, needle gauge, injection volume and air bubble in the syringe, etc on the incidence of bruising, haematoma and pain at the injection site (Chan 2001; Kuzu 2001). Other studies have explored the effect of the duration of the injection on the incidence of bruising and pain (Zaybak 2008). For example, Balci Akpinar 2008 has recommended that subcutaneous heparin injections must be given slowly to reduce bruising and pain but other reports in the literature did not show any significant differences between the two techniques (Chenicek 2004; Rahmani 1999).
How the intervention might work
Adverse drug reactions are a relatively common problem that might cause harm to patients. Nurses should apply the techniques that minimise the side effects of subcutaneous injections including site‐pain, haematoma and bruising. The injection speed of heparin might have a significant effect on pain, haematoma and bruising at the injection site. It is argued that when heparin is administered slowly it allows time for subcutaneous tissue to accommodate the injected volume, and this results in reducing pressure, capillary bleeding, site‐pain and other likely damages (Chan 2001).
Why it is important to do this review
Several studies have been conducted comparing slow versus fast subcutaneous injection of heparin, but their results differ and studies normally do not reach a clear final conclusion about the exact speed of heparin injection (Chenicek 2004; Zaybak 2008). This controversy highlights the importance of conducting a systematic review to explore the effect of different durations of heparin injections on complications at the injection site.
Objectives
To assess the effect of the duration (speed) of subcutaneous injection of heparin on pain, haematoma and bruising at the injection site in people admitted to hospitals or clinics who require treatment with UFH or LMWH.
Methods
Criteria for considering studies for this review
Types of studies
We searched for randomised controlled trials (RCT) to include in the study. We excluded clinical controlled trials (CCT), quasi‐randomised controlled trials (QRCT) and quasi‐experimental studies.
Types of participants
Participants were males and females ≥ 18 years old admitted to hospitals or clinics who were treated with subcutaneous injections of heparin including LMWH and UFH. We excluded trials involving people treated with other anticoagulant drugs.
Types of interventions
Interventions were slow subcutaneous administration of heparin (LMWH or UFH) in one site of the body and controls were fast subcutaneous administration of LMWH or UFH in another site of the same body.
In this review we considered an injection speed of less than 20 seconds as the fast injection and an injection speed of 20 seconds or more as the slow injection. We then considered the slow injection of heparin as intervention and compared it with the fast injection of heparin as control.
Types of outcome measures
Primary outcomes
The first primary outcome for this review was the pain intensity. We included studies that measured pain intensity at the injection site by any scales, including visual analogue scale, numeric rating, McGill scales, descriptive or other pain scales. The second primary outcome was size of bruising at the injection site.
Secondary outcomes
Secondary outcome was the incidence of haematoma at the injection site.
Search methods for identification of studies
There was no restriction of language of publication.
Electronic searches
The Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator (TSC) searched the Specialised Register (last searched August 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 7, part of The Cochrane Library, (www.thecochranelibrary.com). See Appendix 1 for details of the search strategy used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, AMED, and through handsearching relevant journals. The full list of the databases, journals and conference proceedings which have been searched, as well as the search strategies used are described in the Specialised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com).
The following trial databases were also searched by the TSC for details of ongoing and unpublished studies using the terms subcutaneous and heparin:
World Health Organization International Clinical Trials Registry http://apps.who.int/trialsearch/
ClinicalTrials.gov http://clinicaltrials.gov/
Current Controlled Trials http://www.controlled‐trials.com/
In addition, the authors searched EMBASE (1980 to August 2013), MEDLINE (1947 to August 2013), CINAHL (August 2013) and two Persian databases Iranmedex (http://health.barakatkns.com/irmedex/index.asp) (August 2013) and SID (http://www.sid.ir/En/index.asp) (August 2013) using the search strategies in Appendix 2, Appendix 3, Appendix 4 and Appendix 5.
Searching other resources
We reviewed reference lists of the included studies to identify other studies. In addition, we contacted relevant trial authors to identify any additional studies.
Data collection and analysis
Selection of studies
Two review authors (MM, LJ) independently assessed titles and abstracts of the studies retrieved by searching to determine whether each study met the inclusion criteria. If it was not possible to include or exclude a study on the basis of the title or abstract the reviewers obtained the full version of the articles. The same two reviewers (MM, LJ) then assessed the full papers independently to explore if they met the inclusion criteria. Disagreements were resolved by discussion and, if necessary, by a third reviewer (AAS).
Data extraction and management
We extracted data from the included study using a structured data extraction form. Data extraction was performed independently by two review authors (MM, LJ). Disagreements were resolved by discussion and, if necessary, by a third review author (AAS). The following data were collected from the included study: study design, method of randomisation, method of concealment of allocation, blinding, participants, interventions, duration of intervention, main inclusion and exclusion criteria, outcomes, the methods of measuring pain, bruising and haematoma, and methods of statistical analysis and results.
Assessment of risk of bias in included studies
Two review authors (MM, LJ) independently assessed the quality of the included study. Disagreements were resolved by discussion and, if necessary, by a third reviewer (AAS). We used the 'Risk of bias' tool as described by Higgins 2011 for assessing the risk of bias.
Measures of treatment effect
Bruising size and pain intensity were continuous outcome measures: therefore, we planned to calculate mean difference (MD) and 95% confidence intervals (95% CI) for them. If different scales were used we planned to employ standardised mean difference (SMD).
Unit of analysis issues
Cross‐over trials were eligible for this review because heparin has a temporary effect and the half‐life of heparin is 4.5 to 7 hours after administration. Therefore, the first administration of heparin has no effect on the bruising formation of the second injection. Cluster randomised trials were not expected and none were identified for this review.
Dealing with missing data
The trialists were contacted to provide missing information in the included study.
Assessment of heterogeneity
We planned to use a visual inspection of the forest plots, I2 test and Chi2 statistic to evaluate heterogeneity among the studies if sufficient studies were available. However, because we included only one study it was not possible to assess between‐study heterogeneity.
Assessment of reporting biases
It is recommended that the test for funnel plot asymmetry should be used when there are at least 10 included studies (Higgins 2011). Since there was only one included study it was not appropriate to use a funnel plot, to detect publication bias.
Data synthesis
Study outcomes were summarised using narrative and quantitative methods. In future updates we plan to use a random‐effects model to meta‐analyse the data of the included studies.
Subgroup analysis and investigation of heterogeneity
We planned to perform subgroup analyses if sufficient studies met the criteria for meta‐analysis and could be grouped further according to participants' sex, age, etc.
Sensitivity analysis
We planned to perform a sensitivity analysis to assess possible influences of the following factors on the effect size, if sufficient studies met the inclusion criteria of this review:
• by excluding unpublished studies;
• by taking account of the quality of studies;
• by excluding studies with different languages, or from different countries.
Results
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies.
Results of the search
See Figure 1.
Study flow diagram.
Included studies
Details of the one included study are given in the Characteristics of included studies table. We included a randomised controlled trial (Zaybak 2008) that was conducted in Turkey. The study enrolled 50 participants with mean age 55.25 (SD 12.37) years. The study enrolled both male and female participants who were hospitalised at the neurology, orthopaedics and cardiology units. The study included participants who received subcutaneous injections of LMWH, were conscious and whose platelet values were within the normal limits before the research. Injections were performed in the left and right side of the abdomen. The study used a 30 second injection as the intervention (slow injection) versus a 10 second injection as the control (fast injection). Time between two injections was 12 hours.
Excluded studies
Details of the excluded studies are given in the Characteristics of excluded studies table. We excluded 14 studies for various reasons. Six studies were excluded because of quasi‐experimental design (Babaie Asl 2008; Balci Akpinar 2008; Chan 2001; Gholam Nezhad 2004; Sanagoo 2011; Tehrani Neshat 2005) and one study because of its non‐randomised design (Nair 2008).
In addition, we excluded two other studies because they used other anticoagulant drugs during the study (Chenicek 2004; Rahmani 1999). In another study heparin injection durations were less than 20 seconds in all comparison groups (Pourghaznein 2014). The remaining excluded studies compared various techniques of heparin injection, but they did not explore the effect of injection duration on the study outcomes. Two of these studies compared two techniques (McGowan 1990; Wooldridge 1988), one study compared three different techniques (Vanbree 1984) and one study compared four techniques of heparin injection (Jesús Gómez 2005).
Risk of bias in included studies
For a summary of the 'Risk of bias' see the Characteristics of included studies table and Figure 2.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
In the Zaybak trial (Zaybak 2008) every participant had the slow injection in one side of the abdomen and the fast injection in the other side of the abdomen. Therefore, it was not possible to randomise participants into two separate groups. However, participants could instead be randomised into intervention or control group according to treatment order. Each participant was given one of the two injection techniques (10 or 30 second injection duration) for the first injection and the second technique 12 hours later. For each individual the technique to be used first (10 or 30 second injection duration) was identified randomly using a randomised sequence. However, the method of sequence generation and allocation concealment was not described.
Blinding
In Zaybak 2008 every participant had both slow and fast injections, so blinding of participants was not possible. Due to the nature of the intervention it was also not possible to blind the care givers. However, the outcome assessors were blinded to the allocated intervention for injection pain intensity but it was not reported whether this was also the case for the outcome bruising.
Incomplete outcome data
The included study had an adequate description of the study outcomes (pain and bruising), withdrawals and drop‐outs.
Selective reporting
Although we did not have access to the study protocols, from the study reports it appears that all expected outcomes were reported.
Other potential sources of bias
The Zaybak 2008 study mentioned some aspects of heparin injection including "injection in the lower abdominal wall, the insertion of the needle into the tissue at a 90º angle, grasping the tissue of injection and injecting the drug without aspirating" but there was no clear description about other aspects of the heparin injections (e.g. heparin temperature, syringe size, needle gauge, injection volume and air bubble in the syringe, etc). This may have affected the outcomes. We contacted the trialists for missing information via email, but no reply was received.
Effects of interventions
As only one study was included we were unable to perform the planned random‐effects meta‐analyses, investigations for heterogeneity and subgroup and sensitivity analyses.
Pain intensity
The Zaybak trial (Zaybak 2008) assessed site‐pain intensity by visual analogue scale (VAS) (0 to 100 millimetre) immediately after injection. Higher numbers represented greater pain. The mean pain intensity was 13.9 ± 17.1 mm with the slow injection and 20.6 ± 22.3 mm with the fast injection. Thus, site‐pain intensity was lower with slow injection compared with fast injection (P < 0.001).
Size of bruising
Zaybak 2008 evaluated injection‐site bruising at 48 and 72 hours after each injection. They used millimetric measuring paper to measure the area of the bruise and recorded it as square millimetres (mm2). After 48 hours follow‐up the mean bruising size was 18.76 ± 9.32 mm2 with the slow injection and 109.2 ± 468.66 mm2 with the fast injection (P = 0.033).
After 72 hours follow‐up the mean bruising size was 21.72 ± 76.16 mm2 with the slow injection and 110.12 ± 472.86 mm2 with the fast injection (P = 0.025). Bruising size was lower with slow injection compared with fast injection at both 48 and 72 hours follow‐up.
Incidence of haematoma
Zaybak 2008 did not measure the incidence of haematoma as an outcome.
Discussion
Summary of main results
This systematic review incorporated data from a single trial enrolling 50 participants to assess the effects of the duration of subcutaneous heparin injection on pain and bruising at the injection site. The results of this study show that the slow injection technique yielded significantly lower pain intensity (P < 0.001) and bruising size (P < 0.05) than the fast injection technique.
The level of pain and bruising after the heparin injection was relatively small in both treatment and control groups. In addition, the differences in the study outcomes between the two groups were small from a clinical point of view. Therefore, until new evidence emerges slow injection should be considered as the preferred option.
Overall completeness and applicability of evidence
In Zaybak 2008 heparin was injected in the right or left side of the abdomen, while in some excluded studies heparin was injected in the arm (Babaie Asl 2008; Balci Akpinar 2008). Therefore, it should be considered that the pain intensity and bruising size at the injection site could be different depending on whether heparin was injected in the arm, thigh or abdomen.
In Zaybak 2008 LMWH was used for injection and it should be considered that the outcomes could be different if UFH was used.
There was no clear description about how the analgesic medications were used. As the randomisation of heparin injection was done on a 'participant side' basis, and it is possible that the analgesic medication had an even distribution between slow and fast injection groups, this might not have affected the randomised results. We tried to contact the trialists regarding this issue but no reply was received.
This review was based on a relatively small unblinded RCT and the method of randomisation was not clear. In addition, the differences in the study outcomes between the two groups were relatively small from a clinical point of view. Therefore, the results should be interpreted and used with caution.
Quality of the evidence
Although randomisation is one of the most important factors to assess study quality, the nature of the intervention and the control in the included study made a usual randomisation and allocation concealment impossible; although participants in Zaybak 2008 could be randomised into intervention or control group according to treatment order. However, the method of sequence generation and allocation concealment was not described in this study. Moreover, the nature of the intervention made a double‐blind study design impossible and only the outcome assessors could be blinded in this trial. The overall quality of the evidence is moderate due to the single small included study.
Potential biases in the review process
To minimise the possibility of bias we tried to locate all RCTs by a broad and comprehensive search of several national and international databases. In addition, the study selection, data collection and quality assessment of included studies were performed independently by two trained reviewers. Data collection was performed according to the process suggested by The Cochrane Collaboration. We also followed Cochrane processes as described by Higgins 2011 for assessing the risk of bias.
Agreements and disagreements with other studies or reviews
Two excluded studies that compared slow versus fast heparin injections (Chenicek 2004; Rahmani 1999) reported no statistically significant difference between the two techniques in pain intensity and bruising size. It should be considered that both of these studies used other anticoagulant drugs such as aspirin and this might be a reason for their findings. On the other hand, six studies (Babaie Asl 2008; Balci Akpinar 2008; Chan 2001; Gholam Nezhad 2004; Sanagoo 2011; Tehrani Neshat 2005) with a quasi‐experimental design reported that slow injection had lower pain intensity and bruising size at the heparin injection site, which is similar to the findings of the single RCT included in this review.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
