Venepuncture versus heel lance for blood sampling in term neonates

Shah V, Ohlsson A

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables and Graphs

Dates

Date edited: 22/08/2007
Date of last substantive update: 27/07/2007
Date of last minor update: / /
Date next stage expected 10/07/2009
Protocol first published: Issue 2, 1999
Review first published: Issue 2, 1999

Contact reviewer

Dr Vibhuti S Shah
Staff Neonatologist
Department of Paediatrics
Mount Sinai Hospital
Room 775A
600 University Avenue
Toronto
Ontario CANADA
M5G 1X5
Telephone 1: 416 586 4816
Telephone 2: 416 664 6708
Facsimile: 416 586 8745
E-mail: vshah@mtsinai.on.ca

Contribution of reviewers

Both review authors contributed to all sections of this review and to the updates of this review conducted in 2004 and 2007.

Internal sources of support

Mount Sinai Hospital, Toronto, Ontario, CANADA

External sources of support

None

What's new

This updates the review "Venepuncture versus heel lance for blood sampling in term neonates", published in The Cochrane Library, Issue 2, 1999 (Shah 1999b) and updated in 2004 (Shah 2004).

One additional randomized controlled trial was identified for inclusion. The data from this additional study strengthen the evidence that venepuncture is less painful compared to heel lance to obtain a blood sample from healthy term neonates. However, in the newly identified study, a team of seven trained nurses performed the two procedures and obtained blood samples on the first attempt.

Dates

Date review re-formatted: 13/09/1999
Date new studies sought but none found: / /
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Text of review

Synopsis

In most countries, a blood sample from newborn babies is needed for screening tests. A heel lance is the standard way of taking blood, but it is a painful procedure with no optimal method of pain relief known. This review of trials found evidence that venepuncture, when done by a trained practitioner, caused less pain than heel lance. The evidence included outcome measures using pain scales, how long the baby cried and how the mother rated their baby's pain.

Abstract

Background

Heel lance has been the conventional method of blood sampling in neonates for screening tests. Neonates undergoing this procedure experience pain. Despite various studies evaluating the role of pharmacological and non-pharmacological interventions to date, there are no effective and practical methods to alleviate pain from heel lance.

Objectives

To determine whether venepuncture or heel lance is less painful and more effective for blood sampling in term neonates.

Search strategy

Systematic search was performed in accordance with the Cochrane Neonatal Collaborative Review Group. Randomized controlled trials which compared pain response to venepuncture vs. heel lance were identified using MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), reference lists of identified trials and personal files. No language restrictions were applied.

Selection criteria

Randomized controlled trials which compared pain response to venepuncture vs. heel lance were selected for this review.

Data collection & analysis

Data regarding the primary outcome of pain response to venepuncture vs. heel lance as assessed by validated pain measures were abstracted. Secondary outcomes included the need of repeat blood sampling, bruising/hematoma at local site, and parental perception of their own anxiety and infant's pain. All data were analysed using RevMan 4.2.10. When possible, meta-analyses were performed using relative risk (RR) and risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, number needed to treat (NNT) was calculated. Weighted mean difference (WMD) was used for continuous data. When present, statistically significant between study heterogeneity was reported including the I squared (I² ) test.

Main results

Five trials were eligible for inclusion in the review (including one additional trial identified in this update). Pain assessments were made using validated pain measures including Neonatal Infant Pain Scale (NIPS), Neonatal Facial Action Coding System (NFCS), Premature Infant Pain Profile (PIPP) score and cry characteristics. Two trials did not report on outcomes for all enrolled infants (not intention to treat analyses). Despite the many different pain measures used, all studies showed statistically significantly lower pain scores for venepuncture as compared to heel lance. A meta-analysis of the NIPS scores during the first minute of the procedure (reported in two studies) was statistically significantly lower in the venepuncture group compared to the heel lance group [typical WMD -1.84 (95% CI -2.61, -1.06)]. There was no statistically significant heterogeneity for this outcome (p = 0.22; I² 33.3%). The typical RR for requiring more than one skin puncture for venepuncture vs. heel lance (reported in 4 studies) was 0.30 (95% CI 0.18, 0.49). The RD was -0.31 (95% CI -0.41, -0.22). For this outcome there was statistically significant between study heterogeneity (for RR, p = 0.02, I²74.3%; for RD, p < 0.00001, I² 96.6%). The number needed to treat (NNT) to avoid one repeat skin puncture was 3 (95% CI 2, 5). In one study, maternal anxiety was noted to be higher in the venepuncture group as compared to heel lance group prior to the procedure; however, after observing the procedure, mothers rated their infant's pain to be lower in the venepuncture group.

Reviewers' conclusions

Venepuncture, when performed by a skilled phlebotomist, appears to be the method of choice for blood sampling in term neonates. For each three venepunctures instead of heel lance, the need for one additional skin puncture can be avoided.

Further well designed randomized controlled trials need to be conducted. The interventions should be compared in settings where several individuals perform the venepuncture and/or the heel lance.

Background

Every year millions of neonates require diagnostic blood sampling. Neonates undergoing these procedures cry (Owens 1984; Brown 1987) and exhibit facial expression and body movements (Izard 1979; Grunau 1987; Johnston 1986) that are indicative of pain. Until recently, it was believed that infants and young children could not appreciate pain due to the immaturity of the central nervous system. However, it is now well established that the anatomical, physiological and neurochemical structures which convey pain are well developed in neonates (Fitzgerald 1989, CPS 2000). Recent research suggests that babies' early pain experience may alter their pain response in later infancy (Taddio 1995; Taddio 1997).

Heel lance (HL) has been the conventional method of blood sampling in neonates for screening tests (phenylketonuria and hypothyroidism) or measurements of serum bilirubin or glucose. Sick neonates (preterm and term infants) admitted to neonatal intensive care units (NICUs) undergo this procedure repeatedly as part of routine care. Barker 1995 reviewed the nature and frequency of invasive procedures in a NICU and showed that HL was the most common procedure being performed in a NICU. Apart from discomfort to the infant associated with HL, there are concerns regarding the possibility of puncturing the calcaneus and causing osteochondritis, ecchymosis or hemolyzed samples and the possibility of accidental injuries to personnel (Moxley 1989, Meehan 1998).

Various pharmacological and non-pharmacological interventions have been investigated for management of pain associated with HL. Automated piercing devices (Harpin 1983, Paes 1993), behavioural interventions such as pacifiers (Field 1984) and rocking (Campos 1994), sucrose (Stevens 1999), glucose (Skogdal 1997), non-sucrose sweet tasting solution (Ramenghi 1996), anaesthetic cream such as lignocaine (Rushforth 1995) and EMLA (Larsson 1995, McIntosh 1994), and paracetamol (Shah 1998) have been studied. The use of a mechanical lancet (Autolet) caused less physiological instability than manual HL (Harpin 1983, Paes 1993). The total volume of blood collected with automated device was significantly larger than with lancet device. The time required for blood sampling was significantly reduced and there was reduced hemolysis in the automated device group. Comforting measures were associated with less crying (Field 1984, Campos 1994) and use of sucrose (2 ml of 12% solution) two minutes prior to the procedure reduced composite pain measures (Stevens 1999). Anaesthetic cream (Rushforth 1995, Larsson 1995, McIntosh 1994) and paracetamol (Shah 1998) have been ineffective in decreasing pain scores with HL. Topical amethocaine gel does not have a clinically important effect on pain from HL blood sampling (Jain 2001). Despite various studies to date, there are no effective and practical methods to alleviate pain from HL (Ohlsson 2000).

Venepuncture (VP) is a common procedure performed in older infants and children (McKay 1966). The advantages of VP include a reduced risk of a hemolyzed or clotted sample, increased sample volume and possibly less pain (McKay 1966). The disadvantage of VP is the need for a skilled phlebotomist to perform the procedure (the phlebotomist will have to spend time training and the amount of time required depends on the skill of the individual). In contrast, the benefit of HL is the perceived ease to perform the task even by paramedical personnel.

The aim of this review is to compare pain response from VP vs. HL, the success rate of obtaining an adequate blood sample and sample collection times and possible adverse effects.

Objectives

The primary objective was to compare pain response to VP vs HL in term neonates.
The secondary objectives were to compare the need of repeated sampling, adverse effects, if any, to these interventions, sample collection times and the parent's perception of their infant's pain.

Criteria for considering studies for this review

Types of studies

Randomized and quasi-randomized controlled trials in which pain response from VP was compared to HL.

Types of participants

Healthy neonates of > 37 weeks gestational age (GA) subjected to blood sampling.

Types of interventions

VP or HL

Types of outcome measures

Primary outcome: Neonatal pain response as assessed by a validated pain measure:
1. Neonatal Infant Pain Score (Lawrence 1993)
2. Neonatal Facial Action Coding System (Craig 1994)
3. Premature Infant Pain Profile (Stevens 1996)
4. Cry (latency and duration of first cry, total cry duration and the percentage of crying during each procedure)

Secondary outcomes:
1. Need of repeated blood sampling
2. Bruising/hematoma at local site
3. Sample collection time
4. Parental perception of their own anxiety and infant's pain

Search strategy for identification of studies

See: Cochrane Neonatal Collaborative Review Group search strategy.
MEDLINE was searched (1966 - June 2007) using the terms: venepuncture, heel lance (prick), pain, newborn - infant, blood sampling.
Other databases were searched including: EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007) and reference lists of identified trials.

Methods of the review

Standard methods of the Cochrane Neonatal Collaborative Review Group were used to assess methodological quality of trials.
For each trial, information was sought from the published report regarding method of randomization, blinding, and reporting of all outcomes for all infants enrolled in the trial. Unpublished data were included from the studies by Shah (Shah 1997), Eriksson (Eriksson 1999) and (Kvist 2002). Unpublished data on the six patients that were excluded (because more than two skin punctures were required) from the analyses by Kvist et al (Kvist 2002) could not be obtained. Data regarding infants enrolled in the VP and HL groups without the administration of glucose were available from Eriksson (Eriksson 1999). Retrieved articles were assessed and data were abstracted independently by the two review authors.

The statistical methods included relative risk (RR), risk difference (RD), number needed to treat (NNT) and weighted mean difference (WMD) when appropriate along with 95% confidence intervals (CI). If present, statistically significant between study heterogeneity including the I squared (I²) test was reported. All data were analysed using RevMan 4.2.10.

Description of studies

For details see the table of "Characteristics of Included Studies".

One additional trial was identified for this review (Ogawa 2005). With the addition of this study, five trials enrolling 457 neonates were included. These studies were performed in three countries [UK, Japan and Sweden (n = 3)]. Of the 457 neonates enrolled, information on 317 neonates relevant to this systematic review are included.

All studies except the one by Larsson 1998 strictly fulfilled our inclusion criteria of gestational age > 37 weeks. In the Larsson 1998 study, the gestational ages ranged from 36 weeks to 43 weeks; the median gestational age was 40 weeks. The decision was made to include this study in the review as most infants were term. Two studies compared the effects of sweet tasting solution (Eriksson 1999; Eriksson 1999 and Ogawa 2005) on VP and HL. Information from these two studies are provided only for the VP and HL groups without the administration of a sweet tasting solution.

Pain assessments have been made in these trials using various validated tools. Shah 1997 and Kvist 2002 used the NIPS. The NIPS includes five behavioral groupings (facial expression, crying, movement of arms and legs, and state of arousal) and one physiological indicator (breathing pattern) along with the descriptors for the scores within each grouping (Lawrence 1993). The total score ranges from 0 (relaxed and calm) to seven (crying dissatisfied infant). The scale has been tested for validity and reliability in preterm and term infants subjected to capillary, venous or arterial punctures (Lawrence 1993).

Larsson 1998a used the Neonatal Facial Action Coding System (NFCS) (Grunau 1987). The presence or absence of six facial actions [brow bulge, eyes squeezed shut, deepening of the naso-labial furrow, open lips, a taut cupped tongue, and stretching of the mouth (vertically and horizontally)] were recorded and presented as percent positive scores with a total range of 0 to 600%. The scale has been validated (Craig 1994). The results of the NFCS scores are not included in the meta-analysis of pain response as they were presented as median scores in a table and the centiles in graphic form. Ogawa 2005 used the NFCS to assess pain. These authors assessed the 10 facial actions (brow bulge, eye squeeze, nasolabial furrow, open lips, lip purse, vertical and horizontal mouth stretch, taut tongue, tongue protrusion and chin quiver). The data from Ogawa et al (Ogawa 2005) could not be incorporated in the meta-analysis as results of the NFCS score were reported as median and interquartile ranges.

Eriksson 1999 used the PIPP score to assess pain. The PIPP score assigns points for changes in three facial expressions (brow bulge, eye squeeze and naso-labial fold), heart rate, oxygen saturation, gestational age and behavioral state with a higher score indicating more pain. A score of 0-6 points indicates minimal or no pain, while a score of 12 or more indicates moderate to severe pain.

The blood sampling techniques (VP or HL) were performed by one investigator in the trials of Shah 1997, Larsson 1998 and Eriksson 1999. For the trial by Kvist 2002 two investigators performed the procedure while for the trial of Ogawa 2005 seven experienced nurses were trained to perform VP or HL.

Unpublished data on the six patients that were excluded (because more than two skin punctures were required) in the trial by Kvist 2002 could not be obtained. The analyses presented from this trial do not represent an "intention to treat analysis". The results were presented as median test and odds ratios with 95% CIs. The authors provided us with unpublished data for means and standard deviations for NIPS scores for the small caliber VP needle group and the HL group.

Included Studies:

Shah 1997 was a single centre study performed in Bristol, UK.

Objective: To compare the pain response to different methods of blood sampling (VP vs. HL) in full term infants and the incidence of adverse effects.

Population: Healthy neonates (> 37 weeks GA) having blood taken for measurement of bilirubin or glucose.

Intervention: HL was performed using a commercially available lancet (Becton Dickinson VACUTAINER Systems Eur. 36129). VP was performed using a 21 gauge needle from a vein on the dorsum of the hand.

Outcomes assessed: Pain assessments were made by nurses using Neonatal Infant Pain Scale (NIPS). Infant's pain score as rated by the mother was assessed using a three point scale where 0 = no pain at all, 1 = a little pain and 2 = a lot of pain. Maternal anxiety score prior to the procedure was assessed using a three point scale where 0 = not worried at all, 1 = a little worried and 2 = very worried. The number, reasons for multiple attempts, and occurrence of adverse effects were noted.

Larsson 1998 was a single centre study performed in Stockholm, Sweden.

Objective: To compare the pain response to VP compared to HL either with a standardized lancet or a large lancet.

Population: Healthy neonates (36 - 43 weeks GA) undergoing the phenylketonuria (PKU) screening test.

Intervention: VP was performed using a Microlance needle measuring 0.9 x 40 mm (Becton- Dickinson, Madrid, Spain). Two devices were used for heel lancing. In the small lancet group (SL) a CCS Minilancet (Clean Chemical, Borlänge, Sweden) was used. In the large lancet group (LL) a Microlance (Becton-Dickinson, Meylan Cedex, France) was used.

Outcomes assessed: Pain assessments were made using NFCS (Grunau 1987) and cry [latency (cry within 60 seconds of the skin puncture) and duration of the first cry as well as the total cry duration for the procedure]. The need for more than one skin puncture and sampling times were recorded.

Eriksson 1999 was a single centre study performed in Örebro, Sweden.

Objective: To identify the least painful method to obtain blood sample for PKU test by VP or HL with or without 30% glucose.

Population: Healthy neonates (> 37 weeks GA) undergoing the metabolic screening blood test.

Intervention: HL was performed using a microtainer safety lancet (Microtainer Brand Safety Flow Lancet, Becton Dickinson, Meylan Cedex, France). VP was performed using a 21-gauge needle (Terumo, Leuven, Belgium).

Outcomes assessed: Pain assessments were made using the Premature Infant Pain Profile (PIPP) score, duration of crying within the first 3 minutes after the skin puncture and by changes in heart rate. The need for more than one skin puncture and sampling times were recorded.

Kvist 2002 was a single centre study performed in Helsingborg, Sweden.

Objective: To identify the least painful method of blood sampling for the PKU test.

Population: Healthy neonates (> 37 weeks GA) with normal weight (i.e. > 2,500 g) and breast fed.

Intervention: VP was performed either with a small caliber needle (0.6 x 25 mm) or a large caliber needle (0.9 x 40 mm) and HL was performed using microtainer lancet with a depth of 2 mm).

Outcomes assessed: Pain assessments were made using the NIPS score and the need for more than one skin puncture was recorded.

Ogawa 2005 was a single centre study performed in Osaka, Japan.

Objective: To identify the least painful and most effective method for blood sampling by VP or HL with or without sucrose.

Population: Healthy neonates (> 37 weeks GA) undergoing screening blood test for inborn errors of metabolism.

Intervention: HL was performed using a standard lancet with a sharp triangular edge that was 2.5 mm long and 1 mm wide (Feather Safety Razor Co, Ltd, Osaka, Japan) while VP was performed using a 23 gauge needle.

Outcomes assessed: Pain assessments were performed using NFCS and duration of first cry (the percentage of the first crying time relative to the total procedure time and the number of crying babies). Adverse events of the procedure itself and those occurring after completion including bruising and hematoma were recorded.

Methodological quality of included studies

Randomization was blinded in the five included studies. Intention to treat analyses were not reported in the trials by Larsson (Larsson 1998) and Kvist (Kvist 2002).

Shah (Shah 1997) - Neither blinding of the intervention (not possible) nor of outcome assessments were ensured. Outcomes were given for all neonates enrolled in the study.

Larsson (Larsson 1998a) - Blinding of the intervention was not possible, while blinding of outcome assessment was ensured. Video and audio tapes were analyzed by two observers unaware of the group to which the infant had been allocated. All infants in the study were accounted for. Three infants in the small lancet group were excluded as one infant was of 35 weeks gestation and two infants had screamed before the puncture was performed. Outcomes were reported for 117 out of 120 infants.

Eriksson (Eriksson 1999) - Neither blinding of the intervention (not possible) nor of outcome assessments was ensured. Outcomes were given for all neonates enrolled in the study.

Kvist (Kvist 2002) - Neither blinding of the intervention (not possible) nor of outcome assessments was ensured. Ten of the 30 infants randomized to VP with large caliber VP needle required more than two attempts at VP and had their blood sampling carried out by HL. NIPS scores were not provided for this group. The authors compared the NIPS scores for 25 infants in the small caliber VP needle group (5 infants were excluded because of unsuccessful sampling) and 29 infants in the HL group (one was excluded because of several punctures). Thus complete follow-up was not available from all patients enrolled.

Ogawa (Ogawa 2005) - Randomization was performed using sealed envelopes. Blinding of the intervention was not possible while blinding of outcome assessment was ensured. Audio-video tapes were analyzed by a single investigator who was unaware of the sampling method. All infants in the study were accounted for.

Results

VENEPUNCTURE VS. HEEL LANCE (Comparison 01):

Primary Outcomes:

Pain response using NIPS score (Outcome 01.01):

Two trials enrolling 81 neonates reported on the NIPS score. The NIPS score was significantly lower in the VP group as compared to HL [typical WMD -1.84 (95% CI -2.61, -1.06)]. There was no statistically significant heterogeneity for this outcome (p = 0.22, I² = 33.3%).

Pain response using PIPP score (Outcome 01.02):
One trial enrolling 60 neonates reported on the PIPP score. The PIPP score was significantly lower in the VP group as compared to the HL group [MD -2.46 (95% CI -4.29, -0.63)].

Cry within 60 seconds of the skin puncture (Outcome 01.03):

One trial enrolling 117 neonates reported on this outcome. There was a significantly lower number of neonates who cried in the VP group as compared to the HL group [RR 0.58, (95% CI 0.41, 0.81); RD -0.32 (95% CI -0.49, -0.15); NNT 3 (95% CI 2, 7)].

Duration of first cry (seconds) (Outcome 01.04):

One trial enrolling 50 neonates reported on the duration of first cry. Neonates in the VP group had a significantly shorter duration of first cry as compared to the HL group [MD -112 (95% CI -164, -60)].

First crying time/total procedure time (%) (Outcome 01.05):

One trial enrolling 50 neonates reported on this outcome. The percentage of the first crying time relative to the total procedure time was shorter in the VP group [MD -65 (95% CI -110, -20)]

Number of neonates who cried during the procedure (Outcome 01.06):

Two trials enrolling 110 neonates reported on this outcome. There was a significantly lower number of neonates who cried in the VP group [typical RR 0.58, (95% CI 0.46, 0.74); typical RD -0.40 (95% CI -0.54, -0.26); NNT 3 (95% CI 2, 4)]. There was no significant heterogeneity between studies (RR p = 0.58, I² = 0%; RD p =0.61, I² = 0%).

Secondary Outcomes:

Maternal anxiety score prior to the procedure (Outcome 01.07):

One trial enrolling 27 neonates reported on this outcome. Maternal anxiety prior to the procedure was significantly higher in the VP group [MD 0.80 (95% CI 0.34, 1.26)].

Infant's pain score as rated by the mother (Outcome 01.08):

One trial enrolling 27 neonates reported on the infant's pain score as rated by the mother. Infant's pain score as rated by the mother was lower in the VP group [MD -0.80 (95% CI -1.18, -0.42)].

Sampling time (seconds) (Outcome 01.09):

Two trials with 110 enrolled neonates reported sampling time. There was no statistically significant difference in the sampling time between the groups [typical WMD -36 (95% CI -76, 3)]. There was statistically significant heterogeneity for the outcome (p = 0.01, I² = 85.1%).

Need for more than one skin puncture (Outcome 01.10):

A total of four trials enrolling 254 neonates reported on this outcome. There was a significantly lower number of neonates who required additional skin puncture in the VP group [typical RR 0.30, (95% CI 0.18, 0.49); typical RD -0.31 (95% CI -0.41, -0.22); NNT 3 (95% CI 2, 5)]. There was statistically significant heterogeneity amongst studies (RR p = 0.02, I² = 74.3%; RD p = <0.00001, I² = 96.6%).

Need for more than two skin puncture (Outcome 01.11):

One trial enrolling 60 neonates reported on this outcome. There was no statistically significant difference between groups [RR 5 (95% CI 0.62, 40.28); RD 0.13 (95% CI -0.01, 0.28)].

Additional primary outcomes for which no tables are presented

In the study by Larsson (Larsson 1998a), NFCS scores were statistically significantly lower in the VP group as compared to the HL group. The median NFCS score after the first skin puncture was 247 in the VP group, 333 in the SL group and 460 in the LL group; p < 0.0005. Median NFCS score was 142 in the VP group, 420 in the SL group and 497 in the LL group during manipulation for blood sampling, p < 0.001.

In the study by Eriksson (Eriksson 1999), the duration of crying within the first three minutes after the skin puncture was significantly lower in the VP group (median 11 seconds, range 0 - 174) as compared to the HL group (median 117 seconds, range 0-178), p = 0.0041.

In the study by Ogawa (Ogawa 2005), there were no differences in the NFCS score during the 10 seconds assessment periods after resting, disinfection, application of the plaster and one minute after the application of the plaster. NFCS scores [median (interquartile range)] in the HL group were significantly higher than those of the VP group respectively for the following time points: 58 (46 - 63) vs 20 (10 - 48) after skin puncture, 58 (54 - 65) vs 23 (1-41) during blood sampling (p < 0.001), and 52 (41 - 61) vs 32 (2 - 59) while the bleeding was being stopped.

Discussion

For the update of this review one additional study was identified (Ogawa 2005) and the results of that study are in keeping with previous results. The review indicates that VP is preferable to HL to obtain a blood sample from term neonates. It suggests that VP is less painful than HL as assessed by the various validated pain measures. The reason for this may be that, as compared to VP, the technique of HL consists of multiple painful phases: the lance procedure, squeezing the heel to obtain a blood sample (the duration of this phase varies depending on the flow of blood) and cleaning the heel and applying a cover. In contrast, to VP, once the vein is punctured the time to obtain the blood sample is shorter.

The results of this review need to be interpreted with some caution. In two studies (Kvist 2002; Larsson 1998) the outcomes were not reported on all infants enrolled and therefore intention to treat analyses were not performed. In three (Larsson 1998; Shah 1997; Eriksson 1999) of the five studies included in this review, the procedures were performed by a single investigator, respectively a pediatrician or a nurse. In one study, the procedures were performed by two midwives who were relatively inexperienced in performing VPs (according to the authors) (Kvist 2002), while in the trial by Ogawa 2005, seven experienced nurses were trained to perform the procedures. There was statistically significant between study heterogeneity for the outcome "Need for more than one skin puncture" with a large I²value of 97 %. The between study heterogeneity may in part be explained by the variable skills among the phlebotomists. The reproducibility of the results from these studies needs to be tested in a large study with multiple health care workers obtaining the blood samples. Before embarking on such a study, adequate training of the personnel undertaking heel lances and venepunctures would be required.

The heterogeneity of the outcomes reported, the outcome measures, and the reporting of the data prevented synthesis of data pertaining to other pain scores using meta-analytic techniques. However, all studies used validated pain measures and showed that infants in the VP group had lower scores as compared to the HL group. Even though the changes in pain scores are statistically significant, the question remains as to whether these changes represent a clinically significant difference. The conventional method to determine this would be to ask patients how painful the procedure was as perceived by them. This is impossible in neonates and, therefore, clinicians have to rely on surrogate measures of pain. One study measured parents' judgement regarding their own anxiety and their infant's pain using a categorical rating scale. Parents favoured VP. This observation requires confirmation.

In the study by Larsson (Larsson 1998), the success rate with either the SL or the LL was poor as compared to the study by Shah (Shah 1997). This finding is hard to explain by poor technique, as neonatal nurses are well trained to perform HL. Larsson (Larsson 1998) evaluated the role of EMLA to reduce pain from VP in term neonates. In comparison to placebo, neonates in the EMLA group were noted to have significantly lower pain scores. However, when this study was compared to a previous study by the same investigators (Larsson 1998a), pain scores were higher in the VP-EMLA group as compared to VP group without EMLA (Shah 1999a).

In conclusion, VP is less painful as assessed by validated pain measures and parental rating and is associated with less maternal anxiety. In view of the limitations of the studies performed to date, these promising results need confirmation in a study of appropriate sample size using multiple operators on the postnatal floor.

Reviewers' conclusions

Implications for practice

When performed by a trained phlebotomist, venepuncture appears to be the method of choice for blood sampling in term neonates.

Implications for research

Further well designed randomized controlled trials need to be conducted. The interventions should be compared in settings where several individuals perform the VP and the HL.

Acknowledgements

We are thankful to Dr. Mats Eriksson (Eriksson 1999) and Ms. Linda J Kvist (Kvist 2002) who provided clarifications and unpublished information regarding their studies.

Potential conflict of interest

Dr. Vibhuti Shah is the principal author of one of the included trials in this review (Shah 1997).

Characteristics of included studies

Study	Methods	Participants	Interventions	Outcomes	Notes	Allocation concealment
Eriksson 1999	Randomized controlled trial Blinding of randomization: Yes Blinding of intervention: No Complete follow-up: Yes Blinding of outcome: Can't tell	Healthy full term infants undergoing metabolic screening blood test (n = 60) Demographic data: Values are presented as mean (SD) or percentage (%) Venepuncture group: n = 30 Birth weight (g) 3667 (449) Gestational age (wks) 39.7 (1.4) Sex (%) male 40 Heel lance group: n = 30 Birth weight (g) 3578 (465) Gestational age (wks) 40.2 (1.2) Sex (%) male 53	Venepuncture (n=30) Heel lance (n=30)	Pain assessments were made using the duration of cry within the first 3 minutes after the skin puncture, the Premature Infant Pain Profile (PIPP) score and by changes in the heart rate	Infants were randomized using a block randomization technique with sealed envelopes into one of the four groups - HL and VP with and without oral administration of 1 ml of 30% glucose Data on HL and VP group without the administration of glucose are included for this review	A
Kvist 2002	Randomized controlled trial Blinding of randomization: Yes Blinding of intervention: No Complete follow-up: No Blinding of outcome: No	Healthy full term infants undergoing PKU screening (n = 90) Demographic data for the small caliber venepuncture needle group (n = 25) and the HL group (n = 29) are presented Values are presented as mean (range) or percentage (%) Small caliber venepuncture needle group; weight 3613 g (range 2690 - 4740), gestational age (40, 37-42), age 4 days (3-6), male sex 44%; For the heel lance group (n = 29) weight 3525 g (2710 - 4650), gestational age 39 weeks (37 - 42), age 5 days (3 - 6), male sex 66%	Venepuncture with large caliber needle (n = 30) (results not reported) Venepuncture with small caliber needle (n = 30; 5 infants excluded) Heel lance (n = 30; 1 infant excluded)	NIPS (Neonatal Infant Pain Scale) reported at the beginning of each minute, the first minute starting at the moment of puncture All infants were observed for a minimum of 5 minutes Number of punctures were also noted	Infants were randomized using consecutively numbered envelopes No envelope was taken out of sequence Data for the large caliber venepuncture needle group were not presented as in 33% of the infants the venepuncture was unsuccessful 5 infants in the small caliber venepuncture needle group and 1 infant in the heel lance group were excluded from the analyses because more than two skin punctures were required	A
Larsson 1998	Randomized controlled trial Blinding of randomization: Yes Blinding of intervention: No Complete follow up: No Blinding of outcome measurement: Yes	Healthy term infants undergoing blood testing for phenylketonuria (n=120) Three infants in the small lancet group were excluded as one infant was of 35 weeks gestation and two infants screamed prior to heel lance Demographic data: Values are presented as median (range) or % Venepuncture group: n = 50 Birth weight (g) 3410 (2440-5035) Gestational age (wks) 40 (36-43) Age (days) 3 (3-7) Sex (%) male 44 Small lancet group: n = 47 Birth weight (g) 3570 (2650-4540) Gestational age (wks) 40 (36-43) Age (days) 4 (3-6) Gender (%) male 55 Large lancet group: n = 20 Birth weight (g) 3398 (2160-4330) Gestational age (wks) 40 (37-42) Age (days) 4 (3-7) Gender (%) male 45	Venepuncture (n=50) Heel lance with a small lancet (n=47) Heel lance with a large lancet (n=20) The authors do not explain the reasons for the unequal group sizes	Pain assessments were made using Neonatal Facial Action Coding System (NFCS) and cry [latency (cry within 60 seconds of the skin puncture) and duration of first cry and total duration of cry] Audiotapes were reviewed to determine the latency to cry from the skin puncture, duration of first cry and total time the infant cried during the procedure Cry was defined as high-pitched vocalization	Infants were randomized using envelopes to receive VP, HL using a small lancet (SL) [three later excluded (one was a preterm infant and two infants screamed prior to heel lance)] or a large lancet (LL) One investigator (neonatal nurse) performed all procedures	A
Ogawa 2005	Randomized, double blind, placebo controlled trial Blinding of randomization: Yes Blinding of intervention: No Complete follow up: Yes Blinding of outcome assessment: Yes	Healthy full term neonates of > = 37 weeks gestational age undergoing the newborn screening test Demograpic data: Values are presented as median (range) Venepuncture group: n = 25 Birth weight (g) 3274 (2295-3715) Gestational age (weeks) 39 (37-41) Male sex (n) 12/25 Apgar scores: 1 minute 9 (8-10) 5 minutes 10 (7-10) Heel lance group: n = 25 Birth weight (g) 3030 (2530-3550) Gestational age (weeks) 40 (38-42) Male sex (n) 12/25 Apgar scores: 1 minute 10 (7-10) 5 minutes 10 (6-10)	Venepuncture (n=25) Heel lance (n=25)	Pain assessments were made using NFCS and duration of first cry	Infants were randomized using sealed envelopes A team of seven nurses performed the procedure A single investigator blinded to the sampling techniques performed the outcome assessments	A
Shah 1997	Randomized controlled trial Blinding of randomization: Yes Blinding of intervention: No Complete follow up: Yes Blinding of outcome measurement: Can't tell	Healthy neonates of > =37 weeks gestational age (n=27) Demographic data: Values are mean (SD) or number (%) Heel lance group: Age (days) 3.1 (1.1) Sex (% male) 8 (57%) State (% awake before procedure) 5 (36%) Reason for test (% bilirubin) 13 (93%) Venepuncture group: Age (days) 2.8 (1.2) Sex (% male) 8 (62%) State (% awake before procedure) 7 (58%) Reason for test (% bilirubin) 12 (97%)	Venepuncture (n=13) Heel lance (n=14) 0.25 ml of blood was obtained with either method	Pain assessments were made using Neonatal Infant Pain Scale (NIPS) Parental rating of their own anxiety was assessed using a three point scale where 0= not worried at all, 1= a little worried and 2= very worried and infant's pain using a scale where 0= no pain at all, 1= a little pain and 2= a lot of pain	Randomization was computer generated Allocation was by sealed envelopes One investigator (well-trained pediatrician) performed all procedures One infant in each group had the procedure performed while being breat fed One of the reviewers (V. Shah) for this systematic review is the primary author of this paper	A

References to studies

References to included studies

Eriksson 1999 {published and unpublished data}

Eriksson M, Gradin M, Schollin J. Oral glucose and venepuncture reduce blood sampling pain in newborns. Early Human Development 1999;55:211-8.

Kvist 2002 {published and unpublished data}

Kvist LJ, Jonsson K, Tornestrand BM, Edwinson Mansson M. Can venepuncture reduce the pain of neonatal PKU-sampling? A randomised study. Vard i Norden 2002;22:27-30.

Larsson 1998 {published data only}

Larsson BA, Tannfeldt G, Lagercrantz H, Olsson GL. Venipuncture is more effective and less painful than heel lancing for blood tests in neonates. Pediatrics 1998;101:882-6.

Ogawa 2005 {published data only}

Ogawa S, Ogihara T, Fujiwara E, Ito K, Nakano M, Nakayama S et al. Venepuncture is preferable to heel lance for blood sampling in term neonates. Archives of Disease in Childhood 2005;90:F432-6.

Shah 1997 {published and unpublished data}

Shah VS, Taddio A, Bennett S, Speidel BD. Neonatal pain response to heel stick vs. venepuncture for routine blood sampling. Archives of Disease in Childhood 1997;77:F143-4.

* indicates the primary reference for the study

Other references

Additional references

Barker 1995

Barker DP, Rutter N. Exposure to invasive procedures in neonatal intensive care unit admissions. Archives of Disease in Childhood 1995;72:F47-8.

Brown 1987

Brown L. Physiologic responses to cutaneous pain in neonates. Neonatal Network 1987;5:18-21.

Campos 1994

Campos GR. Rocking and pacifiers: Two comforting interventions for heel stick pain. Research in Nursing and Health 1994;17:321-31.

CPS 2000

Fetus and Newborn Committee, Canadian Paediatric Society, and Committee on Fetus and Newborn, Committee on Drugs, Section on Anesthesiology and Section on Surgery, American Academy of Pediatrics. Prevention and management of pain and stress in the neonate. Journal of Paediatrics and Child Health 2000;5:31-8.

Craig 1994

Craig KD, Hadjistavropoulos HD, Grunau RVE. A comparison of two measures of facial activity during pain in the newborn child. Journal of Pediatric Psychology 1995;19:305-18.

Field 1984

Field T, Goldson E. Pacifying effects of non-nutritive sucking on term and preterm neonates during heel stick procedures. Pediatrics 1984;74:1012-5.

Fitzgerald 1989

Fitzgerald M, McIntosh N. Pain and analgesia in the newborn. Archives of Disease in Childhood 1989;64:441-3.

Grunau 1987

Grunau RVE, Craig KD. Pain expression in neonates: facial action and cry. Pain 1987;28:395-410.

Harpin 1983

Harpin VA, Rutter N. Making heel pricks less painful. Archives of Disease in Childhood 1983;58:226-8.

Izard 1979

Izard CE. The maximally discriminative facial movement coding system (MAX). Newark DE: University of Delaware Instructional Resources Centre, 1979.

Jain 2001

Jain A, Rutter N, Ratnayaka M. Topical amethocaine gel for pain relief of heel prick blood sampling: a randomized double blind controlled trial. Archives of Disease in Childhood Fetal Neonatal Edition 2001;84:F56-9.

Johnston 1986

Johnston CC, Strada ME. Acute pain response in infants: a mutidimensional description. Pain 1986;24:373-82.

Larsson 1995

Larsson BA, Jylli L, Lagercrantz H, Olsson GL. Does a local anaesthetic cream (EMLA) alleviate pain from heel lancing in neonate? Acta Anaesthesiologica Scandinavica 1995;39:1028-31.

Larsson 1998a

Larsson BA, Tannfeldt G, Lagercrantz H, Olsson GL. Alleviation of the pain of venepuncture in neonates. Acta Paediatrica 1998;87:774-9.

Lawrence 1993

Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool to assess neonatal pain. Neonatal Network 1993;12:59-66.

McIntosh 1994

McIntosh N, van Vee L, Brameyer H. Alleviation of the pain of heel prick in preterm infants. Archives of Disease in Childhood 1994;79:177-81.

McKay 1966

McKay RJ. Diagnosis and treatment: risks of obtaining samples of venous blood in infants. Pediatrics 1966;38:906-8.

Meehan 1998

Meehan RM. Heelsticks in neonates for capillary blood sampling. Neonatal Network 1998;17:17-24.

Moxley 1989

Moxley S. Neonatal heel puncture. The Canadian Nurse 1989;1:25-7.

Ohlsson 2000

Ohlsson A, Taddio A, Jadad AR, Stevens BJ. Evidence-based decision making, systematic reviews and the Cochrane Collaboration: implications for neonatal analagesia.. In: Anand KJS, Stevens BJ, McGrath PJ, editor(s). Pain in neonates. 2nd edition. Vol. 10. Amsterdam: Elsevier, 2000:251-268.

Owens 1984

Owens ME, Todt EH. Pain in infancy: neonatal reaction to heel lance. Pain 1984;20:77-86.

Paes 1993

Paes B, Janes M, Vegh P, LeDuca F, Andrew M. A comparative study of heel stick devices for infant blood collection. American Journal of Diseases of Children 1993;147:346-8.

Ramenghi 1996

Ramenghi LA, Griffiths GC, Wood CM, Levene MI. Effect of non-sucrose sweet tasting solution on neonatal heel prick responses. Archives of Disease in Childhood 1996;74:F129-31.

Rushforth 1995

Rushforth JA, Griffiths G, Thorpe H, Levene MI. Can topical lignocaine reduce behavioural response to heel prick? Archives of Disease in Childhood 1995;72:F49-51.

Shah 1998

Shah VS, Taddio A, Ohlsson A. Randomized controlled trial of paracetamol for heel prick pain in neonates. Archives of Disease in Childhood 1998;79:F209-11.

Shah 1999a

Shah V, Ohlsson A. Alleviation of the pain of venepuncture in neonates. Acta Paediatrica 1999;88:351-52.

Skogdal 1997

Skogdal Y, Eriksson M, Schollin J. Analgesia in newborns given oral glucose. Acta Paediatrica 1997;86:217-20.

Stevens 1996

Stevens B, Johnston C, Petryshen P, Taddio A. Premature infant pain profile: development and initial validation. The Clinical Journal of Pain 1996;12:13-22.

Stevens 1999

Stevens B, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database of Systematic Reviews 2004, Issue 3.

Taddio 1995

Taddio A, Goldbach M, Ipp M, Stevens B, Koren G. Effect of neonatal circumcision on pain responses during vaccination in boys. Lancet 1995;345:291-2.

Taddio 1997

Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet 1997;349:599-603.

Other published versions of this review

Shah 1999b

Shah V, Ohlsson A. Venepuncture versus heel lance for blood sampling in term neonates. Cochrane Database of Systematic Reviews 1999, Issue 2.

Shah 2001

Shah V, Ohlsson A. Venepuncture versus heel lance for blood sampling in term neonates. Cochrane Database of Systematic Reviews 2001, Issue 1.

Shah 2004

Shah V, Ohlsson A. Venepuncture versus heel lance for blood sampling in term neonates. Cochrane Database of Systematic Reviews 2004, Issue 4.

Comparisons and data

Comparison or outcome	Studies	Participants	Statistical method	Effect size
01 Venepuncture vs. heel lance
01 Pain response using NIPS score	2	81	WMD (fixed), 95% CI	-1.84 [-2.61, -1.06]
02 Pain response using PIPP score	1	60	WMD (fixed), 95% CI	-2.46 [-4.29, -0.63]
03 Cry within 60 seconds of the skin puncture	1	117	RR (fixed), 95% CI	0.58 [0.41, 0.81]
04 Duration of first cry (seconds)	1	50	WMD (fixed), 95% CI	-112.00 [-163.99, -60.01]
05 First crying time/total procedure time (%)	1	50	WMD (fixed), 95% CI	-65.00 [-110.12, -19.88]
06 Number of neonates who cried during the procedure	2	110	RR (fixed), 95% CI	0.58 [0.46, 0.74]
07 Maternal anxiety score prior to the procedure	1	27	WMD (fixed), 95% CI	0.80 [0.34, 1.26]
08 Infant's pain score as rated by the mother	1	27	WMD (fixed), 95% CI	-0.80 [-1.18, -0.42]
09 Sampling time (seconds)	2	110	WMD (fixed), 95% CI	-36.25 [-75.56, 3.05]
10 Need for more than one skin puncture	4	254	RR (fixed), 95% CI	0.30 [0.18, 0.49]
11 Need for more than two skin punctures	1	60	RR (fixed), 95% CI	5.00 [0.62, 40.28]

01 Venepuncture vs. heel lance

01.01 Pain response using NIPS score

01.02 Pain response using PIPP score

01.03 Cry within 60 seconds of the skin puncture

01.04 Duration of first cry (seconds)

01.05 First crying time/total procedure time (%)

01.06 Number of neonates who cried during the procedure

01.07 Maternal anxiety score prior to the procedure

01.08 Infant's pain score as rated by the mother

01.09 Sampling time (seconds)

01.10 Need for more than one skin puncture

01.11 Need for more than two skin punctures

Contact details for co-reviewers

Dr Arne Ohlsson
Director Evidence Based Neonatal Care and Outcomes Research
Department of Paediatrics
Mount Sinai Hospital
600 University Avenue
Toronto
Ontario CANADA
M5G 1X5
Telephone 1: +1 416 586 8379
Telephone 2: +1 416 341 0444
Facsimile: +1 416 586 8745
E-mail: aohlsson@mtsinai.on.ca

This review is published as a Cochrane review in The Cochrane Library, Issue 4, 2007 (see http://www.thecochranelibrary.com for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent version of the review.