Home > Health & Research > Health Education Campaigns & Programs > Cochrane Neonatal Review > Intravenous in-line filters for preventing morbidity and mortality in neonates

Intravenous in-line filters for preventing morbidity and mortality in neonates

Skip sharing on social media links
Share this:

Authors

Jann P Foster1, Robyn Richards2, Marian G Showell3

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


1Central Clinical School - Discipline of Obstetrics & Gynaecology, University of Sydney, Sydney, c/- Newborn Care, Camperdown, Australia [top]
2Newborn Care, Liverpool Hospital, Liverpool, Australia [top]
3Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand [top]

Citation example: Foster JP, Richards R, Showell MG. Intravenous in-line filters for preventing morbidity and mortality in neonates. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD005248. DOI: 10.1002/14651858.CD005248.pub2.

Contact person

Jann P Foster

Central Clinical School - Discipline of Obstetrics & Gynaecology, University of Sydney, Sydney
c/- Newborn Care
RPA Women & Babies, Missenden Road
Camperdown
NSW
2050
Australia

E-mail: jann.foster@sydney.edu.au

Dates

Assessed as Up-to-date: 09 June 2011
Date of Search: 02 April 2011
Next Stage Expected: 09 June 2013
Protocol First Published: Issue 2, 2005
Review First Published: Issue 2, 2006
Last Citation Issue: Issue 2, 2006

What's new

Date / Event Description
02 April 2011
Updated

This updates the review "Intravenous in-line filters for preventing morbidity and mortality in neonates (Foster 2006).

Updated search in April 2011 did not identify any new studies.

Conclusions remain the same.

History

Date / Event Description
15 February 2011
Amended

Contact details updated.

04 December 2008
Updated

This updates the review "Intravenous in-line filters for preventing morbidity and mortality in neonates" published in The Cochrane Library, Issue 2, 2006 (Foster 2006).

One eligible trial was found and has been included in this review.

18 September 2008
Amended

Converted to new review format.

Abstract

Background

Venous access is an essential part of caring for the sick neonate; however, problems such as contamination of fluids with bacteria, endotoxins and particulates have been associated with intravenous infusion therapy. Intravenous in-line filters claim to be an effective strategy for the removal of bacteria, endotoxins and particulates associated with intravenous therapy in adults and are increasingly being recommended for use in neonates.

Objectives

To determine the effect of in-line filters on intravenous lines on morbidity and mortality in neonates.

Search methods

We used the standard search strategy of the Cochrane Neonatal Group. We searched the electronic databases MEDLINE (from 1966 to April 2, 2011), EMBASE (from 1980 to April 2, 2011), CINAHL (from 1982 to April 2, 2011) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2011). There was no language restriction. Further searching included cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching.

Selection criteria

Randomised or quasi-randomised controlled trials that compared the use of intravenous in-line filters with placebo or nothing in neonates were included in the review.

Data collection and analysis

The procedures of the Cochrane Neonatal Review Group (CNRG) were followed throughout.
Titles and abstracts identified from the search were checked by the review authors. The full text of all studies of possible relevance were obtained. The review authors independently assessed the trials for their methodological quality and subsequent inclusion in the review. Authors were contacted for further information as needed.

Statistical analysis followed the procedures of the Cochrane Neonatal Review Group. Dichotomous data is expressed as relative risk and 95% confidence intervals, and risk difference and 95% confidence intervals.

Results

There were four eligible studies that recruited a total of 704 neonates. This review found no significant effect of in-line filters in any of the reported outcomes of overall mortality, proven and suspect septicaemia, local phlebitis and thrombus, necrotizing enterocolitis, duration of cannula patency, length of stay in hospital, number of catheters inserted and financial costs.

Authors' conclusions

There is insufficient evidence to recommend the use of intravenous in-line filters to prevent morbidity and mortality in neonates.

Plain language summary

Intravenous in-line filters for preventing morbidity and mortality in neonates

Preterm or sick newborn infants are often fed with nutrients and fluids that are delivered directly into a vein. This intravenous delivery can be associated with infection, toxins released by bacteria, and tiny particles that may be in the fluids, such as rubber and plastic, going into the blood. In adults, placing a filter in the intravenous line has been reported to be effective in reducing such risks and filters are increasingly being recommended for use in newborn infants. The review authors searched the medical literature and identified four eligible studies that recruited a total of 704 newborns. Septicaemia and illness, deaths or problems with the intravenous catheters were no different with or without a filter. This review is unable to recommend their use due to insufficient evidence.

[top]

Background

Description of the condition

Venous access is an essential part of caring for the sick neonate; however, problems associated with intravenous (IV) infusion therapy include contamination of fluids with bacteria, endotoxins and particulates (Bethune 2001).

Infusion therapy carries a risk for catheter-associated septicaemia (Geiss 1992). Infection can originate from the catheter tubing, the ports, at the cannula site or from contaminated infusion fluid. Factors cited as increasing the risk for catheter related infection include type of IV fluid, for example total parenteral nutrition solutions or solutions with high concentrations of dextrose (Pearson 1996). While not all infections lead to septicaemia, immuno-compromised patients such as neonates, are at greater risk, and infection becomes a major problem (Ng 1989). In adult patients, use of the bacterial retention filter lead to fewer clinically significant bacteremias (Quercia 1986).

Contamination of IV administration sets with gram-negative bacteria has been reported to lead to rapid proliferation of endotoxins (Bethune 2001). In adults, endotoxins have been implicated in several serious disease processes, including respiratory distress syndrome (Parsons 1989), septic shock (Glauser 1991), multiple organ failure, endotoxic shock and systemic inflammatory response syndrome (Suffredini 1989a; Casale 1990; Glauser 1991). Cardiovascular changes such as increased heart rate, decreased vascular resistance and depressed left ventricular function (Suffredini 1989b) and increased intestinal permeability (O'Dwyer 1988) have also been reported. Periventricular leukomalacia (PVL) is an ischaemic lesion of the periventricular white matter that is primarily seen in premature neonates (Hill 1992). Animal studies have demonstrated the development of PVL in the brains of newborn kittens following injection of endotoxins (Gilles 1977) and it has been postulated that endotoxins may be involved in the pathogenesis of a proportion of cases of PVL in the human neonate (Volpe 2001).

Particulate matter may cause localized phlebitis (Marshall 1987). The duration of cannulation has been found to contribute to the development of infusion-related phlebitis (Maki 1991), and this may require the cannula to be replaced. Frequent cannula change is an added cost to treatment and may cause the patient pain and distress (Chee 2002).

Adverse systemic effects of particulate matter including granulomata formation in the lung (Marshall 1987) and ischaemic necrosis, are a common finding in necrotizing enterocolitis (Ballance 1990). Garvan examined IV fluids available in Australia, England, Europe and the United States of America for the presence of particulates. Microscopic analysis found rubber particles, crystals, cellulose fibers, fungal spores, starch granules and a crustacean claw (Garvan 1964). More recent studies found glass fragments from the opening of glass ampoules (Shaw 1985), and particles from rubber stoppers and intravenous equipment (Kirkpatrick 1988). Inorganic elements such as calcium, silicon, aluminium, lead and iron, that may have originated from the manufacture and packaging processes (Backhouse 1987), have also been found. Positively-charged in-line filters are reported to be effective in the retention of endotoxins (Barnett 1996).

Description of the intervention

There are two main IV filter pore sizes; the 0.22 micron filter is used for aqueous solutions, and the 1.2 micron filter is recommended for larger molecule solutions such as lipids. The 0.22 micron filter has also been reported to remove air, microorganisms and particulate matter. In addition, endotoxin retention is reportedly achieved by using a positively charged filter membrane; toxic macro-molecules are released by gram-negative bacteria and are claimed to be effective for up to ninety six hours (Bethune 2001).

How the intervention might work

In-line IV filters were conceived and first utilized in the 1960s for the retention of particulate contamination. Since then, filter systems have been further refined. In-line IV filters are currently claimed to be an effective strategy for the removal of bacteria, endotoxins and particulates associated with intravenous therapy in adults (Kunac 1999; Ball 2003) and have also been cited as leading to favourable patient outcomes such as shortened duration of hospital stays (Koekenberg 1983). Several adult studies have shown that IV in-line filtration significantly reduces the incidence (Roberts 1994; Chee 2002) and delays the onset of phlebitis, (Allcutt 1983; Roberts 1994) resulting in extended line survival (Roberts 1994), fewer recannulations (Chee 2002) and lower costs.The use of in-line filters in adults has also been shown to be effective in the removal of particulates, and particularly effective in the removal of particles caused from drug precipitate such as antibiotics (Roberts 1994; Chee 2002; Ball 2003).

Why it is important to do this review

The benefits of using IV in-line filters in adults have also been challenged by several authors. The Centre for Disease Control and Prevention recommends the filtration of infusates during manufacture as a more cost-effective and practical way to remove particulates than IV in-line filters (Pearson 1996; Newell 1998). Friedland (Friedland 1985) reported that some solutions caused a reduction in flow rate or clogging of the filter. He also reported that certain drugs such as antibiotics may be retained in the filters causing a reduction in potency. There are no known adverse effects from the use of IV in-line filters. If the filters block, they need to be changed leading to the increased manipulation of the IV administration set creating a potential for the introduction of contamination. However, blocking of the filter is claimed to be indicative of a problem such as microprecipitation that is a potentially harmful source of particulate matter (Bethune 2001). Friedland (Friedland 1985) also argued that filters could not reduce the risk of infection caused by contaminants entering the line below the in-line filter. A study by Newell (Newell 1998) found no difference in the rate of septicaemia between children in an oncology unit who had filters fitted and those who did not. They concluded from their results that the added cost of using IV in-line filters was not warranted.

In-line IV filters are also increasingly being recommended for use in neonates (Kunac 1999; Bethune 2001). Therefore, the aim of this review is to systematically assess the evidence on the effectiveness of in-line filters on intravenous lines in neonates.

Objectives

To determine the effect of in-line filters on intravenous lines on morbidity and mortality in neonates.

Pre-specified subgroup analysis will be carried out according to:

  1. type of filter (approximate diameter 0.2 micron; 1.2 micron);
  2. gestation: term and preterm (defined as < 37 weeks) or extreme preterm (defined as < 30 weeks gestation);
  3. type of intravenous line (central; peripheral);
  4. type of intravenous fluid (crystalloid solutions, total parenteral nutrition, antibiotics, lipids).

[top]

Methods

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised controlled trials were included in the review.

Types of participants

Neonates with intravenous infusions who were randomised in the neonatal period (< 29 days post delivery).

Types of interventions

In-line intravenous filter versus placebo or nothing.

Types of outcome measures

Primary outcomes
  1. Mortality from any cause.
  2. Proven septicaemic infection; positive bacterial or fungal blood culture.
Secondary outcomes
  1. Localised phlebitis; redness, inflammation and tenderness at location of cannula.
  2. Duration of cannula patency (days).
  3. Number of catheters inserted.
  4. Suspected septicaemic infection; clinical symptoms consistent with septicaemia but not proven.
  5. Thrombus, local (cannula insertion site); diagnosed by ultrasound.Thrombus, systemic; diagnosed by ultrasound.
  6. Proven necrotizing enterocolitis; Bell's stage two or greater.
  7. Suspected necrotizing enterocolitis (NEC); clinical symptoms consistent with NEC, but not proven.
  8. Periventricular leukomalacia (PVL); cystic changes in the periventricular areas.
  9. Neurodevelopment assessed up to two years corrected age as measured by a validated assessment tool.
  10. Financial costs.
  11. Length of stay in hospital (days).
  12. Adverse effects reported in the trials (if any).

Search methods for identification of studies

Electronic searches

Searches were made of the electronic databases MEDLINE (from 1966 to April 2, 2011), EMBASE (from 1980 to April 2, 2011), CINAHL (from 1982 to April 2, 2011), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2011). There was no language restriction. The following MeSH terms were used: infant OR newborn AND text terms 'intravenous catheter' OR 'infusion filter' OR 'filtration' OR 'in-line filter' OR 'infusions' OR 'endotoxins' OR 'bacterial' OR 'particulate contamination', OR 'phlebitis' OR 'infection', OR 'intravenous infusion'.

Searching other resources

We examined the references in all studies identified as potentially relevant. We searched the abstracts from the annual meetings of the Pediatric Academic Societies (1993 to 2010), the European Society for Pediatric Research (1995 to 2010), the UK Royal College of Paediatrics and Child Health (2000 to 2010) and the Perinatal Society of Australia and New Zealand (2000 to 2010). No new trials were identified. Clinical trials registries were also searched for ongoing or recently completed trials (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp).

Data collection and analysis

We followed the procedures of the Cochrane Neonatal Review Group (CNRG) throughout.

Selection of studies

Two review authors screened the title and abstract of all studies identified by the above search strategy. The full text of any potentially eligible reports was reassessed and those studies that did not meet all of the inclusion criteria were excluded. We discussed any disagreements until consensus was achieved.

Data extraction and management

We used a data collection form to aid extraction of relevant information from each included study.Two review authors extracted the data separately. The two reviewers independently assessed the trials for their methodological quality and subsequent inclusion in the review. Any disagreements were discussed until consensus was achieved. If data from the trial reports were insufficient, the investigators were contacted for further information.

Assessment of risk of bias in included studies

The criteria and standard methods of the Cochrane Neonatal Review Group were used to assess the methodological quality of any included trials. Additional information from the trial authors was requested to clarify methodology and results as necessary. The following issues were evaluated and reported in the Risk of Bias tables:

  1. Sequence generation: Was the allocation sequence adequately generated? We categorised the method used to generate the allocation sequence as:
    • low risk (any random process e.g. random number table; computer random number generator);
    • high risk (any non random process e.g. odd or even date of birth; patient case-record number);
    • unclear risk.
  2. Allocation concealment:Was allocation adequately concealed? We categorised the method used to conceal the allocation sequence as:
    • low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
    • high risk (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth);
    • unclear risk.
  3. Blinding: Was knowledge of the allocated intervention adequately prevented at study entry, during the study, and at the time of outcome assessment? We assessed blinding separately for different outcomes and categorised the methods as low risk, high risk or unclear risk for participants, clinicians and caregivers, and outcome assessors.
  4. Incomplete outcome data:Were incomplete outcome data adequately addressed? We described the completeness of data including attrition and exclusions from the analysis for each outcome and any reasons for attrition or exclusion where reported. We assessed whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported or supplied by the trial authors, we re-included missing data in the analyses. We categorised completeness as:
    • low risk (< 20% missing data);
    • high risk ( 20% missing data);
    • unclear risk.
  5. Selective reporting bias. Were reports of the study free of suggestion of selective outcome reporting? We aimed to assess whether methods were:
    • low risk (clear that all of the trial’s pre-specified outcomes and all expected outcomes of interest to the review have been reported);
    • high risk (where not all the trial’s pre-specified outcomes have been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);
    • unclear risk.

Measures of treatment effect

Statistical analysis followed the procedures of the Cochrane Neonatal Review Group. Dichotomous data is expressed as relative risk (RR and 95% confidence intervals (CI)), risk difference (RD with 95% CI) and number needed to treat (NNT) for dichotomous outcomes. Continuous variables was analysed using weighted mean differences (WMD) and 95% confidence intervals. The heterogeneity of studies was estimated using an I-squared statistic.

Unit of analysis issues

The unit on analysis is the participating infant in individually randomised trials.

Assessment of heterogeneity

If more than one trial was included in a meta-analysis, we examined the treatment effects of individual trials and
heterogeneity between trial results by inspecting the forest plots. We calculated the I² statistic for each analysis to quantify inconsistency across studies and describe the percentage of variability in effect estimates that may be due to heterogeneity rather than sampling error. If substantial (I² > 50%) heterogeneity was detected, we explored the possible causes (for example, differences in study design, participants, interventions, or completeness of outcome assessments) in sensitivity analyses.

Data synthesis

We used the fixed effects model in RevMan 5 for meta-analysis.

[top]

Results

Description of studies

See tables:Characteristics of Included Studies and Characteristics of excluded studies.

Results of the search

Four published studies met the inclusion criteria. No trials were excluded. A total of 704 neonates were included in these studies (range 63 to 442). The details of each of these four studies are given in the table of Characteristics of Included Studies.

Included studies

van den Hoogen 2006: The most recent study by van den Hoogen 2006 evaluated the effect of using 0.22 micron Pall Posidyne ELD96TM in-line filters versus no filter in 442 neonates on mortality, sepsis, phlebitis, number of catheter days and financial cost. The manufacturer recommends using this filter for the elimination of particles, microbes, air and endotoxins. All IV fluids in the study group (with the exception of lipids which were administered through a 1.2 micron LipiporTM filter) were given through the 0.22 micron in-line filter, and the administration sets were changed every four days. The intravenous sets in the control group and the LipiporTM filters (that are not able to retain endotoxins) were changed daily. The filters were positioned at the distal end of the IV-administration catheter after a series of stopcocks. The authors noted that this construction guaranteed that all clear fluids including IV medication were administered via the filter. The LipiporTMfilter was placed distally to the 0.22 micron in-line filter. No information on cannula site preparation was provided.

van Lingen 2004 studied 88 neonates to evaluate the effectiveness of the 0.22 micron Pall Posidyne ELD96TM in-line filters with no filters to prevent complications such as bacteraemia, phlebitis, extravasation, thrombosis, septicaemia and necrotizing enterocolitis in neonates who required an intravenous catheter. van Lingen 2004 also evaluated the economic impact of the use of IV in-line filters. All IV fluids in the study group (with the exception of lipids, blood or blood products) were given through the in-line filter and the administration sets were changed every four days. The intravenous sets in the control group were changed daily. In the study group, bacterial cultures were obtained at the time of change from both sides of the discarded filter and from the lipid solution. For the control group, bacterial cultures were obtained from the IV fluids every four days. In addition, catheter tips were cultured after removal. Blood was cultured only when sepsis was suspected. No information was provided on cannula site preparation. van Lingen 2004 reported that four patients in the control group died from "causes unrelated to catheter usage" i.e. NEC, pulmonary bleeding, severe intraventricular haemorrhage, circulatory insufficiency. However, these four neonates were included in the mortality outcome in this review.

Thomas 1989 assessed the effect of in-line filters on duration of cannula patency in 63 neonates requiring IV fluids. Thomas 1989 used a 0.2 micron CathivexTM filter that is only recommended for the removal of particulate and air. The filters in the study group were positioned before the cannulae, except where fluids such as blood, plasma protein fraction, fresh frozen plasma or emulsions were being administered. On these occasions, the filter was positioned upstream of the three way tap used for adding such fluids to the primary infusion line. In the control group, an extension set was substituted for the filter. This was included as it provided an equal number of connections and manipulations in the lines for both groups. The intravenous lines and filters were changed every 24 hours in the control and study groups. Cannula site preparation was limited to swabbing the skin with isopropyl alcohol. Following cannulation, the site was covered with a sterile dressing. No extra cannula site care was performed (such as application of antibiotic cream or spray) during the study. Cannula life was assessed by duration of patency and volume of IV fluid passed by the site. Nursing staff observations of the infusion site were used to subjectively determine the end point. Nursing staff routinely checked and recorded the condition of the IV cannula sites and the volume of fluid delivered every hour. No information was provided on the length of the study period.

Bennion 1991 assessed the effect of IV in-line filters on serum gentamicin level results, incidence of necrosed areas at the infiltration site and cost of administration sets with and without an IV in-line filter in 111 neonates. Bennion 1991 used a 0.22 micron Pall Posidyne ELD96TMthat was used by van Lingen 2004 and van den Hoogen 2006. The intravenous sets were changed every four days in the treatment group and daily in the control group. A record of the administration sets was made each day together with serum gentamicin level results for each baby and any necrosed areas that developed. Serum gentamicin levels were checked on the third dose of the antibiotic. No information was provided on cannula site preparation.

All studies were single centre studies. All four studies used 0.2 micron filters. The Bennion 1991 and Thomas 1989 studies used peripheral catheters, and the van Lingen 2004 and van den Hoogen 2006 studies used central venous (percutaneous or umbilical) catheters to deliver the IV fluids. While all the studies compared the use of in-line filters with no in-line filter, the outcomes that were measured varied.

There were no other identified studies that assessed whether intravenous in-line filters prevent morbidity and mortality in neonates.

Excluded studies

There were no excluded studies.

Risk of bias in included studies

Details of the methodological quality of each trial are given in the table Characteristics of Included Studies.

Allocation (selection bias)

Only the study of van Lingen 2004 was randomised (computer-generated randomisation with sealed numbered envelopes that were opened on admission of each neonate). Three studies (Bennion 1991; Thomas 1989; van den Hoogen 2006) were quasi-randomised (alternate allocation).

Blinding (performance bias and detection bias)

A placebo was not used in any of the four studies and, therefore, there was no blinding of the intervention. Outcome measurements were not blinded in any of the studies.

Incomplete outcome data (attrition bias)

The four studies examined short-term outcomes and accounted for all neonates in the intervention and control groups. Thirteen percent of the neonates in the van den Hoogen 2006 study were excluded from the study following randomisation because of incomplete data, either because the infant died or the patient was discharged soon after birth.

Effects of interventions

In-line intravenous filter vs. placebo

No studies were identified for this comparison.

In-line intravenous filter vs. no filter

Four studies were identified for this comparison (van den Hoogen 2006; van Lingen 2004; Bennion 1991; Thomas 1989).

Primary outcomes:

Mortality from any cause (Outcome 1.1)

Mortality was reported in 2 of the studies. For the van Lingen 2004 study of 88 infants there were four deaths in the control group and none in the treatment group. For the van den Hoogen 2006 study of 442 infants there were twenty two deaths in the control group and twenty four in the treatment group. There were no statistical difference for mortality in either of the studies. [Summary RR 0.87 (95% CI 0.52 to 1.47), RD -0.01 (95% CI -0.06 to 0.04)]

Proven septicaemic infection (positive bacterial or fungal blood culture) (Outcome 1.2)

Proven septicaemic infection was reported in two of the studies. There was no statistical difference found in the van Lingen 2004 study of 88 infants and in the van den Hoogen 2006 study of 442 infants. [Summary RR 0.86 (95% CI 0.59 to 1.27), RD -0.02 (95% CI -0.09 to 0.04)]

Secondary outcomes:

Localised phlebitis (redness, inflammation and tenderness at location of cannula) (Outcome 1.3)

Localised phlebitis was reported in three studies. Bennion 1991 reported the incidence of localised necrosis (undefined) in 111 infants with no statistical difference between the treatment and control groups. Phlebitis did not occur in the van den Hoogen 2006 and van Lingen 2004 studies in either study group. [Summary RR 1.22 (95% CI 0.40 to 3.77), RD 0.01 (95% CI -0.05 to 0.08)].

Thomas 1989 reported the incidence of 'tissuing' (undefined by authors but regarded as infiltration or leaking of fluids into the area surrounding the vein) related to number of cannulations rather than number of neonates and, therefore, could not be included in the above analysis. There were 59 incidences of phlebitis from 81 cannulations in the treatment group (n = 30) compared to 67 incidences of phlebitis from 86 cannulations in the control group (n = 33). There was no difference between the treatment and control groups.

Duration of cannula patency

Three studies reported on duration of cannula patency. In the van Lingen 2004 study, the total duration for the catheters remaining in place for all neonates in the study group (n = 44) was a total of 525 patient days (mean 8.1 days per neonate). In the control group, the total duration for the catheters remaining in place for all neonates (n = 44) was a total of 493 patient days (mean 8.8 days per neonate). A difference between the treatment and control groups was not found.

In the Thomas 1989 study, the median duration of catheter patency in the treatment group was 59 hours compared to 49 hours in the control group. The authors reported a statistical difference between the two groups (log rank test Chi squared = 4.024, p < 0.05) with a median increase in cannula patency of twenty percent in the treatment group compared to the control group. van den Hoogen 2006 compared the number of catheter days for umbilical venous, percutaneous and central venous catheters and found no difference between the treatment and control groups.

Number of catheters inserted

Two studies reported on the number of catheters inserted (Thomas 1989; van Lingen 2004). There was no difference between the treatment and control groups. In the van Lingen 2004 study there was a total of 65 IV catheter insertions. These were reported as 23 percutaneous and 42 umbilical central venous catheter insertions (43 first, 17 second and 5 third) for the neonates in the study group (n = 44). There were 56 (40 percutaneous and 16 umbilical) catheter insertions (42 first, 12 second and 2 third) for the neonates in the control group (n = 44). For the Thomas 1989 study there was a total of 81 catheter (peripheral) insertions in the study group (n = 30) compared to 86 catheter (peripheral) insertions in the control group (n = 33). Standard deviations were not provided and, therefore, a weighted mean difference could not be performed.

Suspected septicaemic infection (clinical symptoms consistent with septicaemia, but not proven) (Outcome 1.4)

The van Lingen 2004 study of 88 infants was the only study to report suspected septicaemic infection and found no difference. [RR 0.57 (95% CI 0.18 to 1.81), RD -0.07 (95% CI -0.21 to 0.07)].

Local thrombosis (cannula insertion site, diagnosed by ultrasound) (Outcome 1.5)

Local thrombosis was only reported in the van Lingen 2004 study. No significant difference was found. [RR 0.20 (95% CI 0.01 to 4.05), RD -0.05 (95% CI -0.12 to 0.03)].

Systemic thrombus (diagnosed by ultrasound)

No data were available.

Proven necrotizing enterocolitis (Bell's stage two or greater) (Outcome 1.6)

Proven necrotizing enterocolitis (NEC) was only reported in the van Lingen 2004 study and there were no significant differences. [RR 0.20 (95% CI 0.01 to 4.05), RD -0.05 (95% CI -0.12 to 0.03)].

Suspected necrotizing enterocolitis (clinical symptoms consistent with NEC, but not proven)

No data were available.

Periventricular leukomalacia (cystic changes in the periventricular areas)

No data available

Neurodevelopment (assessed up to two years corrected age, as measured by a validated assessment tool)

No data were available.

Financial costs

van den Hoogen 2006 compared the costs of disposable materials per patient per four days. In the study group, two filters (clear fluid and lipid) and intravenous sets were changed every 96 hours and the intravenous sets in the control group were changed daily. The total cost per neonate in the control group was 241.76 Euros and 238.63 in the study group showing that the cost of using an in-line filter was compensated by the reduced consumption of intravenous administration sets. van den Hoogen 2006 also used filters for fat emulsions that had to be changed daily. Without the inclusion of these filters in the calculation, costs of disposable materials in the in-line filter group would have been much lower at 107.73 Euros over the four day period, less half that in the control group. This study also found that the time necessary for changing the IV-administration sets was significantly longer in the non-filter group: the mean time was 14 plus ± 7 minutes in the non-filter group, compared to 10 ± 5 minutes in the filter group (P=0.000).

For the van Lingen 2004 study, costs attributable to patients in both control and study groups were calculated on a 'cost of disposables' basis during a standard eight day stay. Additionally, the time taken for line change was calculated by 'direct assessment', and an estimate of the relative nursing costs was built into the analysis. In the study group, filters and intravenous sets were changed every 96 hours and in the control group, the intravenous sets were changed daily. However, unlike the van den Hoogen 2006 study, lipid filters were not included in the calculation. The total cost per neonate in the control group was 85.75 Euro and for the study group was 37.44 Euro showing a saving of 48.31 Euros per neonate over a period of eight days.

The Bennion 1991 study reported the average cost of an administration system as approximately 17.28 Pounds per day for the control group compared to 8.84 Pounds per day in the study group (showing a daily saving of 8.44 Pounds in the treatment group). This was calculated by dividing the total cost of the equipment used by the number of cot days occupied by infants in each group. The intravenous sets were changed every 96 hours in the control group and in the control group, the intravenous sets were changed daily.

Adverse affects reported in the trials

In the Bennion 1991 study, precipitate was found to clog the filter and the flow of intravenous fluids. The IV in-line filter also became blocked in one patient in the van den Hoogen 2006 study that was reported to be possibly due to the administration of very high glucose concentrations (50%).

There was no data available to be able to perform subgroup analysis on type of filter, gestation, type of intravenous line, type of intravenous fluid.

Discussion

Summary of main results

None of the outcomes of mortality, proven or suspected septicaemia, localised phlebitis, localised thrombi, necrotizing enterocolitis, and length of stay between the treatment and control groups were statistically different. There was also no difference between the treatment and control groups for duration of cannula patency and number of catheters inserted.

Evaluation of a composite outcome was not prespecified in this review. van Lingen 2004 reported a composite outcome for thrombi, proven sepsis, unproven sepsis and NEC. This demonstrated a reduction of 62% in risk of adverse outcome in the treatment group [RR 0.38 (95% CI 0.19 to 0.77), RD -0.30 (95% CI -0.48 to -0.11)].

Cost savings were reported by Bennion 1991; van Lingen 2004 and van den Hoogen 2006. We found no data available from randomised controlled trials that compared periventricular leukomalacia, incidence of systemic thrombus and neurodevelopmental outcomes.

Overall completeness and applicability of evidence

There is insufficient evidence to recommend the use of intravenous in-line filters to prevent morbidity and mortality in neonates. However, an increase in morbidity, mortality or adverse events was not demonstrated with the less frequent changing of the intravenous sets (every four days) when an IV in-line filter was used compared to daily changing of the IV administration sets in the control group.

Quality of the evidence

Four trials of variable quality were included in the review (Thomas 1989; Bennion 1991; van Lingen 2004; van den Hoogen 2006).

Authors' conclusions

Implications for practice

There is insufficient evidence to recommend the use of intravenous in-line filters to prevent morbidity or mortality in neonates. However, cost savings were found with the less frequent changing of the intravenous sets when a 0.2 micron IV in-line filter that removes endotoxins was used without an increase in adverse outcomes.

Implications for research

Further trials are needed to be able to assess the effectiveness of 0.22 micron positively charged 96 hour IV in-line filters and 1.2 micron IV in-line filters used for lipid administration for use in term and preterm neonates for the outcomes of periventricular leukomalacia, necrotizing enterocolitis, systemic and local thrombus and local phlebitis.

Acknowledgements

Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract NO. HHSN267200603418C.

Contributions of authors

Jann Foster (JF), Robyn Richards (RR) and Marian Showell (MS) independently assessed studies for inclusion in this review.
JF and RR wrote the review with the assistance of MS.
JF acts as guarantor for the review.

Declarations of interest

There are no potential conflicts of interest.

Differences between protocol and review

  • None noted.

Additional tables

  • None noted.

Potential conflict of interest

  • None noted.

[top]

Characteristics of studies

Characteristics of Included Studies

Bennion 1991

Methods

Parallel randomised controlled trial.

Participants

111 neonates requiring IV fluids via peripheral venous line.
Gestation - 28-37 weeks
Birthweight - 1170-3240g
No exclusions

Interventions

Exp. group - 0.22 micron intravenous in-line filter (N=55)
Control group - No filter or placebo. Administration set changed daily in control group and every 96 hours in treatment group
(N=56).

Outcomes
  1. Effect of intravenous in-line filters on gentamycin level results
  2. Incidence of necrosed area at infiltration site
  3. Cost of administration sets when an in-line filter is used, compared to the cost when a filter is not used
  4. Duration of IV in progress
  5. Duration of IV infusion in progress
Notes
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) High risk

Quasi-randomised

Each baby that required intravenous infusion was entered into the study with alternate babies having an in-line filter.

Allocation concealment (selection bias) High risk
Blinding (performance bias and detection bias) High risk

Unblinded

Blinding of participants and personnel (performance bias) High risk
Blinding of outcome assessment (detection bias) High risk
Incomplete outcome data (attrition bias) Low risk
Other bias Low risk

Thomas 1989

Methods

Parallel randomised controlled trial.

Participants

63 neonates requiring IV fluids via peripheral venous line.
Mean gestation - 34.13- 34.91wks
Mean birthweight - 2230-2350g
No exclusions

Interventions

Exp. group - 0.2 micron intravenous filter (N=30)
Control group - No filter but extension set substituted for filter. (N=33)
Administration sets changed every 24 hours in treatment and control groups

Outcomes
  1. Duration of cannula patency
  2. Extravasation
  3. Leaking at infusion site
  4. Number of catheter insertions
Notes
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) High risk

Quasi-randomised

Each baby that required intravenous infusion was entered into the study with alternate babies having an in-line filter.

Allocation concealment (selection bias) High risk
Blinding (performance bias and detection bias) High risk

Unblinded

Blinding of participants and personnel (performance bias) High risk
Blinding of outcome assessment (detection bias) High risk
Incomplete outcome data (attrition bias) Low risk
Other bias Low risk

van den Hoogen 2006

Methods

Parallel randomised controlled trial.

Participants

442 neonates requiring IV fluids via an umbilical or percutaneous central venous catheter or a catheter inserted in the subclavian or femoral vein (CVC). All neonates admitted to the NICU and required fluids via a central venous catheter were eligible.
Gestation - 25-43 weeks
Birthweight 600 - 4640 grams

Interventions

Exp. group - 0.22 micron intravenous filter (N=228)
Control group - No filter (N=214)
Catheter tips cultured after removal
Administration set changed daily in the control group. Administration set changed every 96 hours in treatment group

Outcomes
  1. Mortality
  2. Phlebitis: defined as 'signs of local infection and a positive culture from the infected site'
  3. Proven Sepsis: defined as 'occurrence of clinical signs of local infection and a positive blood culture'
  4. Number of catheter days
  5. Length of stay in hospital
  6. Financial costs
Notes
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) High risk

Quasi-randomised

Each baby that required intravenous infusion was entered into the study with alternate babies having an in-line filter.

Allocation concealment (selection bias) High risk
Blinding (performance bias and detection bias) High risk

Unblinded

Blinding of participants and personnel (performance bias) High risk
Blinding of outcome assessment (detection bias) High risk
Incomplete outcome data (attrition bias) Low risk
Other bias Low risk

van Lingen 2004

Methods

Parallel randomised controlled trial.

Participants

88 neonates requiring IV fluids via an umbilical or percutaneous central venous line. Premature infants with RDS and term infants with asphyxia or pneumonia/ septicaemia were eligible
Gestation - 26.3-42.3 weeks
Birthweight 585 - 4100g
Ineligible if congenital malformation present and infants < 26 weeks gestation

Interventions

Exp. group - 0.22 micron intravenous filter (N=44)
Control group - No filter or placebo (N=44)
Full blood count on admission
Catheter tips cultured after removal
Administration set changed daily in the control group. Administration set changed every 96 hours in treatment group

Outcomes
  1. Phlebitis
  2. Extravasation
  3. Thrombosis
  4. Proven Sepsis: 'characteristic clinical symptoms' positive blood culture, and abnormal tests, (leucocytosis, leucopenia, granulocytopenia CRP> 10mg/l)
  5. Unproven sepsis: 'characteristic clinical symptoms' and negative blood culture and abnormal tests
  6. NEC
  7. Duration of cannula patency
  8. Number of catheter insertions
  9. Duration of catheter insertion

Secondary septicaemia

Notes
Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Computer generated randomisation and sealed numbered envelopes were opened on admission of the neonate; neonates allocated to either study or control group

Allocation concealment (selection bias) Low risk
Blinding (performance bias and detection bias) High risk

Unblinded

Blinding of participants and personnel (performance bias) High risk
Blinding of outcome assessment (detection bias) High risk
Incomplete outcome data (attrition bias) Low risk
Other bias Low risk

Characteristics of excluded studies

  • None noted.

Characteristics of studies awaiting classification

  • None noted.

Characteristics of ongoing studies

  • None noted.

[top]

References to studies

Included studies

Bennion 1991

Bennion D, Martin K. In-line filtration. Paediatric Nursing 1991;June:20-21.

Thomas 1989

Thomas PH. In-line terminal filtration of intravenous fluids and its. Effect on cannula patency in neonates. Proceedings- Guild of Hospital Pharmacy 2004;26:3-10.

van den Hoogen 2006

van den Hoogen A, Krediet TG, Uiterwaal C, Bolenius J, Gerards LJ, Fleer A. In-line filters in central venous catheters in a neonatal intensive care unit. Journal of Perinatal Medicine 2006;34:71-74.

van Lingen 2004

van Lingen RA, Baerts W, Marquering AC, Ruijs GJ. The use of in-line intravenous filters in sick newborn infants. Acta Paediatrica 2004;93:658-62.

References to excluded studies

  • None noted.

Studies awaiting classification

  • None noted.

Ongoing studies

  • None noted.

Other references

Additional references

Allcutt 1983

Allcutt DA, Lort D, McCollum CN. Final inline filtration for intravenous infusions: a prospective hospital study. British Journal of Surgery 1983;70:111-13.

Backhouse 1987

Backhouse CM, Ball PR, Booth S, Kelshaw MA, Potter SR, McCollum CN. Particulate contaminants of intravenous medications and infusions. Journal of Pharmacy and Pharmacology 1987;39:241-5.

Ball 2003

Ball PA. Intravenous in-line filters: filtering the evidence. Current Opinion in Cinical Nutrition and Metabolic Care 2003;6:319-25.

Ballance 1990

Ballance WA, Dahms BB, Shenker N, Kliegman RM. Pathology of neonatal necrotizing enterocolitis: a ten year experience. Journal of Pediatrics 1990;117:S6-S13.

Barnett 1996

Barnett MI, Cosslett AG. Endotoxin retention capabilities of positively charged nylon and positively charged polysulphone membrane intravenous filters. Pharmaceutical Sciences 1996;2:319-20.

Bethune 2001

Bethune K, Allwood M, Grainger C, Wormleighton C; British Pharmaceutical Nutrition Group Working Party. Use of filters during the preparation and administration of parenteral nutrition: position paper and guidelines prepared by a British pharmaceutical nutrition group working party. Nutrition 2001;17:403-8.

Casale 1990

Casale T, Ballas Z, Kaliner M, Keahey T. The effect of intravenous endotoxin on various host-effector molecules. Journal of Allergy and Clinical Immunology 1990;85:45-51.

Chee 2002

Chee S, Tan W. Reducing infusion phlebitis in Singapore hospitals using extended life end-line filters. Journal of Infusion Nursing 2002;25:95-104.

Friedland 1985

Friedland G. Infusion-related phlebitis--is the in-line filter the solution? New England Journal of Medicine 1985;312:113-5.

Garvan 1964

Garvan JM, Gunner BW. The harmful effects of particles in intravenous fluids. Medical Journal of Australia 1964;17:1-6.

Geiss 1992

Geiss H, Batzer A, Sonntag H. Investigations on the retention of microorganisms by inline-filters for intravenous infusions in ICU patients. Hygiene Medizin 1992;17:421-6.

Gilles 1977

Gilles FH, Averill DR Jr, Kerr CS. Neonatal endotoxin encephalopathy. Annals of Neurology 1977;2:49-56.

Glauser 1991

Glauser MP, Zanetti G, Baumgartner JD, Cohen J. Septic shock: pathogenesis. Lancet 1991;338:732-6.

Hill 1992

Hill A, Volpe JJ. Textbook of Neonatology. 2nd edition. London: Churchill Livingstone, 1992.

Kirkpatrick 1988

Kirkpatrick C. Particulate matter in intravenous fluids: The importance for medicine. Krankenhauspharmazie 1988;9:487-90.

Koekenberg 1983

Koekenberg H. A case for I.V. filtration. Infusion 1983;7:76-82.

Kunac 1999

Kunac D, Ball P, Broadbent R. In-line intravenous filtration in neonates-help not hindrance. Australian Journal of Hospital Pharmacy 1999;29:321-27.

Maki 1991

Maki DG, Ringer M. Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. Annals of Internal Medicine 1991;114:845-54.

Marshall 1987

Marshall L, Lloyd G. Intravenous fluid infiltration. Care of the Critically Ill 1987;3:10-17.

Newell 1998

Newell F, Ranson K, Robertson J. Use of in-line filters in pediatric intravenous therapy. Journal of Intravenous Nursing 1998;21:166-70.

Ng 1989

Ng P, Herrington RA, Beane CA, Ghoneim A, Dear PR. An outbreak of acinetobacter septicaemia in a neonatal intensive care unit. Journal of Hospital Infection 1989;14:363-8.

O'Dwyer 1988

O'Dwyer ST, Michie HR, Zeigler TR, Revhaug A, Smith RJ, Wilmore DW. A single dose of endotoxin increases intestinal permeability in healthy humans. Archives of Surgery 1988;123:1459-64.

Parsons 1989

Parsons PE, Worthen GS, Moore EE, Tate RM, Henson PM. The association of circulating endotoxin with the development of adult respiratory distress syndrome. American Review of Respiratory Diseases 1989;140:294-301.

Pearson 1996

Pearson ML. Guideline for prevention of intravascular device-related infections: Part 1. Intravascular device-related infections: an overview. The Hospital Infection Control Practices Advisory Committee. American Journal of Infection Control 1996;24:262-77.

Quercia 1986

Quercia RA, Hills SW, Klimek JJ, McLaughlin JC, Nightingale CH, Drezner AD, Sigman R. Bacteriologic contamination of intravenous infusion delivery systems in an intensive care unit. American Journal of Medicine 1986;80:364-8.

Roberts 1994

Roberts GW, Holmes MD, Staugas RE, Day RA, Finlay CF, Pitcher A. Peripheral intravenous line survival and phlebitis prevention in patients receiving intravenous antibiotics: heparin/hydrocortisone versus in-line filters. The Annals of Pharmacotherapy 1994;28:11-6.

Shaw 1985

Shaw NJ, Lyall EG. Hazards of glass ampoules. British Medical Journal (Clinical Research Ed) 1985;291:1390.

Suffredini 1989a

Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. New England Journal of Medicine 1989;320:1165-72.

Suffredini 1989b

Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parrillo JE. The cardiovascular response of normal humans to the administration of endotoxin. New England Journal of Medicine 1989;321:280-7.

Volpe 2001

Volpe J. Neurobiology of periventricular leukomalacia in the premature infant. Pediatric Research 2001;50:553-62.

Other published versions of this review

Foster 2006

Foster JP, Richards R, Showell MG. Intravenous in-line filters for preventing morbidity and mortality in neonates. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD005248. DOI: 10.1002/14651858.CD005248.pub2.

Classification pending references

  • None noted.

[top]

Data and analyses

1 In-line intravenous filter vs. no filter

For graphical representations of the data/results in this table, please use link under "Outcome or Subgroup".

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
1.1 Mortality 2 530 Risk Ratio (M-H, Fixed, 95% CI) 0.87 [0.52, 1.47]
1.2 Proven Septicaemia 2 530 Risk Ratio (M-H, Fixed, 95% CI) 0.86 [0.59, 1.27]
1.3 Localised Phlebitis 3 641 Risk Ratio (M-H, Fixed, 95% CI) 1.22 [0.40, 3.77]
1.4 Suspected Septicaemia 1 88 Risk Ratio (M-H, Fixed, 95% CI) 0.57 [0.18, 1.81]
1.5 Localised Thrombi 1 88 Risk Ratio (M-H, Fixed, 95% CI) 0.20 [0.01, 4.05]
1.6 Proven Necrotizing Enterocolitis 1 88 Risk Ratio (M-H, Fixed, 95% CI) 0.20 [0.01, 4.05]

Figures

  • None noted.

Sources of support

Internal sources

  • NSW Pregnancy and Newborn Services Network, Sydney, Australia

External sources

  • No sources of support provided.

This review is published as a Cochrane review in The Cochrane Library, Issue 9, 2011 (see http://www.thecochranelibrary.com External Web Site Policy 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.