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Saline irrigation for the management of skin extravasation injury in neonates

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Authors

PN Gopalakrishnan1, N Goel1, Sujoy Banerjee1

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


1Department of Neonatology, Singleton Hospital, ABM University NHS Trust, Swansea, UK [top]

Citation example: Gopalakrishnan PN, Goel N, Banerjee S. Saline irrigation for the management of skin extravasation injury in neonates. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008404. DOI: 10.1002/14651858.CD008404.pub2.

Contact person

PN Gopalakrishnan

Department of Neonatology
Singleton Hospital, ABM University NHS Trust
Sketty Lane
Swansea
Wales
SA2 8QA
UK

E-mail: sukagopa@hotmail.com

Dates

Assessed as Up-to-date: 11 July 2011
Date of Search: 24 June 2011
Next Stage Expected: 11 July 2013
Protocol First Published: Issue 3, 2010
Review First Published: Issue 2, 2012
Last Citation Issue: Issue 2, 2012

Abstract

Background

Extravasation injury is a common complication of neonatal intensive care and can result in scarring with cosmetic and functional sequelae. A wide variety of treatments are used in practice including subcutaneous irrigation with saline (with or without hyaluronidase), liposuction, use of specific antidotes, different topical applications and normal wound care with dry or wet dressings. All such treatments aim to prevent or reduce the severity of complications.

Objectives

To determine the efficacy and safety of saline irrigation or saline irrigation with prior hyaluronidase infiltration on tissue healing in neonates with extravasation injury when compared to no intervention or normal wound care.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011), EMBASE (Jan 1980 to June 2011), CINAHL (Jan 1988 to June 2011) and the Web of Science (up to July 2011).

Selection criteria

Randomised controlled trials (RCT) and quasi-randomised controlled trials comparing saline irrigation with or without hyaluronidase infiltration with no intervention or normal wound care in the management of extravasation injury in neonates.

Data collection and analysis

Three review authors independently reviewed and identified articles for possible inclusion in this review.

Results

No eligible studies were found. There were a few case reports and case series describing successful outcomes with different interventions in this condition.

Authors' conclusions

To date, no randomised controlled trial is available that examines the effects of saline irrigation with or without prior hyaluronidase infiltration in the management of extravasation injury in neonates. Saline irrigation is a frequently reported intervention in the literature that is used in the management of extravasation injury in neonates. Research should be initially directed at evaluating the efficacy and safety of this intervention through randomised controlled trials. It will also be important to determine the size of the effect according to timing of intervention, nature of the infusate and the severity of injury at the time of intervention.

Plain language summary

Saline irrigation for the management of skin extravasation injury in neonates

Preterm and sick term infants requiring intravenous fluids and medications are vulnerable to tissue injury secondary to extravasation that is, leakage of fluid into the surrounding tissue. Such injury can result in scarring with consequent cosmetic issues and, in some infants, functional limitation. Remedial surgical intervention may be required for some babies. Saline flush out, with or without prior infiltration of hyaluronidase (a protein that helps the breakdown of barriers that hold tissue planes together), is widely used in the management of severe extravasation injury in neonates and aims to prevent or reduce complications following the extravasation. Conservative treatment with normal wound care and various topical dressings is commonly used. We planned to examine if saline flush out with or without prior hyaluronidase infiltration into the injured area resulted in better short and long-term cosmetic and functional outcomes when compared to normal wound care. We did not find any study that currently answers this question.

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Background

Description of the condition

Many preterm and sick term infants in neonatal intensive care units require intravenous nutrition and medication as part of their care and are particularly vulnerable to extravasation (leakage of fluid into surrounding tissue) injury. Extravasation or infiltration of intravenous fluid into the surrounding tissue is known to occur at some point in up to 70% of the neonates undergoing intensive care (Irving 1999). A survey of regional neonatal intensive care units (NICU) in the United Kingdom (UK) reported the prevalence of extravasation injury resulting in skin necrosis (local tissue death) as 38/1000 neonates, with 70% of these injuries occurring in infants of 26 weeks gestation or less (Wilkins 2004). About 4% of infants leave NICU with cosmetically or functionally significant scars caused by extravasation injuries (Wilkins 2004). Extravasation of intravenous infusion into the interstitial space may result from either displacement of the intravascular catheter or increased vascular permeability. Some medications and infusions are more toxic to the veins than others. The mechanism of extravasation necrosis is not completely understood, but the degree of damage appears to be related to osmolality, pH and the dissociability of ions in the infusate (intravenous fluid) (Davies 1994).

Depending upon the nature and volume of the infusate, the extravasation may go unnoticed or may cause severe inflammation. In the short-term, this may lead to partial or complete skin loss, infection, nerve or tendon damage and, infrequently, compartment syndrome leading to amputation of the affected limb (Gault 1993). Scarring leading to contractures and disfigurement, functional loss of the affected part, complex regional pain syndrome (Hadaway 2007) and major limb deformities (Fullilove 1997) are well known long-term sequelae (Cartlidge 1990). It has been reported that 70% of scars sustained due to minor extravasation injuries disappeared by eight years of age while more serious scars were still seen at eight years of age but were less prominent (Fox 1998).

Extravasation injury has been classified into four stages (Millam 1988; Flemmer 1993; McCullen 2006).

  • Stage 1: painful intravenous site, no erythema and swelling, flushes with difficulty.
  • Stage 2: painful intravenous site, slight swelling, redness, no blanching, brisk capillary refill below infiltration site, good pulse volume below infiltration site.
  • Stage 3: painful intravenous site, marked swelling, blanching, cool to touch, brisk capillary refill below infiltration site, good pulse volume below infiltration site.
  • Stage 4: painful intravenous site, very marked swelling, blanching, cool to touch, capillary refill more than four seconds, decreased or absent pulse, skin breakdown or necrosis.

The best management approach should be preventative and requires hypervigilant monitoring of the intravenous site (Patnaik 2004). However, once extravasation has occurred, there is no agreement on the best practice that would reduce tissue damage and its consequent complications. A number of treatments are used in practice, including irrigation with saline (with or without prior infiltration of hyaluronidase), liposuction, use of specific antidotes, various topical applications and normal wound management with dry or wet dressings (Ramasethu 2004). Successful outcomes without sequelae have been reported with multiple needle puncture of the extravasation site followed by gentle squeezing (Chandanvasu 1986). Various topical applications such as silver sulphadiazine cream (Friedman 1998), silver sulphadiazine ointment, topical povidone iodine ointment and saline wash (Brown 1979), topical application of silver sulphadiazine and paraffin tulle (Kumar 2001), hydrocolloid gel (Thomas 1997; Sawatzky-Dickson 2006), fibrinolysin and deoxyribonuclease ointment (Falcone 1989) and a combination of antibacterial ointment, sesame oil and a herbal mixture (Cho 2007) have all been reported to be effective. In a tense extravasation injury, gentle massaging of the affected limb to allow good capillary flush has been reported to be beneficial (Davidson 1985). Infiltration of 'recombinant human hyaluronidase' (rHuPh30) into the extravasation injury site has been reported recently (Kuensting 2010). It has been suggested that the effectiveness of the intervention may depend on the injury-intervention interval (Casanova 2001). Limb elevation and observation has shown to effective when the extravasation resulted in erythema and swelling (Reynolds 2007). The stage of the injury at intervention may also be important and it has been suggested that saline irrigation for stage 3 or 4 extravasation may prevent further damage (Sawatzky-Dickson 2006).

Description of the intervention

Subcutaneous irrigation in extravasation injury is carried out using the ‘flush-out technique’ first proposed by David Gault in 1993 (Gault 1993). Dilute hyaluronidase is infiltrated into the affected area following a local anaesthetic infiltration under aseptic conditions. Four small stab incisions are made around the periphery of the extravasated area. Saline is then infiltrated into the subcutaneous tissue in small volumes of 20 to 50 ml (Gault 1993) using a blunt ended needle with a side hole so that it dilutes the extravasate and comes out freely through the exit stab incisions. A total of 500 ml of saline is recommended for the ‘flush-out’ (Gault 1993; Davies 1994; Harris 2001). Residual fluid is then manipulated down to the exit holes and expressed. After flush-out, a wound dressing is applied and the limb is elevated for 24 hours.

Although this is the standard procedure described by Gault, there is wide variation in the flush-out process, dosage of hyaluronidase (Bruera 1999) and the total volume of saline used for irrigation. The published literature does not provide specific guidance on the time interval allowed between injection of hyaluronidase and subsequent saline flush-out. However, the majority of the reports mention that this should be undertaken soon after the hyaluronidase infiltration.

How the intervention might work

Immediate saline irrigation with or without hyaluronidase is increasingly used in neonatal units across the world. The idea is that saline irrigation will dilute the extravasate and flush it out from the local area as quickly as possible. This technique is theoretically possible in neonates who have very little subcutaneous fat.

Hyaluronidase is an enzyme that hydrolyses the mucopolysaccharides present in the subcutaneous connective tissues. Hyaluronidase reversibly hydrolyses hyaluronic acid polymers in the extracellular space (Jaworski 1950). This is thought to enhance the permeability within the subcutaneous tissue compartment and allow diffusion of the extravasate through larger areas in the subcutaneous space, which can then be flushed out more easily by saline irrigation (PPAG 2005).

Why it is important to do this review

Extravasation injury is associated with serious morbidity in neonates. In the short-term this may cause pain, tissue necrosis, ulceration and infection. In the medium to long-term this may lead to scar formation with disfigurement and functional impairment.If effective, saline irrigation with or without hyaluronidase infiltration may reduce this morbidity. However, the intervention is highly invasive and involves a great deal of manual handling of the sick and vulnerable neonate. Potentially it can lead to pain, hypothermia, infection and cardiorespiratory destabilisation. The multiple stab incisions integral to the procedure may in themselves result in scar formation. It is important to establish if, in the short and long-term, this form of intervention is superior to conservative wound management only.

Objectives

Primary objective

To evaluate the efficacy and safety of: 1) saline irrigation or 2) saline irrigation with prior hyaluronidase on tissue healing in neonates with extravasation injury when compared to no intervention or normal wound care.

Secondary objective

To evaluate by subgroup analysis of the controlled trials the influence of the type of extravasate, the timing of irrigation following extravasation and postmenstrual age (PMA) of the neonate at the time of injury on the outcome and adverse effects.

Specifically, we planned to perform subgroup analysis, if appropriate, for the primary outcome by:

  1. time to irrigation from identified extravasation injury (less than one hour or greater than one hour);
  2. type of extravasate (parenteral nutrition fluidor other fluids or medications);
  3. amount of saline used (less than 500 ml or greater than 500 ml);
  4. postmenstrual age at injury (less than 37 completed weeks or more than 37 completed weeks).

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Methods

Criteria for considering studies for this review

Types of studies

All randomised and quasi-randomised controlled trials comparing saline irrigation, with or without hyaluronidase infiltration, with no intervention or normal wound care only. Relevant studies published only as abstracts in conference proceedings were considered eligible and the principal author contacted for further details. There were no language restrictions applied.

Types of participants

Neonates of any gestational age at birth (defined as up to 28 days of postnatal age at enrolment) with extravasation of intravenous infusate from peripheral or central venous catheters, where extravasation has led to any one of the following:

  1. moderate swelling and erythema of the overlying area;
  2. blanching or discolouration of the overlying skin;
  3. pressure symptoms (capillary refill more than four seconds and reduced or absent pulse below the site of extravasation);
  4. ulceration of the overlying skin.

Types of interventions

Irrigation therapy is defined as any intervention where saline is instilled into the site of extravasation, with the aim of diluting the extravasate, followed by provision for it to drain through the skin incisions. Any prior infiltration with hyaluronidase and its dosage was also recorded.

Normal wound care is defined as that involving no irrigation or other invasive interventions but including wound care with dry or wet dressings and wound debridement if clinically indicated.

Types of outcome measures

Primary outcomes

Complete tissue healing (defined as no residual breach of skin or inflammatory signs) without scar formation at discharge or latest assessment, preferably at least three months from the time of injury as complete wound healing is expected by this time.

Secondary outcomes
Short-term outcomes
  1. Time to complete tissue healing.
  2. Infection, defined as at least one of the following:
    1. purulent discharge from the site;
    2. organisms isolated from an aseptically obtained culture of fluid or tissue obtained from the site;
    3. clinical diagnosis made by the physician requiring topical or systemic antibiotics.
  3. Pain during the intervention (measured on validated neonatal pain scales).
  4. Hypothermia during or at the end of the intervention (defined as temperature < 36 °C or a drop of 2 °C from baseline measurement).
  5. Anaphylactic reactions.
  6. Fluid and electrolyte status.
  7. Any other adverse effects reported in the trials.
Long-term outcomes
As measured in the latest assessment, preferably at least three months from the injury.
  1. Severity of the scar, as measured by a quantifiable validated scar scale. The scar measurement scales could include, but are not limited to the Vancouver Scar Scale, a visual analogue scale, the Patient and Observer Scar Assessment Scale and the Manchester Scale.
  2. Contractures – permanent tightening of non-bony tissues such as muscles, tendons, ligaments or skin, with or without restriction of joint motion (dichotomous outcome).
  3. Functional impairment – restriction of function of the injured body part, as reported by caregivers or physician (dichotomous outcome).
  4. Disfigurement - substantial scarring which is cosmetically offensive, measured by caregivers or physician reporting (dichotomous outcome).
  5. Need for further surgical procedures.

Search methods for identification of studies

Electronic searches

We used the standardised search strategy of the Cochrane Neonatal Review Group (CNRG) as outlined in The Cochrane Library (CNRG 2011). We searched the following sources from 1966 to June 2011 for eligible studies in any language:

  • the Cochrane Neonatal Review Group Trials Register;
  • the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2) (28 June 2011);
  • MEDLINE (24 June 2011);
  • EMBASE (27 June 2011);
  • CINAHL (28 June 2011);
  • the Web of Science (11 July 2011).

MeSH subject headings are given in detail in the Appendix 1. We limited the search to human studies and randomised controlled trials and quasi-randomised controlled trials. A summary of the literature is mentioned in Appendix 1.

Searching other resources

We reviewed the reference lists from the above articles and from review articles on the subject.

Where relevant we attempted to communicate with the primary authors from the above to identify unpublished data.

Proceedings of the Nutrition Society: Nestle Foundation (2004).

Proceedings of summer meetings of the British Association of Plastic Surgeons (2001 to 2010).

Proceedings of the annual conferences of the European Society for Paediatric Research (2001 to 2010).

Proceedings of the Pediatric Academic Societies (2001 to 2010).

One abstract was retrieved from the abstract archives of the Pediatric Academic Societies meetings and found not relevant to this review (Valente 2001).

One abstract from the proceedings of the British Association of Plastic Surgeons Summer Meeting in July 2001 could not be retrieved in full. Therefore the primary author of the presentation (Moss 2001) was contacted by e-mail. The primary author replied back to inform us that he has no current access to the abstract.

A search of the several trial registries: Clinical trials.gov, NIH clinical trials.gov register (international), IsrcTN Register (international), Medical Research Council (UK) for any current ongoing trials yielded no relevant ongoing trials.

Data collection and analysis

We used the standardised methods of The Cochrane Collaboration and the Cochrane Neonatal Review Group.

Selection of studies

Three review authors independently reviewed all identified articles for possible inclusion in this review. In the event of any disagreements on the suitability of a trial for inclusion in the review, consensus was reached by discussion.

Data extraction and management

Each review author extracted data separately using pre-designed data extraction forms and then compared results. However, no suitable randomised controlled trial (RCT) or quasi-RCT was identified for further analysis.

Assessment of risk of bias in included studies

The review authors planned to evaluate the methodology of the included trials independently. This would have included evaluations regarding quality of randomisation, quality of intervention, quality of outcome measure assessment and completeness of follow-up using The Cochrane Collaboration's tool for assessing risk of bias.

Specifically, we planned to evaluate the following issues and present our assessments in a 'Risk of bias' table.

  1. Sequence generation: was the allocation sequence adequately generated?
  2. Allocation concealment: was allocation adequately concealed?
  3. Blinding of participants, personnel and outcome assessors: was knowledge of the allocated intervention adequately prevented during the study, at study entry and at the time of outcome assessment?
  4. Incomplete outcome data: were incomplete outcome data adequately addressed?
  5. Selective outcome reporting: are reports of the study free from suggestion of selective outcome reporting?
  6. Other sources of bias: was the study apparently free from other problems that could put it at a high risk of bias?

Measures of treatment effect

We planned to use the standardised statistical methods of The Cochrane Collaboration. For categorical data we aimed to calculate the relative risk (RR), risk difference (RD), number needed to treat (NNT) and number needed to harm (NNH). For continuous data we aimed to calculate the weighted mean difference (WMD). The 95% confidence interval (CI) for all estimates was to be reported.

Assessment of heterogeneity

We planned to undertake an assessment of heterogeneity, if applicable, by the I2 statistic and to consider 25% as low and 75% as high heterogeneity.

Subgroup analysis and investigation of heterogeneity

We planned to perform subgroup analysis, if appropriate, for the primary outcome by:

  1. time to irrigation from identified extravasation injury (less than one hour or greater than one hour);
  2. type of extravasate (parenteral nutrition fluidor other fluids OR medications);
  3. amount of saline used (less than 500 ml or greater than 500 ml);
  4. corrected gestation at injury (less than 37 completed weeks or more than 37 completed weeks).

However, this was not undertaken as no suitable data were identified for analysis.

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Results

Description of studies

The search strategy used for this review did not find any RCT or quasi-RCT but a number of case reports, case series and cohort studies were identified. Since there were no RCTs or quasi-RCTs retrieved for the intended study age group, we repeated the search with no age restrictions but this did not identify any additional relevant study that matched our inclusion criteria.

Included studies

No eligible RCTor quasi-RCT was found.

Excluded studies

Nine studies identified in the search were not eligible for inclusion but have been used for discussion and are mentioned below under additional tables (Gault 1993; Davies 1994; Martin 1994; Chen Y Y 1996; Casanova 2001; Harris 2001; Chowdhury 2004; Siu 2007; Kuensting 2010) (Table 1; Table 2).

Risk of bias in included studies

Not applicable as no eligible studies were found.

Effects of interventions

No results are forthcoming as no eligible studies were found.

Discussion

Although our search found no relevant trials for the review, we present a brief summary of case reports and case series on the topic that highlight important issues related to current practice and its variations where saline irrigation with or without hyaluronidase infiltration was the main intervention. Most reported good outcomes but this may represent publication bias inherent in case reports.

In a retrospective review of all venous line-related extravasation injuries in neonates in the NICU and the surgical ward over an 18 month period, 24 stage 3 and 4 injuries out of the 36 extravasation injuries were treated with hyaluronidase infiltration and saline irrigation. No surgical debridement was requiredfor any of the 36 cases (Chowdhury 2004) suggesting a good outcome with the intervention even in advanced stages of extravasation injury.

A case series highlighting drug-related extravasation injuries and different variations of intervention using saline and hyaluronidase also reported good outcomes. Extravasation injury secondary to leakage of dopamine (n = 9), caffeine (n = 2), calcium (n = 2) and beta blocker (n = 1) were identified in 14 neonates of which 12 were treated with hyaluronidase infiltration and aspiration, one with saline irrigation followed by aspiration and the remaining one with hyaluronidase infiltration alone. Three cases developed skin necrosis but all healed spontaneously (Casanova 2001). Complete wound healing has been reported following extensive subcutaneous extravasation caused by use of corrosive drugs at cardiac catheterization. The injury was managed with infiltration of hyaluronidase followed by liposuction and saline irrigation (Martin 1994).

Good outcomes were reported in two preterm neonates less than 29 weeks of gestation with total parenteral nutrition (TPN) fluid extravasation that were treated with hyaluronidase infiltration and saline irrigation. Both lesions healed with minimal or no scarring (Davies 1994).

Rapid tissue healing within three to five days was reported in two separate case reports in neonates with TPN fluid extravasation. They were both treated with saline irrigation with prior hyaluronidase infiltration but the injury-irrigation intervals were different (90 minutes versus four hours) (Chen Y Y 1996; Siu 2007).

A retrospective review over three years from a regional neonatal unit described 56 confirmed cases of extravasation injury secondary to leakage of infusate of TPN, inotropic agents, calcium, potassium, sodium bicarbonate and high concentration dextrose. All the injuries were irrigated with 500 ml of normal saline. There was no episode of skin loss and none of these neonates required reconstructive surgery (Harris 2001).

In a retrospective review of the outcome of extravasation injury following referral to a tertiary plastic surgical unit, patients were divided into two groups - 'early', that is within the first 24 hours of extravasation and 'late', that is after 24 hours of the injury. Of the 96 patients referred (ranging from premature infants to 70 year olds), 44 were in the 'early' and 52 in the 'late' group. A range of interventions were offered to the 'early' group including saline flush-out (n = 37), saline flush-out and liposuction (n = 6) and liposuction alone (n = 1). The 'late' group was offered conservative wound management only. Of the 52 patients referred late, 8 (15%) healed without any tissue necrosis, 17 (33%) suffered only minor sloughing of the skin and in 27 (52%) extensive damage to the soft tissue was observed. Several complications including three amputations in babies were seen in this 'late' group. In the 'early' group where saline irrigation was used, there were no signs of soft tissue damage in 39 (88.5%) cases and only five (11.5%) showed minor skin blistering with delayed healing. The range of agents causing extravasation was similar in both groups (Gault 1993). This report, however, only describes serious extravasation injuries referred to a tertiary plastic surgery centre and may not be representative of all such injuries.

A recent case report describes infiltration with 'recombinant human hyaluronidase' (rHuPh30) without saline irrigation in the management of antibiotic extravasation injury in a term neonate (Kuensting 2010). The swollen and tense foot returned to normal appearance within 24 hours.

We did not identify any paper that advocated complete non-intervention (masterly inactivity) in the management of severe skin extravasation injury in neonates.

Extravasation injury is an inevitable complication of neonatal intensive care. Increasingly, more babies born at the borderline of viability are being successfully treated with intensive care. Such babies require prolonged periods of intravenous access, including the need for vasoactive medications, total parenteral nutrition and other infusions. Adequate training of medical and nursing staff in the care of central and peripheral lines including frequent monitoring of the infusion site has been advocated extensively in the literature as the most effective way of preventing extravasation injury (Brown 1979; Irving 2001; McCullen 2006; Tong 2007). Our review shows that many different methods are used in the management of extravasation injury in the neonate that include saline irrigation with or without prior hyaluronidase infiltration. All these methods are reported to be successful without any significant adverse events. However, there is an impression that mild extravasation injuries (stage 1 and stage 2) heal well with conservative management while invasive methods are used frequently for more severe stages of injury (stage 3 and stage 4).

Authors' conclusions

Implications for practice

To date, no randomised controlled trial is available that investigated the effects of saline irrigation with or without prior hyaluronidase infiltration in the management of extravasation injuries in neonates. Based on the current available evidence, we are unable to recommend any particular intervention in the management of serious extravasation injury in a neonate.

Implications for research

Research should initially be directed at evaluating the efficacy and safety of this intervention through multicenter randomised controlled trials. It will also be important to determine the size of the effect according to timing of intervention, nature of the infusate and the severity of injury at the time of intervention.

Acknowledgements

  • Ms Diane Haughton (Review Group Coordinator, Cochrane Neonatal Review Group)
  • Dr R Soll (Coordinating Editor, Cochrane Neonatal Review group)
  • Dr J Sinclair
  • Dr J Horbar
  • Prof M Bracken
  • Dr G Suresh
  • Dr A Ohisson
  • Ms Eryl Smith (Library Services - Glan Clwyd Hospital, UK)
  • Ms Susan Prosser (Library Services - Singleton Hospital, UK)
  • Ms Yolanda Montagne (Trial Search Coordinator, Cochrane Neonatal Review Group)

Contributions of authors

  • Banerjee S conceptualised this review, was involved in all stages and guided this review.
  • Goel N contributed to the literature search, study selection, data management, communications, development of discussion and conclusion and was involved in all stages of this review.
  • Gopalakrishnan PN contributed to the literature search, study selection, data management, communications, development of discussion and conclusion and was involved in all stages of this review.

Declarations of interest

  • None noted.

Differences between protocol and review

No deviation from the original protocol

Additional tables

  • None noted.

Potential conflict of interest

  • None noted.

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Characteristics of studies

Characteristics of Included Studies

  • None noted.

Additional tables

1 Summary of the excluded studies - study design, population, intervention and outcome

Study

Type of study

No of neonates

Extravasate

Intervention

Outcome

Chowdhury 2004

Retrospective review

31 neonates had 36 extravasations

TPN - 13

Medications - 10

Blood products - 6

Crystalloids - 5

Contrast - 2

Hyaluronidase infiltration and saline irrigation used for 24 extravasation injuries

No surgical graft required

Casanova 2001

Case series

14 neonates

Dopamine - 9

Caffeine - 2

Calcium - 2

Beta blocker - 1

Hyaluronidase infiltration and aspiration - 12

Saline irrigation and aspiration - 1

Hyaluronidase infiltration alone - 1

3 cases developed skin necrosis but healed spontaneously

Davies 1994

Case report

2 preterm neonate less than 29 weeks gestation

TPN

Hyaluronidase infiltration and saline irrigation

Minimal or no scarring, no functional sequelae

Siu 2007

Case report

1 neonate

TPN

Hyaluronidase infiltration and saline irrigation

Healed fully by 5 days

Harris 2001

Retrospective review

56 neonates

TPN

Inotrope

Calcium

Potassium chloride

Sodium bicarbonate

High concentration of dextrose

(exact numbers not mentioned)

Saline irrigation alone

No skin loss. None required reconstructive surgery

Gault 1993

Retrospective review

Total 96 cases referred to a tertiary plastic surgical unit

(Age range - preterm neonate to 72 years - exact distribution not mentioned)

44 early referrals i.e. within 24 hours

52 late referral i.e. after 24 hours

TPN

Inotrope

Ca

KCl

Bicarbonate

Dextrose:10-20%

Chemotherapeutics

Contrast

Antibiotics

(exact numbers not mentioned)

Early referral group: 44 (saline irrigation alone - 37, liposuction and saline irrigation - 6, liposuction alone - 1)

Late referral group: wound and surgical management

Early referral group:

[39 (88.5%) no soft tissue damage, 5 (11.5%) minor skin blistering]

Late referral group: [8 (15%) healed without tissue necrosis, 17 (33%) minor skin sloughing, 27 (52%) extensive damage to tissues - 3 amputations]

Kuensting 2010

Case report

1 neonate

Antibiotics

Infiltration with recombinant human hyaluronidase (rHuPh30)

Wound healed completely by 8 days

Chen Y Y 1996

Case report

1 neonate

TPN

Infiltration with hyaluronidase with saline irrigation

Healing in 3 days

Martin 1994

Case report

1 neonate

Dobutamine, adrenaline, 8.4% sodium bicarbonate, 10% calcium gluconate

Infiltration of hyaluronidase followed by liposuction and saline irrigation

No signs of soft tissue damage at 2 weeks

2 Summary of excluded studies - stage of extravasation, intervention and its outcome

Study

Stage of extravasation

Intervention

Outcome

Reason for exclusion

Chowdhury 2004

Erythema and oedema (stage 1-2): n=12

Skin necrosis (stage 3): n=24

Stage 1-2 - standard wound management

Stage 3 - hyaluronidase and saline irrigation

No sequelae

No sequelae

Neither a randomised nor a quasi-randomised study

Casanova 2001

Skin necrosis (stage 3): n=3

Swelling, oedema, discolouration (stage 1-2): n=11

Hyaluronidase and aspiration in 12 cases

Hyaluronidase infiltration alone - 1

Saline irrigation and aspiration - 1

Treatment allocation not specified by stage of injury

No sequelae

Neither a randomised nor a quasi-randomised study

Davies 1994

Skin necrosis (stage 3); n=2

Hyaluronidase & saline irrigation

Minimal scarring, no sequelae

Neither a randomised nor a quasi-randomised study

Siu 2007

Skin necrosis (stage 3): n=1

Hyaluronidase & saline irrigation

No sequelae

Neither a randomised nor a quasi-randomised study

Harris 2001

Exact stage of extravasation injury not specified: n=56

Saline irrigation

No sequelae

Neither a randomised nor a quasi-randomised study

Gault 1993

Skin necrosis (stage 3):

Early referral n=44

Delayed referral (stage 3-4): n=52

Stage 3:

Saline irrigation alone: n=37

Liposuction and saline irrigation: n=6

Liposuction alone: n=1

Stage 3-4:

Wound debridement and surgical flap

No sequelae

8 (15%) healed without tissue necrosis, 17 (33%) minor skin sloughing, 27 (52%) extensive damage to tissues - 3 amputations

Neither a randomised nor a quasi-randomised study

Kuensting 2010

Discolouration, oedema, cool, pulses not palpable (stage 4): n=1

Infiltration with recombinant human hyaluronidase (rHuPh30)

No sequelae

Neither a randomised nor a quasi-randomised study

Chen Y Y 1996

Swelling, erythema and induration (stage 3); n=1

Hyaluronidase and saline irrigation

No sequelae

Neither a randomised nor a quasi-randomised study

Martin 1994

Oedema, pallor, cold and no capillary filling

Infiltration with hyaluronidase, liposuction and saline irrigation

No sequelae

Neither a randomised nor a quasi-randomised study

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References to studies

Included studies

  • None noted.

References to excluded studies

  • None noted.

Studies awaiting classification

  • None noted.

Ongoing studies

  • None noted.

Other references

Additional references

Brown 1979

Brown AS, Hoelzer GJ, Piercy SA. Skin necrosis from extravasation of intravenous fluids in children. Plastic and Reconstructive Surgery 1979;64(2):145-50.

Bruera 1999

Bruera E, Neumann CM, Pituskin E, Calder K, Hanson J. A randomised controlled trial of local injections of hyaluronidase versus placebo in cancer patients receiving subcutaneous hydration. Annals of Oncology 1999;10(10):1255-8.

Cartlidge 1990

Cartlidge PH, Fox PE, Rutter N. The scars of newborn intensive care. Early Human Development 1990;2(1):1-10.

Casanova 2001

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Chandanvasu 1986

Chandanvasu O, Garrow E, Valda V, Alsheikh S, Vega SD. A new method for the prevention of skin sloughs and necrosis secondary to intravenous infiltration. American Journal of Perinatology 1986;3(1):4- 5.

Chen Y Y 1996

Chen YY, Wang HZ, Pan CH, Hsieh KS. Treatment of extravasation of intravenous fluid: A case report. Clinical Neonatology 1996;3:27-9.

Cho 2007

CHo KY, Lee SJ, Burm JS, Park EA. Successful combined treatment of accidental infusion leakage in the newborn: report of 14 cases. British Journal of Plastic Surgery 2001;54(5):396-9.

Chowdhury 2004

Chowdhury M, Wong LH, Horn V, Eaton S, Pierro A. Extravasation injury in surgical neonates and children. Proceedings of the Nutrition Society 2004;63 Suppl(1):23A.

Davidson 1985

Davidson DC, Gilbert J. Severe extravasation injury. British Medical Journal 1985;291(6489):217.

Davies 1994

Davies J, Gault D, Buchdahl R. Preventing the scars of neonatal intensive care. Archies of Disease in Childhood 1994;70(1):F50-1.

Falcone 1989

Falcone PA, Barrell DT, Jeyarajah DR, Grossman JAI. Nonoperative management of full-thickness intravenous extravasation injuries in premature neonates using enzymatic debridement. Annals of Plastic Surgery 1989;22(2):146-9.

Flemmer 1993

Flemmer L, Chan JS. A paediatric protocol for management of extravasation injuries. Pediatric Nursing 1993;19(4):355-8.

Fox 1998

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Friedman 1998

Friedman J. Plastic surgical problems in the neonatal intensive care unit. Clinics in Plastic Surgery 1998;25(4):599-617.

Fullilove 1997

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Gault 1993

Gault DT. Extravasation injuries. British Journal of Plastic Surgery 1993;46(2):91-6.

Hadaway 2007

Hadaway L. Infiltration and extravasation. American Journal of Nursing 2007;107(8):64-72.

Harris 2001

Harris PA, Bradley S, Moss ALH. Limiting the damage of iatrogenic extravasation injury in neonates. Plastic and Reconstructive Surgery 2001;107(3):893-94.

Irving 1999

Irving V. Management of a neonatal wound on a newborn infant. Journal of Wound Care 1999;8(10):485-6.

Irving 2001

Irving V. Managing extravasation injuries in preterm neonates. Nursing Times 2001;97(35):40-4.

Jaworski 1950

Jaworski A, Farley JE Jr. Hyaluronidase in administration of fluids. American Journal of Diseases of Children 1950;79(1):59-64.

Kuensting 2010

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Kumar RJ, Pegg SP, Kimble RM. Management of extravasation injuries. ANZ Journal of Surgery 2001;71:285-9.

Martin 1994

Martin PH, Carver N, Petros AJ. Use of liposuction and saline washout for the treatment of extensive subcutaneous extravasation of corrosive drugs. British Journal of Anaesthesia 1994;72(6):702-4.

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Reynolds BC. Neonatal extravasation injury: Case report. Infant 2007;3(6):230-2.

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Siu SLY, Kwong KL, Poon SST, So KT. The use of Hyaluronidase for treatment of extravasations in a premature infant. HK Journal Paediatrics 2007;12:130-2.

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Other published versions of this review

  • None noted.

Classification pending references

  • None noted.

[top]

Data and analyses

  • None noted.

Figures

  • None noted.

Sources of support

Internal sources

  • Library services, Singleton Hospital, ABM University NHS Trust, Swansea, UK
  • Department of Neonatology, Singleton Hospital, ABM University Health Board, Swansea, UK
  • Library services, Glan Clwyd Hospital, UK

External sources

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA
  • 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. HHSN275201100016C.

Feedback

  • None noted.

Appendices

1 Literature search details

MeSH subject headings were infant, newborn, neonates, preterm infant, extravasation, saline, hyaluronidase, irrigation, therapeutic irrigation and infiltration

Summary of literature search details

MEDLINE - (searched from 1950 - 24/06/2011) 28 references retrieved.

EMBASE - (searched from 1980 - 24/06/2011) 26 references retrieved.

CINAHL - (searched from 1981 - 28/06/2011) 38 references retrieved.

Cochrane Central Database of Clinical Trials (CENTRAL) - (searched up to 28/06/2011) 26 references retrieved.

Web of Science -(searched from 1911 - 11/07/2011) 1 references retrieved.

Total references retrieved (after de-duplication):64

MEDLINE (Ovid) - full search up to 24 June 2011

  1. "Extravasation of Diagnostic and Therapeutic Materials"/pc, su, th (Prevention & Control, Surgery, Therapy)
  2. Saline Solution, Hypertonic/or Saline.mp.
  3. 1 and 2
  4. limit 3 to (English language and "newborn infant (birth to 1 month)")
  5. "Extravasation of diagnostic and Therapeutic Materials"/
  6. 2 and 5
  7. limit 6 to (English language and "newborn infant (birth to 1 month)")
  8. from 4 keep 1-3
  9. extravasation.mp. or inflammation/
  10. swelling.mp. or Edema/
  11. Erythema/
  12. 9 or 10 or 11
  13. catheterization, Peripheral/ or Infusions, Intravenous/
  14. 2 and 12 and 13
  15. limit 14 to (English language and "newborn infant (birth to 1 month)")
  16. neonate.mp
  17. Infant, Newborn/or Infant, Premature/
  18. 16 or 17
  19. 14 and 18
  20. 3 and 18
  21. 13 and 18
  22. 2 and 21
  23. 5 and 18
  24. limit 23 to English language
  25. limit 24 to yr=Current
  26. Therapeutic irrigation/ or irrigation.mp
  27. hyaluronidase.mp. (mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier)
  28. 5 and 26 and 27
  29. 5 and 27
  30. 18 and 29

EMBASE (Ovid) up to 27 June 2011

  1. "Extravasation of Diagnostic and Therapeutic materials"/
  2. extravasation.mp.
  3. 1 or 2
  4. Infusions, Intravenous/
  5. Catheterization, Peripheral/
  6. 4 or 5
  7. Inflammation/
  8. Erythema/
  9. swelling.mp.
  10. Edema/
  11. 7 or 8 or 9 or 10
  12. 6 and 11
  13. 3 or 12
  14. Saline Solution, Hypertonic/ or Saline.mp.
  15. hyaluronidase.mp. or hyaluronoglucosaminidase/
  16. Therapeutic irrigation/ or Irrigation.mp.
  17. 13 and 14 and 15 and 16
  18. 13 and 14 and 15
  19. limit 18 to English language (not limited to age)
  20. limit 19 to "newborn infant (birth to 1 month)"(limit not valid in Embase; records were retained)
  21. 13 and 14 and 16
  22. limit 21 to English language
  23. 13 and 14
  24. limit 23 to English language
  25. limit 20 to infant
  26. 2newborn"/
  27. infant/
  28. neonatal.mp.
  29. neonate.mp.(mp=title, abstract, subject heading, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword)
  30. 26 or 27 or 28 or 29
  31. 24 and 30

Web of Science up to 11/07/2011

  1. Topic = (extravasation)
  2. Title = Extravasation
  3. #1 AND #2
  4. Topic = Saline
  5. Topic = hyaluronidase
  6. Topic = therapeutic irrigation
  7. #7 or #6
  8. #8 AND #5 AND #4 AND #3
  9. #5 AND #4 AND #3
  10. #8 AND #4 AND #3
  11. #4 AND #3
  12. #4 AND #3 limited to2007 - 2010
  13. #4 AND #3 limited to 2007 - 2010 and Neonat #10
  14. #4 AND #3 limited to 2011

CINAHL (EBSCO) up to 28 June 2011

S21 S3 or S11 Limiters - English language; published Date from 20000101-20111231; Age groups: infant, Newborn, : birth 1 month, Infant 1-23 months

Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S20 S3 or S11Limiters - English language; Age groups: infant, Newborn, : birth 1 month, Infant 1-23 months

Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S19 S12 and S13 Limiters - Age groups: infant, Newborn, : birth 1 month, Infant 1-23 months

Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S18 S12 and S13 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S17 S12 and S13 and S14 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S16 S12 and S13 and S14 and S15 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S15 (MH " Feeding Tube irrigation") OR (MH " Catheter irrigation, Vascular") OR (MH " Irrigation") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S14 ( MH " HYaluronidase") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S13 ( MH "Saline Solution, Hypertonic") OR " Saline" Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S12 S3 or S11Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S11 S6 and S10 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S10 S7 or S8 or S9 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S9 (MH " Erythema") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S8 (MH "inflammation") OR "Inflammation" Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S7 "swelling" OR (MH "Edema") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S6 S4 OR S5 Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S5 (MH " Catheterization, Peripheral" ) OR (MH " Catheterization, Peripheral Central venous") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S4 (MH "intravenous therapy") OR (MH " Fluid Resuscitation") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S3 S1 or S2Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S2 "extravasation" Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

S1 (MH "Extravasation of Diagnostic and Therapeutic Materials") Expanders - Also search within the full text of the articles

Search modes - Boolean/phrase

The Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library2011, Issue 2) 28 June 2011

  1. MeSH descriptor Extravasation of Diagnostic and Therapeutic Materials explode all trees
  2. extravasation
  3. (#1 OR #2)
  4. MeSH descriptor Infusions, Intravenous explode all trees
  5. MeSH descriptor Catheterization, Peripheral explode all trees
  6. (#4 OR #5)
  7. MeSH descriptor inflammation, this term only
  8. MeSH descriptor Erythema explode all trees
  9. swelling
  10. edema
  11. (#7 OR #8 OR #9 OR10)
  12. (#6 AND #11)
  13. (#3 OR #12)
  14. MeSH descriptor Saline Solution, hypertonic explode all trees
  15. saline
  16. hyaluronidase
  17. MeSH descriptor Hyaluronoglucosaminidase explode all trees
  18. (#17 OR #18)
  19. MeSH descriptor Therapeutic Irrigation, this term only
  20. irrigation
  21. (#20 OR #21)
  22. (#13 AND #16 AND #19 AND #22)
  23. (#13 AND #16 AND #19)
  24. (#13 AND #16)
  25. ( #13 AND #16)
  26. neonat*
  27. MeSH descriptor Infant, Newborn explode all trees
  28. infant
  29. ( #27 Or #28 Or #29)
  30. (#25 AND #30)
  31. (#13 AND #30)
  32. (#32 AND NOT #25)
  33. (#33 AND NOT #31)

This review is published as a Cochrane review in The Cochrane Library, Issue 2, 2012 (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.