Dr. V. Shah
Literature search and identification of trials
Evaluation of methodological quality of trials
Revision of the review
The updated review provides information from one randomized controlled trial which was eligible for inclusion.
There is not enough evidence to show the effect of heparin for preventing complications when used with central catheters to give access to the tiny veins of premature and critically ill babies.
Critically ill or premature babies (born before 37 weeks) often need medication and feeding through their veins. These veins are small and fragile so repeated injections can be hard and painful for the baby. A central catheter is a small tube that can be inserted into the vein, allowing medications and other liquids to be given to the baby for a prolonged period. It can get dislodged, blocked or infected. The drug heparin is sometimes used to reduce these complications but it can cause bleeding and allergic reactions. The review found that there was not enough evidence to show neither benefit or harm of heparin. More research is needed.
Peripherally placed percutaneous central venous catheters (PCVC) are used in neonates to provide long-term vascular access. Major complications associated with these catheters include mechanical complications (catheter thrombosis, occlusion or dislodgement) and infection. Strategies to prevent catheter thrombosis and occlusion include the use of heparin. Systematic review has revealed that heparin is effective in prolonging the umbilical arterial catheter stay in neonates. However, heparin is known to be associated with complications such as bleeding and thrombocytopenia which may result in serious long-term sequelae.
The primary objective is to assess the effectiveness of heparin for prevention of catheter related thrombosis.
The secondary objectives are to assess the effectiveness of heparin on catheter occlusion, duration of catheter patency, catheter related sepsis and complications associated with the use of heparin.
A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) and abstracts from the annual meetings of the Society for Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2005). No language restrictions were applied.
Selection criteria applied to the clinical trials were: the population had to be neonates, intervention had to be heparin infusion compared to placebo or no treatment for prevention of any of the complications related to peripherally placed PCVC, the trial had to be randomized or quasi-randomized and at least one of the primary or secondary outcomes reported.
The methodological quality of included trials was assessed using criteria for masking of randomization, masking of intervention, completeness of follow-up and masking of outcome measurement. Data on relevant outcomes were extracted and the effect size was estimated by calculating relative risk (95% CI), risk difference (95% CI) and weighted mean difference (95% CI).
Two randomized trials on the use of heparin for peripherally placed PCVC were identified . One trial (Kamala et al) of 66 neonates of adequate methodology met the eligibility criteria. There was no statistically significant differences in the incidence of thrombosis (RR 0.79, 95% CI 0.35, 1.79), occlusion (RR 0.63, 95% CI 0.22), catheter related sepsis (RR 0.89, 95% CI 0.06, 13.57), extension of intraventricular hemorrhage (RR 0.87, 95% CI 0.25, 3.03), mortality (RR 0.59, 95% CI 0.18, 1.90) or duration of catheter patency (WMD 1.50 days, 95% CI -1.35 days, 4.35 days) between heparin and no heparin groups. Another trial (Betremieux et al) was excluded due to several methodological issues: 1. randomization was at the time of umbilical catheter placement rather than later PCVC placement 2. multiple PCVC were used in some infants, with reported results based on number of catheters rather than infants.
Implications for practice: Prophylactic use of heparin for prevention of complications related to peripherally placed PCVC has been examined in only one randomized controlled clinical trial that was eligible for inclusion in this review. No significant differences in the incidence of thrombosis, occlusion, sepsis, mortality and duration of catheter patency were observed. With the current state of knowledge, routine use of heparin for this purpose can not be recommended.
Implication for research: Increasing survival of extremely low birth weight infants may be accompanied by prolonged intravenous access for nutrition. Well designed randomized controlled trials of sufficient power to determine the benefits and risks of continuous infusion of heparin in neonates with peripherally inserted PCVC are warranted.
Vascular access is a major challenge in the management of preterm and critically ill term infants in neonatal intensive care units. Shaw 1973 first described the successful placement of peripherally inserted percutaneous central venous catheters (PCVC) in neonates. In sick neonates these catheters have been shown to provide long term vascular access necessary for the prolonged administration of parenteral nutrition and intravenous medications (Dolcourt 1982; Klein 1992; Chathas 1986; Durand 1986; Loeff 1982; Puntis 1986; Harms 1992).
Despite perceived benefits in neonates, peripherally inserted PCVC are associated with mechanical and infectious complications. Mechanical complications including occlusion, extravasation, dislodgement and thrombosis occur in 15-48% of inserted PCVC (Harms 1992; Klein 1992; Chathas 1986; Durand 1986; Nakamura 1990). Nakamura 1990 found complete (33%) and partial (33%) occlusion in catheter tips on electron microscopic examination. In addition, 39% of all catheter tip sheaths showed thrombosis. Factors that have been associated with initiation and propagation of thrombosis include endothelial damage during catheter placement, blood vessel occlusion, low flow states, turbulent flow, patient and infusate characteristics and catheter composition (Pottecher 1984; Krafte-Jacobs 1995). Infectious complications include bacterial or fungal sepsis. Thrombosis of the line can act as a nidus for infection.
Heparin has been administered by intermittent injection or continuous infusion to prevent thrombus formation and prolong catheter patency (Randolph 1998; Schmidt 1988; Brismar 1982). In a systematic review involving all ages including neonates, Randolph 1998 evaluated the effectiveness of heparin (administered intermittently or as continuous infusion) on catheter patency and prevention of complications associated with peripheral arterial or venous catheters. The authors concluded that the use of heparin flushes at concentrations of 10 units/ml demonstrated no effect on catheter patency for peripheral venous lines; however, low dose heparin infusion through peripheral arterial catheters prolonged the patency of the catheter. The benefits of using heparin have to be weighed against the risks involved. Risks include allergic reactions, bleeding complications due to dosing error and occurrence of heparin-induced thrombocytopenia which has been described in 3% of patients exposed to heparin (Spadone 1992).
In a systematic review, Barrington 2000 documented that heparin infusion is effective in improving umbilical arterial catheter patency in neonates, with no statistically significant evidence of adverse outcomes. The effectiveness of heparin use to prevent thrombosis in neonates with peripherally placed PCVC has not been systematically evaluated.
The aim of this review is to determine the benefits and risks of continuous infusion of heparin in neonates with a peripherally inserted PCVC.
The primary objective of this review was to determine the effect of heparin infusion in neonates with a peripherally inserted PCVC on the incidence of thrombosis along the length of, or at the tip of the catheter.
Secondary objectives were to determine the effect of heparin infusion on:
1. Occlusion of catheter (defined as inability to infuse fluids through the catheter due to blockage)
2. Number of days of catheter patency (duration of patency of first catheter)
3. Episodes of catheter related sepsis (defined as symptoms and signs suggestive of sepsis, accompanied by positive blood cultures obtained from a normally sterile site different to the central line, and from the line or catheter tip, each growing the same microorganism)
4. Number of additional peripheral intravenous catheter insertions
5. Arrythmia (defined as abnormal rhythm on electrocardiogram while catheter is in situ)
6. Abnormality of coagulation profile
7. Allergic reactions to heparin
8. Heparin induced thrombocytopenia (development of thrombocytopenia after starting heparin in an infant with previously normal platelet count after exclusion of all other causes of thrombocytopenia)
9. Intraventricular/intracranial hemorrhage [development of recent onset of hemorrhage or extension of preexisting hemorrhage after starting heparin, according to the classification of Papile 1978]
10. Mortality
Randomized and quasi-randomized controlled trials of heparin infusion in neonates with peripherally placed PCVC. Studies in which the unit of randomization was catheter, the primary authors were to be contacted to obtain data for the first catheter after randomization and only those data were to be included. If authors were unable to provide the data or could not be contacted the study were to be described and only data on long term outcome such as intraventricular hemorrhage were included.
Term or preterm infants who required peripherally placed PCVC during their stay in neonatal intensive care unit.
Heparin infusion versus control (placebo or no treatment), without restriction to specific dosage regimen. Heparin or placebo infusion must have been administered during the entire duration of catheter placement.
Studies that reported on one or more of the following outcomes amongst all randomized:
As per Cochrane Neonatal Collaborative Group search strategy
MEDLINE was searched (1966 to February 2005) using the terms: heparin, infant, newborn; percutaneous central venous catheter, silastic catheter, epicutaneocaval catheter.
Other databases that were searched include: EMBASE (1980 to February 2005); CINAHL (1982 to February 2005); the Cochrane Controlled Trials Register (Cochrane Library, Issue 1, 2005). We also searched the reference lists of identified trials and abstracts from the annual meetings of the Society of Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied.
The following types of articles were excluded: letters, editorials/commentaries, reviews, lectures.
All published articles identified as potentially relevant by the literature search were assessed for inclusion in the review by two reviewers. In order to be included the trial had to meet the following criteria: 1) the study population had to be term or preterm infants admitted to a neonatal intensive care unit 2) the intervention had to be heparin infusion in addition to regular maintenance fluid via peripherally placed PCVC, compared to placebo or no treatment 3) the study had to be a randomized or quasi randomized controlled trial and 4) one or more primary or secondary outcome measures were reported.
Standard methods of the Cochrane Neonatal Review Group were used to assess methodological quality of studies.
Quality of included trials were evaluated by the following criteria:
1. Masking of randomization
2. Masking of intervention
3. Complete follow-up
4. Masking of outcome measurement
Attempt was made to collect the data from the primary author when published data provided inadequate information for the review. Retrieved articles were assessed and data were abstracted independently by the reviewers. Discrepancy was resolved by consensus.
Statistical methods included relative risk (RR), risk difference (RD), number needed to treat (NNT) and weighted mean difference (WMD) when appropriate as per the methods of the Cochrane Neonatal Review Group. No subgroup analysis was planned a priori.
One study was identified that met eligibility criteria for this review (Kamala 2002). Kamala 2002 randomized 68 neonates (36 neonates in heparin group and 32 neonates in no heparin group). Each infant received only one catheter for the purpose of the study. The eligible neonates were stratified in three groups according to birth weight before randomization. Neonates in the heparin group received 1 IU of heparin per ml of parenteral nutrition solution. The neonates in the no heparin group didn't receive heparin in the parenteral nutrition solution. Premicath (27G) and Epicutaneocava (23 G) silicone catheters were used depending upon the size of infants. All patients were monitored for hyperbilirubinemia, hypertriglyceridemia, coagulation profile and platelet counts prior to insertion of catheter, at four days and eight days after catheter insertion or on removal of catheter if it was removed before four days. Catheter blockage was diagnosed (a) when there was inability to infuse fluid and (b) when clots were noted at the time of removal of catheter. The duration of catheter patency was defined as number of days the catheter stayed in situ. Catheter related sepsis was diagnosed when clinical symptoms and signs of sepsis were associated with positive catheter tip culture and blood culture were positive for the same organism. There was protocol violation for two patients (one in each group). The details of the patients enrolled in this study are described in the table Characteristics of included studies.
Another study relevant to the objectives of this review (Betremieux 1988) was identified. It was published in French and was translated to English for this review. The trial did not meet the entry criteria specified a priori for this review. The reasons for exclusion of this study are given in the table Characteristics of excluded studies.
Kamala 2002 performed a double blind placebo controlled randomized trial of use of heparin for peripherally inserted central venous catheters in neonates. The randomization was done by one of the investigators (Pharmacist) from previously prepared randomization cards. No other investigators were aware of the treatment allocation. The heparin was mixed in the parenteral nutrition fluid. One patient each from both heparin and placebo group was removed from analysis because of the protocol violation. The authors have not reported masking of outcome assessment, however, the attending team was unaware of allocation when making decision regarding discontinuation of the catheter among the patients in whom the randomization codes were not broken. The randomization codes were broken prior to completion of the study in 13 patients (n = 5 heparin group and n = 8 no heparin group). The reasons for the breaking the code were development of bleeding tendencies (n = 2 heparin group and n = 4 no heparin group) and thrombocytopenia (n = 3 heparin group and n = 4 no heparin group). After breaking the code heparin was removed from the parenteral solutions from patients in heparin group and none of the patients developed blocked catheters. None of the patients were described to have more than one outcome.
1. Thrombosis of the catheter (along the length of, or at the tip of the catheter) as determined by Doppler ultrasonography or contrast venography
There was no statistically significant differences in the incidence of thrombosis between heparin and no heparin group (RR 0.79, 95% CI 0.35, 1.79; and RD -0.06, 95% CI -0.27, 0.15). Kamala 2002 identified thrombosis by flushing the catheter after removal and observing the presence of clots.
2. Occlusion of the catheter (identified by inability to infuse fluids)
There was no statistically significant difference in the incidence of catheter occlusion between heparin and no heparin group (RR 0.63, 95% CI 0.22, 1.79; and RD -0.08, 95% CI -0.27, 0.10).
3. Days of catheter patency (duration of patency of first catheter)
There was no statistically significant difference in the duration of catheter patency between heparin and no heparin group (WMD 1.50 days, 95% CI -1.35 days, 4.35 days).
4. Episodes of catheter related sepsis (infants with one or more episode)
There was no statistically significant difference in the incidence of catheter related sepsis between heparin and no heparin group (RR 0.89, 95% CI 0.06, 13.57; and RD -0.00, 95% CI -0.09, 0.08). None of the patients had more than one episode.
5. Number of additional peripheral intravenous catheters needed
This outcome was not reported.
6. Arrhythmia
This outcome was not reported.
7. Side effects of heparin (allergic reactions, hemorrhage, heparin-induced thrombocytopenia, abnormal coagulation profile)
There was no statistically significant difference in the activated partial thromboplastin time between heparin and no heparin group (WMD -5.7 sec, 95% CI -22.2 sec, 10.8 sec).
8. Extension of pre-existing IVH or appearance of new IVH
Cranial ultrasonography was performed in 43 infants (23 infants in the heparin group and 20 infants in no-heparin group). There was no statistically significant difference in the appearance of new IVH between heparin and no heparin group (RR 0.87, 95% CI 0.25, 3.03; and RD -0.03, 95% CI -0.26, 0.21).
9. Mortality during stay in neonatal intensive care unit
There was no statistically significant difference in the mortality between heparin and no heparin group (RR 0.59, 95% CI 0.18, 1.90; and RD -0.08, 95% CI -0.25, 0.10).
After an extensive search for the update of this review only one randomized controlled study (Kamala 2002) was identified. The study was of good methodological quality, however, was small (n = 66) and had 20% of patients who required opening of randomization code because of safety issues. Increased incidences of complications (bleeding tendencies and thrombocytopenia) reported in this study may have resulted due to higher dose of heparin used. Infants in the heparin group received heparin in the dose of 1 IU/ml of parenteral nutrient solution, which could result in on an average > 100 IU/kg/d of heparin delivered to those infants. Most of the studies of heparin for peripheral intravenous catheters and umbilical artery catheters have used 0.25 - 0.5 IU/kg/hr resulting in a maximum of 12 IU/kg/d delivered to infants and have shown no increase in these complications. There were no statistically significant differences in the incidence of thrombosis, occlusion, catheter related sepsis, extension of intraventricular hemorrhage and mortality between heparin and no heparin group. However, the sample size to assess some of these outcomes was inadequate.
Barrington 2001 has evaluated the effectiveness of heparin for umbilical arterial catheter placement in a systematic review. Even in concentrations as low as 0.25 units/ml heparin was found to prolong umbilical artery catheter patency without significant adverse outcomes. However, the data from that review cannot be extrapolated to PCVC placement as the size of the catheters (internal diameter) used for umbilical arterial catheters is larger than that used for PCVC placement. In addition, the flow patterns in the aorta, where umbilical catheters are usually placed, differ from the relatively sluggish circulatory states of the venous system in which PCVC are placed, thus making PCVCs more prone to thrombus formation. In another systematic review, Randolph 1998 found that heparin was effective in preventing complications for peripheral arterial catheters but not for venous catheters. However, that review was not limited to the neonatal population. Thus, there is a need to conduct a well-designed randomized controlled trial to assess the benefits of heparin for PCVC placement in neonates.
Future clinical trials should be directed at the following important issues: (1) establishment of incidence of complications associated with PCVC placements, (2) efficacy of prophylactic interventions (heparin infusions, catheters impregnated with heparin etc.) in reducing the incidence of thrombosis or occlusion, (3) long term implications of detection of asymptomatic complications (catheter related thrombosis) and (4) efficacy of treatment modalities (heparin therapy, low molecular heparin therapy) after the detection of complications. The incidence of catheter related complications is low. Thus, in trials of prophylactic interventions such as use of heparin infusion or heparin bonded catheters, a composite outcome such as duration of catheter patency (which can be affected by various complications) should be utilized. These trials should be of sufficient power to clarify the effect of intervention. Immaturity of the neonatal coagulation system, especially in preterm infants, needs careful consideration in such trials. A minimal dose should be assessed initially (0.25 to 0.5 units/kg/hr as shown to be effective in studies of other vascular catheters).
Prophylactic use of heparin for peripherally placed PCVC has not been adequately evaluated in randomized controlled trials in neonates. At present there is no evidence to support its use in practice.
With increasing survival of extremely preterm infants the need for peripherally placed PCVC is growing. Strategies that help to prolong the catheter patency will be useful. Research should be directed to identify the benefits and risks of heparin in neonates with peripherally placed PCVC.
Authors acknowledge Dr. Y Diambomba for translation of the Betremieux 1988 study from French to English.
After concluding in the first version of the review (Shah 2001)
that there were no randomized controlled trials on the subject, the authors
have initiated a randomized controlled trial evaluating this intervention.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Kamala 2002 | Double blind randomized controlled study 1. Masking of randomization: Yes 2. Masking of intervention: Yes 3. Completeness of follow-up: Yes 4. Masking of outcome assessment: Yes | Infants who needed peripherally inserted central venous catheters were enrolled. Patients were stratified according to birth weight (<1250, 1250-2500 and >2500 grams) after parental consent. Heparin group (35 neonates): Mean (SD) birth weight was 1454 (600) g and gestational age was 30.9 (3.9) weeks No Heparin group (31 neonates): Mean (SD) birth weight was 1430 (630) g and gestational age was 31.9 (4.2) weeks Exclusion criteria: Neonates with clinical evidence of bleeding tendencies, severe intraventricular hemorrhage grade 3/4, thrombocytopenia (platelet count <100), prolonged activated partial thromboplastin time >51s for term infants and > 74s for preterm infants | Heparin group: Neonates
in the heparin group received heparin in the parenteral nutrition solution
at a concentration of 1 IU/ml. No heparin group: no heparin was added to the parenteral solution in this group of patients. | Number of blocked catheters Number of patients who had elective removal of catheter (completed administration of parenteral solution) Phlebitis Catheter related septicemia Mortality Duration of peripherally inserted central venous catheter in situ Coagulation abnormality | 1 patient each in both group had protocol violation | A |
| Study | Reason for exclusion |
| Betremieux 1988 | 1.
The infants were randomized to heparin or control at the time of insertion
of umbilical catheters and later on when they needed the placement of PCVC
they were kept in the same treatment group. There was no separate randomization
at the time of PCVC placement. 2. The results are expressed based on number of catheters rather than infants. Four infants had multiple catheter insertions and separate data were not available for first catheter placement. |
| Study | Trial name or title | Participants | Interventions | Outcomes | Starting date | Contact information | Notes |
| Shah | Continuous infusion of heparin to prolong the patency of peripherally placed percutaneous central venous catheters (PCVC) : a randomized controlled trial | Term or preterm neonates who need placement of peripherally inserted central venous catheter for the purpose of parenteral nutrition or other therapy | Heparin or placebo as continuous infusion from the placement of catheter at the dose of 0.5 IU/kg/hr | Duration of catheter patency Thrombosis Catheter related sepsis Cathether occlusion Phlebitis | July 2003 | Dr Prakesh Shah Staff Neonatologist Department of Paediatrics Mount Sinai Hospital 775A - 600 University Avenue Toronto Ontario Canada M5G 1X5 Tel 416 586 4761 Fax 416 586 8745 E mail: pshah@mtsinai.on.ca |
Kamala F, Boo NY, Cheah FC, Birinder K. Randomized controlled trial of heparin for prevention of blockage of peripherally inserted central catheters in neonates. Acta Paediatrica 2002;91:1350-6.
Betremieux P, Odent S, Prigent JY, Dabadie A, Roussey M, Lefrancois C, Le marec B. Etude de la perfusion continue de faibles doses d'heparine dans la prevention des complications liees aux catheters dans la periode neonatale [Study of continuous infusion of low doses of heparin in the prevention of complications of catheters during the neonatal period]. La Revue de Pediatrie 1988;14:311-5.
Shah PS, Kalyn A, Dunn M, Ohlsson A, Daneman A, Glanc P, Shah V. Continuous infusion of heparin to prolong the patency of peripherally placed percutaneous central venous catheters (PCVC): a randomized controlled trial.
* indicates the primary reference for the study
Barrington KJ. Umbilical artery catheters: heparin usage. In: The Cochrane Database of Systematic Reviews, Issue 2, 2000.
Brismar B, Hardstedt C, Jacobson S, Kager L, Malmborg AS. Reduction of catheter-associated thrombosis in parenteral nutrition by intravenous heparin therapy. Archives of Surgery 1982;117:1196-9.
Chathas MK. Percutaneous central venous catheters in neonates. Journal of Obstetrics, Gynecological and Neonatal Nursing 1986;15:324-32.
Dolcourt JL, Bose CL. Percutaneous insertion of silastic central venous catheters in newborn infants. Pediatrics 1982;70:484-6.
Durand M, Ramanathan R, Martinelli B, Tolentino M. Prospective evaluation of percutaneous central venous silastic catheters in newborn infants with birth weights of 510 to 3,920 grams. Pediatrics 1986;78:245-50.
Harms K, Herting E, Kruger T, Compagnone D, Speer CP. Percutaneous silastic catheters in newborn and premature infants. A report of experience with 497 catheters in 5 years. Monatsschrift fur Kinderheilkd 1992;140:464-71.
Klein JF, Shahrivar F. Use of percutaneous silastic central venous catheters in neonates and the management of infectious complications. American Journal of Perinatology 1992;9:261-4.
Krafte-Jacobs B, Sivit CJ, Mejia R, Pollack MM. Catheter-related thrombosis in critically ill children: comparison of catheters with and without heparin bonding. Journal of Pediatrics 1995;126:50-4.
Loeff DS, Matlak ME, Black RE, Overall JC, Dolcourt JL, Johnson DG. Insertion of a small central venous catheter in neonates and young infants. Journal of Pediatric Surgery 1982;17:944-9.
Nakamura KT, Sato Y, Erenberg A. Evaluation of a percutaneously placed 27-gauge central venous catheter in neonates weighing less than 1200 grams. Journal of Parenteral and Enteral Nutrition 1990;14:295-9.
Papile L, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 grams. Journal of Pediatrics 1978;92:529-34.
Pottecher T, Forrler M, Picardat D, Krause D, Bellocq JP, Otteni JC. Thrombogenicity of central venous catheters: prospective study of polyethylene, silicone and polyurethane catheters with phlebography or postmortem examination. European Journal of Anaesthesiology 1984;1:361-5.
Puntis JW. Percutaneous insertion of central venous feeding catheters. Archives of Diseases of Childhood 1986;61:1138-40.
Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials. British Medical Journal 1998;316:969-75.
Schmidt B, Andrew M. Neonatal thrombotic disease: prevention, diagnosis, and treatment. Journal of Pediatrics 1988;113:407-10.
Shaw JCL. Parenteral nutrition in the management of sick low birth weight infants. Pediatric Clinics of North America 1973;20:333-58.
Spadone D, Clark F, James E, Laster J, Hoch J, Silver D. Heparin-induced thrombocytopenia in the newborn. Journal of Vascular Surgery 1992;15:306-11.
Shah P, Shah V. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. In: The Cochrane Database of Systematic Reviews, Issue 2, 2001.
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Heparin versus no heparin group | ||||
| 01 Thrombosis | 1 | 66 | RR (fixed), 95% CI | 0.79 [0.35, 1.79] |
| 02 Catheter occlusion | 1 | 66 | RR (fixed), 95% CI | 0.63 [0.22, 1.79] |
| 03 Days of catheter patency (duration of patency of first catheter in days) | 1 | 66 | WMD (fixed), 95% CI | 1.50 [-1.35, 4.35] |
| 04 Episodes of catheter related sepsis | 1 | 66 | RR (fixed), 95% CI | 0.89 [0.06, 13.57] |
| 05 Abnormality in coagulation | 1 | 66 | WMD (fixed), 95% CI | -5.70 [-22.19, 10.79] |
| 06 Appearance of new IVH or extension of IVH in infants examined | 1 | 43 | RR (fixed), 95% CI | 0.87 [0.25, 3.03] |
| 07 Mortality | 1 | 66 | RR (fixed), 95% CI | 0.59 [0.18, 1.90] |
| The review is published as a Cochrane review in The
Cochrane Library, Issue 3, 2005 (see http://www.thecochranelibrary.com for
information). Cochrane reviews are regularly updated as new evidence emerges
and in response to comments and criticisms, and The Cochrane Library should
be consulted for the most recent version of the Review. |