Combined shoulder adduction and elbow fl exion causes a basilic vein PICC to have the greatest movement towards the heart (15.11 ± 1.22 mm). Therefore, the position of the arm when the radio- graph is taken must be considered when deciding whether an upper limb PICC tip is in a safe position and while using the basilic vein, consideration must be given for a 1.5 cm movement of the tip during spontaneous arm movement.
Although upper limb PICC lines are more likely to be associated with pericardial effusions and lower limbs with epidural, renal and peritoneal extravasation, in a study comparing upper limb with lower limb PICC insertion, there was some evidence to suggest that there were less infective compli- cations with lower limb insertion; however, there were no cases of signi fi cant extravasation in either group to make a comparison about safety from that aspect [ 44 ] . The most commonly used vein in the lower limb for PICC insertion is the long saphenous and a study of 46 PICCs inserted into the long saphenous vein at the medial malleolus resulted in a formula based on the infant’s weight which will calculate a safe position for the PICC tip between the ninth thoracic vertebral body (T9) and the third lumbar body (L3) [ 37 ] . The position between T9 and L3 takes into consideration the movement of the PICC tip with leg movement to ensure the tip remains out of the right atrium and beyond the ascend- ing lumbar veins. Insertion length (mm) should be between 0.55 × birth weight (kg) – 4 and 0.44 × birth weight (kg) – 3 and again the website www.nicutools.org has tools to make this calculation [ 9 ] .
In summary, to reduce serious extravasation injury and improve the safety of PICCs used for the delivery of PN, the most important intervention is to ensure that there is clear radiographic con fi rmation of the PICC tip in a safe and appropriate position using radio-opaque contrast. If choosing the lower limb the PICC insertion length should be calculated to place the tip between T9 and L3 and con fi rmed radio-graphically using. When using the upper limb, the PICC tip should be outside the heart by up to 1.5 cm to take into consideration the full range of tip migration with arm movements. Should the line not be able to be inserted to the calculated distance, then injection of contrast during the radiograph may help to determine if the line is in a super fi cial tributary and therefore likely to extravasate. PICC use for the delivery of PN should be restricted to units that are familiar with PICC insertion and management.
Improving Safety by Minimising Central Line Associated Blood Stream
CLABSI [ 42 ] . An earlier review found rates of up to 29% and up to 15.3 infections per 1,000 catheter days [ 59 ] . One of the most recent reports of CLABSI in preterm infants reported a rate of 8.3 infec- tions per 1,000 catheter days [ 60 ] . The risk of CLABSI in infants receiving PN is increased with lower gestational age, lower weight and the longer the central line remains in situ [ 60– 64 ] .
Late onset or nosocomial septicaemia is associated with increased rates of death, severe intraven- tricular haemorrhage, periventricular leukomalacia, chronic lung disease and with increased time on respiratory support and increased hospital stay [ 65 ] . In a recent study of 514 preterm infants (24–27 weeks gestation) in Switzerland, proven sepsis was shown to independently increase the risk of cere- bral palsy (OR 3.23, 95% CI: 1.23, 8.48, p = 0.017) and increase the likelihood of neurodevelopmental impairment (OR 1.85, 95% CI: 1.12, 3.05, p = 0.016) [ 66 ] .
CoNS infections are sometimes regarded as minor illnesses, but CLABSI with CoNS are a signi fi cant problem in NICUs and result in prolonged hospital stay, increased hospital costs and increased mortality [ 55, 56, 67, 68 ] . There is also an association with CoNS CLABSI and NEC, although causality is unproven [ 56 ] . Thus CLABSI in preterm infants is a signi fi cant cause of death and neurodevelopmental disability and is a signi fi cant cause of increased time on respiratory support, increased time in intensive care and increased overall hospital stay and therefore increased health costs.
Infections associated with central lines can also be localised with phlebitis and local in fl ammation and it is postulated that local in fl ammation secondary to infection is a risk factor for extravasation, a serious complication we have already covered in this chapter [ 69 ] .
Practices That Reduce CLABSI and Improve the Safety of Providing PN
Considering the signi fi cant morbidity, mortality and health costs associated with nosocomial infections and the increased use of central lines, it is critically important that all possible measures are taken to reduce CLABSI in NICUs in order to facilitate the safe delivery of PN to preterm infants (see Table 12.2 ).
In the literature there are many studies looking at the individual components of central line insertion, most often focussing on PICC insertion and management, to provide evidence to guide safe practice.
Recently, there have been several collaborative studies combining all the evidence-based best prac- tices from the literature into “bundles” and implementing these to demonstrate a reduction in CLABSI [ 103– 105 ] . For the purposes of this review, we will look at the individual components shown to reduce CLABSI before dwelling on the impact that best practice “bundles” have on improving the safety of PN delivery via a central line.
Methods to reduce the risk of developing CLABSI can be divided into prevention during insertion and prevention during catheter maintenance. Although there is a paucity of evidence, it is important to consider that during central line use there are other procedures completely separate from central line insertion or maintenance that may introduce bacteria into the blood stream and contribute to the risk of developing CLABSI such as peripheral venous cannula insertion, blood sampling (venepuncture or heel prick), oral or nasal suctioning, gastric tube insertion and other procedures/conditions that result in a loss of skin integrity (tape removal, napkin dermatitis, pressure lesions, etc.). Due to a lack of evidence surrounding the risk these procedures pose in the development of CLABSI and the lack of preventative evidence, this will not be discussed any further, other than to recommend that any procedure likely to have an impact on skin integrity should be kept to a minimum and should be performed using aseptic techniques.
Central line insertion is a key moment in the development of CLABSI and so there needs to be appropriate preparation. In fact, preparation should be at a unit level before any individual patient has a central line inserted and this requires an emphasis on quality control. Achieving and maintaining
low rates of CLABSI require a central line insertion and maintenance policy associated with a con- tinuing education programme and regular feedback of surveillance data [ 70– 73 ] . A simple quality measure, the creation of a central line kit or cart where all the equipments required for insertion can be kept, thus reducing the number of steps and the amount of travel required to prepare for insertion,
Table 12.2 Summary of strategies to reduce the incidence of CLABSI and so improve the safety of the delivery of PN to preterm infants
Unit level, quality interventions and policy
Developing a central line insertion and maintenance guideline or protocol [ 70– 72 ] Continuous education around insertion and maintenance of central lines along with regular
feedback of surveillance data [ 70, 72, 73 ] Creating a central line insertion kit or cart [ 72 ]
Restricting staff who insert central lines to a highly trained team within the service [ 73, 74 ] Hand hygiene before and after any patient contact combined with policy and education around
promoting and enforcing hand hygiene [ 75– 83 ] Central line
insertion
Selecting lower limb if possible (evidence cannot recommend avoiding upper limb insertion) [ 44 ] Avoiding femoral line insertion [ 60 ]
Maximal sterile barrier precautions during insertion (mask, hat, sterile hand wash, sterile gown, sterile gloves, large sterile drape) [ 70, 84, 85 ]
Do not attempt insertion through incubator port holes [ 71 ] Disinfect skin with an appropriate antiseptic solution [ 70– 72, 85 ] Avoid any iodine based antiseptic solutions [ 86, 87 ]
Use a chlorhexidine-based antiseptic solution [ 88– 91 ]
Avoid concentrated chlorhexidine-based antiseptic solutions or solutions with alcohol in extremely preterm infants in the fi rst few days [ 92– 94 ]
Combined with alcohol for more mature or older infants [ 91, 95 ]
Do not use the same needle for several attempts at central line insertion (“one needle, one puncture”) [ 71 ]
Central line management
Minimise any manipulation of the central line [ 96, 97 ] Avoid accessing the catheter for blood sampling
Reduce the number of line changes—stretch out the time between PN changing to as long as recommended by the PN supplier
Strict sterile precautions for any line changes or when accessing the line [ 98, 99 ] Use the same precautions as during insertion of the line
Use concentrated chlorhexidine with alcohol to sterile the lines and hubs Promoting care of the catheter exit site [ 96, 100, 101 ]
Changing the dressing and sterilising the site if soiled, wet or visibly dirty Regular cleaning and dressing changes even when visibly clean
Use of heparin in the PN solution at a concentration of 0.5 IU/mL [ 102 ]
Promoting enteral feed progression and actively assessing the ongoing need for the central line so as to promote prompt line removal [ 60– 63 ]
Combining strategies
Use of “bundles” [ 103 ] of evidence-based risk reduction strategies (similar to those described in this table) combined with policy, education and promotion [ 76, 103– 106 ]
Recognition, diagnosis and management of CLABSI
Emphasis, promotional and educational, on vigilance and awareness of the possibility of CLABSI to promote early recognition and diagnosis [ 70, 75, 76 ]
Draw a single appropriate volume sample for blood culture, 0.5 mL likely to be adequate [ 107– 109 ]
Combine clinical judgement with measures of in fl ammatory mediators to differentiate between true CLABSI (whether culture negative or positive) and false positive and true negative blood culture results [ 110– 113 ]
Promote the judicious use of vancomycin as over use is associated with VRE [ 111, 114 ] Prompt removal of any central line where there is suspected or proven CLABSI with
Staphylococcus aureus or gram-negative organisms or where ongoing CLABSI is suspected or proven despite appropriate treatment [ 115 ]
reduces CLABSI [ 72 ] . Reducing the number of people who insert PICCs to create a highly trained team within a service will also reduce CLABSI [ 73, 74 ] .
Hand hygiene is an extremely important quality issue within neonatal intensive care and in the prevention of CLABSI [ 75– 83 ] . Before any patient contact, particularly before palpating for veins, one cannot stress enough the importance of thorough and effective hand washing or hand hygiene with an alcohol-based hand product.
The site of insertion of the central line may also have an impact on the safety of PN delivery.
A study comparing upper limb insertion with lower limb insertion found that there were less compli- cations when the PICC was inserted in the lower limb [ 44 ] . There were no cases of serious extravasa- tion injury in either upper or lower limb PICCs in this study; so there is still no answer as to whether there is a difference in extravasation complications related to which limb the PICC is sited in, but rates of CLABSI with CoNS were higher (5.7% compared with 10%, p < 0.05) and cholestasis were greater (30% compared with 21.5%, p < 0.05) in the upper limb PICCs. This was a small study and there was no statistically signi fi cant difference in the overall rates of CLABSI (9.3% lower limb compared with 11.6%, not statistically signi fi cant) and the rates of cholestasis are extremely high suggesting that the de fi nition may not be clinically relevant. However, if possible, preference should be for a lower limb PICC.
Central line insertion via the femoral vein, however, should be avoided as this is associated with a signi fi cant increase in CLABSI compared with non-femoral central catheters (risk ratio [RR] 1.76; 95%
CI: 1.01, 3.07, p = 0.045) [ 60 ] .
Central line insertion is a strictly aseptic procedure and there needs to be a strong focus on sterility from the beginning to the end of the procedure. Maximal sterile barrier precautions during insertion, including wearing a mask and hat, performing a sterile hand wash, wearing a sterile gown and sterile gloves and covering the area with a large sterile drape reduces CLABSI [ 70, 84, 85 ] . Anything that hampers the ability to maintain sterility during the procedure needs to be avoided, including attempt- ing insertion through incubator port holes [ 71 ] .
Although it is clear that the infant’s skin needs to be thoroughly disinfected with an appropriate antiseptic solution [ 70– 72, 85 ] , it is unclear as to what is the best solution for a preterm infant. In adult studies, chlorhexidine-based solutions are more effective than either povidone-iodine or alcohol- based solutions in reducing CLABSI [ 88– 90 ] . In a meta-analysis comparing chlorhexidine, often with 70% alcohol, with povidone-iodine for the prevention of CLABSI the authors estimated that for every 1,000 catheter sites disinfected with chlorhexidine gluconate, 11 episodes of CLABSI would be prevented [ 88 ] . Two percent chlorhexidine gluconate in 70% alcohol is more effective at skin antisep- sis than aqueous chlorhexidine gluconate without alcohol [ 95 ] .
In preterm infants, the skin is fragile and in the fi rst few days it is not fully keratinised and so is highly susceptible to chemical burns when concentrated chlorhexidine gluconate or chlorhexidine gluconate with alcohol is used as a skin disinfectant [ 92– 94 ] . It is also important that iodine-based solutions are not used in preterm infants as these are easily absorbed and can result in iodine overload and signi fi cant hypothyroidism [ 86, 87 ] . For more mature or older infants, 0.5% chlorhexidine with 70% alcohol may be safe and effective and is more ef fi cacious than povidone-iodine [ 91 ] .
Thus chlorhexidine ± alcohol is the best solution for skin disinfectant, but the concentration and whether alcohol is used need to be a compromise between skin disinfectant and maintaining skin safety. It is therefore appropriate for each unit to develop a protocol for skin disinfection based on gestational age, days of life and weight of the infant (e.g. infants ³ 1,000 g use chlorhexidine 0.5%
in 70% alcohol, infants <1,000 g use aqueous chlorhexidine 0.1% in the fi rst 2 weeks of life and then chlorhexidine 0.5% in 70% alcohol [ 116 ] ).
Once preparation of skin disinfectant is over, the central line is ready for insertion. The procedure of inserting a PICC can be dif fi cult and is not always successful on the fi rst attempt, but to reduce CLABSI it is important that each attempt to insert the PICC uses a new introducing needle; “one needle, one puncture” [ 71 ] .
Once the central line has been inserted, there needs to be constant vigilance and emphasis on sterility throughout the time the catheter is in situ. Although mentioned earlier, strict and thorough hand hygiene for every patient contact is an important aspect of neonatal care, but is of even more impor- tance when there is a central line in situ [ 75– 83, 117 ] .
Organisms that cause CLABSI can gain entry to the blood stream through colonisation of the cath- eter hub and exit site and migration along the internal and external surface of a PICC [ 97, 100, 101 ] . It is therefore of utmost importance that catheter hub site colonisation is minimised. Any manipula- tion of the catheter can result in colonisation with evidence linking increased rates of CLABSI directly with catheter manipulation, particularly accessing the catheter for blood sampling and disconnecting the catheter for PN changes [ 96, 118 ] . Thus, PICC lines should not be used for blood sampling and this probably should be extended to sampling for a blood culture. PN should be hung for as long as the solution remains stable so that line changes are kept to a minimum. However, line changes do become necessary and thus any accessing of a PICC line should be treated as a strictly sterile proce- dure and all the same processes for line insertion should be followed with all connections thoroughly disinfected with a strong disinfectant such as 2% chlorhexidine and 70% alcohol [ 98, 99 ] .
Care for the catheter exit site is also important. If the exit site is soiled, wet or dirty, then the site needs to be cleaned and the dressing changed antiseptically and even if visibly clean, regular disinfec- tion of the site reduces CLABSI [ 96, 100, 101 ] .
Prompt removal of the catheter is a key preventative measure. We have already discussed in this chapter how the risk of CLABSI is associated with the length of time the catheter is in situ [ 60– 63 ] . Thus, regular assessment of the need for the central line to remain in situ needs to take place and there should be a concerted effort to advance enteral feeding so that as soon as the catheter is no longer required it can be immediately removed.
A simple measure that is effective in the prevention of CLABSI in infants with PICCs used for the delivery of PN is the use of heparin in the PN. Heparin as a continuous infusion in preterm infants prolongs the duration of PICC usability and reduces PICC obstruction without any adverse effects [ 119 ] . Heparin has been shown to reduce microthrombi formation that can act as foci for infection as well as reduce the ability of staphylococcal species from adhering to and colonising foreign sur- faces [ 101, 120– 123 ] . The use of heparin in adults receiving PN through a central venous catheter has been shown to reduce CLABSI [ 124 ] . In a study of 210 infants randomly assigned to PN with or without heparin at a concentration of 0.5 IU/mL, Birch et al. found a statistically signi fi cant reduction in all episodes of culture-positive CLABSI in those infants receiving heparin (RR 0.57, 95% CI 0.32, 0.98, p = 0.04, number needed to treat 9, 95% CI 4.6, 212.4) [ 102 ] . We also found that in extremely low birth weight infants (<850 g) the reduction in CLABSI in the heparin group was protective against progression of intraventricular haemorrhage. There were no adverse effects associated with the use of heparin in preterm infants in this study or the study of Shah et al. [ 102, 119 ] .