or a Peripheral Venous Cannula
PN, as the name suggests, is intravenous nutrition, usually made up of an amino acid/carbohydrate solution with electrolytes, minerals and trace elements and a lipid solution. Delivery of this solution can be into a central vein or via a peripheral vein. In newborn infants, there is a unique opportunity to access umbilical vessels and so PN delivered via a central vein can be through a central line, a periph- erally inserted central catheter (PICC) or an umbilical venous catheter (UVC). In this fi rst section, we will explore the non-infective complications associated with the delivery of PN via three main routes (peripheral vein, PICC or UVC) and methods to reduce these complications and improve safety (see Table 12.1 ).
Delivering PN Via an Umbilical Venous Catheter
In the fi rst few days of life, PN is often delivered via a UVC, particularly in the extremely preterm or extremely low birth weight infants who also have an umbilical arterial catheter in situ. The main complications associated with UVC use are related to malposition of the catheter, extravasation, infection, thrombosis and there may be an association with necrotising enterocolitis (NEC).
One of the key points in improving safety with UVC use is ensuring correct placement. Pericardial extravasation and cardiac tamponade, hepatic venous thrombosis and necrosis, hepatic and intraperi- toneal extravasation and portal vein thrombosis and subsequent portal venous hypertension are all reported serious complications of UVC use in preterm infants, and are often, although not always, associated with incorrect placement of the catheter [ 2– 7, 13, 14, 40, 41 ] .
It is important before inserting the UVC that an estimation of insertion length is made. A simple and commonly used calculation for insertion distance from the base of the umbilical stump is derived from birth weight – insertion distance (cm) = 1.5 × birth weight (kg) + 5.5 [ 8 ] . The website www.nicutools.org has tools to make the calculation of estimated UVC insertion length based on this formula [ 9 ] .
Once inserted, it is then imported to ensure correct placement of the UVC, in the ductus venosus or inferior vena cava (IVC) and not in hepatic or portal veins or within the heart. Generally, the place- ment is checked using an antero-posterior (AP) chest radiograph (CXR); however, more accurate estimation of the tip of the UVC may be made if this is accompanied by a lateral CXR [ 10, 11 ] or using echocardiography [ 12 ] .
The other important complication of UVC delivery of parenteral nutrition is serious invasive bacterial and fungal infections, including localised hepatic abscesses secondary to malposition of the catheter [ 16 ] . UVCs are central lines and as such are prone to central line associated blood stream infections (CLABSI). A more in-depth discussion of methods to prevent infection associated with the delivery of PN through a central line will take place later in this chapter.
Prompt removal of an UVC is important for the prevention of any complication; so one should always be cognisant of the ongoing need for the central line, but there is evidence to suggest than an appropriately placed catheter can be left in situ for 14 days without increasing complication rates [ 15 ] .
Table 12.1 Summary of non-infective complications of PN delivery and methods to improve the safety of the delivery of PN
Route of delivery Complications Methods to improve safety
UVC Pericardial effusion ± tamponade [ 2– 5 ] Estimate UVC insertion distance prior to insertion Hepatic venous thrombosis ± necrosis
[ 6, 7 ]
Distance(cm) = 1.5 × birth weight (kg) + 5.5 [ 8, 9 ] Check correct UVC tip placement [ 10– 12 ] In the umbilical vein or ductus venosus Hepatic extravasation [ 5, 13 ] Not in portal or hepatic vessels and outside of
cardiac silhouette
Use antero-posterior chest radiograph in combination with lateral chest radiograph and/or
echocardiography
Portal vein thrombosis [ 6, 14 ] Prompt removal of UVC as soon as no longer required, but not to remain in situ for >14 days [ 15 ]
Hepatic abscess [ 16 ] Peripheral venous
cannula
Compared to peripherally inserted central catheter (PICC) use
Delivery via a PICC confers some bene fi t with no evidence of increasing the risk of invasive bacterial or fungal infection [ 17 ]
There is an increased incidence of painful procedures [ 17, 18 ] There may be an increased incidence
of extravasation injury [ 17 ] There is inconsistent and reduced
nutritional delivery [ 19 ] PICC Pericardial effusion ± tamponade
[ 20– 23 ]
Always check the position of the PICC after insertion by instilling radio-opaque contrast into the catheter prior to performing a radiograph [ 24 ]
Extravasation into Ensure that the catheter tip is outside of the cardiac silhouette/pericardial re fl ection on chest radiograph [ 20, 22, 23 ]
Epidural space [ 25– 28 ] Withdraw or remove any PICC where there is a
“cobweb” sign suggesting tip is in a super fi cial tributary [ 29 ]
Pleural space [ 30– 33 ] When using an upper limb vein ensure that correct placement taking into consideration tip movement of up to 1.5 cm [ 34 ]
Kidneys [ 35, 36 ] When using the lower limb calculate the insertion distance from the long saphenous at the medial malleolus (between 0.55 × birth weight (kg) – 4 and 0.44 × birth weight (kg) – 3) so as to ensure tip placement avoids right atrium and ascending lumbar veins (T9–L3) [ 9, 37 ]
Peritoneum [ 38, 39 ] Restrict PICC use to units that insert and manage PICCs frequently [ 21 ]
If it is envisaged that the PN is likely to be required beyond 14 days then the UVC may be removed earlier and other forms of delivery of PN, discussed next, should be utilised.
Delivery of PN Via a PICC Versus a Peripheral Venous Cannula
In infants who do not require umbilical lines or when PN is ongoing, beyond what clinicians feel is safe for the UVC to remain in situ, the question is whether to deliver PN through a peripherally inserted central venous catheter (PICC) or via a peripheral venous cannula. PICCs generally remain usable for longer than peripheral venous cannulae and are less likely to extravasate into super fi cial
tissues, but there are concerns that PICCs are associated with more complications including invasive bacterial and fungal infections and more serious extravasation injuries.
A Cochrane review of PICCs vs. peripheral cannulae for delivery of PN to neonates, including fi ve small clinical trials with a combined total of 432 infants, found no signi fi cant difference in death or invasive bacterial or fungal infection [ 17 ] .
Three of the fi ve randomised controlled trials compared extravasation injuries in infants where PN was delivered via PICCs vs. peripheral venous cannulae and although the results were not statistically signi fi cant, there was a trend towards less extravasation with PICC use [ 17 ] .
The advantage that PICC lines have over peripheral venous cannulae is that they are able to remain in situ for longer and thus reduce the number of painful procedures the infant has to undertake.
The meta-analysis showed a signi fi cant reduction in peripheral intravenous cannulae replacement in those infants where PN was delivered through a PICC: mean difference −4.3 (95% con fi dence interval (CI): −5.24, −3.43) [ 17 ] . A cohort study not included in the Cochrane review also showed a reduction in peripherally inserted cannulae replacement when PICCs were used with no increase in bacterial infections [ 18 ] .
It is possible that PICCs may confer another advantage in that nutritional delivery may be better when the PN is infused through a PICC compared to PN infused through a peripheral venous cannula.
A small study of 49 infants showed a statistically signi fi cant difference in the de fi cit of delivered PN (from that actually prescribed) favouring PN delivered through a PICC compared with that through a peripheral venous cannula [ 19 ] . This was related to an increase in pauses in PN delivery when periph- eral venous cannulae required resiting. The difference was a mean de fi cit of 3.2% in the PICC group vs. 10.3% in the peripheral cannula group. The mean difference in the percentage of the prescribed nutritional intake actually received was −7.1% (95% CI: −11.02, −3.2). This 7.1% difference over a week represents 12 h less nutrition in peripheral venous cannula group, a signi fi cant amount in a preterm infant where nutrition is very important for growth and development.
The evidence was not felt to be strong enough for the Cochrane review authors to recommend either PICC or peripheral venous cannula use for the delivery of PN, but the limited evidence suggests that delivery through a PICC confers bene fi ts without increasing the risk of invasive infections [ 17 ] . Delivery through a PICC may reduce episodes of extravasation injury, reduce painful procedures through a reduction in peripheral venous cannulae replacement and deliver better nutrition more con- sistent with what is prescribed.
Delivering PN Via a PICC
PICC use is now widespread in neonatal intensive care for the delivery of PN and it is therefore impor- tant to minimise the risks involved. The two commonly reported and serious complications associated with PICC use are extravasation injuries and central line associated blood stream infections (CLABSI).
This section will concentrate on minimising extravasation injury with the next section concentrating on CLABSI.
There are multiple reports in the literature of severe extravasation injuries secondary to the use of PICC lines used for the delivery of PN to preterm infants. The most serious of these is pericardial extravasation causing effusion and at times cardiac tamponade with a high associated mortality. An important report from the United Kingdom (UK), Department of Health publically highlighted four deaths in Manchester from cardiac tamponade as a result of extravasation of central lines inserted for the administration of PN (two PICCs, one surgically inserted central catheter and an UVC) [ 20 ] . There are three large series published on the use of PICCs for the delivery of PN and all report low rates of pericardial effusion and even lower rates of fatal cardiac tamponade. In a series of 2,186 PICCs in 1,862 infants in a large Australian perinatal centre, there was one case of non-lethal pericardial
effusion giving a rate of 0.05% [ 42 ] . In a series of 46,000 PICCs in 168 neonatal intensive care units (NICUs) across the UK over a 5-year period, there were 82 cases of pericardial effusion (0.18%) and 30 infants died as a result of cardiac tamponade (0.07%) [ 21 ] . In a survey of 92 NICUs in Japan where there was an estimated 5,000–7,500 PICCs inserted per year over a 5-year period, there were 28 cases of pericardial effusion (0.07–0.11%) [ 22 ] .
The reported rates of pericardial effusion associated with the use of PICCs (0.05–0.11%) for the delivery of PN to preterm infants is low, but the mortality associated with this complication is very high and so it remains a real fear for neonatologists. It is therefore important to consider ways of avoiding this serious complication so as to safely delivery PN.
In the report out of Manchester, all four deaths occurred in infants where the position of the line was in the right atrium and the very strong and public recommendation of that report was that central lines should not be placed with the tip inside the heart [ 20 ] . This is backed up by a report from Texas reviewing 14 local cases and 47 case reports in the literature of pericardial effusion associated with PICC use for the delivery of PN to neonates which found that 92% of cases had the PICC tip located within the pericardial re fl ection on chest radiography [ 23 ] . Their recommendations were that CXRs should be performed to check the position of all PICCs and that the tip should be outside of the cardiac silhouette, but still within the vena cava. In the Japanese series, the rates of pericardial effusion associated with PICC tended to be higher in NICUs that allowed tip position in the right atrium ( p = 0.09) [ 22 ] .
In the UK series, the tip position could not be veri fi ed, although the units surveyed claim the choice of tip position was within either the IVC or superior vena cava (SVC), and so conclusions about safe position of a PICC could not be made [ 21 ] . However, they did fi nd a statistically signi fi cantly increase in pericardial effusion associated with PICCs in units that inserted fewer lines.
Thus to increase safety and minimise the risk of pericardial effusion, PICC insertion should be restricted to units that are familiar with their use and the tip position needs to be con fi rmed by CXR to be outside of the cardiac silhouette.
Serious injury from extravasation associated with PICC use is not restricted to pericardial effusion.
There have been literature reports of extravasation of PN into the epidural space [ 25– 28 ] , the pleural space [ 30– 33 ] , the kidneys [ 35, 36 ] and the peritoneum [ 38, 39 ] all with serious consequences.
In these anecdotal reports, there is a common thread of malposition of the PICC. Therefore, like reducing the risk of pericardial effusion, it is important that the tip position is con fi rmed. However, con fi rming tip position of a PICC can be dif fi cult and interobserver and intraobserver reliability has been shown to be relatively poor [ 43 ] . Interobserver reliability is improved when radio-opaque contrast is instilled, not injected, into the PICC prior to performing the radiograph [ 24 ] .
When a PICC is unable to be placed to the calculated full length, then it may be better to inject the radio-opaque contrast while the radiograph is being taken because a “cobweb sign” (multiple thin rays of radio-opaque contrast visible in different directions like a cobweb) indicates that the tip is a super fi cial tributary and is at a high risk of extravasation [ 29 ] . If this situation arises, then the PICC needs to be withdrawn and the position rechecked using the same radiological technique, or removed and resited.
Con fi rming the PICC tip position by radiography is essential in improving safety when delivering PN via a PICC, but the position of the tip at the time of the radiograph is not necessarily the position the tip will stay all the time. The SVC is considerably shorter than the IVC and there are concerns that when a PICC is inserted into the upper limb, arm movement may result in movement of the PICC tip and may result in the tip entering the right atrium and placing the infant at risk of pericardial effu- sion. Nadroo et al. compared 280 radiographs of 60 neonates with PICCs inserted into the upper limb and found that arm movements signi fi cantly affected the tip position of the PICC and that the migra- tion towards or away from the heart differed with the same arm movement depending on which vein was used—basilic, axillary or cephalic [ 34 ] . Shoulder adduction will bring a basilic or axillary vein PICC closer to the heart, but a cephalic vein PICC will be displaced away. Flexion of the elbow moves a basilic or cephalic vein PICC towards the heart, but has no effect on an axillary vein PICC.
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.