Complications related to PN can be classified as insertion related, line related and metabolic complications. The latter are further divided into short-term and long-term, depending on the duration of PN.

Insertion complications Line complications Metabolic (feed) complications

Pneumothorax

Bleeding

Misplacement

Line sepsis

Thrombosis, phlebitis

Occlusion (kinking, clogging)

Dislodgement, fracture, leaking

Acute(short-term PN)

Refeeding syndrome

Hyper/hypoglycaemia

Electrolyte disturbances

Hypertriglyceridemia

Acute cholestasis

Chronic (long-term PN)

Liver disease

Cholelithiasis 

Metabolic bone disease

Micronutrient imbalances

Line insertion complications

Pneumothorax

This is the most frequent insertion complication, with an incidence of 0.5 – 1% and it mainly occurs during subclavian lines insertion, but it is also possible for the internal jugular approach. If symptomatic (significant shortness of breath or pain), a chest drain should be placed for drainage then immediately removed.  

Misplacement

Chest X-ray is mandatory after subclavian and jugular cvc insertion for checking the correct tip position (in the inferior third of superior vena cava or at the atriocaval junction) and identifying possible pneumothorax or misplacement (i.e. in the pleural space or in another vessel). Tip position above this level can cause thrombophlebitis secondary to administering high osmolarity solutions and should be avoided.

Line complications

Line sepsis

Line sepsis, also called CRBSI (catheter related blood stream infection) is a severe complication, with significant morbidity and mortality. Hospitals monitor and report line sepsis as a quality indicator. Its incidence depends on the insertion and maintenance techniques, number of lumens and manipulations and also the insertion site (subclavian < jugular < femoral). PICC lines may have a lower sepsis incidence, especially if they are single lumen and dedicated to PN administration only.

Line sepsis is best prevented by:  using strict aseptic technique and ultrasound guidance at insertion, inserting the line with the minimum possible number of lumens, using a dedicated lumen for PN, inspecting the insertion site and changing the dressings at recommended intervals, minimising the number of manipulations and using anaseptic technique for this, regularly flushing all the lumens and removing the line immediately when it is no longer needed.

Hospitals should have strict policies (usually available on Intranet) about central lines insertion and maintenance. Only professionals with special training (doctors, critical care practitioners or vascular access nurses) can insert central lines and they should monitor these strictly while in place.

If line sepsis is suspected, blood cultures should be taken from the line and peripheral blood and the line should not be used until the results are available. For acute patients, if the pyrexia settles and cultures from the line are positive, the line should be removed. Microbiology will give appropriate advice about antibiotic treatment. If a fungal infection is present, the line should be removed except in exceptional circumstances. Fungaemia should be followed up with ophthalmic review to exclude uveitis and echocardiogram to exclude bacterial endocarditis. 

For tunnelled or implanted lines in home parenteral nutrition with difficult venous access, antibiotics may be used down the line but this should be done under the supervision of experienced practitioners

Thrombosis and phlebitis 

Thrombophlebitis of the vein where the PN line was inserted is not uncommon and may have serious consequences, including superior vena cava (SVC) occlusion and pulmonary embolism. Intravenous anticoagulation is a standard treatment, but in cases such as acute SVC thrombosis, fibrinolysis may be necessary and longer term endovascular intervention such as angioplasty, stenting and even sharp recanalization maybe employed. Thrombophlebitis is mainly due to administering high osmolarity solutions into a small calibre vein, but major venous thrombosis is also associated with infection. PN solutions with an osmolarity higher than 850 mOsm/L should be administered only into a central vein, namely the superior or inferior vena cava. The tip of the PN line should be in the lower third of the SVC or the right atrium, to ensure high blood flow. Femoral lines should not be used for PN, due to the high risk of infection associated with this insertion site. If peripheral PN is used, midline catheters are preferred whenever possible and PN with lipids should be used, as lipids have been reported to have some protective effects on the vascular endothelium, and reduce the osmolarity of the feed.

Line blockage

Line clogging or obstruction can be prevented by limiting the number of manipulations, flushing the line before and after each manipulation, including drug administration and using a dedicated lumen for PN. Unclogging a line or a lumen can be tried by locking it with heparin-saline or with thrombolytic agents, but this should be done only by a trained professional (see above).

Acute metabolic complications

Electrolyte disturbances should be identified and corrected; these are more frequent at the beginning of PN, therefore close monitoring is important to identify these before clinical symptoms occur.

Refeeding syndrome

This may be a life-threatening complication in the first days after the start of feeding in severely malnourished patients. It may occur with both enteral and parenteral nutrition.  Hypophosphataemia occurs with fluid and electrolyte shifts between intracellular and extracellular compartments. Clinical manifestations are non-specific and can include arrhythmias, muscle weakness, signs of respiratory and/or cardiac failure, oedemas, lethargy or seizures. Fortunately the full-blown syndrome is rare because, unrecognized and untreated, this complication can be rapidly fatal. Typical laboratory findings are hypophosphatemia, hypokalaemia, hypocalcaemia, hypomagnesemia and lactic acidosis. Preventionshould be by cautiously initiating nutrition support in at risk patients, usually administering less than 50% of target requirements within first.24 hours and slowly increasing the next days, while concomitantly frequently monitoring and replacing phosphate, potassium, the other electrolytes and intravenous vitamin B1. 

Hyperglycaemia

High blood glucose is less frequent now because critical care units commonly use strict glycaemic control with an insulin sliding scale if needed, although hypoglycaemia can occur if PN is interrupted and insulin on a sliding scale continued.

Hypertriglyceridaemia

Acute hypertriglyceridemia has a low incidence (although can be a limiting factor for PN in acute pancreatitis patients) and can be treated by reducing the amount of lipids in the PN, using lipid free solutions or cyclical PN. 

Abnormal liver function tests

Patients who are unwell enough to require PN often have or develop abnormal liver function tests. There is often more than one precipitating factor. Sepsis is often a precipitant, whether intra-abdominal, due to line sepsis or from another source. Antibiotics used to treat sepsis may contribute. Concomitant liver disease may be present such as that due to alcohol excess, autoimmune disease or gallstones. Over feeding with energy, whether carbohydrate or fat, causes excess fat deposition in the liver. 

Chronic metabolic complications

Complications associated with long-term PN are less understood and more difficult to treat. 

Liver Disease

The incidence of liver disease in long-term PN patients varies between reports. At least 25% of patients on home PN have cholestatic liver function tests. In a much smaller percentage this disease progresses to fibrosis and then cirrhosis. It is difficult to separate the effects of parenteral nutrition from those of short bowel and therefore the established liver disease in these patients is now referred to as “Intestinal failure associated liver disease” (IFALD). An increased risk of IFALD has been associated with extreme short bowel, lack of colonic continuity, lack of enteral intake, high energy and fat in feed and older lipid preparations which are thought to be proinflammatory because of the omega 6 fatty acids which they contain.

Fatty liver is common, especially in children and can be ameliorated by using lipid free PN solutions several times a week, or by changing the lipid composition to a more balanced one (i.e. adding fish oil). NASH is a serious complication considered to be an infectious hepatitis, associated with bacterial overgrowth and gut translocation of bacteria into the portal circulation. Other causative factors may be the alteration in enterohepatic bile acids cycle associated with a non-functional gut and to a lesser extent, the composition of lipids in the PN. In these cases, the best treatment is restarting enteral nutrition as soon as possible.

Cholelithiasis

Gallstones are more common in patients with short bowel syndrome who lack the enterohepatic circulation of bile salts. Cholecystitis, obstructive jaundice, cholangitis and pancreatitis may all occur.

Metabolic bone disease

Metabolic bone disease is not uncommon in patients on home PN, and manifests itself as osteoporosis or osteomalacia which can lead to fractures and/or kidney stones. Potential causative factors are inadequate calcium, phosphorus and vitamin D intake, chronic immobilisation, steroid treatment, etc. Prevention and treatment include supplementation of Ca, phosphate and vitamin D and sometimes, bisphosphonates.

Micronutrient imbalances

Deficiency or excess of vitamins or trace elements is difficult to diagnose and requires regular measurements in addition to consideration of the clinical situation. The clinical manifestations may be non-specific (i.e. anaemia, hair loss, neurological symptoms, etc). 

Further reading

ESPEN guidelines for adult parenteral nutrition Clinical Nutrition 2009; 28:359-479 http://www.espen.org/education/espen-guidelines

NICE guideline – Nutritional Support for adults 2006 www.nice.org.uk/guidance/cg32/evidence/full-guideline-194889853

Safe vascular access AAGBI guideline 2016 http://www.aagbi.org/sites/default/files/Safe%20vascular%20access%202016.pdf