16.3 PN Complications & IFALD

Catheter-Related Complications

Because PN requires central venous access for weeks to years, line complications dominate the morbidity profile and the exam blueprint.

• Central line–associated bloodstream infection (CLABSI) is the most common serious complication of pediatric PN. Prevention rests on insertion and maintenance bundles: maximal sterile barrier at insertion, chlorhexidine antisepsis, meticulous hub disinfection before every access, prompt removal of unneeded lines, and a dedicated PN lumen never used for medications or blood sampling. In children on long-term home PN with recurrent infections, ethanol lock therapy reduces CLABSI rates. Common organisms include coagulase-negative staphylococci, Staphylococcus aureus, gram-negative bacilli, and Candida — and every bloodstream infection also accelerates liver injury in intestinal failure, which is why sepsis prevention is liver prevention.
• Occlusion is managed by identifying the cause: thrombotic occlusions respond to alteplase (tPA) dwells, lipid residue to ethanol or sodium hydroxide clears, and precipitates to dilute hydrochloric acid.
• Thrombosis and vessel loss accumulate silently over years of access; children on lifelong PN may run out of patent central veins, making line preservation a long-range clinical priority. Breakage, dislodgement, and air embolism round out the mechanical list, and home PN families must be trained in emergency line clamping.

Metabolic Complications

Hyperglycemia from excessive GIR and rebound hypoglycemia from abrupt cessation bookend the carbohydrate problems. Hypertriglyceridemia reflects impaired lipid clearance, especially in preterm infants, sepsis, and malnutrition — paradoxically, both overfeeding and underfeeding raise triglycerides. Electrolyte and acid-base disturbances (hyperchloremic metabolic acidosis from unbalanced chloride loads, hypokalemia and hypophosphatemia during anabolism) require daily attention early on. Metabolic bone disease — osteopenia and fractures in long-term PN children — results from the ceiling on calcium and phosphorus solubility in PN, chronic acidosis, vitamin D issues, and aluminum contamination of PN additives, which deposits in bone and brain. Two trace element toxicities are exam favorites:

• Manganese is excreted in bile; in cholestasis it accumulates and deposits in the basal ganglia, producing Parkinsonian neurologic signs and symmetric T1 hyperintensity on MRI. Remove manganese from PN in any cholestatic child on long-term therapy.
• Copper is also biliary-excreted and reduced in cholestasis — but never remove it blindly, because copper deficiency causes anemia and neutropenia; monitor levels. Conversely, long-term PN without adequate zinc causes acrodermatitis-like periorificial and perineal dermatitis, and fat-free PN causes essential fatty acid deficiency (dry scaly skin, poor wound healing, thrombocytopenia) within weeks.

Intestinal Failure–Associated Liver Disease (IFALD)

Intestinal failure–associated liver disease (IFALD) — the modern term replacing "PN-associated cholestasis" — is liver injury occurring in the setting of intestinal failure and PN therapy, classically flagged by a direct (conjugated) bilirubin of 2 mg/dL or higher sustained in a PN-dependent child. It begins as canalicular cholestasis and steatosis and can march through fibrosis to cirrhosis, portal hypertension, and end-stage liver disease — historically the leading indication for combined liver–small bowel transplant in children with intestinal failure.

Risk factors, roughly in order of exam weight:

1. Prematurity and low birth weight — the immature bile acid transport system is exquisitely vulnerable; the lower the birth weight, the higher the risk.
2. Duration of PN exposure — risk climbs with every week of exclusive PN.
3. Absence of enteral feeding — lack of luminal nutrients eliminates cholecystokinin-driven bile flow and promotes bacterial overgrowth and translocation.
4. Recurrent sepsis / CLABSI — each episode delivers an inflammatory hit to the liver.
5. Lipid emulsion type and dose — prolonged soybean-only lipid at full dose delivers omega-6 fatty acids and phytosterols that are directly hepatotoxic.
6. Overfeeding — excess dextrose calories drive hepatic steatosis.

IFALD Prevention and Treatment Ladder

First and most powerful: feed the gut. Even small trophic enteral volumes stimulate bile flow and are the strongest protective factor; advancing enteral autonomy is the definitive cure. Then the lipid strategies, in order:

• Composite/mixed-oil emulsion (SMOFlipid) as first-line for children expected to need prolonged PN — ESPGHAN favors mixed oils because they reduce omega-6 and phytosterol exposure while preserving energy and essential fatty acids.
• Lipid minimization — reducing soybean emulsion to about 1 g/kg/day — lowers phytosterol load while still preventing essential fatty acid deficiency; it is a prevention/dose strategy, not a treatment for established cholestasis.
• Fish oil monotherapy (Omegaven) at ~1 g/kg/day is the rescue therapy for established IFALD with rising direct bilirubin; its omega-3 profile and absence of phytosterols allow bilirubin to fall over weeks to months. A nuance worth knowing: fish oil alone treats cholestasis but, as monotherapy at 1 g/kg/day, provides fewer calories and different fatty acid balance than mixed emulsions, so growth and EFAD status need monitoring.
• Cycle the PN once stable — intermittent infusion reduces hepatic steatosis compared with continuous 24-hour dextrose.
• Adjuncts — remove manganese and copper in cholestasis, treat bacterial overgrowth with enteral antibiotics in selected cases, and consider ursodeoxycholic acid, although evidence for ursodiol in pediatric IFALD is limited. Prevention of every avoidable CLABSI is part of liver protection.

When cholestasis progresses despite these measures, referral to an intestinal rehabilitation program is the next step; multidisciplinary programs (gastroenterology, surgery, nutrition, pharmacy) have markedly improved survival and weaning rates. Serial liver assessment tracks direct bilirubin, GGT, transaminases, INR and albumin as synthetic markers, and ultrasound or elastography for fibrosis; a rising INR or falling albumin signals advancing disease far more ominously than transaminase elevation alone.