HPN COMPLICATIONS

Metabolic • liver abnormalities• Gallbladder sludge &

stones• metabolic bone disease• trace element and /or

vitamins deficiencies• manganese toxicity• renal function impairment

B Messing. Approved centre for Intestinal failure. Paris1 title, 6 sub titles, 25 materials + 4 additional

HPN-long term ComplicationsHPN-long term Complications

• Renal function impairment

* in SBS : avoid hyperoxaluria and oxalate-Ca renal stone Up to 25% of patients if steatorrhea and colon. Prevention : oral Ca and food with low oxalate content

Serious Renal Impairment Is Associated With Long-Term Parenteral Nutrition

- 33 (13M, 20 W) adult 51 (21-79) yr old - on Long-term HPN : 8.3±4.4 yrs- Protein load : 1.28± 0.32 g.Kg.d- Nephrotoxic drug : 3.4±4.0% of all HPN days- Bacteriemia/fungemia : 2.3 (0.5±0.5 / yr) episode - Cr clearance (CrCl) decline was 3.5±6.3% per year

- age + 3 above factors : 50% change in CrCl- age + infection factor : idem- excessive urinary phosphate excretion (? aciduria)- but no association with amino acid content of TPN - this decline in renal function is largely unexplained

From L.-A. Buchman; A. Moukarzel, M.-E. Ament et al. JPEN 1993;17: 438-444

Buchman JPEN 1993; 17: 438-44

HPN - ComplicationsHPN - Complications

• deficiencies of trace elements • manganese toxicity • deficiencies of vitamins

Healing of Zn deficiency after a few days of IV supplements BM 0094

TRACE-METAL DEFICIENCIES during (H)PN

Blood & MRIExtrapyramidal syndrome+Mn*

Porotic ±painful osteopathy +Al*

Liver thesaurismosis, perls+Fe

UrGoitre (nil po)+I

Acrodermatitis, diarrhea, hair loss, - NB++Zn

Heme-SynthaseAplastic anemia ± mild leucopenia++Cu

Xanthine ox

Sulfite ox

Coma, ? Met, Uric acidNeuromyelopathie

?Mo

Diabetes-Cr

Glutathion peroxydaseCardiomyopathie / failure++Se

Perls,ferritine

* Excess and toxicity (chronic dehydration, renal insufficiency, cholestasis) (Chonic Zn deficit : altered growth in children with nanism) Mo 0.62±0.29 (Clin Chemistry 2001; 47(2)279 BM. 0093

blood, Ur

Zn blood, Ur, hair

Cr blood

Mn toxicity :Brain MRI / hypersignal in T1, basal ganglia + white matter BM 0099

Vitamin deficiencies and (H)PNDeficiency Presentation

B1, Thiamine Wermicke's encephalopathy

Cardio myopathy,

Refractory lactic acidosis

Folique (B9) Megaloblastic anemia ± cytopenia

B12 Irritability, megaloblastic anemia Cordonal posterior Syndrome

PP, Niacin, Dermatosis (pellagra), Diarrhea, Demencia

B6 Sideroblastic anemia, convulsions

B2 Cheilosis, red swollen tongue, folliculitis

Biotin Dermatitis, alopecia, hypotonia in 1 child

BM 0097

Vitamin deficiency during (H)PNDeficiency Presentation

Vitamin A Night blindness, xerophammia,dark field adaptation, defective bone mineralization

Vitamin E In vitro plateled hyper-aggregation and H2O2 - induced RBC hemolysis.

Signs and symptoms suggestive of subacute combined degeneration (postero-lateral columns) in the presence of normal B12,ophthalmoplegia

Vitamin D Osteomalacia

Vitamin K Bleeding tendencies,defective II,VII,IX,XII

Bone mineralization (Gla proteins)

Vitamin C Scurvy, bleeding sore gums,

peri joint and bone hemorrhages

BM 0096

HPN-LD ComplicationsHPN-LD Complications

• Multifactorial metabolic bone disease

Contributing factors of *Metabolic bone disease associated with HPN

Contributing factors of *Metabolic bone disease associated with HPN

- PN dependent - Patient ’s dependentContinuous > cyclic SteroidsAl in hydrolysates (past) ImmobilisationAl in additives Inflammation / sepsisToo much Ca Age of disease occurrence

Inappropriate vitamine DVitamin K deficit Vitamin K antagonistsVitamin A deficit

Decreased BMI or LBM Mg deficiency Physical inactivityP deficiency Tobacco use

* patchy osteomalacia; low remodeling (resorption> formation)

Metabolic bone disease & LT-HPN- Cross sectional study Cohen-Solal 2003 Pironi 2002 - median age (yr) 52 52- patients (n) 88 165- bone pain 35%- Bone fragility fractures 10% 10%- osteoporosis (T score < 2.5 BMD) 67% 41%- Associated Factors (Z score)

sex - post menopausalage at PN start younger younger BMI + +diseases steroids -

- Longitudinal study Cohen-Solal 2003 Pironi 2004 - patients (n) 56 65- HPN duration (month) 66±15 18±5- BMD evolution (Z score)

Lumbar (trabecular) Increased increased p =0.04

better ≥ 21 yr oldFemoral (cortical) NS change NS change

Cohen-Solal M et al JBMR 2003; Pironi L et al Clin Nutr 2002 & 2004

0 2 4 6 8 10

-2.5

-2

-1.5

-1

-0.5

0

0.5

Lu

mb

ar

sp

ine

Z-

Sc

ore

15y

35y

55y

21y

0 2 4 6 8 10

-2.5

-2

-1.5

-1

-0.5

0

0.5

15y

35y

55y

21y

Figure 2 : Mean change of lumbar spine Z-Score during long term HPN among 56 patients with or without osteoporosis according to the age at IF onset.

To illustrate the results, we chose 3 ages equally spaced within the age-range of our patients, and we calculated the evolution, using the regression equation. As the duration of treatment decreased linearly with age, we did not extrapolate the evolution above the duration of follow-up. The negative evolution under HPN in young patients became positive with aging, and the change was reversed when the patients reached the age of 21. Similar evolutions were observed among patients with osteoporosis. However their Z-Scores were much lower (all values were reduced by 1.1 SD).

With osteoporosisWithout osteoporosis

Duration of HPN (years) Duration of HPN (years)

Cohen-Solql M et al JBMR 2003

Haderslev KV et al AJCN 2002; 76: 482-8.IV Pamidronate (1500 mg/3mo) vs placebo in 20 HPN patients with a T score < 1.

Metabolic bone disease & LT-HPN• Osteomalacia :

- Check vit D metabolites & Ca, P and Mg balances• Low remodeling bone :

- ibid & reinforces Ca, Mg, Vit D metabolites orally- Avoid too much N & Ca IV (calciuria & lower PTH)- Check Al in Blood & in All-in-One (& in renal risk patients ++)

- Check DEXA & BMD at PN start & annually- Check bone markers : osteocalcin & cross laps / deoxypyridinoline

• Specific treatments of osteoporosis :- Biphoshonates ° : positive moderate results at lumbar site,be careful with Ca & vit D status before treatment to avoid deficits

- Near future : trophic factors (GLP2*) or rH-PTH** * Haderslev KV Scand J Gastroenterol 2002; ° Haderslev KV et al Am J Clin Nutr 2002, D ’aoust L et al Clin Nutr 2002 (A)** Khosla S. N Eng J Med. 2003 (editorial)