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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. Paris
1 title, 6 sub titles, 25 materials + 4 additional
HPN-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 - 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
Se
Cr
Mo
++ Cardiomyopathie / failure
- Diabetes
? Coma, ? Met, Uric acid
Neuromyelopathie
Cu
Zn
I
Fe
Al*
Mn*
++
++
+
+
+
+
Glutathion peroxydase
Cr blood
Xanthine ox
Sulfite ox
Aplastic anemia ± mild leucopenia
Heme-Synthase
Acrodermatitis, diarrhea, hair loss, - NB
Zn blood, Ur, hair
Goitre (nil po)
Liver thesaurismosis, perls
Porotic ±painful osteopathy
Extrapyramidal syndrome
Ur
Perls,ferritine
blood, Ur
Blood & MRI
* 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
Mn toxicity :Brain MRI / hypersignal in T1, basal ganglia + white matter
BM 00 99
Vitamin deficiencies and (H)PN
Deficiency
B1, Thiamine
Folique (B9)
B12
PP, Niacin,
B6
B2
Biotin
Presentation
Wermicke's encephalopathy
Cardio myopathy,
Refractory lactic acidosis
Megaloblastic anemia ± cytopenia
Irritability, megaloblastic anemia
Cordonal posterior Syndrome
Dermatosis (pellagra), Diarrhea,
Demencia
Sideroblastic anemia, convulsions
Cheilosis, red swollen tongue, folliculitis
Dermatitis, alopecia, hypotonia in 1 child
BM 0097
Vitamin deficiency during (H)PN
Deficiency
Vitamin A
Vitamin E
Vitamin D
Vitamin K
Vitamin C
Presentation
Night blindness, xerophammia,dark field
adaptation, defective bone mineralization
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
Osteomalacia
Bleeding tendencies,defective II,VII,IX,XII
Bone mineralization (Gla proteins)
Scurvy, bleeding sore gums,
peri joint and bone hemorrhages
BM 0096
HPN-LD Complications
• Multifactorial metabolic
bone disease
Contributing factors of *Metabolic bone
disease associated with HPN
- PN dependent
- Patient ’s dependent
Continuous > cyclic
Al in hydrolysates (past)
Al in additives
Too much Ca
Inappropriate vitamine D
Vitamin K deficit
Vitamin A deficit
Steroids
Immobilisation
Inflammation / sepsis
Mg deficiency
P deficiency
Age of disease occurrence
Vitamin K antagonists
Decreased BMI or LBM
Physical inactivity
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 menopausal
age 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 old
Femoral (cortical)
NS change
NS change
Cohen-Solal M et al JBMR 2003; Pironi L et al Clin Nutr 2002 & 2004
Without osteoporosis
55y
0.5
Lumbar spine Z-Score
With osteoporosis
0.5
0
0
35y
-0.5
-0.5
-1
21y
15y
-1.5
-1
35y
-1.5
-2
-2
-2.5
-2.5
0
2
4
6
8
Duration of HPN (years)
10
55y
21y
15y
0
2
4
6
8
10
Duration of HPN (years)
Figure 2 : Mean change of lumbar spine Z-Score during long term HP N 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).
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)