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research-article2014
Brief Communication
Abstract
Background: Hypertriglyceridemia is a frequent metabolic complication associated with fat administration in parenteral nutrition (PN).
No clear guidelines have been published on how to proceed once hypertriglyceridemia has been detected. A new strategy could be
to substitute the initial fat emulsion with another emulsion with faster clearance. Our objective was to determine the effectiveness
in reducing triglyceridemia values, maintaining the caloric intake, and improving nutrition parameters in patients who had moderate
hypertriglyceridemia during PN when an olive oilbased fat emulsion (OOFE) was substituted with a multiple-source oil fat emulsion
(MOFE). We also assessed the safety of this substitution in hepatic and glycemic profiles. Materials and Methods: We performed a
retrospective, observational study that included 38 adult patients to whom OOFE in PN was substituted with MOFE when moderate
hypertriglyceridemia (250400 mg/dL) was detected. Results: Triglyceridemia values decreased in 36 (94.7%) patients. The mean
reduction was 71 (8822) mg/dL. Fat load was slightly reduced after substitution (0.14 [0.23 to 0] g/kg/d; P < .001), but total caloric
intake increased from 22.5 (19.725.1) to 23.1 (19.826.8) kcal/kg/d (P = .053). After substitution, nutrition parameters improved, liver
parameters remained unchanged, and insulin requirements increased. Conclusion: The substitution of OOFE with MOFE in patients with
moderate hypertriglyceridemia during PN resulted in a reduction in triglyceridemia values of about 70 mg/dL. That allowed maintaining
the caloric intake and improved nutrition parameters without affecting the hepatic profile. For some patients, insulin requirements
increased moderately. (JPEN J Parenter Enteral Nutr. 2016;40:705-712)
Keywords
energy intake; hypertriglyceridemia; intravenous fat emulsion; olive oil; parenteral nutrition; plant oils
Introduction
Hypertriglyceridemia is a frequent metabolic complication
associated with fat administration in parenteral nutrition (PN).
Its incidence ranges from 6%38%.1
Hypertriglyceridemia occurs if the infusion rate exceeds the
capacity of plasma fat clearance. Several factors are known to
increase its risk during PN. They include renal failure, sepsis,
pancreatitis, hyperglycemia, high-output enterocutaneous fistulas, diabetes, obesity, alcoholism, multiple organ failure, and
administration of certain drugs such as corticosteroids, cyclosporine, tacrolimus, sirolimus, propofol, or glucose.2,3 No clear
guidelines have been published on how to proceed once hypertriglyceridemia during PN has been detected. Fat withdrawal
has been proposed at different triglyceridemia values (eg, >400
mg/dL,4,5 >440 mg/dL,6 >500 mg/dL,7 or even >1000 mg/dL8).
At lower plasma levels, a fat dose reduction has been
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to evaluate the safety of this substitution by assessing alterations in hepatic and glycemic profiles.
Methods
Characteristic
Study Design
Composition, g/100 mL
Soybean oil
Medium-chain triglycerides
Olive oil
Fish oil
Glycerol
Egg phospholipids
Sodium oleate
Fatty acid content, %
Caprylic acid
Capric acid
Miristic acid
Palmitic acid
Palmitoleic acid
Stearic acid
Oleic acid
Linoleic acid
-Linolenic acid
Arachidonic acid
Eicosapentaenoic acid
Docosahexaenoic acid
Other fatty acids
Ratio -6/-3
We performed a retrospective, observational study at our 400bed, third-level university hospital situated in the urban area of
Barcelona, Spain. The Clinical Research Ethics Committee of
our institution reviewed and approved the study.
Study Period
From September 2009 through March 2013, a total of 38 consecutive patients were included.
PN Support
PN was designed to provide the calculated resting energy
expenditure (REE) by the MifflinSt Jeor equation. In general,
the composition corresponded to 2025 kcal/d, <5 g glucose/
kg/d, <1 g fat/kg/d, and 11.25 g protein/kg/d. The composition was individually modified if necessary according to clinical conditions and laboratory parameters.
PN was prepared following usual hospital practices as an
all-in-one admixture and administered in a 24-hour perfusion. All patients received the same products used to prepare
PN: glucose solutions, standard amino acid solution
(Aminoplasmal L, B.Braun, Rub, Spain), OOFE (Clinoleic
20%; Baxter Clintec, Maurepas, France), MOFE (SMOFLipid
20%; Fresenius Kabi, Uppsala, Sweden), vitamins (Cernevit;
Baxter Clintec), trace element solution (Addamel; Fresenius
Kabi), and electrolytes. The detailed composition of both fat
emulsions is shown in Table 1.
Intervention
Intervention was defined as the substitution of OOFE in the PN
with MOFE when the first episode of hypertriglyceridemia
was detected.
Olive Oil
Based Fat
Emulsion
Multiple
Source Oil
Fat Emulsion
16
2.25
1.20
0.03
6
6
5
3
2.50
1.20
0.03
12
1
2
65
17
3
0.5
9.5
9
16
11
1
9
1
3
28
19
2
0.5
2
2
6.5
2.5
General Parameters
Data collected from the patients were demographic (sex, age)
and anthropometric (weight, height, body mass index [BMI])
values, REE, type of patient (medical, surgical, trauma),
comorbidities (hypertension, heart failure, cardiovascular disease, stroke, dyslipidemia, diabetes, obesity defined as BMI
between 25 and 35 kg/m2, chronic renal failure, liver disease,
neoplasm, human immunodeficiency virus, alcoholism), severity according to the Charlson index, indication of PN, and
duration of PN.
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PN Parameters
Macronutrients and kilocalories provided were collected
before and after the intervention. Date of intervention and date
of next triglyceridemia control were also recorded.
Parameters of Effectiveness
Triglyceridemia, total serum protein, serum albumin, prealbumin,
lymphocytes, and C-reactive protein were recorded at the beginning of PN, before and after the intervention, and at the end of PN.
Parameters of Safety
Alanine aminotransferase (ALAT), aspartate aminotransferase
(ASAT), alkaline phosphatase, -glutamyl transferase (GGT),
and total bilirubin were recorded as parameters of liver toxicity
at the beginning of PN, before and after the intervention, and at
the end of PN.
Hyperglycemia was defined as blood glucose >180 mg/dL.
Days with at least a determination of hyperglycemia, peak of
hyperglycemia, and insulin requirements were calculated
before and after the intervention.
Other Outcomes
Days of PN, length of stay (LOS), and mortality were also
recorded.
Statistical Analysis
Data were analyzed using the Wilcoxon signed-rank test for
nonparametric paired data, McNemar test to compare paired
proportions, Mann-Whitney U test to compare nonparametric
independent data, and Pearson correlation coefficient to correlate between 2 variables. Data are presented as median values
and quartiles 1 and 3 (Q1Q3).
(3 [7.9%]), and other (7 [18.4%]). Detailed patient characteristics are shown in Table 2. The indications for PN were postoperative complications in 18 (47.4%) patients, intolerance to
enteral nutrition or inability to have enteral access in 7 (18.4%),
intestinal obstruction in 4 (10.5%), intestinal ischemia in 3
(7.9%), protocolled postoperative fasting in 3 (7.9%), and
other indications in 3 (7.9%).
Nutrition and biochemical parameters at the beginning of
PN are shown in Table 3. As main features, patients had a moderate inflammatory state with severe hypoalbuminemia and
low prealbuminemia. Median triglyceridemia values were
within the high side of the normal range, and liver parameters
were normal except for GGT, which was mildly elevated.
Triglyceridemia and PN
Results
Patients
Forty-seven patients were initially selected for the study. Nine
patients were later excluded5 for basal triglyceridemia values
>250 mg/dL, 3 for mixed nutrition, and 1 for BMI 35 kg/m2
resulting in a total of 38 patients. Most patients were women,
with an average age of 68 years, with a BMI in the normal
range, a Charlson index moderately high, and a high rate of
hypertension, neoplasm, and diabetes. Patients were admitted
in the departments of surgery (21 [55.3%]), urology
(4 [10.5%]), oncology (3 [7.9%]), surgical intensive care unit
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Median
(Q1Q3)
Laboratory
Normal Range
146 (120194)
5.0 (4.15.5)
2.4 (1.92.6)
12.1 (8.716.3)
0.9 (0.71.5)
40150
6.08.3
3.85.1
18.038.0
1.54.0
115 (88134)
0.4 (0.30.7)
20 (1432)
20 (1133)
94 (43159)
107 (73177)
9.9 (4.622.8)
80110
0.21.2
1038
741
561
35129
00.8
Effectiveness
The subsequent control of triglyceridemia was done on day 7
(48) after the intervention, corresponding to day 15 (1019)
from the beginning of PN. Nutrition and biochemical parameters before and after the intervention are shown in Table 5. The
variation in triglyceridemia values before and after the intervention did not correlate with the variation in fat provided
daily (P = .773) or fat provided by kilogram daily (P = .775).
Triglyceridemia values before the intervention did not
Safety
Liver parameters did not change after intervention (see Table
5). Nineteen (50%) patients had hyperglycemia before the
intervention and 15 (39.5%) had hyperglycemia after the intervention (P = .219). The peak of hyperglycemia was 233 (201
261) mg/dL preintervention and 223 (200276) mg/dL
postintervention, without differences between them (P = .394).
Insulin requirements in these patients were 0.12 (0.04 0.22)
IU/kg/d preintervention and increased to 0.26 (0.110.34) IU/
kg/d postintervention (P = .006). At the end of PN, triglyceridemia values, nutrition parameters, and liver parameters did
not change from postintervention values (data not shown).
Outcomes
PN lasted 21.0 (12.039.0) days. LOS was 48.0 (23.869.5)
days, and 5 (13.2%) patients died during admission.
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Table 4. Macronutrients and Total Kilocalories Provided Before and After Intervention.
Characteristic
Protein, g/d
Protein load, g/kg/d
Glucose, g/d
Glucose load, g/kg/d
Fat, g/d
Fat load, g/kg/d
Total kcal/d
Total kcal/kg/d
Ratio total kcal/REE
Preintervention, Median
(Q1Q3)
Postintervention, Median
(Q1Q3)
Variation, Median
(Q1Q3)
P Value
.012
.007
<.001
<.001
<.001
<.001
.084
.053
.056
Preintervention, Median
(Q1Q3)
Postintervention, Median
(Q1Q3)
Variation, Median
(Q1Q3)
P Value
<.001
.002
.002
.007
.753
71 (88 to 22)
0.3 (0.2 to 1.0)
0.2 (0 to 0.5)
4.7 (0.7 to 12.1)
0.05 (0.32 to 0.41)
0 (0 to 0.2)
1 (17 to 8)
0 (11 to 11)
19 (71 to 170)
3 (62 to 44)
0.3 (5.7 to 3.4)
.160
.406
.754
.546
.905
.441
ALAT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, -glutamyl transferase; Q1, quartile 1; Q3, quartile 3.
Discussion
To our knowledge, this is the first study assessing the effectiveness and safety of substituting a fat emulsion for hypertriglyceridemia during PN. The substitution of OOFE with MOFE for
patients with moderate hypertriglyceridemia during PN was an
effective strategy in reducing triglyceridemia values, maintaining caloric intake, and improving nutrition parameters without
affecting patients liver and glycemic profiles.
At our institution, MOFE containing -3 fatty acids was
initially protocolled for critically ill patients receiving PN with
a high level of systemic inflammation, while OOFE was used
in the rest of the patients. We had surprisingly detected lower
triglyceridemia values in many critically ill patients than in
noncritically ill patients. In view of those findings, we decided
to use MOFE in cases of hypertriglyceridemia in noncritically
ill patients.
Around 85% of our patients had risk factors for hypertriglyceridemia. Some of these factors changed during the PN
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Figure 1. Evolution of triglyceridemia during parenteral nutrition. *Different from basal value (P < .001). Different from preceding
hypertriglyceridemia peak (P < .001). Different variation of triglyceridemia comparing patients continuing with MOFE with patients
reverting to OOFE (P = .004). MOFE, multiple-source oil fat emulsion; OOFE, olive oilbased fat emulsion.
increased again in the 5 patients to whom OOFE was reintroduced after the MOFE course. In comparison, patients maintained on MOFE did not have a change in triglyceridemia
values despite increasing the fat load.
Currently, several fat emulsions are marketed as an alternative to the classic soybean oil fat emulsion (SOFE), mainly in
Europe. SOFE may have deleterious effects due to its high
content of -6 fatty acids, considered to increase the proinflammatory state present in many patients requiring PN.9
Unlike SOFE, those alternative emulsions are composed of fat
from several sources with a lower content of -6 fatty acids.9
Each has a different plasma clearance profile.
In relation to the fat emulsions used in our study, few studies assessed their plasma clearance, mostly in comparison to
SOFE. In 6 young healthy normolipemic participants in a
kinetic precommercialization study,10 OOFE resulted in higher
triglyceridemia values (142%) and in a slower maximum clearance rate (81%) and fractional catabolic rate (61%) compared
with SOFE. This crossover study was performed in experimental conditions with an initial bolus of 0.1 g fat/kg followed by
an infusion of 0.25 g fat/kg/h during 1 hour and without administration of other nutrients. In an early review11 of metabolic
studies mostly in healthy participants, it was concluded that
OOFE in short infusions increased triglyceridemia values in
around 30%, whereas SOFE in short infusions decreased them
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Statement of Authorship
J. Mateu-de Antonio contributed to the conception/design of the
research. J. Mateu-de Antonio and M. Florit-Sureda contributed to
the acquisition, analysis, and interpretation of the data; drafted the
manuscript; critically revised the manuscript; agree to be fully
accountable for ensuring the integrity and accuracy of the work;
and read and approved the final manuscript.
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