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Comparison of the effects of different intravenous fat emulsions in patients with sirs and sepsis. nutr clin pract 2011-sungurtekin-665-71

Comparison of the effects of different intravenous fat emulsions in patients with sirs and sepsis. nutr clin pract 2011-sungurtekin-665-71






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    Comparison of the effects of different intravenous fat emulsions in patients with sirs and sepsis. nutr clin pract 2011-sungurtekin-665-71 Comparison of the effects of different intravenous fat emulsions in patients with sirs and sepsis. nutr clin pract 2011-sungurtekin-665-71 Document Transcript

    • Nutrition in Clinical Practice http://ncp.sagepub.com/ Comparison of the Effects of Different Intravenous Fat Emulsions in Patients With Systemic Inflammatory Response Syndrome and SepsisHulya Sungurtekin, Sezai Degirmenci, Ugur Sungurtekin, Berna Elibol Oguz, Nuran Sabir and Bunyamin Kaptanoglu Nutr Clin Pract 2011 26: 665 DOI: 10.1177/0884533611418783 The online version of this article can be found at: http://ncp.sagepub.com/content/26/6/665 Published by: http://www.sagepublications.com On behalf of: The American Society for Parenteral & Enteral Nutrition Additional services and information for Nutrition in Clinical Practice can be found at: Email Alerts: http://ncp.sagepub.com/cgi/alerts Subscriptions: http://ncp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav >> Version of Record - Dec 28, 2011 What is This? Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • Clinical Research Nutrition in Clinical Practice Volume 26 Number 6 December 2011 665-671Comparison of the Effects of Different © 2011 American Society for Parenteral and Enteral NutritionIntravenous Fat Emulsions in Patients 10.1177/0884533611418783 http://ncp.sagepub.com hosted atWith Systemic Inflammatory Response http://online.sagepub.comSyndrome and SepsisHulya Sungurtekin, MD1; Sezai Deg ˘irmenci, MD1;Ugur Sungurtekin, MD, FACS, FACRS (Int)2; Berna Elibol Oguz, MD1;Nuran Sabir, MD3; and Bunyamin Kaptanoglu, MD4Financial disclosure: none declared.Background: In this study, the authors aimed to compare the between the different feeding groups. Sepsis groups who receivedeffects that a medium- and long-chain triglyceride (MCT/LCT) fat MCT/LCT revealed higher grades of liver steatosis by ultrasoundinfusion and a fish oil–based (ω-3) fat infusion for parenteral nutri- on days 7 and 10 (P < .05). Tumor necrosis factor (TNF)–α andtion (PN) had on systemic inflammation, cytokine response, and interleukin (IL)–6 values in sepsis group 1 (S1) were higher thanhepatic steatosis in mixed intensive care unit (ICU) patients. in sepsis group (S2) on day 7, whereas IL-1 values were higher onMethods: This was a single-center, placebo-controlled, randomized days 3, 7, and 10 in group S1 than in group S2. Conversely, IL-10clinical trial in a university hospital. Four patient groups, including values on days 3 and 7 were significantly higher in group S2.systemic inflammatory response syndrome (SIRS) and sepsis Conclusion: Fish oil–based fat emulsions might have anti-inflam-patients, were assigned to receive PN employing the MCT/LCT fat matory and hepatoprotective effects in hyperinflammatory diseaseinfusion or the fish oil–based fat infusion over 7 days. Blood bio- such as sepsis. (Nutr Clin Pract. 2011;26:665-671)chemistry and liver steatosis were evaluated. Results: Twenty sepsisand 20 SIRS patients were included in this study. There was no Keywords:  fish oils; sepsis; systemic inflammatory responsestatistically significant difference in terms of biochemical values syndrome; fatty liver; cytokines; fat emulsions, intravenous;and Acute Physiology and Chronic Health Evaluation II scores parenteral nutritionT oday, with increasing numbers of critically ill the concept of pharmaconutrition is based on the impact patients and advances in medicine, fluids, and of nutrients being greater than just the provision of nutri- electrolyte support, nutrition support, mechanical tion alone.1 In recent times, there has been increasedventilation therapy, and other supports in vital areas have awareness of the fat component of parenteral nutritioncome into prominence in hospitalized patients in the inten- (PN), with the understanding that this supplies not onlysive care unit (ICU). Patients experience a degree of hyper- energy and essential building structure but also bioactiveinflammation, oxidative stress, mitochondrial dysfunction, fatty acid molecules.2 Conventionally used fat emulsionsand cellular immune dysfunction during acute illness. are based solely on soybean oil, which is rich in the ω-6Depending on the severity and duration of these distur- fatty acid linoleic acid, or a 50:50 mix of vegetable oil richbances in metabolism, multiorgan failure and death may in medium-chain saturated fatty acids and soybean oiloccur. To date, nutrition has been accepted as adjunctive (often termed MCT/LCT to indicate the mixture ofcare and not as an active therapeutic approach; however, medium-chain and long-chain triglycerides). More recently, fish oil, which contains very long-chain ω-3 fatty acids, has been introduced into some fat emulsions. The rationale isFrom 1Anesthesiology and Reanimation, 2General Surgery, partly that ω-3 fatty acids act to reduce inflammatory3 Radiology, and 4Biochemistry, Pamukkale University, Denizli, Turkey. responses,3 which may be promoted by an excessive or unbalanced supply of ω-6 fatty acids. Compared with ω-6Address correspondence to: Hulya Sungurtekin, Anesthesiologyand Reanimation, Pamukkale University, 593 Sok No 13 fatty acid–rich vegetable oil, fish oil reduces the metabolicLalekent, Yesilkoy Servergazi, Denizli 20100, Turkey; e-mail: signs of endotoxemia in experimental animals, lowershsungurtekin@yahoo.com. plasma cytokine concentrations, and improves survival.4 665 Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • 666   Nutrition in Clinical Practice / Vol. 26, No. 6, December 2011 During the sepsis process, hepatic dysfunction has a Patients were assigned to receive PN employingcommon manifestation, ranging from mild elevation of either the MCT/LCT fat infusion (Lipofundin 20% 500 mL;serum bilirubin and/or liver enzymes to severe hepatic B. Braun Melsungen AG, Melsungen, Germany) or thefailure.5 The pathophysiology of liver injury is multifacto- fish oil–based ω-3 fat infusion (Omegaven 10% 100 mL;rial and involves metabolic disturbances, drugs, infection, Fresenius Kabi, Linz, Austria) via central venous catheterand a large spectrum of inflammatory mediators in sep- over 7 days. Patients were divided into 4 groups accordingsis.6 Steatosis is also evident in the liver of most septic to both PN methods, which were given to each sepsis andpatients. Koskinos et al7 reported in their study that most SIRS patient. Groups were defined as follows:patients had moderate to severe fatty liver change com-prising 40%–80% of the liver parenchyma. It is known Group 1 (group S1): patients with sepsis were given athat sepsis, bacterial toxins, drugs, and PN may cause 0.6-g/kg MCT/LCT-based fat emulsion (Lipofundinmacrovesicular or microvesicular steatosis,8 and hypoxia 20% 500 mL; B. Braun Melsungen).may play a role in these cases. Alwayn et al,9,10 who Group 2 (group S2): patients with sepsis were given areported that a fish oil–based fat emulsion attenuated 0.6-g/kg ω-3-based fat emulsion, fish oil emulsionfatty liver changes and prevented steatosis in mice, also (Omegaven 10% 100 mL; Fresenius Kabi).demonstrated that fish oil supplementation in mice with Group 3 (group SR1): patients with SIRS were given apreexisting macrovesicular hepatic steatosis resulted in 0.6-g/kg MCT/LCT-based fat emulsion (Lipofundinmarked reversal of steatosis and reduction of liver 20% 500 mL; B. Braun Melsungen).enzymes. Parenteral fish oil may prevent hepatic steatosis Group 4 (group SR2): patients with SIRS were given aand PN-associated cholestasis.11,12 0.6-g/kg ω-3-based fat emulsion, fish oil emulsion This study was designed to compare the effect of both (Omegaven 10% 100 mL; Fresenius Kabi).fish oil–based fat emulsions and MCT/LCT-based fat emul-sions on laboratory parameters such as liver function tests, All fat emulsions were infused over 24 hours. Daily nutri-serum lipid profile, inflammation, degree of liver steatosis, tion composition other than fat was calculated as 20%and cytokine balance in sepsis and SIRS patient groups. glucose (4 g/kg) and 10% arachidonic acid (1.5 g/kg).Because of insufficient reported trials, we evaluated liver The patient’s age, gender, height, and weight weresteatosis with bedside ultrasound in all patients with sepsis recorded at admission. In addition, data were collected onand SIRS who were given different fat emulsions. days 0, 1, 3, 7, and 10. Clinical status (SIRS or sepsis) and Acute Physiology and Chronic Health Evaluation (APACHE)–II score were recorded. Patients’ nasopharyn- Materials and Methods geal temperature, heart rate, respiratory rate, blood pres- sure, and central venous pressure (via jugular venousThis study was a prospective, randomized investigation catheter) were monitored (Datex-Ohmeda modular moni-comparing effects of parenteral fish oil vs MCT/LCT tor, Helsinki, Finland). Laboratory analysis was done in theemulsion administered to ICU patients with sepsis and central laboratory of the university hospital, includingSIRS. The Ethics Committee from the Pamukkale complete blood count; blood levels of urea nitrogen, glu-University Medical Faculty approved the study. Written cose, sodium, potassium, calcium, aspartate amino trans-informed consent was obtained from each patient or ferase (AST), alanine aminotransferase (ALT), γ-glutamylpatient’s relative. transferase (GGT), lactate dehydrogenase (LDH), choles- Forty SIRS and sepsis patients who needed PN were terol, triglycerides (TGs), activated partial thromboplastinenrolled in the study between November 2006 and time, albumin, and C-reative protein. An arterial blood gasJanuary 2008. The American College of Chest Physicians/ was also analyzed. Blood sugar analyses were obtained atSociety of Critical Care Medicine consensus classifica- 8 am for all patients. Blood samples were centrifuged attion was used for diagnosing SIRS and sepsis.13 Sepsis 1500 g for 5 minutes (Rotina 35; Cheftich Zentrifugen,was defined as suspected or proven infection plus SIRS Hennigsdorf, Berlin, Germany), and serum for cytokine(ie, presence of pyrexia, tachycardia, tachypnea, and/or was collected in sterile tubes. Serum samples were storedleukocytosis). Patients younger than 18 years or with at –85°C until assayed in the Nu-6511E (Nuare, Tokyo,known or suspected pregnancy were excluded from the Japan). CRP was measured using a routine turbidimetrystudy. Other exclusion criteria were treatment with major assay (ILAD-900; Instrumentation Laboratory, Milan,immunosuppressive drugs, infection with human immu- Italy); a value >10 mg/L was considered abnormally ele-nodeficiency virus, unstable diabetes mellitus, recent vated. Tumor necrosis factor (TNF)–α, interleukin (IL)–1,myocardial infarction (within past 3 months), stroke, IL-6, and IL-10 were measured using industrially availablesevere hematological diseases, and hypertriglyceridemia cheluminesan kits (IMMULITE BIODPC IMMULITE(ie, plasma triglyceride levels >500 mg/dL). 1000 machine with kits for Immulite TNF-α, Immulite Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • Nutrition and Intravenous Fat Emulsion / Sungurtekin et al   667 Table 1.   Demographic Values of Patients in SIRS and Sepsis Groups Group SR1 Group SR2 Group S1 Group S2 (n = 10) (n = 10) (n = 10) (n = 10) P ValueAge, y 61.40 ± 13.25 54.00 ± 20.54 69.60 ± 13.00 44.40 ± 16.80 NSLength, cm 166.60 ± 6.40 168.00 ± 5.75 162.70 ± 7.30 169.00 ± 7.37 NSBody weight, kg 72.70 ± 9.44 71.70 ± 12.41 74.10 ± 13.53 75.00 ± 13.33 NSGender, M/F, No. 6/4 7/3 4/6 7/3 NSValues reported as mean ± SEM unless otherwise indicated. S, sepsis group; SIRS, systemic inflammatory response syndrome; SR,SIRS group. Table 2.  Patients’ Admission Diagnoses Group SR1 Group SR2 Group S1 Group S21 ARF Postoperative acute abdomen Pneumonia UTI2 COPD Trauma UTE Pneumonia3 ARDS Cardiac arrest Pneumonia Pulmonary tuberculosis4 CHF ACS Pneumonia Peritonitis5 CHF ARDS Pneumonia Pneumonia6 ACS Intoxication Pneumonia Peritonitis7 DKA Postoperative acute abdomen IC abscess Peritonitis8 CHF MI Pneumonia Pneumonia9 ARF ARF Pneumonia Pneumonia10 Trauma ARDS Pneumonia PeritonitisACS, acute coronary syndrome; ARDS, acute respiratory syndrome; ARF, acute renal failure; CHF, congestive heart failure; COPD,chronic obstructive pulmonary disease; DKA, diabetic ketoacidosis; IC, intracranial; MI, myocardial infarction; S, sepsis group;SIRS, systemic inflammatory response syndrome; SR, SIRS group; UTI, urinary tract infection.IL-1, Immulite IL-6, and Immulite IL-10; Medical CRP, TNF-α, IL-1, IL-6, IL-10, and APACHE II scores.Solutions Diagnostics SIEMENS, Surrey, UK; Dade Grade of liver ultrasound values was compared using theBehring Diagnostik, İstanbul, Türkiye). χ2 test. A value of P < .05 was accepted as statistical sig- Initially and on days 1, 3, 7, and 10, the grade of fatty liver nificance. Data are presented as mean ± SEM or percent-was evaluated by the same person with a bedside ultrasound. age.Evaluation of fatty infiltration was classified as follows13: Grade 0: normal echogenicity, with the diaphragm and Results intrahepatic vessel wall normal in appearance Grade I: mild diffuse increase in echogenicity, with There was no significant difference in demographics normal visualization in the intrahepatic vessels and between SIRS and sepsis groups according to the fat diaphragm emulsion (Table 1; P > .05). Admission diagnoses of Grade II: moderate increase in echogenicity, with slight patients are shown in Table 2. impairment in visualizing the hepatic vessels and There was no statistically significant difference in diaphragm terms of WBC count; serum levels of AST, ALT, GGT, or Grade III: significant increase in echogenicity, with poor CRP; and APACHE II scores between different feeding visualization of the hepatic vessels and diaphragm groups of patients with sepsis and SIRS. Serum LDH and TG values were significantly high on days 7 and 10 (P <Statistical analyses were performed using SPSS (version .05) for the SIRS group fed with MCT/LCT (group SR1)15.0; SPSS, Inc, an IBM Company, Chicago, IL). Within but were significantly high only on day 7 in the sepsisthe same diagnostic groups, a paired t test was used for group fed with MCT/LCT (group S1; Table 3).comparisons between age, height, weight, white blood Grade of liver ultrasound values did not differ betweencells (WBCs), AST, ALT, GGT, LDH, cholesterol, TGs, groups of SIRS patients according to the fat type, but Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • 668   Nutrition in Clinical Practice / Vol. 26, No. 6, December 2011 Table 3.   Patients’ Recorded Data Group SR1 Group SR2 Group S1 Group S2APACHE 20.50 ± 3.68 19.80 ± 3.48 28.00 ± 3.80 21.90 ± 5.15AST Initial 91.50 ± 70.31 62.20 ± 53.13 58.10 ± 40.50 46.10 ± 21.44  Day 1 69.40 ± 52.66 68.60 ± 48.50 52.80 ± 43.01 62.00 ± 42.46  Day 3 67.30 ± 68.53 59.9 ± 39.18 49.80 ± 39.80 62.10 ± 33.10  Day 7 44.00 ± 36.20 53.11 ± 39.50 35.60 ± 22.04 60.33 ± 39.32  Day 10 40.66 ± 40.52 52.75 ± 29.12 32.66 ± 28.9 51.83 ± 19.01ALT Initial 62.20 ± 46.43 55.50 ± 48.55 47.20 ± 55.85 57.80 ± 50.86  Day 1 65.10 ± 44.28 69.00 ± 56.84 45.60 ± 47.42 56.80 ± 51.90  Day 3 59.10 ± 44.76 53.80 ± 35.96 42.10 ± 46.74 50.80 ± 42.84  Day 7 45.83 ± 34.30 47.11 ± 33.80 47.40 ± 25.03 49.88 ± 38.58  Day 10 41.00 ± 26.03 48.50 ± 33.93 35.66 ± 31.46 42.00 ± 33.98LDH Initial 412.00 ± 181.49 350.50 ± 187.14 317.60 ± 90.09 301.30 ± 69.09  Day 1 396.00 ± 149.52 288.40 ± 117.45 311.50 ± 102.55 323.40 ± 72.58  Day 3 415.80 ± 151.36 250.40 ± 89.49 346.40 ± 118.63 282.10 ± 50.75  Day 7 440.33 ± 207.45 216.44 ± 63.90* 401.00 ± 156.26 242.22 ± 46.63*  Day 10 481.66 ± 224.82 214.75 ± 59.91* 399.00 ± 80.91 198.50 ± 42.69TG Initial 139.20 ± 51.03 121.30 ± 39.14 158.30 ± 50.43 153.90 ± 57.91  Day 1 148.70 ± 35.50 130.60 ± 27.45 203.90 ± 116.11 150.20 ± 53.59  Day 3 168.30 ± 58.51 131.70 ± 29.18 235.10 ± 155.32 150.30 ± 60.93  Day 7 179.16 ± 58.89 126.88 ± 27.52* 239.20 ± 206.62 140.22 ± 54.61*  Day 10 180.50 ± 53.24 135.75 ± 29.13* 179.33 ± 89.36 143.83 ± 37.96Values reported as mean ± SEM. ALT, alanine aminotransferase; APACHE, Acute Physiology and Chronic Health Evaluation; AST,aspartate aminotransferase; LDH, lactic dehydrogenase; S, sepsis group; SIRS, systemic inflammatory response syndrome; SR, SIRSgroup; TG, triglyceride.*P < .05 (SR1 vs SR2 or S1 vs S2). Table 4.   Liver Ultrasound Grade Values of Patients in the Sepsis Groups Grade 0 Grade 1 Grade 2 Grade 3 P ValueInitial Group S1 4 (40) 5 (50) 1 (10) 0 NS Group S2 3 (30) 7 (70) 0 0Day 1 Group S1 0 7 (70) 3 (30) 0 NS Group S2 3 (30) 6 (60) 1 (10) 0Day 3 Group S1 0 1 (10) 9 (90) 0 NS Group S2 3 (30) 3 (30) 4 (40) 0Day 7 Group S1 0 (25) 0 (18) 3 (60) 2 (40) .047 Group S2 2 (25) 4 (50) 2 (25) 0Day 10 Group S1 0 0 0 3 (10) .029 Group S2 1 (17) 3 (50) 2 (33) 0Values presented as No. (%). S, sepsis group.these values were different in the sepsis groups. ference in cytokine values for different days in the sepsisSpecifically, the septic patients who received MCT/LCT groups. TNF-α and IL-6 values in group S1 were higherfat emulsion had significantly higher grades of fatty liver than in group S2 on day 7, IL-6 values in group S1 wereon ultrasound on days 7 and 10 than did septic patients higher than in group S2 on day 10, and IL-1 values inwho received the fish oil emulsion. group S1 were higher on days 3, 7, and 10 than in group Although there was no statistically significant differ- S2. Conversely, IL-10 values on days 3 and 7 were sig-ence between groups SR1 and SR2 for TNF-α, IL-1, IL-6, nificantly higher in group S2. Details are provided inand IL-10 values, there was a statistically significant dif- Table 5. Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • Nutrition and Intravenous Fat Emulsion / Sungurtekin et al   669 Table 5.   Cytokine Values of Patients in the Sepsis and the other diagnostic criteria of sepsis are plasma CRP Groups >2 SD above the normal value.14 Wang et al16 compared groups of patients with SIRS receiving PN with either a Group S1 Group S2 fish oil–based or a soybean oil–based fat emulsion. They (n = 10) (n = 10) P Value showed no statistically significant difference in WBCTNF-α count and CRP value among both groups. Madeleine17 Initial 28.00 ± 18.29 24.17 ± 30.40 NS evaluated 24 malnourished patients requiring PN who  Day 1 27.16 ± 20.72 23.61 ± 15.30 NS were randomly assigned to receive a daily infusion of  Day 3 33.43 ± 33.12 29.44 ± 24.12 NS either MCT-LCT or LCT but found no statistically sig-  Day 7 34.37 ± 20.82 12.71 ± 6.47 .01 nificant difference between groups for WBC count. Mayer  Day 10 29.63 ± 11.06 8.88 ± 3.28 NS et al18 determined a decrease in WBC count and CRPIL-1 value within days in patients with septic shock who Initial 7.26 ± 4.22 6.31 ± 4.14 NS received the ω-3 and ω-6 fat emulsion, and another group  Day 1 9.00 ± 8.56 6.64 ± 4.74 NS  Day 3 13.45 ± 17.86 6.15 ± 2.52 .003 reported the same result in patients with septic shock and  Day 7 6.20 ± 2.58 5.0 ± 0.0 .014 acute peritonitis who received olive oil, but in both groups,  Day 10 8.00 ± 3.36 5.0 ± 0.0 .006 there were no statistically significant differences.19 In ourIL-6 study, WBC count and CRP were reduced similarly in a Initial 131.50 ± 154.91 126.96 ± 307.16 NS number of days in patients with SIRS and sepsis, but the  Day 1 173.67 ± 316.75 128.20 ± 155.05 NS differences were not statistically significant.  Day 3 253.89 ± 397.04 214.06 ± 309.97 NS Parenteral LCTs, derived from soya oil or safflower oil,  Day 7 502.78 ± 460.89 51.65 ± 53.25 .001 have a high ratio of ω-6 to ω-3 polyunsaturated fatty acids  Day 10 392.53 ± 526.30 31.58 ± 36.44 .002 (PUFAs; 7:1). This has been considered a disadvantageIL-10 that might encourage the overproduction of proinflamma- Initial 21.78 ± 21.34 26.66 ± 16.26 NS tory eicosanoids and increase oxidative stress in clinical  Day 1 24.62 ± 42.51 58.65 ± 71.52 NS  Day 3 25.47 ± 15.68 51.83 ± 95.44 .047 situations (eg, sepsis and trauma) that are already domi-  Day 7 20.58 ± 10.80 46.46 ± 31.98 .001 nated by imbalanced immune responses. Fish oil contain-  Day 10 24.56 ± 8.55 42.52 ± 30.69 NS ing PN has been used in surgical patients demonstrating possible improvements in immune function and reducedValues reported as mean ± SEM. IL, interleukin; S, sepsis; inflammation, which may lead to a shorter stay in the ICUTNF-α, tumor necrosis factor–α. and in the hospital.20,21 Although not many studies have been reported about fish oil–containing fat emulsions in the ICU, 2 studies by Mayer et al15,18 described diminished inflammation, including reduced TNF-α, IL-1β, IL-6, IL-8, Discussion and IL-10 production by cultured monocytes, in septic patients receiving a soybean oil–fish oil mix compared toSIRS with infection is defined as sepsis.14 Hemodynamic, those receiving soybean oil alone, which did not reveal anymetabolic, and immune changes in the organism during clinical outcomes. Heller et al22 studied different patientsepsis occur through mediators and cytokines, which take groups with abdominal sepsis, multiple trauma, and severepart in intracellular signal transduction. Although some head injury with a parenteral ω-3 infusion. They found amediators have a proinflammatory response (TNF-α, significantly lower rate of infection and shorter lengths ofIL-1, IL-8), others have an anti-inflammatory response ICU and hospital stays in those patients receiving more(IL-4, IL-10). Diets with a specific fat composition may than 0.05 g fish oil/kg/d. Nevertheless, mortality was sig-manipulate immunologic and inflammatory events. nificantly decreased in those patients who received moreEicosanoids have been involved in both proinflammatory than 0.1 g fish oil/kg/d. These data strongly suggest aand anti-inflammatory events in sepsis. The most impor- clinical benefit from the inclusion of long-chain ω-3tant members of the ω-3 fatty acids are eicosapentaenoic PUFAs in PN given to critically ill patients. These resultsacid and docosahexaenoic acid. Major sources of ω-3 were also supported by using fish oil in PN in severe pan-fatty acids are cold-water fish and seal meat, and ω-3 fatty creatitis, leading to decreased inflammatory response,acids may serve as alternative lipid precursors for both improved respiratory function, and shortened continuouscyclooxygenase and lipoxygenase pathways.15 Diet fat renal replacement therapy time.16 Friesecke et al23 exam-composition may also affect hepatobiliary function. In ined the effects of fish oil on 166 consecutive patientsthis study, we evaluated different fat nutrition in septic admitted to the ICU who were randomly assigned toand SIRS patients. receive either an MCT/LCT emulsion with an ω-3/ω-6 One of the diagnostic criteria of SIRS is abnormal PUFA ratio of 1:7 or the same emulsion supplementedWBC count (>12,000/µL or <4000/µL or >10% bands), with fish oil, with an ω-3/ω-6 PUFA ratio of 1:2. They Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • 670   Nutrition in Clinical Practice / Vol. 26, No. 6, December 2011reported no differences between MCT–soybean oil and significantly high in both SIRS and sepsis groups fed withMCT–soybean oil–fish oil given over 7 days in medical MCT/LCT on day 7, and an increase of this value alsoICU patients in several outcomes, including immune was established on day 10 in the SIRS groups.markers, inflammatory markers, bleeding, ventilation The manufacturer (Fresenius Kabi) does not recom-requirement, number of infections and length of ICU stay, mend fish oil–based fat emulsions as a nutrition mono-or mortality. Therefore, there is inadequate and conflicting therapy. Theoretically, fish oils may cause oxidative stress,information on the influence of fish oil–containing PN on but lipid peroxidation products do not accumulate in livermarkers of inflammation and on clinical end points in sep- tissue after parenteral fish oil administration. On thetic ICU patients. In our study, sepsis and SIRS patients fed other hand, parenteral fish oils are enriched with highwith MCT/LCT had higher proinflammatory cytokine levels of the antioxidant a-tocopherol (150–296 mg/mL)(TNF-α, IL-1, and IL-6) values and lower anti-inflamma- to counteract this possible oxidative risk. The other waytory cytokine (IL-10) values than patients fed with fish oil, to minimize oxidative stress is the partial replacement ofbut statistical significance was seen only at the middle and PUFA-rich oils with alternative fatty acid sources, such asend of the study periods in the septic groups. As well, the MCTs, which are more resistant to oxidative damage.results of our study support that fish oil may be signifi- MCT/LCT emulsion includes 100 mg/mL a-tocopherol.cantly more effective than MCT/LCT fat emulsion, espe- In our study, the small differences in vitamin E content incially in infectious conditions. the 2 emulsions did not affect our findings. The other PN is life saving in patients unable to absorb adequate concern about monotherapy with fish oil is EFAD. Inenteral nutrients, usually secondary to insufficient intesti- humans, biochemical changes associated with EFAD cannal length or function. However, prolonged use of PN has occur in infants in a few days and within several weeks inbeen associated with hepatobiliary dysfunction, commonly older children and adults. EFAD typically occurs whenreferred to as PN-associated liver disease (PNALD).24 <1%–2% of total calories are provided from essential fattyPNALD is a spectrum of PN-associated hepatobiliary dis- acids. Adults have a larger storage of essential fatty acids,orders, ranging from simple steatosis to cholestasis, chole- and symptoms of EFAD such as dry skin, alopecia, andlithiasis, hepatic fibrosis, and ultimately progression to dermatitis rarely occur.27 Gura et al28 first described 2cirrhosis, portal hypertension, and end-stage liver disease. infants with PNALD who were successfully treated withIntrahepatic cholestasis is most often found in neonates a fish oil–based fat emulsion, as demonstrated by nor-and infants, whereas steatosis is the most common finding malization of direct bilirubin levels from >2 mg/dL toin adults.25 Septic episodes are also one of the risk factors normal. Their article showed that parenteral fish oilfor the development of PNALD.25 PN is typically applied in monotherapy at a dosage of 1 g/kg/d did not cause EFAD,a mixture with a parenteral fat emulsion to provide a even in a patient who received no enteral nutrition. Pudersource of nonprotein calories and prevent essential fatty et al29 did an open-label trial of a pure fish oil–based fatacid deficiency (EFAD). Proinflammatory metabolites of emulsion in 42 infants with short bowel syndrome whoω-6 fatty acids,24 decreased hepatic clearance of the paren- developed cholestasis (serum direct bilirubin >2 mg/dL)teral lipid,26 and phytosterols found in soybean-derived while receiving a soybean oil–based fat emulsion. Findingslipids have been shown to be associated with PNALD. revealed that fish oil–based fat emulsion was well toler-Fish oil–based emulsions address these problems: ω-3 ated and may be effective in treating PNALD whilefatty acid metabolites are less involved in the inflamma- reducing mortality and organ transplantation rates intory response than are ω-6 fatty acid metabolites, and children with short bowel syndrome. In another study, deanimal models have shown that parenteral fish oil does Meijer et al30 evaluated 10 PN-dependent pediatricnot impair biliary secretion and may prevent steatosis.9,12 patients dosed at 1 g/kg/d on fish oil monotherapy forAraya et al,12 who studied 11 control subjects and 19 evidence of EFAD, and fish oil–based fat emulsions werepatients with nonalcoholic fatty liver disease, reported found to contain a sufficient amount of essential fattythat in patients with nonalcoholic fatty liver disease, the acids to prevent biochemical or clinical EFAD and main-levels of PUFAs in the liver, total lipids, triacylglycerols tain growth in PN-dependent patients. These authors(triglycerides), and phospholipids in relation to those in followed patients for 18.4 weeks, and no other sideadipose tissue and the hepatic indexes related to oxidative effects developed from using monotherapy in the studystress were factors that contributed to hepatic steatosis, groups. Although there is no information about dosing ofwhich has been scored histologically as absent (0), mild fish oil monotherapy to prevent EFAD in adults, we used(1), moderate (2), and severe (3). We used ultrasono- fish oil 0.6 g/kg/d during the study, which was less thangraphic evaluation for assessing liver steatosis and deter- the previously reported doses in infants. No other sidemined fatty liver in septic patients given MCT/LCT on the effects developed from using the monotherapy in ourlast day of PN (day 7) and on day 10, but there was no study. In our study, patients were given study nutrient fordifference between SIRS patients according to their fat 7 days. We suggest laboratory analysis for longer periodscomposition of PN. Moreover, triglyceride values were for this dose of fish oil or nutrition in terms of EFAD. Downloaded from ncp.sagepub.com by Javier Restrepo on January 9, 2013
    • Nutrition and Intravenous Fat Emulsion / Sungurtekin et al   671 This study, which evaluated fish oil monotherapy in patients with nonalcoholic fatty liver disease. Clin Sci (Lond).SIRS and septic patients, had several limitations. First, 2004;106:635-643. 13. Wilson SR, Rosen IE, Chin-Sang HB, Arenson AM. Fatty infiltra-the sample size was relatively small because of cost. tion of the liver: an imaging challenge. J Can Assoc Radiol. 1982;Other similar studies in the literature had approximately 33(4):227-232.the same number of patients. However, despite the small 14. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/sample size, significant effects on plasma cytokines and ACCP/ATS/SIS International Sepsis Definitions Conference. Crithepatic ultrasound values were observed. Also, the labora- Care Med. 2003;31(4):1250-1256. 15. Mayer K, Gokorsch S, Fegbeutel C, Hattar K. Parenteral nutritiontory examination (triene:tetraene ratio, which may be with fish oil modulates cytokine response in patients with sepsis.used as a diagnostic marker for EFAD) may be done for Am J Respir Crit Care Med. 2003;167(10):1321-1328.objective results for EFAD. The other concern was the 16. Wang X, Li W, Li N, Li J. ω 3 Fatty acids–supplemented parenteraldose of fish oil. We used a dose that was less than the nutrition decreases hyperinflammatory response and attenuatesdose used in other monotherapy studies.28-30 Our study systemic disease sequelae in severe acute pancreatitis: a rand- omized and controlled study. JPEN J Parenter Enteral Nutr.patients (septic and SIRS patients), however, were differ- 2008;32:236-241.ent from patients in other monotherapy studies, and it 17. Madeleine JB. Hematological and biochemical effects of paren-was difficult to decide a dose for septic patients because teral nutrition with medium-chain triglycerides: comparison withthere is no recommended dose for these patients receiv- long-chain triglycerides. Am Soc Clin Nutr. 1991;53:916-922.ing monotherapy. 18. Mayer K, Fegbeutel C, Hattar K, et al. ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: In conclusion, fish oil–based fat emulsions might impact on plasma fatty acids and lipid mediator generation.have anti-inflammatory and hepatoprotective effects in Intensive Care Med. 2003;29:1472-1481.hyperinflammatory disease such as sepsis. The optimal 19. Reimund JM, Arondel Y, Joly F, Messing B, Duclos B, Baumann R.ω-6/ω-3 ratio remains to be defined, and a well-designed Potential usefulness of olive oil–based lipid emulsions in selectedprospective randomized controlled trial is necessary to situations of home parenteral nutrition–associated liver disease. Clin Nutr. 2004;23:1418-1425.evaluate the safety and efficacy of ω-3 fatty acids for PN. 20. Weiss G, Meyer F, Matthies B, Pross M, Koenig W, Lippert H. Immunomodulation by perioperative administration of n-3 fatty acids. Br J Nutr. 2002;87:S89-S94. References 21. Wachtler P, Konig W, Senkal M, Kemen M, Koller M. Influence of a total parenteral nutrition enriched with ω-3 fatty acids on leuko- 1. Jones NE, Heyland DK. Pharmaconutrition: a new emerging para- triene synthesis of peripheral leukocytes and systemic cytokine digm. Curr Opin Gastroenterol. 2008;24(2):215-222. levels in patients with major surgery. J Trauma. 1997;42:191-198. 2. Furst P, Kuhn KS. 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