Intensive Care Med (1998) 24: 1029±1033 Ó Springer-Verlag 1998 ORIGINAL V.Smirniotis Long chain versus medium chain G.Kostopanagiotou J.Vassiliou lipids in patients with ARDS: N.Arkadopoulos P.Vassiliou effects on pulmonary haemodynamics A.Datsis E.Kourias and gas exchange Abstract Objective: To compare tion was only associated with an ele- Received: 23 July 1997 Accepted: 15 May 1998 pulmonary haemodynamic and gas vation of oxygen consumption exchange alterations in septic pa- (VO2) from 329 ± 14 to 396 ± 12 ml/ tients with ARDS receiving long- min. During lipid infusion group 1 chain triglycerides (LCT) versus patients presented higher Qva/Qt medium-chain triglycerides (MCT). (37% ± 6% vs 25 % ± 4%), MPAP Design: Prospective, randomised, (33 ± 4vs27±3 mmHg) and VO2 clinical study. (359 ± 11 vs 396 ± 12 ml/min) and Setting: Surgical ICU patients in a lower PaO2/FIO2 (180 ± 35 vs University Hospital. 235 ± 30) values compared to Patients: Twenty-one septic patients group 2. with ARDS were randomly assigned Conclusion: In conclusion, we have to receive 50 % of their non-protein shown that, in septic patients with caloric requirements as either 20 % respiratory failure, LCT administra- LCT (group 1, n = 10) or 20% 1 : 1 tion was associated with more sig- mixture of LCT/MCT (group 2, nificant changes of Qva/Qt, MPAP n = 11). and PaO2/FIO2 compared to infu- Intervention: Intravenous infusion of sion of an LCT/MCT 1 : 1 emulsion. V.Smirniotis ()) × G.Kostopanagiotou × LCT and LCT/MCT combinations at Clinically, these transient alterations J.Vassiliou × N.Arkadopoulos × a rate of 12 g × h1. might cause serious problems in pa- P.Vassiliou × A.Datsis × E.Kourias 2nd Department of Surgery, Measurements and results: The LCT tients with marginal arterial oxyge- University of Athens Medical School, infusion was associated with an in- nation and cardio-respiratory im- ªAreteionº Hospital, crease of pulmonary venous admix- pairment. Athens, Greece ture (Qva/Qt) from 24% ± 5%to 37% ± 6%, an increase of mean Key words Fat emulsion × Medium Mailing address: pulmonary artery pressure (MPAP) chain triglycerides Long chain 22 Hanioti St. GR-15452, Athens, Greece × Tel.: + 30-1-728-6000 from 25 ± 5to33±4 mmHg and de- triglycerides × Pulmonary Fax: +30-1-721-1007 crease of PaO2/FIO2 from 240 ± 30 haemodynamics × Gas exchange × email: [email protected] to 180 ± 35. LCT/MCT administra- ARDS Introduction cleared from the serum and do not contribute to the adi- pose stores [13]. They are independent of carnitine acyl- Many studies have been carried out to examine the me- transferase and are easily transferred into mitochondria tabolic properties of long chain triglyceride (LCT) for beta-oxidation [15]. MCTs may also have a greater emulsion [1±6]. Recently, medium chain triglyceride nitrogen-sparing effect than LCTs [12]. In addition, (MCT) emulsion have emerged as an alternative energy LCTs have been shown to decrease arterial oxygen ten- source which may have significant advantages over stan- sion (PaO2) and increase pulmonary venous admixture dard LCT formulas [3±4, 6±15]. MCTs are rapidly (Qva/Qt) and mean pulmonary artery pressure (MPAP) 1030 Table 1 Clinical characteristics of the patients Group 1 (LCT) Group 2 (LCT/MCT) Sex/ Weight (kg)/ Cause Sex/ Weight (kg)/ Cause Age (year) Height (cm) Age (year) Weight (cm) M/65 70/175 Oesophagectomy M/75 70/180 Oesophagectomy M/45 54/170 Necrotising pancreatitis M/40 68/170 Necrotising pancreatitis F/68 65/170 Small bowel necrosis M/56 72/175 Colon resection M/42 70/175 Colon resection F/60 60/160 Colon resection F/62 60/155 Colon resection F/70 71/165 Rupture of aortic aneurysm M/72 58/165 Necrotising pancreatitis M/40 63/170 Colon resection F/38 68/170 Pancreatic resection M/48 73/165 Pancreatic resection F/65 71/165 Necrotising pancreatitis M/62 70/180 Multiple trauma M/45 52/180 Pancreatic resection F/72 56/180 Splenectomy M/48 68/181 Necrotising pancreatitis M/68 55/160 Necrotising pancreatitis F/42 60/170 Necrotising pancreatitis [1, 5, 7, 13, 16]. These side effects appear to be aggravat- 2. Mean pulmonary artery pressure (MPAP), pulmonary artery oc- ed by the co-existence of sepsis [1, 8, 15]. LCT/MCT clusion pressure (PAOP), and mean systemic arterial pressure emulsions contain less linoleic, linolenic and arachido- (MAP) were measured using a Swan-Ganz catheter (Opticath P7110, Abbott Critical Care Systems, North Chicago, Ill.) and a nic acid compared to pure LCTs [17±18]. These differen- radial artery catheter (20G, Arrow, Reading, Pa.). ces may be important because the aforementioned acids 3. Thermodilution cardiac output was calculated from three elec- are precursors of prostaglandins and other eicosanoids, tronically integrated temperature decay curves, generated after which have been shown to affect pulmonary haemody- indicator injection (monitor: Horizon 2000, Mennen Medical namics, gas exchange and intrapulmonary shunt quo- Ltd, Rehovot, Israel). tient [17, 19±21]. 4. Qva/Qt and oxygen consumption (VO2) were calculated via standard formulas. We hypothesised that, in patients suffering from in- tra-abdominal sepsis complicated by ARDS, LCT/ MCT mixtures may be associated with less prominent Study design changes of pulmonary haemodynamic and gas exchange parameters compared to pure LCT emulsion. Twenty-one consecutive post-operative ICU admissions with sep- sis-related ARDS were randomly assigned to one of two groups: group 1 (n = 10) or group 2 (n = 11) (Table 1). In group 1, 50% of non-protein caloric requirements was infused as a 20% LCT emul- Material and methods sion (Intralipid, Pharmacia). In group 2, the corresponding energy needs were administered as a 20% mixture of LCTs/MCTs (Lipo- All procedures were conducted in full compliance with the stan- fundin MCT/LCT, B.Braun Melsungen AG, Melsungen, Ger- dards of the Institutional Committee for the Protection of Human many). Fat emulsion was intravenously infused over an 8-h period Subjects, in accordance with the Helsinki Declaration of 1975. using a pump (Life Care Pump, model 4, Abbott Laboratories, Our survey included patients with respiratory failure due to in- North Chicago, Ill.) at a rate of 12 g × h1. The remaining 50% of tra-abdominal sepsis (Table 1). All patients met the standard cri- the non-protein energy requirements were covered with glucose, teria for diagnosis of ARDS, presenting lung injury scores of infused continuously i.v. over a 24-h period. more than 2.5 [22]. Sepsis was confirmed by clinical and laboratory Measurements were obtained on the third post-operative day findings as well as positive blood cultures [23]. Patients with pre- at three time points: existing cardiovascular, respiratory, renal or metabolic diseases were excluded from the study. Mechanical ventilation was insti- 1. 30 min before the 8-h lipid infusion was started (before), tuted via an endotracheal tube using a volume-cycled ventilator 2. 30 min before the infusion was completed (during) and (Puritan 7200 Series, Bennett Corporation, Carlsbad, Calif.) and 3. 4 h following suspension of lipid infusion (after). was titrated to maintain arterial PCO2 within the normal range. Pulmonary end-expiratory pressure (PEEP) levels were kept at Each sample was the average of three measurements. No further 8±15 cm H2O (12 ± 2; mean ± SD). All patients received low mole- therapeutic interventions were undertaken during the study peri- cular weight heparin for the prevention of deep vein thrombosis od. and low-dose (2 mg × kg1×min1 i.v.) dopamine. All patients re- ceived total parenteral nutrition and antibiotics. Sedation was maintained with fentanyl (100±200 mg × h1 i.v.) and midazolam Statistical analysis (1±2 mg × h1i.v.). The following measurements were obtained: The comparison of measurements in each cohort was performed 1. Arterial PO2, PCO2, haemoglobin concentration and haemoglo- using a non-parametric Wilcoxon signed rank test for paired data. bin oxygen saturation were measured using a blood gas analyser Mann-Whitney-U test was used to compare group 1 versus (ABL 300, Radiometer Medical A/S, Copenhagen, Denmark). group 2. Statistical significance was accepted if p was less than 0.05. 1031 Table 2 Pulmonary haemodynamic parameters during lipid infu- occlusion pressure, CO cardiac output, Before 30 min before the sion (HR heart rate, MPAP mean pulmonary artery pressure, infusion was started, During 30 min before the infusion was com- MAP mean systemic arterial pressure, PAOP pulmonary artery pleted, After 4 h following suspension of infusion) Group 1 (LCT) Group 2 (LCT/MCT) Before During After Before During After HR (/min) 125 ± 12 110 ± 10 115 ± 8 115 ± 10 126 ± 10 118 ± 8 MPAP (mmHg) 25 ± 533±4a,b 26 ± 626±627±325±5 MAP (mmHg) 90 ± 20 85 ± 15 90 ± 15 90 ± 20 95 ± 15 80 ± 15 PAOP (mmHg) 11 ± 213±210±211±29±310±3 CO (L/min) 8.6 ± 2.5 9 ± 2 9.5 ± 2.5 9.6 ± 2.1 10.5 ± 1.5 8.9 ± 2 Values are presented as mean ± SD a p K 0.05 vs before and after lipid infusion for the same cohort (Wilcoxon signed rank test) b p K 0.05 vs group 2 during lipid infusion (Mann-Whitney U-test) Table 3 Gas exchange parameters during lipid infusion (PaO2 arterial PO2, Qva/Qt pulmonary venous admixture, FIO2 fractional in- spired oxygen, VO2 oxygen consumption) Group 1 (LCT) Group 2 (LCT/MCT) Before During After Before During After pH 7.36 ± 0.7 7.35 ± 0.9 7.36 ± 0.8 7.38 ± 0.2 7.35 ± 0.8 7.35 ± 0.9 a,b Qva/Qt (%) 24 ± 537±625 ± 423±525±424±4 a,b PaO2/FIO2 240 ± 30 180 ± 35 235 ± 35 240 ± 30 235 ± 30 235 ± 25 b a VO2 (ml/min) 333 ± 12 359 ± 11 338 ± 10 329 ± 14 396 ± 12 336 ± 13 Values are presented as mean ± SD a p < 0.05 vs before and after infusion in the same cohort b p < 0.05 vs the other cohort during infusion time Results During lipid infusion, group 1 patients presented higher Qva/Qt and MPAP as well as lower PaO2/FIO2 The data are expressed as means ± SD.