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Nutritional status was assessed, as usual, by anthropometric, ... Serum albumin, transferrin and peripheral ... spontaneous tidal volume >5 mL/kg bw, max-.

RIANIMAZIONE ARTICOLI ORIGINALI MINERVA ANESTESIOL 2007;73:65-76

M I C N O E P RV Y R A IG M H ED T® I C A

Parenteral nutrition in ventilated patients with chronic obstructive pulmonary disease: long chain vs medium chain triglycerides G. IOVINELLI, F. MARINANGELI, A. CICCONE, A. CICCOZZI M. LEONARDIS, A. PALADINI, G. VARRASSI

Aim. The aim of this study was to assess the usefulness of a lipid formulation containing a physical mixture of medium (MCT) and long chain triglycerides (LCT) compared with a long chain triglycerides emulsion in patients affected by chronic obstructive pulmonary disease with acute respiratory failure. Methods. Twenty-four patients requiring mechanical ventilation were randomly selected in 2 groups and received total parenteral nutrition. Twelve patients received a MCT/LCT emulsion (50:50), the others used a 100% LCT emulsion. Nutritional status, metabolic rate, time of ventilatory support and weaning were evaluated. Results. Both groups showed an improvement of all nutritional parameters evaluated; oxygen uptake, carbon dioxide output and respiratory gas exchange ratio were similar in both groups. The duration of mechanical ventilation was not significantly different; however, the time of weaning in the MCT/LCT group was significantly shorter. The longer weaning time in the LCT group patients could be related to vasoactive intermediates deriving from long chain fatty acids. The T-cell subsets, which were evaluated for both groups, showed a significant decrease of T helper-T suppressor ratio in the LCT group. Conclusion. MCT/LCT emulsion is an effective lipid supplementation and should be considered the therapy of choice in COPD patients; Received on July 9, 2005. Accepted for publication on October 15, 2006.

Address reprint requests to: F. Marinangeli, MD, Cattedra di Anestesia e Rianimazione, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy. E-mail: [email protected]

Vol. 73, N. 1-2

Department of Anesthesiology Intensive Care and Pain Management University of L’Aquila, L’Aquila, Italy

however, the relationship between lipid emulsions administered and length of weaning requires further investigations. Key words: Pulmonary disease, chronic obstructive - Parenteral nutrition - Lipids - Respiration, artificial.

A

balanced nutritional support is believed to be useful in patients affected by chronic obstructive pulmonary disease (COPD) undergoing ventilatory support. In fact, it may improve functional respiratory characteristics and consequently influence the weaning from mechanical ventilation.1, 2 Moreover, 30-50% of COPD hospitalized patients are malnourished and present a hypercatabolic state with a decrease of diaphragmatic muscle strength, decrease in ventilatory drive, increased risk of pneumonia and lung phospholipids metabolism alteration.3 Malnutrition is more frequent and more severe in COPD patients with acute respiratory failure requiring ventilatory support.3 In this setting, enteral nutrition is generally preferred but it requires a healthy and working gastroenteric apparatus and a period of start regimen.

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45 mmHg. An inspired oxygen concentration of 30% or higher was used to maintain PaO2 above 70 mmHg. The other ventilator settings were chosen for optimum patient care without any regard to this study. Patients were sedated with midazolam administered in a loading dose of 0.1 mg/kg bw over 30 s followed by a continuous intravenous infusion (0.05 to 0.15 mg/kg bw/h). Doses of midazolam were modified by the attending physician in order to obtain patient’s synchrony with the ventilator. Nutritional status was assessed, as usual, by anthropometric, biohumoral and immunologic parameters. Body weight was expressed as percentage of ideal body weight in accordance to a reference value based on height, sex and frame size of the Metropolitan Life Insurance Company Weight Standards.6 Triceps skinfold thickness was measured with a skinfold caliper on the posterior surface of the left arm. Mid-arm circumference of the same upper arm was measured. Biochemical data were evaluated before the beginning of the nutritional support and then every 5 days. Serum albumin, transferrin and peripheral blood lymphocyte count were used to evaluate the visceral protein stores. The markers used to evaluate the nutritional status, in the acute phase, were chosen because of their extensive use in many studies.7, 8 However, the evaluation of the nutritional status wasn’t the main goal of the study. Total water and electrolytes were adjusted daily for each patient as needed. Each patient received total parenteral nutrition (TPN) through central venous subclavian access. Caloric requirements were initially based on the Harris-Benedict formula for resting energy expenditure (REE) and an additional 30% stress factor was taken into account. Fifty per cent of the non protein calories was given as lipids and the protein intake was standardized as 1g/kg bw/day. The protein intake is consistent with that reported by several authors.9, 10 Twelve patients (group A) randomly selected, received a lipid emulsion containing 50% medium chain triglycerides (MCT) and 50% long chain triglycerides (LCT; Lipofundin® MCT/LCT, B. Braun Melsungen AG, Melsun-

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Moreover, it is frequently followed by several problems such as intolerance to customary volumes of food in the stomach, possible aspiration of gastric content or diarrhea which require a reduction or even a cessation of the nutritional support. Total parenteral nutrition ensures quick and adequate fuel administration with an earlier positive nitrogen balance, so it is often chosen in these situations.4 To prevent the increased CO2 production associated with high carbohydrate intake, the provision of 30% to 50% of caloric intake as fat is recommended.5 This investigation was designed to compare the effects and usefulness of 2 different intravenous lipid formulations: long chain triglycerides (LCT) vs medium chain-long chain triglycerides mixture (MCT/LCT) in COPD patients requiring ventilatory support. Materials and methods

This investigation was approved by the Institutional Ethic Committee. Twenty-four patients (19 men and 5 women) with COPD requiring mechanical ventilation (MV) were included in the study. Exclusion criteria were: heart failure (class III or IV of NYHA), renal failure (serum creatinine >3.5 mg/dL), liver failure (protein concentration 5 mg/dL), thyroid diseases, cancer and tuberculosis. On admission to the Intensive Care Unit (ICU), the patients were evaluated by APACHE II scale and during the first 24-48 h were strictly observed for their hemodynamic and respiratory variables. Arterial blood pH below 7.20, PaCO2 above 90 mmHg, PaO2 below 60 mmHg despite O2 administration by face mask (4 L/min), mental obtundation and signs of inspiratory muscle fatigue were considered indications for mechanical ventilation. Ventilation was provided through an endotracheal tube by a Servo C Siemens ventilatory system. Controlled ventilation was the first mode used in all the patients. A tidal volume of 8-10 mL/kg body weight (bw) was used with a constant inspiratory flow rate. The respiratory rate was adjusted to maintain PaCO2 between 35 and

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endotracheal tube removed. If the patient showed signs of distress he/she was designated to wean by pressure support ventilation (PSV) that was set at a level of 20±4.3 cm H2O and then reduced at least twice a day by 2 cm H2O. Patients who tolerated PSV at a setting of 5 cm H2O for 2 h without signs of distress were switched to spontaneous breathing and then extubated. Success in weaning was defined as spontaneous breathing for 24 consecutive hours. The aim of the study was to evaluate the influence of different nutritional support on weaning in ventilated patients. The study was considered concluded when the patient was successfully weaned. However, the study was stopped after 15 days of ventilation because of failed weaning.

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gen, Germany), the others (group B) received a 100% LCT emulsion (Intralipid®). Each nutritional regimen was administered as an “all in one” bag by continuous 24 h infusion. The plasma triglycerides measurement was performed by an enzymatic colorimetric method (Aeroset - Abbott®). Nitrogen balance was calculated as the nitrogen intake (g/day) minus the urinary urea nitrogen output multiplied by 1.25 to correct for non urea nitrogen components plus 4 g for daily insensible losses. Monitoring of the nutritional support was carried out daily by routine laboratory and arterial blood gas tests. All measurements were performed at similar times of the day. Metabolic effects of nutritional support where checked every day using a metabolic gas monitor (Deltatrac® Datex) in order to optimize nutritional management. When the patient was hemodynamically stable and requiring a fractional inspired oxygen (FiO2) 60 mmHg with FiO2 ≥0.4, respiratory rate 5 mL/kg bw, maximal inspiratory pressure ≤20 cm H2O and body temperature lower than 38.5 °C. Short spontaneous breathing periods of 30 min were performed through a T tube circuit with a FiO2 similar to that used during MV. If these spontaneous breathing trials appeared well tolerated (maximal inspiratory pressure 5 mL/kg bw and respiratory rate less than 35 breaths per minute) a spontaneous breathing period of at least 3 h was allowed. When no sign of respiratory or circulatory distress occurred (respiratory rate >35 breaths per minute, SaO2 140 beats per minute, systolic blood pressure >180 mmHg or 0.05). . . Table II shows the mean values of VCO2, VO2 and RQ evaluated daily during MV and weaning. After nutritional support, plasma triglycerides mean values rose in both groups when compared to basal values. This increase was significantly higher in group B patients: 124±36 mg/dL for group A vs 180±49 mg/dL for group B (P0.05). Mechanical ventilation was started between the first and the second day following admission in ICU. The mean time of MV in group B was greater than in group A, but the difference was not statistically significant (322±85 h vs 254±73 of mechanical ventilation). Two patients in group A and 1 in

TABLE I.—Patients’ nutritional parameters at the entry in ICU and during the study. Data are expressed as mean ± SD. Group

Day 1 (T0)

Day 5 (T1)

Day 10 (T2)

Day 15 (T3)

Percentual of ideal weight

A (n=7) B (n=7)

89±10 95±15

90±9 96±14

91±10 96±12

92±7 96±14

Triceps skinfold (% of normal) (normal: men, 12.5 mm; women, 16.5 mm)

A (n=7) B (n=7)

85±21 92±9

86±17 94±9

87±16 94±7

87±13 94±6

Mid-arm muscle circumference (normal: men, 25.3 mm; women, 23.2 mm)

A (n=7) B (n=7)

85±10 93±11

87±10 94±11

87±9 95±10

86±8 96±10

Serum albumin (g/dL)

A (n=7) B (n=7)

3.6±0.8 3.8±0.4

3.7±0.7 3.7±0.3

3.8±0.7 3.8±0.4

3.8±0.6 3.9±0.5

Transferrin (mg/dL)

A (n=7) B (n=7)

189±27 189±31

193±29 191±29

194±27 192±30

194±25 195±38

Total lymphocytes (×mm3)

A (n=7) B (n=7)

1893±518 1816±225

1941±470 1871±219

2006±406 1877±231

2046±373 2000±231

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IOVINELLI

. . TABLE II.—Mean values of VCO2, VO2 and RQ during MV and weaning. Data are expressed as mean±SD. . VO2 (mL/min) (MV)

RQ (MV)

. VCO2 (mL/min) (Weaning)

. VO2 (mL/min) (Weaning)

RQ (mL/min) bb (Weaning)

201±25 206±33

179±18 188±27

0.90 0.91

207±27 214±30

193±23 198±26

0.93 0.92

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Group A Group B

. VCO2 (mL/min) (MV)

Hyperglycemia was the most frequent nutrition-related complication. Serum glucose >250 mg/dL, requiring incremental doses of insulin, occurred in 5 patients of group A and 3 of group B. One patient of group A and 2 patients of group B had catheter-related complications: occlusion or displacement which required catheter removal and substitution.

Group A (n=7) Group B (n=7)

TO

TE

99±54 103±67

124±36 180±49*

* Significantly different from group A (P0,05). Il valore medio APACHE II, al momento dell’ingresso, era 19±2 per il gruppo A e 19±3 per il gruppo B (P>0,05). La ventilazione meccanica (VM) è stata iniziata fra il primo ed il secondo giorno dopo l’ingresso in ICU. La durata della VM nel gruppo B è stata maggiore che nel gruppo A, ma la differenza non è risultata statisticamente significativa (322±85 ore vs 254±73 ore). Due pazienti del gruppo A ed 1 del gruppo B sono stati estubati dopo il periodo stabilito di 3 ore di respirazione spontanea, gli altri hanno mostrato segni di distress respiratorio e circolatorio e sono stati svezzati con supporto di pressione. I risultati evidenziano un periodo di svezzamento significativamente più breve nel gruppo A (52±36 h vs 127±73 h, P0,05). La Tabella I mostra i parametri nutrizionali valutati nel primo giorno di permanenza in ICU (T0) e dopo 5, 10 e 15 giorni (rispettivamente T1, T2 e T3). Questi dati indicano uno stato nutrizionale compromesso all’arrivo dei pazienti in ICU. Successivamente i parametri nutrizionali sono lentamente migliorati, come mostrato dall’aumento dei valori di transferrina ed albumina plasmatica alla fine dello studio. L’urea, misurata all’ingresso in ICU, era pari a 118±37 mg/kg bw/d nel gruppo A e 94±30 mg/kg bw/d nel gruppo B (P>0,05). La Tabella II mostra i valori medi di VCO2, VO2 e RQ rilevati quotidianamente durante la VM e lo svezzamento. Dopo supporto nutrizionale, i valori medi dei trigliceridi plasmatici sono saliti in entrambi i gruppi, rispetto ai valori basali. Questo incremento è risultato significativamente più alto nei pazienti del gruppo B: 124±36 mg/dl per il gruppo A vs 180±49 mg/dl per il gruppo B (P250 mg/dl, che ha richiesto incrementi nelle dosi di insulina, si è verificata in 5 pazienti del gruppo A ed in 3 pazienti del gruppo B. Un paziente del gruppo A e 2 pazienti del gruppo B hanno presentato complicanze legate al catetere: occlusione o dislocazione che hanno richiesto rimozione e sostituzione del catetere stesso.

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I criteri di partenza per lo svezzamento, uguali per tutti i pazienti, erano i seguenti: stabilità cardiopolmonare, PaO2 >60 mmHg con FiO2 ≤0,4, frequenza respiratoria 5 ml/kg peso corporeo, massima pressione inspiratoria ≤20 cm H2O e temperatura corporea inferiore a 38,5 °C. Brevi periodi di 30 min di ventilazione spontanea veniavno eseguiti attraverso un circuito a T, con una FiO2 simile a quella usata in corso di VM. Se queste prove di respirazione apparivano ben tollerate (massima pressione inspiratoria 5 ml/kg peso corporeo e frequenza respiratoria inferiore a 35 respiri/min) era concesso un periodo di almeno 3 h di ventilazione spontanea. Quando non si evidenziavano segni di stress respiratorio o circolatorio (frequenza respiratoria >35 respiri/min, SaO2 140 battiti/ min, pressione arteriosa sistolica >180 mmHg o