Table 74Parenteral nutrition (PN): continuous vs cyclic

Bibliographic referenceStudy
Type
Evidence levelNo. of patientsPatients characteristicsInterventionComparisonLength of follow upOutcome measuresEffect sizeComments (including source of funding)
Aldamiz- Echevarria et al 19967RCT1+24 patients

Intervention: n=12

Comparison: n=12
Patients who had undergone bone marrow transplant.

Mean +/− SD Age: Intervention: 37 +/− 9.3 Comparison: 35.4 +/− 11.1

Mean Weight (kg): Intervention: 62.6 +/− 12.9
Comparison: 67.1 +/− 14.6

Gender (M/F):
Intervention: 7/5
Comparison: 5/7

Exclusion criteria: patients below 15 years of age, renal failure, insulin dependent diabetes mellitus and cardiac conditions. Also PN interrupted for more than 5 days and/or those with cardiac insufficiency.
PN initiated 24 h after transplantation.

Continuous: infusion pump over 24 h period.

35 kcal/kg/day (29 non-protein kcal of which 65% were carbohydrates and 35% lipids) administered as 140 non-protein kcal/g of nitrogen and with an energy content of 1 kcal/ml. Daily support: nitrogen 0.22 g/kg, glucose 4.9 g/kg and lipids 1.121 g/kg. Electrolytes, trace elements and vitamins were given according to individual requirements.
PN initiated 24 h after transplantation.

Cyclic: infusion pump over 12 h period.

35 kcal/kg/day (29 non-protein kcal of which 65% were carbohydrates and 35% lipids) administered as 140 non-protein kcal/g of nitrogen and with an energy content of 1 kcal/ml. Daily support: nitrogen 0.22 g/kg, glucose 4.9 g/kg and lipids 1.121 g/kg. Electrolytes, trace elements and vitamins were given according to individual requirements.
Until end of PNIntervention: n=12
Comparison: n=12
Mean +/− SD Energy provided by PN (Kcal/kg/day)Intervention: 27.2 +/− 3.7
Comparison: 25.9 +/− 4.2 [p=0.45]
Mean +/− SD duration of PN (days)Intervention: 20.4 +/− 7.9
Comparison: 27.3 +/− 13.4 [p=0.14]
Mean +/− SD weight change from beginning and end of PN (kg)Intervention: −1.4 +/− 1.7 kg
Comparison: 0.1115 +/− 2.6 [p=0.12]
Mean +/−SD neutropenia time (days)Intervention: 19.6 +/− 11.7
Comparison: 22.5 +/− 7.6 [p= 0.55]
Use of hematopoietic growth factorsIntervention: n=7
Comparison: n= 9 [Not significant]
Incidence of hepatic veno-occlusive diseaseIntervention: n=2
Comparison: n=2 [Not significant]
Incidence of catheter infectionIntervention: n= 0
Comparison: n= 0
Incidence of feverIntervention: n= 7
Comparison: n= 7
Mean +/− SD post-transplantation hospitalisation period (days)Intervention: 29 +/− 18.1
Comparison: 31 +/− 15.3 [Not significant]
Mean +/− SD glucose levels (mg/dl)Beginning:
Intervention: 110.8 +/− 27.1
Comparison: 119.6 +/− 35.7 [p=0.50]
Mean +/− SD glucose levels during the trial (mg/dl)Intervention: 153.4 +/− 40.9
Comparison: 158.0 +/− 64.2 [p=0.8]
Mean +/− SD total protein levels (g/l)Beginning:
Intervention: 5.4 +/− 0.5
Comparison: 5.8 +/− 0.5 [p=0.05]
End PN:
Intervention: 5.5 +/− 0.8
Comparison: 6.2 +/− 0.7 [p=0.07]
Hepatic parameters:
Mean +/− SD aspartate aminotransferase (SGOT) values (U/l)Beginning:
Intervention: 27.6 +/− 16.9
Comparison: 76.2 +/− 116.3 [Not significant]

1st week:
Intervention: 21.5 +/− 14.61
Comparison: 18.9 +/− 8.5 [Not significant]

2nd week:
Intervention: 19.5 +/− 10.51
Comparison: 3.5 +/− 7.7 [Not significant]

Month:
Intervention: 28.0 +/− 13.4
Comparison: 22.2 +/− 0.5 [Not significant]
Mean +/− SD Alanine aminotransferase (GPT) values (U/l)Beginning:
Intervention: 43 +/− 57.7
Comparison: 74.3 +/− 98 9 [Not significant]

1st week:
Intervention: 38.5 +/− 39.9
Comparison: 41.5 +/− 39.1 [Not significant]

2nd week:
Intervention: 42.1 +/− 34.4
Comparison: 34.9 +/− 17.1 [Not significant]

Month:
Intervention: 70.3 +/− 42.5
Comparison: 22.6 +/− 6.8 [Not significant]
Mean +/− SD gamma glutamyl transferase (GGT) values (U/l)Beginning:
Intervention: 20.9 +/− 10.6
Comparison: 40.4 +/− 48.8 [Not significant]

1st week:
Intervention: 47.6 +/− 40.9
Comparison: 78.2 +/− 68.1 [Not significant]

2nd week:
Intervention: 88.3 +/− 86.8
Comparison: 131.4 +/− 81.5 [Not significant]

Month:
Intervention: 192 +/− 59.2
Comparison: 124.4 +/− 91.3
Mean +/− SD alkaline phosphatase (U/l)Beginning:
Intervention: 72.9 +/− 42.2
Comparison: 97.7 +/− 72.4 [Not significant]

1st week:
Intervention: 73.3 +/− 35.2
Comparison: 97.8 +/− 52.1 [Not significant]

2nd week:
Intervention: 86.0 +/− 56.9
Comparison: 125 +/− 44.8 [Not significant]

Month:
Intervention: 156 +/− 124.2
Comparison: 114.0 +/− 62.5 [Not significant]
Mean +/− SD total bilirubin (mg/dl)Beginning:
Intervention: 0.5 +/− 0.2
Comparison: 0.6 +/− 0.3 [Not significant]

1st week:
Intervention: 0.8 +/− 0.5
Comparison: 0.5 +/− 0.1 [Not significant]

2nd week:
Intervention: 0.8 +/− 0.5
Comparison: 0.7 +/− 0.3 [Not significant]

Month:
Intervention: 0.7 +/− 0.1
Comparison: 0.84 +/− 0.5 [Not significant]
Plasma biochemical parameters: urea, sodium, chlorine, potassium, phosphorus, calcium, uric acid and creatinineWithin normal range at the beginning and subsequent analysis (Data not reported).
Plasma levels of cholesterol, triglycerides, albumin.Data not extracted
Forsberg et al 1994115RCT1+16 patients

Intervention: n=8

Comparison: n=8
Mechanically ventilated patients with trauma and/or severe infection

Mean +/− SD age:
Intervention: 57 +/− 7
Comparison: 69 +/− 7

Gender (M/F)
Intervention: 6/2
Comparison: 5/3

Mean +/− SD BMI:
Intervention: 24 +/− 2
Comparison: 25 +/− 4
Duration of total PN before the study (days) Mean +/− SD:
Intervention: 3 +/− 2
Comparison: 7 +/−7

Exclusion criteria: renal failure requiring renal replacement therapy, insulin-dependent diabetes mellitus prior to intensive care, circulatory failure (MAP < 70 mmHg), severe hepatic failure, inspired O2 fractions above 55%, bronchopleural fistula and organ transplantation.

Criteria for exclusion during the study: failure to comply with the nutritional protocol, weaning off the mechanical ventilation and re-operation.
First 24 h, low energy glucose infusion was administered at a constant rate of 1.25 kJ/kg/h. After this study was divided into four consecutive 12 h periods:

Period 1: First 12 hours from 10.00 to 22.00

Period 2:
From 22.00 to 10:00

Period 3: From 10.00 to 22.00

Period 4: From 22.00 to 10.00

Glucose, fat and amino acids infused at a constant rate (1.3 x baseline energy expenditure) throughout periods 1, 2,3, 4.

In both groups the total energy supply was equal to 1.3 X baseline energy expenditure.

The non-protein energy was provided as glucose and lipids (Intralipid, 20%, Kabi Pharmacia AB, Stockholm, Sweden) with a ratio of 1:1. Amino acids (Vamin 14, Kabi Pharmacia AB, Sweden) were administered with a nitrogen: energy ratio of 1.3 N/1000 KJ.

Electrolytes, vitamins and trace elements were supplied daily and patients had no oral or enteral intakes during the study.
First 24 h, low energy glucose infusion was administered at a constant rate of 1.25 kJ/kg/h. After this study was divided into four consecutive 12 h periods:

Period 1: First 12 h, from 10.00 to 22.00: infusion of glucose, fat and amino acids

Period 2: from 22.00 to 10.00, low energy glucose infusion 1.25 kJ/Kg/h

Period 3: from 10.00 to 22.00, infusion of glucose, fat and amino acids

Period 4: from 22.00 to 10.00, low energy glucose infusion 1.25 kJ/Kg/h

In both groups the total energy supply was equal to 1.3 X baseline energy expenditure.

The non-protein energy was provided as glucose and lipids (Intralipid, 20%, Kabi Pharmacia AB, Stockholm, Sweden) with a ratio of 1:1. Amino acids (Vamin 14, Kabi Pharmacia AB, Sweden) were administered with a nitrogen: energy ratio of 1.3 N/1000 KJ.

Electrolytes, vitamins and trace elements were supplied daily and patients had no oral or enteral intakes during the study.
Until dischargeIntervention: n=8
Comparison: n=8
Energy supply in the comparison group during periods 1 and 3 was approximately 75% higher than during the corresponding periods in the intervention group.

Two patients in the continuous group with a history of diabetes mellitus (type II) required insulin infusions (1–3 units/hour) during total PN.
Mean +/− SD energy supply kJ/kg BW/hBaseline:
Intervention: 1.25 +/− 0
Comparison: 1.25 +/−0

Periods 1 and 3:
Intervention: 5.9 +/− 0.6
Comparison: 9.2 +/− 1.9

Periods 2 and 4:
Intervention: 5.9 +/− 0.6
Comparison: 1.25 +/− 0
Mean +/− SD amino acid supply (mg N/kg BW/h)Baseline:
Intervention: 0
Comparison: 0

Periods 1 and 3:
Intervention: 7.6 +/− 0.8
Comparison: 13.5 +/− 2.5

Periods 2 and 4:
Intervention: 7.6 +/− 0.8
Comparison: 0
Mean +/− SD energy expenditure (kJ/kg BW/h) (%, average increase in relation to baseline periods)Baseline:
Intervention: 4.5 +/− 0.5 (0)
Comparison: 4.0 +/− 0.7 (0)

Period 1:
Intervention: 4.7 +/− 0.4 (5)
Comparison: 4.5 +/− 0.8 (13)

Period 2:
Intervention: 4.8 +/− 0.3 (6)
Comparison: 4.2 +/− 0.7 (7)

Period 3:
Intervention: 4.8 +/− 0.4 (6)
Comparison: 4.6 +/− 0.6 (17)

Period 4:
Intervention: 4.7 +/− 0.4 (4)
Comparison: 4.4 +/− 0.5 (11)

Periods 1–4:
Intervention: 4.8 +/− 0.4 (5)
Comparison: 4.4 +/− 0.6 (12) [p<0.05] (percentage increase from the baseline)
Mean +/− SD respiratory quotientBaseline:
Intervention: 0.82 +/− 0.06
Comparison: 0.83 +/− 0.05

Period 1:
Intervention: 0.84 +/− 0.05
Comparison: 0.86 +/−0.04

Period 2:
Intervention: 0.86 +/− 0.06
Comparison: 0.89 +/− 0.05

Period 3:
Intervention: 0.86 +/− 0.05
Comparison: 0.88 +/− 0.03

Period 4:
Intervention: 0.87 +/− 0.05
Comparison: 0.87 +/− 0.05

Periods 1–4:
Intervention: 0.85 +/− 0.05
Comparison: 0.88 +/− 0.04
Mean +/− SD O2Baseline:
uptake (ml x (min/m2)-1, (%)Intervention: 151 +/− 34 (0)
Comparison: 133 +/− 20 (0)

Periods 1–4:
Intervention: 158 +/− 37 (5)
Comparison: 146 +/− 17 (11) [p<0.05] (percentage increase from the baseline)
Mean +/− SD CO2 elimination (ml x (min/m2) –1) (%)Baseline:
Intervention: 123 +/− 24 (0)
Comparison: 110 +/− 17 (0)

Periods 1–4:
Intervention: 133 +/− 25 (9)
Comparison: 129 +/− 16 (18) [p<0.05] (percentage increase from the baseline)
Mean +/− SD Nutrient-induced thermogenesis during periods 1–4Intervention: 5.3 +/− 4.5 %
Comparison: 12.4 +/− 7.1 % [p<0.05]
Mean +/− SD Energy balance (kJ/Kg BW/h)Intervention: 1.3 +/− 0.3
Comparison: 0.8 +/− 0.4 [p< 0.05]
Mean +/− SD plasma glucose (nmol/L)Before PN:
Intervention: 8.3 +/− 4.6
Comparison: 6.4 +/− 1.5 [Not significant]
During PN:
Intervention: 10.8 +/− 5.6
Comparison: 8.4 +/− 3.3
Administration of morphine equivalents (mg/24h)
Mean +/− SD
Before PN:
Intervention: 171+/− 328
Comparison: 48 +/− 104

During PN:
Intervention: 118 +/− 175
Comparison: 50 +/− 105 [Not significant]
Benzodiazepines (mg/24h) Mean +/− SDBefore PN:
Intervention: 61 +/− 84
Comparison: 55 +/− 111 [Not significant]

After PN:
Intervention: 41 +/− 51
Comparison: 56 +/− 113 [Not significant]
Mean +/− SD artificial ventilation (days)Before the study:
Intervention: 2 +/− 1
Comparison: 8 +/− 9

After study:
Intervention: 17 +/− 22
Comparison: 9 +/− 7
Mean +/− SD
Intensive care (days)
Before study:
Intervention: 3 +/− 1
Comparison: 8 +/− 8

After study:
Intervention: 23 +/− 22
Comparison: 14 +/− 17
Mean +/− SD hospitalisation (days)Before study:
Intervention: 7 +/− 5
Comparison: 11 +/− 10

After study:
Intervention: 32 +/− 25
Comparison: 34 +/− 30
Num. patients died in the intensive care unitIntervention: 1
Comparison: 3
Num. patients who died after intensive care during subsequent hospitalisationIntervention: 0
Comparison: 2
Nitrogen balance and urine excretion of noradrenaline, adrenaline, cortisol and glucose.Data not extracted
Plasma insulin, glucagon, serum cortisol, triglyceridesData not extracted
Heart rate, body temperature, systolic blood pressureDuring periods 1–4, the average values for heart rate, systolic blood pressure and temp. did not differ from baseline, nor where there any differences between the two groups. Data not extracted
Sandstrom et al 1995305RCT1+65 patients

Group A: n=21 (Data from this group not extracted)
Group B
(Continuous):
n=21

Group C
(Bolus):
n=23
Patients undergoing acute or elective major surgery.

Mean +/− SEM age:
Continuous: 68 +/− 2
Bolus: 63 +/− 2

Gender (M/F):
Group Continuous: 16/5
Group Bolus: 16/7

Mean SE body weight (kg):
Continuous: 75 +/− 3
Bolus: 74 +/− 3
NS

Mean +/− weight loss (%)
Continuous: 4 +/− 1
Bolus: 5 +/− 1

Arm circumference (cm)
Continuous: 30 +/− 1
Bolus: 30 +/− 1

Exclusion criteria: serum creatinine concentrations > 175 mmol/L and juvenile or adult onset diabetes mellitus that required tablet or insulin injection medication.
Group A n=21: Fat and amino acids were infused simultaneously from 8 AM to 4 PM and glucose alone form 4 PM to 8 AM next day. (Data from this group not extracted).

Group B (Continuous) n=21: 24-hour constant infusion of an all-in-one mixture with fat, amino acids, and glucose in a 3-L plastic bag that contained the entire prescription for 24 hours. The mixture was delivered by means of a pump at 125 mL/h.

Glucose only (250 g) was given on the first postoperative day. All patients started with total PN on the second postoperative day and received prescriptions for the 6 consecutive days according to randomisation. Only tap water was allowed as oral intake during the experimental period.

All patients received the same composition of nutrients. Nonprotein calories were provided to cover 100% of the predicted energy expenditure according to the Harris and Benedict formula and consisted of 40% lipids (Intralipid 20% Farmacia AB, Stockholm, Sweden) and 60% carbohydrate (D-glucose). Crystalline amino acids (Vamin 14, Kabi Pharmacia S.A, Limoges, France) were given corresponding to 0.2 g N/kg per day. Vitamins (Souvit, Vitalipid, Pharmacia AB), electrolytes (Na, K, Mg, phosphates), and trace elements (Addamel Phramacia AB, Stockholm, Sweden) were provided according to minimum requirements.
Group C (Bolus) n=23: Bolus infusion consisting o f the same nutrient mixture as Group B but provided in five small bags, each infused during 1 hour followed by 2 hours without infusions. These infusions were given during the major part of the day (12 hours). The first bag was infused beginning at 8 AM and the last bag at 8 PM. No infusion during the night hours were provided. The infusion rate was ~580 mL/h.

Glucose only (250 g) was given on the first postoperative day. All patients started with total PN on the second postoperative day and received prescriptions for the 6 consecutive days according to randomisation. Only tap water was allowed as oral intake during the experimental period.

All patients received the same composition of nutrients. Nonprotein calories were provided to cover 100% of the predicted energy expenditure according to the Harris and Benedict formula and consisted of 40% lipids (Intralipid 20% Farmacia AB, Stockholm, Sweden) and 60% carbohydrate (D-glucose). Crystalline amino acids (Vamin 14, Kabi Pharmacia S.A, Limoges, France) were given corresponding to 0.2 g N/kg per day. Vitamins (Souvit, Vitalipid, Pharmacia AB), electrolytes (Na, K, Mg, phosphates), and trace elements (Addamel Phramacia AB, Stockholm, Sweden) were provided according to minimum requirements.
Continuous: n= 21
Bolus: n= 23
Mean +/S SE total amount of fluids (mL/24 hr)Continuous: 3027 +/− 106
Bolus: 2915 +/− 102 [Not significant]
Total amount of blood, plasma and albumin Heart rateData not extracted

All nutrition regimens caused a significant stimulation of heart rate [p< 0.01] which was not statistically different on an overall daily basis among the infusion regimens. Electrocardiogram did not reveal any hazardous episodes of tachycardia or arrhythmia during bolus infusion. Data not reported.
Mean +/− SE body temperature (fC)Continuous: 37.5 +/− 0.1
Bolus: 37.7 +/− 0.1 [Not significant]
Nausea: patients days (%)Continuous: 3/126 (2)
Bolus: 8/138 (6) [Not significant]
Mean +/− SE bilirubin in serum (μmol/L)Continuous: 18 +/− 2
Bolus: 19 +/− 1
Mean +/− SE Serum alkaline phosphatase (μkat/L)Continuous: 3.8 +/− 0.4
Bolus: 4.8 +/− 0.4
Mean +/− SE serum
ASAT (μkat/L)
Continuous: 1.13 +/− 0.14
Bolus: 1.61 +/− 0.16
Serum ALAT (μkat/L)Continuous: 0.74 +/− 0.11
Bolus: 1.23 +/− 0.14
Blood glucose in the morning (g/L)Continuous: 8.3 +/− 0.3
Bolus: 5.8 +/− 0.2
Blood glucose increase during infusion (g/L)Continuous: 1.5 +/− 0.4
Bolus: 2.7 +/− 0.4
Energy balanceContinuous: −368 +/− 25 kcal/d
Bolus: −292 +/− 20 kcal/d
“Minimum” nitrogen balance (calculated accounting for the nitrogen content of infused amino acid solutions only)Continuous: −0.2 +/− 0.6 g/d
Bolus: −2.8 +/− 0.3 g/d [p<0.01]
“Maximum” nitrogen balance (calculated accounting for measured nitrogen content in all blood and plasma products provided during operation and the entire study period in addition to the amino acid nitrogen)Continuous: +3.3 +/− 1.2 g N/d
Bolus: 0.4 +/− 0.9 g N/day [p<0.05]
Daily urine excretions and external losses of nitrogenData not extracted

From: Appendix Four, Evidence Tables

Cover of Nutrition Support for Adults
Nutrition Support for Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition.
NICE Clinical Guidelines, No. 32.
National Collaborating Centre for Acute Care (UK).
Copyright © 2006, National Collaborating Centre for Acute Care.

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