Metabolic and thermogenic response to continuous and cyclic total parenteral nutrition in traumatised and infected patients

Clinical Nurritron (1994) 13: 291-301 0 Longman Group Ltd 1994

Metabolic and thermogenic response to continuous and cyclic total parenteral nutrition in traumatised and infected patients E. FORSBERG, M. SOOP, A. LEPAPE” and A THoRNEt Departments of Anaesthesiology and ?Turgery, Huddinge University Hospital, Karolinska Institute, S- 14 1 86 Huddinge, Stockholm, Sweden, and *Service de RBanimation, Centre Hospitalier Lyon-Sud, France (Reprint requests to EFI

ABSTRACT-16 traumatised or infected patients on mechanical ventilation were randomised to continuous TPN or to cyclic TPN after a 24-h period of glucose infusion (1.25 kJ x kg BW-’ x h-l). Energy supply was equivalent to 1.3 x baseline energy expenditure. Glucose, fat and amino acids were administered at a constant rate over 24 h in the continuous TPN group and over 12 h, followed by glucose (1.25 kJ x kg BW-I x h-l), in the cyclic TPN group. Nutrientinduced thermogenesis was lower during continuous than during cyclic TPN (5 + 4 vs. 12 * 7%, mean f SD, p < 0.05), as was the increase in CO2 elimination (13 f 11 vs. 30 + 7%, respectively, p < 0.01). Energy balance was more positive during continuous TPN. In both groups, energy expenditure reached a plateau during the first 12 h of TPN infusion. The lower nutrient-induced thermogenesis and more positive energy balance, indicates a more efficient utilisation of nutrients during continuous than during cyclic TPN. The lower CO;, production during continuous TPN, may be advantageous when respiratory function is compromised. The plateau in energy expenditure in response to TPN infusion may be useful as a guideline for nutritional therapy.

Introduction

nitrogen balance were revealed. Hence, intermittent nutrition has been advocated, since it may promote physical activity during the periods when the patient is not receiving infusions, and since it has been claimed to mimic the normal hormonal alterations between the fed and post-absorptive states. However, this may not be as relevant during trauma and infection in hypercatabolic patients. Data from a study in patients after surgical trauma (cholecystectomy) suggest that the energy balance was more positive during continuous total parenteral nutrition (TPN) throughout 24 h than during a regimen administered only over periods of 12 h (10). In mechanically ventilated patients with trauma/infection, the metabolic responses to these two methods of nutrient administration have not, to our knowledge, been compared. Consequently, the purpose of the present study was to determine whether the timing of TPN administration (24-h vs. 12-h) influences energy metabolism in mechanically ventilated patients with severe infection and/or trauma.

Critically ill patients with trauma and/or severe infection need nutritional support to reduce the rate of tissue wasting and to promote healing. Since such patients have compromised organ functions, they are susceptible to side-effects of ovemutrition (l-6). Seriously ill patients, rather than those with an uncomplicated clinical course, are probably the major potential beneficiaries of an individualised nutritional therapy, especially when nutritional treatment is required for long periods. Two important issues are the definition of the optimal level of energy balance, plus the assessment of whether the daily nutrient supply should be administered continuously throughout 24 h or intermittently over shorter periods. These two methods of intravenous nutrient administration have been evaluated, using indirect calorimetry in undernourished and non-stressed adult patients (7, 8) and in children (9), and no major differences with regard to energy and 291

292 CONTlNUOUSVERSUSCYCLICTPNINTRAUMAlINFECTION

Material and methods Patients

16 mechanically ventilated patients (postoperative infection following abdominal surgery = 10, pneumonia = 3, major accidental trauma = 2 and urosepsis = 1) were randomly allocated to receive continuous (24-h) or cyclic (12-h) infusions of glucose, fat and amino acids. Patients were excluded on the basis of the following criteria: renal failure requiring renal replacement therapy, insulin-dependent diabetes mellitus prior to intensive care, circulatory failure (MAP < 70 mmHg), severe hepatic failure (serum alanine aminotransferase concentrations > 1.5 l_tkat/L and bilirubin concentrations > 100 pmol/L), inspired 0, fractions above 55%, bronchopleural fistula and organ transplantation. The criteria for exclusion during the study were failure to comply with the nutritional protocol, weaning off the mechanical ventilation and re-operation. The infectious complications were verified by positive blood cultures and/or drainage of any intraabdominal abscess. 6 of the patients had undergone at least one re-operation. Prior to the study, TPN had been given during a minimum of 1 day (average 5 days). At the time of the study, no patient had shock or overt sepsis and a11had a stable circulation, judged by a bedside assessment, arterial blood pressure and arterial base excess. None of the patients required correction of metabolic acidosis or showed clinical signs of overhydration during the study. Table 1 shows the pre-operative diagnoses, post-operative complications, number of operations, demographic parameters and the durations of TPN, artificial ventilation, intensive care and hospitalisation. The severity of illness was assessed, using APACHE II (1 I), on the day of admission to the ICU. The value of the

STUDY

PERIODS

DAY. >

TPN GROUP->

TPN GROUP- >

Indirect calorimetry

Energy expenditure (EE) and the respiratory quotient (RQ) were recorded continuously, using open-circuit indirect calorimetry (Engstrom Metabolic Computer, Gambro Engstrom AB, Bromma, Sweden). This automatic device incorporates the Haldane correction in the calculations of 0, uptake and CO, elimination. Energy expenditure was computed from the O2 uptake and the RQ (12). The accuracy of the inspiratory pneumotachometer was checked with a calibration syringe. The CO, analywr was manually calibrated daily and the O2 analyser every 4 h, using an automatic calibration cycle. Controlled mechanical ventilation, with ventilatory settings in compliance with the optimal measuring range of the equipment, was employed (12).

Study design and nutritionaf protocol

A schematic illustration of the protocol is shown in Figure 1. During the first 24 h, a low-energy glucose infusion was administered at a constant rate of 1.25 kJ x kg BW-’ x h-‘. After 19 h of glucose infusion, EE was recorded over a period of 3 h (05:0&O&00 = baseline period) and the average EE was referred to as the baseline EE (BEE). After that, the glucose infusion was continued for two more hours, so that a total period of 24 h of low energy glucose infusion was obtained. Thereafter, TPN was initiated. In both

1

OF CALORIMETRY->

CONTINUOUS CYCLIC

I

Glasgow Coma Score was not used in the calculation of the APACHE II-score because sedatives had been administered. Since the patients were unable to give informed consent to participation in the study, this was obtained from their relatives. The protocol was reviewed and approved by the Ethics Committee of Huddinge University Hospital.

2

I

pg/

1

G

I

G

1

f

I

2

I

3

G

I 1

TPN-G

TPN TPN-G

1

1

3

I

I4

]

TPN 1

G

t

Fig. 1. Study design. Periods l-4 denote four consecutive 12-h periods. B refers to the period of measurement of baseline energy expenditure (BEE). G indicates glucose infusion (1.25kJ x kg BW-’ x h-l). TPN denotes a continuous infusion of energy (glucose. fat and amino acids) at a rate corresponding to 1.3 x BEE. TPN-G denotes an energy supply over periods I and 3 adjusted so that the total energy supply, taking G during periods 2 and 4 into account, was also equal to 1.3 x BEE. Arrows indicate arterial blood sampling for hormones.

CLINICAL

NUTRITION

293

Table 1 Demographic and clinical data Diagnosis/ complications(s): no. of operations Continuous TPN (n = 8) Aortic aneurysm, intestinal perforation, RDb, abdominal abscesses: 2 Duodenal ulcer/septic shock, wound rupture, abdominal abscess: 2 Accidental trauma, multiple fractures, hepatic rupture: 1 Pneumonia/sepsis Oesophageal cancer/sepsis, pneumonia: 1 Accidental trauma, diaphragmatic rupture, multiple fractures: 1 Pneumonia Colon cancer/sepsis. pneumonia: 1 Mean + SD Cyclic TPN (n = 8) Iatrogenic papilloduodenal perforation (ERCP)/sepsis, abdominal abscesses. RD: 3 Aortic aneurysm/ compartment syndrome, RD, sepsis: 2 Bronchopneumonia, chronic bronchitis Oesophageal cancer/sepsis: 2 Oesophageal stricture/ pneumonia: 1 Urosepsis/septic chock. pneumonia, RD Perforated gastric ulcer/abdominal abscesses, RD: 2 Aortic aneurysm/ pneumonia: 1 Mean + SD

Sex

Age (years)

Weight (kg*)

Body mass index

TPN (days)+

Artificial ventilation before/after study (days)

Intensive Hospitalisation before/after care before/after study (days) study (days)

Outcome*

M

66

67

23

7

219

2120

15145

S

M

60

61

22

4

l/l

l/l2

5114

s

F

30

65

24

2

2/10

2112

2117

S

M M

63 66

60 80

20 26

3 3

4i70 3110

3177 3114

14189 5129

s

M

25

75

24

1

l/9

l/12

1121

S

F M

66 76

67 87

23 26

4 3

l/11 4114

4/l 1 4124

4/l 1 9132

D s

57f7

70flO

24f2

3f2

2+ 11 17?r22

3+ I/ 23 * 22

7 f 51 32_+25

F

64

80

29

24

28114

28154

28167

S

M

64

85

23

5

414

615

9187

(D)

M

68

85

27

1

l/6

117

1121

S

M

57

68

20

11

12117

12117

25117

D

F

74

44

20

6

313

715

8134

(D)

M

79

60

23

5

6/l

6/l

6/l

D

F

77

78

30

3

415

415

515

D

M

68

91

27

3

4/18

4121

4139

S

69+7

74f6

25f4

7f7

8 f 91 9*7

8 + 8/ 14f.17

11 f 101 34+30

S

There were no significant differences between the cyclic and continuous TPN groups. *average body weight during the study +duration of total parenteral nutrition before the study *S = patients who survived hospitalisation, D = patient who died during intensive care, (D) = patients who died after intensive care during subsequent hospitalisation *Renal dysfunction (serum creatinine > 177 mmolL = 2 mg/dL).

groups the total energy supply was equal to 1.3 X BEE. In patients randomised to cyclic TPN (CY), glucase, fat and amino acids were infused during the first 12 h (lO:OO-22:00 = period 1). The energy provided during the following 12 h (22:00-10:00 = period 2)

was administered as a low energy glucose infusion (1.25 k.I x kg BW-’ x h-l). The same protocol as in periods 1 and 2 was then repeated in the two subsequent 12-h periods (lO:OO-2290 = period 3, 22:001090 = period 4). In the patients randomised to

294 CONTINUOUSVERSUSCYCLICTPNlNTRAUMA/INF'ECTION

continuous TPN (CO), all three substrates were infused at a constant rate (1.3 x BEE) throughout periods 1, 2, 3 and 4. Consequently, the energy supply in the CY group during periods 1 and 3 was approximately 75% higher than that during the corresponding periods in the CO group. 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. All nutrients were administered using infusion pumps (IVAC AB, Taby, Sweden). Electrolytes, vitamins and trace elements were supplied daily and the patients had no oral or enteral intake of nutrients during the study. Appropriate analgesia and sedation were maintained with morphine and phenoperidine and bensodiazepines. No paralysing agents were used. Body temperature was measured in the axilla 16-24 times a day. Paracetamol was given occasionally when body temperatures rose above 39°C. Body weight was determined daily, using a bed scale (Scale Tronix 2001, Scale Tronix Inc, Wheaton, IL, U.S.A). Blood sampling Arterial blood samples were collected for determinations of the concentrations of serum cortisol and insulin and glucagon in plasma immediately before and 5 h after the onset of TPN (period 1). Arterial blood samples were drawn immediately before the intiation, at the middle and before the termination of each of the periods for analyses of plasma glucose (periods 14) and serum triglycerides (periods 1-3). Urine sampling

Urine was collected for determinations of glucose, total nitrogen, cortisol and catechokunines by means of an indwelling bladder catheter during each of the periods 14 and during the 24 h preceding period 1. Analytical procedures

Catecholamines were analysed in urine by highpressure liquid chromatography, using electrochemical detection (13, 14). Concentrations of insulin and glucagon in plasma were analysed by radioimmunoassay (15, 16). Serum and urinary cortisol concentrations were analysed with a radioimmunoassay kit; Cortisol lz51R(Farmos Diagnostica, Turku, Finland). Plasma and urine glucose levels were analysed by the hexokinase method (kits from Boehringer, Mannheim, Germany) and triglyceride levels were also analysed enzymatically (17).

The urinary nitrogen excretion was determined by a chemoluminescence technique (771C pyroreactor, 720C nitrogen detector; ANTEK, Houston, TX, USA). Calculations

Energy expenditure was expressed in relation to the average body weight during the study and as the per cent above the estimated basal metabolic rate, according to Fleisch (18), which is referred to as hypermetabolism. The percentage increase in EE was calculated as (EE-BEE)/BEE x 100, where EE is the average EE and BEE is the measured baseline (see above). The nutrient-induced increase in EE (nutrientinduced thermogenesis) was calculated as the increase above BEE in per cent of the increase in energy supply during periods l-4; (EE-BEE)/(EI-EI,) x 100, where EI is the energy supply corrected for urinary glucose losses and EIn is the energy supply during the baseline period. This calculation takes into account the amount of glucose energy administered during the baseline period. The energy contents of the administered albumin and plasma were not considered when calculating the energy intake. Nitrogen balance was determined for each of the periods 14 separately and for the 24-h period of low-energy glucose infusion that preceded period 1. The analyses were based on the nitrogen content of the amino acid solutions administered (as specified by the manufacturer), the total nitrogen loss in urine, corrections for changes in body urea nitrogen content (assuming a total body water of 60% of body weight in men and 57% in women) and an assumed nitrogen faecal and integumental loss of 1 g x 12 h-l (19). All weight-related variables were calculated using the average body weight during the study. Statistical methods

All data are given as mean f SD. Analysis of variance for repeated measures, Student’s t-test for paired and unpaired samples, Wilcoxon’s two-sample test and Fischer’s exact probability test were used when appropriate. A p-value (two-tailed) of less than 0.05 was considered significant. Results 8 patients received continuous TPN and 8 patients cyclic TPN. 1 patient in the CO group and 3 patients in the CY group died in the intensive care unit. In the CO group, 2 patients with a history of diabetes mellitus (type II) required insulin infusions (l-3 units x hour’) during TPN.

CLINICAL NUTRITION

295

The APACHE II scores on admission to the ICU did not differ between the CO group (19 f 4) and the CY group (20 + 6, NS). No differences in demographic or clinical data were observed (Table 1).

increase in CO, elimination from baseline reached a maximum 13 + 11% in the CO group and 30 + 7% in the CY group (p < 0.01) (Fig. 2), in response to TPN.

Pulmonary O2 uptake and CO2 elimination

Energy expenditure and RQ

During the baseline period, similar levels were observed in the CO and CY groups in O2 uptake (15 1 + 34 and 133 & 20 ml x [mm/m2 BSA]-‘, NS) and CO;! elimination (123 f 24 and 110 f 17 ml x [mm/m* BSA]-‘, NS) (Table 2). Calculated for all values during periods l-4, the percentage increase from the baseline was lower in the CO group than in the CY group, both in 0, uptake (5 + 5 vs. 11 + 6%, p < 0.05) and in CO, elimination (9 + 5 vs. 18 rt 6%, p < 0.01) (Table 2, Fig. 2). On analysing l-h mean values, the

During the baseline period, average values for all patients were: EE 4.3 f 0.6 kJ x kg BW-r x h-l, RQ 0.82 f 0.05 and hypermetabolism 18 + 13%. No significant differences in EE, RQ or hypermetabolism were observed, although EE tended to be higher in the CO group than in the CY group (p = 0.11) (Table 2). Within each group, there were significant increases in EE and RQ in response to TPN, whether values during the baseline period were compared to the average of all values during period 1 or to the average

Table 2

Nutritional

supply, energy metabolism

and pulmonary

Period

Energy supply (kJ x kg BW-’ x h-‘) Amino acid supply (mg N x kg BW-’ x h-‘) Energy expenditure (kJ x kg BW-’ x h-‘), [%lb

RQ

0, uptake (ml x (min/m2)-‘),

[%lb

CO, elimination (ml x (min/m2)-‘),

[%lb

gas exchange Continuous TPN (n = 8)

Cyclic TPN (n = 8)

Baseline” land3 2and4 Baseline land3 2and4 Baseline 1 2 3 4 l-4

1.25&O 5.9 XL0.63 5.9 + 0.63 0 7.6 f 0.LX3 7.6 f 0.83 4.5 * 0.5 [O] 4.7 f 0.4 [5] 4.8 _+0.3 [6] 4.8 f 0.4 [6] 4.7 + 0.4 [4] 4.8 f 0.4 [5]

1.25 +O 9.2 k 1.93 1.25 ir0 0 13.5 f 2.53 0 4.0 f 0.7 [O] 4.5 _+0.83 [13] 4.2 f 0.72 [7] 4.6 + 0.63 1171 4.4 f 0.52 [ 1 l] 4.4 f 0.63 [12*]

Baseline 1 2 3 4 14 Baseline 1 2 3 4 1-4 Baseline 1 2 3 4 14 mean f SD

0.82 + 0.06 0.84 + 0.05 0.86 f 0.06’ 0.86 * 0.05’ 0.87 IL0.052 0.85 + 0.05’ 151* 34 [O] 157 f 37 [4] 158 a! 36 [5] 159 f 38 [6] 155 f 37 [3] 158 f 37 [5] 123 f 24 [0] 130 f 25 [7] 134+23 [lo] 135 f 27 [lo] 134+26 [lo] 133 _+25 [9]

0.83 + 0.05 0.86 f oLMz 0.89 4 0.05? 0.88 + 0.033 0.87 f 0.05? 0.88 f 0.043 133 I? 20 [O] 149 + 20 [12] 139 f 19 [5] 152 + 18 [15] 144 f 15 [IO] 146 + 17 [ll*] 110 f 17 [O] 128 IL 18 [17] 124 f 16 [14] 135 f 17 [24] 128 + 14 [17] 129 f 16 [18*]

a Baseline denotes values collected over 3 h, after 19 h of glucose infusion at a rate of 1.25 kJ x BW-’ x h-‘, preceding fat and amino acid infusions. 1,2,3,4 denote average values during four consecutive 12-h periods, see Fig. 1) b the average increase (%) in relation to the baseline period is given in brackets * denotes p < 0.05 for differences between groups ‘, 2. 3 p < 0.05, p < 0.01 and p < 0.001 denote differences within each group in relation to baseline

the start of glucose,

296

CONTINUOUS VERSUS CYCLIC TPN IN TRAUMA/INFECTION

body-weight related energy expenditure did not differ of all values in periods l-4 (Table 2). Between the between the groups (Table 2, Fig. 2, upper panels). groups, EE increased less in the CO group than in the CY group (p < 0.05), while the change in RQ did not differ (Table 2, Fig. 2). Despite the difference Nutrient-induced themogenesis and energy balance in TPN infusion rates during periods 1 and 3 (5.9 +_ 0.6 vs. 9.2 IL 1.9 kJ x kg BW-’ x h-‘) the values of On considering all values during periods l-4, the

Energy

supply

e

I

2

in energy

Increase

B Respiratory

t

supply

Increase

2

3

in energy

e

1

Respiratory

3

Increesr

1

2

elimination

3

t

1 in 4

e

1

Increese

expenditure

2

2

2

2

4

Quotient

B

4

uptake

in COt

L expenditure

1

Ouotient

in 0,

e Increere

2

expenditure

0.7oJ~i...,.i.,...;...,.:.,.-rrrlB 1 2 hCreaSe

Energy

L expenditure

1

2

in CO*

Fig. 2. B = baseline period. Periods I, 2.3 and 4 denote consecutive panels: continuous TPN group. Right panels: cyclic TFN group.

1

uptake

3

elimination

12-h periods (see Fig. 1). Left

4

CLINICAL NUTRITION

Table3

297

Nitrogen balance and urine excretion of hormones and glucose Period

Nitrogen balance (mg x kg BW-’ x 24 h-l) Noradrenaline (nmol x 24 h-’ )b Adrenaline (nmol x 24 h-l)b Cortisol (nmol x 24 h-‘)h Glucose excretion (kJ x kg BW-’ x h-‘)

Continuous TPN (n = 7)

Before TPN 1-4a

-287 f 86 -121 * 892

Before TPN l-4

231 i. 170 304 f 273

Before TPN l-4

20+8 31224

Before TPN 14

205f91 193f74

Before TPN l-4

o+o 0.001 + 0.005

Cyclic TPN (n = 8)

-303 + 136 -148 + 130’ 66 * 50 102f90 36 f 30 26+1 187f 125 132+63 Ok0 0.003 f 0.007

mean f SD. a Before TPN denote values the fist 24 h during glucose infusions at a rate of 1.25 k.J x kg BW-’ x h-‘, preceding the start of glucose, fat and ammo acid infusions l-4 denote average values during four consecutive 12-h periods (see Fig. 1). b Values are given for a body surface area of 1.73 m2. ‘,*p < 0.05 and p < 0.001 for differences between values before TPN and during TPN (average values for period IA), within each group. There were no significant differences between the groups.

nutrient-induced thermogenesis was lower in the CO group (5.3 4 4.5%) than in the CY group (12.4 + 7.1%, p < 0.05). The energy balance was positive in both groups though it was more positive in the CO group than in the CY group (1.3 + 0.3 vs. 0.8 + 0.4 kI x kg BW-’ x h-l, p < 0.05). Nitrogen balance and urinary hormone excretion rates The average nitrogen balance was negative throughout

the study. In both groups, nitrogen balance improved during periods l-4 in response to TPN but did not differ between the groups, whether analysis was performed using values related to body weight or related to the levels before TPN (Table 3). Similar analyses revealed no differences between the two groups in adrenaline, noradrenaline or cortisol excretion rates (Table 3, Fig. 3).

Blood concentrations of hormones and substrates

Before TPN, glucose, triglyceride and hormone concentrations did not differ between the two groups. Hormones and triglyceride concentrations were within normal limits, while the glucose level was slightly elevated in both groups in relation to normal fasting values. Within each group, there were increases in plasma glucose and serum triglyceride concentrations in response to TPN (Table 4). The concentrations of insulin increased significantly only

in the CY group while there was a tendency to an increase in the CO group (p = 0.07). There was a decrease in serum cortisol in the CY group but no change in the CO group. There was a tendency to an increase in glucagon in response to TPN in the CO group (p = 0.10) and in the CY group (p = 0.15). Between the two groups, there were no differences in plasma glucose, serum triglycerides or any of the hormones, except cortisol (p c 0.05), on comparing the responses to TPN (Table 4). In the CY group, serum glucose and triglyceride concentrations varied considerably (Fig. 3, Table 4). Temperature, heart rate, blood pressure, sedatives and inotropic therapy

During the baseline period, no differences were observed between the CO and CY groups in heart rate (97 + 21 vs. 84 + 16 BPM) or systolic blood pressure (122~19~~.122~17mmHg).Therewasatendency towards higher baseline values in body temperature in the CO group (38.5 + 5 vs. 37.7 k 0.6”C, p = 0.10). During the periods 1-4, the average values for heart rate, systolic blood pressure and temperature did not differ from baseline, nor were there any differences between the two groups, whether the analyses were performed using absolute values or those related to the baseline levels. In the CY group, body temperature increased 0.54 f 0.45”C from baseline, 6-8 h after the initiation of TPN, which was different (p < 0.05) from the response to TPN in the CO group

298 CONTINUOUS VERSUS CYCLIC TPN IN TRAUMA/INFECTION PLASMA QLIJCOSE 04

PLASMA OLWOS2 18

1

T

BASELINE

LINE

SERUM TRIOLYCERDES

1

2

2

4

SERUM TRIOLYCfRIDES T T

I BASE-

BASE-

LINE

Fig. 3. Periods 1,2, 3 and 4 denote consecutive group. Right panels: cyclic TPN group.

LINE

12-h periods (see Fig.

(-0.16 f 052°C). When analysing heart rate and systolic blood pressure in a similar fashion, no difference was found. 3 of the patients in each group received dopamine (approximately 2.5 pg x kg BW-’ x min-‘) and/or dobutamine (approximately 5 yg x kg BW-’ x min-‘) at the time of the study. The administration of morphine equivalents and bensodiazepines (midazolam) did not differ between the groups (Table 4).

Discussion The present findings in traumatised and infected patients show that the administration of glucose, fat and amino acids continuously over a 24-h period, gives a more positive energy balance than does a cyclic regimen with administration over 12 h, alternating with a low-energy glucose infusion. This difference may, at least partly, be attributed to the difference in nutrient-induced thermogenesis. The results agree with data reported in a study in patients

1

P&D

3

4

I ). Left panels: continuous TPN

given TPN after cholecystectomy (10) and with observations in normal subjects receiving continuous enteral nutrition, as compared to a bolus dose of nutrients (20). The magnitude of the interindividual variations in EE (Fig. 2, upper panels) imply that individual measurements of EE are required for adequate control of energy balance, in the present type of patient. The difference in energy balance (periods I-4) between the two groups, extrapolated to a body weight of 70 kg, was equivalent to approximately 30 g of glucose or 13 g of fat. It is conceivable that, with the cyclic regimen, the excess provision of substrates entailed energy costs both for nutrient storage during the periods of high energy supply and for mobilisation during the periods of low-energy glucose infusion, whereas with the continuous regimen, these costs may have been smaller, since nutrients were utilised ‘on line’. On analysing the 12-h periods of solitary glucose infusion (periods 2 and 4) in the CY group, we found unchanged levels in EE and RQ during the first few

CLINICAL NUTRITION

299

Table 4 Plasma and serum concentrations of hormones, glucose and triglycerides and the administration of morphine and benzodiazepines Continuous TPN n=8 Before During TPN TPN Plasma insulin (mu/L, normal < 20) Plasma glucagon (pmol/L, normal < 116) Serum co&sol (nmol x L-t, normal < 740) Plasma glucose (nmol x L-t, normal < 6.4) Serum triglycerides (mm01 x L-t, normal <:2.2) Morphine equivalents (mg x 24 h-t) Benzodiazepinesb (mg x 24 h-l)

19+ 13 30+18 503 f 170 8.3 + 4.6 1.7 * 1.1 171+ 328 61f84

48+41 38526 508 + 151 10.8 + 5.6’ 2.2 + 1.02 118f175 41 f 51

Cyclic TPN n=8 Before TPN 17_+8 42 f 35 651+ 194 6.4 f 1.5 1.9kO.7 48+104 55* 111

During

55 + 29a 90f90 514f2232 8.4 + 3.3’ 2.5 + l.O? 50 _+105 56+ 113

f

mean Z!Y SD. Normal values are given for fasting conditions. ‘Before TPN’ denotes values after 24 h of glucose infusion (1.25 kJ x kg BW-’ x h-‘) and ‘During TPN’ denotes values in samples taken 5 h after initiation of TPN (period 1). *J denote p < 0.05 and p < 0.01 for differences before and during TPN within each group. f denotes p i 0.05 for differences between groups in response to TPN. a the sum of administered doses of morphine and phenoperidine assuming that 1 mg of morphine is equivalent to 0.1 mg of pbenoperidine, b the sum of administered doses of benzodiazepines (midazolam).

hours, followed by a tendency towards small declines at the end of the periods (Fig. 2). It is conceivable that these findings reflect persistence of the thermogenic effect of the high energy loads given during the preceding periods (periods 1 and 3) and that a substantial amount of energy -i.e. -30% of the simultaneously measured EE- was supplied during the periods of solitary glucose infusion. It should be noted that the present energy supply (1.3 x BEE) was lower than in most other studies comparing continuous 24-h administration of TPN with regimens where all or most of the energy was supplied over a shorter period of time (7, 8, 10). It is probable that in the present study, greater differences between the regimens would have occured if a larger energy supply had been given. However, the present level was chosen as it was not expected to substantially exceed utilisation. We believed this was essential to prevent the incorporation of possible effects of over-nutrition or precipitation of metabolic complications in this study of patients susceptible to the side-effects of TPN. The response to TPN, as evaluated by the levels of stress hormones in urine, suggest that neither of the nutritional regimens had any substantial stress effects (Table 3). The large rise in pulmonary CO2 elimination during the cyclic regimen (Table 2, Fig. 2) suggests that this regimen imposes a higher workload on the respiratory muscles and therefore may be less suitable for spontaneouslybreathing patients with compromised respiratory function or when weaning patients off the ventilator. The cyclic regimen may also be expected to induce variations in arterial carbon dioxide tension in mechanically ventilated patients which may be unde-

sirable in the presence of cerebral oedema. During both nutritional regimens, EE apparently increased to a plateau. We have previously observed this plateau in EE in response to a sustained infusion of energy at rate substantially above that of EE (21). Interestingly, data in a previous study suggest that the absolute level of EE is only influenced to a minor extent by the infusion rate of energy at different levels above EE (22). We believe that this plateau may reflect the capacity for substrate utilisation and hence may be used as a guideline for nutritional therapy. This approach takes into account the variations in the thermogenic response and patients need not be fasted in the pursuit of a value for ‘basal energy expenditure’. As shown in Figure 2, the continuous regimen induced increases in pulmonary gas exchange and energy expenditure that persisted unaltered during TPN, indicating a rapid metabolic adaptation. Interestingly, in the cyclic group the diurnal variations in these variables appeared to occur at a higher level during the second 24-h period of TPN (periods 3 and 4) than during the first (periods 1 and 2). Although these differences did not reach statistical significance, they may suggest that the metabolic adaptation to cyclic TPN differs from that to continuous TPN. The value obtained for nutrientinduced thermogenesis agrees with our previous findings in traumatised/infected, mechanically ventilated patients (21), when taking the nutritional protocol into account. In that study, TPN, with a content similar to that used in the present study, was infused over a period of 16 h and was followed by a period of low-energy glucose infusion during 8 h. This resulted in a nutrient-induced thermogenesis of

300

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the order of 6-7%. as compared to the present 4-5% in the continuous TPN group and 9- 12% in the cyclic TPN group. Nutrient-induced thermogenesis during the cyclic regimen was only approximately half of the 9-12% mentioned previously, when performing the calculations with data from the baseline period and period 1 or when the data from period 3 and the last 3 h of period 2 were used. Evidently, the interpretation of nutrient-induced thermogenesis requires scrutiny of the periods chosen for analysis. Nitrogen balance, demonstrated that the patients in both groups were hypercatabolic. A better nitrogen retention when using a continuous regimen, as compared to a cyclic regimen of TPN, has been reported in hypercatabolic patients with gastrointestinal disease, who were receiving steroids (23) and in patients with Crohn’s disease (24). In the present study there was no difference in nitrogen balance between the groups. However, the short duration of the study, the small number of patients and variations in the supply of blood products makes the interpretation of nitrogen balance data, other than for a descriptive purpose, very uncertain. The significant decrease in serum cortisol in response to cyclic TPN may be related to the comparatively high rate of amino acid infusion. We have previously observed an inverse relationship between the concentrations of plasma amino acids and serum cortisol in the present type of patients (25). A positive relationship was observed between the increase in energy expenditure and the increase in body temperature (Fig. 4). during cyclic TPN administration. This suggests that the infusion rate of Chanae

1.25

in body temperature

-I

0 0.75

n

0.50 0.25 0.00

I

I

0

5

I

I

1

I

15 20 10 Change in energy expenditure

25 (Xl

Fig. 4. The relationship between the change in energy expenditure and the change in body temperature in response to cyclic TPN administration. TPN values were chosen after 6-8 h of glucose, fat and amino acid infusions. r = 0.79

30

nutrients may be a factor worth consideration in the differential diagnosis of fever in the present type of patient. In conclusion, in mechanically ventilated traumatised and/or infected patients, continuous TPN infusion resulted in a lower nutrient-induced thermogenesis and an energy balance that was more positive, suggesting a more efficient utilisation of nutrients, than a cyclic TPN regimen. The continuous regimen entailed lower rates of CO, production, which may be advantageous when respiratory function is compromised. The variations in the CO2 elimination rate observed during cyclic TPN may be disadvantageous in the presence of cerebral oedema. The maximum level of energy expenditure attained in response to TPN infusion did not differ substantially between the groups, despite a large difference in substrate infusions. We believe this level reflects the capacity for substrate utilisation and may be used as a guideline for nutritional therapy.

Acknowledgements We thank Associate Professor Jan Wernerman for providing urinary nitrogen analyses. We acknowledge the technical assistance of Miss Jenny Vesterberg.

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receiving bolus intermittent total parenteral nutrition infusion. Journal 1993: 158-164. 11. Knaus WA, Draper E A, Wagner D P, Zimmerman J E. APACHE II: a severity and disease classification system. Crit Care Med 1985; 13: 818-829. 12. Carlsson M, For&erg E, Theme A, Nordenstrom J, Hedenstiema G. Evaluation of an apparatus for continuous monitoring of gas exchange in mechanically ventilated patients. Int J Clin Monit Comput 1985; 1: 21 l-220. 13. Keller R, Oke A, Mefford I. Liquid chromatography analysis of catecholamines. Routine assay for regional brain mapping. Life Sci 1976; 19: 995-1004. 14. Riggin R M, Kissinger P T. Determination of catecholamines in urine by reversed-phase liquid chromatography with electrochemical detection. Anal Chem 1977; 49: 2109-2111. 1.5. Midgeley A R, Rebar R W, Niswender G D. Radioimmunoassays employing double antibody techniques. Acta Endocrin 1967; 142 (Suppl.): 247-254. 16. Aguilar-Parada E, Eisentraut A M, Unger R H. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med 1969; 257: 415-419. 17. Bucola G, David H. Quantitative determination of serum triglycerides by use of enzymes. Clin Chem 1973; 19: 476. 18. Fleisch A. Le metabolisme basal standard et sa determination au moyen du ‘Metabocalculator’. Helvetica Medica Acta 1951; 18: 23-44.

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19. Mackenzie T A. Clark N G, Bistrisan B R et al. A simple method for estimating nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J Am Co11Nutr 1985; 4: 575-58 1. 20. Nacht C A, Schutz Y, Vemet 0, Christin L, Jequier E. Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans. Am J Physiol 1986; 251: E524529. 21. Forsberg E. Soop M, Theme A. Thermogenic response to total parenteral nutrition in depleted patients with multiple organ failure. Clin Nutr 1993; 12: 253-260. 22. Lindmark L, Eden E, Temell M, Bennegard K, Svaninger G, Lundholm K. Thermic effect and substrate oxidation in response to intravenous nutrition in cancer patients who lose weight. Ann Surg 1986; 204: 628-636. 23. Messing B, Pontal P J, Bemier J J. Metabolic study during cyclic total parenteral nutrition in adult patients with and without corticosteroid-induced hypercatabolism: comparison with standard total parenteral nutrition. JPEN 1983; 7: 21-25. 24. Nub6 M, Bos L P, Winkelman A. Simultaneous and consecutive administration of nutrients in parenteral nutrition. Am J Clin Nutr 1979; 32: 150.5-1510. 25. Soop M, Forsberg E, Theme A, Bergstrom J. Muscle and plasma amino-acid patterns in severely depleted surgical patients. Clin Nutr 1990; 9: 206-213.

June 1994