The relationship between delayed hypersensitivity response, nutritional status and clinical outcome in surgical patients referred for nutritional support

Delayed hypersensitivity responses to recall antigens were measured in 125 surgical patients referred for nutritional assessment and support. On initial testing 57 patients were skin test positive and 68 were anergic each of these patient groups being closely matched in terms of surgical conditions. There was a mortality of 4 in the skin test positive group and 26 in the anergic group. The anergic patients were significantly older and in biochemical and anthropometric terms were in poorer nutritional status than the skin test positive group. Of 33 anergic patients who were repeat tested, 15 remained anergic and 18 converted to a positive response. Conversion from anergy to a positive response was not associated with changes in the measured indices of nutritional status and did not improve clinical outcome. The value of repeat skin testing is therefore in doubt.     

Metabolic effects of four intravenous nutritional regimens after elective surgery. I. Clinical data and biochemistry

Biochemical variables have been determined in 28 patients before and after resection of carcinoma of colon or rectum. A synthetic oral diet was given for four days before operation, (0.1 gN.kg/day and 165 kJ.kg/day) and four isocaloric intravenous regimens with different amounts and proportions of amino acids were given for six days after operation. During the preoperative diet the serum urea, glucose, urate, inorganic phosphate and cholesterol concentration decreased while those of triglyceride, iron and alanine amino-transferase increased. After operation the serum triglyceride, protein, albumin, iron, TIBC and urate concentrations decreased. The serum calcium fell in all groups receiving amino acids after operation while magnesium increased in all groups except the one receiving the highest amount of amino acids. The urea concentration decreased when no amino acids were given but increased when amino acids were administered whereas the reverse situation occurred with cholesterol. The highest increase in glucose level was observed when the highest amount of amino acids were given.     

Metabolic effects of four intravenous nutritional regimens in patients undergoing elective surgery II.--Muscle amino acids and energy-rich phosphates

Muscle amino acids and energy-rich phosphates have been determined in 28 patients before and after resection of a carcinoma of colon or rectum. Before operation the patients received a synthetic diet (Vivasorb for four days and postoperatively four different intravenous regimens with different amounts and proportions of amino acids were given for six days, the energy intake being the same for all groups. When compared with age-matched healthy controls the patients showed only slight increases in phenylalanine and isoleucine concentration in muscle and plasma with elevated plasma glutamate during the four days prior to the operation. Vivasorb treatment increased the concentration of alanine, glycine and methionine in both muscle and plasma while increases of threonine and histidine were seen only in muscle. Decreased concentrations of valine were found in muscle and plasma, while lysine and leucine decreased only in plasma. As an effect of operation, but independent of the nutritional regimen, muscle asparagine increased and muscle glutamine and glutamate decreased in all groups. The unique pattern of amino acid changes in postoperative trauma was confirmed in the present investigation but few differences in amino acid concentrations could be related to the various nutritional intakes. Alterations in the individual amino acid concentrations were not influenced by the intake of amino acids and seemed to have little relationship to the composition of any solution infused. Prior to operation there were low levels of ATP in muscle possibly due to immobilisation and chronic semistarvation but no changes in the energy rich phosphates could be attributed to trauma or nutrition. The content of muscle glycogen increased as a result of the Vivasorb supply indicating that the preoperative carbohydrate administration promotes muscle glycogen synthesis and postoperatively muscle glycogen was reduced significantly indicating enhanced glycogenolysis in the postoperative state. This finding emphasizes the importance of providing the patients with ample amount of glucose before and after surgery.     

The effect of intralipid on human lymphocyte and monocyte function

Peripheral blood lymphocyte function (PHA) was unaffected by Intralipid in patients receiving lipid as part of a parenteral nutrition regime, and in volunteers receiving a small intravenous bolus. However monocyte function (chemotaxis) was significantly impaired by Intralipid in both groups. Three measures of monocyte function confirmed depression following in vitro exposure to Intralipid. Electronmicrographs of circulating monocytes and autoradiographs of cells exposed to 14C-Intralipid in vitro suggested that this detrimental effect on monocytes may follow phagocytosis of lipid particles. These findings suggest that caution should be exercised with the use of Intralipid in patients at particular risk of sepsis.     

The effect of continuous enteral tube feeding on various nutritional parameters in patients with disseminated malignant melanoma during intensive chemotherapy

In a prospective study the effect of continuous enteral tube feeding was evaluated on various nutritional parameters in patients with disseminated malignant melanoma during 13 chemotherapy courses employing bleomycin, DTIC, vindesine and actinomycin D. The patients received a quantity of calories according to their pretreatment intake, but complete metabolic equilibrium could not be obtained during chemotherapy. Although the weight/height index remained unchanged, a decrease of serum albumin and prealbumin level occurred during all 13 treatment courses. Transferrin level decreased during 11 of these courses and cholinesterase level during 12. Triceps skinfold thickness and arm muscle circumference diminished equally. Serum prealbumin was the first nutritional parameter to fall during chemotherapy and seems to be a very sensitive indicator of the occurrence of nutritional imbalance. The plasma vitamin C level was low before treatment while during treatment both vitamin C and vitamin A level fell quickly even though the nutritional intake of these vitamins was adequate. We conclude that continuous enteral tube feeding, which is a feasible method of feeding, can to some extent fulfill the nutritional needs of patients treated with intensive chemotherapy.     

Effects of preoperative parenteral nutrition on cell-mediated immunity in malnourished patients

Cell-mediated immunity was studied in 19 malnourished patients admitted for major abdominal surgery. Nine of them received total parenteral nutrition (TPN) before operation (the TPN group), while ten (the control group) were operated on without a period of TPN. In vitro lymphocyte proliferative responses to phytohaemagglutinin (PHA), concanavalin A (Con A) and purified protein derivative of tuberculin (PPD), were measured in whole blood cultures preoperatively, at the end of surgery and 5 days after operation. In vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD was studied preoperatively and 5 days after operation. Complications in both groups were observed and recorded. Nutritional assessment was carried out by evaluating the extent of recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and serum albumin and prealbumin concentrations. The patient was considered to be malnourished and was included in the study, if at least three of these criteria were abnormal. In the TPN group changes in mitogen induced lymphocyte proliferative responses caused by surgery were not significant. By contrast, responses in the control group decreased significantly (P < 0.01) during surgery and most of these responses differed from the preoperative values even at the fifth postoperative day. Anergy was equally common in both groups before and after surgery. The number of infectious complications was lower in the TPN group.     

Undernutrition in elective colorectal surgery. Implications for post operative morbidity

The nutritional status of 65 patients undergoing elective colorectal surgery was assessed using 5 conventional nutritional indices, percentage ideal weight, mid arm muscle circumference, triceps skin fold thickness, serum albumin and serum total iron binding capacity. Only 9 patients had values for all five indices which are taken to represent normal nutritional status. This survey suggests that many patients undergoing elective colorectal surgery in this country have subnormal values of the indices commonly used for nutritional assessment but only severe depression of serum albumin however appears to adversely affect the outcome of surgery.     

Prolonged impairment of cell-mediated immunity after major abdominal surgery in malnourished patients

The effect of the nutritional status on postoperative impairment of the immune response was studied in adults undergoing major abdominal surgery. The immune function was evaluated by measuring in vitro the lymphocytic response to phytohaemagglutinin (PHA), concanavalin A (Con A) and the purified protein derivative of tuberculin (PPD) in whole blood cultures, and in vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD. Nutritional assessment was carried out by evaluating recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and the serum concentration of albumin and prealbumin. The patient was considered malnourished, if at least three of these criteria were abnormal. The immune parameters were measured preoperatively, at the end of the surgery and five days after operation. Before the operation both malnourished and well-nourished patients had normal lymphocytic responses, but the malnourished patients had a slower recovery of immune responses after the operation and they had an increased number of postoperative complications. No significant differences in the incidence of anergy were observed between the well and malnourished patients pre or postoperatively.     

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).     

Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood

Acute responses in hormone and substrate concentrations to intravenous administration of a fat emulsion were studied in metabolically normal subjects. Eight subjects were infused with either a fat emulsion or an aqueous solution of glycerol for 3 h. Serum triglycerides (TG), free fatty acids (FFA), glucose, glycerol, 3-hydroxybutyrate (3-OH butyrate), insulin, thyroid hormones, plasma glucagon, norepinephrine, and amino acids were measured. The infusion of a fat emulsion induced a 30% increase in glucose and a 22% decrease in alanine together with significant elevations of TG (> 10 mM) and FFA (> 1 mM). A small increase in insulin (4 microU/ml) and a reduction in glucagon (40 pg/ml) were observed. Eight-fold increases in glycerol occurred with both the fat emulsion and glycerol infusions. The administration of a fat emulsion resulted in a 4-fold increase in 3-OH butyrate, whereas glycerol infusion reduced its level by 50%. Glycerol infusion produced no measurable effects on the substrates other than glycerol or 3-OH butyrate. No significant changes were observed in thyroid hormones or norepinephrine after either solution was given. The data suggest that acute elevation of FFA by means of intravenous fat emulsions leads to preferential oxidation of FFA and stimulates hepatic ketogenesis with resulting glucose conservation as well as inhibition of alanine production without many alterations in hormonal concentrations.     

The effect of environmental temperature on protein and energy changes following burn injury in the rat

The metabolic response to a standard burn injury in rats (25% of body surface area) was investigated at environmental temperature 20 degrees C and 30 degrees C. With an intake of 15 g diet (20% w/w protein) per day, burned rats at 20 degrees C were found to be in negative energy balance mainly due to increased insensible (evaporative) losses, and they lost weight. Fat was the main endogenous source of energy, although protein was also catabolised from both carcass and pelt. At 30 degrees C, insensible losses of burned rats were still high, but they had lower sensible (mainly radiative) losses leading to a positive energy balance and a gain in weight. This consisted mainly of carcass water, fat and protein. Urine catecholamines were higher in burned rats at 20 degrees C than at 30 degrees C and correlated with heat loss, urine nitrogen and urine 3-methylhistidine, supporting the hypothesis that catecholamines play a central role in mediating the protein and energy changes following burn injury. For the first 4-6 days, urine nitrogen and 3-methylhistidine excretion increased in rats at 30 degrees C, suggesting that this early part of the metabolic response is obligatory. These findings support the use of raised environmental temperatures to reduce the metabolic response to burns.     

The effect of solutions of varying branched-chain concentration on the plasma amino acid pattern and metabolism in intensive care patients

30 intensive care surgical patients were investigated over a period of five days following trauma or major surgery. They were randomised by card into two groups, Group I received an amino acid solution containing 45 per cent branched-chain amino acids (BCAA), and group II an amino acid solution with a 10 per cent content of BCAAs. After 24 hours of infusion, the total amino acid concentration and branched-chain amino acid concentration in the plasma of Group I patients already clearly exceeded the normal range, and continued to increase during the period of study. In Group II these parameters rapidly returned to normal where they remained. Cumulative negative nitrogen balance and nitrogen excretion on each day of investigation were significantly less in Group II. These results indicate that after severe trauma or major surgery amino acid solutions containing high concentrations of BCAAs may be an unphysiological load on the already stressed metabolism, rather than a benefit.     

Influence of intravenous hyperalimentation on cardiac dimensions and heart function

Eleven severe malnourished patients, mean age 34 yrs and mean weight 66 per cent of ideal body weight, were studied to evaluate the effect of intravenous hyperalimentation on the function and size of the heart. Left ventricular size and systolic function were measured before and after a mean weight gain of 19 per cent with electro, vector, echo and phonomechanographic methods. During hyperalimentation a statistically significant increase in left ventricular mass (p<0.01) was observed. Correction for body weight showed a parallel increase between the parameters and weight gain. Echocardiographic and phonomechanographic indexes of left ventricular systolic function remained unchanged. A decrease of the amplitude of the maximal spatial QRS vector was shown by vectocardiography. These results indicate that during intravenous hyperalimentation of the severe malnourished a proportional increase in cardiac size and mass occurs with preservation of the left ventricular systolic function.     

Effect of Intralipid on some immunological parameters and leukocyte functions in patients with esophageal and gastric cancer

This study has been undertaken to investigate if the intravenous (i.v.) infusion of fat emulsions may be associated with impairment of some immunological functions thus increasing the risk of septic complications. Fifteen malnourished patients with advanced gastric or esophageal cancer received for 2 weeks preoperatively and 1 week after surgery an isocaloric and isonitrogenous TPN treatment with Intralipid (group A: n=8) or glucose alone (group B: n=7) as energy substrate. Cluster analysis of 11 nutritional parameters and some tests of the humoral and cellular immunity (IgG, IgM, C3c, Factor B; polymorphonuclear (PMN) cells, total lymphocytes, T and B lymphocyte counts; 'in vitro' PMN chemotaxis, adherence to nylon fibers, phagocytosis of latex particles) were sequentially determined. The incidence and severity of post-operative infections were investigated and a 'sepsis score' was calculated for each patient. Pre- and postoperative TPN were not associated with an improvement of the nutritional status. The humoral and cellular immune parameters showed the same behaviour in patients receiving Intralipid and in controls. The chemotactic activity of PMN cells was constantly normal, granulocyte adherence fluctuated below the normality range in controls, whereas phagocytosis of latex was similar in both groups. Post-operative infectious episodes were less severe in patients receiving Intralipid. Our results do not confirm that Intralipid adversely affects some aspects of the humoral and cellular immune response.     

Causes of anergy in the surgical patient and its relationship to postoperative sepsis

Between June 1981 and June 1983 the delayed hypersensitivity response (DHR) was studied in 401 patients considered for major surgical procedure: 320 of these patients underwent surgery. The incidence of sepsis and postoperative mortality was higher in anergic and relative anergic patients than in normal responders (p<0.001). To evaluate whether DHR depression in cancer patients was due to the direct effect of cancer or to tumour-linked malnutrition, the 401 patients were divided into 4 groups: 1) 140 malnourished cancer patients, 2) 51 malnourished non-cancer patients, 3) 120 well-nourished cancer patients and 4) 90 well-nourished non-cancer patients. The mean age was not significantly different for the 4 groups. The results showed a relationship between DHR and nutritional status (p<0.001). The tumour-related DHR impairment disappeared when the cancer and non-cancer patient groups were homogeneous with regard to their nutritional status. Therefore, the tumour was able to determine the DHR depression because of the cancer-linked malnutrition. We did not observe any relationship between local extension of the tumour and lymph node involvement and DHR depression. In 90 well-nourished non-cancer patients the relation between DHR and age was investigated. The incidence of anergy and relative anergy was higher in patients over 59 years than in patients under 60 years (p<0.001).     

Nitrogen sparing effects and mechanisms of branched-chain amino acids in the injured rat

A series of experiments in a rat injury model were designed to elucidate the role and mechanisms of branched-chain amino acids in the post-injury catabolism. Our results suggest that: 1. Nutritional support can maintain nitrogen equilibrium in the early post-operative state. 2. Branched chain amino acids exert a nitrogen sparing effect and thus prevent or minimise post-operative catabolism. 3. Increasing the amount of infused branched chain amino acids results in nitrogen retention. 4. A balanced amino-acid mixture containing 45 per cent branched chain amino acids seems to be optimal for nutritional support in the post-injury state.     

Effect of surgical stress on the erythrocyte insulin receptor

The aim of this study was to investigate whether surgical trauma causes changes in insulin receptors which may have significance on the causation of post-traumatic insulin resistance. Twenty-four patients scheduled for lumbar intervertebral disc operations or thoracotomy were investigated. In patients who did not receive glucose during operation blood glucose and plasma insulin concentrations did not change but lipolysis was induced as indicated by the increase of serum free fatty acids concentration. Glucose infusion (5% w/v) caused a hyperglycaemic and hyperinsulaenemic response without lipolysis. In patients not receiving a glucose load the number of insulin receptors on erythrocyte measured 4 h postoperatively increased from the preoperative values and the affinity of the receptors to insulin in physiological concentration range increased. In patients with glucose load the number of receptors decreased and receptor affinity to insulin at physiological concentration decreased. The results suggest that in patients receiving a glucose load the receptor changes indicate the perioperative development of insulin resistance at receptor level.     

The influence of light on vitamin A degradation during administration

Vitamins are an essential part of total parenteral nutrition. Vitamin A is known to be very sensitive to light and may be absorbed to plastic containers and administration sets. The rate of loss of Vitamin A was therefore assessed from T.P.N. regimens in 3 litre bags during administration. Results indicated that Vitamin A palmitate was not absorbed to P.V.C. and degradation occurred during exposure to daylight, both in the bag and the administration set. Only 7 per cent of the added Vitamin A was delivered from a bag situated close to a source of daylight. Covering the bag reduced losses, although Vitamin A degradation in the administered set remained considerable. Moving the bag and set away from the source of daylight reduced degradation. Artificial light had no detectable effect on Vitamin A stability. Light-induced degradation can cause clinically significant losses of Vitamin A from T.P.N. infusions.     

Blood and urinary amino acids in children receiving total parenteral nutrition

Plasma concentrations and urinary outputs of amino acids were estimated in nineteen patients receiving intravenous hyperalimentation to evaluate the adequacy of dosage and composition of the infusates for the maintenance of normal blood concentrations of essential amino acids. The use of high concentrations of branched chain amino acids seems to be appropriate for valine and isoleucine but not for leucine. The high concentration of cysteine in the infusates used induces a very high urinary excretion of cysteine and cystine and are ineffective to bring the decreased plasma cystine levels back to normal.