Submited on: 01 Feb 2013 12:29:51 AM GMT
Published on: 01 Feb 2013 06:27:46 AM GMT

Reply to Dr Driyneash Belekar Review:

Thanks for your review and comments. This study was a retrospective pilot study to ascertain the incidence of malnutrition and the effect of Body Mass Index (BMI) and serum albumin on certain outcomes especially days off food after surgery, length of hospital stay, wound infection and death. It had all the limitations of retrospective study and with the exclusion criteria, only fifty patients met the entry criteria. However it was aimed to guide me in a prospective study.

Hypoalbuminaemia is said to cause a lot of complications in the literature which include delayed wound healing, anastomotic dehiscence and increased wound infection rate. These complications in modern day surgery seem to be dependent on multiple factors than just hypoalbuminaemia. Indeed when patients are malnourished the disturbance in function at the cellular level can lead to poor wound healing and anastomotic breakdown

In 1936 Studley1 studied the relationship between weight loss and surgical complications and found that patients who had lost 20% or more of their body weight, who were operated upon for peptic ulcer disease had increased post-operative complications particularly wound dehiscence and pneumonia when compared with those with normal weight. Detsky2 et al found a six-fold increase in significant complications in patients undergoing gastrointestinal surgery who were identified as being severely malnourished prior to surgery.

Patients recovering from major abdominal surgery suffer few ill effects from starvation lasting 3 to 5 days and traditionally, oral fluids are started 3 to 5 days post-operatively when post-operative ileus would have resolved3.  However, beyond this time, malnutrition develops if patients receive 5% dextrose as the only source of energy. It has been shown that small amounts of glucose reduced the rate of catabolism and excretion of nitrogen in the urine. Infusion of 50-100gm of glucose spared 50-75gm of protein. This quantity of glucose is detected by the ?-cells of the pancreas, resulting in increased secretion of insulin, which inhibits muscle proteolysis as the liver does not need to produce glucose by gluconeogenesis from amino acids and ketogenesis stops in parallel to the decrease in gluconeogenesis5. During starvation, glucose infusion inhibits hepatic gluconeogenesis immediately, but after injury, the point at which a rise in blood glucose level switches off gluconeogenesis is said to be set at a higher level.

 DELAYED WOUND HEALING Wound healing is an anabolic process that requires energy and adequate nutritional building blocks.  Several vitamins and mineral deficiencies lead to impaired wound healing. Vitamins C, A and B6, are required for collagen synthesis and cross-linking. Patients who are actively catabolic show impaired wound healing. The metabolic response to trauma results in a net breakdown of body protein for gluconeogenesis that results in loss of lean body mass that can compromise wound healing.  Gluconeogenesis is however essential as the healing wound is a glucose obligatory tissue. Wilmore et al6  showed that in patients who had sustained severe burns on one leg and minor burns on the other, the glucose uptake of the severely burned was four times that of the other leg. There was also a corresponding increase in lactate output from the severely burned leg, suggesting a requirement of the injured tissue for glucose, which it metabolises anaerobically. Nutritional supplementation and the use of anabolic agents have been shown to restore lean body mass and promote wound healing7.

Reducing calorie in-take by 50% in rats was shown to decrease collagen synthesis, matrix protein deposition and granulation tissue formation. The decrease in collagen synthesis was shown to be directly related to weight loss rather than to defective hydroxylation8. Diabetes mellitus affects wound healing qualitative and quantitatively although the mechanism is unknown. The strength of wounds in diabetic animals was found to be low compared with controls but improved with insulin treatment, maintenance of nutrition and treatment of systemic illness9.

In humans modest protein energy malnutrition has been shown to impair fibroplasias10. Pre-operative illness or decreased nutritional intake, in the pre-injury period, has been shown to significantly reduce collagen synthesis while pre-operative enteral or parenteral nutrition has been shown to decrease impairment in wound healing11.

However, it has also been shown that wounds generally heal following oncological operations in the presence of significant malnutrition. The biological priority given to wound healing by the body is said to account for the finding that most wounds heal even in the presence of moderate pre-operative or post-operative malnutrition.  However, severe malnutrition and symptomatic specific nutrient deficiencies do impair wound healing to the extent of delaying the healing process12.

 Incidence of Wound Infection An acquired immune incompetence is thought to be responsible for the increased incidence and virulence of infections seen in patients with protein energy malnutrition13.  Protein energy malnutrition (PEM) in children has been shown to be associated with thymus gland atrophy.  Changes in lymphoid tissues have also been reported and these may adversely affect the process of phagocytosis.  However, surgery itself is immunosuppressive The aetiology of peri-operative immunosuppression is multi-factorial and may be due to the type and degree of operative injury, anaesthesia, blood transfusion, the type of malignancy, patient’s age and nutritional status. All circulating lymphocyte subpopulations except B-lymphocytes have been shown to fall significantly after surgery14. The magnitude and duration of the fall in cell number and the subpopulation affected was related to the degree of surgical trauma. The immune response and the metabolic response to trauma can be modulated by combining nutritional support with attempts to limit the severity of the stimulus producing the response. These include • restoration of adequate fluid volume to correct hypovolaemia, • adequate oxygenation and tissue perfusion •  reducing the degree of trauma with appropriate and careful surgery, • Controlling pain. Pain and anxiety are potent stimuli of the adreno-sympathetic axis and adequate pain control reduces metabolic rate significantly. • correcting acid-base disturbance • reducing infection with good wound care technique and antibiotic prophylaxis and • enteral nutrition15 Removing the thermo-genic response to cold by nursing patient at around 28o C (thermo-neutral temperature) can reduce the metabolic response to injury.  The metabolic response to trauma has been shown to be surgeon dependent, the more skilful the surgeon and the less traumatic the surgery, the less the catabolism. Improved anaesthesia, in particular the use of regional technique, has resulted in lessening of the catabolic response.

 Anastamotic Dehiscence Wound dehiscence and anastomotic leaks are probably more dependent on technical factors than on the rate of collagen synthesis and cross linkage.  Malnutrition is however thought to play a significant role16. Haydock et al using a technique in which the accumulation of hydroxyproline was measured in subcutaneous polytetrafluoroethlene implants, showed improvement in wound healing response in patients who were fed intravenously.


1. Study HO. Percentage of weight loss: A basic indicator of surgical risk in patients with peptic ulcer. Journal of the American Medical Association 1936: 458 – 460 2. Detsky AS, McLaughlin JR, Baker JP, Johnson N, Whittaker S, Mandelson RA, Jeejeebhoy KN. What is Global Assessment of Nutrition? Journal of Parenteral and Entreal Nutrition. 1987; 11(1): 8 – 13 3. Savage A. Nutrition for small bowel disorders. In Morris PJ, Malt R Editors. Oxford Textbook of Surgery. 1st edition. Oxford: Oxford University Press; 1994. p 1008 -1010 4. Fouzia Sadiq, Leslie A Crompton, Jes R Scarfe, Michael Lomax. Effects of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin- conjugating enzyme gene expression in calves. Nutrition & Metabolism 2008, 5:5 5. Clarke D. Studies on whole-body nitrogen turnover, protein synthesis and breakdown in man using 15N glycine. (MD Thesis). Newcastle: University of Newcastle 1994. 6. Wilmore DW, Long JM, Mason AD, Skreen RW, Pruitt BA. Catecholamine’s: Mediator of the hyper-metabolic response to thermal injury. Ann. Surg. 1974; 180(4): 653 – 669 7. Demling RH, DeSanti L. Involuntary weight loss and the non healing wound: the role of anabolic agents. Advanced wound care 199; supplement 1(12):114; quiz 15 -16 8. Spanheimer RG, Peterkofsky B. A specific decrease in collagen synthesis in acutely fasted, vitamin C- supplemented guinea pigs. The journal of Biological Chemistry 1985; 260(7): 3955 – 3962 9. Yu Liu, MD,1 Danqing Min, PHD,2 Thyra Bolton,3 Vanessa Nubé,3 Stephen M. Twigg, PHD, MD,1,2,3 Dennis K. Yue, PHD, MD,1,2,3 and Susan V. McLennan, PHD1,2             Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic              Foot Ulcers.  Diabetes Care. 2009 January; 32(1): 117–119. 10. Goodson WH 3rd, Lopez-Sarmiento A, Jenson JA, West J, Granja-Mena L,     Chavez-Estrella J. The influence of a brief pre-operative illness on post-operative healing. Annals of Surgey 1987; 205(3): 250 -255 11. Haydock DA, Hill GL. Improved wound healing response in surgical patients receiving intravenous nutrition. British Journal of surgery 1987; 74(4): 320 – 323. 12. Albani JE. Nutrition and wound healing. Journal of Parenteral and Enteral Nutrition 1994; 18 367 13. MacLean LD. Host resistance in surgical patients. Journal of trauma 1979; 19(5): 279 – 304. 14. Lennard TW, Shenton BK, Borzotta A, Donnelly PK, White M, Gerrie LM, Proud G, Taylor RM. The influence of surgical operations on components of human immune system. British journal of Surgery 1985; 72 (10): 771 -776. 15. Holte K, Kehlet H. Epidural anaesthesia and analgesia – effects on surgical stress responses and implications for post- operative nutrition. Clinical Nutrition 2002; 21(3): 199-206. 16. Haydock DA, Hill GL. Impaired wound healing in surgical patients with varying degrees of malnutrition. Journal of Parenteral & Enteral Nutrition 1986; 10 (6): 550- 554