Evidence-based surgical care and the evolution of fast-track surgery.

BACKGROUND: Optimization of postoperative outcome requires the application of evidence-based principles of care carefully integrated into a multimodal rehabilitation program. OBJECTIVE: To assess, synthesize, and discuss implementation of "fast-track" recovery programs. DATA SOURCES: Medline MBASE (January 1966-May 2007) and the Cochrane library (January 1966-May 2007) were searched using the following keywords: fast-track, enhanced recovery, accelerated rehabilitation, and multimodal and perioperative care. In addition, the synthesis on the many specific interventions and organizational and implementation issues were based on data published within the past 5 years from major anesthesiological and surgical journals, using systematic reviews where appropriate instead of multiple references of original work. DATA SYNTHESIS: Based on an increasing amount of multinational, multicenter cohort studies, randomized studies, and meta-analyses, the concept of the "fast-track methodology" has uniformly provided a major enhancement in recovery leading to decreased hospital stay and with an apparent reduction in medical morbidity but unaltered "surgery-specific" morbidity in a variety of procedures. However, despite being based on a combination of evidence-based unimodal principles of care, recent surveys have demonstrated slow adaptation and implementation of the fast-track methodology. CONCLUSION: Multimodal evidence-based care within the fast-track methodology significantly enhances postoperative recovery and reduces morbidity, and should therefore be more widely adopted. Further improvement is expected by future integration of minimal invasive surgery, pharmacological stress-reduction, and effective multimodal, nonopioid analgesia.

Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial.

OBJECTIVE: To determine if growth hormone (GH) and glutamine (Gln) might allow for a reduction in parenteral nutrition (PN) in individuals with short bowel syndrome. BACKGROUND DATA: Following massive intestinal resection, patients frequently sustain severe nutrient malabsorption and are dependent on PN for life. GH treatment with or without Gln might allow for a reduction in PN. METHODS: A prospective, double-blind, randomized, placebo-controlled clinical trial performed in 41 adults dependent on PN. Following screening, patients were admitted to an in-house facility for 6 weeks. After 2 weeks of stabilization and dietary optimization, patients were randomized to one of 3 treatment arms (1:2:2 ratio): oral Gln (30 g/day) + GH placebo (control group, n = 9), Gln placebo + GH (0.1 mg/kg per day, n = 16), or Gln + GH (n = 16). Standard criteria based on clinical and laboratory measurements were followed to determine PN volume and content. After 4 weeks of treatment, patients were discharged and monitored; GH and GH placebo were discontinued, but the diet with Gln or Gln placebo was continued for 3 months. RESULTS: Patients receiving GH + Gln placebo + diet showed greater reductions in PN volume (5.9 +/- 3.8 L/wk, mean +/- SD), PN calories (4338 +/- 1858 calories/wk), and PN infusions (3 +/- 2 infusions/wk) than corresponding reductions in the Gln + diet group (3.8 +/- 2.4 L/wk; 2633 +/- 1341 calories/wk; 2 +/- 1 infusions/wk, P < 0.05). Patients who received GH + Gln + diet showed the greatest reductions (7.7 +/- 3.2 L/wk; 5751 +/- 2082 calories/wk; 4 +/- 1 infusions/wk, P < 0.001 versus Gln + diet). At the 3-month follow-up, only patients who had received GH + Gln + diet maintained significant reductions in PN (P < 0.005) compared with the Gln + diet. CONCLUSIONS: Treatment with GH + diet or GH + Gln + diet initially permitted significantly more weaning from PN than Gln + diet. Only subjects receiving GH + Gln + diet maintained this effect for at least 3 months.

Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome.

BACKGROUND & AIMS: We evaluated perioperative plasma endotoxin, plasma soluble CD14 molecule (sCD14), plasma endotoxin inactivation capacity (EIC) changes and clinical outcome after glutamine was provided in parenteral feedings to patients on whom gastrointestinal operations were performed using a prospective, randomized, double-blind study design. METHODS: Forty patients undergoing gastrointestinal operations were randomized into two groups, each had 20 patients. One group received standard parenteral nutrition and the other received the same formulation but supplemented with the dipeptide alanyl-glutamine, the two groups were isonitrogenous. The infusion was started from 1 day before operation to the 3rd day after operation for 5 days. Blood samples were collected on the morning of 1 day before operation, 3h after operation, and on the morning of 1, 4 and 7 days after operation and analyzed for plasma endotoxin level, plasma sCD14 level and EIC. RESULTS: There were no differences between the two groups on plasma endotoxin level. After surgery a rapid reduction in plasma EIC was observed in both groups, a significant restoration of the plasma EIC was observed on the morning of 1 and 4 days after surgery in the study group (0.12+/-0.02 and 0.078+/-0.022 EU/mL, respectively, P < 0.01). A significant rise in plasma sCD14 level was found in the study group on the morning of 1 and 4 days after surgery (14.32+/-1.69 and 10.34+/-1.14 microg/mL, respectively, P < 0.01). Shortened hospital stay was observed in the study group (11.7+/-2.0 days in the control group and 10.6+/-1.2 days on the study group respectively, P = 0.03). CONCLUSION: Perioperative parenteral nutrition supplemented with dipeptide alanyl-glutamine ameliorated postoperative immunodepression without direct effect on endotoxemia.

Basic science faculty in surgical departments: advantages, disadvantages and opportunities.

The number of Ph.D. faculty in clinical departments now exceeds the number of Ph.D. faculty in basic science departments. Given the escalating pressures on academic surgeons to produce in the clinical arena, the recruitment and retention of high-quality Ph.D.s will become critical to the success of an academic surgical department. This success will be as dependent on the surgical faculty understanding the importance of the partnership as the success of the Ph.D. investigator. Tighter alignment among the various clinical and research programs and between surgeons and basic scientists will facilitate the generation of new knowledge that can be translated into useful products and services (thus improving care). To capitalize on what Ph.D.s bring to the table, surgery departments may need to establish a more formal research infrastructure that encourages the ongoing exchange of ideas and resources. Physically removing barriers between the research groups, encouraging the open exchange of techniques and observations and sharing core laboratories is characteristic of successful research teams. These strategies can meaningfully contribute to developing successful training program grants, program projects and bringing greater research recognition to the department of surgery.

Enteral and parenteral arginine supplementation to improve medical outcomes in hospitalized patients.

The amino acid L-arginine has been administered as a single supplement to humans in an effort to improve the outcome of seriously ill patients. In normal individuals, markers of collagen biosynthesis have increased with daily oral doses ranging from 14 to 24.8 g of free arginine for 14 d. No clinical evidence of improved wound healing has been reported in the few patient studies performed to date. Administration of enteral, but not intravenous, arginine has been associated with markers of improved immune function in normal individuals and in some, but not all, patient groups studied. A single study in premature infants suggested that supplementation of L-arginine (261 mg . kg(-1) . d(-1)) administered by both the parenteral and enteral routes decreased the incidence of necrotizing enterocolitis. A single study demonstrated that oral arginine administration in conjunction with conventional chemotherapy for active tuberculosis to HIV- but not HIV+ individuals enhanced treatment responses. In both these area, larger multicenter investigations are needed. For a difference to be a difference it has to make a difference. Supplementation of only L-arginine does not to date universally show benefit, nor does it show harm. At this time there is no rationale for the routine supplementation of arginine alone to enhance recovery from serious illness. Because of the potential for harm, this amino acid should only be administered to critically ill patients in large doses under carefully monitored study conditions.

Indications for specific therapy in the rehabilitation of patients with the short-bowel syndrome.

Diarrhoea, malabsorption and malnutrition characterize the short-bowel syndrome. Following the initial intestinal resection, complications such as fistulas and intra-abdominal abscesses may occur, but these usually resolve with appropriate surgical care. All residual intestine should be placed in continuity before serious attempts at rehabilitation with oral feedings are initiated. Small hourly oral feedings composed of food items high in complex carbohydrate and low in fat are started when appropriate and the diet is gradually increased as intestinal adaptation occurs. The goal during this process is to prevent diarrhoea and allow the formation of semiformed stools. With time, parenteral nutrition (PN) can be reduced, and the time required depends on both length of residual bowel and the particular anatomy involved-for example, the presence or absence of the colon. A programme of optimal diet plus growth hormone (0.1 mg/kg) and oral glutamine (30 g/day) enhances the adaptive process and allows many patients independence from PN. However, those with extremely short segments of jejuno-ileum (<50 cm) and no colon have excessive fluid and electrolyte losses, and intestinal transplantation may be the only therapy which allows such patients to be independent of PN.

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.

BACKGROUND: This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. METHODS: Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. RESULTS: The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay was significantly shorter in the gln group than controls (67 +/- 4 days versus 73 +/- 6; p = .026). On day 30, wound healing was 86% +/- 2% complete in the gln group compared with 72% +/- 3% in controls (p = .041). Total cost of hospitalization was 62794 +/- 6178 RMB (dollar 7593 +/- 747 US dollars) in the gln group and 68996 +/- 8620RMB (dollar 8343 +/- 1042, p = .031) in controls, although the cost of the enteral nutrition was higher in the gln-supplemented patients. CONCLUSION: Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels, improved gut permeability, and initially decreased plasma endotoxin levels in severely thermally injured patients. These alterations were associated with a reduction in the length of hospitalization and lower costs.

Jonathan Roads Symposium Papers. History of parenteral nutrition.

A survey is given of the development of parenteral nutrition with the beginning of William Harvey's fantastic discovery of the circulation to today's discussion of what is an optimal regime of parenteral nutrition. The important and different steps of development during the 17th and 19th centuries are discussed. The modern steps during the last century leading to the concept we have today of parenteral nutrition is mentioned, with reference to all pioneers all over the world. Glucose, protein hydrolysates and crystalline amino acids, development of safe fat emulsions, and the current concepts of parenteral nutrition and future considerations are discussed.

Impact of perioperative treatment of recombinant human growth hormone on cell immune function and intestinal barrier function: randomized, double-blind, controlled trial.

The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation ( p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values ( p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.

From Cuthbertson to fast-track surgery: 70 years of progress in reducing stress in surgical patients.

OBJECTIVE: To evaluate the evolution of knowledge concerning the stress response in surgical patients and to determine the therapeutic benefit of stress reduction therapy. SUMMARY BACKGROUND DATA: The stress response in surgical patients is associated with tissue catabolism, organ failure, and prolonged recovery. Understanding the neural-hormonal basis for these events has stimulated efforts to attenuate these undesirable effects. A review of the results of these efforts is important for the application of stress reduction therapy and further improvement of surgical care. METHODS: Medline was searched from 1980 to the present using the terms "stress response," "neural-hormonal response," "fast track surgery," and "outcome in surgical patients." These papers were reviewed along with historical information relating to early descriptions of metabolic and stress responses in surgical patients. RESULTS: Improved understanding of the stress response in surgical patients has occurred over the past 70 years. Multiple examples of stress reduction associated with decreased morbidity and mortality are reported. CONCLUSIONS: Reduction of stress in surgical patients has improved outcome. The use of stress reduction techniques will continue to expand and contribute to the improvement of future surgical care.

Multimodal strategies to improve surgical outcome.

OBJECTIVE: To evaluate the effect of modifying perioperative care in noncardiac surgical patients on morbidity, mortality, and other outcome measures. BACKGROUND: New approaches in pain control, introduction of techniques that reduce the perioperative stress response, and the more frequent use of minimal invasive surgical access have been introduced over the past decade. The impact of these interventions, either alone or in combination, on perioperative outcome was evaluated. METHODS: We searched Medline for the period of 1980 to the present using the key terms fast track surgery, accelerated care programs, postoperative complications and preoperative patient preparation; and we examined and discussed the articles that were identified to include in this review. This information was supplemented with our own research on the mediators of the stress response in surgical patients, the use of epidural anesthesia in elective operations, and pilot studies of fast track surgical procedures using the multimodality approach. RESULTS: The introduction of newer approaches to perioperative care has reduced both morbidity and mortality in surgical patients. In the future, most elective operations will become day surgical procedures or require only 1 to 2 days of postoperative hospitalization. Reorganization of the perioperative team (anesthesiologists, surgeons, nurses, and physical therapists) will be essential to achieve successful fast track surgical programs. CONCLUSIONS: Understanding perioperative pathophysiology and implementation of care regimes to reduce the stress of an operation, will continue to accelerate rehabilitation associated with decreased hospitalization and increased satisfaction and safety after discharge. Developments and improvements of multimodal interventions within the context of "fast track" surgery programs represents the major challenge for the medical professionals working to achieve a "pain and risk free" perioperative course.

Nutrition and Metabolic Support in the 21st Century / 中国临床营养杂志

Objective　New approaches to nutritional support are necessary to test therapies that may potentially enhance outcomes.Such approaches include the move to rely on the enteral route for nutrient delivery,the ability to reduce exogenous calories in our nutritional support systems,the need to utilize nutrients for their pharmacological effects,the ability to use growth factors to enhance nutrient efficacy,and the ability to institute nutritional supplementation before elective operations,thus practicing preventative nutrition.Testing these approaches in the years to come should allow us to identify modalities that will permit us to move away from nutritional therapy as a supportive modality and use it as a primary or secondary method fo patient care.

Impedimentos para el uso exitoso de anabolicos en el cuidado clinico / Impediment for successfull use of anabolics in clinical care

Los factores de crecimiento son uno de los medios que dentro de poco tendrán gran importancia en los esfuerzos para proveer nutrición deficiente y efectiva a los pacientes catabólicos. Antes de eso, sin embargo, será necesario aclarar algunos puntos para hacer óptima su utilización. Por ejemplo, se deben conocer mejor los efectos de tales sustancias en los pacientes desnutridos, la influencia de las desciendas nutricionales sobre ios efectos anabólicos, el efecto de la inflamación sobre la síntesis de proteínas estimulada por factores de crecimiento, y se deben apreciar ciertas cuestiones relativas a seguridad y costos. La preparación adecuada de los médicos y algunos cambios en nuestra manera actual de tratar a los pacientes, pueden ser los mayores obstáculos que se deban vencer si en verdad se desea aplicar plenamente esta biotecnología al cuidado clínico de los enfermos

Nutricion y soporte metabolico en el siglo XXI / Nutrition and metabolic support in XXI century

Se necesitan nuevos estudios del soporte nutricional, para probar tratamientos que pudieran mejorar los resultados finales de los pacientes. Entre los temas para estudio se incluyen la tendencia a depender sobre todo de la vía entera; para el suministro de nutrientes, la capacidad para reducir las calorías exógenas en nuestros sistemas de soporte nutricional, la necesidad de utilizar nutrientes por sus efectos farmacológicos, la habilidad para utilizar los factores de crecimiento con el fin de incrementar la eficacia de los nutrientes, y la capacidad de iniciar suplementación nutricional antes de intervenciones quirúrgicas electivas, con lo que se practica la nutrición preventiva. Las comprobaciones sobre estos asuntos en los años venideros deberán permitir la identificación de modalidades que hagan salir la terapia nutricional de su modalidad de soporte para llevarla a sermétodo primario o secundario de tratamiento para los pacientes