Manipulations of the Metabolic Response for Management of Patients with Severe Surgical Illness: Review

The metabolic response to severe surgical illness is complex and varied. Much recent laboratory and clinical research has focused on increasing our understanding of the metabolic response and the development of new therapies designed to modify this response. Antiinflammatory agents can target harmful aspects of the metabolic response; the immune system can be stimulated; and anabolic factors can be used in an attempt to enhance recovery. The nutritional support of the surgical patient remains crucial, but the effects of new additives are being studied in a variety of surgical conditions. As yet, few of these “novel” agents have found an established role in the management of surgical patients. This review focuses on many “novel” agents or those that do not yet have a clearly defined role in surgical illness. Clinical trials in the areas of severe sepsis, major surgical trauma, and major elective surgery have been emphasized.     

Wound Healing Associated with Severe Surgical Illness

Severe injury or infection is associated with a hypermetabolic response that, when excessive, results in impaired wound healing and as a consequence increased morbidity and mortality. The objective examination of wound healing in humans is difficult and generally requires the use of models. Evidence is accumulating that nutritional and growth factors play important roles in improving the wound healing response, particularly after thermal injury and uncomplicated major surgery. The septic patient represents the biggest challenge to those seeking to optimize wound healing capacity. Advances in molecular biology have provided promising therapies in experimental studies of wound healing that await clinical investigation.     

Changes in Intermediary Metabolism in Severe Surgical Illness

Under normal circumstances there is a reciprocal relation between the availability of free fatty acids (FFAs) and glucose in plasma. In the fasted state, FFAs predominate in both availability and the relative contribution to energy production, whereas the same is true for glucose in the fed state. The extent of glucose oxidation is directly determined by its availability, whereas FFAs are normally available well in excess of their rate of oxidation. The rate of FFA oxidation is determined by the rate of transfer into the mitochondria via the carnitine palmitoyltransferase (CPT) enzyme system, which in turn is regulated by the metabolism of glucose. With critical illness the stress response involves mobilization of both plasma glucose and FFAs simultaneously in both the fed and fasted states. In the situation of excess availability of substrates, the metabolism of glucose limits the oxidation of FFAs, thereby channeling those fatty acids into triglyceride (TG) stores in the muscle and the liver. The high FFA concentrations and increased tissue TG stores can limit glucose clearance from the blood, thereby contributing to the development of hyperglycemia. Also, the excessive metabolism of glucose can result in lacticacidemia and can contribute to the depletion of muscle glutamine. The nutritional treatment of such patients must account for these underlying metabolic responses to avoid amplifying potentially detrimental responses to the excess availability of substrates already present in the fasting state.     

Metabolic Response to Preoperative Chemotherapy Predicts Prognosis for Patients Undergoing Surgical Resection of Colorectal Cancer Metastatic to the Liver

Background

Biological characteristics of colorectal cancer liver metastases (CRCLM) are increasingly recognized as major determinants of patient outcome. The purpose of this study was to evaluate the prognostic value of metabolic response to preoperative chemotherapy as quantified by ¹⁸F-FDG positron emission tomography (PET) for patients undergoing liver resection of CRCLM.

Methods

All patients (n = 80) who had staging PET before liver resection for CRCLM at Austin Health in Melbourne between 2004 and 2011 were included. Thirty-seven patients had PET and CT imaging before and after preoperative chemotherapy. Semiquantitative PET parameters—maximum standardized uptake variable (SUV_max), metabolic tumour volume (MTV), and total glycolytic volume (TGV)—were derived. Metabolic response was determined by the proportional change in PET parameters (?SUV_max, ?MTV, ?TGV). Prognostic scores, CT RECIST response, and tumour regression grading (TRG) were also assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan–Meier survival and multivariate analysis.

Results

Semiquantitative parameters on staging PET before chemotherapy were not predictive of prognosis, whereas all parameters after chemotherapy were prognostic for RFS and OS. Only ?SUV_max was predictive of RFS and OS on multivariate analysis. Patients with metabolically responsive tumours had an OS of 86 % at 3 years vs. 38 % with nonresponsive or progressive tumours (p = 0.003). RECIST and TRG did not predict outcome.

Conclusions

Tumour metabolic response to preoperative chemotherapy as quantified by PET is predictive of prognosis in patients undergoing resection of CRCLM. Assessing metabolic response uniquely characterizes tumour biology, which may allow future optimization of patient and treatment selection.     

Oversight in Surgical Innovation: A Response to Ethical Challenges

Background

Surgical innovation has advanced outcomes in the field, but carries inherent risk for surgeons and patients alike. Oversight mechanisms exist to support surgeon-innovators through difficulties associated with the innovation process.

Methods

A literature review of ethical risks and oversight mechanisms was conducted.

Results

Oversight mechanisms range from the historical concept of surgical exceptionalism to departmental, hospital, and centralized committees. These fragmentary and non-standardized oversight mechanisms leave surgeon-innovators and patients open to significant risk of breaching the ethical principles at the core of surgical practice. A systematized approach that mitigates these risks while maintaining the independence and dignity of the surgical profession is necessary. We propose an oversight framework that incorporates multiple structures tailored toward the ethical risk introduced by different forms of innovation.

Discussion

We summarize ethical risks and current regulatory structures, and we then use these findings to outline an oversight framework that may be applied to surgical practice.

     

General Metabolic Response to Trauma Including Pain Influence

A review is presented of the posttraumatic response from the endocrine and metabolic aspects. The importance of afferent nerve impulses and other factors of importance in the activation of the response are discussed.     

Metabolic Management of Severe Acute Pancreatitis

The metabolic management of severe acute pancreatitis involves early identification of patients with severe pancreatitis, aggressive fluid resuscitation, organ support, and careful monitoring in an intensive care environment. Recent evidence has helped to define the roles of enteral feeding, prophylactic antibiotics, endoscopic retrograde cholangiopancreatography, computed tomography, and fine-needle aspiration for bacteriology. The most difficult decision in the management of these patients is whether surgery is required and which of the complementary approaches to necrosectomy and drainage is appropriate. Key metabolic events in the acinar cell, pancreas, and intestines are now being unraveled, as is the basis for the systemic manifestations and organ dysfunction associated with pancreatitis. This gives hope for the development of more specific metabolic interventions, which will likely target the maintenance of intestinal integrity and function, preservation of pancreatic microcirculation, and balanced modulation of the inflammatory response.     

Cardiovascular and Metabolic Response to Acute Normovolemic Anemia: Effects of Anesthesia

Background: The maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution.

Methods: Forty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl-nitrous oxide-isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 +/- 222 ml (mean +/- SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups.

Results: In the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 +/- 0.5 to 4.8 +/- 1.0 l [middle dot] min-1 [middle dot] m-2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 +/- 0.5 to 3.1 +/- 0.7 l [middle dot] min-1 [middle dot] m-2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased.     

Initiators and Propagators of the Metabolic Response to Injury

Injury produces tissue hypoperfusion and subsequent reperfusion, afferent neural activity, and immune and vascular endothelial activation. These, in turn, set up a cascade of events coordinated by the central nervous system and at the level of individual tissues such as the liver, gut, and skeletal muscle. They are mediated by a complex array of neutrophil and macrophage products. The changes result in hypermetabolism, lypolysis, lysis of skeletal muscle and visceral protein, and expanded extracellular fluid with consequent organ failure.     

Metabolic Management of Patients with Severe Burns

Burn injury results in profound metabolic abnormalities perpetuated by an exaggerated stress response to injury. Hypermetabolism and marked catabolism, with rapid erosion of lean body mass, becomes evident shortly after injury. Much of the morbidity and mortality of a major burn can be attributed to this process, which increases infection risks, decreases the healing rate, and alters cell function. Rapid removal of devitalized burn tissue combined with early aggressive nutritional support significantly attenuates this autodestructive process. The addition of anabolic agents decreases the degree of lean mass loss and increases the rate of restoration. Immediate attention to the metabolic response to a severe burn significantly decreases complications and improves outcome.     

Metabolic Profile of Clinically Severe Obese Patients

Background

Since low basal metabolic rate (BMR) is a risk factor for weight regain, it is important to measure BMR before bariatric surgery. We aimed to evaluate the BMR among clinically severe obese patients preoperatively. We compared it with that of the control group, with predictive formulas and correlated it with body composition.

Methods

We used indirect calorimetry (IC) to collect BMR data and multifrequency bioelectrical impedance to collect body composition data. Our sample population consisted of 193 patients of whom 130 were clinically severe obese and 63 were normal/overweight individuals. BMR results were compared with the following predictive formulas: Harris?CBenedict (HBE), Bobbioni-Harsch (BH), Cunningham (CUN), Mifflin?CSt. Jeor (MSJE), and Horie-Waitzberg &; Gonzalez (HW &; G). This study was approved by the Ethics Committee for Research of the University of Brasilia. Statistical analysis was used to compare and correlate variables.

Results

Clinically severe obese patients had higher absolute BMR values and lower adjusted BMR values (p?p?=?0.0002 and p?=?0.0193, respectively), while the BH and CUN underestimated this value; only the MSJE formulas showed similar results to those of IC.

Conclusions

The clinically severe obese patients showed low BMR levels when adjusted per kilogram per body weight. Body composition may influence BMR. The use of the MSJE formula may be helpful in those cases where it is impossible to use IC.     

Surgical Technique: A Cup-in-Cup Technique to Restore Offset in Severe Protrusio Acetabular Defects

Background  

Severe medial and/or superior defects encountered in revision THA are currently managed with jumbo (≥ 66 mm) acetabular components and modular augments, with reconstruction cages, or with the cup-cage technique. Preoperative planning can indicate when these techniques may not restore vertical and horizontal offset. Failure to restore offset can lead to impingement, leg length inequality, abductor weakness, and dislocation.     

The Omentum: Anatomical, Metabolic, and Surgical Aspects

Introduction  The omentum is acknowledged to have diverse functions in the pathophysiology of intra-abdominal disease. Its angiogenic properties act as a natural defense mechanism in peritonitis and intra-abdominal sepsis. With advancing technology the omentum is revealing itself as a new player in the field of molecular surgery with special reference to cancer, obesity and tissue reconstruction. Materials and methods  This article reviews the existing and potential surgical applications of the omentum.