James L. Mullen

Prognostic nutritional index in gastrointestinal surgery

Based on assessment of 161 nonemergency general surgical patients, a multiparameter index of nutritional status was defined relating the risk of postoperative complications to baseline nutritional status. When applied prospectively to 100 gastrointestinal surgical patients, this index provided an accurate, quantitative estimate of operative risk, permitting rational selection of patients to receive preoperative nutritional support.

Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.

Background The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). Methods and Results Peak Vo2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of <7.4 mg/cm and/or upper arm circumference of <5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675±84 cm3/m2; HF, 567±112 cm3/m2; p < 0.05). Fat stores were largely perserved with triceps skinfold of <5% of normal and/or IBW of <80% in only 8% of patients. Modest linear correlations were observed between peak Vo2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p < 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = −0.42, p<0.05). Conclusions These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.

The link between nutritional status and clinical outcome: can nutritional intervention modify it?

Most clinicians subjectively feel that malnutrition in surgical patients is associated with poor clinical outcome. This overview provides a chronologic review of studies relating poor nutritional status to increased surgical morbidity. Techniques for identifying surgical patients with clinically important nutritional deficits are discussed. Retrospective and/or non-randomized clinical studies evaluating the efficacy of perioperative forced feeding are reviewed. These data suggest a possible role for preoperative nutritional support of selected malnourished surgical candidates and provide the rationale for a large-scale nutrition-intervention clinical trial.

Energy expenditure in malnourished cancer patients.

It is widely believed that the presence of a malignancy causes increased energy expenditure in the cancer patient. To test this hypothesis, resting energy expenditure (REE) was measured by bedside indirect calorimetry in 200 heterogeneous hospitalized cancer patients. Measured resting energy expenditure (REE-M) was compared with expected energy expenditure (REE-P) as defined by the Harris-Benedict formula. The study population consisted of 77 males and 123 females with a variety of tumor types: 44% with gastrointestinal malignancy, 29% with gynecologic malignancy, and 19% with a malignancy of genitourinary origin. Patients were classified as hypometabolic (REE < 90% of predicted), normometabolic (90–110% of predicted) or hypermetabolic(>110% of predicted). Fifty-nine per cent of patients exhibited aberrant energy expenditure outside the normal range. Thirty-three per cent were hypometabolic (79.2% REE-P), 41% were normometabolic (99.5% REE-P), and 26% were hypermetabolic (121.9% REE-P) (p < 0.001). Aberrations in REE were not due to age, height, weight, sex, nutritional status (% weight loss, visceral protein status), tumor burden (no gross tumor, local, or disseminated disease), or presence of liver metastasis. Hypermetabolic patients had significantly longer duration of disease (p < 0.04) than normometabolic patients (32.8 vs. 12.8 months), indicating that the duration of a malignancy may have a major impact upon energy metabolism. Cancer patients exhibit major aberrations in energy metabolism, but are not uniformly hypermetabolic. Energy expenditure cannot be accurately predicted in cancer patients using standard predictive formulae.

A randomized clinical trial of total parenteral nutrition in malnourished surgical patients: the rationale and impact of previous clinical trials and pilot study on protocol design.

The rationale for a large-scale clinical trial of preoperative total parenteral nutrition (TPN) is described in the context of previous clinical trials that have attempted to demonstrate reduction of operative morbidity with preoperative TPN. Defects in study design or execution potentially compromising the validity of these studies are analyzed. Results of a single-institution pilot study performed during the planning phase of the multiinstitutional preoperative TPN trial are presented. This literature review and pilot study provided the data necessary to permit appropriate design of many critical elements in the protocol for the clinical trial including sample size, eligibility criteria, duration and intensity of treatment regimens, and end-point criteria. The rationale underlying critical decisions in protocol design are presented in detail to allow more meaningful interpretation of the results of the clinical trial.

Host‐tumor interaction and nutrient supply

Adequate parenteral nutritional support improves nutritional status in cancer patients, but its effect on tumor growth remains controversial. Using a transplantable mammary adenocarcinoma in a rat‐TPN model, the relative effect of different exogenous intravenous nutrients on tumor growth and host maintenance was studied. Relative to chow controls, starvation increased host depletion without reducing tumor growth. Adequate carbohydrate calories alone neither improved host maintenance nor stimulated tumor growth, yet adequate amino acids alone did improve host maintenance but also stimulated tumor growth. Adequate amino acids and carbohydrates given simultaneously maximized both host maintenance and tumor growth. In contrast, an isocaloric, isonitrogenous, intravenous diet providing non‐nitrogenous calories as fat promoted host maintenance equivalent to carbohydrate‐based TPN with no tumor stimulation. This apparent differential utilization of fat calories by normal and malignant cells may permit manipulation of the relative benefit of parenteral nutrition to host or to tumor, permitting host repletion without tumor stimulation or alternatively tumor stimulation at appropriate times to increase sensitivity to phase‐specific antineoplastic therapy.

Energy expenditure in malnourished gastrointestinal cancer patients.

Cancer cachexia, a common finding in patients with gastrointestinal (GI) malignancy, is frequently attributed to tumor‐induced aberrations in host energy expenditure. To characterize the frequency and severity of aberrations in energy expenditure in GI cancer patients, and to identify the potential influence of tumor characteristics in this group, the authors measured resting energy expenditure (REE) by indirect calorimetry in 173 patients and compared REE to predicted energy expenditure (PEE) from the Harris‐Benedict formulae based on current body weight. Fifty‐eight percent of patients had abnormal REE (normal REE = ±10% PEE); 36% (62 of 173) were hypometabolic (REE <90% PEE), and 22% (39 of 173) were hypermetabolic (REE >110% PEE). Host and tumor factors were compared between metabolic groups to identify potential determinants of abnormal energy expenditure. Differences between groups cannot be explained by differences in patient age, sex, body size, nutritional status, tumor burden, or duration of disease. Resting energy expenditure does not correlate with percent of weight loss, serum albumin, or duration of disease. Analysis by tumor site reveals patients with pancreatic or hepatobiliary tumors to be predominantly hypometabolic; gastric cancer patients tend to be hypermetabolic, whereas patients with colorectal or esophageal neoplasms are more evenly distributed across metabolic groups, the largest portion being normometabolic (X2 = 20.7, P <0.02). The majority of GI cancer patients have abnormal REE which is unpredictable and not uniformly hypermetabolic. The determinants of these abnormalities do not appear to be age, sex, body size, nutritional status or tumor burden. Primary tumor site is a major determinant of energy expenditure in GI cancer patients. Cancer 53:1265‐1273, 1984.

The efficacy of nutritional assessment and support in cancer surgery.

Malnutrition is common in cancer patients and may be an important determinant of operative morbidity and mortality. To determine whether preoperative nutritional assessment can be used to identify a group of high‐risk patients, and whether preoperative TPN decreases morbidity and mortality in this group, retrospective, nonrandomized review of 159 patients who were subjected to major cancer surgery was performed. All patients underwent preoperative multiparameter assessment. A previously developed and validated nutritional assessment model (Prognostic Nutritional Index) was used to evaluate the probability of operative complications. Based on predicted outcome (PNI), patients were assigned to either a high‐risk or low‐risk group for statistical comparison with actual outcome. The effect of preoperative TPN was then analyzed in both risk groups for determination of efficacy of preoperative nutritional support. Substantial malnutrition was found to exist among patients undergoing major cancer surgery and was closely correlated with subsequent morbidity and mortality. This predictive nutritional assessment model accurately identifies a subset of cancer surgery patients at increased risk of operative morbidity and mortality. In this high risk group (PNI ≥ 40%), preoperative nutritional support significantly reduces operative morbidity (P <0.001) and mortality (P <0.025).

Resting energy expenditure in patients with pancreatitis.

ObjectiveTo assess the resting energy-expenditure of hospitalized patients with pancreatitis. DesignProspective, case-referent study. SettingNutrition support service in a university tertiary care hospital. PatientsPatients referred to the Nutrition Support Service with the diagnosis of pancreatitis. Excluded from study entry included those with cancer, obesity (>150% ideal body weight), those measured within 3 postoperative days, or patients requiring ventilator support with an Fio2 of >0.5. Forty-eight patients with either acute pancreatitis (n = 13), chronic pancreatitis (n = 24), acute pancreatitis with sepsis (n = 7), or chronic pancreatitis with sepsis (n = 7) were studied. The two septic groups were combined into a single pancreatitis-with-sepsis group, since no significant differences among measured variables were observed between individual septic groups. InterventionsNone. Measurements and Main ResultsResting energy expenditure was measured by indirect calorimetry and compared with the predicted energy expenditure, as determined by the Harris-Benedict equations. Resting energy expenditure (percent of predicted energy expenditure) was significantly (p < .02) greater for patients with pancreatitis complicated by sepsis (120 ± 11%) compared with the nonseptic chronic pancreatitis group (105 ± 14%). Resting energy expenditure for the nonseptic acute pancreatitis patients (112 ± 17%) was not significantly different from the other groups. The septic pancreatitis group had the largest percentage (82%) of hypermetabolic (resting energy expenditure >110% of predicted energy expenditure) patients, whereas 61% and 33% of the acute and chronic pancreatitis groups were hypermetabolic, respectively (p < .02). ConclusionsResting energy expenditure is variable in patients with pancreatitis (77% to 139% of predicted energy expenditure). The Harris-Benedict equations are an unreliable estimate of caloric expenditure. Septic complications are associated with hypermetabolism and may be the most important factor influencing resting energy expenditure in pancreatitis patients. (Crit Care Med 1991; 19:484)

Consequences of Malnutrition in the Surgical Patient

A series of studies is reviewed in which a multiparameter prognostic nutritional index was developed and tested for its ability to identify operative patients in whom preoperative nutritional repletion can reduce operative morbidity and mortality.