Bioelectrical impedance plethysmographic analysis of body composition in critically injured and healthy subjects.

BACKGROUND: Determination of body composition during critical illness is complex because of various patient-related and technical factors. Bioelectrical impedance is a promising technique for the analysis of body composition; however, its clinical utility in critically injured patients is unknown. OBJECTIVE: The purpose of this study was to compare bioelectrical impedance with metabolic activity in healthy and critically injured patients. If bioelectrical impedance accurately determines body composition during critical illness, the slope between body-composition variables and oxygen consumption would be the same in critically injured and healthy subjects. DESIGN: There is a strong linear relation between body composition and metabolic activity. In the present study, body composition (fat-free mass and body cell mass) was determined by using bioelectrical impedance and resting metabolic activity (metabolic rate and oxygen consumption) by using gas exchange analysis in a group of healthy and critically injured subjects. The relation between these variables was compared by using linear regression to a similar relation established by hydrostatic weighing in a large historical control group. RESULTS: The slope of the line relating fat-free mass to resting metabolic rate was the same in the healthy and critically ill groups (P = 0.62) and each was similar to the slope of the line for the control group. However, in 37% of the critically injured group, overhydration contributed to an increase in fat-free mass, disturbing the relation with resting metabolic rate. The slope of the line relating body cell mass to oxygen consumption in our healthy and critically ill groups was almost identical. CONCLUSION: These results support the use of bioelectrical impedance to determine body cell mass in healthy and critically ill subjects.

Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators.

Skeletal muscle protein wasting is a prominent feature of the metabolic response to sepsis. Persistent protein wasting leads to muscle dysfunction and prolongs recovery from the septic insult. Unfortunately, conventional nutritional support alone does not prevent the sepsis-induced weight loss and catabolism of muscle. Hence, mechanisms other than substrate deficiency appear to be involved in the derangements in protein metabolism during sepsis. The catabolism of muscle during sepsis results from a stimulation of proteolysis and an inhibition of protein synthesis. This review summarizes the mechanisms responsible for alterations in protein synthesis and degradation in muscle during sepsis at the biochemical level. The ability of hormones (insulin, insulin-like growth factor I, glucocorticoids) or cytokines (tumor necrosis factor, interleukin-1) to act as mediators of protein catabolism is also examined. Finally, we discuss the potential role of anticytokine therapies in preventing derangements in protein metabolism during sepsis. A picture is emerging which suggests that cytokines may influence skeletal muscle protein metabolism during sepsis both indirectly through inhibition of the regulatory actions of anabolic hormones on protein turnover, and directly through modulation of the protein synthesis and degradation enzymatic machinery.

Sepsis inhibits synthesis of myofibrillar and sarcoplasmic proteins: modulation by interleukin-1 receptor antagonist.

The breakdown of myofibrillar and sarcoplasmic (nonmyofibrillar) proteins are regulated independently in sepsis, however, the factors regulating their synthesis are unknown. In this study, we assessed the effects of sepsis and interleukin-1 receptor antagonist on sarcoplasmic and myofibrillar protein synthesis in gastrocnemius. The rate of sarcoplasmic protein synthesis was 3.5 times that of myofibrillar proteins in control and septic rats. The synthesis of both sarcoplasmic and myofibrillar proteins was diminished proportionately during sepsis (p < .05). Infusion of interleukin-1 receptor antagonist (2 mg.kg.-1.h.-1) prevented the sepsis-induced inhibition of total, sarcoplasmic, and myofibrillar protein synthesis. Changes in the abundance of messenger RNA could not account for the inhibition of protein synthesis observed in sepsis. Furthermore, in vitro translation of messenger RNA isolated from control and septic muscle revealed no major differences. These results suggest the following: 1) the inhibition of total mixed proteins during sepsis is a consequence of reduced synthesis of both myofibrillar and sarcoplasmic proteins; 2) IL-1ra maintains control values of protein synthesis by sparing the reduction in synthesis of both myofibrillar and sarcoplasmic proteins during sepsis; and 3) the abundance of messenger RNA is not a rate-limiting determinant of protein synthesis in muscle from septic rats. An alteration in the translational efficiency of existing mRNA appears to be the major mechanism responsible for the inhibition of protein synthesis during sepsis.

Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle.

Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1alpha infusion on protein synthesis in Individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the epsilon-subunit of eukaryotic initiation factor 2B (elF2Bepsilon) in gastrocnemius from IL-1 -treated animals. However, the content of the alpha-subunit of elF2 (elF2alpha) was unaffected. In contrast, the elF2alpha content in heart was increased by IL-1, although elF2Bepsilon levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2Bepsilon. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.

Nonoperative management of the ruptured spleen: a revalidation of criteria.

BACKGROUND: Our goal was to revalidate this institution's original criteria for safe nonoperative management of splenic injury. METHODS: This was a prospective series between October 1991 and December 1995 entering all patients with splenic injury to a modified algorithm. Patients were taken to the operating room if hemodynamically unstable (systolic blood pressure less than 90 mm Hg; pulse greater than 110 beats per minute) after 2 liters of fluid resuscitation, positive abdominal examination findings, American Association for the Surgery of Trauma Organ Injury Scale Grade IV or V injuries by computed tomographic scan (unless younger than 15 years old), or associated severe head injuries (unless younger than 15 years old), or age greater than 55. The remainder of the patients were closely observed. RESULTS: One hundred seventy-three patients were entered-six were excluded by death before operating room salvage, and one was excluded because of operation for a ruptured thoracic aorta. Therefore 166 patients were reviewed. Seventy splenectomies and 18 splenorrhaphies were performed, and 78 patients were treated nonoperatively (58% splenic salvage). Two failures occurred in the nonoperative group: a 16-year-old with a grade IV hilar injury was operated on on the eighth day after injury because of a continually falling hematocrit, and a 25-year-old with unresolved tachycardia was operated on at 6 hours (97% success rate). The patients in the operative group had a greater severity of injury as determined by mean Injury Severity Score of 32, 18 deaths, a mean transfusion requirement of 14 units of blood compared with mean injury severity score of 21, two deaths from brain injury, and no transfusions given in 58 of the 78 nonoperative cases. CONCLUSIONS: Prospectively applied, these guidelines allow the safe nonoperative management of patients with blunt splenic injury.

Validation of several established equations for resting metabolic rate in obese and nonobese people.

OBJECTIVE: To evaluate several equations for predicting resting metabolic rate against measured values in obese and nonobese people. DESIGN: Resting metabolic rate was measured with indirect calorimetry. Four calculation standards using various combinations of weight, height, and age were used to predict resting metabolic rate: a) Harris-Benedict equation, b) Harris-Benedict equation using adjusted body weight in obese individuals, c) Owen, and d) Mifflin. Main outcome was percentage of subjects whose calculated metabolic rate was outside a +/-10% limit from measured values. Subjects/Setting 130 nonhospitalized adult volunteers grouped by degree of obesity (range of body mass index, 18.8 to 96.8). Statistical Analysis Performed Analysis of proportions was used to determine differences in the percentage of subjects estimated accurately by each equation; alpha was set at 0.05. RESULTS: Calculated resting metabolic rate was more than 10% different from measured in 22% of subjects using the Mifflin equation, 33% using the Harris-Benedict equation (P=.05 vs Mifflin), and 35% using the Owen equation (P<.05 vs Mifflin). The error rate using Harris-Benedict with adjusted weight in obesity was 74% (vs 36% in obese subjects using actual weight in the standard Harris-Benedict equation). APPLICATIONS/CONCLUSION: Of the calculation standards tested, the Mifflin standard provided an accurate estimate of actual resting metabolic rate in the largest percentage of nonobese and obese individuals and therefore deserves consideration as the standard for calculating resting metabolic rate in obese and nonobese adults. Use of adjusted body weight in the Harris-Benedict equation led to less overestimation by that equation in obese people at the expense of increased incidence of underestimation.

Limits of body mass index to detect obesity and predict body composition.

Body mass index (BMI) is commonly used to identify obesity. In this study, we determined how accurately BMI could determine body composition and identify obese from non-obese individuals. Fat-free mass and body fat were determined with bioelectrical impedance. Adiposity was calculated as body fat per body mass and as body fat divided by body height (m2). Obesity was defined as a BMI of at least 30 kg/m2 or an amount of body fat of at least 25% of total body mass for men and at least 30% for women. Obesity as defined by percentage of body fat was always present with a BMI of at least 30 kg/m2. However, 30% of men and 46% of women with a BMI below 30 kg/m2 had obesity levels of body fat. The greatest variability in the prediction of percentage of body fat and body fat divided by height (m2) from regression equations using BMI was at a BMI below 30 kg/m2. In conclusion, using impedance-derived body-fat mass as the criterion, people with BMI of at least 30 kg/m2 are obese. However, significant numbers of people with a BMI below 30 kg/m2 are also obese and thus misclassified by BMI. Percent of body fat and body fat divided by height (m2) are predictable from BMI, but the accuracy of the prediction is lowest when the BMI is below 30 kg/m2. Therefore, measurement of body fat is a more appropriate way to assess obesity in people with a BMI below 30 kg/m2.

Accelerated nitrogen loss after traumatic injury is not attenuated by achievement of energy balance.

BACKGROUND: We wanted to determine if achievement of energy balance decreases myofibrillar protein catabolism and nitrogen loss during posttraumatic catabolic illness. METHODS: Surgical intensive care unit of a level I trauma center in a university medical center. Trauma patients expected to be mechanically ventilated for at least 4 days were randomly assigned to one of three parenteral feeding groups: (1) nonprotein calorie group: dextrose and lipid intake equal to measured energy expenditure; (2) total calorie group: dextrose, lipid, and protein intake equal to measured energy expenditure; and (3) hypocaloric group: dextrose and lipid intake equal to 50% of measured energy expenditure. Target protein intake for all groups was 1.7 g/kg body wt. On day 4 of nutrition support, a 24-hour balance study was conducted. Urine urea and total nitrogen production, 3-methylhistidine excretion, energy expenditure, and substrate utilization were measured. RESULTS: Despite significant differences in nonprotein and total calorie balance among the groups, nitrogen loss, nitrogen balance, and catabolic rate were not significantly different. Nitrogen loss correlated with catabolic rate but not with energy expenditure or energy balance. Catabolic rate was associated with energy expenditure but not with energy balance. Nitrogen loss was positively correlated with the percentage of nonprotein energy expenditure met by nonprotein calorie intake. CONCLUSIONS: Achievement of energy balance (nonprotein or total energy) failed to decrease catabolic rate or nitrogen loss acutely in multiple trauma patients. Provision of caloric intake equal to energy expenditure does not seem necessary during the acute phase of posttraumatic catabolic illness.

Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle.

BACKGROUND: Hyperlactatemia is observed commonly in patients with severe inflammation syndrome or sepsis. Elevated plasma lactate concentrations may be caused by cytokine-mediated alterations in specific organ systems responsible for lactate homeostasis. The role of interleukin 1 (IL-1) in inducing hyperlactatemia and derangements in skeletal muscle and hepatic lactate metabolism was investigated by examining the consequences of infusing IL-1 continuously into normal rats. METHODS: Male Sprague-Dawley rats were anesthetized, and catheters were placed in the jugular vein. Rats were allowed to recover for 48 hours and were infused subsequently with either saline (control) or human recombinant IL-1alpha (20 microg/kg/d) for 6 days. On day 6, plasma, liver, and muscle samples were extracted and assayed for lactate and pyruvate dehydrogenase (PDH) activity. RESULTS: Plasma glucose concentrations were not different in the two groups. IL-1 infusion resulted in a twofold (p < .05) increase in the plasma lactate concentration compared with controls. IL-1 infusion also resulted in an elevated lactate content in skeletal muscle (p < .05) but not in liver. The proportion of PDH in the active form (PDHa) was reduced significantly (p < .05) in the skeletal muscle of animals infused with IL-1 compared with controls. In contrast to muscle, hepatic PDHa did not differ between the two groups. Total PDH complex activity was not affected in either liver or skeletal muscle. CONCLUSIONS: IL-1 infusion results in hyperlactatemia, increased skeletal muscle lactate, and a reduced PDHa in skeletal muscle. We conclude that IL-1 is a potential mediator of the derangements in lactate metabolism in skeletal muscle but not in liver.

Superior mesenteric artery syndrome in a tube-fed patient.

Obstruction resulting from superior mesenteric artery syndrome is not often considered a possible cause for gastrostomy-tube complications in tube-fed patients. This case report details our experience with a patient who had had a feeding gastrostomy tube in place for 2 years. She then developed continuous leakage around the area of the gastrostomy insertion site associated with pain and inability to tolerate feedings. Her gastrointestinal series revealed compression of the third portion of the duodenum with delayed emptying of the stomach and dilatation of the proximal duodenum. After resection of the necrotic gastrostomy site, takedown of the ligament of Treitz to free the fourth portion of the duodenum, and insertion of a feeding jejunostomy, the patient was again able to gain weight and tolerate her tube feedings. We present this as an unusual complication occurring in a tube-fed patient.

Carcinoid of the appendix during laparoscopic cholecystectomy: unexpected benefits.

Carcinoid tumors of the midgut arise from the distal duodenum, jejunum, ileum, appendix, ascending and right transverse colon. The appendix and terminal ileum are the most common location. The majority of carcinoid tumors originate from neuroendocrine cells along the gastrointestinal tract, but they are also found in the lung, ovary, and biliary tracts. We report the first case of elective laparoscopic cholecystectomy in which we found a suspicious lesion at the tip of the appendix and proceeded to perform a laparoscopic appendectomy. The lesion revealed a carcinoid tumor of the appendix.

Regulation of peptide-chain initiation in muscle during sepsis by interleukin-1 receptor antagonist.

The mechanism by which interleukin-1 (IL-1) regulates protein synthesis in skeletal muscle during hypermetabolic sepsis in rats was investigated. Treatment of septic rats with a specific interleukin-1 receptor antagonist (IL-1ra) prevented the sepsis-induced inhibition of protein synthesis and translational efficiency in gastrocnemius. Analysis of ribosomal subunits revealed that the increase in free 40S and 60S ribosomal subunits observed in septic rats was prevented by infusion of IL-1ra, indicating peptide-chain initiation was maintained at control values. The failure of sepsis to inhibit peptide-chain initiation after infusion of IL-1ra correlated with a maintenance of the epsilon-subunit of eukaryotic initiation factor (eIF) 2B (eIF-2B epsilon) protein at control values. The alterations in the eIF-2B epsilon protein content in gastrocnemius of septic rats treated with or without IL-1ra were associated with corresponding changes in the abundance of eIF 2B epsilon mRNA. The results provide evidence that infusion of IL-1ra attenuates the sepsis-induced inhibition of protein synthesis by preventing the inhibition of peptide-chain initiation and downregulation of eIF-2B expression during sepsis.

Age-related differences in the metabolic response to injury.

OBJECTIVE: To investigate the effect of age on the metabolic response to injury. METHODS: Fifty-two trauma patients meeting entrance criteria were prospectively enrolled. Patients were grouped by age: elderly, >60 years; and young, < or =60 years. After 4 days of nutrition support, physiologic and laboratory data were collected. Energy and nitrogen metabolism, and body composition were evaluated. RESULTS: Elderly patients demonstrated a reduced incidence of fever (48% vs. 77%,p = 0.027). Independent of body composition, temperature, and injury severity, oxygen consumption was 8% lower in the elderly (p = 0.0032). However, nitrogen loss and myofibrillar catabolic rate was not altered by age. Elderly subjects were more often hyperglycemic (38% vs. 0%, p < 0.0001) and azotemic (62% vs. 22%, p = 0.004), despite similar carbohydrate and protein intake. CONCLUSION: Fever is less common and oxygen consumption lower in elderly trauma patients. Postinjury myofibrillar protein catabolism and nitrogen loss are not influenced by aging. Metabolic complications of nutrition support (hyperglycemia, azotemia) are more common in elderly trauma patients.

Effects of tumor necrosis factor-binding protein on hepatic protein synthesis during chronic sepsis.

BACKGROUND: Cytokines are thought to play a role in the stimulation of protein synthesis in liver during inflammation and sepsis. We previously showed that administration of tumor necrosis factor-binding protein (TNFbp) prevents the sepsis-induced inhibition of protein synthesis in skeletal muscle. The purpose of the present set of experiments was to investigate the effect of TNFbp on hepatic protein synthesis and its ability to modulate the mechanisms responsible for increased hepatic protein synthesis during chronic (5-day) intraabdominal sepsis. MATERIALS AND METHODS: We examined the effects of TNFbp on hepatic protein synthesis during sepsis in four groups of rats: control, control + TNFbp, septic, and septic + TNFbp. Saline (1.0 ml) or TNFbp (1 mg/kg, 1.0 ml) was injected daily starting 4 h prior to the induction of sepsis. The effect of sepsis and TNFbp administration on hepatic protein synthesis in vivo was examined 5 days later. RESULTS: Sepsis increased the rate of protein synthesis by 35% relative to controls. Accelerated rates of protein synthesis were accompanied by increased total RNA content, eukaryotic initiation factor (eIF) 2alpha content, and phosphorylation of p70S6 kinase. Injection of TNFbp into septic rats for 5 days did not diminish the sepsis-induced stimulation of hepatic protein synthesis. Compared with controls, septic rats treated with TNFbp also showed elevated total RNA content, elF2alpha content, and phosphorylation of p70S6 kinase. No significant differences in any of the parameters measured were observed between untreated and TNFbp-treated septic rats. Treatment of control animals with TNFbp for 5 days was without effect on any of the parameters examined. CONCLUSIONS: TNFbp did not prevent the sepsis-induced stimulation of hepatic protein metabolism or modulate the septic-induced changes in factors regulating protein synthesis. Global rates of protein synthesis in livers from septic rats are accelerated by increases in the abundance or activity of components of translational apparatus.

Prevention of skeletal muscle catabolism in sepsis does not impair visceral protein metabolism.

We investigated whether the preservation of gastrocnemius proteins by interleukin-1 receptor antagonist (IL-1ra) during sepsis altered protein metabolism in visceral tissues. Sepsis was induced by creation of an abdominal abscess followed by infusion of saline of IL-1ra. Five days later, the tissue protein content and rate of protein synthesis were measured. IL-1ra did not significantly alter hepatic protein metabolism in septic or control animals. In kidney, the protein content and rate of protein synthesis were both decreased by sepsis and significantly ameliorated by the infusion of IL-1ra. Sepsis decreased the rate of protein synthesis in the small intestine. IL-1ra increased intestinal protein synthesis in both control and septic animals; however, the effects were localized to the seromuscular layer. The preservation of muscle protein by IL-1ra in sepsis did not adversely affect protein synthesis in any of the visceral tissues examined. IL-1 appears to mediate the sepsis-induced changes in protein synthesis in kidney and small intestine but not in liver or spleen. Protein synthesis in each visceral organ responds differently to the septic insult and modulation of IL-1 bioactivity.

TNF binding protein prevents hyperlactatemia and inactivation of PDH complex in skeletal muscle during sepsis.

BACKGROUND: Hyperlactatemia is a metabolic complication of hypermetabolic, hyperdynamic sepsis. An important mechanism responsible for elevating plasma lactate concentrations in sepsis is altered regulation of the pyruvate dehydrogenase complex (PDH) in skeletal muscle. We investigated the ability of a specific tumor necrosis factor binding protein, TNFbp, to modulate lactate concentrations and skeletal muscle PDH activity in a rodent model of chronic abdominal sepsis. MATERIALS AND METHODS: We examined the regulation of lactate metabolism in four groups of animals: Control, Control + TNFbp, Septic, and Septic + TNFbp. Chronic (5 days) sepsis was induced by the creation of a stable intraabdominal abscess using a sterile fecal-agar pellet inoculated with E. coli plus B. Fragilis as the foreign body nidus. TNFbp (1 mg/kg/day) was injected subcutaneously daily. RESULTS: Sepsis increased plasma and skeletal muscle lactate concentrations 2-fold compared with control. In septic rats treated with TNFbp, plasma and skeletal muscle lactate concentrations were significantly decreased compared with untreated septic rats. In skeletal muscle, sepsis resulted in a 70% decrease in the proportion of the PDH in the active form compared with controls. The sepsis-induced inhibition in the PDH complex activity was prevented by TNFbp. PDH kinase was enhanced 1.8-fold in sepsis, and the increase in PDH kinase activity was prevented by treatment with TNFbp. TNFbp treatment did not have any effects on plasma lactate or the proportion of active skeletal muscle PDH activity in control animals. CONCLUSIONS: TNFbp prevents the sepsis-induced hyperlactatemia and derangements in skeletal muscle lactate concentrations and PDH activity. These observations suggest that TNF is an important mediator responsible for lactate dyshomeostasis during sepsis.

Tumor necrosis factor binding protein improves incisional wound healing in sepsis.

BACKGROUND: Sepsis is associated with poor wound healing; however, the exact role of tumor necrosis factor (TNF) as a mediator of sepsis-induced alterations in different types of tissue repair is unknown. This study examines the effects of a specific TNF antagonist (TNFbp) on the healing of intestinal anastomoses, incisional wounds, and polyvinyl (PVA) sponge implants in chronic abdominal sepsis. METHODS: Three groups of male Sprague-Dawley rats were studied: control, sepsis, and sepsis + TNFbp. Jejunal resection and anastomosis were performed through a 4-cm upper midline incision on day 1. On day 3, sepsis was induced by creation of a chronic abdominal abscess. Saline (0.1 ml) or TNFbp (1.0 mg/kg, 0.1 ml) was injected subcutaneously every day starting 4 h prior to sepsis. On day 7, the wound-breaking strength (WBS) of the skin incision and intestinal anastomoses was determined using a tensiometer. Wound histology and collagen deposition were evaluated by comparison of Sirius red-stained sections. The hydroxyproline content of PVA sponges was used to quantitate collagen content under the different experimental conditions. RESULTS: Septic mortality (20% vs 26%) was not significantly altered by TNFbp. Septic animals demonstrated a reduction in food consumption on days 3 to 5 that was not affected by TNFbp administration. Neither sepsis nor TNFbp altered the breaking strength or histologic appearance of intestinal anastomoses. However, the breaking strength of incisional wounds was decreased by 40% in septic rats (P < 0.001 vs controls). Administration of TNFbp to septic rats significantly improved incisional WBS (P < 0.01 vs sepsis), but not to control levels. Serius red staining of incisional wounds and PVA sponges demonstrated a decrease in collagen organization and deposition in septic rats that was ameliorated by TNFbp. Similarly, the reduction in hydroxyproline content of PVA sponges from septic animals was prevented by TNFbp. CONCLUSIONS: The process of tissue repair in intestine and skin wounds appears to be significantly different following the septic insult. The healing of jejunal anastomoses was refractory to the catabolic effects of sepsis. In contrast, collagen deposition and organization are significantly decreased in cutaneous wounds during chronic sepsis. TNFbp significantly ameliorated the inhibitory effects of sepsis on cutaneous wound healing. These results suggest that TNF is an important mediator of the decrease in collagen deposition observed in cutaneous wounds during the septic state.

The impact of a clinical pathway for gastric bypass surgery on resource utilization.

BACKGROUND: Clinical pathways are believed to improve patient care and reduce costs. Our hypothesis was that a gastric bypass pathway would decrease hospital resource utilization and cost of care without adversely affecting patient care. METHODS: The prepathway (Pre) group consisted of 16 gastric bypasses (6/98 to 3/99). The postpathway (Post) group includes 12 gastric bypass procedures performed after institution of the clinical pathway (4/99 to 12/99). The impact of the clinical pathway on hospital length of stay (LOS) and resource utilization was investigated. A comparison of costs was performed using cost/charge ratios. Hospital readmissions and postoperative complications were also examined. RESULTS: Despite increased obesity/medical acuity of the Post group, hospital LOS decreased by 3 days (P < 0.0001). Total hospital costs decreased by over $1600/case (>15%). Postpathway savings were greatest for room and board (34%), supplies (41%), and lab/radiology costs (50%). An increase in OR costs (22%) was observed in the Post group. This was due to an increase in anesthesia time (epidural catheter placement) and equipment costs (ultrasonic shears). Despite reductions in hospital LOS and resource utilization, the complication rate (Pre 12%, Post 16%) was similar and two patients in each group required brief readmission. CONCLUSIONS: A pathway for gastric bypass decreased hospital LOS and resource utilization. OR-related expenses account for 34-50% of total costs and must be monitored closely for surgical patients. The reduction in costs observed with this clinical pathway was not associated with an increase in postoperative complications or hospital readmission.

Acute effects of growth hormone in alcohol-fed rats.

The present study examined whether administration in vivo of a maximally stimulating dose of growth hormone (GH) was capable of modulating selected aspects of the GH-insulin-like growth factor (IGF) system to the same extent in alcohol-fed and control animals. Rats were maintained on an alcohol-containing diet for 14 weeks, while control animals were fed isocalorically. After surgical implantation of a catheter in the carotid artery, rats were starved overnight. The next morning, rats were injected with recombinant human GH (500 microg/kg, s.c.) or an equal volume of saline at time 0 and 12 h. Blood samples were collected prior to GH and at 6, 12 and 24 h thereafter; tissues were collected at the end of the study. Time-matched control and alcohol-fed rats not receiving GH were also included. Although the plasma concentrations of both total and free IGF-I were decreased 30-40% in alcohol-fed rats, the ability of GH to elevate circulating IGF-I was not diminished. GH was equally effective at increasing IGF-I peptide levels in both liver and skeletal muscle. GH also produced comparable increases in IGF-I mRNA in muscle in both groups. Hepatic GH receptor (GHR) peptide levels were not significantly altered by either alcohol or GH. Alcohol feeding decreased plasma levels of IGF binding protein (IGFBP)-3 and increased IGFBP-1, and GH did not significantly alter this profile. Hepatic expression of suppressor of cytokine signalling (SOCS-3) mRNA was not different between the groups. However, SOCS-3 mRNA was increased by approximately 50% in control animals in response to GH, but remained unchanged in alcohol-fed rats. These data indicate that the decrease in hepatic IGF-I synthesis and plasma IGF-I observed in alcohol-fed rats was independent of a change in GHR levels. In contrast, the ability of a maximally stimulating dose of GH to modulate selected biological responses in vivo was not impaired by chronic alcohol consumption and was associated with a lack of a GH-induced increase in SOCS-3 mRNA.

Validation of a 5-minute steady state indirect calorimetry protocol for resting energy expenditure in critically ill patients.

OBJECTIVE: Numerous protocols are used for indirect calorimetry in research and clinical settings. The objective of the current study was to validate in critically ill patients an abbreviated protocol that uses five consecutive stable 1-minute readings of oxygen consumption (VO2), carbon dioxide production (VCO2), and minute ventilation (VE) in a range of +/- 5%, versus a more standard protocol that uses 30 consecutive stable one minute readings of VO2, VCO2, and VE in a range of +/- 10%. METHODS: Indirect calorimetry was performed on resting, mechanically ventilated, critically ill patients. The first 5-minute period in which coefficients of variation for VO2, VCO2, and VE were < or = 5% was compared to the first 30-minute period in which coefficients of variation for these variables were < or = 10%. RESULTS: Thirty-four critically ill patients were studied. Twenty four patients (70%) successfully completed both protocols (Success Group). Eighteen percent of subjects completed neither the abbreviated nor the 30 minute protocol, and 12% completed only one protocol (Fail Group). The Success Group was marked by a higher incidence of sedation and/or medical paralysis. There were no significant differences in VE, VO2, VCO2, respiratory quotient, or energy expenditure between the protocols in the Success Group or the Fail Group. Coefficients of determination (R2) for VO2 and VCO2 between the two methods in the Success Group were 0.99. In the Fail Group, R2 values ranged from 0.75 for VCO2 to 0.91 for VO2. CONCLUSION: In sedated, mechanically ventilated patients, an indirect calorimetry test of five consecutive 1-minute periods with coefficient of variation < or = 5% is equivalent to a longer test consisting of 30 consecutive 1-minute periods with coefficient of variation < or = 10%.