Obesity and the metabolic response to severe multiple trauma in man.

In the obese state profound metabolic disturbances exist and it is not known how this disrupted metabolism in obese subjects (body mass index greater than 30) may change their ability to respond to the superimposed, injury-induced stress. Understanding the mechanisms that modify the metabolic parameters in traumatized obese patients is essential in their nutritional assessment and further treatment. We have investigated in 7 obese and 10 nonobese multiple trauma patients, on a whole-body level, the energy metabolism, protein kinetics, and lipolysis in the early catabolic "flow phase" of severe injury when they were receiving maintenance fluids without calories or nitrogen. Traumatized obese patients mobilized relatively more protein and less fat compared with nonobese subjects. A relative block both in lipolysis and fat oxidation is experienced by injured obese patients that results in a shift to preferential use of proteins and carbohydrates. Reduced endogenous protein synthetic efficiency observed in obese patients implies increased protein recycling. Thus obese patients could not effectively use their most abundant fat fuel sources and have to depend on other fuel sources. The nutritional management of obese trauma victims should therefore be tailored towards provision of enough glucose calories to spare protein.

Effect of major trauma on plasma free amino acid concentrations in geriatric patients.

Age-associated decrease in lean body mass may lead to varied responses to severe trauma. Hypoaminoacidemia is generally common among trauma victims. We measured the plasma free amino acids in the early "flow," ie, catabolic, phase of injury in 9 elderly (aged 61-81 y) and 13 young (aged 20-38 y) traumatized patients. Postabsorptive control samples were obtained from 8 elderly and 10 young volunteers. The results were analyzed for age-related responses to major trauma. Older healthy control subjects showed a decrease in total amino acids, essential amino acids, proline, histidine, taurine, and cystine. The hypoaminoacidemia was less pronounced in geriatric trauma, mainly because of a larger decrease in nonessential amino acids in young trauma victims. Significant decreases in arginine and methionine and increases in ornithine and citrulline concentrations were seen in geriatric trauma. These results suggest a sluggish protein metabolic response to trauma in elderly individuals, which should be considered in their nutritional management.

Aminoaciduria of severe trauma.

Plasma and urine levels of free amino acids were measured in 15 severely traumatized adult patients while they were receiving fluids free of calories and nitrogen. Endogenous plasma clearance and the relative rates of reabsorption of free amino acids from renal tubules were calculated. These data were compared with similar studies of eight control subjects. Multiple injury provoked distinct patterns of free amino acids in plasma and urine. Hypoaminoacidemia and hyperaminoaciduria were seen in severe trauma. There was a marked depletion of nonessential amino acids in plasma of trauma victims. In contrast, the urinary loss of all amino acids was increased 5-10 times. This enhanced loss in patients, however, represented only 2.1% of total N excreted compared with 0.7% in control subjects. Considerable variations were seen in the selectivity with which various amino acids were reabsorbed by renal tubules. This may partly be due to the abnormal pattern of amino acids presented to renal tubules.

Mild orotic aciduria and uricosuria in severe trauma victims.

Hypermetabolic responses with respect to pyrimidine and purine kinetics in trauma victims were investigated during the catabolic phase before and after nutritional support. Orotic acid and uric acid excretions were measured in 32 adult, severely traumatized, hypermetabolic, and highly catabolic patients while they were receiving fluids with no calories or nitrogen. Patients were then fed intravenously amino acids and glucose or glucose alone or fed enterally for 5-6 d. Daily excretions of orotic acid, uric acid, urea, nitrogen, and creatinine were monitored. Mild orotic aciduria and uricosuria with hypouricemia were the basal-trauma responses. The significant (P = 0.001, r = 0.70) positive correlation between orotic and uric acid excretion demonstrates the parallelism between pyrimidine and purine metabolism. Feeding for 5-6 d could decrease but not readily abolish the injury-induced metabolic changes in nitrogen, pyrimidine, and purine metabolism. Glucose infusion alone may be sufficient to counteract the metabolic effects of trauma in the early flow phase of injury.

Muscle protein catabolism in the septic patient as measured by 3-methylhistidine excretion.

Muscle protein catabolism has been evaluated using the excretion of urinary 3-methylhistidine (3-MEH) is six normal male and six normal female subjects and in four surgical patients, two of whom developed febrile episodes during the course of their study. In addition, their nutritional status was also evaluated using percentage body weight losses before hospital admittance, creatinine-height ratios, and, in two patients, serum alkaline ribonuclease levels. The results indicate that: 1) prolonged starvation may produced decreased 3-MEH excretion because of an adaptive diminution of muscle breakdown in sustained starvation, decreased 3-MEH excretion also may simply reflect diminished lean body mass, 3-MEH excretion may be increased above basal levels because of superimposed stresses such as fever, and the acute phases of starvation produce increased levels of 3-MEH excretion until adaptive mechanisms occur; 2) creatinine-height ratios are low in starvation, and increase not only with improved nutrition but in response to fever and stress of operation, even when these are superimposed on malnutrition; and 3) alkaline RNAase levels are elevated in malnutrition and decrease with improved nutrition but in response to fever and stress of operation, even when these are superimposed on malnutrition; and 3) alkaline RNAase levels are elevated in malnutrition and decrease with improved nutrition. The enzyme may also be elevated by the stress of operations.

Decreased growth hormone levels in the catabolic phase of severe injury.

BACKGROUND: Human growth hormone (hGH) is a potent anabolic agent, which has profound effects on protein, carbohydrate, and lipid metabolism. The role of this primarily anabolic hormone in the severe catabolic state of trauma is not known. METHODS: In a group of young, obese, and elderly patients with multiple traumas, plasma hGH levels were measured in the catabolic "flow" phase of injury, once before and then after 4 to 6 days of nutritional support sufficient to match their initial loss of calories and nitrogen. RESULTS: A decreased hGH level was noted in the hyperglycemic and hypercatabolic injured state, particularly in victims of trauma who were young and not obese, compared to respective volunteers. A significant (p = 0.025) inverse relationship was observed between age and plasma hGH levels in this group of patients who had experienced trauma. Nutritional therapy improved the protein and fat metabolism but could not reverse to the normal state. In young patients who had experienced trauma and who were not obese, the hGH levels were significantly improved because of dietary intake, whereas in elderly patients or patients who were obese no change was noted. CONCLUSION: These results are consistent with less lipid mobilization and inefficient utilization of fatty acids in the elderly patients or patients who were obese who had abundant fat sources to spare. Elevation of hGH level by exogenous administration may improve the nitrogen economy and lipid mobilization, particularly so in the elderly patients or patients who were overweight. Our study supports the view that provision of adequate nutrition with daily administration of human hGH in the first week after trauma would enhance the metabolic status of the patient, resulting in reduced morbidity and earlier discharge from the hospital.

Energy cost of fat-fuel mobilization in geriatric trauma.

Age-related changes in body composition may result in varied responses to acute accidental injury. Gaining fat as age advances is common and therefore the mobilization of fat fuel resources in traumatized geriatric patients needs closer examination. We have measured in six elderly (age, 60 to 74 years) and seven young (age, 18 to 46) traumatized, hypermetabolic, and highly catabolic patients, in the "flow phase" of the metabolic response to injury, the rates of whole-body lipolysis and net fat oxidation. This enabled us to calculate the rate of triglyceride/free fatty acid (TG/FFA) cycling in the whole body and to assess its contribution to energy expenditure. Energy metabolism in general and the fat metabolism in particular were found to be somewhat slowed in elderly trauma patients compared with equally injured young individuals, although the aged patients had more total body fat. The energy cost of TG/FFA cycling is significantly (P less than .025) lower in elderly trauma victims (0.28 +/- 0.06 kcal/kg/d) compared with young patients (0.63 +/- 0.1 kcal/kg/d). This can account for approximately 3% to 4% of the elevation in metabolic rate over that predicted in the uninjured state.

Endogenous protein-synthesis efficiency in trauma victims.

Hyperglycemia despite increased glucose oxidation and hypoaminoacidemia despite increased rate of protein breakdown are frequently seen in hypermetabolic and highly catabolic patients with major trauma. The extent of reutilization of endogeneously produced amino acids in the synthesis of new proteins (protein recycling) by the traumatized human is poorly understood. The protein synthesis efficiency was measured in ten multiple trauma patients during the early "flow" phase of injury, and these data were compared with normal and depleted patients. In acute trauma the synthetic efficiency of protein is significantly (P = .01) low (61% +/- 4%) compared with other pathologic states (78% +/- 1%). This suggests that the priority is preferentially set to meet the increased demands of glucose production, and a major portion of the amino acids are utilized for purposes other than synthesis of body proteins. This observation should be taken into account in the early management of acute trauma patients before the body adapts to accept the exogenous supply of amino acids.

Altered plasma free amino acid levels in obese traumatized man.

Obesity is a major nutritional disorder that produces many abnormal metabolic responses. The effect of injury-induced stresses acting synergistically with the state of excessive body fat is not well known. Plasma levels of circulating free amino acids reflect the net status of protein breakdown and utilization. Hypoaminoacidemia is a common finding in severe injury and its significance in obese subjects was investigated. We measured in 10 obese (body mass index [BMI] greater than 30) and 10 non-obese (BMI less than 30) traumatized (Injury Severity Score [ISS] 17 to 50) patients, the plasma levels of free amino acids in the early "flow" phase of injury when subjects were receiving maintenance fluids without calories or nitrogen. Postabsorptive control samples were obtained from 10 obese and 10 non-obese volunteers. Obese controls showed an increase in valine, leucine, isoleucine, and glutamic acid levels, and a decrease in glycine, tryptophan, threonine, histidine, taurine, citrulline, and cystine levels compared with lean controls. Hypoaminoacidemia was equally seen in traumatized obese and non-obese patients, and it was mainly due to a 24% decrease in nonessential amino acids. Remarkably, essential amino acid levels were the same in all groups. Arginine and ornithine levels were significantly different in traumatized obese compared with non-obese patients. The hypoglycinemia seen in non-obese trauma patients was absent in obese patients. The changes in levels of sulphur-containing amino acids also suggest that monitoring of these levels should be included in the nutritional management of obese trauma patients.

Polyamine levels as biomarkers of injury response in polytrauma victims.

Enhanced protein mobilization and synthesis are common responses to severe trauma. The hypothesis that extracellular polyamine levels could be valid biomarkers for these responses has been investigated. The three polyamines, spermidine, spermine and their precursor putrescine are directly involved in cell growth/death kinetics through regulation of protein metabolism. The lack of tissue uptake of extracellular polyamines and their rapid conjugation and excretion make them excellent biomarkers of variations in cellular kinetics. The polyamine levels in plasma and urine of severely traumatized patients were measured during the early "flow" phase of injury and compared with unstressed normals. Significantly elevated urinary levels of free and total putrescine and spermidine indicate the increase in the protein synthesis and breakdown rates, respectively, in polytrauma patients. Urinary spermidine level correlates well with other known parameters of protein catabolism, such as isotopically measured whole body protein breakdown rate in the basal state and 3-methylhistidine excretion and nitrogen loss in the basal condition and during nutritional therapy. Whole-body protein synthesis rate positively correlates with putrescine levels in urine. Based on these observations, urinary levels of the polyamines spermidine and putrescine may be applied as valid biomarkers of protein breakdown and synthesis rates, respectively, both for the existing pathology of severe trauma and for the response to nutritional therapy.

Glucose infusion improves endogenous protein synthesis efficiency in multiple trauma victims.

Metabolic costs of excessive nutritional support in stressed patients have been increasingly recognized. The decreased endogenous protein synthesis efficiency (PSE) following major injury has been attributed to the predominant need of amino acid precursors for gluconeogenesis. The present study tested the hypothesis that provision of glucose alone, not to exceed the resting energy expenditure (REE), for the first 4 to 5 days after trauma would be enough to restore PSE and stimulate the injured body to accept full nutrition. Eight severely injured, adult, hypermetabolic, and highly catabolic patients admitted to the Trauma Intensive Care Unit (TICU) served as our subjects. Integrated measurements of whole body fuel-substrate kinetics were obtained for energy metabolism (indirect calorimetry), protein kinetics (primed constant infusion of 15N-glycine), and glucose kinetics (labeled glucose infusions). Two studies were conducted on each same subject, one in the early flow phase of injury (48 to 60 hours after trauma) and a second after 4 to 5 days of hypertonic glucose (4.1 +/- 0.5 mg/kg/min; 80% REE calories) infusion with electrolytes, trace elements, and minerals. Significant (P less than .05) increases in PSE (14%, 65% +/- 2% to 74% +/- 2%), plasma growth hormone and insulin levels, and respiratory quotient (RQ) (31%, 0.74 +/- 0.03 to 0.97 +/- 0.04), and decreases in endogenous glucose appearance rate (55%, 3.1 +/- 0.5 to 1.4 +/- 0.1 mg/kg/min), and negative N balance (48%, 219 +/- 26 to 114 +/- 15 mgN/kg/d) were observed. The results suggest that hypertonic glucose infusion alone may be sufficient for physiological adaptation in the immediate posttrauma days. This therapy restores normal PSE, which should protect the labile protein pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary excretion of 3-methylhistidine: an assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma.

The urinary excretion of 3-methylhistidine (3 MEH) has been shown to be a reliable index of muscle protein breakdown. It is decreased in protein-calorie malnutrition and increased during the hypercatabolic phase of sepsis and thermal trauma. Losses of 3 MEH after moderate to severe skeletal trauma in man and animals are reported as increased or unchanged. To clarify this response, 24 male and 6 female skeletal trauma patients were evaluated for 24 hr urinary losses of 3 MEH, nitrogen and creatinine. Eight of the 24 males also received a catabolic steroid for treatment of a head injury. In addition, 3 male and 1 female septic patients were similarly evaluated. Controls consisted of 10 volunteers on a meat free diet for 4 days and of 8 volunteers who were given only intravenous 5% dextrose in water for 3 days. The 3 MEH excretion for all control males was 3.6 mumole/Kg/day and for females was 2.8 Skeletal trauma produced a 280% increase for the males and a 225% increase for the females. Trauma with steroids caused a 325% increase. Sepsis induced a 227% increase in 3 MEH losses for males and 292% for females during the febrile episode. Creatinine excretion also increased significantly in response to trauma and sepsis but the magnitude of the increase was less than for 3 MEH. This was reflected in the 3 MEH to creatinine molar ratio increase from 0.018 for controls to 0.030-0.040 in sepsis and trauma. Patients with extensive body weight loss showed decreases in 3 MEH and creatinine excretion and a molar ratio similar to controls. The calculated contribution of muscle protein to whole body protein breakdown in the trauma and septic groups showed a twofold increase compared to the control group. The data indicate that the increased muscle protein catabolic response following stress of skeletal trauma and sepsis provides an insight on the origin of the large urinary nitrogen losses following such insults.

Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients.

Forty-five acute head trauma patients were randomized into a neurotrauma nutritional study to compare the efficacy of two forms of standard nutritional supplementation; namely total parenteral nutrition (TPN) versus enteral nutrition (NG). Forty patients were male, 5 were female, with a median age of 28 years. The mean admitting Glasgow coma scale score was 5.8. Patients were given high calorie and nitrogen feedings for the 14 days of the study period in an attempt to achieve positive calorie and nitrogen balance. TPN patients had significantly higher mean daily nitrogen intakes (P less than 0.01) and mean daily nitrogen losses (P less than 0.001) than the NG fed patients; however, no significant differences were discovered with respect to maintenance of serum albumin levels, weight loss, the incidence of infection, nitrogen balance, and final outcome. The exaggerated nitrogen excretion experienced by patients fed large nitrogen loads illustrates a problem in achieving nitrogen equilibrium in acute head injured patients.

Efficacy of ornithine-alpha-ketoglutarate (OKGA) as a dietary supplement in growing rats.

New substrates of potential benefit to critically ill patients receiving traditional nutritional support have been suggested to meet organ or tissue specific needs. The addition of an anabolic stimulus during nutritional support therefore appears to be a reasonable adjunct to augment protein synthesis. The purpose of this investigation was to evaluate the efficacy of the neutral salt ornithine alphaketoglutarate (OKGA) as a dietary supplement to promote growth in young rats by enhancing protein metabolism. A group of 16 male Sprague-Dawley rats (150-170g) were housed in individual metabolic cages and after dark-light cycle adaptation were fed ad libitum an oral liquid diet for 7 days. Half of the animals were given the control diet and the other half was fed a test diet. This isonitrogenous test diet contained the control diet with 2.3% of nitrogen (N) replaced by N from OKGA. Daily weight, food intake and urinary excretions of N, creatinine, urea, orotic acid, polyamines and amino-acids were determined. At the end of 7 days of free-feeding, the rats were sacrificed and blood was collected for free amino-acids. Rats fed the OKGA supplemented diet consumed 16% more diet, retained 11% more nitrogen and gained 15% more weight. The accelerated protein metabolism is reflected in the changes in plasma and urinary free amino-acid levels. Enhanced protein anabolism is evident from the increased urinary excretion of polyamines in the OKGA fed rats. The increased ratio of urinary urea N to total N and the decreased orotic acid excretion in OKGA fed rats suggests thata NH(4)(+) was efficiently diverted through urea cycle. It is concluded that in growing rats, supplementing isonitrogenous diet with OKGA significantly stimulates food intake compared to controls. This results in better weight gain and improvement in protein metabolism.

Trend toward nonoperative management of splenic injuries.

Treatment of splenic injuries has evolved over the past decade to reflect more effort to conserve function of the spleen. Records of 169 patients admitted over a 6-year period were identified as documenting the treatment of splenic injuries. We collected data regarding patient age, gender, degree of hemodynamic stability, number of units of blood required, severity of splenic injury, Injury Severity Score, and results of treatment. There were 143 adults (age greater than 16 years) and 26 pediatric patients (age less than 17 years), with mean age in the 2 groups of 31.6 and 11.4 years, respectively. Males comprised 72% of the group, and blunt injury occurred in 154 of the 169 patients. In the adults, splenectomy, splenorrhaphy, laparotomy without operative treatment of the spleen, and nonoperative management were observed 48%, 30%, 14%, and 8% of the time and in the pediatric group 31%, 27%, 19%, and 23% of the time, respectively. By using operative splenic repair techniques and increased use of nonoperative management, the splenic salvage rate has increased in the last 6 years from 41% to 61% without an increase in morbidity and mortality. Incidence of spleen salvage correlated with severity of spleen and overall injury and cardiovascular stability.

Prolonged ileus after severe pelvic fracture.

The data derived from 105 severe pelvic fractures have provided guidelines for managing paralytic ileus associated with fracture. Fracture types I, II, IV, and double type III can be treated expectantly with a high degree of confidence that ileus will resolve within 2 days. Type III diametric fractures can be managed similarly for 5 days with a 70 percent (14 of 20 patients in this study) likelihood that ileus will resolve. However, should ileus in patients with diametric fractures continue longer than 5 days, parenteral nutrition should be started, since ileus will persist for an average of 2 weeks. A direct correlation between type of pelvic fracture, amount of retroperitoneal blood, loss and duration of ileus has been documented.

Management of central venous catheters using a wire introducer.

The wire introducer method is a satisfactory technique for management of central venous catheters if bacteriologic monitoring of the removed catheter is used to determine whether the introduced catheter should be allowed to remain. The data indicate that when central venous catheters become infected, they do so through the whole length of the catheter, from subcutaneous tunnel to intravascular tip. An intravenous catheter which produces negative cultures can be safely changed by the introducer method aseptically. An infected catheter must be removed as soon as the diagnosis is apparent, since the replacement catheter will be seeded by the colonized tract. Blood specimens drawn through central venous lines do not reflect the status of the line itself but rather the presence or absence of systemic bacteremia.

Pancreatic enzyme levels in bile of patients with extrahepatic biliary tract disease.

A total of ninety three patients with biliary tract disease were studied to determine the concentration of the pancreatic enzymes, amylase and lipase, in bile obtained from the gallbladder and/or common bile duct. Of seventy gallbladder bile samples, amylase levels were higher than actual or predicted serum levels in 87 per cent, while bile lipase were higher than serum lipase values in 66 per cent. Bile obtained from the common bile duct had enzyme concentrations which fluctuated from values similar to those in serum to remarkably high levels. This suggests that pancreatic enzymes enter the biliary system through a common terminal ampulla which is known to exist in 60 to 90 per cent of human subjects. The premise is advanced that pancreatic enzymes may initiate inflammatory changes in the gallbladder and could play a role in gallstone formation by altering the constituents which maintain cholesterol in a soluble state. Biliary reflux of pancreatic enzymes could play a role in the pathogenesis of some cases of cholecystitis can cholelithiasis.

Survival in major burn injuries is predicted by early response to Swan-Ganz-guided resuscitation.

BACKGROUND: Two years ago the authors began to use Swan-Ganz catheters to generate more complex hemodynamic data as a better guide to resuscitation of burns. This study uses the information to identify differences between survivors and nonsurvivors. PATIENTS AND METHODS: Fifty-three consecutive patients with major burns were treated using Swan-Ganz-generated data. Additional information was collected, including demographics, intake and output, medications, and arterial blood gas (including calculated oxygen consumption). Statistical analysis incorporated adjustments for autocorrelation. RESULTS: The patients included 38 men and 15 women, averaged 43.7 years of age, and had a mean burn size of 40%. Thirteen patients suffered severe inhalation injury. Data collected hourly over 3 days were collapsed across 6-hour observation periods. Mean values, when plotted across time, discriminated the 37 survivors from the 16 nonsurvivors. Poor response to resuscitation as evidenced by increased use of colloid fluid and cardiotonic drugs plus failure to maximize oxygen consumption were associated with nonsurvival. CONCLUSIONS: Unsustained or inadequate response to hyperdynamic resuscitation of burns was associated with nonsurvival.

Effect of nutritional therapy on polyamine metabolism in severely traumatized patients.

The polyamines (PA) spermidine (SD) and spermine and their precursor putrescine (PU) play a leading role in the regulation of protein, RNA and DNA synthesis. We examined the role of PA along with other biomarkers of injury in eight victims of multiple trauma in the early post-traumatic period when they were hypermetabolic and highly catabolic. Intravenous nutritional therapy (TPN) was started 48 to 60h after trauma and continued for 6 days. The basal response to severe trauma was a significant (twofold to threefold) rise in urinary PU (p = 0.05) and SD (p = 0.025) levels compared to normal subjects. Six days of TPN further enhanced the basal excretion of PU (157%) and SD (137%) peaking on the third day. There was a 20% reduction in the excretion of 3-methylhistidine on the first day of TPN, but it was still 40% above normal on the sixth day. The negative nitrogen balance was improved but not reversed. Injury stimulated ribonuclease and catecholamine levels were also enhanced by nutritional therapy, peaking on the first and fourth day of TPN, respectively. This study demonstrated for the first time elevated levels of PA in trauma patients that correlated well with the other known measures of protein metabolic response to injury and changes during nutritional therapy. Extracellular PA levels could be used as markers of both catabolic pathology in trauma and of its response to nutritional therapy.