Linda Ott

Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients.

Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown to worsen outcome before or during cerebral ischemia. To better define the relationship between human head injury and hyperglycemia, glucose levels were followed in 59 consecutive brain-injured patients from hospital admission up to 18 days after injury. The patients who had the highest peak admission 24-hour serum glucose levels had the worse 18-day neurologic outcome (p = 0.01). Patients with peak 24-hour admission glucose levels greater than 200 mg/dL had a two-unit increase in Glasgow Coma Scale score while patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a four-unit increase in Glasgow Coma Scale score during the 18-day study period (p = 0.04). There was a significant relationship between 3-month and 1-year outcome and peak admission 24-hour serum glucose level (p = 0.02 and p = 0.02, respectively). Those patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a greater percentage of favorable outcome at 18 days, 3 months, and 1 year than those with admission peak 24-hour glucose levels greater than 200 mg/dL (p = 0.0007, p = 0.03, and p = 0.005, respectively). A significant relationship between admission peak 24-hour Glasgow Coma Scale score and 18-day, 3-month, and 1-year outcomes was found (p = 0.0001, p = 0.0002, and p = 0.0002, respectively). Patients with mean admission peak 24-hour Glasgow Coma Scale scores of 3.5, 6, and 10 had mean admission 24-hour peak serum glucose levels of 252 +/- 23.5, 219.1 +/- 19, and 185.8 +/- 21, respectively (p = 0.05). These relationships were not significantly altered when confounding variables such as the amount of glucose given over the initial 24-hour postinjury period, the presence of diabetes or multiple injuries, and whether patients were given steroids, dilantin, or insulin were statistically incorporated. These data suggest that admission hyperglycemia is a frequent component of the stress response to head injury, a significant indicator of severity of injury, and a significant predictor of outcome from head injury.

Relationship of visceral proteins to nutritional status in chronic and acute stress.

Visceral protein levels are used as indicators of prognosis, severity of injury, and nutritional status in hospitalized patients. Clinicians often use visceral protein levels to assess efficacy of nutritional support. The purpose of this study was to test the validity of such practices. Visceral protein levels were determined in patients in a medical ICU, head injury unit, and burn unit. The serum albumin and thyroxine-binding prealbumin (TBPA) levels correlated significantly with mortality in the medical ICU patients. Burn patients had depressed albumin and TBPA concentrations over the duration of hospitalization that related to the severity of thermal injury but not to adequacy of nutritional support. Head-injured patients had depressed admission albumin and TBPA levels, with neither protein level adequately related to caloric or protein supplementation. We conclude that visceral proteins may reflect severity of injury and prognosis in critically ill hospitalized patients, but they often do not accurately reflect nutritional status or adequacy of nutritional support.

High Protein Enteral Feedings: A Means of Achieving Positive Nitrogen Balance in Head Injured Patients

In an attempt to improve early enteral nitrogen replacement, nitrogen status was compared in two groups of head injured patients receiving enteral regimens of 38 to 51 kcal/kg/day with different protein concentrations. Eleven control patients received 1.5 g protein/kg/day and 10 study patients received 2.2 g protein/kg/day. Daily nitrogen excretion, corrected nitrogen balance, blood urea nitrogen changes, and enteral formula tolerance were compared between groups over a 10-day period. Those receiving 2.2 g protein/kg/day had significantly higher daily and cumulative nitrogen balances despite their higher nitrogen excretion levels. Over 10 days, the study group retained 9.2 g nitrogen. By comparison, the control group sustained a cumulative loss of 31.2 g nitrogen over 10 days, despite a mean intake of 109 g protein/day. In both groups, full strength, full rate feedings were not possible until day 10 postinjury. These data indicate that once enteral formulas are tolerated high nitrogen regimens are required to achieve positive nitrogen balance in acute severe head injury patients.

Resting energy expenditure in patients with alcoholic hepatitis.

Patients with alcoholic hepatitis are typically malnourished. A hypermetabolic state would explain, at least in part, the muscle wasting observed in these patients. However, data on hypermetabolism in liver disease are limited and conflicting. In this study, we evaluated measured energy expenditure (MEE) vs predicted energy expenditure (PEE), and MEE in relation to urinary creatinine excretion in 20 patients with moderate and severe alcoholic hepatitis, and 20 controls. Patients with alcoholic hepatitis had depressed creatinine height index (moderate 66%, severe 78%) demonstrating muscle depletion. Patients with alcoholic hepatitis also had depressed mean serum albumin concentrations, the moderate group 2.6 g/dl and the severe group 2.0 g/dl. The mean values for measured energy expenditure in moderate alcoholic hepatitis patients, severe alcoholic hepatitis patients, and the control group were: 1556 kcal, 1878 kcal, and 1943 kcal, respectively. The mean measured energy expenditures per g of creatinine for the same groups were: 1520 kcal, 1813 kcal, and 1043 kcal, respectively. The mean measured energy expenditure/predicted energy expenditure ratio was not increased in alcoholic hepatitis patients compared to controls. However, when related to urinary creatinine excretion, the alcoholic hepatitis patients had a mean measured energy expenditure that was 55% higher than controls. In conclusion, whereas the measured energy expenditure to predicted energy expenditure ratio was not elevated in alcoholic hepatitis patients compared to controls, the measured energy expenditure per gram of creatinine was significantly increased in alcoholic hepatitis patients, supporting the concept of alcoholic hepatitis as a hypermetabolic state.

Comparison of Urinary Urea Nitrogen Excretion and Measured Energy Expenditure in Spinal Cord Injury and Nansteroid-Treated Severe Head Trauma Patients

Severe head trauma patients (HT) exhibit markedly elevated energy expenditure and 24-hr urinary urea nitrogen excretion (UUN) values. The objective of this study was to compare seven spinal cord injured patients (SCI) to seven HT for changes in UUN and measured energy expenditure (MEE) over the first 18 days following injury. Energy expenditure was measured by indirect calorimetry and compared to values predicted by the Harris Benedict Equation (PEE). There were six quadriplegics and one paraplegic in the SCI group. HT patients had peak Glasgow Coma Scale scores of 3 to 10 for the first 24 hr postinjury. Patients were studied prospectively and matched for age, sex, and admitting weight Week 1 following the injury, SCI had mean UUN values of 0.18 +/- 0.04 g/kg/day vs 0.18 +/- 0.01 for HT patients. The mean MEE/PEE ratio was 0.56 for the SCI and 1.4 for HT (p less than 0.01). Over the entire study period the mean UUN value for SCI was 0.23 +/- 0.03 g/kg vs 0.21 +/- 0.01 for HT. The mean MEE/PEE ratio for SCI was 0.94 while HT remained elevated at 1.5 (p less than 0.05). Although the UUN was comparable in SCI vs HT, there was a significant difference in MEE/PEE between the groups. The elevation in UUN observed in SCI is not due to a hypermetabolic state. This suggests that different mechanisms promote the increased nitrogen excretion observed in these two populations.

Comparison of Administration of Two Standard Intravenous Amino Acid Formulas to Severely Brain-Injured Patients

Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4–9 were prospectively randomized to receive one of two standard amino acid formulas, starting with the first day of hospital admission up to day 14 postinjury. Formula 2 (patient group 2) had 54 percent more leucine, 53 percent more isoleucine, 74 percent more valine, 28 percent less phenylalanine, 31 percent less methionine, 111 percent more proline, 38 percent less alanine, and 38 percent less glycine than formula 1 (patient group 1). Groups 1 and 2 received statistically equal overall mean parenteral nutrition calories and protein (2173 ± 147 vs. 2059 ± 143 kcal, and 77 ± 12 vs. 83.1 ± 6 g, respectively). There was a significant difference in overall mean urinary urea nitrogen excretion (group 1 = 24.6 ± 1.3 vs. group 2= 18.3 ± 1.1, p = 0.02) and nitrogen balance (group 1 = −8.0 ± 2.1 vs. group 2 = + 1.8 ± 1.2, p = 0.01). Mean overall isoleucine values were significantly higher in group 2 (overall mean 77 μmol/L vs. 62 μmol/L, p = 0.04). Phenylalanine levels were significantly higher in group 1 (107 μmol/L) versus group 2 (82 μmol/L) patients (p = 0.01). Arginine levels were significantly higher in group 1 (78 μmol/L) versus group 2 (49 μmol/L) patients (p = 0.0002). This observation suggests that some standard intravenous amino acid formulas may be more apt to promote positive nitrogen balance than others.

Brain Injury and Nutrition

This review has discussed the current status of metabolic alterations and demands, nutrient administration, and nutritional assessment of the head-injured patient. More work is necessary in all areas to further describe and ascertain the nutritional requirements of these patients. Future research in this area should involve specific nutrient requirement, modification of the acute-phase response, and possibly administration of growth factors.

Nutritional and metabolic variables correlate with amino acid forearm flux in patients with severe head injury.

ObjectiveTo measure the arterial-venous amino acid flux across the forearm muscle in patients with severe head injury. DesignProspective, interventional study. SettingLevel I trauma hospital in the neuro-surgery intensive care unit (ICU) at a university medical center. PatientsEight nonsteroid-treated patients with severe head injury. InterventionsPatients were prospectively randomized to receive either standard or supplemental intravenous zinc therapy. Measurements and Main ResultsNet forearm alanine, glutamine, tyrosine, phenylalanine, and branch-chain amino acid forearm flux were measured and compared with metabolic markers of energy expenditure and nitrogen excretion.There was a significant inverse relationship between the measured energy expenditure/predicted energy expenditure ratio and glutamine flux (r2 = .62; p < .05). The patients with the highest measured energy expenditure/predicted energy expenditure ratio had the greatest release of glutamine from forearm muscle. Nitrogen balance was significantly correlated with leucine flux (r2 = .53; p < .05) and with isoleucine flux (r2 = .67;p < .05). The patients with the most positive nitrogen balance had the least release of branch-chain amino acids from skeletal muscle. Tyrosine flux was highly correlated with net amino acid flux (r2 = .76; p < .01). Tyrosine flux was therefore indicative of overall muscle catabolism. Four patients had an overall negative flux of amino acids from skeletal muscle. Three patients had an overall negative flux of branch-chain amino acids. ConclusionsThis preliminary descriptive report suggests that increased skeletal muscle efflux of amino acids correlates significantly with metabolic variables of hypermetabolism and hypercatabolism in nonsteroid-treated, headinjured patients. (Crit Care Med 1994; 22:393–398)

Cytokines in Severe Head Injury

During the 1970s and early 1980s the morbidity and mortality rate from severe head injury significantly decreased. There still are patients who succumb to this severe injury or survive with poor recovery. Currently, about 30% survive with poor recovery, and this rate of poor outcome has not significantly changed during the past decade (1). In an effort to improve the outcome further, investigators have started to study intensively the type of damage inflicted by secondary factors that lead to secondary injury, and those caused by systemic effects of brain injury. Factors that block these negative effects are being developed and studied in an attempt to improve patient outcome. It is our hypothesis that cytokines play an important role in the metabolic response to head injury and that medical intervention that modulates the cytokine response may improve the adverse metabolic effects of head injury. The present chapter focuses on the role of cytokines in the metabolic response to head injury. Specifically, we will present evidence for increased cytokine levels and biologic effects following clinical and experimental brain injury. We will show that cytokine infusion mimics the systemic response to brain injury, and we will discuss potential roles of cytokine modulation following brain injury.

Invited Review: Nutrition in the Neurologically Injured Patient:

Head injury is characterized by both the direct injury to the brain and the overall systemic response to the brain injury. The systemic response usually includes an increase in energy expenditure, which can be quantitated by using indirect calorimetry, increased urinary nitrogen excretion, hyperglycemia, hypoalbuminemia, and elevated liver function tests. The mechanism for this hypermetabolism is probably multifactorial and includes the release of mediators in response to the injury (eg, catecholamines, cytokines), steroid therapy, nutrient administration and intercurrent complications, eg, infection. The nutritional management of the patient remains controversial. The issues that have been and that continue to be investigated are the amount and type of nutrients that will optimally allow for nerve regeneration and the optimal route of nutrient administration—enteral versus parenteral. This article reviews the proposed mechanisms for the metabolic response to head injury and the experience with nutritional support in this patient population.