Effects of nitric oxide synthase inhibitors and a substrate, L-arginine, on the cardiac function of juvenile salmonid fish.

Control of cardiac function was investigated juvenile brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss Walbaum) using inhibitors of nitric oxide synthase (NOS), (L-NAME, NG-nitro-L-arginine and L-NMMA, NG-monomethyl-L-arginine) and a substrate of NOS (L-arginine). Salmonid alevins are excellent models for such studies since they are transparent, the beating heart is easily observed, diffusing distances are small, and they respond within a few seconds to exogenously administered chemicals. The response to inhibitors of NOS (L-NAME or L-NMMA) was tachycardia interpreted as vasoconstriction through lowered capacity for synthesis of NO. This could be reversed by addition of L-arginine and the subsequent bradycardia was explained as a vasodilation resulting from increased synthesis of NO. Blood flow into the heart is mainly via the vitelline vein and changes of flow resulting from constriction or dilation of this vessel may be probably major determinants of heart rate. The results provide evidence for the presence NOS in juvenile fish and indicate a physiological role for NO in cardiovascular control.

Opioid analgesics versus ketorolac in spine and joint procedures: impact on healthcare resources.

BACKGROUND: Ketorolac's efficacy as a postoperative analgesic has been shown to be comparable to that of narcotic analgesics, but with significantly fewer narcotic-related adverse events. OBJECTIVE: To assess whether the choice of postoperative analgesic, narcotic or ketorolac, has an impact on healthcare resource utilization and cost durng inpatients' recovery period. DESIGN: Retrospective, multicenter, controlled, parallel, cost-minimization analysis. SETTING: Six US teaching hospitals. PATIENTS: This study included 559 patients that underwent either a spine or joint procedure and received adequate doses of narcotic (n = 284 of either morphine or meperidine) or ketorolac (n = 275). MEASUREMENTS: Time to reach recovery milestones, average utilization of healthcare resources, and average per-case postoperative treatment cost. RESULTS: Several recovery milestones, including time to first bowel movement, first oral intake, and first unassisted ambulation, were reached sooner in the ketorolac group, with a resultant shorter mean length of postoperative stay (narcotic 3.78 d, ketorolac 2.80 d; p = 0.01). Total per-patient cost of treatment was 32% greater in the narcotic group, resulting primarily from higher costs associated with hospitalization. CONCLUSIONS: Despite the higher acquisition cost of medication, healthcare resource utilization and total per-patient cost of treatment were lower for patients in the ketorolac group compared with patients in the narcotic analgesic study group. The majority of patients in the ketorolac group were also given concurrent narcotic analgesics; therefore, the beneficial effects observed may be secondary to the combination of ketorolac and narcotic analgesics.

Revising appointment, promotion, and tenure procedures to incorporate an expanded definition of scholarship: the University of Kentucky College of Medicine experience.

Scholarly activity and scholarly productivity are key features of the academic health center (AHC) and the work of college of medicine faculty. Recent changes in the academic environment of the University of Kentucky (UK) College of Medicine led to an examination of its appointment, promotion, and tenure procedures. This, in turn, led to a re-examination of the college's definition of scholarship. This article describes three of UK's scholarship-related challenges, particularly those related to clinical departments. The authors describe some of the new procedures being implemented to address these challenges; these include new faculty designations, clearer articulation of promotion procedures, explicit recognition of multiple forms of scholarship, expectations for investment in junior faculty, and mandatory discussion of faculty success in chairs' annual reviews. Faculty reactions, positive and negative, to these changes in procedures are also presented.

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.

CONTEXT: For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established. OBJECTIVE: To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival. DESIGN: Multicenter, randomized, parallel group trial. SETTING: University-affiliated cancer treatment facilities. PATIENTS: Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study. INTERVENTIONS: Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively. MAIN OUTCOME MEASURES: The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently. RESULTS: Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P<.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P=.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent. CONCLUSIONS: Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.

A phase I trial of neutron brachytherapy for the treatment of malignant gliomas.

We performed a phase I trial to test the feasibility of neutron brachytherapy using californium-252 (252Cf) as the sole source of radiation, and to determine the maximum tolerable dose (MTD), for the treatment of malignant gliomas. Previous studies using external beam neutron radiation have shown that neutrons are capable of totally eradicating malignant gliomas. However, in most cases, fatal widespread radiation necrosis resulted. Radioactive implants are a logical method of increasing the dose to the tumour and decreasing the dose to normal brain. 252Cf is a relatively stable neutron-emitting isotope suitable for implant therapy. The study was an open ended dose-escalation study. All radiation was delivered by using only 252Cf implants, without external beam therapy of any type. The first dose step was 900 neutron cGy (ncGy); each subsequent step was increased by 100 ncGy. Three patients with newly diagnosed malignant gliomas were entered at each dose step, and the number was increased to six patients in dose steps at which necrosis of brain occurred. The study ended when two patients at any dose step developed radiation necrosis of brain outside the prescribed radiation field. 33 patients were entered into the study. 10 patients developed scalp necrosis associated with scalp doses above 900 ncGy. The study ended when two patients at the 1300 ncGy dose step developed radiation necrosis of brain. We conclude: (1) neutron brachytherapy using 252Cf as the sole source of radiation is a feasible treatment for malignant gliomas; (2) the scalp tolerates less neutron radiation than the brain; (3) the MTD (and the recommended dose for a phase II trial) of interstitial neutron brachytherapy is 1200 ncGy.

A step-wise protocol for stress ulcer prophylaxis in the neurosurgical intensive care unit.

BACKGROUND: Neurosurgical patients are at risk for stress induced gastric erosion. Clinical criteria for monitoring stress ulcer prophylaxis (SUP) efficacy and predicting clinical bleeding are limited. SUP in the neurosurgical intensive care unit (NSICU) was evaluated utilizing a multidisciplinary quality assurance program with defined criteria for therapy. METHODS: All patients admitted to the NSICU were managed using this protocol. Therapy was initiated with a single drug (cimetidine 300 mg IV every 6 hours, or continuous infusion up to 2400 mg/day) in 136 evaluable cases. Combination therapy was implemented if continued gastric pH < 4 and guaiac positive aspirates occurred (N = 45). RESULTS: Significant correlations were observed between low gastric pH values and both GCS < 8 (P < or = 0.01) and length of ventilatory support (P < or = 0.005). Single agent therapy was more effective in patients with GCS > or = 8 (P < or = 0.001). Endoscopy was performed in 25 patients. No patient with GCS < 8 had pathologic lesions. The presence of asymptomatic gastrointestinal lesions was higher in patients requiring longer ventilatory support (P < or = 0.001) and intensive care unit stay (P < or = 0.0001). Patients requiring pentobarbital and vasopressors had statistically higher rates of clinical bleeding (P < 0.05). Patients with GCS < 8 had increased rates of pneumonia (P < or = 0.005) with a higher pneumonia rate when treated with combination therapy (P < or = 0.05). Overall, the incidence of clinical bleeding was 3.7%. CONCLUSIONS: This protocol was effective for prospective monitoring of SUP efficacy and limited multiple drug therapy to patients at risk for clinical bleeding.

Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury.

Sixty-eight patients were entered into a randomized, prospective, double-blinded controlled trial of supplemental zinc versus standard zinc therapy to study the effects of zinc supplementation on neurologic recovery and nutritional/metabolic status after severe closed head injury. One month after injury, the mortality rates in the standard zinc group and the zinc-supplemented group were 26 and 12%, respectively. Glasgow Coma Scale (GCS) scores of the zinc-supplemented group exceeded the adjusted mean GCS score of the standard group at day 28 (p = 0.03). Mean motor GCS score levels of the zinc-supplemented group were significantly higher on days 15 and 21 than those of the control group (p = 0.005, p = 0.02). This trend continued on day 28 of the study (p = 0.09). The groups did not differ in serum zinc concentration, weight, energy expenditure, or total urinary nitrogen excretion after hospital admission. Mean 24-h urine zinc levels were significantly higher in the zinc-supplemented group at days 2 (p = 0.0001) and 10 (p = 0.01) after injury. Mean serum prealbumin concentrations were significantly higher in the zinc-supplemented group (p = 0.003) at 3 weeks after injury. A similar pattern was found for mean serum retinol binding protein level (p = 0.01). A significantly larger number of patients in the standard zinc group had craniotomies for evacuation of hematoma; thus a bias may have been present. The results of this study indicate that zinc supplementation during the immediate postinjury period is associated with improved rate of neurologic recovery and visceral protein concentrations for patients with severe closed head injury.

Long-term follow-up results of thoracolumbar fractures after posterior instrumentation.

STUDY DESIGN: This retrospective study examined the hospital records of 60 patients with thoracolumbar fractures treated with posterior fusion and spinal instrumentation. The mean follow-up period was 66 months. OBJECTIVES: The goal of this study was to evaluate and analyze the long-term outcome and socioeconomic conditions of patients who had sustained a thoracolumbar fracture. SUMMARY OF BACKGROUND DATA: In four patients, additional spinal injuries were detected. Three of the patients evaluated with magnetic resonance imaging showed cord contusion and edema. In six patients, ruptured disc fragments were detected by preoperative magnetic resonance imaging or during surgery. METHODS: Long-term follow-up results in 60 patients with unstable thoracolumbar fractures treated with posterior fusion and spinal instrumentation were analyzed. Neurologic outcomes and independence in function and daily living activities were reviewed. Age, sex, mechanism of injury, associated injuries to the spinal cord, and associated injuries to the spinal cord and other systems were analyzed. Fractures were classified according to the system of Ferguson and Allen. RESULTS: The patients with incomplete spinal cord injury showed significant functional improvement. During the follow-up period, 28 patients showed neurologic improvement. Postoperative complications occurred in 11 patients. Five patients required late rod removal because of rod dislocation. CONCLUSION: Regardless of neurologic recovery, most patients reported some disability, usually caused by pain. Inability to return to alternative jobs resulted from insufficient educational background rather than neurologic dysfunction. Advanced academic achievement was the single most important predictive factor of ability to return to work.

Altered gastric emptying in the head-injured patient: relationship to feeding intolerance.

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.

Intravenous ciprofloxacin versus ceftazidime for treatment of nosocomial pneumonia and urinary tract infection.

Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the treatment of nosocomial pneumonia and urinary tract infection (UTI). Patients with nosocomial pneumonia were randomized to receive ciprofloxacin (as the lactate salt) 300 mg i.v. every 12 hours or ceftazidime (with sodium carbonate) 2 g i.v. every eight hours. Patients with UTI were randomized to receive ciprofloxacin 200 mg i.v. every 12 hours or ceftazidime 1 g i.v. every eight hours. Sputum and urine specimens were collected before, during, and after therapy. For patients with pneumonia, the organisms most frequently isolated before treatment began were Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus mirabilis. Of the 17 pneumonia patients who completed ciprofloxacin treatment, 15 (88%) had resolution of signs and symptoms or improvement. Of the 15 ceftazidime-treated pneumonia patients, 13 (87%) had resolution or improvement. Staphylococcus aureus, Streptococcus species, Acinetobacter species, and K. pneumoniae infections persisted for the ciprofloxacin treatment failures. Infections by Enterobacter cloacae and Acinetobacter species persisted for the ceftazidime treatment failures. For UTI patients, E. coli was the organism most frequently isolated before treatment. All 14 UTI patients who completed treatment showed resolution or improvement. In the ciprofloxacin group two patients were superinfected by Enterococcus species, and in the ceftazidime group there were two superinfections by Enterococcus species and one by Enterobacter cloacae. Intravenous ciprofloxacin was as effective as ceftazidime in the treatment of nosocomial pneumonia and urinary tract infection. Caution should be exercised when treating serious infections by streptococci or staphylococci.

A randomized trial of surgery in the treatment of single metastases to the brain.

To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

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.

Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-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 mumol/L vs. 62 mumol/L, p = 0.04). Phenylalanine levels were significantly higher in group 1 (107 mumol/L) versus group 2 (82 mumol/L) patients (p = 0.01). Arginine levels were significantly higher in group 1 (78 mumol/L) versus group 2 (49 mumol/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.

The acute-phase response of the brain-injured patient.

The acute response to injury and infection is manifested by increased synthesis of acute-phase proteins by the liver, an increased white blood cell count, fever, a negative nitrogen balance, and altered serum mineral levels (zinc, iron, and copper). This response is thought to be partially mediated by cytokines such as interleukin-1, but has not been well studied in head-injured patients. In this study, 25 patients were studied for evidence of the acute-phase response extending from hospital admission up to 21 days postinjury. The patients were divided into two groups to determine if severity of injury influenced the response. Group 1 consisted of nine patients with admission peak 24-hour Glasgow Coma Scale (GCS) scores of 4 or less; Group 2 consisted of 16 patients with admission peak 24-hour GCS scores of 8 or greater. All patients demonstrated some evidence of the acute-phase response. Serum alpha-1 acid glycoprotein, ceruloplasmin, and C-reactive protein levels were elevated on admission and throughout the study. Serum albumin and zinc levels were depressed on admission; zinc levels gradually normalized by Day 21 in both groups, but hypoalbuminemia was observed throughout the study period. Serum copper levels were normal on admission but increased to above normal in both groups by Day 11 postinjury. Urinary urea nitrogen excretion was elevated in both groups and peaked on Day 7 for Group 1 and Day 11 for Group 2 patients. The patients with admission GCS scores equal to or less than 4 had overall higher temperatures than were seen in those with GCS scores greater than or equal to 8 (p = 0.009). All patients but one had an elevated white blood cell count on admission. It is concluded that brain-injured patients with admission GCS scores of 3 to 4 and 8 to 14 demonstrate an acute-phase response which lasts for at least 3 weeks postinjury. It is speculated that this response is at least partially mediated by increased intraventricular interleukin-1 activity.

Prophylactic parenteral antibiotics in clean neurosurgical procedures: a review.

Clean surgical procedures carry a risk of postoperative wound infection that is less than 5% in most hospitals. The use of prophylactic antibiotic agents in clean neurosurgical cases is controversial, and the neurosurgical literature through 1980 contains no controlled clinical trials to study its effectiveness in such cases. A report of 1732 consecutive procedures without a single postoperative wound infection in patients receiving systemic gentamicin, vancomycin, and streptomycin irrigation fluids is often quoted by neurosurgeons; however, these results have not yet been duplicated by others. Since 1980, there have been several controlled trials that support the use in clean neurosurgical cases of prophylactic antibiotics, including the vancomycin/gentamicin/streptomycin regimen and the first-generation cephalosporins. A report in 1986 of 1602 cases without a primary wound infection supports the use of a single perioperative dose of cefazolin. A review of causative organisms in postoperative wound infections demonstrates the preponderance of Gram-positive pathogens. Therefore, when antibiotic prophylaxis is indicated, adequate Gram-positive bacterial coverage, including protection against Staphylococcus infection, is required. With consideration of the present data, the cost of antibiotic therapy, and the danger of drug toxicity, a short perioperative regimen of cefazolin as prophylaxis is preferred in clean neurosurgical cases.

Cerebellar hemangioblastoma symptomatic during pregnancy.

An 18-year-old woman presented during the 2nd month of her pregnancy with noncommunicating hydrocephalus due to a cerebellar hemangioblastoma. The tumor rapidly enlarged over a 12-day period after ventriculoperitoneal shunting, probably because of expansion of the vascular compartment. Serial computed tomography and magnetic resonance imaging observations support previous speculations in the literature that vascular engorgement of hemangioblastomas probably accounts for the rapid deterioration of some patients during pregnancy.

Intolerance to enteral feeding in the brain-injured patient.

Calorie and protein supplementation improves nutritional status. This support may improve outcome and decrease morbidity and mortality in acutely brain-injured patients. Investigators have observed a poor tolerance to enteral feedings after brain injury and have noted that this persists for approximately 14 days postinjury. This delay has been attributed to increased gastric residuals, prolonged paralytic ileus, abdominal distention, aspiration pneumonitis, and diarrhea. In the present investigation, 23 brain-injured patients with an admission 24-hour peak Glasgow Coma Scale (GCS) score between 4 and 10 were studied for 18 days from hospital admission. The mean duration from injury to initiation of full-strength, full-rate enteral feeding was 11.5 days. Seven of the 23 patients tolerated enteral feedings within the first 7 days following hospital admission (mean 4.3 days), four patients tolerated feedings between 7 and 10 days postadmission (mean 9 days), and 12 patients did not tolerate feedings until after 10 days postinjury (mean 15.9 days). There was a marginally significant relationship between low GCS scores on admission and length of days to enteral feeding tolerance (p = 0.07). A significant inverse relationship was observed between daily peak intracranial pressure (ICP) and time to tolerance of feedings (p = 0.02). There was no significant relationship between feeding tolerance and days to return of bowel sounds (p = 0.12). Serum albumin levels decreased during the investigation (mean +/- standard error to the mean: 3.2 +/- 0.12 gm/dl on Day 1; 2.7 +/- 0.23 gm/dl on Day 16; normal = 3.5 to 5.0 gm/dl), whereas the percentage of patients tolerating feedings increased over the course of the study. The authors conclude that patients with acute severe brain injury do not adequately tolerate feedings via the enteral route in the early postinjury period. Tolerance of enteral feeding is inversely related to increased ICP and severity of brain injury. It is suggested that parenteral nutritional support is required following brain injury until enteral nutrition can be tolerated.