Jane A. Norton

Metabolic and nutritional sequelae in the non-steroid treated head injury patient.

Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 +/- 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended] was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 +/- 0.2 on admission to 1.98 +/- 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 +/- 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.

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.

Cutaneous reactions in head-injured patients receiving phenytoin for seizure prophylaxis.

Two types of adverse effects are caused by phenytoin, reversible dose-dependent central nervous system effects and non-dose dependent hypersensitivity effects. The most common presenting symptom of the hypersensitivity reaction is the development of a morbilliform rash. During a 45-month period, 151 head-injured patients received phenytoin for seizure prophylaxis using an 11-mg/kg i.v. and a 13-mg/kg i.m. parenteral loading dose followed by an i.m. or p.o. maintenance dose for therapeutic blood concentrations (10 to 20 micrograms/ml). The patients were followed for 18 months. The incidence of skin reaction to phenytoin was 19.4%, or 24 of 124 patients. Cutaneous reactions occurred from Day 5 through Day 91 of phenytoin therapy. Two patients had more serious reactions after the cutaneous reaction. One patient developed exfoliative dermatitis, and 1 had a pseudolymphoma type syndrome. Both recovered. Patients with cutaneous reactions had higher absolute eosinophil counts (P = 0.01). Other laboratory parameters of the white blood count and the total lymphocyte counts did not differ significantly. Patients receiving dexamethasone had a higher incidence of rash, but this did not reach statistical significance. Because recent data have not documented a seizure-prophylactic effect of phenytoin, only a head-injured patient who has experienced a first posttraumatic seizure should receive the drug.

Relaxation training and opioid inhibition of blood pressure response to stress

The present study was designed to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Opioid mechanisms were assessed by examination of the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and after relaxation training. Thirty-two young men with mildly elevated casual arterial pressure were recruited for placebo-controlled naltrexone stress tests and relaxation training. The results indicated that relaxation training significantly reduced the diastolic pressure response to mental arithmetic stress. Opioid receptor blockade with naltrexone antagonized the effects of relaxation training. These findings suggest that some of the physiological effects of relaxation training are mediated by augmentation of inhibitory opioid mechanisms.

Posttraumatic Epilepsy Prophylaxis

Summary: Despite a large body of experimental evidence suggesting that posttraumatic epilepsy can be prevented, there is no generally accepted pharmacological regimen for posttraumatic seizure prophylaxis. This article describes a phenytoin anticonvulsant regimen specifically tailored for the patient with acute head injury and designed to provide immediate and sustained plasma concentrations of phenytoin between 10 and 20 jug/ml. Initially, an intravenous phenytoin dose of 11 mg/kg body weight is immediately followed by an intramuscular dose of 13 mg/kg body weight. This is followed by daily intramuscular maintenance doses, usually 8.8 mg/kg body weight, until oral medication can be tolerated. Maintenance dosage adjustments, when necessary, are based on serial plasma concentrations of the drug. Eighty‐four patients with severe head injuries with substantial risk of posttraumatic epilepsy were administered this regimen. Only 6% of these patients had seizures during the first year after injury (first week excluded), and this is considerably less than the rates reported elsewhere in the literature. Only one‐third of these patients are known to have continued to take phenytoin after the first month, and only half of these had plasma phenytoin concentrations above the desired minimal level. The greatly reduced incidence of posttraumatic seizures in these patients, despite the low rate of long‐term drug compliance, suggests that a prophylactic effect, rather than a suppressive effect, is produced.

Failure of Prophylactically Administered Phenytoin to Prevent Post-Traumatic Seizures in Children

We report the results of a randomized, double-blind, placebo-controlled study to determine whether phenytoin administered soon after a head injury lessens the incidence of late post-traumatic epilepsy in children. 41 patients were randomized into either a phenytoin or placebo group and followed for 18 months. The patients were administered phenytoin or placebo intravenously or intramuscularly within 24 h of hospital admission. The patients were parenterally administered phenytoin or placebo until oral doses could be tolerated. There was no significant difference in the percentage of children having seizures in the treated and placebo groups (p = 0.25).

An unusual reaction to opioid blockade with naltrexone in a case of post‐traumatic stress disorder

An unusual behavioral and cardiovascular reaction was observed during opioid blockade with naltrexone in a 32-year-old male who met DSM III-R criteria for post-traumatic stress disorder (PTSD). As part of an ongoing placebo-controlled investigation of the effects of naltrexone on laboratory and ambulatory blood pressure reactivity, this participant reported experiencing feelings of rage, explosive behavior, and other unpleasant symptoms. When compared to all other subjects (N=24), this individual showed significantly greater effects of naltrexone on blood pressure reactivity during the laboratory stressor. His ambulatory blood pressures, when compared to placebo, were significantly increased during the 24-hr period following naltrexone. The unusual behavioral and cardiovascular responses following ingestion of naltrexone suggest an important role for endogenous opioids in adjustment to stress in this case of PTSD.

Endogenous opioids inhibit ambulatory blood pressure during naturally occurring stress.

Objective Laboratory experiments suggest that endogenous opioids inhibit blood pressure responses during psychological stress. Moreover, there seem to be considerable individual differences in the efficacy of opioid blood pressure inhibition, and these differences may be involved in the expression of risk for cardiovascular disease. To further evaluate the possible role of opioid mechanisms in cardiovascular control, the present study sought to document the effects of the long-lasting oral opioid antagonist naltrexone (ReVia, DuPont, Wilmington, DE) on ambulatory blood pressure responses during naturally occurring stress. Method Thirty male volunteers participated in a laboratory stress study using naltrexone followed by ambulatory blood pressure monitoring during the subsequent 24-hour period. Within-subject analyses were performed on ambulatory blood pressures under placebo and naltrexone conditions. Results Laboratory results indicate no significant group effects of naltrexone on blood pressure levels or reactivity. Ambulatory results indicate that during periods of low self-reported stress, no effect of opioid blockade was apparent. In contrast, during periods of high stress, opioid blockade increased ambulatory blood pressure. Conclusions These findings suggest that naltrexone-sensitive opioid mechanisms inhibit ambulatory blood pressure responses during naturally occurring stress.

Psychological coping with acute pain: An examination of the role of endogenous opioid mechanisms

This study examined the relationship among endogenous opioids, Monitoring and Blunting coping styles, and acute pain responses. Fifty-eight male subjects underwent a 1-min pressure pain stimulus during two laboratory sessions. Subjects experienced this pain stimulus once under endogenous opioid blockade with naltrexone and once in a placebo condition. Blunting was found to be negatively correlated with pain ratings, but this relationship was significantly more prominent under opioid blockade. Results for coping behaviors subjects used to manage the experimental pain were generally consistent with the Blunting results, indicating that cognitive coping was related more strongly to decreased pain ratings and cardiovascular stress responsiveness under opioid blockade. Overall, the beneficial effects of Blunting and cognitive coping on pain responses did not depend upon endogenous opioids and, in fact, became stronger when opioid receptors were blocked. The relationship between endogenous opioids and coping appears to be dependent upon situational and stimulus characteristics.

A Comparative Study of Laboratory Parameters in Head-Injured Patients Receiving Either Phenytoin or Placebo for 24 Months

The effects of chronic phenytoin therapy on serum calcium, phosphorus, folate, and various hematological indices were assessed. One hundred and fifty-one patients, ages 18 months to 81 years, received phenytoin in a previously-conducted, double-blind, placebo-controlled study. Of the patients receiving phenytoin, initially 127 were evaluable while for control patients receiving placebo, 116 were evaluable. All patients had various laboratory parameters monitored at one day post-loading dose, one week, 1,3,6,9,12,15,18,21, and 24 months. Laboratory values examined were serum calcium, phosphorus, folate, white blood cell count with differential, hemoglobin, hematocrit, and red blood cell and platelet counts. A statistical analysis using the t-test method was employed to evaluate data. Data are reported as mean values ± standard deviation. Patients suffering early hypersensitivity, manifested by a morbilliform skin rash, were removed from the drug by day 30 and were not included in the chronic therapy review. Results indicate that the various laboratory values examined were not significantly affected by phenytoin administration in the patient population. Therefore, chronic phenytoin therapy following the initial hypersensitivity period does not cause abnormal laboratory values as followed in this study.