Subclinical thyroid disease after radiation therapy detected by radionuclide scanning.

PURPOSE: The actuarial risk for developing benign or malignant thyroid disease following radiation therapy (RT) is controversial, but may be as high as 50% at 20 years. An effective screening modality should be specific but not overly sensitive, a limitation of ultrasound. We questioned whether Technetium-99 m pertechnetate ((99m)Tc TcO(4)(-)) scanning could detect clinically significant disease in ostensibly disease-free cancer survivors. METHODS AND MATERIALS: Eligibility criteria included an interval of at least 5 years after RT to the cervical region, a thyroid gland that was normal to palpation, euthyroid status determined by clinical examination, free T4 and TSH. The 34 patients scanned included 16 children (<18 years old) and 18 adults at the time of RT, 16 females and 18 males. The mean age at RT was 20 years (range, 2.1-50.3 years), and the mean age at (99m)Tc TcO(4)-scanning was 33 years (range, 13.6-58 years), providing a mean interval of 13 years (range, 5.3-26.6 years). The mean RT dose to the thyroid was 36.4 Gy (range, 19.5-52.5). Thyroid scanning was performed with a 5 mCi dose of (99m)Tc TcO(4)(-) obtaining flow, immediate and delayed static, and pinhole collimator images. RESULTS: Seven patients (21.6%) had abnormal scans, and the percentage was higher among children (25%) and females (25%) compared to adults (16.7%) and males (16.7%), respectively. Two of 34 patients (5.9%) were discovered to have a thyroid cancer; histopathologies were papillary and follicular carcinoma. CONCLUSION: In this population of clinically normal cancer survivors who had been irradiated to the cervical region, subclinical thyroid disease, of potential clinical significance, was detected by (99m)Tc TcO(4)(-) in about 20%. Children may be more commonly affected. Although the cost effectiveness of screening will require a larger sample number, we propose a surveillance schema for this patient population.

Effect of N(G)-nitro-L-arginine methyl ester on autonomic modulation of heart rate variability during hypovolemic shock.

OBJECTIVE: To study the changes in neuroautonomic regulation of heart rate and the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, on efferent sympathetic cardiac activity and blood pressure during hypovolemic shock. Hypotension during hypovolemic shock may be attributable, in part, to the failure of neuroautonomic regulation of heart rate and blood pressure. In addition, the release of nitric oxide may contribute to hypotension through vasodilation and inhibition of efferent sympathetic activity. DESIGN: Prospective, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Seventeen anesthetized adult male New Zealand White rabbits. INTERVENTIONS: The rabbits were divided into four groups: control (n = 3), control plus L-NAME (n = 5), hypovolemic (n = 4), and hypovolemic plus L-NAME (n = 5). Hypovolemic rabbits were bled of 10% of their circulating blood volume (85 mL/kg) every 10 mins until 30% cumulative hypovolemia was reached. Rabbits received either three doses of saline 1 mL/kg every 10 mins or L-NAME 10 mg/kg in 1 mL/kg of saline solution administered after each hemorrhage for a total of three doses. Changes in heart rate, respiratory rate, mean arterial pressure, plasma catecholamine levels, and heart rate power spectra were recorded every 10 mins during serial hypovolemia and during a 30-min recovery period. MEASUREMENTS AND MAIN RESULTS: During hypovolemic shock there was a decrease in log low-frequency heart rate power (p = .001) and in systolic (p = .003), diastolic (p < .001), and mean (p < .001) blood pressures compared with control rabbits. Treatment with L-NAME during hypovolemia resulted in increased log low-frequency heart rate power (p = .03) and systolic (p = .01), diastolic (p = .007), and mean (p = .009) blood pressures compared with hypovolemic rabbits who received saline placebo. CONCLUSIONS: We found that treatment with L-NAME increased efferent sympathetic cardiac activity and mean arterial pressure during hypovolemic shock compared with control rabbits. We conclude that L-NAME may blunt hypotension during hypovolemic shock by inhibiting nitric oxide synthase and may act to restore neuroautonomic cardiovascular reactivity. Spectral analysis of heart rate variability may allow for insights into the pathophysiology of shock and provide a means of monitoring the neuroautonomic cardiovascular response to therapy.

Sympathetic activation cannot fully account for increased plasma renin levels during water deprivation.

This study was designed to determine if the increase in plasma renin activity (PRA) that occurs during water deprivation is mediated by the renal sympathetic nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were studied while conscious and unrestrained. In intact or sham-operated rats, 48 h of water deprivation resulted in at least a threefold increase in PRA and plasma renin concentration (PRC) but no significant change in plasma norepinephrine or epinephrine concentration. Renal denervation decreased basal PRA, reduced the magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin-suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal demedullation also reduced basal and water-deprived PRA and PRC. However, even the combination of renal denervation and adrenal demedullation did not prevent a significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1) x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05). Therefore, some mechanism in addition to sympathoadrenomedullary activation plays a major role in mediating increased PRA during water deprivation.

Thyroid evaluation of hospitalized psychiatric patients: the role of TSH screening for thyroid dysfunction.

The incidence and pattern of changes in thyroid function tests were studied in acutely hospitalized psychiatric patients and the cost effectiveness of a systematic screening program for thyroid dysfunction was estimated. Thyroid testing was performed on 1275 of 1424 (90%) admissions to the psychiatric wing of Strong Memorial Hospital between April 1, 1993 and March 30, 1994. Discharge samples were obtained in 232 patients who were hospitalized at least 2 days; 163 patients were admitted multiple times. Psychiatric diagnosis was coded using DSM-III-R criteria. TSH, T4, free T4, and T3 levels were measured within 48 h of admission. TSH values were most frequently abnormal (7.8%) and free T4 the least (1.3%). Admission and discharge thyroid tests were similar. Significant differences in the four parameters of thyroid function were present among the psychiatric groups. By analysis of variance every 1 microU/mL increase in TSH levels was associated with a 2.5% increase in length of stay (LOS) (95% confidence intervals: 0.21%, 4.75%), holding psychiatric diagnosis, age, and gender constant. For patients with elevated TSH levels, the average LOS was increased by 10.7 days (95% confidence intervals: 2.8, 18.7 days). It is concluded that patients hospitalized for psychiatric illness have an incidence of thyroid dysfunction at or slightly higher than the general population. However, patients with elevated TSH levels are hospitalized longer than those with normal or suppressed values.

Autonomic control of heart rate after brain injury in children.

OBJECTIVES: To study sequential changes in heart rate, respiratory rate, blood pressure, heart rate power spectra, and plasma catecholamine concentrations in patients with acute brain injury and correlate these variables with the severity of neurologic dysfunction and patient outcome. DESIGN: Prospective, clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Thirty-seven pediatric patients with acute brain injury caused by trauma, anoxia/ischemia, hemorrhage, or infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found significant associations between low-frequency (0.01 to 0.15 Hz) heart rate power and severity of neurologic dysfunction (as assessed by the admission Glasgow Coma Scale) (p < .001) and patient outcome (as assessed by the Glasgow Outcome Scale) (p = .05). The admission (p = .05) and maximum (p < .001) values for low-frequency heart rate power and the minimum value for high-frequency (0.15 to 0.50 Hz) heart rate power obtained during hospitalization (p = .001) predicted an increased likelihood of survival. Ten brain-dead patients had significantly decreased low-frequency heart rate power (p = .008) and plasma norepinephrine (p = .015), epinephrine (p = .03), and dopamine (p = .04) concentrations when compared with six non-brain-dead patients with a Glasgow Coma Scale score of 3. CONCLUSIONS: Our results imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult in children after acute brain injury. Thus, heart rate power spectral analysis and plasma catecholamine concentrations may prove to be useful adjuncts in determining severity of neurologic injury and prognosis for recovery in children suffering from brain injury. In addition, these techniques may aid in the determination of brain death.

Autonomic modulation of heart rate variability during endotoxin shock in rabbits.

OBJECTIVE: Gram-negative septic shock is associated with severe hypotension and autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as measured by power spectral analysis of heart rate (HR) variability, would be decreased compared with the anesthetized control rabbits. DESIGN: Experimental, comparative study. SETTING: Laboratory of a university hospital. SUBJECTS: Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were studied under anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied the absolute and temporal changes in HR power spectra and plasma catecholamine concentrations in eight experimental and six control New Zealand white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations, arterial blood pressure (BP), HR power spectra, and plasma catecholamine concentrations were measured at 5- to 10-min intervals for 60 mins in control rabbits or until the mean arterial pressure (MAP) decreased by > or = 20 mm Hg in experimental rabbits. There were no differences in basal HR, respiratory rate, BP, HR power spectra, or catecholamine concentrations between groups. After endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p < .05) as did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p < .05). Low-frequency HR power and MAP remained unchanged in control animals. Log high-frequency HR power decreased in control and experimental rabbits (-1.02 +/- 1.34 vs. -1.69 +/- 2.12 [control], p < .05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85 beats/min2 [experimental], p < .05). While there was an inverse relationship between low- and high-frequency HR power and MAP, the direction of change was opposite in six of six rabbits in the control group and in six of eight rabbits in the experimental group. Plasma catecholamine concentrations did not change during the experiment in either group. CONCLUSIONS: Sympathetic modulation of cardiac activity decreased, while the sympathomedullary response remained unchanged during endotoxin shock. We speculate that a concomitant decrease in low-frequency HR power as MAP decreases may prove to be an early marker for impending shock.

Heart rate power spectrum and plasma catecholamine levels after postural change and cold pressor test.

During stress, low-frequency (0.01-0.15 Hz) heart rate power and plasma catecholamine levels increase in response to increased sympathetic efferent activity. To test the hypothesis that low-frequency heart rate power, a measure of sympathetic control of heart rate, directly correlates with plasma catecholamine concentrations during periods of increased sympathetic tone, we compared heart rate power spectral measures with antecubital vein norepinephrine, epinephrine, and dopamine concentrations during postural change and after cold pressor testing. We analyzed absolute levels and changes in mean heart rate, respiratory rate, blood pressure, heart rate power spectra, and concentration of norepinephrine, epinephrine, and dopamine in 14 healthy volunteers (seven female/seven male) after postural change and in six (three female/three male) during cold pressor testing. Postural change from supine to standing position resulted in increased heart rate [61 +/- 8 versus 83 +/- 11 (SD) bpm, p < 0.05], diastolic (68 +/- 7 versus 77 +/- 6 mm Hg, p < 0.05) and mean blood pressures (84 +/- 6 versus 91 +/- 9 mm Hg, p < 0.05), norepinephrine concentration (2.09 +/- 1.11 versus 3.23 +/- 1.62 nmol/L, p < 0.05), and low-frequency heart rate power (7.55 +/- 5.63 versus 33.79 +/- 23.55 bpm2, p < 0.05). High-frequency heart rate power, a measure of parasympathetic control of heart rate, decreased with standing (5.38 +/- 4.22 versus 2.94 +/- 2.69 bpm2, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cardiovascular effects of mu- and delta-opioid receptor antagonists in dogs with congestive heart failure.

We have shown previously that right heart failure (RHF) in dogs is associated with activated endogenous opiate systems, and that administration of the opioid receptor antagonist, naloxone, increases arterial pressure, cardiac contractile function and organ blood flows. To study whether the cardiovascular effects of naloxone are mediated via the mu- or delta-opioid receptors, we administered ICI-154,129, a delta-receptor antagonist, and naloxonazine, a mu-receptor antagonist, to 10 conscious dogs with RHF on 2 separate days. Like naloxone, ICI-154,129 increased mean aortic pressure, cardiac output, peak positive first derivative of left ventricular pressure, and blood flows to the myocardium, kidneys, splanchnic beds, and skeletal muscle. These changes were associated with increases in plasma epinephrine and norepinephrine. In contrast, naloxonazine had no effects on systemic hemodynamics, regional blood flow distribution, and plasma catecholamines in RHF. These findings suggest that the increased endogenous opioids during heart failure act on the delta-opioid receptors to decrease myocardial mechanical performance and alter regional blood flow distribution. Opioid receptor-blocking agents may exert beneficial cardiovascular effects in heart failure.

Management of patients with small cell carcinoma and the syndrome of ectopic corticotropin secretion.

BACKGROUND: Small cell carcinoma (SCC) associated with clinical evidence of tumor corticotropin (ACTH) production is common, and management of this syndrome is difficult. The purpose of this retrospective analysis is to describe clinical features, prognosis, and treatment results in patients with SCC and the syndrome of ectopic ACTH secretion to permit formulation of management guidelines for these patients. METHODS: Using tumor registry data and chart review, the authors identified patients with SCC and ectopic ACTH secretion treated over 11 years at two large teaching hospitals. They recorded clinical and laboratory data regarding the patients' tumors and their endocrine syndrome along with results of treatment for the malignancy and the hypercortisolism. RESULTS: Ten patients with SCC and ectopic ACTH secretion were identified. These patients were initially seen with adverse prognostic features, including elevations of serum lactate dehydrogenase and extensive stage disease. Cytotoxic chemotherapy and standard doses of anti-adrenal medications rarely controlled the paraneoplastic syndrome. Bacterial or opportunistic infections, although not neutropenic, developed in most patients. Median survival of patients diagnosed with the paraneoplastic syndrome at the same time as the initial diagnosis of cancer was 4 months. However, three patients whose cortisol secretion was controlled survived longer than 6 months. CONCLUSIONS: Patients with SCC and ectopic ACTH syndrome have a poor prognosis. However, in the minority of patients whose hypercortisolism can be controlled with cytotoxic chemotherapy combined with treatment to inhibit cortisol biosynthesis, effective palliation can be achieved.

Short-term effects of naloxone on hemodynamics and baroreflex function in conscious dogs with pacing-induced congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the effects of naloxone on systemic hemodynamics and reflex function in dogs with congestive heart failure induced by rapid pacing. BACKGROUND: We have shown previously that naloxone, an opiate receptor antagonist, improves cardiac output, aortic blood pressure, systolic performance and the baroreflex function in conscious dogs with chronic right-sided congestive heart failure. However, whether endogenous opioids also play a role n mediating the reduction of myocardial and baroreflex function in animals with left heart failure remains controversial. METHODS: We administered naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing-induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs. In addition to systemic hemodynamic measurements, the slope of pressure-area relation obtained from echocardiography with intravenous bolus injection of phenylephrine was taken as a load-independent index of myocardial contractility. Baroreflex function was estimated by the slope of the regression line relating systolic aortic pressure and RR interval. RESULTS: Plasma beta-endorphin levels were elevated in dogs with congestive heart failure. Naloxone administration increased heart rate, mean aortic pressure, first derivative of left ventricular pressure, cardiac output and myocardial contractility in pacing-induced congestive heart failure. These changes correlated significantly with basal plasma beta-endorphin levels and were accompanied by increases in plasma beta-endorphin and catecholamines after naloxone administration. However, unlike the hemodynamic and cardiac effects of naloxone, baroreflex function did not change after naloxone in dogs with congestive heart failure. CONCLUSIONS: The increase in basal plasma beta-endorphin suggests that the endogenous opiate system is activated in left-sided congestive heart failure. Because naloxone improves the systemic hemodynamics and myocardial contractile function under this condition, the endogenous opioids appear to play an important role in mediating the myocardial depression that occurs in heart failure. However, the endogenous opiate system has no apparent effect on the regulation of baroreflex control in heart failure induced by rapid pacing.

Autonomic cardiovascular state after severe brain injury and brain death in children.

OBJECTIVE: To study and compare the autonomic cardiovascular state of children after severe brain injury and brain death. DESIGN: Prospective clinical study. SETTING: Pediatric ICU. PATIENTS: Pediatric patients suffering severe brain injury caused by trauma, anoxia, or hemorrhage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analyzed cardiorespiratory parameters, heart rate power spectra, plasma catecholamine concentrations, and the response to the cold pressor test in nine brain-dead patients and compared the results with the test findings of 11 patients with severe brain injury. Low-frequency total heart rate power (p < .03), peak amplitude (p < .02), and plasma catecholamine concentrations (p < .001) were different with no overlap of values between groups. Cold pressor testing in patients with severe brain injury showed changes in respiratory rate and low-frequency heart rate power that were +/- 20% to 100% from baseline values; however, there were no measurable changes in brain-dead patients. CONCLUSIONS: Our results support the concept of a damaged sympathetic cardiovascular system in severe brain injury and complete interruption of the autonomic cardiovascular pathways in brain death. Since determination of brain death may be difficult, our findings have implications for corroborating brain death using autonomic cardiovascular testing.

Hypothalamic-pituitary dysfunction after radiation for brain tumors.

BACKGROUND: Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. METHODS: We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. RESULTS: Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. CONCLUSIONS: Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.

The catecholamine response to multisystem trauma.

We studied the catecholamine response in two groups of patients with multisystem injuries according to the presence (group 1, N = 124) or absence (group 2, N = 82) of head injury. Markers of injury severity included the injury Severity Score, the Glasgow Coma Scale, the need for intubation, admission hypotension, the amount of blood products and fluid expanders administered during the first 24 hours, and patient outcome. In group 1, higher norepinephrine levels always and epinephrine concentrations usually were associated with worsening indexes of injury severity. The best correlations were between the Injury Severity Score and the Glasgow Coma Scale and norepinephrine concentrations. In group 2, despite elevated catecholamine levels, such associations were seldom present. Thus, circulating catecholamine levels, especially norepinephrine levels, significantly correlated with the severity of injury in patients who had suffered multisystem injury, but only if the injury included the brain.

Traumatic brain injuries: predictive usefulness of CT.

The computed tomographic (CT) scans from 72 patients with traumatic brain injury were reviewed to determined whether a specific type, location, or size of lesion correlated with changes in neurologic function (assessed with the Glasgow Coma Scale [GCS]), patient outcome (assessed with the Glasgow Outcome Scale [GOS]), or catecholamine levels. The lesions were classified as focal or diffuse. GOS changed as a function of lesions size (P = .00004) in the 48 patients with focal hemorrhages, regardless of whether the lesions were intra- or extraaxial, and in the 19 patients with normal CT scans. Patients with lesions larger than 4,100 mm3 had a twofold greater risk of a poor outcome than patients with smaller lesions (100% vs 50%). Patients with normal CT scans were significantly more likely to have mild neurological dysfunction or none than patients with abnormal CT scans (P = .03), but lesion location, skull fracture, and pineal shift were not significant predictors of GCS or GOS scores. A positive relationship existed between lesion size and both plasma norepinephrine and epinephrine levels (P less than .02); a significant relationship existed between lesion size and GCS score (P = .02).

Hormonal responses to trauma.

OBJECTIVES: To review the hormonal changes that have been reported after trauma, to define their etiologies, and to describe their consequences. DATA SOURCES: Literature review using MEDLINE and original data. DATA SYNTHESIS: Hormonal responses to trauma are bidirectional. Functional derangements include increases in adrenocorticotropin hormone and cortisol, growth hormone, and prolactin levels. In contrast, gonadotropin and gonadal steroid, and thyroid hormone concentrations decrease. The response is immediate but not necessarily sustained for those hormones that respond with increased secretion, whereas the effect may not become apparent for several hours, may be maximal after 1 to 4 days, and may persist for the duration of illness for those hormones that decrease. The reduction in hormone concentrations generally reflect diminished secretion, with the exception of the thyroid hormones where altered metabolic pathways and enhanced metabolic clearance play a major role. CONCLUSIONS: The changes in circulating levels do not appear to be injury specific, but tend to reflect the severity of the traumatic insult, and there are some data for cortisol and thyroxine that show their concentrations may be of predictive value. In head-injured patients, structural as well as functional pituitary changes may be present. Patients may show varying degrees of pituitary insufficiency. However, the presence of hyperprolactinemia strongly suggests involvement of the hypothalamus. With the exception of bonafide hypopituitarism, the relevance of the hormonal changes after trauma awaits clarification.

Effects of intoxication on the catecholamine response to multisystem injury.

In patients suffering isolated head trauma, we have previously shown that levels of circulating catecholamines obtained within 48 hours of trauma correlate with the severity of brain injury and predict outcome and that intoxication blunts this response. The effects of alcohol on the increase in catecholamines in systematically injured patients, however, have not been well defined. From 1983 to 1990, 78 patients (74% male; median age 30 years) with blunt head and multisystem injury, who also had alcohol levels measured within 5 hours of injury, were studied. Norepinephrine and epinephrine levels were assayed by a radioenzymatic technique. Injury severity was assessed by the admission Glasgow Coma Scale (GCS) score (4-15; median, 12), the Injury Severity Score (ISS) (13-50; median, 25) and the volume of blood products administered within the first 24 hours (0-14.4 L; median, 0.5 L). The impact of alcohol on the norepinephrine response to injury was analyzed using multiple linear regression models, including polynomial interaction terms. Norepinephrine levels significantly (p less than 0.0001) correlated with the GCS score and ISS. However, alcohol significantly lowered the norepinephrine response to decreasing GCS score (R = 0.49, p less than 0.002) and to increasing ISS (R = 0.51, p less than 0.0006). The blunting of the catecholamine response was most marked in those severely injured. The rise in norepinephrine concentrations seen with increasing volume of blood replacement was not affected by intoxication. An association between injury severity and epinephrine levels was also present, but not as consistently. Epinephrine concentrations rose with falling GCS score and with increasing ISS values, but unlike norepinephrine, there were no apparent effects of alcohol on changes in epinephrine levels. Thus, in patients suffering head and multisystem injury, catecholamine changes reflect the severity of injury using three different scalers. Furthermore, intoxication blunts only the norepinephrine component of this important biologic response.

The adrenocortical response to brain injury: correlation with the severity of neurologic dysfunction, effects of intoxication, and patient outcome.

To test the hypothesis that cortisol levels reflect the extent of neurologic dysfunction and predict patient outcome, neurologic function and cortisol levels were determined in 120 traumatically brain injured patients who never received glucocorticoid treatment. Their mean age was 29 years and 78% were men. The impact of intoxication was examined in 59 patients who had ethanol levels measured. Ethanol was detectable in 40 patients and greater than or equal to 100 mg/dl in 31. There were significant correlations between the extent of neurologic dysfunction, determined by the Glasgow Coma Score and plasma cortisol concentrations 1 and 4 days postaccident. Cortisol levels were universally elevated on admission and approached normal 7 days later. Multiple linear regression analysis revealed significant effects of circulating ethanol levels on the association between cortisol concentrations and progressively worsening neurologic function, i.e., ethanol reduced the magnitude of the cortisol elevations in a dose dependent manner, abolishing this relationship at levels above 100 mg/dl. Analysis of the relationships between circulating cortisol levels and patient outcome provided a second method for ascertaining the association between injury severity and the magnitude of adrenocortical activation. Admission and day 1 cortisol concentrations were 25 to 40% lower in patients having good recoveries or moderate disabilities than those who remained severely disabled, persistently vegetative or died; serum cortisol values of less than 20 micrograms/dl one day after the accident were more likely to be associated with a good outcome than a poor one (55 vs. 25%, p less than 0.001). The worsening prognosis of patients having higher cortisol values is further reflected in the duration of acute hospitalization of these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)