New European Directive on clinical trials.
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Clinical Trials as Topic↗
Biomedical subjects
Nino Stocchetti
Publications and source records attributed to Nino Stocchetti.
Alpha-melanocyte-stimulating hormone is decreased in plasma of patients with acute brain injury.
The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is a proopiomelanocortin derivative that has potent anti-inflammatory influences within the brain. The aim of the present research was to determine if there are changes in blood concentrations of this peptide in patients with acute traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Concomitantly, we recorded clinical parameters and measured blood concentrations of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Twenty-three patients were enrolled in this study--18 had TBI and five SAH. Blood samples for determination of alpha-MSH and TNF-alpha were collected daily from day 1 to day 4 after injury. Baseline concentration of plasma alpha-MSH in patients with acute brain injury of either traumatic or vascular origin was significantly lower than in controls. Patients with TBI or SAH had similar alpha-MSH concentrations and the peptide remained consistently low over four post-injury days. Circulating TNF-alpha on day one was measurable in all patients and there was a negative correlation between plasma TNF-alpha and alpha-MSH. Alpha-MSH was measured again after the acute phase in eight patients. The peptide was substantially increased in all subjects except for two who had an unfavorable outcome. From the well-known protective anti-inflammatory influences of alpha-MSH in the host, reduction in this circulating peptide may have detrimental consequences in brain injury. The data raise the possibility that restoration of normal circulating alpha-MSH through administration of the peptide could be beneficial in patients with brain injury.
Adolescent↗
Application of guidelines for severe head trauma: data from an Italian database.
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Adolescent↗
Traumatic subarachnoid hemorrhage on the computerized tomography scan obtained at admission: a multicenter assessment of the accuracy of diagnosis and the potential impact on patient outcome.
OBJECT: The goal of this study was fourfold: 1) to determine the incidence of traumatic subarachnoid hemorrhage (tSAH) in patients with traumatic brain injury (TBI); 2) to verify agreement in the diagnosis of tSAH in a multicenter study; 3) to assess the incidence of tSAH on the outcome of the patient; and 4) to establish whether tSAH itself leads to an unfavorable outcome or whether it is a sign of major brain trauma associated with severe posttraumatic lesions. METHODS: Computerized tomography (CT) scans obtained in 169 head-injured patients on admission to 12 Italian intensive care units during a 3-month period were examined. The scans were collected for neuroradiological review and were used for the analysis together with data from a multicenter database (Neurolink). A review committee found a high incidence of tSAH (61%) in patients with TBI and a moderate agreement among centers (K = 0.57). Significant associations were observed between the presence and grading of tSAH and patient outcomes, and between the presence of tSAH and the severity of the CT findings. Logistic regression analysis showed that the presence of tSAH and its grading alone do not assume statistical significance in the prediction of unfavorable outcome. CONCLUSIONS: Traumatic SAH frequently occurs in patients with TBI, but it is difficult to detect and grade. Traumatic SAH is associated with more severe CT findings and a worse patient outcome.
Adolescent↗
Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study.
OBJECT: The authors investigated the effects of hyperoxia on brain tissue PO2 and on glucose metabolism in cerebral and adipose tissue after traumatic brain injury (TBI). METHODS: After 3 hours of ventilation with pure O2, 18 tests were performed on different days in eight comatose patients with TBI. Lactate, pyruvate, glucose, glutamate, and brain tissue PO2 were measured in the cerebral extracellular fluid (ECF) by using microdialysis. Analytes were also measured in the ECF of abdominal adipose tissue. After 3 hours of increase in the fraction of inspired O2, brain tissue PO2 rose from the baseline value of 32.7 +/- 18 to 122.6 +/- 45.2 mm Hg (p < 0.0001), whereas brain lactate dropped from its baseline (3.21 +/- 2.77 mmol/L), reaching its lowest value (2.90 +/- 2.58 mmol/L) after 3 hours of hyperoxia (p < 0.01). Pyruvate dropped as well, from 153 +/- 56 to 141 +/- 56 micromol/L (p < 0.05), so the lactate/pyruvate ratio did not change. No significant changes were observed in glucose and glutamate. The arteriovenous difference in O2 content dropped, although not significantly, from a baseline of 4.52 +/- 1.22 to 4.15 +/- 0.76 m/100 ml. The mean concentration of lactate in adipose tissue fell significantly as well (p < 0.01), but the lactate/pyruvate ratio did not change. CONCLUSIONS: Hyperoxia slightly reduced lactate levels in brain tissue after TBI. The estimated redox status of the cells, however, did not change and cerebral O2 extraction seemed to be reduced. These data indicate that oxidation of glucose was not improved by hyperoxia in cerebral and adipose tissue, and might even be impaired.
Adolescent↗
Pyrexia in head-injured patients admitted to intensive care.
OBJECTIVES: (a) To quantify the occurrence of pyrexia during the first week after head injury; (b) to elucidate the relationships between pyrexia and neurological severity, length of stay in the ICU, intracranial hypertension, and cerebral perfusion pressure (CPP); and (c) to describe the effects of antipyretic therapy on temperature, intracranial pressure (ICP) and CPP. DESIGN AND SETTING: Multicenter retrospective observational study in three ICUs in the Milan area. PATIENTS: 110 patients with traumatic brain injury. MEASUREMENTS AND RESULTS: Eighty patients suffered pyrexia, defined as an external temperature higher than 38 degrees C or internal temperature higher than 38.4 degrees C. Occurrence and duration of pyrexia were associated with the degree of neurological impairment and with prolonged ICU stay. In patients with normal perimesencephalic cisterns the episodes of increased ICP were more frequent in febrile cases. Various antipyretic therapies were used in 66 patients. Pharmacological treatment was slightly effective (mean temperature reduction 0.58+/-0.7 degrees C) but caused a significant drop in CPP (6.5+/-12.5 mmHg). CONCLUSIONS: Pyrexia is extremely frequent in the acute phase after head injury. Its incidence is higher in more severe cases and is correlated with a longer ICU stay. It may affect ICP, but its contribution is difficult to assess when other major causes of increased intracranial volume are present. Antipyretic therapy is poorly effective for controlling body temperature and may be deleterious for CPP.
Adolescent↗
Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study.
PURPOSE: To determine the potential effectiveness of phenytoin (PHT) in preventing early postoperative seizures in patients undergoing craniotomy for supratentorial brain tumors. METHODS: Two hundred patients requiring elective craniotomy for supratentorial brain tumors were randomized to two groups of equal size, with a prospective, open-label, controlled design. One group received PHT (18 mg/kg as an intravenous intraoperative load, followed by additional daily doses aimed at maintaining serum PHT concentrations within the 10- to 20-aeg/ml range) for 7 consecutive days. In the other group, PHT was not administered. More than 90% of patients in both groups continued to take preexisting anticonvulsant medication (AEDs) with carbamazepine or phenobarbital throughout the study. The primary efficacy end point was the number of patients remaining free from seizures during the 7-day period after the operation. RESULTS: Of 100 patients allocated to PHT, 13 experienced seizures during the 7-day observation period, compared with 11 of 100 patients in the placebo group (p > 0.05). Most seizures occurred in the first day after surgery in both groups. There were no differences between groups in the proportion of patients experiencing more than one seizure, but there was a trend for generalized seizures to be more common in PHT-treated patients than in controls (11 vs. five patients, respectively). Status epilepticus occurred in one patient in the PHT group and in two patients in the control group. Of the 13 PHT-treated seizure patients, 11 had serum PHT concentrations within the target range, and only two had concentrations below range on the days their seizures occurred. CONCLUSIONS: PHT, given at dosages producing serum concentrations within the target range, failed to prevent early postoperative seizures in patients treated with concomitant AEDs. Prophylactic administration of PHT cannot be recommended in these patients.
Adolescent↗
Traumatic subarachnoid hemorrhage: demographic and clinical study of 750 patients from the European brain injury consortium survey of head injuries.
OBJECTIVE: Previous reports identified the presence of traumatic subarachnoid hemorrhage (tSAH) on admission computed tomographic (CT) scans as an independent prognostic factor in worsening outcomes. The mechanism underlying the link between tSAH and prognosis has not been clarified. The aim of this study was to investigate the association between CT evidence of tSAH and outcomes after moderate or severe head injuries. METHODS: In a survey organized by the European Brain Injury Consortium, data on initial severity, treatment, and subsequent outcomes were prospectively collected for 1005 patients with moderate or severe head injuries who were admitted to one of the 67 European neurosurgical units during a 3-month period in 1995. The CT findings were classified according to the Traumatic Coma Data Bank classification system, and the presence or absence of tSAH was recorded separately in the initial CT scan forms. RESULTS: Complete data on early clinical features, CT findings, and outcomes at 6 months were available for 750 patients, of whom 41% exhibited evidence of tSAH on admission CT scans. There was a strong, highly statistically significant association between the presence of tSAH and poor outcomes. In fact, 41% of patients without tSAH achieved the level of good recovery, whereas only 15% of patients with tSAH achieved this outcome. Patients with tSAH were significantly older (median age, 43 yr; standard deviation, 21.1 yr) than those without tSAH (median age, 32 yr; standard deviation, 19.5 yr), and there was a significant tendency for patients with tSAH to exhibit lower Glasgow Coma Scale scores at the time of admission. A logistic regression analysis of favorable/unfavorable outcomes demonstrated that there was still a very strong association between tSAH and outcomes after simultaneous adjustment for age, Glasgow Coma Scale Motor Scores, and admission CT findings (odds ratio, 2.49; 95% confidence interval, 1.74-3.55; P < 0.001). Comparison of the time courses for 164 patients with early (within 14 d after injury) deaths demonstrated very similar patterns, with an early peak and a subsequent decline; there was no evidence of a delayed increase in mortality rates for either group of patients (with or without tSAH). CONCLUSION: These findings for an unselected series of patients confirm previous reports of the adverse prognostic significance of tSAH. The data support the view that death among patients with tSAH is related to the severity of the initial mechanical damage, rather than to the effects of delayed vasospasm and secondary ischemic brain damage.
Adult↗
Current recommendations for neurotrauma.
Diagnostic and monitoring procedures for patients with head injury are aimed at early detection of mass lesions and secondary insults. Our therapeutic approach is based on our understanding of pathophysiologic mechanisms that cause secondary brain damage, and includes evacuation of mass lesions and prevention of secondary insults. Basic research has greatly increased our knowledge of these pathophysiologic mechanisms and has prompted the development of many neuroprotective agents, targeted to selected mechanisms. Unfortunately, it has proved difficult to demonstrate the benefit of such agents in the overall population of head-injured patients. Clinical research has emphasized the importance of ischemia in head injury and has demonstrated the deleterious effect of secondary insults on outcome. Medical management of patients with head injury has consequently focused on prevention of secondary insults, treatment of raised intracranial pressure, and maintenance of adequate cerebral perfusion pressure. The introduction of new monitoring techniques in head-injured patients offers the possibilities of more targeted therapy in individual patients, in contrast to the current practice of a staircase approach to treatment of raised intracranial pressure.In the US, an evidence-based approach has resulted in the wide acceptance of general principles, but at the same time highlighted the lack of hard evidence for the use of many therapeutic modalities. Practical guidelines, developed and published by the European Brain Injury Consortium, are based on expert opinion and consensus. Surveys have shown considerable variation in monitoring techniques and treatment. There is still considerable need for further improvements, both from a medical scientific perspective and from an organizational aspect. Particularly relevant are early resuscitation and stabilization at the scene of the accident, the organization of emergency services, admission policy to the intensive care unit, and improved policy for early identification of patients with operable intracranial hematoma. Further dissemination and general acceptance of already published guidelines may be expected to significantly improve care in head injury.
Journal Article↗