Risk of perioperative seizures in patients undergoing craniotomy with intraoperative brain mapping.

BACKGROUND: The identification of risk factors associated with perioperative seizures would be of great benefit to the anesthesiologist in managing brain tumor patients undergoing craniotomy with intraoperative brain mapping. METHODS: A series of 316 supratentorial craniotomies for tumor resection, in which intraoperative brain mapping was used, were analyzed. From January 2005 to December 2010 the occurrence of intraoperative and immediate postoperative clinical seizures was prospectively recorded into a database. Demographic data, tumor characteristics, preoperative seizure control, intraoperative events and anesthetic management were evaluated as risk factors for intraoperative clinical seizures. Additionally, the association between intraoperative clinical seizures and immediate postoperative seizures was evaluated. In order to determine the best predictors of intraoperative and immediate postoperative clinical seizures, a multivariable analysis by logistic regression was performed. RESULTS: Younger age, location of the tumor in the frontal and parietal lobe, brain mapping conducted under general anesthesia and non physiologic values of arterial carbon dioxide (PaCO2) during brain mapping were independent positive risk factors for the development of intraoperative clinical seizures. Location of tumor in the frontal lobe, antiepileptic polytherapy, intraoperative seizures requiring pharmacologic treatment during brain mapping, and blood on postoperative CT scan were independent positive risk factors for the development of immediate postoperative seizures. CONCLUSION: Clinical seizures are common intraoperative and postoperative complications of supratentorial craniotomies with intraoperative brain mapping. The identification of those patients at higher risk of seizures may guide intraoperative and postoperative medical management.

Awake neurosurgery: an update.

Intraoperative brain mapping has the goal of aiding with maximal surgical resection of brain tumors while minimizing functional sequelae. Retrospective randomized studies on large populations have shown that this technique can optimize the surgical approach while reducing postoperative morbidity. During direct electrical stimulation of the language areas adjacent to the tumor, the patient should be collaborative and be able to speak to participate in language testing. Different anesthesiological protocols have been proposed to allow intraoperative brain mapping, which range from local anesthesia to conscious sedation or general anesthesia, with or without airway instrumentation. The most common intraoperative complications are seizure, respiratory depression, and patients' stress and discomfort. Since awake craniotomy carries both benefits and potential risks, the following factors are crucial in the management of patients: 1) careful selection of the patients and 2) communication between the anesthesiological and surgical teams. To date, there remains no consensus about the optimal anesthesiological regimen to use. Only prospective, multicentre randomized studies focused on evaluating the role of different anesthesiological techniques on intraoperative monitoring, postoperative deficits, and intraoperative complications can answer the question of which anesthesiological approach should be chosen when intraoperative brain mapping is requested.

Neuroprotective effect of C1-inhibitor following traumatic brain injury in mice.

BACKGROUND: The goal of the study was to evaluate the effects of Cl-inhibitor (C1-INH), an endogenous glycoprotein endowed with multiple anti-inflammatory actions, on cognitive and histological outcome following controlled cortical impact (CCI) brain injury. METHODS: Male C57B1/6 mice (n=48) were subjected to CCI brain injury. After brain injury, animals randomly received an intravenous infusion of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 microl at 10 min postinjury). Uninjured control mice received identical surgery and saline injection without brain injury. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Mice were subsequently sacrificed, the brains were frozen and serial sections were cut. Traumatic brain lesion was assessed by dividing the area of the ipsilateral hemisphere for the area of the contralateral one at the level of the injured area of the brain. FINDINGS: Brain-injured mice receiving C1-INH at 10 min postinjury showed attenuated cognitive dysfunction compared to brain-injured mice receiving saline (p < 0.01). These mice also showed a significantly reduced traumatic brain lesion compared to mice receiving saline (p < 0.01). Mice receiving C1-INH at 1 hour post injury did not show a significant improvement in either cognitive or histological outcome. Conclusions Our results suggest that administration of C1-INH at 10 minutes postinjury attenuates cognitive deficits and histological damage associated with traumatic brain injury.

Effect of traumatic brain injury on cognitive function in mice lacking p55 and p75 tumor necrosis factor receptors.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has been suggested to play both a deleterious and beneficial role in neurobehavioral dysfunction and recovery following traumatic brain injury (TBI). The goal of this study was to evaluate the specific role of tumor necrosis factor (TNF) receptors p55 and p75 in mediating cognitive outcome following controlled cortical impact (CCI) brain injury by comparing post-traumatic cognitive function in mice with genetically engineered deletion of the gene for either p55 (-/-) or p75 (-/-) receptors. METHOD: Male C57B1/6 mice (WT, n=29), and mice genetically engineered to delete p55 TNF (p55 (-/-), n=8) or p75 TNF (p75 (-/-), n=23) receptors were used. They were anesthetized with intraperitoneal (i.p.) administration of sodium pentobarbital (65 mg/kg) and subjected to CCI brain injury of moderate severity. Sham-injured control mice were anesthetized and surgically prepared similarly but they received no impact. Assessment of mRNA expression of inflammatory, proapoptotic and antiapoptotic genes was done by real time-polymerase chain reaction (RT-PCR). Cognitive outcome was evaluated at 4 weeks postinjury using the Morris water maze (MWM). FINDINGS: mRNA expression of inflammatory, proapoptotic and antiapoptotic genes prior to TBI did not reveal any baseline difference between p55 and p75 (-/-) mice. WT mice showed greater baseline expression of inflammatory genes. The learning ability of p55 (-/-) brain-injured mice was significantly better than that observed in p75 (-/-) brain-injured mice (p < 0.05). Cognitive learning in WT control mice fell between the p55 (-/-) and p75 (-/-) mice. CONCLUSIONS: These data suggest that TNF-alpha may both exacerbate cognitive dysfunction via p55 receptor and attenuate it via p75 receptor.

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

Cortical and subcortical motor mapping in rolandic and perirolandic glioma surgery: impact on postoperative morbidity and extent of resection.

AIM: Surgery for gliomas located inside or in proximity of motor cortex or tracts requires cortical and subcortical mapping to locate motor function; direct electrical stimulation of brain cortex or subcortical pathways allows identification and preservation of motor function. In this study we evaluated the effect which subcortical motor mapping had on postoperative morbidity and extent of resection in a series of patients with gliomas involving motor areas or pathways. METHODS: One hundred and forty-six patients were included in the study. Intraoperative findings of primary motor cortex or subcortical tracts were reported, together with incidence of new postoperative deficits at short (1 week) and long term (1 month) examination. The relationship between intraoperative identification of subcortical motor tracts and extent of resection was reported. RESULTS: The motor strip was found in 133 patients (91%) and subcortical motor tracts in 91 patients (62.3%). New immediate postoperative motor deficits were documented in 59.3% of patients in whom a subcortical motor tract was identified intra-operatively and in 10.9% of those in whom subcortical tracts were not observed; permanent deficits were observed in 6.5% and 3.5%, respectively. A total resection was achieved in 94.4% of patients with high-grade gliomas and in 46.1% of those with low-grade gliomas.

Head injury, subarachnoid hemorrhage and intracranial pressure monitoring in Italy.

BACKGROUND: Intracranial pressure monitoring is recommended for the management of severe head injury and is increasingly used during intensive care for other pathologies, such as subarachnoid hemorrhage. However, it is still not uniformly applied in different centers. The objectives of this paper are to summarize the frequency and the modalities of intracranial pressure (ICP) monitoring in different centers in Italy; to describe its use in traumatic brain injury (TBI) and in subarachnoid hemorrhage (SAH); and to identify areas for improvement. METHODS: The medical directors of either the neurosurgical department or the intensive care unit, or both, of every Italian neurosurgical center were personally interviewed. They answered specific questions about TBI and SAH patients admitted, and ICP monitoring used, in their units. Data were cleared of any obvious inconsistencies and entered in a database for analysis. All analyses were based simply on the data declared. FINDINGS: The clinical information was obtained from 9137 TBI cases, of whom 4240 severe, and 3151 SAH patients. Among the 106 participating centers, 15 did not use ICP monitoring at all. The remaining 91 had used 3293 ICP devices during the year 2001; 146 were used in tumor cases, 2009 in TBI, and 1138 in SAH. Twenty-two percent of TBI cases admitted to centers with ICP equipment were monitored. Restricting this analysis to severe cases, 47% of TBI with a GCS <8 had ICP. On average, 36% of SAH underwent ICP monitoring. The proportions of head injury and SAH cases who underwent ICP monitoring varied widely in the different centers. Dividing the country into three main areas (north, center and south), there were considerable differences both in the rate of admissions per million inhabitants and in the frequency of ICP monitoring. INTERPRETATION: ICP monitoring in Italy is used in most, but not all, centers. ICP is measured fairly extensively in head injury cases, but a significant proportion of SAH patients is monitored as well. There are substantial differences in the frequency of ICP monitoring in different parts of the country. The use of ICP for both these indications, and the rates of admission to specialized centers, could be improved.

Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage.

OBJECTIVES: To assess the frequency of hyperthermia in a population of acute neurosurgical patients; to assess the relation between brain temperature (ICT) and core temperature (Tc); to investigate the effect of changes in brain temperature on intracranial pressure (ICP). METHODS: The study involved 20 patients (10 severe head injury, eight subarachnoid haemorrhage, two neoplasms) with median Glasgow coma score (GCS) 6. ICP and ICT were monitored by an intraventricular catheter coupled with a thermistor. Internal Tc was measured in the pulmonary artery by a Swan-Ganz catheter. RESULTS: Mean ICT was 38.4 (SD 0.8) and mean Tc 38.1 (SD 0.8) degrees C; 73% of ICT and 57.5% of Tc measurements were > or =38 degrees C. The mean difference between ICT and Tc was 0.3 (SD 0.3) degrees C (range -0.7 to 2.3 degrees C) (p=0. 0001). Only in 12% of patients was Tc higher than ICT. The main reason for the differences between ICT and Tc was body core temperature: the difference between ICT and Tc increased significantly with body core temperature and fell significantly when this was lowered. The mean gradient between ICT and Tc was 0.16 (SD 0.31) degrees C before febrile episodes (ICT being higher than Tc), and 0.41 (SD 0.38) degrees C at the febrile peak (p<0.05). When changes in temperature were considered, ICT had a profound influence on ICP. Increases in ICT were associated with a significant rise in ICP, from 14.9 (SD 7.9) to 22 (SD 10.4) mm Hg (p<0.05). As the fever ebbed there was a significant decrease in ICP, from 17.5 (SD 8.62) to 16 (SD 7.76) mm Hg (p=0.02). CONCLUSIONS: Fever is extremely frequent during acute cerebral damage and ICT is significantly higher than Tc. Moreover, Tc may underestimate ICT during the phases when temperature has the most impact on the intracranial system because of the close association between increases in ICT and ICP.

Intensive care management of head-injured patients in Europe: a survey from the European brain injury consortium.

OBJECTIVES: (a) to describe current practice in the monitoring and treatment of moderate and severe head injuries in Europe; (b) to report on intracranial pressure and cerebral perfusion pressure monitoring, occurrence of measured and reported intracranial hypertension, and complications related to this monitoring; (c) to investigate the relationship between the severity of injury, the frequency of monitoring and management, and outcome. METHODS: A three-page questionnaire comprising 60 items of information has been compiled by 67 centres in 12 European countries. Information was collected prospectively regarding all severe and moderate head injuries in adults (> 16 years) admitted to neurosurgery within 24 h of injury. A total of 1005 adult head injury cases were enrolled in the study from 1 February 1995 to 30 April 1995. The Glasgow Outcome Scale was administered at 6 months. RESULTS: Early surgery was performed in 346 cases (35%); arterial pressure was monitored invasively in 631 (68%), ICP in 346 (37%), and jugular bulb saturation in 173 (18%). Artificial ventilation was provided to 736 patients (78%). Intracranial hypertension was noted in 55% of patients in whom ICP was recorded, while it was suspected in only 12% of cases without ICP measurement. There were great differences in the use of ventilation and CPP monitoring among the centres. Mortality at 6 months was 31%. There was an association between an increased frequency of monitoring and intervention and an increased severity of injury; correspondingly, patients who more frequently underwent monitoring and ventilation had a less favourable outcome. CONCLUSIONS: In Europe there are great differences between centres in the frequency of CPP monitoring and ventilatory support applied to head-injured patients. ICP measurement disclosed a high rate of intracranial hypertension, which was not suspected in patients evaluated on a clinical basis alone. ICP monitoring was associated with a low rate of complications. Cases with severe neurological impairment, and with the worse outcome, were treated and monitored more intensively.

Early translaryngeal tracheostomy in patients with severe brain damage.

OBJECTIVES: To describe the effects of early translaryngeal tracheostomy on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and jugular bulb saturation (SjO2); to identify the main mechanisms affecting ICP during tracheostomy; and to evaluate the long-term effects of tracheostomy on tracheal anatomy and function. DESIGN: Prospective, observational, clinical study. SETTING: Neurosurgical intensive care unit in a teaching hospital. PATIENTS: 20 patients admitted to the ICU because of head injury, subarachnoid hemorrhage, or brain tumor with a Glasgow Coma Scale less than 8. INTERVENTIONS: Patients underwent translaryngeal tracheostomy under strict neuromonitoring. MEASUREMENTS AND RESULTS: ICP rose significantly (p < 0.05) at the critical time of cannula placement while all other parameters remained stable. At this time five patients suffered intracranial hypertension (ICP > 20 mmHg). In one of them CPP dropped below 60 mmHg. Arterial CO2 tension (PaCO2) did not rise significantly. No other major complications were recorded during the procedures. Three months after tracheostomy normal findings were detected by tracheoscopy in all cases (11 patients could be examined). CONCLUSIONS: Translaryngeal tracheostomy, performed in selected patients when the risk of intracranial hypertension was reduced to the minimum, was well tolerated in the majority of cases and did not induce persistent intracranial disorders. However, ICP is affected by tracheostomy, and careful monitoring and patient selection is necessary. At follow-up no severe anatomical or functional damage was detected.

Guidelines for the treatment of adults with severe head trauma (part III). Criteria for surgical treatment.

The Guidelines of the surgical management of severe head injury in adults, as evolved by the Neurotraumatology Group of the Italian Neurosurgery Society and the Italian Society for Anaesthesia, Analgesia, Reanimation and Intensive Care are presented and briefly discussed. Guidelines presented here are of a pragmatic nature, based on consensus and expert opinion. Aspects pertaining to specific indications to surgery and/or to the possibility of conservative management of different traumatic intracranial lesions are highlighted. The importance of surgery in preventing secondary insults to the traumatised brain is emphasised.

Neurophysiological consequences of three tracheostomy techniques: a randomized study in neurosurgical patients.

We describe the effects of different tracheostomy techniques on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral extraction of oxygen. We attempted to identify the main mechanisms affecting intracranial pressure during tracheostomy. To do so we conducted a prospective, block-randomized, clinical study which took place in a neurosurgical intensive care unit in a teaching hospital. The patients studied consisted of thirty comatose patients admitted to the intensive care unit because of head injury, subarachnoid hemorrhage, or brain tumor. Ten patients per group were submitted to standard surgical tracheostomy, percutaneous dilatational tracheostomy or translaryngeal tracheostomy. In every technique a significant increase of ICP (P < .05) was observed at the time of cannula placement. Intracranial hypertension (ICP > 20 mm Hg) was more frequent in the percutaneous dilatational tracheostomy group (P < .05). Cerebral perfusion pressure dropped below 60 mm Hg in eleven cases, more frequently during surgical tracheostomy. Arterial tension of CO2 significantly increased in all three groups during cannula placement. No other major complications were recorded during the procedures. At follow-up no severe anatomic or functional damage was detected. We conclude that the three tracheostomy techniques, performed in selected patients where the risk of intracranial hypertension was reduced to the minimum, were reasonably tolerated but caused an intracranial pressure rise and cerebral perfusion pressure reduction in some cases.

High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions.

Arterial hypertension is widely applied to improve regional cerebral blood flow (rCBF). We measured local brain tissue O2 pressure (PtiO2) in low density lesions at computerized tomography (CT) of the head before and after manipulation of mean arterial pressure (MAP) in order to increase cerebral perfusion pressure (CPP). Nine patients, 7 subarachnoid hemorrhage (SAH), 1 severe head injury, 1 meningeoma, were included in our study. A flexible polarographic microcatheter for PtiO2 measurement was placed at the border of the low density area found at CT. PtiO2 was continuously measured for 615 hours. Hypoperfusion in low density areas was detected by perfusional single photon emission computed tomography (SPECT). We recorded 22 episodes of induced or spontaneous increase of MAP. Initial PtiO2 regularly improved after the CPP increase (r2 0.74 in induced episodes). Low PtiO2 showed a greater percent increase for unitary changes of CPP than normal-high PtiO2. Baseline PtiO2 below 20 mm Hg was associated with normal CPPs; 5 readings of PtiO2 below 20 mm Hg normalized when a higher CPP was obtained. Our results show that in ischemic areas PtiO2 is dependent on CPP suggesting both a derangement of pressure autoregulation and high regional cerebrovascular resistences (CVRs). Low PtiO2 was associated with normal CPP, thus indicating that CPP could be an inadequate estimate of rCBF in focal ischemic areas. Arterial hypertension, capable of increasing CPP above normal values, appeared useful in normalizing tissue oxygenation in ischemic areas.

[Clinical evaluation of atracurium besylate in patients at risk: major burns]. / Valutazione clinica dell'atracurium besilato nei pazienti a rischio: il grande ustionato.

Atracurium besylate 0.5 mg/kg-1, an intermediate-duration non-depolarizing neuromuscular relaxant, was administered slowly (over 75 sec) in anesthesia induction of 61 patients with major thermal injury undergoing surgical excision and immediate skin-grafting procedures. Patients' mean +/- SD age was 40 +/- 9, body weight 64 +/- 2, burn size ranging from 20% to 90% of body surface area (BSA), postburn day of surgery 5th and more. Induction of anesthesia was carried out with sodium thiopental 2-5 mg/kg-1 plus fentanyl 2.8 micrograms/kg-1 e.v. and after few minutes atracurium 0.5 mg/kg-1 e.v. Anesthesia was maintained with N2O/O2 (70%/30%), isoflurane and small amounts of fentanyl. The mean arterial pressure and heart rate were recorded at I, II, III, IV, V min post atracurium administration. The endotracheal intubation conditions were assessed by a "IOT score". Results are expressed as mean value +/- standard deviation. The significance of the difference in mean values was analysed by t-test. Little haemodynamic changes occurred; intubating conditions showed a relative hyposensitivity of burn patients to atracurium, more severely burned patients (greater than 50-60%) exhibiting greater resistance.

[Control of the side effects of ketamine: chlordemethyldiazepam vs diazepam in pre-anesthesia]. / Controllo degli effetti collaterali della ketamina: clordemetildiazepam vs diazepam in preanestesia.

The pre-operative circulatory and psychotomimetic side-effects are studied in one hundred patients undergoing elective plastic-reconstructive surgery and anesthetized by ketamine 5-8 mg/kg i.m. Fifty patients were premedicated by atropine 0.01 mg/kg + CDDz 0.0285 mg/kg i.m. (group C), fifty by atropine 0.01 mg/kg + Dz 0.14 mg/kg i.m. (group D). All patients breathed spontaneously. Statistical analysis was performed with X 2 test. Not statistical difference was observed for the circulatory side-effects, whereas the frequency of emergence phenomena fell significantly from 31% to 14% (p less than 0.05) with CDDZ in greater than 16 years old patients. These finding seem confirm that CDDZ is more effective than DZ in reducing the psychotomimetic side-effects of ketamine, though it may be recommended a its wider experiment in this connection.

[Chlordesmethyldiazepam as an anesthesia-inducing agent: time of loss of consciousness. Statistical analysis in man]. / Il clordemetildiazepam come farmaco ipnoinducente: tempo di perdita di coscienza. Analisi statistica nell'uomo.

.1 mg/kg e.v. of chlordesmethyldiazepam, a 1.4 benzodiazepine derivative, were given in induction of anaesthesia of 60 plastic-reconstructive surgery patients respectively in 30 (Group 1.30 patients) and in 60 sec (Group 2.30 patients) to assess the times to spontaneous closing of the eyes and to disappearance of the palpebral reflex. It is concluded that the reflex times are not significantly different in both groups.

[Anesthesiologic management in scleroderma patients. Presentation of a clinical case]. / Condotta anestesiologica nel paziente sclerodermico. Presentazione di un caso clinico.

The scleroderma (literally, hard skin), or progressive systemic sclerosis (PSS), is a multisystem disease and can present various anaesthetic problems. The anaesthesist should be aware of the difficulty in opening mouth wide enough for laryngoscopy and intubation, the possibility that cardiopulmonary changes may be present and the probability of lesions in oesophagus, bowel, kidneys, skin and joints. In this article the authors describe the anesthetic management of a patient with Thibierge-Weissenbach syndrome (scleroderma with calcinosis cutis) and explore potential problems that should be anticipated by the anesthesiologist.