Long-term clinical experience with weekly interferon beta-1a in relapsing multiple sclerosis.

Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFNbeta-1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFNbeta-1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months. Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFNbeta-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.

HLA-DRB1*1501 and response to copolymer-1 therapy in relapsing-remitting multiple sclerosis.

BACKGROUND: Copolymer 1 (Cop-1) is a random synthetic amino acid copolymer, effective in the treatment of the relapsing-remitting form of MS (RRMS). In vitro and in vivo studies suggest that the mechanism of Cop-1 involves its binding to major histocompatibility complex class II molecules as an initial step. OBJECTIVE: To assess a possible relationship between human leukocyte antigen (HLA) alleles and response to Cop-1 therapy. METHODS: Eighty-three patients with RRMS, 44 treated with Cop-1 and 39 with interferon beta-1a (IFNbeta-1a) for 2 years, were typed by molecular methods for HLA class II genes and subgrouped according to clinical outcome. RESULTS: Data have shown a possible positive correlation between presence of DRB1*1501 and response to Cop-1 therapy (p = 0.008). No relationship between HLA alleles and therapy has been found in IFNbeta-1a treated patients. CONCLUSIONS: Results suggest that DRB1*1501 might be relevant for the clinical outcome in Cop-1 treated patients and, if confirmed in larger studies, it could be helpful in the selection of RRMS patients for different therapeutic options.

Propofol EEG burst suppression in carotid endarterectomy.

BACKGROUND: The results of randomized trials indicate that carotid endarterectomy, performed with a low morbidity-mortality perioperative risk, is the best therapeutic option both for patients with high-grade symptomatic and asymptomatic stenosis. Since the main operative risk is represented by embolic or hemodynamic cerebral ischemia, it appears necessary to maintain an adequate intraoperative cerebral blood flow and to carry out a meticulous endarterectomy. METHODS: On the basis of these considerations we prospectively studied a series of 100 consecutive patients operated on for high-grade carotid stenosis, by using a protocol based on: 1) an accurate selection of patients for surgery; 2) meticulous surgical technique without any shunt; 3) perioperative cerebral protection by barbiturate or propofol; 4) pre- and postoperative medical treatment of risk factors. All patients of our series performed preoperatively brain CT scan, transcranial Doppler, carotid duplex scanning, four vessel angiography, brain 99mTc-HMPAO SPECT. Eighty-two patients had symptomatic carotid stenosis ranged between 70 and 90%, 18 had carotid stenosis higher than 90%. RESULTS: In this series there have been one postoperative death due to myocardial infarction and one major stroke. CONCLUSIONS: We think that this protocol can significantly minimize risks of endarterectomy and probably maximize the benefits of surgery, also in patients with asymptomatic high-grade carotid stenosis.

Cerebrovascular reactivity before and after carotid endarterectomy.

BACKGROUND: The hemodynamic relevance of internal carotid artery (ICA) stenosis often does not correlate with anatomic features, as angiographically defined. The cerebrovascular reactivity (CVR) has been advocated as a means of defining the cerebral hemodynamic impairment. METHODS: We assessed the results of pre- and postoperative CVR evaluation, using the CO2 transcranial doppler method, in 25 patients with high-grade ICA stenosis. The patients with history of stroke, evidence of cerebral CT infarction or symptoms from the contralateral circulation or the brain stem were excluded to avoid the effects of cerebral infarction on the hemodynamic studies. Statistical analysis was used to evaluate the CVR changes after carotid endarterectomy. RESULTS: Preoperative evaluation showed that CVR was generally well correlated with the degree of ICA stenosis and concomitant contralateral carotid steno-occlusion. Before endarterectomy the mean CVR value was 66.5% (moderately reduced). After surgery the overall mean value of CVR was 84.1% (normal), with a statistically significant improvement. CONCLUSION: The results of this study suggest that the CVR evaluation allows one to obtain hemodynamic information of clinical interest in the patients with ICA stenosis and that carotid endarterectomy is effective to restore the CVR in patients with cerebral hemodynamic impairment.

Remifentanil vs fentanyl with a target controlled propofol infusion in patients undergoing craniotomy for supratentorial lesions.

AIM: Remifentanil hydrochloride is an ultra-short acting m-opioid receptor agonist. This study compared the use of remifentanil with that of fentanyl during elective supratentorial craniotomy in a target controlled infusion (TCI)-propofol anesthesia regimen and evaluated the quality of recovery from anesthesia. METHODS: After written informed consent for this prospective study, 40 adult patients were randomly divided into 2 groups: in group F analgesia was provided with fentanyl 2-3 mg kg(-1) h(-1) and in group R with remifentanil 0.25 mg kg(-1) h(-1). Anesthesia was induced with thiopental and pancuronium bromide, and maintained with propofol-TCI, pancuronium, air and oxygen and fentanyl (group F) or remifentanil (group R), respectively. After tracheal intubation, infusion rate of remifentanil was reduced and then adjusted to maintain stable hemodynamics. Hemodynamics and recovery time were monitored for 60 min after surgery. Analgesic requirements, propofol intraoperative consumption, nausea and vomiting in postoperative period were monitored. Recovery was evaluated according to a modified Aldrete score. RESULTS: Baseline hemodynamics were similar in both groups. Mean arterial pressure differed between the 2 groups (P<0.05) with the greatest decrease in group R during dura opening (P<0.001). Postoperative mean arterial pressure was higher in group R. Patients in group R exhibited a faster recovery. The incidence of nausea and vomiting was similar in the 2 groups. Noteworthy, there was a reduction in the amount of propofol used in group R. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective surgery of supratentorial lesions.

Effects of ketamine on the catecholamine containing cells of the adrenal gland of the lizard Podarcis s. sicula Raf.

The authors studied the effects of ketamine on the morphology of the adrenal gland of Podarcis s. sicula Raf.. Low doses of the drug failed to anesthetize the lizards and did not cause significant changes in the morphology of the adrenal cells. Higher doses of ketamine caused deep anesthesia and marked depletion of catecholamine granules. The results support the theory that ketamine acts on the peripheral autonomic nervous system and sympathetic ganglia.

[Appropriate arterial pressure management for subarachnoid hemorrhage ]. / Regime pressorio arterioso appropriato per l'ESA.

A correct assessment of arterial pressure state during SAH is one of most critical issue in neurologic intensive care. It is important to evaluate two different clinical conditions: a) during SAH when the aneurysm is open, b) after aneurysmal clipping or embolization. The authors propose pressure parameters appropriated for SAH according to the timing of treatment so as to prevent and treat SAH complications.

Clinical experience with Ciaglia's percutaneous tracheostomy.

During a 6-year period the authors performed percutaneous dilational tracheostomy (PDT) in 304 cases using the technique introduced by Ciaglia in 1985. A following study on 40 patients evaluated late complications of PDT; none of the patients developed laryngotracheal stenosis. In our experience PDT has been a very sure technique of securing the airway.

Spinal anesthesia in children: pro.

Spinal anaesthesia, first introduced in children at beginning of 20th century, offers adequate intraoperative anaesthetic conditions (analgesia and muscle relaxation). The technique is easy to perform even if lumbar puncture is more difficult when the children is smaller. It has not been observed haemodynamic modifications especially in patients under 5 year of age; duration of spinal anaesthesia is shorter if compared to adults and post dural puncture headache (PDPH) after spinal anaesthesia is as common in children as it is in adults, but was usually mild and very short lasting. PDPH has not been correlated with the type of spinal needle used. Hyperbaric solution of local anaesthetics like bupivacaine and tetracaine are preferable. The only adjuvant used for spinal anesthesia in children is morphine, which should be administered only in patients admitted to high dependency unit in the postoperative period. Spinal anaesthesia is indicated mainly in sub umbilical surgical procedures lasting no more than 90 minutes and particularly in the surgical treatment of former premature infants who present an higher risk with regional anaesthesia.

How to prolong postoperative analgesia after caudal anaesthesia with ropivacaine in children: S-ketamine versus clonidine.

BACKGROUND: The aim of the study was to determine whether caudal S-ketamine or clonidine prolonged analgesia together with ropivacaine. METHODS: Sixty-three boys, aged 1-5 years, who were undergoing minor surgery, were allocated in order to receive one of three solutions for caudal anaesthesia. Group R received 2 mg x kg(-1) 0.2% ropivacaine; group C, 2 mg x kg(-1) 0.2% ropivacaine + clonidine 2 microg x kg(-1); and group K, 2 mg x kg(-1) 0.2% ropivacaine + S-ketamine 0.5 mg x kg(-1). RESULTS: Postoperative analgesia assessed by CHEOPS lasted 701 min in group K (P < 0.05) compared with 492 min in group C and 291 min in group R. There were no significant differences between the groups for incidence of haemodynamic and respiratory alterations, motor block or sedation. CONCLUSIONS: This study demonstrates that S-ketamine 0.5 mg x kg(-1) when added to 0.2% caudal ropivacaine provides better postoperative analgesia than clonidine without any clinically significant side-effect.

Hypertonic saline solution: a safe alternative to mannitol 18% in neurosurgery.

BACKGROUND: To evaluate the usefulness of hypertonic saline solutions (HTS) as an alternative to mannitol in neurosurgery. METHODS: Thirty patients subjected to craniotomy for supratentorial cerebral tumors were randomly divided in to three Groups: M: had mannitol 0.5 g.kg-1 as bolus at the start of skin incision, and postoperatively 0.5 g.kg-1 daily three times a day for 3 days (72 hrs); HM: had mannitol 0.25 g.kg-1 as bolus at the start of skin incision plus 3% HTS, 20 ml.h-1 intraoperatively and mannitol 0.25 g.kg-1 daily three times a day for 3 days plus HTS in the concentration of 3% in the first day and 2% and 1% the second and the third day after surgery; H: had 3% HTS 3.5 ml kg-1 as bolus at the start of skin incision plus 3% HTS, 20 ml hr-1 intraoperatively and 3% HTS, 20 ml h-1 on the first day and 2% and 1% the second and the third day after surgery. FR, MAP, ICP, CVP and diuresis were continuously monitored intraoperatively and postoperatively for 72 hrs. ICP was monitored intraoperatively until dural opening and in the postoperative period for 72 hrs at least. RESULTS: Diuresis was increased in the first and second Group (M and HM) more than in the H Group especially in the postoperative period, but this change was not a significative one (35.31 ml.kg-1.h-1+/-4.57 and 36.56+/-3.92 vs 3.23 ml.kg-1.h-1). Mean serum Na+ values declined in the postoperative period, in Groups M and MH and remained stable in the postoperative period in the Group H (137.6+/-7 mEq.l-1 and 136.5+/-6.5 mEq.l-1 vs 139.2+/-5 mEq.l-1). Serum osmolality increased significantly in the postoperative period in group H and remained unchanged in the same period in Group M and MH. Potassium values declined significantly during the whole period in all groups but remained in a normal clinical range. CVP values decreased in Groups M and MH in the postoperative period, and increased although not significantly in the postoperative period in the Group H patients. Ht values declined significantly in all groups without differences among the groups although the reduction was greater in group H. CONCLUSIONS: HTS can safely be used in humans they obtain a reduction of ICP without reducing CVP, serum osmolality and Na+ serum values. Our data underline the possibility of their use as an alternative to mannitol in the treatment of patients scheduled for intracranial surgery, especially when multiple doses are needed.

The dose-response relationship for clonidine added to a postoperative continuous epidural infusion of ropivacaine in children.

UNLABELLED: Epidurally administered clonidine enhances the quality and duration of postoperative analgesia when it is used as an adjunct to local anesthetics in children. We investigated the dose-response relationship for epidural clonidine when added to a continuous postoperative epidural infusion of ropivacaine. By use of an observer-blinded design, 55 pediatric patients (1-4 yr old) were randomly given a postoperative epidural infusion of plain ropivacaine 0.1% 0.2 mg. kg(-1). h(-1) (Group R), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.04 microg. kg(-1). h(-1) (Group RC1), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.08 microg. kg(-1). h(-1) (Group RC2), or ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.12 microg. kg(-1). h(-1) (Group RC3). A clear dose-response relationship could be identified for a continuous infusion of epidural clonidine, with clonidine dosages in the 0.08-0.12 microg. kg(-1). h(-1) range providing improved postoperative analgesia (reduced Children's Hospital of Eastern Ontario pain score, increased time to first supplemental analgesic demand, and a reduced total number of doses of supplemental analgesics during the first 48 h after surgery). Analgesia was improved without any signs of increased sedation or other side effects. The adjunct use of epidural clonidine in the dosage range of 0.08-0.12 microg. kg(-1). h(-1) appears effective and safe for use in children. IMPLICATIONS: The addition of clonidine (0.08-0.12 microg.kg(-1).h(-1))to a continuous epidural infusion of ropivacaine was found to improve postoperative pain relief in children. No clinically significant signs of sedation or other side effects were observed.

Spinal anesthesia with clonidine and bupivacaine in young humans: interactions and effects on the cardiovascular system.

BACKGROUND: Clonidine, an alpha 2 agonist, is known to prolong the action of local anesthetics, and to provide a satisfactory analgesia; hypotension and bradycardia have been observed after its intrathecal administration. The aim of our study was to determine whether intrathecal administration of clonidine can reduce the dose of local anesthetic, and the effects of clonidine on the cardiovascular system, and on arousal level. METHODS: In a prospective, randomized study we evaluated 56 patients scheduled for minor surgical procedure (spermatic vein ligature) under unilateral spinal anesthesia with hyperbaric bupivacaine 1%. One half of patients received clonidine (105 micrograms) in addition to bupivacaine. Mean arterial pressure, heart rate were recorded baseline until 1 hour after surgery. Cardiac output, stroke volume, ejection fraction, systemic vascular resistance and left cardiac work were measured, by thoracic electric bioimpedance method, baseline until 1 hour after surgery. Sensory block, motor block and sedation level were measured at the beginning of anesthesia and for 6 hours after the end of surgery. RESULTS: In the clonidine treated group we did not observe variations of cardiovascular parameters; in the same group we did observe sensory block and motor block significantly prolonged, a higher sedation level and a significant postoperative analgesia. CONCLUSIONS: In summary, the addition of clonidine to hyperbaric bupivacaine seems to be particularly useful in unilateral spinal anesthesia, exerting minimal influence on haemodynamic parameters, and guaranting a satisfactory postoperative analgesia.

[Total intravenous anesthesia in neurosurgery. Our clinical experience]. / Anestesia endovenosa totale in neurochirurgia. Nostra esperienza clinica.

BACKGROUND: The quality of a "neuroanesthetic" technique is the result of its pharmacokinetics, of its effect on intracerebral homeostasis and metabolism, of its antinociceptive and neuroprotective features. Aim of this study is to test the effectiveness of TIVA as the technique of choice in neurosurgical patients throughout a retrospective analysis of 1982 patients scheduled for brain tumors, neurovascular surgery and spine lesions. METHODS: 1982 patients (1023 F, 959 M), ASA I-IV, aging 15-80 yrs scheduled for neurosurgery were studied. Hemodynamic and electrophysiological parameters were monitored carefully. Time of recovery was evaluated although this parameter is influenced by perioperative clinical status and by area and kind of brain damage. RESULTS: A good hemodynamic stability was observed. Recovery time was quick, related with brain damage and time of surgery. Incidence of postoperative nausea, vomiting and seizures was very low. Two cases of awareness were noted. CONCLUSIONS: 1982 neurosurgical operations were carried out in TIVA without major complications and side effects: the authors are therefore sure that TIVA can be considered the anesthetic technique "of choice" in neurosurgical patients.

[The measurement of osmolality in neurologic intensive care]. / La misurazione dell'osmolalità in neurorianimazione. Nota tecnica.

Serum osmolality is one of the end-points in the management of neurologic intensive care patient. Its leading role in the concept of cerebrovascular homeostasis is underlined. Normal plasma osmolality is generally 285 mOsm kg-1, a value determined almost entirely by small molecules and ions (Na+, K+, urea and lactate). The plasma osmolality value is determined by measuring the changes in freezing point related to the zero value of a sample of distilled water. The measurement of plasma osmolality is very easy and inexpensive; its widely use could be very useful in the neurologic intensive care units to improve the treatment of neurological critical patient. According to the authors the monitoring of plasma osmolality should be mandatory to evaluate the effectiveness of treatment of brain edema.

Mivacurium in patients with intracranial pathology.

BACKGROUND: The aim of this study was to evaluate the effects of mivacurium on the cerebrospinal fluid pressure (CSFP) in patients requiring muscle relaxation to facilitate mechanical ventilation and on the intracranial pressure (ICP) in patients undergoing neurosurgery. EXPERIMENTAL DESIGN: prospective study. SETTING: ICU in a hospital and operating room in a neurosurgery department at University. PATIENTS: 12 patients, GCS 6-7, with a mean age of 62.6 +/- 6.2 were studied in ICU and 10 patients, ASA I-II, with a mean age of 58.6 +/- 6.4 were studied in the operating room. INTERVENTIONS: all patients received mivacurium as single bolus dose of 0.2 mg/kg i.v. MEASUREMENTS: Heart rate, SAP, DAP and MAP were recorded at different times. In ICU CSFP was measured via a catheter in lumbar subarachnoid space and in operating room ICP was measured via an intraventricular catheter. CPP was evaluated as the difference between MAP and ICP. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni "t"-test and a value of p < 0.05 was considered to be significant. RESULTS: Mivacurium was found not to influence or to increase ICP or CSFP. No significant changes in cardiocirculatory parameters were recorded in all patients. CONCLUSIONS: In conclusion, mivacurium can be considered a suitable and manageable neuromuscular blocking drug in the management of patients with intracranial pathology.