R. Tufano

Posterior reversible encephalopathy syndrome (PRES) in critically ill obstetric patients.

ObjectiveTo describe clinical, neuroradiological and evolutionary findings in obstetric patients with posterior reversible encephalopathy syndrome (PRES).DesignRetrospective case series.SettingUniversity intensive care unit (ICU).PatientsFour critically ill patients. Two patients experienced PRES in late postpartum without the classical pre-eclamptic signs. All patients showed impairment of consciousness and epileptic seizures; two of them presented cortical blindness and headache, too. True status epilepticus (SE) occurred in two cases. In all patients MRI showed the typical feature of gray-white matter edema, mainly localized to the temporo-parieto-occipital areas.InterventionsNormalization of high blood pressure (BP) and treatment of seizures. Two patients with SE and severe impairment of consciousness were treated with an intravenous valproate (ivVPA) bolus followed by continuous infusion.Measurements and resultsIn three cases, neurological and MRI abnormalities completely resolved in about a week. Another patient died due to subarachnoid hemorrhage.ConclusionPosterior reversible encephalopathy syndrome is a well described clinical and neuroradiological syndrome characterized by headache, altered mental status, cortical blindness and seizures, and a diagnostic MRI picture; usually reversible, PRES can sometimes result in death or in irreversible neurological deficits, thus requiring early diagnosis and prompt treatment. PRES can have various etiologies, but pregnancy and postpartum more frequently lead to this condition. Treatment of seizures deserves special attention since the anti-epileptic drugs currently used in SE management may worsen vigilance as well as autonomic functions. Extensive research is needed to assess the role of ivVPA in this condition.

Effects of ventilation in ventral decubitus position on respiratory mechanics in adult respiratory distress syndrome

Objective: To assess the potential benefits of a period of ventilation in ventral decubitus (VD) on oxygenation and respiratory mechanics in the adult respiratory distress syndrome (ARDS).Design: In a stable condition during baseline ventilation in dorsal decubitus (DD), after 15 min of ventilation in VD and after 10 min of restored DD, the following parameters were studied: arterial blood gas tension, haemodynamics and static respiratory compliance (Crs), evaluated with the rapid airway occlusion technique.Setting: The study was completed in the intensive care units of university hospitals as part of the management of the patients studied.Patients: Twelve patients (7 males, 5 females, mean age 51.8 ± 16.6 years) suffering from ARDS of different aetiologies.Interventions: Before and during each evaluation, the patients were kept under stable haemodynamic and metabolic conditions. The ventilatory setting was kept constant. All the patients were sedated, paralysed and mechanically ventilated.Results: A statistically significant increase in the ratio between the arterial partial pressure of oxygen and fractional inspired oxygen (p<0.01) was observed between the baseline conditions (mean 123.9 ± 22.6) and VD (mean 153.0 ± 16.9), while no statistical significance was noted between baseline conditions and after 10 min of restored DD (mean 141.1 ± 19.7). A significant increase in Crs (p 0.001) was observed between baseline conditions (mean 42 ± 10.1) and VD (mean 48.8 ± 9.6) and between baseline conditions and restored DD (mean 44.7 ± 10.6). Two patients were considered non-responders. All the patients were haemodynamically stable. No side effects were noted.Conclusions: We observed an increase in oxygenation and Crs when the patients were turned from the supine to the prone position with the upper thorax and pelvis supported.

Differential vulnerability of cortical and cerebellar neurons in primary culture to oxygen glucose deprivation followed by reoxygenation

The effects of glucose and O2 deprivation (OGD) on the survival of cortical and cerebellar neurons were examined to characterize the biochemical mechanisms involved in OGD and OGD followed by reoxygenation. To this aim, neurons were kept for different time periods in a hypoxic chamber with a controlled atmosphere of 95% N2 and 5% CO2 in a glucose‐free medium. After OGD, reoxygenation was achieved by exposing the cells to normal O2 and glucose levels. Neither MTT, an index of mitochondrial oxidative phosphorylation, nor malondialdehyde (MDA) production, a parameter measuring lipid peroxidation, were affected by 1 hr of OGD in cortical neurons. When OGD was followed by 24 hr of reoxygenation, MTT levels were reduced by 40% and MDA was significantly increased, whereas cellular ATP content did not change. Cerebellar granule cells, on the other hand, did not show any reduction of mitochondrial activity after exposure to 1 hr OGD or to 1 hr OGD plus 24 hr of reoxygenation. When OGD was prolonged for 2 hr, a significant reduction of the mitochondrial activity and of cellular ATP content occurred, coupled to a significant MDA increase in cerebellar granule cells, whereas in cortical neurons a reduction of MTT levels after 2 hr OGD was not accompanied by a decrease of cellular ATP content nor by an increase of MDA production. Moreover, 24 hr of reoxygenation further reinforced lipid peroxidation, LDH release, propidium iodide positive neurons and the reduction of ATP content in cerebellar granule cells. The results of the present study collectively show that cortical and cerebellar neurons display different levels of vulnerability to reoxygenation followed by OGD. Furthermore, the impairment of mitochondrial activity and the consequent overproduction of free radicals in neurons were observed for the first time occurring not only during the reoxygenation phase, but already beginning during the OGD phase. J. Neurosci. Res. 63:20–26, 2001.

Sepsis associated encephalopathy studied by MRI and cerebral spinal fluid S100B measurement.

The pathogenesis of sepsis associated encephalopathy (SAE) is not yet clear: the blood–brain barrier (BBB) disruption has been indicated among the possible causative mechanisms. S100B, a calcium binding protein, originates in the central nervous system but it can be also produced by extra-cerebral sources; it is passively released from damaged glial cells and neurons; it has limited passage through the BBB. We aimed to demonstrate BBB damage as part of the pathogenesis of SAE by cerebral spinal fluid (CSF) and serum S100B measurements and by magnetic resonance imaging (MRI). This paper describes four septic patients in whom SAE was clinically evident, who underwent MRI and S100B measurement. We have not found any evidence of CSF-S100B increase. Serum S100B increase was found in three out of four patients. MRI did not identify images attributable to BBB disruption but vasogenic edema, probably caused by an alteration of autoregulation, was diagnosed. S100B does not increase in CSF of septic patients; S100B increase in serum may be due to extracerebral sources and does not prove any injury of BBB. MRI can exclude other cerebral pathologies causing brain dysfunction but is not specific of SAE. BBB damage may be numbered among the contributors of SAE, which aetiology is certainly multifactorial: an interplay between the toxic mediators involved in sepsis and the indirect effects of hyperthermia, hypossia and hypoperfusion.

Application of a computerised method to measure static pressure volume curve in acute respiratory distress syndrome.

Objective: To assess the safety and the bedside feasibility of a new computerised method to record the static pressure-volume curves (Pst/V) of the respiratory system.¶Design: The Pst/V curves were recorded in 13 medical patients with the acute respiratory distress syndrome (ARDS). During the Pst/V curve tracing the following parameters were recorded: time required for the recording and the automatic analysis of the Pst/V curve and modifications in electrocardiograms, blood pressure, and arterial oxygen satmation (SaO2).¶Setting: The study was performed in the intensive care unit of the University of Naples “Federico II”.¶Results: No statistically significant modifications in heart rate (HR, b min–1), blood pressure (BP, mmHg), and SaO2 were observed between conditions at baseline (HR 97.2 ± 17.7; BP 65.4 ± 9.3; SaO2 93.6 ± 2.0), during the recording (HR 99.8 ± 19.5; BP 66.2 ± 11.6; SaO2 93.7 ± 2.4), and 2 min after the procedure (HR 98.2 ± 17.8; BP 65.2 ± 11.7; SaO2 93.7 ± 1.9). The Pst/V curves were recorded in 8.38 ± 1.19 min and fully analysed in 2.69 ± 0.85 min. Mean value of static compliance was 41.1 ± 12.7 ml cmH2O–1. A lower inflection point was found in ten patients (mean value 9.2 ± 1.9 cmH2O).¶Conclusions: In ARDS patients, the present new computerised method gave valuable data to ordinary intensivists and was shown to be safe, easy, and fast.

Antithrombin Reduces Ischemic Volume, Ameliorates Neurologic Deficits, and Prolongs Animal Survival in Both Transient and Permanent Focal Ischemia

Background and Purpose— Antithrombin (AT), a glycoprotein belonging to the serpin family, blocks thrombin formation and activity at several steps. Thrombin, beside its relevant role in the coagulation cascade, exerts neurodetrimental effects through the activation of a family of protease-activated receptors, which can be implicated in stroke pathophysiology. The aims of the present study were to evaluate whether AT could reduce brain damage, ameliorate neurologic deficits, and prolong animal survival. Methods— Two different doses of AT (10 and 30 IU/kg IP) were administered 3 hours, 6 hours, or 3 and 6 hours after an ischemic insult to mice and rats subjected to either transient or permanent focal ischemia. Ischemic volume was evaluated 24 hours or 7 days after the ischemic insult. Neurologic deficits were also scored. Results— In mice, 10 or 30 IU/kg AT administered twice, at 3 and 6 hours after transient ischemia, and 30 IU/kg AT administered 3 hours only after transient ischemia substantially reduced total ischemic volume, significantly improved neurologic deficits evaluated 24 hours after the insult, and prolonged animal survival. In rats, the same doses given at the same time intervals significantly reduced ischemic volume, evaluated 24 hours after permanent ischemia. Conclusions— These results indicate that AT remarkably reduces infarct volume, ameliorates neurologic deficit scores, and prolongs animal survival in 2 rodent models of brain ischemia. Taken together, our data suggest that AT, delivered via systemic administration, an easily achievable route of administration and in a clinically useful time window, could represent a new therapeutic strategy to be validated for the clinical treatment of human stroke.

Toll-like receptor kinetics in septic shock patients: a preliminary study.

The aim of this study is to evaluate some inflammatory parameter changes in septic shock patients and their possible correlation with clinical outcome, in particular when continuous veno-venous hemofiltration (CVVH) treatment is required. Considering the objective difficulty in enrolling this kind of patient, a preliminary study was initiated on seventeen septic shock patients admitted to a medical and surgical ICU. The mRNA expression of Toll-like receptor (TLR)-1, TLR-2, TLR-4, TLR-5, TLR-9, TNFα, IL-8 and IL-1β was assessed, the plasmatic concentrations of IL-18, IL-2, IL-10 and TNFα were measured on the day of sepsis diagnosis and after 72 h. In those patients who developed acute renal failure unresponsive to medical treatment and who underwent CVVH treatment the same parameters were measured every 24 h during CVVH and after completion of the treatment. On sepsis diagnosis, gene expression of TLRs was up-regulated compared to the housekeeping gene in all the patients. After 72 h, in 35% of the patients a down-regulation of these genes was found compared to day 1, but it was not associated with a reduction of cytokine serum levels or improved clinical signs, better outcome or reduced mortality. After high volume hemofiltration treatment, cytokine serum levels and TLR expression were not significantly modified. In conclusion, considering the not numerous number of cases, from our preliminary study, we cannot certainly correlate TLR over-expression in septic shock patients with severity or outcome scores.

Thrombin antithrombin complex and IL-18 serum levels in stroke patients

The complex picture of inflammation and coagulation alterations comes to life in acute stroke phases. Increasing evidence points to a strong interaction and extensive crosstalk between the inflammation and coagulation systems: the interest towards this relationship has increased since recent experimental research showed that the early administration of antithrombin III (ATIII) decreases the volume of ischemia in mice and might be neuroprotective, playing an antiinflammatory role. We aimed to establish the extent of the relationship among markers of inflammation (S100B and IL-18) and procoagulant and fibrinolytic markers (ATIII, thrombin-antithrombin III complex (TAT), Fibrin Degradation Products (FDP), D-dimer) in 13 comatose patients affected by focal cerebral ischemia. Plasma levels of TAT, D-dimer and FDP, IL18 and S100B were increased. IL-18 and S100B high serum levels in ischemic patients suggest an early activation of the inflammatory cascade in acute ischemic injury. The basic principles of the interaction between inflammatory and coagulation systems are revised, from the perspective that simultaneous modulation of both coagulation and inflammation, rather than specific therapies aimed at one of these systems could be more successful in stroke therapy.

S100B Induces the Release of Pro-Inflammatory Cytokines in Alveolar Type I-like Cells

S100B, a 21kDa cytosolic calcium-binding protein of the EF-hand type, present in high abundance in the brain, stimulates inflammatory responses in different cellular types inside and outside the central nervous system. Most of extracellular S100B effects are mediated by Receptor for Advanced Glycation End-products (RAGE). RAGE is highly expressed in lung by Alveolar Type-I (AT-I) cells and its activation contributes to ALI/ARDS pathogenesis. In this in-vitro study, we tested the hypothesis that S100B (0.002μg/L, 0.02μg/L, 0.5μg/L, 5μg/L) stimulates an ATI-derived cell line (R3/1) to secrete inflammatory mediators involved in lung inflammation. Our main result is that S100B stimulates R3/1 cells to secrete TNF-alpha and IL-6 (well-known pro-inflammatory cytokines in lung inflammation and neurogenic pulmonary edema), but not sICAM-1, CINC-1 or CINC-3. Soluble RAGE (sRAGE) reduced SlOOB-dependent secretion of TNF-alpha but did not decrease S100B-dependent secretion of IL-6. Moreover, in absence of S100B, sRAGE enhanced IL-6 release. This study demonstrates that in vitro S100B dose-dependently stimulated R3/1 cells, to enhance the secretion of TNF-alpha and IL-6; S100B pro-inflammatory activity might be mediated at least in part by RAGE. Besides acting as decoy receptor, sRAGE could have pro-inflammatory properties.

Update on transfusion solutions during surgery: review of hydroxyethyl starches 130/0.4

Objectives Restoration of circulation is crucial in the surgical patient management. Colloids and crystalloids are widely used for blood volume therapy. We reviewed recent trials to evaluate efficacy and safety of hydroxyethyl starch (HES) 130/0.4 during surgery. Material and methods A subjective, not systematic, review of literature was performed. Papers were searched to answer questions about efficacy of HES, its impact on coagulation and inflammation and its effects on pulmonary mechanics and renal function. Conclusions HES 130/0.4 is effective for volume therapy and is less expensive than human albumin. Its effects on coagulation and renal function are manageable; it may ameliorate pulmonary permeability and reduce inflammation.