The Effect of Sepsis on the Erythrocyte.

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

Ascorbate inhibits platelet-endothelial adhesion in an in-vitro model of sepsis via reduced endothelial surface P-selectin expression.

Plugging of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous ascorbate injection reduces platelet adhesion to the capillary wall and capillary plugging in septic mice. Both platelet adhesion and capillary plugging require P-selectin, a key adhesion molecule. To elucidate the beneficial effect of ascorbate, we hypothesized that ascorbate reduces platelet-endothelial adhesion by reducing P-selectin surface expression in endothelial cells. We used mouse platelets, and monolayers of cultured microvascular endothelial cells (mouse skeletal muscle origin) stimulated with lipopolysaccharide, to examine platelet-endothelial adhesion. P-selectin mRNA expression in endothelial cells was determined by real-time PCR and P-selectin protein expression at the surface of these cells by immunofluorescence. Secretion of von Willebrand factor from cells into the supernatant (a measure of P-selectin-containing granule exocytosis) was determined by ELISA. Lipopolysaccharide (10 µg/ml, 1 h) increased platelet-endothelial adhesion. P-selectin-blocking antibody inhibited this adhesion. Lipopolysaccharide also increased P-selectin mRNA in endothelial cells, P-selectin expression at the endothelial surface, and von Willebrand factor secretion. Ascorbate pretreatment (100 µmol/l, 4 h) inhibited the increased platelet adhesion, surface expression of P-selectin, and von Willebrand factor secretion, but not the increase in P-selectin mRNA. The lipopolysaccharide-induced increase in platelet-endothelial adhesion requires P-selectin presence at the endothelial surface. Ascorbate's ability to reduce this presence could be important in reducing both platelet adhesion to the capillary wall and capillary plugging in sepsis.

Sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries.

INTRODUCTION: The microcirculation supplies oxygen (O2) and nutrients to all cells with the red blood cell (RBC) acting as both a deliverer and sensor of O2. In sepsis, a proinflammatory disease with microvascular complications, small blood vessel alterations are associated with multi-organ dysfunction and poor septic patient outcome. We hypothesized that microvascular autoregulation-existing at three levels: over the entire capillary network, within a capillary and within the erythrocyte-was impaired during onset of sepsis. This study had three objectives: 1) measure capillary response time within hypoxic capillaries, 2) test the null hypothesis that RBC O2-dependent adenosine triphosphate (ATP) efflux was not altered by sepsis and 3) develop a framework of a pathophysiological model. METHODS: This was an animal study, comparing sepsis with control, set in a university laboratory. Acute hypotensive sepsis was studied using cecal ligation and perforation (CLP) with a 6-hour end-point. Rat hindlimb skeletal muscle microcirculation was imaged, and capillary RBC supply rate (SR = RBC/s), RBC hemoglobin O2 saturation (SO2) and O2 supply rate (qO2 = pLO2/s) were quantified. Arterial NOx (nitrite + nitrate) and RBC O2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively. RESULTS: Sepsis increased capillary stopped-flow (p = 0.001) and increased plasma lactate (p < 0.001). Increased plasma NOx (p < 0.001) was related to increased capillary RBC supply rate (p = 0.027). Analysis of 30-second SR-SO2-qO2 profiles revealed a shift towards decreased (p < 0.05) O2 supply rates in some capillaries. Moreover, we detected a three- to fourfold increase (p < 0.05) in capillary response time within hypoxic capillaries (capillary flow states where RBC SO2 < 20 %). Additionally, sepsis decreased the erythrocyte's ability to respond to hypoxic environments, as normalized RBC O2-dependent ATP efflux decreased by 62.5 % (p < 0.001). CONCLUSIONS: Sepsis impaired microvascular autoregulation at both the individual capillary and erythrocyte level, seemingly uncoupling the RBC acting as an "O2 sensor" from microvascular autoregulation. Impaired microvascular autoregulation was manifested by increased capillary stopped-flow, increased capillary response time within hypoxic capillaries, decreased capillary O2 supply rate and decreased RBC O2-dependent ATP efflux. This loss of local microvascular control was partially off-set by increased capillary RBC supply rate, which correlated with increased plasma NOx.

Extramural Pilot Project: Designated On-Call Intensivist in Tertiary Care Centre Improves Access to Critical Care Consultation/Referral and Resources.

Timely consultation with an intensivist will promote early and appropriate management of critically ill patients. We determined whether implementing a call roster of intensivists who did not have on-call responsibilities in an intensive care unit (ICU) and who received referrals from community physicians would improve access to critical care services. This program created efficiencies to critical care services by: timely access to consultation with an intensivist (<10 minutes) and/or subspecialist, timely referral to an appropriate institution (<30 minutes) and optimal resource utilization by determining the availability of ICU beds at non-tertiary care hospitals capable of providing the care needs of the patient, thus relieving pressure on the neighbouring tertiary/quaternary care centre.

Impact of Incremental Perfusion Loss on Oxygen Transport in a Capillary Network Mathematical Model.

OBJECTIVES: To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport. METHODS: A computational model was applied to capillary networks with dimensions 84 × 168 × 342 (NI) and 70 × 157 × 268 (NII) µm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis. RESULTS: A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3-4 fold. CONCLUSIONS: These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis.

Effect of ascorbate on plasminogen activator inhibitor-1 expression and release from platelets and endothelial cells in an in-vitro model of sepsis.

The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by ELISA. In platelets, PAI-1 release was measured after LPS, TNFα, or thrombin stimulation, with/without ascorbate. In endothelial cells, LPS and TNFα increased PAI-1 mRNA after 6-24 h, but no increase in PAI-1 release was observed; ascorbate did not affect these responses. In platelets, thrombin, but not LPS or TNFα, increased PAI-1 release; ascorbate inhibited this increase at low extracellular pH. In unstimulated endothelial cells and platelets, PAI-1 is released into the extracellular space. Thrombin increases this release from platelets; ascorbate inhibits it pH-dependently. The data suggest that ascorbate promotes fibrinolysis in the microvasculature under acidotic conditions in sepsis.

Application of subhairline EEG montage in intensive care unit: comparison with full montage.

PURPOSE: Problems with the availability of standard EEG monitoring in the intensive care unit have led to the use of recordings that have limited spatial coverage. We studied the performance of limited coverage EEG compared with more traditional full-montage EEG. METHODS: Continuous EEG recordings were performed on 170 patients using the full-montage 10-20 placement of electrodes as a reference recording and an abbreviated montage of electrodes applied below the hairline (subhairline). Recordings were reviewed independently, with the identity of the patients concealed. RESULTS: Seizures were found in 8% of patients. Sensitivity for detecting patients with seizures using the subhairline system was 0.54 [95% confidence interval (95% CI), 0.29-0.77] with specificity of 1.00 (95% CI, 0.97-1.00) and positive predictive value of 1.00 (95% CI, 0.65-1.00). For detecting interictal epileptiform activity, we found sensitivity to be 0.60 (95% CI, 0.46-0.74), specificity to be 0.94 (95% CI, 0.88-0.97), and positive predictive value to be 0.81 (95% CI, 0.65-0.91). Performance was poor for triphasic waves, alpha/theta/spindle coma, and suppression. CONCLUSIONS: The subhairline montage shows excellent specificity for detecting patients with seizure activity but has limited sensitivity. It has relatively poor performance for other EEG phenomena, but further applications in trending and assessing reactivity should be assessed in further studies.

Effect of ascorbate on fibrinolytic factors in septic mouse skeletal muscle.

Plugging of the capillary bed in tissues correlates with organ failure during sepsis. In septic mouse skeletal muscle, we showed that blood in capillaries becomes hypercoagulable and that ascorbate injection inhibits capillary plugging. In the present study, we hypothesized that ascorbate promotes fibrinolysis, reversing this plugging. Sepsis in mice was induced by fecal injection into peritoneum. Mice were injected intravenously with a bolus of streptokinase (fibrinolytic agent) or ascorbate at 5-6 h. Both agents reversed capillary plugging in muscle at 7 h. Sepsis increased mRNA expression of urokinase plasminogen activator (u-PA) (profibrinolytic) and plasminogen activator inhibitor 1 (PAI-1) (antifibrinolytic) in muscle and liver homogenates at 7 h. Ascorbate did not affect u-PA mRNA in either tissue, but it inhibited PAI-1 mRNA in muscle, suggesting enhanced fibrinolysis in this tissue. However, ascorbate did not affect increased PAI-1 mRNA in the liver (dominant source of soluble PAI-1 in systemic blood). Consistently, ascorbate affected neither elevated PAI-1 protein/enzymatic activity in septic liver nor lowered plasmin antiplasmin level in septic blood. Furthermore, hypocoagulability of septic blood revealed by thrombelastography and thrombin-induced PAI-1 release from isolated platelets (ex-vivo model of sepsis) were not affected by ascorbate. Based on the PAI-1 protein data, the present study does not support the hypothesis that ascorbate promotes fibrinolysis in sepsis.

Short-term effect of ascorbate on bacterial content, plasminogen activator inhibitor-1, and myeloperoxidase in septic mice.

BACKGROUND: Sepsis, a potential risk associated with surgery, leads to a systemic inflammatory response including the plugging of capillary beds. This plugging may precipitate organ failure and subsequent death. We have shown that capillary plugging can be reversed rapidly within 1 h by intravenous injection of ascorbate in mouse skeletal muscle. It is unknown whether, in parallel with this effect, ascorbate negatively affects the protective responses to sepsis involving the fibrinolytic and immune systems. We hypothesized that treatment with ascorbate for 1 h does not alter bacterial content, plasminogen activator inhibitor 1 (PAI-1), and neutrophil infiltration in lung, kidney, spleen, and liver (organs with high immune response) of septic mice. MATERIALS AND METHODS: Sepsis was induced by feces injection into the peritoneum. Mice were injected intravenously with ascorbate at 6 h (10 mg/kg), and samples of peritoneal fluid, arterial blood, and organs collected at 7 h were subjected to analyses of bacterial content, PAI-1 messenger RNA and enzymatic activity, and myeloperoxidase (MPO) (a measure of neutrophil infiltration). RESULTS: Sepsis increased bacterial content in all fluids and organs and increased PAI-1 messenger RNA and enzymatic activity in the lung and liver. Sepsis increased the myeloperoxidase level in the lung and liver, and lowered it in the spleen. Except for decreasing the bacterial content in blood, these responses to sepsis were not altered by ascorbate. CONCLUSIONS: The rapid effect of ascorbate against capillary plugging in the septic mouse skeletal muscle is not accompanied by alterations in PAI-1 or myeloperoxidase responses in the organs with high immune response.

Oral and intravenous thyroxine (T4) achieve comparable serum levels for hormonal resuscitation protocol in organ donors: a randomized double-blinded study.

BACKGROUND: Thyroxine (T4) administration is advocated in the management of organ donors; however, the bioavailability of oral thyroxine is unknown in this patient population. OBJECTIVE: The primary objective of this study was to compare the percentage of the study time (from study drug administration to organ procurement) that patients in the oral vs the intravenous group required inotropic support. Secondary objectives included plasma levels of T3 and T4 and number of organs donated following oral vs intravenous T4 administration. DESIGN: Randomized double-blinded study. SETTING: Adult medical-surgical intensive care unit. PATIENTS: Thirty-two adult solid organ donors. INTERVENTIONS: Patients were randomized to receive either an oral or intravenous dose of T4 (2 µg·kg⁻¹). All patients received an oral and intravenous study drug preparation, one of which was a placebo. The study was double-blinded, and randomization occurred in blocks of four and six. MEASUREMENTS: The number and duration of inotropic/vasopressor therapies and free serum levels of T3 and T4 were determined hourly until procurement. MAIN RESULTS: Following T4 administration, all patients remained on inotropic/vasopressor therapy for the same mean (SD) duration [93 (3)%] of the study period. There was a similar and gradual decrease in the number and dosages of inotropes/vasopressors required in both groups. There was no difference in T3 or T4 levels between groups. Oral bioavailability of T4 was 93% of the intravenous group at six hours and 91% overall. At six hours, the mean area under the curve for T4 was similar between the intravenous group [92.2 (33); 95% confidence interval (CI) 76 to 108.4] and the oral group [86.1 (14); 95% CI 79.4 to 92.8]. CONCLUSIONS: Orally administered T4 is well absorbed and achieves a bioavailability of approximately 91-93% of intravenous T4 in organ donors. Inotropic/vasopressor requirements and hemodynamic responses following oral or intravenous thyroxine administration were comparable. Oral T4 is suitable for hormonal therapy for organ donors. This trial was registered at www.clinicaltrials.gov : NCT00238030.

Ascorbate reduces mouse platelet aggregation and surface P-selectin expression in an ex vivo model of sepsis.

OBJECTIVE: Compromised perfusion of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous injection of ascorbate inhibits platelet adhesion and plugging in septic capillaries. In this study, we hypothesized that ascorbate reduces aggregation of platelets and their surface expression of P-selectin (a key adhesion molecule) in mice. METHODS: Platelets were isolated from control mice and subjected to agents known to be released into the bloodstream during sepsis (thrombin, ADP or U46619, thromboxane A2 analog). Platelet aggregation was analyzed by aggregometry and P-selectin expression by flow cytometry. RESULTS: Platelet-activating agents increased aggregation and P-selectin expression. Ascorbate inhibited these increases. This inhibitory effect was NOS-independent (LNAME had no effect). In contrast to the platelet-activating agents, direct stimuli lipopolysaccharide, TNFα, or plasma from septic mice did not increase aggregation/expression, a finding consistent with the literature. The results suggest a complex mechanism of platelet aggregation and P-selectin expression in sepsis, where generation of platelet-activating stimuli is required first, before platelet aggregation and adhesion in capillaries occur. CONCLUSION: The ability of ascorbate to reduce platelet aggregation and P-selectin expression could be an important mechanism by which ascorbate inhibits capillary plugging in sepsis.

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study.

INTRODUCTION: Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT. METHODS: We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available. RESULTS: In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001). CONCLUSIONS: SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.

Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries.

PURPOSE: Impaired microvascular perfusion in sepsis is not treated effectively because its mechanism is unknown. Since inflammatory and coagulation pathways cross-activate, we tested if stoppage of blood flow in septic capillaries is due to oxidant-dependent adhesion of platelets in these microvessels. METHODS: Sepsis was induced in wild type, eNOS(-/-), iNOS(-/-), and gp91phox(-/-) mice (n = 14-199) by injection of feces into the peritoneum. Platelet adhesion, fibrin deposition, and blood flow stoppage in capillaries of hindlimb skeletal muscle were assessed by intravital microscopy. Prophylactic treatments at the onset of sepsis were intravenous injection of platelet-depleting antibody, P-selectin blocking antibody, ascorbate, or antithrombin. Therapeutic treatments (delayed until 6 h) were injection of ascorbate or the glycoprotein IIb/IIIa inhibitor eptifibatide, or local superfusion of the muscle with NOS cofactor tetrahydrobiopterin or NO donor S-nitroso-N-acetylpenicillamine (SNAP). RESULTS: Sepsis at 6-7 h markedly increased the number of stopped-flow capillaries and the occurrence of platelet adhesion and fibrin deposition in these capillaries. Platelet depletion, iNOS and gp91phox deficiencies, P-selectin blockade, antithrombin, or prophylactic ascorbate prevented, whereas delayed ascorbate, eptifibatide, tetrahydrobiopterin, or SNAP reversed, septic platelet adhesion and/or flow stoppage. The reversals by ascorbate and tetrahydrobiopterin were absent in eNOS(-/-) mice. Platelet adhesion predicted 90% of capillary flow stoppage. CONCLUSION: Impaired perfusion and/or platelet adhesion in septic capillaries requires NADPH oxidase, iNOS, P-selectin, and activated coagulation, and is inhibited by intravenous administration of ascorbate and by local superfusion of tetrahydrobiopterin and NO. Reversal of flow stoppage by ascorbate and tetrahydrobiopterin may depend on local eNOS-derived NO which dislodges platelets from the capillary wall.

Electroencephalogram for prognosis after cardiac arrest.

BACKGROUND: In assessing neurologic prognosis after cardiac arrest (CA), electroencephalogram (EEG) reactivity has not been specifically included with EEG classifications. Most studies have divided recordings into benign and malignant; however, some patterns within these groups may have greater prognostic significance than such broad classifications. We sought to explore reactivity, with broad classifications and subclassifications for their prognostic significance. METHODS: All consecutive adults in coma who had an EEG recording performed at least 1 day after CA or during normothermia after a 24-hour mild hypothermia protocol. Outcomes were dichotomous: recovery of awareness or no recovery of awareness during hospitalization. RESULTS: Twenty-nine patients met the inclusion criteria. Of the 18 patients with no reactivity, only 1 recovered awareness; of the 11 patients who demonstrated reactivity, 10 recovered awareness (sensitivity of 90% [95% confidence interval, or CI, 0.57-1] and specificity of 94% [95% CI, 0.7-1]). Of those with benign patterns, 7 recovered awareness and 1 did not; however, those patients demonstrating malignant patterns, 4 recovered and 17 did not (sensitivity of 94% [95% CI, 0.7-1] and a specificity of 63% [95% CI, 0.32-0.88]). None of the 15 patients with suppression or generalized spikes recovered consciousness, and none of these patients demonstrated reactivity. CONCLUSIONS: Electroencephalogram reactivity after CA is a relatively favorable EEG feature; generalized suppression or generalized epileptiform activity, without reactivity, is associated with lack of recovery of awareness.

Seizure detection with a commercially available bedside EEG monitor and the subhairline montage.

INTRODUCTION: Availability of standard, continuous electroencephalography (cEEG) monitoring in ICU is very limited, although commercially available 4-channel modules are present in many ICUs. We investigated the sensitivity of such modules compared with the more complete monitoring with a standard EEG system. METHODS: Seventy patients at high risk of seizures in the medical-surgical intensive care unit and Epilepsy Monitoring Unit were recorded simultaneously for at least 24 h with a 4-channel commercial ICU bedside monitoring system (Datex-Ohmeda) with a subhairline montage and a standard EEG machine (XLTEK) using the international 10-20 system of electrode placement. Recordings were interpreted independently from each other. RESULTS: The 4-channel recordings demonstrated a sensitivity of 68 and 98% specificity for seizure detection, and a sensitivity of 39% and a specificity of 92% for detection of spikes and PLEDs. CONCLUSIONS: The 4-channel EEG module has limited but practical usefulness for seizure detection when standard cEEG monitoring is not available.

Functional MRI study of the primary somatosensory cortex in comatose survivors of cardiac arrest.

It is difficult to assess cerebral function in comatose patients. Because earlier functional neuroimaging studies demonstrate associations between cerebral metabolism and levels of consciousness, fMRI in comatose survivors of cardiac arrest could provide further insight into cerebral function during coma. Using fMRI, cerebral activation to somatosensory stimulation to the palm of the hand was measured in 19 comatose survivors of cardiac arrest and in 10 healthy control subjects and was compared to somatosensory-evoked potential (SSEP) testing of the median nerve. Changes in the blood oxygenation-level dependent signal (BOLD) in the primary somatosensory cortex (S1) contralateral to the stimulated hand were quantified. Clinical outcome was assessed using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale at 3 months post-cardiac arrest. Five out of 19 patients were alive at 3 months. Patients who survived cardiac arrest showed greater BOLD in S1 contralateral to somatosensory stimulation of the hand compared to patients who eventually did not. Greater BOLD was also seen in S1 of patients who retained their SSEP N20 waveforms. There were also positive correlations between BOLD in S1 with both levels of consciousness and measures of outcome at 3 months. In summary, this study demonstrates that BOLD in the S1 contralateral to somatosensory stimulation of the hand varies with clinical measures of the level of consciousness during coma.

Continuous EEG monitoring in severe Guillain-Barré syndrome patients.

When patients Guillain-Barré syndrome have complete paralysis clinical measures of sedation cannot be applied. In this situation continuous EEG offers a convenient, effective method of monitoring the depth of sedation, using spectral edge frequency (SEF) to quantify EEG activity. The authors report 3 patients with severe Guillain-Barré syndrome managed with sedation aimed at a SEF95 below 4.0 Hz (delta coma), using a subhairline montage with the DATEX bedside EEG module. Two of the patients were easily managed using this system for an average of 16 days, and both were completely amnestic of this period of time with no serious complication. The third one had still some residual muscle activity and SEF was unreliable in this case, so its use was abandoned. Continuous EEG monitoring using SEF is a useful tool to manage sedation in the most severely paralyzed Guillain-Barré syndrome patients. Incorporation of a low-pass filter would be of benefit to remove any residual muscle activity, which confounds the target level of sedation with this method; SEF has theoretical advantages over the bispectral index in this population. Comparative studies of various continuous EEG monitoring methods in such patients should better define their relative effectiveness.

Usefulness of a 1.5 T MRI-compatible EEG electrode system for routine use in the intensive care unit of a tertiary care hospital.

BACKGROUND: Continuous electroencephalogram (cEEG) recordings are being increasingly used in intensive care units (ICUs) to detect epileptic seizures and other changes. MRI scans can interrupt such recordings if the EEG electrodes need to be removed and important data can be missed. METHODS: We retrospectively examined EEG recordings from ICU patients who underwent MRI scans, comparing those from patients with the MRI-compatible EEG electrodes with those who had to have the EEG electrodes removed before scanning. We also examined technical aspects of the recording and scalp abrasions in both groups. RESULTS: Fourteen of 31 (45%) EEG recordings with the MRI-compatible electrode system in patients that underwent MRI scans between 03:00 p.m. and 07:00 a.m. (when technologists were not available) captured seizures. In contrast, all of the six EEG recordings with the MRI-incompatible electrode system in patients that underwent MRI scanning during the same interval were interrupted and had no data. Recording characteristics of the EEGs were comparable between the two groups and none had scalp abrasions. CONCLUSION: A significant proportion of patients undergoing MRI scans with the MRI-compatible EEG electrodes had seizures that would have been missed if the MRI-incompatible EEG electrodes had been used.