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.

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.

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.

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.

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.

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.

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.

Inhibiting nitric oxide overproduction during hypotensive sepsis increases local oxygen consumption in rat skeletal muscle.

OBJECTIVE: Although nitric oxide (NO) is a known regulator of cardiovascular function, the effect of NO overproduction during sepsis on capillary oxygen transport and local tissue oxygen consumption is not well understood. The objectives of this study were to determine whether sepsis-induced NO overproduction increased capillary stopped-flow and modulated tissue oxygen consumption in skeletal muscle. DESIGN: Prospective, controlled laboratory study. SETTING: Animal laboratory in a university-affiliated research institute. SUBJECTS: Male Sprague-Dawley rats, 165-180 g body weight. INTERVENTIONS: Rats were made septic by cecal ligation and perforation (CLP) and were then ventilated and volume resuscitated (saline). The hind limb extensor digitorum longus (EDL) skeletal muscle was blunt dissected for in vivo microvascular imaging. The inducible NO synthase (iNOS) inhibitor L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) was infused (3 mg/kg body weight per hour) starting 1 hr post-CLP to maintain arterial blood and EDL tissue NO(x)(-) (NO2(-) + NO3(-)) at baseline. MEASUREMENTS AND MAIN RESULTS: Red blood cell hemodynamics, hemoglobin oxygen saturation, capillary geometry, and functional capillary density information were used to calculate capillary oxygen flux (the rate of oxygen diffusion from capillary to tissue) and indices of local oxygen delivery and tissue oxygen consumption. Over the first 5 hrs of septic injury, mean arterial pressure decreased while capillary stopped-flow and capillary oxygen flux both increased (p < .05). Inhibiting iNOS/NO overproduction partially restored mean arterial pressure and increased arterial pH. Within the microcirculation, inhibiting NO increased capillary red cell velocity and increased local tissue oxygen consumption (p < .05). Inhibiting NO failed, however, to prevent capillary stopped-flow. CONCLUSIONS: During the onset of sepsis, concurrent with the onset of microvascular dysfunction, there is an iNOS/NO-mediated reduction in local skeletal muscle tissue oxygen consumption.

Frusemide administration in critically ill patients by continuous compared to bolus therapy.

BACKGROUND: Frusemide is frequently administered to critically ill patients in the intensive care unit (ICU). We investigated whether continuous frusemide infusion therapy was more effective than regular intermittent bolus doses at causing diuresis. METHODS: 59 adult patients with fluid overload admitted to two tertiary multidisciplinary ICUs were randomised to either a continuous frusemide infusion or regular intermittent intravenous boluses of frusemide according to pre-defined algorithms aiming for a minimum hourly urine output. RESULTS: There was no significant difference in diuretic response between the two groups during the first 24 h (5.3 liters in the bolus group vs. 5.4 liters in the infusion group). In the bolus group a significantly higher dose of frusemide was needed to achieve target diuresis (24.1 vs. 9.2 mg/h in the infusion group, p = 0.0002). Mean urine output per dose of frusemide was significantly higher in the infusion group (31.6 vs. 18 ml/mg in the bolus group, p = 0.014). At the end of the study, there were no differences in hospital mortality, number of patients requiring ventilatory support, change in serum creatinine or change in estimated glomerular filtration rate. CONCLUSIONS: Both intermittent boluses and continuous infusion of frusemide were successful in achieving algorithm-driven diuresis. However, continuous infusion therapy was more effective than intermittent boluses since the dose of frusemide required was significantly less.

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.

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.

Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane.

BACKGROUND: Refractory status epilepticus (RSE) is defined as continued seizures after 2 or 3 antiepileptic drugs have failed. Several intravenous agents have been used for RSE; however, problems occur with their toxicity and/or effectiveness. OBJECTIVE: To report our experience with inhalational anesthesia (IA) in patients who were refractory to other antiepileptic drugs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review during a 4-year period of patients with RSE treated with isoflurane and/or desflurane. MAIN OUTCOME MEASURE: Efficacy of IA on therapy in terminating RSE. RESULTS: Seven patients (4 male) aged 17 to 71 years received 7 to 15 (mean, 10) antiepileptic drugs in addition to IAs. The IAs were initiated after 1 to 103 (mean, 19) days of RSE and were used for a mean +/- SD 11 +/- 8.9 days. All patients received isoflurane, and 1 patient in addition received desflurane anesthesia 21 days after the onset of RSE for a total of 19 days. Regardless of seizure type, isoflurane and desflurane consistently stopped epileptic discharges with adequate, sustained electroencephalographic burst suppression within minutes of initiating IA therapy. Four patients had good outcomes, 3 died (1 of acute hemorrhagic leukoencephalitis, 1 of bowel infarction, and 1 of toxic encephalopathy, who remained in a persistent vegetative state until death 5.5 months after the onset of seizures). Complications during IA therapy included hypotension (7/7), atelectasis (7/7), infections (5/7), paralytic ileus (3/7), and deep venous thrombosis (2/7). No patient developed renal or hepatic dysfunction. CONCLUSIONS: Isoflurane and desflurane adequately suppressed RSE in all cases. Complications were common, but mortality and long-term morbidity were related to the underlying disease and duration of RSE. Prolonged use of isoflurane and desflurane is well tolerated.

Efficacy and safety of itraconazole prophylaxis for fungal infections after orthotopic liver transplantation: a prospective, randomized, double-blind study.

BACKGROUND: There is significant morbidity and mortality related to fungal infections in the solid-organ transplant population. METHODS: A prospective, randomized, double-blind, placebo-controlled, restricted sequential design trial was performed in 71 adults undergoing orthotopic liver transplantation. Patients were randomly assigned to receive either itraconazole (5.0 mg/kg orally, preoperatively, 2.5 mg/kg orally, two times a day, postoperatively) or placebo. Therapy continued for a maximum of 56 days or until patient was discharged from hospital or met a predefined endpoint. Measurements included incidence of fungal colonization, superficial or systemic fungal infections requiring systemic therapy, adverse events, and mortality rate. RESULTS: This trial design supported the superiority of itraconazole in preventing fungal infections; nine patients in the placebo group (24%; 95% confidence interval, 0.118-0.412) and one patient in the itraconazole group (4%; 95% confidence interval, 0.001-0.204) developed fungal endpoints requiring therapy with amphotericin B (P=0.04, Fisher's exact test). At the time of enrollment, fungal colonization occurred in 40% and 37% of itraconazole and placebo patients (P=0.43), respectively. Adverse events were reported by 97% and 100% of the intraconazole and placebo groups, respectively, and one itraconazole and six placebo-group patients died within the study period. There was no relation to trial medication for serious adverse events. CONCLUSION: Prophylaxis with itraconazole reduces fungal infections in patients undergoing orthotopic liver transplantation and is well tolerated.

Translaryngeal tracheostomy: experience of 340 cases.

OBJECTIVE: To describe the authors' initial experience with a new and innovative dilational translaryngeal tracheostomy bedside technique. STUDY DESIGN: A prospective documentation of 340 patients who received an elective translaryngeal tracheostomy in a multidisciplinary, tertiary care intensive care unit during a 45-month period. RESULTS: All translaryngeal tracheostomy procedures but one were completed successfully; one was aborted because of bleeding from a thyroid vein. Minor perioperative complications occurred in 42% of patients, which caused no adverse effects. The most common complication was arterial desaturation occurring in 17% of patients; this was short-lived, and the lowest saturation was 79%. Blood loss was minimal (<5 mL) in all but one case, despite an elevated international normalized ratio (INR) and partial thromboplastin time in 42% and 41% of patients, respectively, and a low platelet count in 13% of patients. CONCLUSIONS: Translaryngeal tracheostomy is a safe and reliable technique and can also be used in patients with unstable cervical spines and bleeding diathesis. It has become the authors' procedure of choice for an elective bedside tracheostomy in the intensive care unit.

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.

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.

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.