Hyperoxia after cardiac arrest may not increase ischemia-reperfusion injury

In the last decade, moderate hypothermia has become the mainstay of treatment in the post-resuscitation period. However, for the damaged brain, optimizing oxygen transport, including arterial oxygenation, may also be important. The current view states that hyperoxia in the immediate post-resuscitation period may worsen cerebral outcome, and international guidelines recommend a target arterial oxygen saturation of 94% to 98%. An article in the previous issue of Critical Care challenges this viewpoint. In an elegant study using a Cox proportional hazards model combined with sensitivity analyses and time period matching, the authors show no independent association between hyperoxia and in-hospital mortality. The present commentary discusses these contradictory findings and suggests a practical solution to solve these differences

Intravenous magnesium in subarachnoid hemorrhage

Contains fulltext : 97062.pdf (publisher's version ) (Open Access

Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study

Contains fulltext : 52086.pdf ( ) (Open Access)BACKGROUND: Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury. METHODS: Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as degrees C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2 degrees C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant. RESULTS: Temperature decline was significantly higher with the water-circulating blankets (1.33 +/- 0.63 degrees C/h), gel-pads (1.04 +/- 0.14 degrees C/h) and intravascular cooling (1.46 +/- 0.42 degrees C/h) compared to conventional cooling (0.31 +/- 0.23 degrees C/h) and the air-circulating blankets (0.18 +/- 0.2 degrees C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 +/- 18.7% of the time out of range, which was significantly less compared to all other methods. CONCLUSION: Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature

Hypothermia does not increase the risk of infection: a case control study

Contains fulltext : 96995.pdf (publisher's version ) (Open Access)INTRODUCTION: Hypothermia may improve outcome in patients after traumatic brain injury, especially when hypothermia is maintained for more than 48 hours. In the acute phase, patients with severe brain injury are more vulnerable to infections. Prolonged hypothermic treatment may further enhance the risk of infection. Selective decontamination of the digestive tract (SDD) reduces the risk of respiratory tract infections. The aim of this study was to investigate the incidence of infections in patients treated with hypothermia and normothermia while receiving SDD. METHODS: In this retrospective case control study 35 patients treated with prolonged hypothermia (cases) were identified and 169 patients with severe brain injury were included (controls). Propensity score matching was performed to correct for differences in baseline characteristics and clinical parameters. Primary outcome was the incidence of infection. The secondary endpoints were the micro-organisms found in the surveillance cultures and infection. In addition, a number of clinical characteristics were assessed. Results : The demographic and clinical data indicated that the cases and controls were well matched. The overall risk of infection during ICU stay was 20% in the hypothermia groups versus 34.4% in the normothermia group (P = 0.388). Pneumonia was diagnosed in 11.4% of patients in both groups (P = 1.000). The incidence of meningitis, wound infection, bacteremia, and urinary tract infection was low and comparable between the groups. SDD surveillance cultures indicated a higher colonization with gram-negative bacteria in the rectal samples of the hypothermia patients. CONCLUSIONS: Hypothermia does not increase the risk of infection in patients treated with SDD

Intensive insulin therapy does not alter the inflammatory response in patients undergoing coronary artery bypass grafting: a randomized controlled trial [ISRCTN95608630]

INTRODUCTION: Strict control of plasma glucose in diabetic and non-diabetic patients has been shown to improve outcome in several clinical settings. There is extensive evidence that glucose can stimulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6, with no effect on the anti-inflammatory cytokine IL-10. We hypothesized that strict glucose regulation results in a change in cytokine balance from a pro-inflammatory state to a more balanced anti-inflammatory condition. In a randomized controlled trial we studied the effect of strict glycemic control on the local and systemic pro-inflammatory and anti-inflammatory balance in non-diabetic patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass. METHODS: After surgery patients were randomly assigned to intensive insulin therapy (blood glucose between 80 and 110 mg/dl) or conventional insulin therapy (blood glucose less than 200 mg/dl). At 0, 1, 2, 4, 8, 12, 16 and 24 hours after admission to the intensive care unit, plasma samples and samples from the mediastinal drains were obtained. We measured the concentrations of the pro-inflammatory cytokines TNF-α and IL-6 and the anti-inflammatory cytokine IL-10 by enzyme-linked immunosorbent assay. RESULTS: Both patient groups were comparable in demographics, clinical characteristics and peri-operative data. In the intensive treatment group, glucose levels were significantly lower than in the conventionally treated group. No differences were found between both groups in the concentrations of TNF-α, IL-6 and IL-10 in plasma samples or in fluid draining the mediastinal cavity. Levels of IL-6 and IL-10 were significantly higher in mediastinal fluid samples than in plasma samples, suggesting a compartmentalized production of cytokines. CONCLUSION: The protective effect of intensive insulin therapy in patients after cardiac surgery with cardiopulmonary bypass is not related to a change in cytokine balance from a pro-inflammatory to an anti-inflammatory pattern. Systemic cytokine levels are not representative of the local inflammatory response

Advances in Li-Ion battery management for electric vehicles

This paper aims at presenting new solutions for advanced Li-Ion battery management to meet the performance, cost and safety requirements of automotive applications. Emphasis is given to monitoring and controlling the battery temperature, a parameter which dramatically affects the performance, lifetime, and safety of Li-Ion batteries. In addition to this, an innovative battery management architecture is introduced to facilitate the development and integration of advanced battery control algorithms. It exploits the concept of smart cells combined with an FPGA-based centralized unit. The effectiveness of the proposed solutions is shown through hardware-in-the-loop simulations and experimental results

No relationship between left ventricular radial wall motion and longitudinal velocity and the extent and severity of noncompaction cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Noncompaction cardiomyopathy (NCCM) is characterized by a prominent trabecular meshwork and deep intertrabecular recesses. Although systolic dysfunction is common, limited information is available on differences in wall motion of the normal compacted and noncompacted segments. The purpose of this study was to assess radial wall motion and longitudinal wall velocity in patients with NCCM, according to the extent and severity of noncompaction.</p> <p>Methods</p> <p>The study comprised 29 patients in sinus rhythm (age 41 ± 15 years, 15 men), who fulfilled stringent diagnostic criteria for NCCM and compared to 29 age and gender matched healthy controls. Segmental radial wall motion of all compacted and noncompacted segments was assessed with the standard visual wall motion score index and longitudinal systolic (Sm) wall velocity with tissue Doppler imaging of the mitral annulus. For each LV wall a normalized Sm value was calculated. The extent and severity of NC in each LV segment was assessed both in a qualitative and quantitative manner.</p> <p>Results</p> <p>Heart failure was the primary clinical presentation in half of the patients. NCCM patients had a wall motion score index of 1.68 ± 0.43 and a normalized Sm of 82 ± 20%. The total and maximal noncompaction scores were not related to the wall motion score index and the normalized Sm. NCCM patients with and without heart failure had similar total and maximal noncompaction scores.</p> <p>Conclusions</p> <p>In NCCM patient's radial wall motion and longitudinal LV wall velocity is impaired but not related to the extent or severity of noncompaction.</p

Endotoxemia-induced inflammation and the effect on the human brain

Introduction: Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described.Methods: Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-?, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined.Results: Following LPS infusion, circulating pro- and anti inflammatory cytokines, and cortisol increased (P &lt; 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-? changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found.Conclusions: Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness

Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients

BACKGROUND: Next-generation sequencing (NGS) is increasingly used for clinical evaluation of cardiomyopathy patients as it allows for simultaneous screening of multiple cardiomyopathy-associated genes. Adding copy number variant (CNV) analysis of NGS data is not routine yet and may contribute to the diagnostic yield. OBJECTIVES: Determine the diagnostic yield of our targeted NGS gene panel in routine clinical diagnostics of Dutch cardiomyopathy patients and explore the impact of exon CNVs on diagnostic yield. METHODS: Patients (N = 2002) referred for clinical genetic analysis underwent diagnostic testing of 55-61 genes associated with cardiomyopathies. Samples were analyzed and evaluated for single nucleotide variants (SNVs), indels and CNVs. CNVs identified in the NGS data and suspected of being pathogenic based on type, size and location were confirmed by additional molecular tests. RESULTS: A (likely) pathogenic (L)P variant was detected in 22.7% of patients, including 3 with CNVs and 25 where a variant was identified in a gene currently not associated with the patient's cardiomyopathy subtype. Only 15 out of 2002 patients (0.8%) were found to carry two (L)P variants. CONCLUSION: The yield of routine clinical diagnostics of cardiomyopathies was relatively low when compared to literature. This is likely due to the fact that our study reports the outcome of patients in daily routine diagnostics, therefore also including patients not fully fulfilling (subtype specific) cardiomyopathy criteria. This may also explain why (L)P variants were identified in genes not associated with the reported subtype. The added value of CNV analysis was shown to be limited but not negligible

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015