Intensive Care Med 2004;30:556–575

Hypothermia has been used for medicinal purposes since ancient times. This paper reviews the current potential clinical applications for mild hypothermia (32–35^oC).

Design and setting
Induced hypothermia is used mostly to prevent or attenuate neurological injury, and has been used to provide neuroprotection in traumatic brain injury, cardiopulmonary resuscitation, stroke, and various other disorders. The evidence for each of these applications is discussed, and the mechanisms underlying potential neuroprotective effects are reviewed. Some of this evidence comes from animal models, and a brief overview of these models and their limitations is included in this review.

Results
The duration of cooling and speed of re-warming appear to be key factors in determining whether hypothermia will be effective in preventing or mitigating neurological injury. Some other potential usages of hypothermia, such as its use in the perioperative setting and its application to mitigate cardiac injury following ischemia and reperfusion, are also discussed. Conclusions: Although induced hypothermia appears to be a highly promising treatment, it should be emphasized that it is associated with a number of potentially serious side effects, which may negate some or all of its potential benefits. Prevention and/or early treatment of these complications are the key to successful use of hypothermia in clinical practice. These side effects, as well as various physiological changes induced by cooling, are discussed in a separate review.

Intensive Care Med 2004;30:757–769

Induced hypothermia can be used to protect the brain from post-ischemic and traumatic neurological injury. Potential clinical applications and the available evidence are discussed in a separate paper. This review focuses on the practical aspects of cooling and physiological changes induced by hypothermia, as well as the potential side effects that may develop. These side effects can be serious and, if not properly dealt with, may negate some or all of hypothermia’s potential benefits. However, many of these side effects can be prevented or modified by high-quality intensive care treatment, which should include careful monitoring of fluid balance, tight control of metabolic aspects such as glucose and electrolyte levels, prevention of infectious complications and various other interventions. The speed and duration of cooling and rate of rewarming are key factors in determining whether hypothermia will be effective; however, the risk of side effects also increases with longer duration. Realizing hypothermia’s full therapeutic potential will therefore require meticulous attention to the prevention and/or early treatment of side effects, as well as a basic knowledge and understanding of the underlying physiological and pathophysiological mechanisms. These and other, related issues are dealt with in this review.

NEJM 2010;362:779-789

Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other.

Methods
In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 µg per kilogram of body weight per minute for dopamine or a dose of 0.19 µg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events.

Results
The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan–Meier analyses).

Conclusions
Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events.

JAMA. 2010;303:841-848

A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments.

Objective
To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population.

Design, setting and participants
The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28 980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events.

Interventions
Once daily 100 mg aspirin (enteric coated) or placebo.

Main outcome measures
The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality.

Results
After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval [CI], 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio [HR], 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the  group (HR, 1.71; 95% CI, 0.99-2.97).

Conclusion
Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events.

JAMA. 2008;300:197-208

Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.

Objective
To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.

Data sources
Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.
Study Selection  Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.

Data extraction
Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.

Results
Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480 325 person-years of follow-up of 24 955 men and 23 339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (<0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (<0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.

Conclusion
Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

This guidance is about the care and treatment of people who are at risk of developing deep vein thrombosis (DVT) while in hospital in the NHS in England and Wales.

The advice in the NICE guideline covers the care and treatment that should be offered to all adults (aged 18 and over) who are admitted to hospital as inpatients (including those admitted for day-case procedures).

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Anaesthesia 2010;65:12-17

Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients was evaluated using two doses of local anaesthetic. In this randomised, blinded prospective study, 40 ml of atomised 1% (n = 11) or 2% (n = 10) lidocaine was administered with high oxygen flow as carrier. Outcomes included time for intubation, patient tolerance to airway manipulation, haemodynamic parameters, the bronchoscopist’s overall satisfaction, and serial serum lidocaine concentrations. Patients receiving lidocaine 1% had a longer mean (SD) time from the start of topicalisation to tracheal tube cuff inflation than those receiving lidocaine 2% (8.6 (0.9) min vs 6.9 (0.5) min, respectively; p < 0.05). Patients in the 1% cohort demonstrated increased responses to airway manipulation (p < 0.0001), reflecting lower bronchoscopist’s satisfaction scores (p < 0.03). Haemodynamic responses to topicalisation and airway manipulation were similar in both groups. Peak plasma concentration was lower in the 1% group (mean (SD) 1.4 (0.3) and 3.8 (0.5) μg.ml−1, respectively; p < 0.001). Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in the morbidly obese is efficacious, rapid and safe. Compared with lidocaine 1%, the 2% dose provides superior intubating conditions.

Critical Care 2009, 13:1014

Despite 21st century definitions, the management of acute kidney injury remains steadfastly rooted in the 20th century with treatment being principally supportive. Protection from potential causative agents is an essential part of management and to that end protection against contrast-induced nephropathy has received yet more attention. When optimization of volume status, haemodynamic parameters, electrolyte and acid-base disturbances have failed we turn to renal replacement therapy. The time ‘bought’ on renal support gives a period for renal recovery but although renal replacement therapy is widely employed, many management issues remain unanswered, including the timing, duration and the dose of treatment. In contrast to respiratory support for acute lung injury, for example, there is a paucity of large randomized studies addressing these fundamental issues. We describe some recent studies focusing on these issues with the hope that they may lead to better treatment for our patients.

Ann Int Med 2010;152:10-17

Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown.

Objective
To test the hypothesis that smoking cessation increases diabetes risk in the short term, possibly owing to cessation-related weight gain.

Design
Prospective cohort study.

Setting
The ARIC (Atherosclerosis Risk in Communities) Study.

Patients
10 892 middle-aged adults who initially did not have diabetes in 1987 to 1989.

Measurements
Smoking was assessed by interview at baseline and at subsequent follow-up. Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004.

Results
During 9 years of follow-up, 1254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years.

Limitation
Residual confounding is possible even with meticulous adjustment for established diabetes risk factors.

Conclusion
Cigarette smoking predicts incident type 2 diabetes, but smoking cessation leads to higher short-term risk. For smokers at risk for diabetes, smoking cessation should be coupled with strategies for diabetes prevention and early detection.

Crit Care Med 2010;38:288-291

To develop and validate an equation to predict dead space to tidal volume ratio (Vd/Vt) from clinically available data in critically ill mechanically ventilated patients.

Design
Prospective, observational study using a convenience sample of patients whose arterial blood gas and respiratory gas exchange had been measured with indirect calorimetry.

Setting
Medical and surgical critical care units of a university medical center.

Patients
Adult, mechanically ventilated patients at rest with Fio2 ≤0.60 and no air leaks who had recent arterial blood gas recordings and end-tidal carbon dioxide concentration monitoring.

Intervention
Observational only.

Measurements and main results
Indirect calorimetry was used to determine carbon dioxide production and expired minute ventilation in 135 patients. Tidal volume and respiratory rate were recorded from the ventilator. End tidal carbon dioxide concentration, body temperature, arterial carbon dioxide partial pressure (Paco2), and other clinical data were recorded. Vd/Vt was calculated using the Enghoff modification of the Bohr equation (Paco2 − PECO2/Paco2). Regression analysis was then used to construct a predictive equation for Vd/Vt using the clinical data: Vd/Vt = 0.32 + 0.0106 (Paco2 − ETCO2) + 0.003 (RR) + 0.0015 (age) (R2 = 0.67). A second group of 50 patients was measured using the same protocol and their data were used to validate the equations developed from the original 135 patients. The equation was found to be unbiased and precise.

Conclusions
Vd/Vt is predictable from clinically available data. Whether this predicted quantity is valuable clinically must still be determined.

NEJM 2009;361:1627-1638

The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury.

Methods
We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization.

Results
Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001).

Conclusions
In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days.

Critical Care 2009, 13:R157

Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Methods
Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.

Results
One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05).

Conclusions
During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.

Critical Care 2009, 13:1013

Cardiogenic shock is a lethal condition. Physicians are searching for hemodynamic markers which could help risk-stratification of patients in this picture. Torgersen and coworkers present an hourly time integral of the cardiac power index and cardiac index drops to predict outcomes in the setting of cardiogenic shock. Continuous monitoring of hemodynamic markers may have a role in prediction of outcomes.

Critical Care 2009, 13:R205

Mortality of severe acute respiratory distress syndrome in adults is still unacceptably high. Extracorporeal membrane oxygenation (ECMO) could represent an important treatment option, if complications were reduced by new technical developments.

Methods
Efficiency, side effects and outcome of treatment with a new miniaturized device for veno-venous extracorporeal gas transfer were analysed in 60 consecutive patients with life-threatening respiratory failure.

Results
A rapid increase of PaO2/FiO2 from 64 (48-86) mmHg to 120 (84-171) mmHg and a decrease of PaCO2 from 63 (50-80) mmHg to 33 (29-39) mmHg were observed after start of the extracorporeal support (p<0.001). Gas exchange capacity of the device averaged 155 (116-182) mL/min for oxygen and 210 (164-251) mL/min for carbon dioxide. Ventilatory parameters were reduced to a highly protective mode, allowing a fast reduction of tidal volume from 495 (401-570) mL to 336 (292-404) mL (p < 0.001) and of peak inspiratory pressure from 36 (32-40) cmH2O to 31 (28-35) cmH2O (p < 0.001). Transfusion requirements averaged 0.8 (0.4-1.8) units of red blood cells per day. 62% of patients were weaned from the extracorporeal system, and 45% survived to discharge.

Conclusions
Veno-venous extracorporeal membrane oxygenation with a new miniaturized device supports gas transfer effectively, allows for highly protective ventilation and is very reliable. Modern ECMO technology extends treatment opportunities in severe lung failure.

Crit Care Med 2010;38:283-287

Severity scores such as Acute Physiology and Chronic Health Evaluation II have been advocated as entry criteria for clinical trials and in clinical decision-making. We present ten reasons why we believe this approach is not appropriate and may even be detrimental.

Data sources
Available relevant literature from authors’ personal databases and personal knowledge of past and future clinical trial development.

Data synthesis
Severity scores were not designed for use in individual patients or for therapeutic decision-making for specific interventions. Difficulties with the time window needed to calculate these scores and the need to administer therapies early further limit their use in this context. The complex nature of the scores makes it difficult to use them at the bedside and there is considerable interobserver variability in score calculation. Inclusion of chronic health and age points in severity scores may prevent younger, previously healthy patients, with similar acute physiological dysfunction and therefore total lower severity scores, from trial inclusion or from receiving therapies that may be beneficial.

Conclusions
We believe severity of illness scores are poor surrogates for risk stratification and should not be used as a criterion for patient enrollment into clinical trials or as the basis for individual treatment decisions.

Crit Care Med 2010;38:152-160

Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS.

Design
A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004

Setting
Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: The prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndromeTertiary care university hospital.

Patients and interventions
Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP.

Measurements and main results
Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 ± 2.88) than survivors (18.1 ± 1.66, p < .05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results.

Conclusions
In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point.

Crit Care Med 2010;38:72-83

Endotoxin is a potent stimulus of proinflammatory response and systemic coagulation in patients with severe sepsis. Endotoxin is a component of Gram-negative bacteria that triggers an innate immune response through Toll-like receptor 4 signaling pathways in myeloid cells. We evaluated safety and tolerability of two dose regimens of eritoran tetrasodium (E5564), a synthetic Toll-like receptor 4 antagonist, and explored whether it decreases 28-day mortality rate in subjects with severe sepsis.

Design
Prospective, randomized, double-blind, placebo-controlled, multicenter, ascending-dose phase II trial.

Setting
Adult intensive care units in the United States and Canada.

Patients
Three hundred adults within 12 hrs of recognition of severe sepsis, with Acute Physiology and Chronic Health Evaluation (APACHE) II-predicted risk of mortality between 20% and 80%.
Interventions
Intravenous eritoran tetrasodium (total dose of either 45 mg or 105 mg) or placebo administered every 12 hrs for 6 days.

Measurements and main results
Prevalence of adverse events was similar among subjects treated with 45 mg or 105 mg of eritoran tetrasodium or with placebo. For modified intent-to-treat subjects, 28-day all-cause mortality rates were 26.6% (eritoran tetrasodium 105 mg), 32.0% (eritoran tetrasodium 45 mg), and 33.3% in the placebo group. Mortality rate in the eritoran tetrasodium 105-mg group was not significantly different from placebo (p = .335). In prespecified subgroups, subjects at highest risk of mortality by APACHE II score quartile had a trend toward lower mortality rate in the eritoran tetrasodium 105-mg group (33.3% vs. 56.3% placebo group, p = .105). A trend toward a higher mortality rate was observed in subjects in the lowest APACHE II score quartile for the eritoran 105-mg group (12.0% vs. 0.0% placebo group, p = .083).

Conclusions
Eritoran tetrasodium treatment appears well tolerated. The observed trend toward a lower mortality rate at the 105-mg dose, in subjects with severe sepsis and high predicted risk of mortality, should be further investigated.

Critical Care 2009, 13:235

Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young, healthy adults. Clinicians should maintain a high index of suspicion for this diagnosis in patients presenting with influenza-like symptoms that progress quickly (2-5 days) to respiratory distress and extensive pulmonary involvement. The sensitivity of rapid diagnostic techniques in identifying infections with the pandemic 2009 H1N1v influenza strain is currently suboptimal. The most reliable real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) molecular testing is available in limited clinical settings. Despite 6 months of pandemic circulation, most novel H1N1v pandemic strains remain susceptible to oseltamivir. Ensuring an appropriate oxygenation and ventilation strategy, as well as prompt initiation of antiviral therapy, is essential in management.

Best Pract Res Clin Anaesthesiol 2007; 21:241–256

Performing a surgical procedure on a patient undergoing anti-platelet therapy raises a dilemma: is it safer to withdraw the drugs and reduce the haemorrhagic risk, or to maintain them and reduce the risk of myocardial ischaemic events? Based on recent clinical data, this review concludes that the risk of coronary thrombosis on anti-platelet drugs withdrawal is much higher than the risk of surgical bleeding when maintaining them. In secondary prevention, aspirin is a lifelong therapy and should never be stopped. Clopidogrel is mandatory as long as the coronary stents are not fully endothelialized, which takes 6–24 weeks depending on the technique used, but might be required for a longer period

Critical Care 2009, 13:R208

Hydroxyethyl starch (HES) solutions are widely used for volume replacement therapy but are also known to compromise coagulation, impair renal function and increase long-term mortality. To test the hypotheses that HES 130/0.4 has less adverse effects than HES 200/0.5 and exerts anti-inflammatory properties we compared the effects of HES130/0.4, HES200/0.5 and saline on in vitro haemostasis and pro-inflammatory platelet function.

Methods
Whole blood samples from healthy volunteers were mixed with 6% HES130/0.4, 10% HES200/0.5, or normal saline to achieve a final haemodilution rate of 10 % or 40 %. Haemostatic capacity was characterised by thromboelastography (ROTEM) and measurement for FXIIIa activity. Platelet activation and pro-inflammatory platelet functions were characterised by flow cytometry measuring the platelet activation marker CD62P and binding of fibrinogen to platelets as well as the formation of heterotypic platelet-leukocyte conjugates.

Results
Compared to saline, HES130/0.4 dose-dependently impaired formation and firmness of the fibrin clot but did not affect the fibrin-crosslinking activity of FXIIIa. At 40 % but not at 10 % haemodilution rate HES200/0.5 also increased platelet fibrinogen binding and both HES solutions increased expression of CD62P, the main receptor for platelet-leukocyte adhesion. HES130/0.4 but not HES200/0.5 increased formation of platelet-neutrophil conjugates and, to a lesser degree, platelet-monocyte conjugates.
HES130/0.4 impairs haemostasis and stimulates pro-inflammatory blood platelet function
Conclusions
Our data demonstrate that HES130/0.4 has similar adverse effects as HES200/0.5. In particular, both types of HES impair coagulation capacity and stimulate rather than attenuate pro-inflammatory platelet function.