Showing papers in "Critical Care in 2010"

Sepsis biomarkers: a review

Abstract: Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. The search retrieved 3370 references covering 178 different biomarkers. Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.

Management of bleeding following major trauma: an updated European guideline

Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate

Abstract: The appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates. This retrospective analysis included trauma patients who received ≥ 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM®). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was 1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score. Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014). ROTEM®-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.

Clinical review: Scoring systems in the critically ill

Abstract: General illness severity scores are widely used in the ICU to predict outcome, characterize disease severity and degree of organ dysfunction, and assess resource use. In this article we review the most commonly used scoring systems in each of these three groups. We examine the history of the development of the initial major systems in each group, discuss the construction of subsequent versions, and, when available, provide recent comparative data regarding their performance. Importantly, the different types of scores should be seen as complementary, rather than competitive and mutually exclusive. It is possible that their combined use could provide a more accurate indication of disease severity and prognosis. All these scoring systems will need to be updated with time as ICU populations change and new diagnostic, therapeutic and prognostic techniques become available.

Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit.

Abstract: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. We retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission. Significant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean ± standard deviation 176 ± 138 mg/l vs. 116 ± 103 mg/l; P = 0.042), lymphocyte count (0.8 ± 0.5 × 109/l vs. 1.2 ± 0.7 × 109/l; P < 0.0001) and NLCR (20.9 ± 13.3 vs. 13.2 ± 14.1; P < 0.0001) but not regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81). In an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra costs.

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial

Abstract: Recent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation. We performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality. One hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury. Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation. ISRCTN82533884

Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality

Abstract: Introduction: Burn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death Methods: The systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google The reference lists and the Science Citation Index were used for hand searching (snowballing) Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included Language restrictions were set on English, French, and Dutch Results: The search led to 76 eligible studies, including more than 186,500 patients in total The annual incidence of severe burns was 02 to 29/10,000 inhabitants with a decreasing trend in time Almost 50% of patients were younger than 16 years, and ~60% were male patients Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated Mortality was usually between 14% and 18% and is decreasing in time Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases (Multi) organ failure and sepsis were the most frequently reported causes of death The main causes of early death (<48 hours) were burn shock and inhalation injury Conclusions: Despite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care

Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial

Abstract: Patients recovering from critical illness have been shown to be at risk of developing Post Traumatic Stress disorder (PTSD). This study was to evaluate whether a prospectively collected diary of a patient's intensive care unit (ICU) stay when used during convalescence following critical illness will reduce the development of new onset PTSD. Intensive care patients with an ICU stay of more than 72 hours were recruited to a randomised controlled trial examining the effect of a diary outlining the details of the patients ICU stay on the development of acute PTSD. The intervention patients received their ICU diary at 1 month following critical care discharge and the final assessment of the development of acute PTSD was made at 3 months. 352 patients were randomised to the study at 1 month. The incidence of new cases of PTSD was reduced in the intervention group compared to the control patients (5% versus 13%, P = 0.02). The provision of an ICU diary is effective in aiding psychological recovery and reducing the incidence of new PTSD. NCT00912613.

Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study

Abstract: Stroke volume variation (SVV) is a good and easily obtainable predictor of fluid responsiveness, which can be used to guide fluid therapy in mechanically ventilated patients. During major abdominal surgery, inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity. The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery. Patients undergoing elective intraabdominal surgery were randomly assigned to a Control group (n = 60) with routine intraoperative care and a Vigileo group (n = 60), where fluid management was guided by SVV (Vigileo/FloTrac system). The aim was to maintain the SVV below 10% using colloid boluses of 3 ml/kg. The laboratory parameters of organ hypoperfusion in perioperative period, the number of infectious and organ complications on day 30 after the operation, and the hospital and ICU length of stay and mortality were evaluated. The local ethics committee approved the study. The patients in the Vigileo group received more colloid (1425 ml [1000-1500] vs. 1000 ml [540-1250]; P = 0.0028) intraoperatively and a lower number of hypotensive events were observed (2[1-2] Vigileo vs. 3.5[2-6] in Control; P = 0.0001). Lactate levels at the end of surgery were lower in Vigileo (1.78 ± 0.83 mmol/l vs. 2.25 ± 1.12 mmol/l; P = 0.0252). Fewer Vigileo patients developed complications (18 (30%) vs. 35 (58.3%) patients; P = 0.0033) and the overall number of complications was also reduced (34 vs. 77 complications in Vigileo and Control respectively; P = 0.0066). A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization (9 [8-12] vs. 10 [8-19] days; P = 0.0421). No difference in mortality (1 (1.7%) vs. 2 (3.3%); P = 1.0) and ICU length of stay (3 [2-5] vs. 3 [0.5-5]; P = 0.789) was found. In this study, fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability, decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications. Current Controlled Trials ISRCTN95085011.

Quality of life in the five years after intensive care: a cohort study

Abstract: Data on quality of life beyond 2 years after intensive care discharge are limited and we aimed to explore this area further. Our objective was to quantify quality of life and health utilities in the 5 years after intensive care discharge. A prospective longitudinal cohort study in a University Hospital in the UK. Quality of life was assessed from the period before ICU admission until 5 years and quality adjusted life years calculated. 300 level 3 intensive care patients of median age 60.5 years and median length of stay 6.7 days, were recruited. Physical quality of life fell to 3 months (P = 0.003), rose back to pre-morbid levels at 12 months then fell again from 2.5 to 5 years after intensive care (P = 0.002). Mean physical scores were below the population norm at all time points but the mean mental scores after 6 months were similar to those population norms. The utility value measured using the EuroQOL-5D quality of life assessment tool (EQ-5D) at 5 years was 0.677. During the five years after intensive care unit, the cumulative quality adjusted life years were significantly lower than that expected for the general population (P < 0.001). Intensive care unit admission is associated with a high mortality, a poor physical quality of life and a low quality adjusted life years gained compared to the general population for 5 years after discharge. In this group, critical illness associated with ICU admission should be treated as a life time diagnosis with associated excess mortality, morbidity and the requirement for ongoing health care support.

Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients

Abstract: Introduction: Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI. Methods: In 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours. Results: The median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression. Conclusions: In critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.

Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units

Abstract: Recent evidence suggests that choice of fluid used for resuscitation may influence mortality in critically ill patients. We conducted a cross-sectional study in 391 intensive care units across 25 countries to describe the types of fluids administered during resuscitation episodes. We used generalized estimating equations to examine the association between patient, prescriber and geographic factors and the type of fluid administered (classified as crystalloid, colloid or blood products). During the 24-hour study period, 1,955 of 5,274 (37.1%) patients received resuscitation fluid during 4,488 resuscitation episodes. The main indications for administering crystalloid or colloid were impaired perfusion (1,526/3,419 (44.6%) of episodes), or to correct abnormal vital signs (1,189/3,419 (34.8%)). Overall, colloid was administered to more patients (1,234 (23.4%) versus 782 (14.8%)) and during more episodes (2,173 (48.4%) versus 1,468 (32.7%)) than crystalloid. After adjusting for patient and prescriber characteristics, practice varied significantly between countries with country being a strong independent determinant of the type of fluid prescribed. Compared to Canada where crystalloid, colloid and blood products were administered in 35.5%, 40.6% and 28.3% of resuscitation episodes respectively, odds ratios for the prescription of crystalloid in China, Great Britain and New Zealand were 0.46 (95% confidence interval (CI) 0.30 to 0.69), 0.18 (0.10 to 0.32) and 3.43 (1.71 to 6.84) respectively; odds ratios for the prescription of colloid in China, Great Britain and New Zealand were 1.72 (1.20 to 2.47), 4.72 (2.99 to 7.44) and 0.39 (0.21 to 0.74) respectively. In contrast, choice of fluid was not influenced by measures of illness severity (for example, Acute Physiology and Chronic Health Evaluation (APACHE) II score). Administration of resuscitation fluid is a common intervention in intensive care units and choice of fluid varies markedly between countries. Although colloid solutions are more expensive and may possibly be harmful in some patients, they were administered to more patients and during more resuscitation episodes than crystalloids were.

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

Abstract: Introduction: Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α 2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients. Methods: In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis. Results: Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11). Conclusions: In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results.

Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock.

Abstract: Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review

Abstract: Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Delirium epidemiology in critical care (DECCA): an international study

Abstract: Introduction: Delirium is a frequent source of morbidity in intensive care units (ICUs) Most data on its epidemiology is from single-center studies Our aim was to conduct a multicenter study to evaluate the epidemiology of delirium in the ICU Methods: A 1-day point-prevalence study was undertaken in 104 ICUs from 11 countries in South and North America and Spain Results: In total, 975 patients were screened, and 497 fulfilled inclusion criteria and were enrolled (median age, 62 years; 525% men; 167% and 199% for ICU and hospital mortality); 64% were admitted to the ICU because of medical causes, and sepsis was the main diagnosis (n = 76; 153%) In total, 265 patients were sedated with the Richmond agitation and sedation scale (RASS) deeper than -3, and only 232 (466%) patients could be evaluated with the confusion-assessment method for the ICU The prevalence of delirium was 323% Compared with patients without delirium, those with the diagnosis of delirium had a greater severity of illness at admission, demonstrated by higher sequential organ-failure assessment (SOFA (P = 0004)) and simplified acute physiology score 3 (SAPS3) scores (P < 00001) Delirium was associated with increased ICU (20% versus 57%; P = 0002) and hospital mortality (24 versus 83%; P = 00017), and longer ICU (P < 00001) and hospital length of stay (LOS) (22 (11 to 40) versus 7 (4 to 18) days; P < 00001) Previous use of midazolam (P = 0009) was more frequent in patients with delirium On multivariate analysis, delirium was independently associated with increased ICU mortality (OR = 314 (126 to 786); CI, 95%) and hospital mortality (OR = 25 (11 to 57); CI, 95%) Conclusions: In this 1-day international study, delirium was frequent and associated with increased mortality and ICU LOS The main modifiable risk factors associated with the diagnosis of delirium were the use of invasive devices and sedatives (midazolam)

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

Abstract: Introduction Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.

Posttraumatic stress, anxiety and depression symptoms in patients during the first year post intensive care unit discharge

Abstract: To study the level and predictors of posttraumatic stress, anxiety and depression symptoms in medical, surgical and trauma patients during the first year post intensive care unit (ICU) discharge. Of 255 patients included, 194 participated at 12 months. Patients completed the Impact of Event Scale (IES), Hospital Anxiety and Depression Scale (HADS), Life Orientation Test (LOT) at 4 to 6 weeks, 3 and 12 months and ICU memory tool at the first assessment (baseline). Case level for posttraumatic stress symptoms with high probability of a posttraumatic stress disorder (PTSD) was ≥ 35. Case level of HADS-Anxiety or Depression was ≥ 11. Memory of pain during ICU stay was measured at baseline on a five-point Likert-scale (0-low to 4-high). Patient demographics and clinical variables were controlled for in logistic regression analyses. Mean IES score one year after ICU treatment was 22.5 (95%CI 20.0 to 25.1) and 27% (48/180) were above case level, IES ≥ 35. No significant differences in the IES mean scores across the three time points were found (P = 0.388). In a subgroup, 27/170 (16%), patients IES score increased from 11 to 32, P < 0.001. No differences in posttraumatic stress, anxiety or depression between medical, surgical and trauma patients were found. High educational level (OR 0.4, 95%CI 0.2 to 1.0), personality trait (optimism) OR 0.9, 95%CI 0.8 to 1.0), factual recall (OR 6.6, 95%CI 1.4 to 31.0) and memory of pain (OR 1.5, 95%CI 1.1 to 2.0) were independent predictors of posttraumatic stress symptoms at one year. Optimism was a strong predictor for less anxiety (OR 0.8, 0.8 to 0.9) and depression symptoms (OR 0.8, 0.8 to 0.9) after one year. The mean level of posttraumatic stress symptoms in patients one year following ICU treatment was high and one of four were above case level Predictors of posttraumatic stress symptoms were mainly demographics and experiences during hospital stay whereas clinical injury related variables were insignificant. Pessimism was a predictor of posttraumatic stress, anxiety and depression symptoms. A subgroup of patients developed clinically significant distress symptoms during the follow-up period.

The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia.

Abstract: Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.

Bench-to-bedside review: Chloride in critical illness

Abstract: Chloride is the principal anion in the extracellular fluid and is the second main contributor to plasma tonicity. Its concentration is frequently abnormal in intensive care unit patients, often as a consequence of fluid therapy. Yet chloride has received less attention than any other ion in the critical care literature. New insights into its physiological roles have emerged together with progress in understanding the structures and functions of chloride channels. In clinical practice, interest in a physicochemical approach to acid-base physiology has directed renewed attention to chloride as a major determinant of acid-base status. It has also indirectly helped to generate interest in other possible effects of disorders of chloraemia. The present review summarizes key aspects of chloride physiology, including its channels, as well as the clinical relevance of disorders of chloraemia. The paper also highlights current knowledge on the impact of different types of intravenous fluids on chloride concentration and the potential effects of such changes on organ physiology. Finally, the review examines the potential intensive care unit practice implications of a better understanding of chloride.

Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial.

Abstract: Critical illness polyneuromyopathy (CIPNM) is a common complication of critical illness presenting with muscle weakness and is associated with increased duration of mechanical ventilation and weaning period. No preventive tool and no specific treatment have been proposed so far for CIPNM. Electrical muscle stimulation (EMS) has been shown to be beneficial in patients with severe chronic heart failure and chronic obstructive pulmonary disease. Aim of our study was to assess the efficacy of EMS in preventing CIPNM in critically ill patients. One hundred and forty consecutive critically ill patients with an APACHE II score ≥ 13 were randomly assigned after stratification to the EMS group (n = 68) (age:61 ± 19 years) (APACHE II:18 ± 4, SOFA:9 ± 3) or to the control group (n = 72) (age:58 ± 18 years) (APACHE II:18 ± 5, SOFA:9 ± 3). Patients of the EMS group received daily EMS sessions. CIPNM was diagnosed clinically with the medical research council (MRC) scale for muscle strength (maximum score 60, <48/60 cut off for diagnosis) by two unblinded independent investigators. Duration of weaning from mechanical ventilation and intensive care unit (ICU) stay were recorded. Fifty two patients could be finally evaluated with MRC; 24 in the EMS group and 28 in the control group. CIPNM was diagnosed in 3 patients in the EMS group as compared to 11 patients in the control group (OR = 0.22; CI: 0.05 to 0.92, P = 0.04). The MRC score was significantly higher in patients of the EMS group as compared to the control group [58 (33 to 60) vs. 52 (2 to 60) respectively, median (range), P = 0.04). The weaning period was statistically significantly shorter in patients of the EMS group vs. the control group [1 (0 to 10) days vs. 3 (0 to 44) days, respectively, median (range), P = 0.003]. This study suggests that daily EMS sessions prevent the development of CIPNM in critically ill patients and also result in shorter duration of weaning. Further studies should evaluate which patients benefit more from EMS and explore the EMS characteristics most appropriate for preventing CIPNM. ClinicalTrials.gov NCT00882830

PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction.

Abstract: Introduction Lymphocyte apoptosis and monocyte dysfunction play a pivotal role in sepsis-induced immunosuppression. Programmed death-1 (PD1) and its ligand programmed death ligand-1 (PD-L1) exert inhibitory function by regulating the balance among T cell activation, tolerance, and immunopathology. PD-1 deficiency or blockade has been shown to improve survival in murine sepsis. However, PD-L1 and PD-1 differ in their expression patterns and the role of PD-L1 in sepsis-induced immunosuppression is still unknown.

Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial

Abstract: Introduction: Several studies have shown that goal-directed hemodynamic and fluid optimization may result in improved outcome. However, the methods used were either invasive or had other limitations. The aim of this study was to perform intraoperative goal-directed therapy with a minimally invasive, easy to use device (FloTrac/ Vigileo), and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a standard management protocol. Methods: In this randomized, controlled trial 60 high-risk patients scheduled for major abdominal surgery were included. Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard management group (Control-group, n = 30), based on standard monitoring data. Results: The median duration of hospital stay was significantly reduced in the GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and fewer patients developed complications than in the Control-group [6 patients (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was reduced in the GDTgroup (17 versus 49 complications, P = 0.001). Conclusions: In high-risk patients undergoing major abdominal surgery, implementation of an intraoperative goaldirected hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a standard management protocol. Trial Registration: Clinical trial registration information: Unique identifier: NCT00549419

Increased duration of mechanical ventilation is associated with decreased diaphragmatic force: a prospective observational study

Abstract: Respiratory muscle weakness is an important risk factor for delayed weaning. Animal data show that mechanical ventilation itself can cause atrophy and weakness of the diaphragm, called ventilator-induced diaphragmatic dysfunction (VIDD). Transdiaphragmatic pressure after magnetic stimulation (TwPdi BAMPS) allows evaluation of diaphragm strength. We aimed to evaluate the repeatability of TwPdi BAMPS in critically ill, mechanically ventilated patients and to describe the relation between TwPdi and the duration of mechanical ventilation. This was a prospective observational study in critically ill and mechanically ventilated patients, admitted to the medical intensive care unit of a university hospital. Nineteen measurements were made in a total of 10 patients at various intervals after starting mechanical ventilation. In seven patients, measurements were made on two or more occasions, with a minimum interval of 24 hours. The TwPdi was 11.5 ± 3.9 cm H2O (mean ± SD), indicating severe respiratory muscle weakness. The between-occasion coefficient of variation of TwPdi was 9.7%, comparable with data from healthy volunteers. Increasing duration of mechanical ventilation was associated with a logarithmic decline in TwPdi (R = 0.69; P = 0.038). This association was also found for cumulative time on pressure control (R = 0.71; P = 0.03) and pressure-support ventilation (P = 0.05; R = 0.66) separately, as well as for cumulative dose of propofol (R = 0.66; P = 0.05) and piritramide (R = 0.79; P = 0.01). Duration of mechanical ventilation is associated with a logarithmic decline in diaphragmatic force, which is compatible with the concept of VIDD. The observed decline may also be due to other potentially contributing factors such as sedatives/analgesics, sepsis, or others.

Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review

Abstract: Triple-H therapy and its separate components (hypervolemia, hemodilution, and hypertension) aim to increase cerebral perfusion in subarachnoid haemorrhage (SAH) patients with delayed cerebral ischemia We systematically reviewed the literature on the effect of triple-H components on cerebral perfusion in SAH patients We searched medical databases to identify all articles until October 2009 (except case reports) on treatment with triple-H components in SAH patients with evaluation of the treatment using cerebral blood flow (CBF in ml/100 g/min) measurement We summarized study design, patient and intervention characteristics, and calculated differences in mean CBF before and after intervention Eleven studies (4 to 51 patients per study) were included (one randomized trial) Hemodilution did not change CBF One of seven studies on hypervolemia showed statistically significant CBF increase compared to baseline; there was no comparable control group Two of four studies applying hypertension and one of two applying triple-H showed significant CBF increase, none used a control group The large heterogeneity in interventions and study populations prohibited meta-analyses There is no good evidence from controlled studies for a positive effect of triple-H or its separate components on CBF in SAH patients In uncontrolled studies, hypertension seems to be more effective in increasing CBF than hemodilution or hypervolemia

The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis

Abstract: Introduction: Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death. Methods: This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and inhospital mortality were analyzed. Results: A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91. Conclusions: Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest

Abstract: Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous “burst-suppression” activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Treatment of hypophosphatemia in the intensive care unit: a review

Abstract: Introduction: Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients. Methods: We performed a narrative review of the medical literature to identify the incidence, symptoms, and treatment of hypophosphatemia in critically ill patients. Specifically, we searched for answers to the questions whether correction of hypophosphatemia is associated with improved outcome, and whether a certain treatment strategy is superior. Results: Incidence: hypophosphatemia is frequently encountered in the intensive care unit; and critically ill patients are at increased risk for developing hypophosphatemia due to the presence of multiple causal factors. Symptoms: hypophosphatemia may lead to a multitude of symptoms, including cardiac and respiratory failure. Treatment: hypophosphatemia is generally corrected when it is symptomatic or severe. However, although multiple studies confirm the efficacy and safety of intravenous phosphate administration, it remains uncertain when and how to correct hypophosphatemia. Outcome: in some studies, hypophosphatemia was associated with higher mortality; a paucity of randomized controlled evidence exists for whether correction of hypophosphatemia improves the outcome in critically ill patients.

Recommendations for the intra-hospital transport of critically ill patients

Abstract: This study was conducted to provide Intensive Care Units and Emergency Departments with a set of practical procedures (check-lists) for managing critically-ill adult patients in order to avoid complications during intra-hospital transport (IHT). Digital research was carried out via the MEDLINE, EMBASE, CINAHL and HEALTHSTAR databases using the following key words: transferring, transport, intrahospital or intra-hospital, and critically ill patient. The reference bibliographies of each of the selected articles between 1998 and 2009 were also studied. This review focuses on the analysis and overcoming of IHT-related risks, the associated adverse events, and their nature and incidence. The suggested preventive measures are also reviewed. A check-list for quick execution of IHT is then put forward and justified. Despite improvements in IHT practices, significant risks are still involved. Basic training, good clinical sense and a risk-benefit analysis are currently the only deciding factors. A critically ill patient, prepared and accompanied by an inexperienced team, is a risky combination. The development of adapted equipment and the widespread use of check-lists and proper training programmes would increase the safety of IHT and reduce the risks in the long-term. Further investigation is required in order to evaluate the protective role of such preventive measures.

On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study

Abstract: Introduction Patients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting.