Variation in red cell transfusion practice in the intensive care unit - An international survey.

PURPOSE: Unclear recommendations in transfusion guidelines may possibly lead to inconsistency in treatment of patients admitted to the intensive care unit. This study aimed to uncover variation in red blood cell (RBC) transfusion decisions in the ICU worldwide. METHODS: Members of the European Society of Intensive Care Medicine (ESICM) were requested to complete an online questionnaire which included four different hypothetical clinical scenarios. The scenarios represented patients with acute myocardial infarction (AMI), abdominal sepsis, traumatic brain injury (TBI) and post-surgical complications. Hemoglobin level was 7∙3 g/dL in all scenarios. The questionnaire explored the physicians' transfusion decision in each clinical scenario and identified patient characteristics that were most influential in the transfusion decision. RESULTS: In total 211 members participated in the study, of whom 142 (67%) completed the entire survey. Most variation was observed in the clinical scenario of sepsis, in which 49% decided to transfuse and 51% decided not to. In the clinical scenarios of AMI, TBI and post-surgical complications this was respectively; 75/25%, 35/65% and 66/34%. CONCLUSIONS: Critical care physicians differed in outcome of RBC transfusion decisions and weighed patient characteristics differently. These findings indicate that variation in transfusion practice amongst critical care physicians exists.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.

High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury.

PURPOSE: Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI to whole-blood tacrolimus trough concentrations and other factors causing kidney injury. METHODS: We retrospectively studied kidney injury in 186 lung-transplantation patients at the UMC Utrecht between 2001 and 2011. Kidney function and whole-blood tacrolimus trough concentrations were determined from day 1 to 14 and at 1, 3, 6, and 12 months postoperative. Systemic inflammatory response syndrome (SIRS), septic shock, and nephrotoxic medications were evaluated as covariates for AKI. We analyzed liver injury and drug-drug interactions. RESULTS: AKI was present in 85 (46%) patients. Tacrolimus concentrations were supra-therapeutic in 135 of 186 patients (73%). AKI in the first week after transplantation was related to supra-therapeutic tacrolimus concentrations (OR 1.55; 95% CI 1.06-2.27), ≥3 other nephrotoxic drugs (OR 1.96; 95% CI 1.02-3.77), infection (OR 2.48; 95% CI 1.31-4.70), and cystic fibrosis (OR 2.17; 95% CI 1.16-4.06). Recovery rate of AKI was lower than expected (19%), and the cumulative incidence of severe CKD at 1 year was 15%. CONCLUSIONS: After lung transplantation, AKI is common and often evolves into severe CKD, which is a known cause of morbidity and mortality. Supra-therapeutic whole-blood tacrolimus trough concentrations are related to the early onset of AKI. Conscientious targeting tacrolimus blood concentrations might be vital in the early phase after lung transplantation. What is known about this subject? • Lung transplant recipients often develop acute kidney injury evolving into chronic kidney disease increasing both morbidity and mortality. • To date, the pathophysiology of kidney injury after lung transplantation has not been fully elucidated. • The immunosuppressant tacrolimus is difficult to dose, especially in the unstable clinical setting, and is nephrotoxic. WHAT THIS STUDY ADDS: • For the first time, supra-therapeutic whole-blood tacrolimus trough concentrations are related to the emergence of acute kidney injury in the first days after lung transplantation. • Supra-therapeutic whole-blood tacrolimus trough concentrations often occur early after lung transplantation. • AKI after lung transplantation shows low recovery rates.

Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation.

Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi-) organ failure. Limited understanding of tacrolimus pharmacokinetics in these circumstances is hampering daily practice. Tacrolimus dose adjustments are generally based on whole blood trough levels, which widely vary early after transplantation. Moreover, whole blood trough levels are difficult to predict and are poorly related to the area under the concentration-time curve. Even within the therapeutic range, toxicity may occur. These shortcomings of tacrolimus monitoring may not hold for the unbound tacrolimus plasma concentrations, which may better reflect tacrolimus toxicity. This review focuses on posttransplant tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus (nephro-) toxicity in heart and lung transplantation patients.

Use of selective digestive tract decontamination in European intensive cares: the ifs and whys.

BACKGROUND: Several studies have shown that the use of selective digestive tract decontamination (SDD) reduces mortality. However, fear for increasing multidrug resistance might prevent wide acceptance. A survey was performed among the units registered in the European Registry for Intensive Care (ERIC), in order to investigate the number of ICUs using SDD and the factors that prevented the use of SDD. METHODS: One invitation to the electronic survey was sent to each ERIC unit. The survey focused on department characteristics (intensive care type, local resistance levels), local treatment modalities (antibiotic stewardship) and doctors' opinions (collaborative issues concerning SDD). All ICU's in countries participating in the European Centre for Disease Prevention and Control resistance surveillance program were analysed. RESULTS: Seventeen percent of the ICUs registered in the ERIC database used SDD prophylaxis. Most of these ICUs were located in the Netherlands or Germany. ICUs using SDD were four times more likely to use antibiotic stewardship. Also larger ICUs were more likely to use SDD. On the contrary, resistance to antibiotics was not related to the use of SDD. Also the doctor's opinion that SDD is proven in cluster-randomized trials was not a determinant for not using SDD. CONCLUSION: SDD is used in a minority of the European ICUs registered in the ERIC database. Larger ICUs and ICUs with a prudent antibiotic policy were more likely to use SDD. Neither antibiotic resistance nor the cluster randomized study design were determinants of the non-use of SDD.

Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa.

BACKGROUND: The tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a catalytically active TF-FVIIa complex will be formed. OBJECTIVE: To study mortality in SIRS patients as a function of FVIIa and FVII levels in plasma. METHODS: This was a cohort study of 275 patients presenting with SIRS, aged 18 years or older and with an anticipated Intensive Care Unit (ICU) stay of at least 24 h. FVIIa was measured using a novel, quantitative assay that recognizes FVIIa, but not FVII. All-cause hospital mortality was followed over a period of 60 days. RESULTS: The percentage of FVII measured as FVIIa was higher in non-survivors than survivors (2.8%, IQR = 1-5.5% vs. 1.5%, IQR = 0.6-3.3%; P = 0.034). High levels of FVIIa were associated with decreased 60-day cumulative survival (62% vs. 81%, P = 0.030); the opposite was observed for FVII (84% vs. 76%, P = 0.039). Patients with high-FVIIa and low-FVII levels had a three-fold increased hazard ratio (HR) compared with the patients that had low-FVIIa and high-FVII levels (HR = 3.24, 95% confidence interval [CI] = 1.41-7.36). This association persisted after adjusting for the APACHE IV score (adjusted HR = 2.75, 95% CI = 1.2-6.27). CONCLUSIONS: SIRS patients with high-FVIIa and low-FVII on admission have an increased mortality risk, an association that is independent from the parameters included in the APACHE IV score.

Prolonged use of extracorporeal membrane oxygenation combined with prone positioning in patients with acute respiratory distress syndrome and invasive Aspergillosis.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used in patients with severe acute respiratory distress syndrome. In two large cohorts of such patients, the median duration of treatment with ECMO was 9 and 10 days. We describe two patients, both with H1N1 pneumonia complicated by invasive Aspergillosis, who required ECMO support significantly longer at 45 and 52 days, but eventually made a full recovery. In both patients, prone positioning was used during ECMO treatment.

[Delirium in the intensive care unit]. / Delirium op de intensive care.

Delirium is a common condition in the intensive care unit (ICU). Between 16-89% of all ICU patients experience an episode of delirium during admission. Several detection tools have been developed for use specifically in the ICU. The Confusion Assessment Method for the intensive care unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) combine high sensitivity with high specificity. Treatment consists of treatment of underlying disorders, nonpharmacological measures and symptomatic drug therapy. The prognosis for ICU patients who experience delirium is worse than for those who do not. Delirious patients are more likely to develop complications, spend longer in hospital and have a higher mortality rate. In view of the high frequency, poor prognosis, high costs and lack of studies into the treatment of ICU delirium, research into the possibilities for prevention, early detection and treatment of the condition is essential.

[Mechanical ventilation in acute respiratory distress syndrome (ARDS): lung protecting strategies for improved alveolar recruitment]. / Mechanische beademing bij 'acute respiratory distress'-syndroom (ARDS): longbeschermende strategieën voor betere alveolaire rekrutering.

For patients with acute respiratory distress syndrome (ARDS) the most important objective of mechanical ventilation is opening and keeping open the alveoli to achieve adequate oxygenation, without further damaging the lungs or negatively affecting the circulation. Alveolar recruitment is achieved by making use of positive end-expiratory pressure (PEEP). The best PEEP level is that with which the largest improvement in oxygen transport and lung compliance is achieved, without a decrease in the stroke volume of the left ventricle. In addition to the usual volume-controlled ventilation with PEEP, pressure-limited ventilation is also possible. In this a preselected pressure is never exceeded, whereas a maximum inspiratory airflow at the start of inspiration provides more opportunity for gaseous exchange. The oxygenation can possibly be further improved by increasing the inspiration-expiration ratio. As a result of the reduced expiratory period the alveoli which tend to collapse at the end of a normal expiration are kept open. Mechanical ventilation with a lower tidal volume decreases mortality. Ventilation in a prone position increases the end-expiratory lung volume and reduces the intrapulmonary shunt and the regional differences in the degree of ventilation. These factors possibly contribute to preventing ventilation-induced lung damage. Administration of natural surfactant during the ventilation of patients with ARDS seems to be a highly promising strategy; the clinical effectiveness still needs to be demonstrated.

Lodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome.

Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine x mL(-1)) or in 1:1 saline-iodixanol (160 mg iodine x mL(-1)), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH2O, lung volume at transpulmonary pressure of 5 cmH2O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH2O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.

Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.

Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also attenuate inflammatory responses during sepsis. Low circulating levels of AT and protein C have been associated with poor outcome. Replacement therapy with AT, activated protein C (APC), and TFPI has been shown to attenuate thrombin generation and to reduce mortality in experimental sepsis models. Experience with AT and APC in patients is promising. Data from large phase III trials of AT and APC as treatment of patients with severe sepsis will soon be available. Recombinant TFPI is currently in phase II clinical trials for severe sepsis.

Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.

BACKGROUND: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. METHODS: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. FINDINGS: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. INTERPRETATION: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

The Critical Nursing Situation Index for safety assessment in intensive care.

OBJECTIVE: The assessment of critical nursing situations can be a valuable tool in the detection of weak elements in the safety of patients and the quality of care in the ICU. A critical nursing situation can be defined as any observable situation, which deviates from good clinical practice and which may potentially lead to an adverse event. The aim of our study was to establish the feasibility, reliability and validity of the Critical Nursing Situation Index (CNSI) as a tool for assessing the safety and the quality of nursing in the ICU. DESIGN: We described the deviations from standards and protocols in daily ICU nursing care, selected those with an implicit, clear risk for the patients and translated them into explicitly observable items. If an item was applicable during observation of the ICU practice, a critical nursing situation could be recorded as either true or false. The reliability of the CNSI was defined in terms of inter-observer agreement. The validity was assessed by exploring the relationship between the nursing time available (more or less than 30 min per patient per hour) and the incidence of critical nursing situations. SETTING: The study was performed in the ICU of a teaching hospital (30 IC beds) in which all disciplines, including cardiothoracic surgery and neurosurgery, were represented. PATIENTS: The CNSI was randomly applied to 83 ICU patients over a period of 3 months (200 times). MEASUREMENTS AND RESULTS: The reliability of the index was substantial (Kappa values in the range > or =0.70 to > 0.80). In terms of validity, less nursing time resulted in more critical situations (pooled relative risk (RR) 1.36; 95% confidence limits 1.11/1.67). CONCLUSION: The CNSI is simple to use and has encouraging metric properties, whereas the assessments are closely related to direct patient care. Moreover, the CNSI provides a tool for safety assessment by monitoring potentially dangerous situations that are generally regarded as needing to be avoided.

Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia.

Activation of coagulation induces a proinflammatory response in in vitro and animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative sepsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endotoxin-induced inflammatory responses in healthy humans. Eight men were studied in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.05 mg/kg) or placebo. Endotoxin induced-activation of coagulation was prevented completely by TFPI. In contrast, TFPI did not influence leukocyte activation, chemokine release, endothelial cell activation, or the acute phase response. Thus, complete prevention of coagulation activation by TFPI does not influence activation of inflammatory pathways during human endotoxemia.

Gut decontamination of critically ill patients reduces Helicobacter pylori acquisition by intensive care nurses.

The prevalence of Helicobacter pylori is increased in healthcare workers and in intensive care nurses. Exposure to H. pylori from gastric secretions and faeces are probably the main sources of transmission to healthcare workers. Routine use of selective decontamination of digestive tract (SDD) in an intensive care unit suppresses H. pylori in critically ill patients. It was questioned whether this suppression and the subsequent decreased exposure to H. pylori for intensive care nurses would lead to a lower prevalence of H. pylori infection. Helicobacter pylori infection prevalence in intensive care nurses from a unit routinely using SDD (group I) was compared to that of nurses from a unit not using SDD (group II). Heathcare workers from other departments of the hospital where no SDD was used (group III) served as a control group. Persons using proton pump inhibitors were excluded. Helicobacter pylori was detected by Laser Assisted Ratio Analyser(13)C-urea breath test (UBT) and serology. This could not be performed in three out of 64 in group I, five out of 55 in group II and five out of 55 in group III (total UBTs = 169). The prevalence of H. pylori infection was 11% (7/61) in group I and 25.5% (14/50) in group II (P= 0.027). In group III, the prevalence of H. pylori infection was 16% (8/45), which was not significantly different from both group I and II. Sero-prevalence in group I was 18.6%, 27% in group II (ns) and 24% in group III. Mean age in the three groups was 35.9, 37.8 and 36.6 years, respectively (ns). In conclusion, the prevalence of H. pylori infection among intensive care nurses is lower in nurses from a unit using SDD compared to a non SDD-using unit. Acquisition of H. pylori by transmission from critically ill patients appears to be diminished through SDD use.

Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects.

OBJECTIVE: Impairment of haemostasis has been described with slowly degradable medium molecular weight hydroxyethyl starch (MMW-HES), whereas rapidly degradable MMW-HES is generally considered to have no important effects on blood coagulation. This study was undertaken to investigate the effects of a rapidly degradable MMW-HES plasma substitute on primary haemostasis and blood coagulation in human subjects. DESIGN: Randomised, cross-over study. SETTING: Research unit of a university hospital. PARTICIPANTS: Nine healthy, adult male volunteers. INTERVENTIONS: A 60-min intravenous infusion of 1 l HES 200/0.5/6 (HAES-steril 6%) or 4% albumin (control). MEASUREMENT AND RESULTS: The infusion of HES resulted in decreased circulating levels of von Willebrand factor antigen (from 85+/-8% to 59+/-6% after HES vs from 80+/-7% to 69+/-8% after albumin, p<0.05) and ristocetin cofactor activity (from 93+/-4 to 67+/-4% after HES vs from 79+/-5 to 75+/-5% after albumin, p<0.01). This was associated with an impairment of in vitro platelet function as determined with the PFA-100 platelet function analyser (closure time with collagen/epinephrine from 120+/-7 to 159+/-14 s after HES vs from 121+/-7 to 137+/-10 s after albumin, p<0.05; with collagen/ADP from 88+/-3 to 116+/-9 s and from 103+/-4 to 114+/-7 s after HES and albumin, respectively, p=0.01). CONCLUSIONS: The infusion of 1 l of HES 200/0.5/6 in healthy human subjects results in moderately decreased plasma levels of von Willebrand factor associated with impairment of platelet function.