Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members-A Multicenter, Multinational, Before-and-After Intervention Trial.

OBJECTIVES: To assess the feasibility and efficacy of implementing "Family Care Rituals" as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members. DESIGN: Prospective, before-and-after intervention evaluation. SETTING: Two U.S. academic medical ICU's, and one Italian academic medical/surgical ICU. SUBJECTS: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. INTERVENTIONS: A novel intervention titled "Family Care Rituals" during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay. MEASUREMENTS AND MAIN RESULTS: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge. CONCLUSIONS: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients.

Cardiac output: a central issue in patients with respiratory extracorporeal support.

The iLA-activve® Novalung is a new extracorporeal device specifically designed for lung support in patients with hypercapnic and/or hypoxemic respiratory failure. To date, only low-flow applications for decompensated hypercapnic chronic obstructive pulmonary disease have been reported in the literature. Here, we briefly report three cases of iLA-activve use in patients with hypercapnic-hypoxemic acute lung failure assisted with mid-flow (up to 2.4 L/min) and different single/double venous cannulation. The main findings of our small case series were: firstly, extracorporeal blood flows over 2.0 L/min across the membrane provided clinically satisfying decarboxylation and improved oxygenation; secondly, the ratio between blood flow through the membrane and the patient's cardiac output (CO) was a major determinant for the oxygen increase. The latter could, therefore, be a useful indicator for understanding performance in the complex and multifactorial evaluation of patients with extracorporeal veno-venous lung support.

Consensus guidelines on severe acute pancreatitis.

This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments.

How to manage aspergillosis in non-neutropenic intensive care unit patients.

Invasive aspergillosis has been mainly reported among immunocompromised patients during prolonged periods of neutropenia. Recently, however, non-neutropenic patients in the ICU population have shown an increasing risk profile for aspergillosis. Associations with chronic obstructive pulmonary disease and corticosteroid therapy have been frequently documented in this cohort. Difficulties in achieving a timely diagnosis of aspergillosis in non-neutropenic patients is related to the non-specificity of symptoms and to lower yields with microbiological tests compared to neutropenic patients. Since high mortality rates are typical of invasive aspergillosis in critically ill patients, a high level of suspicion and prompt initiation of adequate antifungal treatment are mandatory. Epidemiology, risk factors, diagnostic algorithms, and different approaches in antifungal therapy for invasive aspergillosis in non-neutropenic patients are reviewed.

FloTrac/Vigileo(TM) (third generation) and MostCare(®)/PRAM versus echocardiography for cardiac output estimation in vascular surgery.

OBJECTIVE: To compare the FloTrac/Vigileo(TM) cardiac output (COFT/V) and the MostCare(®)/PRAM cardiac output (COMC/P) versus transthoracic echocardiographic cardiac output estimation (reference method; CO(ECHO)). DESIGN: Prospective observational study. SETTING: Single center, Cardio-Thoracic and Vascular Surgery/Intensive Care Unit. PARTICIPANTS: Patients undergoing elective vascular surgery. INTERVENTIONS: Cardiac output measurement with two pulse contour methods: the FloTrac/Vigileo(TM) and the MostCare(®)/PRAM before (T1) and after (T2) fluid loading versus echocardiography (reference method). MEASUREMENTS AND MAIN RESULTS: One hundred fifty-six CO measurements were performed in 26 patients. The data showed poor agreement between CO(ECHO) and CO(FT/V): r(2) = 0.29 (T1) and 0.27 (T2); bias -0.37 (T1) and -0.40 (T2) L/min; limits of agreement from -3.10 to 2.42 (T1) and from -3.0 to 2.2 (T2) L/min. The percentage error was 51.7% (T1) and 49.3% (T2). Conversely, COMC/P resulted in agreement with echocardiography: r(2) = 0.76 (T1) and 0.80 (T2); bias -0.01 (T1) and -0.06 (T2) L/min; limits of agreement from -1.13 to 1.11 (T1) and from -0.90 to 0.80 (T2) L/min, with a PE of 22.4% (T1) and of 17.0% (T2). CONCLUSIONS: In patients undergoing vascular surgery, the FloTrac/Vigileo(TM) did not demonstrate that it was a reliable system for CO monitoring when compared with echocardiography-derived CO. However, MostCare(®)/PRAM was shown to estimate CO with a good level of agreement with echocardiographic measures.

A survey on infection management practices in Italian ICUs.

INTRODUCTION: An online survey was conducted to characterize current infection management practices in Italian intensive care units (ICUs), including the antibacterial and antifungal drug regimens prescribed for various types of infections. METHODS: During February and March 2011, all 450 ICUs in public hospitals in Italy were invited to take part in an online survey. The questionnaire focused on ICU characteristics, methods used to prevent, diagnose, and treat infections, and antimicrobials prescribing policies. The frequency of each reported practice was calculated as a percentage of the total number of units answering the question. The overall response rate to the questionnaire was 38.8% (175 of the 450 ICUs contacted) with homogeneous distribution across the country and in terms of unit type. RESULTS: Eighty-eight percent of the responding facilities performed periodical surveillance cultures on all patients. In 71% of patients, cultures were also collected on admission. Endotracheal/bronchial aspirates were the most frequently cultured specimens at both time points. Two-thirds of the responding units had never performed screening cultures for methicillin-resistant Staphylococcus aureus. Around 67% of the ICUs reported the use of antimicrobial de-escalation strategies during the treatment phase. In general, the use of empirical antimicrobial drug regimens was appropriate. Although the rationale for the choice was not always clearly documented, the use of a combination therapy was preferred over antibiotic monotherapy. The preferred first-line agents for invasive candidiasis were fluconazole and an echinocandin (64% and 25%, respectively). Two-thirds of the ICUs monitored vancomycin serum levels and administered it by continuous infusion in 86% of cases. For certain antibiotics, reported doses were too low to ensure effective treatment of severe infections in critically ill patients; conversely, inappropriately high doses were administered for certain antifungal drugs. CONCLUSIONS: Although infection control policies and management practices are generally appropriate in Italian ICUs, certain aspects, such as the extensive use of multidrug empirical regimens and the inappropriate antimicrobial dosing, deserve careful management and closer investigation.

[Antibiotics and artificial nutrition in the cardiac intensive care unit]. / Nutrizione e terapia antibiotica in terapia intensiva cardiologica.

Patients admitted to cardiac intensive care units are at high risk for infections, particularly nosocomial pneumonia, pacemaker's pocket and sternotomic wound infections. These complications delay recovery, prolong hospitalization, time on mechanical ventilation, and increase mortality. Both behavioral and pharmacological measures are needed to prevent and control infections in these patients, as well as specific antibiotic treatment and nutritional support. In infected critically ill patients, pathophysiological alterations modify distribution and clearance of antibiotics, and hypercatabolic state leads to malnutrition and immune paralysis, which both contribute to increased infectious risk and worsened outcome. A deep understanding of antibacterial agents pharmacology in the critically ill is essential in order to treat severe infections; moreover, it is necessary to know routes of administration and composition of artificial nutrition solutions. The aim of this review is to define main and specific aspects of antibiotic therapy and nutritional support in cardiac critical care patients in light of recent literature data.

Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.

CONTEXT: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. OBJECTIVE: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. DATA SOURCES: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. STUDY SELECTION: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. DATA EXTRACTION: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. RESULTS: We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P = .05; I(2) = 53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P < .001; I(2) = 0%). CONCLUSIONS: Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

Carbamylated erythropoietin is neuroprotective in an experimental model of traumatic brain injury.

OBJECTIVE: The well-documented neuroprotective effects of recombinant human erythropoietin (rhEPO) are commonly associated with untoward erythrocyte-stimulating effects (polycythemia), with subsequent risk of thromboembolic complications. A carbamylated-rhEPO (CEPO) derivative, which is neuroprotective but lacks hematopoietic activity, has been recently developed. In this study, we evaluated the neuroprotective capability of CEPO in an in vitro model of cerebral trauma in which rhEPO was previously shown to reduce posttraumatic cell death. DESIGN: Prospective, controlled experiment. SETTING: Animal, basic science laboratory. SUBJECTS: Wistar rats, 8 days old. INTERVENTIONS: Organotypic hippocampal slices, obtained from rat brains, were subjected to a well-characterized model of mechanical injury followed by addition of 10 IU/mL rhEPO, 10-100 IU/mL CEPO, or vehicle (injured control) to the incubation medium at different times to assess the temporal window of therapeutic neuroprotection. MEASUREMENTS AND MAIN RESULTS: Posttraumatic cell death was quantified at 12, 24, or 48 hrs after injury by measuring propidium iodide fluorescence in the selectively vulnerable CA1 hippocampal area. Posttraumatic injury, observed in injured, vehicle-treated hippocampal slices, was significantly attenuated by addition of either 10 IU/mL rhEPO or 10 IU/mL CEPO. The neuroprotective efficacy of 10 IU/mL rhEPO or CEPO remained intact even when administration was delayed 1 hr after trauma. Qualitative microscopy in semithin sections showed that both rhEPO and CEPO exerted a marked pyramidal neuron-sparing effect. CONCLUSION: Our study shows that 10 IU/mL CEPO exerts neuroprotective effects comparable with those of rhEPO in an in vitro model of mechanical cerebral trauma. Because CEPO lacks hematopoietic effects and seems to possess a prolonged therapeutic time window, this erythropoietin derivative may represent an exciting new pharmacologic tool in treating patients with mechanical injury to the brain.

Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion.

Pharmacokinetics and pharmacodynamics are significantly altered in critically ill septic patients and the risk of prolonged periods with concentrations below the minimum inhibitory concentration (MIC) and of low area under the serum concentration-time curve/MIC (AUC/MIC) ratios is of concern. We compared the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid administered by intermittent or continuous infusion in critically ill septic patients. Patients were divided into two groups: intermittent infusion (Group I) (600mg/12h); or continuous infusion (Group C) (300mg intravenous loading dose +900mg continuous infusion on Day 1, followed by 1200mg/daily from Day 2). Linezolid serum levels were monitored for 72h and microbiological data were collected. The clinical outcome was monitored. Sixteen patients completed the study. MICs of susceptible pathogens were 2mg/L for 80% of the isolates. In Group I, linezolid trough serum levels (C(min)) varied widely and were below the susceptibility breakpoint (4mg/L) during the study period; in 50% of patients C(min) was <1mg/L. In Group C, mean linezolid serum levels were more stable and, starting from 6h, were significantly higher than C(min) levels observed in Group I and were always above the susceptibility breakpoint. Time that the free drug concentration was above the MIC (T(free)>MIC) of>85% was more frequent in Group C than in Group I (P<0.05). Finally, with continuous infusion it was possible to achieve AUC/MIC values of 80-120 more frequently than with intermittent infusion (P<0.05). According to PK/PD parameters, continuous infusion has theoretical advantages over intermittent infusion in this population of patients.

Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism.

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. METHODS: The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. RESULTS: When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. CONCLUSIONS: These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.

Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness.

BACKGROUND: Many factors over which there may be little control may influence the response of a patient to therapy. However, therapy with antibiotics can be readily optimised. DISCUSSION: Concentration-dependent agents such as aminoglycosides appear effective and to entail fewer side effects when given in large, infrequent doses. There is also evidence that time-dependent antibiotics often fail to reach adequate concentrations throughout the treatment period. To date no randomised controlled prospective trial has demonstrated improvement in clinical outcome following infusion rather than intermittent boluses of time-dependent antibiotics. Critical illness alters antibiotic pharmacokinetics principally through increases in volume of distribution. Other than glycopeptides and aminoglycosides, antibiotic blood concentrations are rarely monitored and therefore adequate concentrations can only be inferred from clinical response. CONCLUSIONS: Failure to respond within the first few days of empirical treatment may be due to antibiotic resistance or inadequate doses. Therefore the same rigor should be applied to achieving adequate antibiotic concentrations as is applied to inotropes, which are titrated to achieve predetermined physiological targets.