Simone Piva

Chemokine detection in the cerebral tissue of patients with posttraumatic brain contusions

OBJECT The clinical outcome of patients with severe head injuries is still critically dependent on their secondary injuries. Although hypoxia and hypotension appear to mediate a substantial proportion of secondary injuries, many studies associate secondary brain injury with neuroinflammatory responses. Chemokines have been detected in the cerebrospinal fluid but not in the brain tissue of patients with head trauma. This study was performed to determine if chemokines were expressed in pericontusional brain tissue in patients with moderate or severe head trauma who underwent surgical evacuation of their brain contusions. METHODS Twelve patients with posttraumatic cerebral contusion requiring a surgical evacuation were studied. A 20- to 40-mg sample of white matter was removed from the surgical cavity in the pericontusional area. Two patients undergoing elective surgery for clip ligation of an unruptured aneurysm were used as controls. The median interval from trauma to biopsy procedure was 44 hours (range 3-360 hours). Total RNA was isolated from these samples and a ribonuclease protection assay was performed to measure the mRNA levels of several chemokines: CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, and XCL1. RESULTS The CCL2, a monocyte chemoattractant produced by activated astrocytes, was the most strongly expressed chemokine, followed by CXCL8, CCL3, and CCL4. The chemokines CXCL10 and CCL5 were expressed at very low levels, and XCL1 was not detected. CONCLUSIONS Chemokine activation occurs early after moderate or severe head trauma and is maintained for several days after trauma. This event may contribute to neuroinflammatory exacerbation of posttraumatic brain damage in the pericontusional brain tissue.

Quality of reporting of randomized controlled trials published in Intensive Care Medicine from 2001 to 2010

PurposeTo evaluate the methodological quality of randomized controlled trials (RCTs) published in Intensive Care Medicine from 2001 to 2010, and to compare it with a previous review of RCTs published from 1975 to 2000.MethodsWe assessed the quality of reporting of randomization, blinding and participant flow, both individually and combined within the Jadad scale, and compared them with findings from our previous review. For RCTs published from 2001 to 2010, we also evaluated the frequency of distorted finding presentation (spin) and inflated predicted treatment effect (delta inflation).ResultsIn the 221 RCTs from 2001 to 2010, the sample size was significantly larger than in the older series, and there was a higher proportion of studies with negative findings. Reporting of the rationale for sample size estimation and allocation concealment increased significantly, but reporting of other important individual methodological components did not change substantially compared with the previous period and remained low. Among RCTs from 2001 to 2010, a spin strategy was used in 69 of 111 RCTs with statistically negative results, while delta inflation was present in 7 of 11 RCTs evaluating survival as a primary outcome. Papers with higher Jadad scores were cited more often than the others.ConclusionsQuality of reporting of RCTs published in Intensive Care Medicine has only partly improved over time, and spin and delta bias are of frequent occurrence. There is a need for stronger adherence to CONSORT recommendations, with special emphasis on accurate description of randomization and blindness, and correct reporting of statistically non-significant results.

The Surgical Optimal Mobility Score predicts mortality and length of stay in an Italian population of medical, surgical, and neurologic intensive care unit patients

PURPOSE We validated the Italian version of Surgical Optimal Mobility Score (SOMS) and evaluated its ability to predict intensive care unit (ICU) and hospital length of stay (LOS), and hospital mortality in a mixed population of ICU patients. MATERIALS AND METHODS We applied the Italian version of SOMS in a consecutive series of prospectively enrolled, adult ICU patients. Surgical Optimal Mobility Score level was assessed twice a day by ICU nurses and twice a week by an expert mobility team. Zero-truncated Poisson regression was used to identify predictors for ICU and hospital LOS, and logistic regression for hospital mortality. All models were adjusted for potential confounders. RESULTS Of 98 patients recruited, 19 (19.4%) died in hospital, of whom 17 without and 2 with improved mobility level achieved during the ICU stay. SOMS improvement was independently associated with lower hospital mortality (odds ratio, 0.07; 95% confidence interval [CI], 0.01-0.42) but increased hospital LOS (odds ratio, 1.21; 95% CI: 1.10-1.33). A higher first-morning SOMS on ICU admission, indicating better mobility, was associated with lower ICU and hospital LOS (rate ratios, 0.89 [95% CI, 0.80-0.99] and 0.84 [95% CI, 0.79-0.89], respectively). CONCLUSIONS The first-morning SOMS on ICU admission predicted ICU and hospital LOS in a mixed population of ICU patients. SOMS improvement was associated with reduced hospital mortality but increased hospital LOS, suggesting the need of optimizing hospital trajectories after ICU discharge.

Neuroinflammation in Sepsis: Sepsis Associated Delirium

Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement of the central nervous system (CNS) during sepsis. The purpose of this review is to provide a concise overview of SAD including the epidemiology and current diagnostic criteria for SAD. We present in detail the pathophysiology with regards to blood-brain-barrier breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about 50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology of SAD is poorly understood, but involves microvascular, metabolic and, not least, inflammatory mechanisms leading to CNS dysfunction. These mechanisms can be different in SAD compared to ICU delirium associated with other conditions. SAD is diagnosed clinically using validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which have good specificity but low sensitivity. Neuroimaging studies and EEG (Electroencephalography) can be useful complement to clinical evaluation to define the severity of the condition. Prompt diagnosis and eradication of septic foci whenever possible is vital. Preventive measures for SAD in the critically ill patient requiring long-term sedation include maintaining light levels of sedation using non-benzodiazepine sedatives (either propofol or dexmedetomidine). Early mobilization of patients in the ICU is also recommended. Antipsychotic drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but firm evidence of their efficacy is lacking.

Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol for an international, multicentre, randomised controlled trial focused on goal-directed early mobilisation of surgical ICU patients.

Introduction Immobilisation in the intensive care unit (ICU) leads to muscle weakness and is associated with increased costs and long-term functional disability. Previous studies showed early mobilisation of medical ICU patients improves clinical outcomes. The Surgical ICU Optimal Mobilisation Score (SOMS) trial aims to test whether a budget-neutral intervention to facilitate goal-directed early mobilisation in the surgical ICU improves participant mobilisation and associated clinical outcomes. Methods and analysis The SOMS trial is an international, multicentre, randomised clinical study being conducted in the USA and Europe. We are targeting 200 patients. The primary outcome is average daily SOMS level and key secondary outcomes are ICU length of stay until discharge readiness and ‘mini’ modified Functional Independence Measure (mmFIM) at hospital discharge. Additional secondary outcomes include quality of life assessed at 3 months after hospital discharge and global muscle strength at ICU discharge. Exploratory outcomes will include: ventilator-free days, ICU and hospital length of stay and 3-month mortality. We will explore genetic influences on the effectiveness of early mobilisation and centre-specific effects of early mobilisation on outcomes. Ethics and dissemination Following Institutional Review Board (IRB) approval in three institutions, we started study recruitment and plan to expand to additional centres in Germany and Italy. Safety monitoring will be the domain of the Data and Safety Monitoring Board (DSMB). The SOMS trial will also explore the feasibility of a transcontinental study on early mobilisation in the surgical ICU. Results The results of this study, along with those of ancillary studies, will be made available in the form of manuscripts and presentations at national and international meetings. Registration This study has been registered at clinicaltrials.gov (NCT01363102).

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle.

Objectives: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. Design: Worldwide online survey. Setting: Intensive care. Intervention: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. Measurement and Main Results: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was “prescribed” by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. Conclusions: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.

Determination of Imminent Brain Death Using the Full Outline of Unresponsiveness Score and the Glasgow Coma Scale: A Prospective, Multicenter, Pilot Feasibility Study

Purpose: To evaluate the accuracy of the imminent brain death (IBD) diagnosis in predicting brain death (BD) by daily assessment of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale (GCS) with the assessment of brain stem reflexes. Materials and Methods: Prospective multicenter pilot study carried out in 5 adult Italian intensive care units (ICUs). Imminent brain death was established when the FOUR score was 0 (IBD-FOUR) or the GCS score was 3 and at least 3 among pupillary light, corneal, pharyngeal, carinal, oculovestibular, and trigeminal reflexes were absent (IBD-GCS). Results: A total of 219 neurologic evaluations were performed in 40 patients with deep coma at ICU admission (median GCS 3). Twenty-six had a diagnosis of IBD-FOUR, 27 of IBD-GCS, 14 were declared BD, and 9 were organ donors. The mean interval between IBD diagnosis and BD was 1.7 days (standard deviation [SD] 2.0 days) using IBD-FOUR and 2.0 days (SD 1.96 days) using IBD-GCS. Both FOUR and GCS had 100% sensitivity and low specificity (FOUR: 53.8%; GCS: 50.0%) in predicting BD. Conclusions: Daily IBD evaluation in the ICU is feasible using FOUR and GCS with the assessment of brain stem reflexes. Both scales had 100% sensitivity in predicting IBD, but FOUR may be preferable since it incorporates the pupillary, corneal, and cough reflexes and spontaneous breathing that are easily assessed in the ICU.

The IN-PANCIA Study: Clinical Evaluation of Gastrointestinal Dysfunction and Failure, Multiple Organ Failure, and Levels of Citrulline in Critically Ill Patients

Purpose: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. Materials and Methods: This is a 1-year, monocentric (Italian hospital), prospective observational study. Inclusion criteria were adult patients with GID/GIF, with or without MOF. The GIF score was daily evaluated in 39 critically ill patients. Amino acids were measured at the time of GID or GIF. Results: We enrolled 39 patients. Nine patients developed GID and 7 GIF; 6 of patients with GID/GIF developed MOF. Citrulline was lower (P < .001) in patients with GID/GIF (11.3 [4.4] µmol/L), compared to patients without GID/GIF (22.4 [6.8] µmol/L); likewise, glutamine was lower in patients with GID/GIF, whereas arginine was nonstatistically different between the 2 groups. Intra-abdominal pressure was higher in patients affected by MOF (13.0 [2.2] mm Hg) than in patients with GIF/GID without MOF (9.6 [2.6] mm Hg) and compared to patients without GID/GIF (7.2 [2.1] mm Hg). Conclusions: Both GID and GIF in critically ill patients are associated with low levels of citrulline and glutamine, which could be considered as markers of small bowel dysfunction. The higher the GIF score, the lower the citrulline levels. Patients affected by MOF had higher levels of intra-abdominal pressure.