Search

Objective Impaired arousal is associated with negative outcomes in intensive care units, but studies in acute medical wards are scanty. The study aim was to evaluate the association between impaired arousal, as measured using an ultrabrief screen, and risk of both 1- and 6-month mortality and discharge to nursing home (NH) or hospice. Design Prospective cohort study with 6-month follow-up. Setting An acute geriatric unit (AGU) of a university-based hospital in Northern Italy. Participants All patients aged 65 years or older, admitted to the AGU between September 2012 and February 2015. Measurements The modified Richmond Agitation Sedation Scale (m-RASS) was used to assess patients' arousal; a score of 0 denotes normal arousal, scores ranging from +1 to +4 denote increased arousal, and scores ranging from −1 to −5 denote decreased levels. The association of m-RASS scores with 6-month mortality was assessed by a Kaplan-Meier analysis. The impact of impaired arousal, defined by the m-RASS as anything other than “awake and alert,” was determined using Cox proportional hazard regression for 1- and 6-month mortality after admission and logistic regressions were used for discharge to NH or hospice. The models were adjusted for age, sex, dementia, Sequential Organ Failure Assessment score, and disability. Results Patients (n = 2477) had a mean age of 84 years, and were predominantly women (59.8%). Impaired arousal on admission was present in 644 (25.9%) patients: 33 (1.3%) were comatose (m-RASS = −5), 56 (2.3%) awakened to pain only (m-RASS = −4), 43 (1.7%) were very drowsy (m-RASS = −3), 93 (3.8%) drowsy (m-RASS = −2), and 212 (8.6%) were slightly drowsy (m-RASS = −1), but there were also 110 (4.4%) patients with restlessness, 75 (3.0%) with agitation, 17 (0.7%) with severe agitation, and 3 (0.1%) with combative behavior. Globally, 337 patients died within 1 month and 689 patients within 6 months. After adjustment for covariates, patients with impaired arousal had a significantly higher chance of having died at 1-month (adjusted hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.22–2.03) and 6-month follow-up (adjusted HR 1.31, 95% CI 1.10–1.57). Those with impaired arousal were more likely to be discharged to a new NH (odds ratio [OR] 1.75, 95% CI 1.19–2.57) or to hospice (OR 1.96, 95% CI 1.18–3.23) than those without impaired arousal. Conclusions An abnormal arousal level is an independent predictor of increased risk of 1- and 6-month mortality and of discharge to a new NH or hospice. The assessment of arousal with m-RASS should be routinely performed on all older patients on admission to acute hospital wards to screen potentially critical conditions.

Purpose of review To describe the incidence, major risk factors, and the clinical, electrophysiological, and histological features of critical illness myopathy (CIM). Major pathogenetic mechanisms and long-term consequences of CIM are also reviewed. Recent findings CIM is frequently associated with critical illness polyneuropathy (CIP), and may have a relevant impact on patients' outcome. CIM has an earlier onset than CIP, and recovery is faster. Loss of myosin filaments on muscle biopsy is important to diagnose CIM, and has a good prognosis. Critical illness, use of steroids, and immobility concur in causing CIM. Summary A rationale diagnostic approach to CIM using clinical, electrophysiological, and muscle biopsy investigations is important to plan adequate therapy and to predict recovery.

Objective: To define the electrophysiologic tests to diagnose critical illness myopathy and critical illness polyneuropathy in intensive care unit patients. Design: Literature review. Measurements and Main Results: Critical illness myopathy and neuropathy are common complications in the critically ill patient. Myopathy and neuropathy are equally common, and often coexist. Electrophysiological alterations of peripheral nerves and muscle have an early onset in the first days of intensive care unit stay or shortly after sepsis, and precede the structural alterations. Conventional electrophysiologic evaluation can be performed easily on most intensive care unit patients, including patients with altered consciousness; in conjunction with direct muscle stimulation, it can differentiate myopathy from neuropathy, which might be important to define the long-term prognosis. However, electrophysiologic tests are not universally available; their interpretation requires special expertise; and their application is time consuming. A recently proposed simplified test of peroneal nerve stimulation could be used as a screening method to select patients who merit in-depth neurologic evaluation. Conclusions: Early identification of neuromuscular alterations by means of electrophysiologic tests may be of value for targeted treatments and to anticipate the risk of short-term disability. Complete neurologic and electrophysiological evaluation is important to define the risk of long-term disability after intensive care unit discharge.

Reduction of cerebral blood flow plays a crucial role in causing posttraumatic cerebral ischemia. However, the methodologic adequacy of studies from which currently used cerebral blood flow thresholds in traumatic brain injury have been derived has not been evaluated.To systematically evaluate the evidence available on cerebral blood flow thresholds and its methodologic adequacy in adults with traumatic brain injury.Included were primary studies on adults with traumatic brain injury in which cerebral blood flow thresholds were evaluated and reported, and follow-up brain computed tomography or magnetic resonance imaging was used as the gold standard for diagnosing the finally infarcted area.Among the 53 diagnostic studies identified, 31 did not report any threshold value, whereas 20 studies used thresholds derived from the literature, mainly animal or clinical studies on ischemic stroke. One study measured cerebral blood flow thresholds, but did not use accepted neuroradiological criteria for the diagnosis of posttraumatic cerebral ischemia. The remaining study fulfilled all methodologic inclusion criteria, but was restricted to 14 patients with severe traumatic brain injury and cerebral contusion. This study proposed a cerebral blood flow threshold of 15 mL/100 mL/min, with sensitivity and specificity of 43% and 95%, respectively.Cerebral blood flow thresholds for the diagnosis of posttraumatic cerebral ischemia are based on weak evidence, and cannot be recommended.

Objective: The pressure–volume index (PVI) can be used to assess the cerebrospinal fluid dynamics and intracranial elastance in critically ill brain injured patients. The dependency of PVI on the state of cerebral autoregulation within the physiologic range of cerebral perfusion pressure (CPP) can be described by mathematical models that account for changes in cerebral blood volume during PVI testing. This relationship has never been verified clinically using direct PVI measurement and independent cerebral autoregulation assessment. Design, setting, and patients: PVI and cerebral autoregulation were prospectively assessed in a cohort of 19 comatose patients admitted to an academic intensive care unit in Brescia, Italy. Intervention: None. Methods: PVI was measured injecting a fixed volume of 2 ml of 0.9% sodium chloride solution into the cerebral ventricles through an intraventricular catheter. Cerebral autoregulation was assessed using transcranial Doppler transient hyperaemic response (THR) test. Measurements and results: Fiftynine PVI assessments and 59 THR tests were performed. Mean PVI was 20.0 (SD 10.2) millilitres in sessions when autoregulation was intact (THR test C1.1) and 31.6 (8.8) millilitres in sessions with defective autoregulation (THR test\1.1) (DPVI = 11.7 ml, 95% CI = 4.7–19.3 ml; P = 0.002). Intracranial pressure, CPP and brain CT findings were not significantly different between the measurements with intact and disturbed autoregulation. Conclusions: Cerebral autoregulation status can affect PVI estimation despite a normal CPP. PVI measurement may overestimate the tolerance of the intracranial system to volume loads in patients with disturbed cerebral autoregulation.

Background and objectiveStewart’s and Fencl’s methods have recently been proposed to interpret acid–base disorders where traditional theory has proven inadequate. Our objectives were to evaluate: (1) the occurrence of acid–base disturbances in critically ill patients and their trend over the first 3 intensive care unit days, (2) whether Stewart’s theory offers advantages over the traditional theory in the diagnosis of acid–base metabolic disturbances and (3) whether variables derived from Stewart’s and Fencl’s methods offer advantages over the traditional method to predict patient mortality.MethodsA prospective cohort study in a general intensive care unit. Blood samples were analysed for arterial blood gases, electrolytes and proteins. PaCO2, pH, bicarbonate, base excess, standard base-excess, sodium, potassium, chloride, phosphorous, calcium, magnesium and lactate were measured. Anion gap, Stewart’s and Fencl’s variables were calculated.ResultsWhen using Stewart’s method, metabolic acidosis and metabolic alkalosis were found in 92.9% and 93.4% of samples, respectively. Corresponding figures obtained with the traditional method were 15% and 18.7%. In 245 (64.5%) samples, Stewart’s method revealed that metabolic acidosis and alkalosis were simultaneously present, whereas the traditional method revealed a normal acid–base status. Strong ion gap increased significantly over the first 3 intensive care unit days. Strong ion gap and lactate were independent predictors of 28-day mortality.ConclusionsMetabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

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.

Data regarding the efficacy of programmes to control meticillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) are limited. We performed an observational 'before-and-after' study to evaluate the search-and-destroy (SD) strategy as compared with SD and isolation (SDI), to control MRSA in a general ICU. SD included active surveillance, contact precautions and treatment of carriers; in SDI, isolation or cohorting were added. Three phases were identified: period 1 (p1), 1996-1997, before the introduction of programme; period 2 (p2), 1998-2002, with SD programme; period 3 (p3), 2003-2005, with SDI in a new ICU. During the 10 years of the study we observed 3978 patients; 667, 1995 and 1316 patients in p1, p2 and p3 respectively. The numbers of MRSA-infected patients were 19 in p1, 23 in p2, and 6 in p3. The infection rate was 3.5, 1.7 and 0.7 cases per 1000 patient-days in p1, p2 and p3, respectively; a significant reduction was observed between p1 vs p2 (P=0.024) and p2 vs p3 (P=0.048), although the latter was not confirmed by a segmented regression analysis. The proportion of ICU-acquired MRSA cases was 80%, 77% and 52% during p1, p2 and p3, respectively (P=0.0001 for trend). The proportion of S. aureus isolates resistant to meticillin was 51%, 32% and 23% during p1, p2 and p3, respectively (P0.0001 for trend). SD strategy was effective in significantly reducing MRSA infection, transmission rates and proportion of meticillin resistance in an ICU with endemic MRSA. SDI may further enhance SD efficacy.

Muscle weakness is common in the surgical intensive care unit (ICU). Low muscle mass at ICU admission is a significant predictor of adverse outcomes. The consequences of ICU-acquired muscle weakness depend on the underlying mechanism. Temporary drug-induced weakness when properly managed may not affect outcome. Severe perioperative acquired weakness that is associated with adverse outcomes (prolonged mechanical ventilation, increases in ICU length of stay, and mortality) occurs with persistent (time frame: days) activation of protein degradation pathways, decreases in the drive to the skeletal muscle, and impaired muscular homeostasis. ICU-acquired muscle weakness can be prevented by early treatment of the underlying disease, goal-directed therapy, restrictive use of immobilizing medications, optimal nutrition, activating ventilatory modes, early rehabilitation, and preventive drug therapy. In this article, the authors review the nosology, epidemiology, diagnosis, and prevention of ICU-acquired weakness in surgical ICU patients.

Donation after circulatory death (DCD) is a valuable option for the procurement of functioning organs for transplantation. Clinical results are promising and public acceptance is quite good in most western countries. Yet, although DCD is widespread in Europe, several problems still persist in Italy as well as in some other countries. This paper aims to describe the main clinical, organisational, ethical and legal issues at stake, bearing in mind the particular situation created by Italian legislation. Currently, as regards DCD, Italy is somewhat different from other countries. Therefore, every effort should be made for the safe and effective implementation of DCD programs: uncontrolled DCD programs should be promoted and encouraged, within the framework of shared and authoritative rules. At the same time, we need to tackle the question of controlled DCD, promoting debate among all involved subjects regarding the fundamental issues of end-of-life care within protocols that best integrate the highest standard of care for the dying and the legitimate interests of those awaiting a life-saving organ.

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.

Dear Editor, We thank Dr. Lazaridis very much for his insightful comments [1] on our paper [2]. In response, we would like to stress some concepts. First, to our knowledge, in controlled donation after circulatory death (cDCD) programs (absence of previous cardiopulmonary resuscitation) no case of autoresuscitation has ever been reported after 2–5 min of absence of circulation [3]. Thus, logically, at least 2 min should be used as a clear indicator of irreversibility. Second, the no-touch period is a morally and socially important defense against suspicions of possible donor exploitation: vital support is withdrawn according to the donors’ wishes (usually reported by their next of kin) and organs are retrieved without undue interference in the process of dying after declaration of death using circulatory criteria (irreversible cessation of circulation). The donor is always treated as a means in itself and the donor’s dignity is continuously promoted. Third, the 2 vs. 5 min no-touch period debate is above all a cultural issue. In the absence of widespread agreement, a 5-min period represents an adequate compromise because it better ensures confirmation of a spontaneously irrecoverable and sufficiently advanced dying process (a safeguard in the eyes of the relatives) and because it is unlikely to materially affect any subsequent organ function. A 5-min no-touch period is, therefore, a clinically and operationally workable tutioristic option. We think that, at this stage, it is socially unsafe to abandon the dead donor rule in favor of a more aggressive policy. Accordingly, we stress the importance of an adequate no-touch period, which can neither be too short (autoresuscitation should be excluded) or too long (organ protection is jeopardized). Finally, Dr. Lazaridis writes about ‘‘minimizing harms by performing the procurement under general anesthesia’’. This concept is not acceptable to us. Certainly, adequate sedation is a mandatory step for withdrawal of life support during end-of-life care in conscious patients. Yet great care must be taken in order to avoid any interference with the patient’s ability to ventilate spontaneously. For this reason, general anesthesia administered before forgoing life support is morally and legally quite problematic (if combined with muscleblocking agents, it would be considered the direct cause of death). After cessation of circulation, general anesthesia is both impossible (there is no circulation carrying any drug to the brain) and illogical (noone would consider giving anesthesia to a cadaver). In this complex field, therefore, we contend that the Roman advice festina lente (hasten slowly) continues to provide sensible guidance. Compliance with ethical standards

Objective: Use of external ventricular drains and lumbar catheters is associated with a risk of ventriculitis and meningitis ranging from 2% to 24% because of lack of standardized diagnostic criteria. We evaluated the prevalence of ventriculitis or meningitis in 13 Italian ICUs. Design: Multicenter, prospective study. Setting: Thirteen Italian ICUs. Patients: Two hundred seventy-one patients (mean age, 57 yr) receiving a total number of 311 catheters. Two hundred fifty patients (92.2%) had an external ventricular drain, 17 patients (6.3%) had a lumbar catheter, and four patients (1.5%) had both external ventricular drain and lumbar catheter. Interventions: ICUs enrolled at least 10 consecutive adult patients with an external ventricular drain or lumbar catheter in place for more than 24 hours. Confirmed cerebrospinal fluid infection was defined by presence of a positive cerebrospinal fluid culture, a cerebrospinal fluid/blood glucose ratio less than 0.5, a neutrophilic cerebrospinal fluid pleocytosis (> 5 cells/?L), and fever. Abnormal cerebrospinal fluid findings with negative cultures were defined as suspected infection. Measurements and Main Results: Median duration of device use was 13 days (interquartile range, 8-19). Fifteen patients (5.5%) had a confirmed ventriculitis or meningitis, and 15 patients (5.5%) had a suspected ventriculitis or meningitis. Cerebrospinal fluid glucose and cerebrospinal fluid/blood glucose ratio were lower in patients with confirmed ventriculitis or meningitis and suspected ventriculitis or meningitis; proteins and lactates were significantly higher in confirmed ventriculitis or meningitis. Gram-negative and Gram-positive bacteria were equally cultured. Risk factors for infection were a concomitant extracranial infection (odds ratio, 2.34; 95% CI, 1.01-5.40; p = 0.05) and placement of catheters outside the operation room (odds ratio, 4.01; 95% CI, 0.98-16.50; p = 0.05). Conclusions: Ventriculitis or meningitis remains a problem in Italian ICUs, and a strategy for reducing the prevalence is worth planning.

A gain-scheduled proportional-integral-derivative controller is proposed for the closed-loop dosing of propofol in anesthesia (with the bispectral index as a controlled variable). In particular, it is shown that a different tuning of the parameters should be used during the infusion and maintenance phases. Further, the role of the noise filter is investigated.

Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity., Sepsis patients often develop muscle atrophy that can last for years. Here the authors show in a mouse model that sepsis causes long-term impairment of the satellite cells, affecting mitochondrial function and energy metabolism, and that injection of mesenchymal stem cells restores satellite cell metabolism and muscle regeneration.

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.

Background and Purpose— Cerebral blood flow (CBF) reduction below critical thresholds discriminates between irreversible infarct core, penumbra, and benign oligemia (penumbra that recovers spontaneously). Thresholds are based on animal studies, and their diagnostic accuracy in humans has never been established. The purpose of this study was to assess the evidence available on CBF thresholds for infarct core and penumbra in adult stroke patients. Methods— Electronic database searching using Medline, Embase and the Cochrane Library, crosschecking of references, and contact with experts and authors of primary studies was used. Studies on adult stroke patients were included if they compared CBF measurements with a diagnostic gold standard (follow-up brain CT/MRI), and reported CBF thresholds. Two reviewers independently extracted the data and assessed study quality. Results— A meta-analysis could not be carried out because of insufficient data. The optimal reported CBF thresholds varied widely, from 14.1 to 35.0 and from 4.8 to 8.4 mL/100 g per minute for penumbra and infarct core, respectively. Conclusions— The use of CBF thresholds in commercial software for imaging methods cannot be recommended without further evaluation.

To investigate the impact of critical illness polyneuropathy and critical illness myopathy on short-term and long-term patient outcome.In the acute-care setting, critical illness polyneuropathy and critical illness myopathy are important causes of acute paralysis in critically ill comatose patients, and may cause inappropriately pessimistic prognoses. Duration of weaning from artificial ventilation is 2 to 7 times greater in patients with critical illness polyneuropathy than in patients without critical illness polyneuropathy. After intensive care unit and hospital discharge, many patients diagnosed with critical illness polyneuropathy or critical illness myopathy are reported to complain of profound muscle weakness. Chronic disability was a common finding among them. Complete functional recovery with patients regaining the ability to breathe spontaneously and to walk independently was reported in 180 of 263 patients (68.4%); severe disability with tetraparesis, tetraplegia, or paraplegia was reported in 74 patients (28.1%). Persisting milder disabilities were common even in patients with complete functional recovery, and included reduced or absent deep tendon reflexes, stocking and glove sensory loss, muscle atrophy, painful hyperesthesia, and foot drop. An association of critical illness polyneuropathy and critical illness myopathy with increased intensive care unit and hospital mortality has been demonstrated only in selected intensive care unit populations; data are insufficient to demonstrate any association with long-term mortality.Intensive care unit-acquired critical illness polyneuropathy and critical illness myopathy influence the evaluation of acutely ill comatose patients and may instigate unreasonably pessimistic prognosis. Critical illness polyneuropathy and critical illness myopathy are an important cause of difficult weaning of patients from the ventilator and of persisting muscle weakness and disability after intensive care unit discharge.

Profound muscle weakness during and after critical illness is termed intensive care unit-acquired weakness (ICUAW).To develop diagnostic recommendations for ICUAW.A multidisciplinary expert committee generated diagnostic questions. A systematic review was performed, and recommendations were developed using the Grading, Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Severe sepsis, difficult ventilator liberation, and prolonged mechanical ventilation are associated with ICUAW. Physical rehabilitation improves outcomes in heterogeneous populations of ICU patients. Because it may not be feasible to provide universal physical rehabilitation, an alternative approach is to identify patients most likely to benefit. Patients with ICUAW may be such a group. Our review identified only one case series of patients with ICUAW who received physical therapy. When compared with a case series of patients with ICUAW who did not receive structured physical therapy, evidence suggested those who receive physical rehabilitation were more frequently discharged home rather than to a rehabilitative facility, although confidence intervals included no difference. Other interventions show promise, but fewer data proving patient benefit existed, thus precluding specific comment. Additionally, prior comorbidity was insufficiently defined to determine its influence on outcome, treatment response, or patient preferences for diagnostic efforts. We recommend controlled clinical trials in patients with ICUAW that compare physical rehabilitation with usual care and further research in understanding risk and patient preferences.Research that identifies treatments that benefit patients with ICUAW is necessary to determine whether the benefits of diagnostic testing for ICUAW outweigh its burdens.

Increased survival of critically ill patients has focused the attention on secondary complications of intensive care unit (ICU) stay, mainly ICU-acquired weakness (ICUAW). ICUAW is relatively common with significant impact on recovery. Prolonging mechanical ventilation and overall hospitalization time, increased mortality, and persistent disability are the main problems associated with ICUAW. The chapter deals mainly with the differential diagnosis of neuromuscular generalized weakness that develops in the ICU, but focal ICUAW is reviewed too. The approach to the diagnosis and the yield of various techniques (mainly electrophysiological and histological) is discussed. Possible therapeutic interventions of this condition that modify the course of this deleterious situation and lead to better rehabilitation are discussed. The current postulated mechanisms associated with ICUAW (mainly the more frequent critical illness neuropathy and myopathy) are reviewed.

OBJECTIVE To evaluate, in a prospective, observational study, whether bilateral monitoring of jugular bulb oxyhemoglobin saturation (SjO2), in addition to standard monitoring, results in modification of the management of severe head trauma. METHODS The patients underwent bilateral jugular bulb cannulation and observation at 8-hour intervals, during which SjO2 was measured and the neurological condition and physiological variables were assessed. The study group was responsible for evaluating whether the physician's decision-making process was influenced by the detection of SjO2 abnormalities. The SjO2 discrepancy in simultaneous bilateral samples was also evaluated to determine whether it interfered with the interpretation of data and with clinical decision-making. The SjO2-related complications were monitored. RESULTS Thirty patients underwent 319 observations. In 96% of patients, SjO2 was normal or high and had no influence on the diagnostic or therapeutic strategies. Treatment decisions were dictated by changes in clinical status and in intracranial and cerebral perfusion pressure. When these parameters were abnormal, treatment was administered, even if SjO2 was normal (101 observations). Conversely, when SjO2 was the only detected abnormality (34 observations), no treatment was administered. Abnormally low SjO2 values, caused by hypovolemia and hypocapnia, were detected in 3.4% of observations and actually modified the management. The discrepancies in simultaneous bilateral samples were substantial and gave rise to relevant interpretation problems. Fifteen percent of jugular catheters showed evidence of bacterial colonization. CONCLUSION Intermittent SjO2 monitoring did not substantially influence the management of severe head trauma. Therefore, recommendation for its routine use in all patients seems inadvisable, and indications for this invasive method should no longer be defined on the basis of experts' opinions, but rather on randomized, prospective studies.

OBJECTIVE AND IMPORTANCE: Cerebral venous and dural sinus thrombosis is a rare cause of stroke. Although morbidity and mortality have greatly decreased in recent years as a result of early diagnosis and timely medical treatment, when coma occurs the prognosis remains poor. We evaluated whether emergent decompressive craniectomy has a role in the treatment of patients with brain herniation from dural sinus thrombosis and hemorrhagic infarct. CLINICAL PRESENTATION: Three patients developed large hemorrhagic infarct with coma and bilaterally fixed and dilated pupils resulting from aseptic dural sinus thrombosis. INTERVENTION: Two patients underwent emergent surgical decompression as soon as brain herniation developed, and these patients had complete functional recovery. One underwent delayed surgical decompression and remained severely disabled. CONCLUSION: Our results provide preliminary evidence that emergent decompressive craniectomy is effective in patients with brain herniation from dural sinus thrombosis, provided that the clinical onset is recent. We therefore recommend consideration of this aggressive surgical technique for such patients, who may survive with good outcomes.

Increased survival of critically ill patients has focused the attention on secondary complications of intensive care unit (ICU) stay, mainly ICU-acquired weakness (ICUAW). ICUAW is relatively common with significant impact on recovery. Prolonging mechanical ventilation and overall hospitalization time, increased mortality, and persistent disability are the main problems associated with ICUAW. The chapter deals mainly with the differential diagnosis of neuromuscular generalized weakness that develops in the ICU, but focal ICUAW is reviewed too. The approach to the diagnosis and the yield of various techniques (mainly electrophysiological and histological) is discussed. Possible therapeutic interventions of this condition that modify the course of this deleterious situation and lead to better rehabilitation are discussed. The current postulated mechanisms associated with ICUAW (mainly the more frequent critical illness neuropathy and myopathy) are reviewed.

Background The exact pathophysiology of the development and rupture of saccular aneurysms is still controversial. Several lines of evidence indicate a role for inflammatory processes. Similarly, abnormal angiogenesis might be related to aneurysm growth. Expression of angiogenesis factors is higher in patients harboring aneurysms. The aim of this study was to verify the association of two functionally active polymorphisms (+ 396 C>T and 18 bp microdeletion) in the vascular endothelial growth factor (VEGF) gene with both susceptibility to and clinical features of aneurysmal subarachnoid hemorrhage (SAH) in an Italian population. Method Allelic and genotypic frequencies of the+396 C>T and the 18 bp microdeletion of the VEGF gene were determined in 200 patients and 200 healthy controls. Results Both allelic and genotypic frequencies of the examined polymorphisms in the VEGF gene were not significantly different between cases and controls. Furthermore, the different VEGF genotypes did not seem to significantly modify the main clinical features of the disease. Conclusions Our data suggest that the VEGF gene is not a major genetic risk factor for aneurysmal subarachnoid hemorrhage.

BackgroundDegeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF.MethodsWe enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (≥ 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay.ResultsOf the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia.ConclusionsSmall fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients.

Background In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. Methods This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. Results All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. Conclusions Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study.

More recent severity scores should be more reliable than older ones because they account for the improvement in medical care over time. To provide more insight into this issue, we compared the predictive ability of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 (originally developed from data collected in 1991–1992 and 2002, respectively) on a sample of critically ill patients. This was a prospective observational study on 3,661 patients from 103 Italian intensive care units. Standardized mortality ratios (SMRs) were calculated. Assessment of calibration across risk classes was performed using the GiViTI calibration belt. Discrimination was evaluated by means of the area under the receiver operating characteristic analysis. Both scores were shown to discriminate fairly. SAPS 3 largely overpredicted mortality, more than SAPS II (SMR 0.63, 95 % CI 0.60–0.66 vs. 0.87, 95 % CI 0.83–0.91). This result was consistent and statistically significant across all risk classes for SAPS 3. SAPS II did not show relevant deviations from ideal calibration in the first two deciles of risk, whereas in higher-risk classes it overpredicted mortality. Both scores provided unreliable predictions, but unexpectedly the newer SAPS 3 turned out to overpredict mortality more than the older SAPS II.

BACKGROUND AND OBJECTIVES Continuous assessment of the cerebrovascular autoregulation (CVA) through use of the pressure reactivity index (PRx), a moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure, has been effective in optimizing cerebral perfusion pressure (CPPopt) in traumatic brain injured (TBI) patients. This study investigates the feasibility of measuring CPPopt in patients with aneurysmal subarachnoid hemorrhage (aSAH) by continuously assessing the CVA. METHODS Twenty-nine aSAH patients were enrolled, and data from CVA status, CPPopt, and periods when CPP was below, within, or above CPPopt were computed daily. Outcome was assessed at 6 months with the Glasgow Outcome Scale. Mann-Whitney U test was used to analyze differences in the duration of impaired CVA and duration of CPP below CPPopt in patients with good and poor outcomes. Multivariable logistic regression analysis was used to identify independent predictors of outcome. RESULTS CVA monitoring data were available for all 29 patients with a total monitoring time of 2757 h. The duration of impaired CVA was 36.5% (interquartile range: 24.6 to 49.8) of the total monitoring time in 15 patients with good outcome and 71.6% of the total monitoring time (51.2 to 80.0) in 14 patients with poor outcome (Mann-Whitney U test 3.295, P=0.0010). PRx-based CPPopt could be identified in 26 patients (89.6%) with a total monitoring time of 2691 h. The duration of CPP below the CPPopt range was 28.0% (interquartile range: 18.0 to 47.0) of the total monitoring time in patients with good outcome and 76.0% (48.5 to 82.5) in patients with poor outcome (Mann-Whitney U test 2.779, P=0.0054). Glasgow Coma Scale score and duration of impaired CVA were independently associated with 6-month outcome (Glasgow Coma Scale score odds ratio: 1.95, 95% confidence interval: 1.01-3.75; duration of impaired CVA odds ratio: 0.88, 95% confidence interval: 0.78-0.99). CONCLUSIONS The assessment of CVA and CPPopt is feasible in aSAH patients and may provide important information regarding long-term outcome. A PRx above the 0.2 threshold and a CPP below the CPPopt range are associated with worse outcome.

Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of critical illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are critically ill and cause chronic disability in survivors of critical illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of critical illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

Background Trigeminal neuralgia is usually caused by microvascular conflict with the fifth cranial nerve in the pontocerebellar angle. Rarely is it secondary to other extra-axial or intra-axial lesions. Few cases of trigeminal neuralgia due to cavernous angiomas have been reported in the literature. This is the first report of surgical decompression of the intra-axial trigeminal nerve tract from a deep pontine cavernous angioma. Methods A 45-year-old man came to our attention for frequent and intense left facial pain episodes compatible with trigeminal neuralgia in the V1 and V2 branches, poorly responsive to carbamazepine treatment. Magnetic resonance imaging revealed a left posterolateral pontine cavernous angioma. No neurovascular conflict was found. Results The cavernous angioma was surgically excised. No new neurological deficit arose and the pain episodes completely disappeared. Conclusions Trigeminal neuralgia can occur occasionally secondary to the compressive effect of a pontine cavernous angioma. In this patient surgical removal of the cavernous angioma can be considered a successful and relatively safe treatment.

Pandemic H1N1 influenza is projected to be unprecedented in its scope, causing acute critical illness among thousands of young otherwise healthy adults, who will need advanced life support. Rigorous, relevant, timely, and ethical clinical and health services research is crucial to improve their care and outcomes. Studies designed and conducted during a pandemic should be held to the same high methodologic and implementation standards as during other times. However, unique challenges arise with the need to conduct investigations as efficiently as possible, focused on the optimal outcome for the individual patient, while balancing the need for maximal societal benefit. We believe that clinical critical care research during a pandemic must be approached differently from research undertaken under nonemergent circumstances. We propose recommendations to clinical investigators and research ethics committees regarding clinical and health services research on pandemic-related critical illness. We also propose strategies such as expedited and centralized research ethics committee reviews and alternate consent models.