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Patients recovering from critical illness may be left with significant muscle mass loss. This study aimed to evaluate whether a 6-week program of enhanced physiotherapy and structured exercise (PEPSE) and an essential amino acid supplement drink (glutamine and essential amino acid mixture [GEAA]) improves physical and psychological recovery.Intensive care patients aged 45 years or older, with a combined intensive care unit stay/pre-intensive care unit stay of 5 days or more were recruited to a randomized controlled trial examining the effect of PEPSE and GEAA on recovery. The 2 factors were tested in a 2 × 2 factorial design: (1) GEAA drink twice daily for 3 months and (2) 6-week PEPSE in first 3 months. Primary efficacy outcome was an improvement in the 6-minute walking test at 3 months.A total of 93 patients were randomized to the study. Patients receiving the PEPSE and GEA had the biggest gains in distance walked in 6-minute walking test (P.0001). There were also significant reductions in rates of anxiety in study groups control supplement/PEPSE (P = .047) and GEAA supplement/PEPSE (P = .036) and for GEAA supplement/PEPSE in depression (P = .0009).Enhanced rehabilitation combined with GEAA supplement may enhance physical recovery and reduce anxiety and depression.

TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the mitochondrial generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the effect of TNF-α on the production of myokines by skeletal muscle. Significant increases were seen in the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of cytokines by muscle cells. An increase was also seen in superoxide in response to treatment with TNF-α, which was localised to the mitochondria and this was also associated with activation of NF-κB. The changes in superoxide, activation of NF-kB and release of myokines were attenuated following pre-treatment with SS-31 peptide indicating that the ability of TNF-α to induce myokine release may be mediated through mitochondrial superoxide, which is, at least in part, associated with activation of the redox sensitive transcription factor NF-kB., Graphical abstract

Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging.

Background Relatives of patients recovering from critical illness are at risk of developing posttraumatic stress disorder. Objectives To test whether providing a diary to intensive care patients and their relatives reduces the level of symptoms related to posttraumatic stress disorder in the relatives. Methods Observational study of close family members of patients who stayed more than 72 hours in an intensive care unit, recruited in 2 centers of a 12-center randomized controlled trial examining the effect of a diary outlining the details of the patients’ stay in the intensive care unit on the development of new-onset posttraumatic stress disorder in patients. The close family members of the patients were recruited to examine the additional effect of the provision of the patient’s diary on the family members’ symptoms related to posttraumatic stress syndrome. Results Thirty-six family members were recruited, and 30 completed the study. Family members of patients who received their diary at 1 month had lower levels of symptoms related to posttraumatic stress disorder (P = .03) at the 3-month follow-up than did the control family members. Conclusions Provision of a diary may help psychological recovery in patients’ families after critical illness.

Severe weakness is being recognized as a complication that impacts significantly on the pace and degree of recovery and return to former functional status of patients who survive the organ failures that mandate life-support therapies such as mechanical ventilation. Despite the apparent importance of this problem, much remains to be understood about its incidence, causes, prevention, and treatment.Review from literature and an expert round-table.The Brussels Round Table Conference in 2009 convened more than 20 experts in the fields of intensive care, neurology, and muscle physiology to review current understandings of intensive care unit-acquired weakness and to improve clinical outcome.Formal electrophysiological evaluation of patients with intensive care unit-acquired weakness can identify peripheral neuropathies, myopathies, and combinations of these disorders, although the correlation of these findings to weakness measurable at the bedside is not always precise. For routine clinical purposes, bedside assessment of neuromuscular function can be performed but is often confounded by complicating factors such as sedative and analgesic administration. Risk factors for development of intensive care unit-acquired weakness include bed rest itself, sepsis, and corticosteroid exposure. A strong association exists between weakness and long-term ventilator dependence; weakness is a major determinant of patient outcomes after surviving acute respiratory failure and may be present for months, or indefinitely, in the convalescence phase of critical illness.Although much has been learned about the physiology and cell and molecular biology of skeletal and diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis, the application of these understandings to the bedside requires more study in both bench models and patients. Although a trend toward greater immobilization and sedation of patients has characterized the past several decades of intensive care unit care, recent studies have demonstrated that early physical and occupational therapy, including during the period of intubation and ventilator support, can be safely performed and will likely improve patient outcomes with regard to functional status.

The physical inactivity of the critically ill patient is an abnormal state that compromises muscle function to an extent that the immobile skeletal muscle may not simply be a bystander in the disease process.Skeletal muscle seems to maintain a system of defense against inflammation through heat shock proteins and the production of myokines. It contributes in a bidirectional role in systemic inflammatory signaling and the modulation of the inflammatory response. Skeletal muscle is a major contributor to whole-body glucose and protein metabolism, exemplified by its role in nutrient provision for the immune system and other rapidly dividing tissues through glutamine production.

Through a personal narrative, the authors discuss the lessons they have learned from 20 years of intensive care follow-up and rehabilitation.There is a greater understanding of the legacies of the physical, psychological and cognitive problems after critical illness, and new momentum toward developing and delivering practical care to both survivors of intensive care and their relatives.The need and demand for care after critical illness is now firmly established.

Purpose of review To examine current research on the psychological needs of both patients and their families following critical illness, and discuss how these may be met in a cost-effective manner. Recent findings Patients and their families have significant psychological problems following critical illness. To date, very few intensive care units have specialist psychological services to help with the aftermath of the illness experience. There are promising simple therapeutic interventions, such as intensive care unit diaries, that may be beneficial, but which require further research at present. Summary Currently, there is an awareness of the psychological sequelae of critical illness for patients and their family caregivers, and with this a responsibility to assess and appropriately help those who are unable to manage their distress. The development and application of specialist psychological services after an episode of critical illness, possibly using a stepped care model, is in its infancy. There are a few centres of excellence that are currently employing these resources, but the vast majority of patients and their families are left to cope on their own. This lack of psychological support has important implications for long-term recovery and quality of life following the episode of critical illness.

We know that critically ill patients suffering from undernutrition with a limited nutritional reserve have a poorer outcome. Furthermore, having a low body mass index has been shown to be an independent predictor of excess mortality in multiple organ failure. Therefore, nutritional support has gained increasing interest in critical illness with the hope of preventing or attenuating the effects of malnutrition. A negative nitrogen balance is the characteristic metabolic feature in critical illness, with the major protein loss derived from skeletal muscle. In particular, glutamine concentrations are rapidly reduced in plasma and muscle. Over the last 20 yrs or so, increasing evidence is emerging to support the use of glutamine supplementation in critical illness. Clinical trials have found a mortality and morbidity advantage with glutamine supplementation. The advantage appears to be greater the more glutamine is given and greater again when given parenterally. Various modes of action have been postulated. Glutamine seems to have an effect on the immune system, antioxidant status, glucose metabolism, and heat shock protein response. However, the benefit of exogenous glutamine on morbidity and mortality is not universally accepted. This review critically appraises the current clinical evidence regarding glutamine supplementation in critical illness.

Purpose of review In the critically ill patient, disease and the therapies we use impact on brain function. Simple tools are now available to recognise such problems. This review highlights neuropsychiatric and cognitive observations that have direct relevance to patient care and outcome. Recent findings Delirium is a common event, especially the hypoactive forms in the elderly. The recognition of significant cognitive dysfunction is worrying since it has profound implications for how we treat and manage patients within intensive care and beyond. The most important message is that the ‘awake’ intensive care unit patient is not necessarily free of significant brain dysfunction. There is also the added complication of psychological disturbances related to real or imagined delusional experiences underlying the importance of memory and recall. Longer-term implications, particularly debilitating conditions such as posttraumatic stress disorder, mean that there is a need for improved post-intensive care unit rehabilitation care. Summary Health professionals working with the critically ill must routinely include the assessment of brain cognitive function. While some of the consequences may be unavoidable, we need to reassess our sedation and care practices to ensure we are not confounding the problem. Practical options to improve outcome are being developed and emphasise that the recovery from critical illness is psychological as well as physical.

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients., SCOPUS: ar.j, info:eu-repo/semantics/published

The exercise-induced expression of heat shock proteins (HSPs) in rodent models is relatively well defined. In contrast, comparable data from human studies are limited and the exercise-induced stress response of human skeletal muscle is far from understood. This study has characterized the time course and magnitude of the HSP response in the skeletal muscles of a healthy active, but untrained, young male population following a running exercise protocol. Eight subjects performed 45 min of treadmill running at a speed corresponding to their lactate threshold (11.7 ± 0.5 km/h; 69.8 ± 4.8% maximum O2uptake). Muscle biopsies were obtained from the vastus lateralis muscle immediately before and at 24 h, 48 h, 72 h, and 7 days postexercise. Exercise induced a significant ( P < 0.05) but variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression with peak increases (typically occurring at 48 h postexercise) to 210, 170, and 139% of preexercise levels, respectively. In contrast, exercise did not induce a significant increase in either HSP27, αB-crystallin, SOD 2 (MnSOD) protein content, or the activity of SOD and catalase. When examining baseline protein levels, HSC70, HSP27, and αB-crystallin appeared consistently expressed between subjects, whereas HSP70 and MnSOD displayed marked individual variation of up to 3- and 1.5-fold, respectively. These data are the first to define the time course and extent of HSP production in human skeletal muscle following a moderately demanding and nondamaging running exercise protocol. Data demonstrate a differential effect of aerobic exercise on specific HSPs.

Recent studies have shown significant cognitive problems some months after critical illness. However there has been no research examining cognitive function within the intensive care unit (ICU) in non-delirious patients. A prospective study in an ICU. Using the Cambridge Neuropsychological Test Automated Battery (CANTAB), 30 long-stay, tracheal-intubated ICU patients were tested. Prior to testing on ICU the Confusion Assessment Measure (CAM-ICU) was administered and only those patients clearly not delirious and off sedation for several days were tested. The CANTAB tests were repeated a week after ICU discharge on the general ward and then again at 2 months. Sixteen patients completed the follow-up. While on ICU all 30 patients showed significant problems with strategic thinking and problem solving; 20 patients had some problems with memory. The degree of difficulty with problem solving on ICU was correlated with length of ICU stay (p = 0.011), age (p = 0.036) and length of hospital stay post ICU (p = 0.044). Problems with memory in ICU and on the general ward were correlated with admission APACHE II score (p = 0.004 and p = 0.005 respectively). At the 2-month follow-up 5 of 16 patients (31%) scored below the 25 percentile for memory and 8 of 16 (50%) below the 25 percentile for problem solving (Slater TA, Jones C, Griffiths RD, Wilson S, Benjamin K (2004) Cognitive impairment during and after intensive care: a pilot study. Intensive Care Med 30 [Suppl 1]:S199). Difficulties with problem solving and poor memory remained a significant issue for 2 months after ICU discharge.

The survival of an intensive care patient is in part related to how well they can defend themselves against the damaging inflammatory processes and how well they can heal and recover. Simply blocking inflammatory mediators has, not surprisingly, proved relatively ineffective. However, a nutrient deficiency of glutamine can occur and compromises many important cellular protective, immune and recovery processes that may influence a patient's survival. This brief review discusses the evidence suggesting that an additional exogenous supply of glutamine is needed and why the systemic delivery of glutamine via the parenteral route has been shown in clinical studies to improve long-term survival.

Objective: To evaluate the effectiveness of a rehabilitation program following critical illness to aid physical and psychological recovery. Design: Randomized controlled trial, blind at follow-up with final assessment at 6 months. Setting: Two district general hospitals and one teaching hospital. Patients: Patients were 126 consecutively admitted intensive care patients meeting the inclusion criteria. Interventions: Control patients received ward visits, three telephone calls at home, and clinic appointments at 8 wks and 6 months. Intervention patients received the same plus a 6-wk self-help rehabilitation manual. Measurements and Main Results: We measured levels of depression and anxiety (Hospital Anxiety and Depression Scale), phobic symptoms (Fear Index), posttraumatic stress disorder (PTSD)-related symptoms (Impact of Events Scale), and scores on the Short-Form Health Survey physical dimension 8 wks and 6 months after intensive care unit (ICU) treatment. Memory for ICU was assessed at 2 wks post-ICU discharge using the ICU Memory Tool. The intervention group improved, compared with the control patients, on the Short-Form Health Survey physical function scores at 8 wks and 6 months (p .006), and there was a trend to a lower rate of depression at 8 wks (12% vs. 25%). However, there were no differences in levels of anxiety and PTSD-related symptoms between the groups. The presence of delusional memories was correlated significantly with both anxiety and Impact of Events Scale scores. Conclusions: A self-help rehabilitation manual is effective in aiding physical recovery and reducing depression. However, in those patients recalling delusional memories from the ICU, further psychological care may be needed to reduce the incidence of anxiety and PTSD-related symptoms. (Crit Care Med 2003; 31:2456‐2461)

Objective: To conduct a review of early assessment of psychological problems experienced by patients following intensive care (ICU) and the efficacy of early psychological intervention.Date sources: Relevant studies were obtained from the medical, nursing and psychology literature, Medline, PsycLit, EMBASE and CINAHL of the past 20 years.Study selection: Articles were selected that provided data on acute stress disorder and post-traumatic stress disorder following intensive care. Articles from similar populations undergoing traumatic stress were included.Data synthesis: Articles were reviewed and relevant data extracted.Conclusion: A number of findings were clearly identified. While psychological problems after ICU are common, there is little research on early assessment and intervention to aid the recovery process. Work in other groups of sufferers of traumatic stress suggests that early assessment and intervention may reduce the chances of developing chronic post-traumatic stress disorder. Work from the...

Both ischemia and reperfusion injury and contractile activity are associated with the generation of reactive oxygen species and free radicals by skeletal muscle. In addition, exercise has been reported to lead to the formation of a circulating free radical species that is detectable in the blood by spin trapping before analysis by electron-spin resonance (ESR) techniques. Previous analysis of the ESR signal indicated that the circulating species is either a carbon- or oxygen-centered lipid-derived free radical. The current data indicate that this species is present in the blood of anesthetized rats after 4-h ischemia and 1 h of reperfusion of a single hindlimb. During 4 h of ischemia, the species was also present in microdialysates from the tibialis anterior muscle but was unchanged in magnitude compared with control tissue. During 1 h of reperfusion, the signal intensity increased by a mean of 420% ( P < 0.05, n = 4). Hydroxyl radical activity in the interstitial fluid also significantly increased during ischemia and further increased by a mean of 210% ( P < 0.05, n = 4) during reperfusion. No changes in interstitial superoxide levels were seen, but interstitial PGE2 content also increased during reperfusion. A significant positive correlation was found between the magnitude of the ESR signal and both the hydroxyl radical activity and PGE2 content of microdialysis fluids. These data support the hypothesis that the circulating free radical species is formed in the interstitial fluid by hydroxyl radical interaction with a lipid that may be released from reperfused tissue with a similar pattern to prostanoids.

Oxidative stress induces adaptations in the expression of protective enzymes and heat shock proteins (HSPs) in a variety of tissues. We have examined the possibility that supplementation of subjects with the nutritional antioxidant, vitamin C, influences the ability of lymphocytes to express protective enzymes and HSPs following exposure to an exogenous oxidant and the response of skeletal muscle to the physiological oxidative stress that occurs during exercise in vivo. Our hypothesis was that an elevation of tissue vitamin C content would reduce oxidant-induced expression of protective enzymes and HSP content. Lymphocytes from non-supplemented subjects responded to hydrogen peroxide with increased activity of superoxide dismutase (SOD) and catalase, and HSP60 and HSP70 content over 48 h. Vitamin C supplementation at a dose of 500 mg day−1 for 8 weeks was found to increase the serum vitamin C concentration by ∼50 %. Lymphocytes from vitamin C-supplemented subjects had increased baseline SOD and catalase activities and an elevated HSP60 content. The SOD and catalase activities and the HSP60 and HSP70 content of lymphocytes from supplemented subjects did not increase significantly in response to hydrogen peroxide. In non-supplemented subjects, a single period of cycle ergometry was found to significantly increase the HSP70 content of the vastus lateralis. Following vitamin C supplementation, the HSP70 content of the muscle was increased at baseline with no further increase following exercise. We conclude that, in vitamin C-supplemented subjects, adaptive responses to oxidants are attenuated, but that this may reflect an increased baseline expression of potential protective systems against oxidative stress (SOD, catalase and HSPs).

This is the third paper on research in accident and emergency medicine. It discusses the ethical issues in emergency medicine with particular regard to informed consent and the privacy of subjects and patients.

OBJECTIVE: We investigated the effect of a glutamine-supplemented parenteral nutrition on intensive-care-acquired infection (ICAI) and its relation to outcome. METHODS: We analyzed new data prospectively collected during a double-blind, randomized, and controlled trial in an adult general intensive care unit previously reported (Nutrition 1997;13:295). Eighty-four patients were randomized to receive glutamine-supplemented total parenteral nutrition or an isonitrogenous, isoenergetic control. Sepsis was present on admission in 71% of the patients. Clinical and microbiological data were collected on all new infective episodes and associated treatment decisions. Data were analyzed blind to the randomization and study outcome. RESULTS: There was no significant difference in the number of patients developing new infections or in the number occurring during the first 5 d. There was a non-significant trend to increased numbers of infections in those patients receiving the control feed for at least 5 d. In these patients the glutamine recipients showed significantly fewer catheter-related infections: 21 versus 12 ( P = 0.026). The difference in overall 6-mo mortality was almost completely described by those patients fed for at least 5 d: 9 of 25 versus 18 of 27 using the control nutrition ( P = 0.05). Of the deaths in the intensive care unit due to multiple organ failure, 8 of 8 in the glutamine group and 14 of 16 in the control group sustained one or more ICAI and accounted for 38% versus 74%, respectively, of the ICAIs occurring in those patients. In those patients, despite a similar high incidence of colonization with Candida , those receiving glutamine developed fewer Candida infections and none died, whereas six control patients who developed Candida infections died from multiple organ failure ( P = 0.02). Survival was not related to the reduced occurrence of the first acquired infection; however, binary logistic regression analysis of glutamine and the incidence of ICAI after starting total parenteral nutrition to outcome showed that only glutamine was significantly associated with improved 6-mo survival ( P = 0.027). CONCLUSIONS: In these severely ill patients, parenteral nutrition containing glutamine may not reduce the overall incidence of ICAI, but it may reduce the risk of dying from acquired infections. The improved survival seen at 6 mo appeared related mostly to reduced mortality in the intensive care unit from multiple organ failure in those patients in whom acquired infections are common.

Objectives. To investigate the influence of current media events on hallucinatory content in ICU patients. Design and methods. Patients were interviewed over a one-year period, and their descriptions of hallucinatory experiences, together with weekly media stories, were assessed for themes of war. Results. Media coverage for war-related stories rose significantly during the period of war in Kosovo (24/3/99-20/6/99). Patients whose ICU stays coincided with this conflict were more likely to have hallucinatory experiences involving themes of war or the military. Older adults (> 70) were also more susceptible to this effect. Conclusions. Contextual variables such as current media events can have a significant impact upon the contents of hallucinatory experiences.

It is well established that critically ill patients have a deficiency of the amino acid glutamine. This article reviews the evidence for supplemental glutamine in the critically ill, focusing on the benefits in terms of reduced mortality and infectious morbidity.

Critically ill patients on intensive care units are at an increased risk of sepsis, which is a major cause of mortality in these patients. Recent evidence suggests that impairment of the functioning of the immune system contributes to the development of sepsis in such patients. In particular, monocytes show reduced expression of HLA-DR antigen, associated with impaired antigen presenting capability and decreased phagocytic activity; lymphocytes show decreased proliferation in response to mitogens and T-helper cells show a shift in the Th1/Th2 ratio consistent with impaired immunity. The amino acid glutamine becomes conditionally essential in the critically ill, yet such patients frequently have a marked deficiency of glutamine; the reasons for this are still unclear. Glutamine is required by the cells of the immune system both as a primary fuel and as a carbon and nitrogen donor for nucleotide precursor synthesis. In vivo studies have demonstrated that glutamine is essential for optimal immune cell functioning for monocytes, lymphocytes and neutrophils. A number of trials of patients fed by the enteral or parenteral route have shown improved infectious morbidity when supplemented with glutamine. However, the exact mechanism of glutamine action in these patients remains to be determined.

Chapter 46 provides an outline to therapeutic and rehabilitation strategies in the post-ICU period, and examines conflict in care between patient and family experiences, types of recovery pathways, relatives' coping strategies, risk assessment and support, and a clinical review of issues that may include drug withdrawal, cessation of unwanted medication, optimization of cardiorespiratory function, and screening for the associated physical problems of immobility. It also covers elements of physical, psychological, and social recoveries, as well as cognitive dysfunction and social challenges.

Post-traumatic stress disorder (PTSD) has been shown to be a significant problem for both patients and relatives after critical illness. For patients the recall of delusional memories from the period in ICU can be a powerful trigger for the development of PTSD. Such memories are described by patients as very vivid and difficult to separate from reality. Early recognition and treatment of PTSD, where needed, can reduce the long term effects. Chronic PTSD, where symptoms have been present for three months after the traumatic event, is associated with a number of long term health problems such as chronic pain. It can also have profound effects on relationships, financial status and overall wellbeing. The provision of an ICU diary has been shown to reduce the incidence of PTSD in patients and reduce the level of PTSD-related symptoms in family members. For the majority of patients this relatively simple intervention helps them to fill in memory gaps and combat any delusional memories they may recall.

TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the role of mito...

Research into the metabolic role of glutamine in trauma and sepsis brings evidence to suggest a conditional deficiency occurs because increased and altered tissue demands exceed endogenous production. Such a deficiency has functional implications, and the restorative provision of parenteral glutamine has been shown to offer improved clinical outcomes in a variety of conditions. In the critically-ill it is associated with improvements in immune function, and improved survival from infection leading to an overall improved outcome.

Microdialysis techniques have been used to detect hydroxyl radical and superoxide release into the interstitial space of anaesthetized rat anterior tibialis muscles during a period of prolonged (4 h) limb ischemia and subsequent reperfusion. Data indicate that reperfusion of the ischemic skeletal muscle was associated with a large increase in hydroxyl radical activity in the interstitial space, which may contribute to the significant oxidation of muscle glutathione, protein thiols, and lipids also seen in this model. No evidence for release of superoxide into the interstitial space was found during reperfusion, although this was observed during electrically stimulated contractile activity of the rat limb muscle. These data imply that therapeutic approaches aimed at reduction of hydroxyl radical generation in the interstitial fluid are more likely to be beneficial in reduction of skeletal muscle reperfusion injury than approaches designed to scavenge superoxide radicals.

To examine prospectively the relationship between memories of intensive care (ICU) and levels of anxiety after ICU discharge, the stability of these memories with time, and their relationship to the development of acute posttraumatic stress disorder (PTSD)-related symptoms.Case series cohort assessed by interview at 2 and 8 wks after ICU discharge.District general hospital (serving a population of 350,000) general intensive care unit.Memories of ICU and anxiety levels were studied in 45 patients after ICU discharge. Thirty patients were examined again at 8 wks to assess memory stability and development of acute PTSD-related symptoms.Standardized interviews and questionnaires were used to assess memory for ICU, anxiety, and depression 2 wks after ICU discharge. In addition, PTSD-related symptoms and panic were assessed 8 wks after ICU discharge. A total of 33 of 45 patients had delusional memories from ICU at 2 wks; nine of the patients with delusional memories had no factual memories, and these patients had higher anxiety levels 2 wks after ICU discharge (p.0001). Thirty patients had paired assessments at 2 and 8 wks. Those patients who had no factual recall of ICU but had delusional memories at 2 wks scored highly for PTSD-related symptoms and panic attacks at 8 wks (p = .023 and .014, respectively). The only predictors of possible acute PTSD-related symptoms at the 8-wk assessment were trait anxiety (p = .006) and having delusional memories without recall of factual events in the ICU at 2 wks (p.0001). Only delusional memories were retained over time, whereas the recall of factual events in the ICU declined.We propose that the development of acute PTSD-related symptoms may be related more to recall of delusions alone. This study suggests that even relatively unpleasant memories for real events during critical illness may give some protection from anxiety and the later development of PTSD-related symptoms when memories of delusions are prominent.

Objective: The absence of a tool for assessing memory after being treated on the intensive care unit (ICU) has inhibited research. Therefore, the objective of this study was to develop and validate a tool known as the ICU Memory Tool (ICUMT) for assessing memory forintensive care during the recovery period. Validity was assessed through internal consistency, construct validity and test-retest reliability. Design: Prospective cohort study. Setting: Single intensive care unit in a district general hospital. Subjects and measurements: Forty-five patients recovering from critical illness. The ICUMT consists of 14 items administered by clinical interview. Main results: The ICU Memory Tool was internally consistent (alpha coefficient 0.86). Some evidence for the tool's construct validity was found as a predicted relationship between infection and memory loss was confirmed (p < 0.04). Good test-retest reliability was found over a 4-month period for factual memories (r = 0.84, p < 0.0001) and delusion memor...

Patients, when admitted to an intensive care unit (ICU), have one thing in common: their illness is life-threatening. Patients may remain on ICU in a critical condition, needing support with their breathing, circulation, and/or kidneys for varying lengths of time, from days to weeks. During that time the patients will receive sedative and analgesic drugs to ensure compliance with artificial ventilation. Patients recovering from critical illness frequently have little or no recall of their period in ICU, or remember nightmare, hallucinations, or paranoid delusions. The nature, extent and reason for these difficulties, have been under-reported and consequently our purpose was to conduct a review of memory problems experienced by ICU patients. A systematic literature review of computer databases (Medline, PsycLit, and CINAHL) identified 25 relevant papers. In addition, other relevant articles were obtained, citation lists and associated articles retrieved. Due to lack of research on processes underlying memory problems in ICU patients all articles that introduced an insight into possible mechanisms were included in the review. There seem to be two possible processes contributing to memory problems in ICU patients. First the illness and treatment may have a general dampening effect on memory. Delirium and sleep disturbance are both common in ICU patients. Delirium can result in a profound amnesia for the period of confusion. Sleep deprivation exacerbates the confusional state. Slow wave sleep is important for the consolidation of episodic memories. Treatment administered to patients in ICU can have effects on memory. Opiates, benzodiazepines, sedative drugs such as propofol, adrenaline, and corticosteroids can all influence memory. In addition, the withdrawal of drugs, such as benzodiazepines, can cause profound withdrawal reactions, which may contribute to delirium. Second, we hypothesise that there is a process that affects memory negatively for external events but enhances memory for internal events. The physical constraints and social isolation experienced by ICU patients and the life-threatening nature of the illness may increase the experience of hypnagogic hallucinations. Attentional shift during hypnagogic images from external stimuli to internally generated images would explain why ICU patients have such poor recall of external ICU events, but can clearly remember hallucinations and nightmares. Patients describe these memories as being very vivid and this is explored in terms of flashbulb memory formation. The absence of memories for real events on ICU can result in ICU patients remembering paranoid delusions of staff trying to kill them, with little information to reject these vivid memories as unreal. This has implications for patients' future psychological health.

Glutamine, a non-essential amino acid, is abundant in the human body and in the food we eat; it is mainly produced in skeletal muscle and acts as a major inter-organ nitrogen and carbon transporter. Its importance to the metabolism is evident during stress, when it becomes a conditionally essential amino acid when endogenous supply fails to meet increased demands. During the past 2 years, an increased understanding has been gained into the role of glutamine in metabolism. A number of new clinical studies of glutamine supplementation have shown interesting outcomes that should be influencing clinical decision-making.

In this short review we will concentrate on just one of the features of the metabolic response to injury (classified as accidental trauma, injury or sepsis) which are collectively known as the 'flow' phase'. These include an increase in energy expenditure (hypermetabolism), changes in substrate utilisation (insulin resistance) and the focus of this chapter muscle wasting or catabolism. It is recognised that the three features are interrelated, for example insulin is believed to be an important factor in controlling amino acid flux in skeletal muscle2 and increasing environmental temperature which may reduce flow phase hypermetabolism3 has been shown to reduce postoperative nitrogen excretion (a marker of protein catabolism)4. However, we will concentrate on muscle wasting and refer the reader to other reviews on insulin resistance5 and metabolic rate6. Muscle wasting Cuthbertson in his pioneering studies of the metabolic responses to injury noted an increase in urinary nitrogen excretion which he interpreted as reflecting protein breakdown7. In starved patients after elective abdominal surgery, nitrogen losses accounted for a smaller proportion of the energy deficit than did fat loss8, but with increasing severity of injury and sepsis loss of lean tissue predominates. In patients admitted to intensive care following either severe trauma or sepsis, there were progressive losses of 17% in water, 16% total body protein and 19% total body potassium over 21 days9. Such losses of lean body mass (whole body water and protein) of almost 1% per day of illness are far Correspondence to

Purpose: To conduct a review of psychological problems experienced by patients following a critical illness necessitating an admission to an intensive care unit (ICU). Methods: Systematic literature review of computer databases - Medline, PsycLit and CINAHL - identified 30 relevant papers. In addition, other relevant articles were obtained, citation lists and associated articles retrieved. Due to the lack of research on patients' psychological reactions following a period in ICU, all articles that introduced a psychological construct into the paper were included in the review and a further 12 were found. Results: A number of findings were clearly identified. Many patients have no recall of their stay on ICU, including memory of their illness. A consequence of this amnesia is an over-optimistic view of recovery, which may also be in conflict with their relatives' perception. Physical recovery, due to muscle weakness, is often slow. Return to normal physical functioning may take six months. Psychological pr...

The potential role of nutrition to influence survival in the critically-ill is discussed. Increasing benefits are described to enteral nutrition but there remain some patients who have high mortality in whom only parenteral nutrition is possible. The clinical relevance of glutamine in parenteral nutrition is reviewed in the context of how it might influence survival from severe illness.

HEALTHY ADULTS HAVE A CLOSELY INTERRELATED NUtritional, metabolic, and immune system that regulates food requirements and responds well to short-term nutritional deprivation but not to nutrient excess. However, when critically ill, patients no longer have control over their food intake, and clinicians may administer nutritional support with little understanding of individual patient needs in the light of inflammatory demands, injury responses, and the underlying influences of genotype and age. Because robust evidence about the nutritional requirements for critically ill patients at the various stages of their illness is lacking, particularly when they are acutely ill, clinicians often base nutritional support on “requirements” based on averages and guesswork. Nutritional support in excess of actual requirements may contribute to metabolic stress. In the intensive care unit (ICU), parenteral nutrition can facilitate excessive early provision of nutrients during a period of considerable uncertainty about requirements. This was illustrated in the study by Casaer et al, in which very early targeting of full feeding requirements with parenteral nutrition in the first few days was not beneficial. The authors of that study suggested the possibility that nutrition might suppress the normal activation of acute mechanisms necessary to remove cellular damage. In patients receiving mechanical ventilation, enteral feeding rarely delivers consistently more than 80% of the target full feeding, but it is still reasonable to question whether further restriction of enteral nutrition would be preferable during the early stages of an acute illness. Inthis issueof JAMA,Riceandcolleagues,writingfor theNational Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, report findings examining whether there is any advantage to restricting the amount of initial enteral intake among mechanically ventilated patients with acute lung injury (ALI). The EDEN study was a large, unblinded trial from 44 sites that recruited 1000 patientssoonafterstartingventilationanddevelopingALI(about 80% of which was attributable to primary pneumonias or sepsis). The study hypothesis was that administration of considerably reduced, trophic feeding (about 25% of the target full feeding) during the first 6 days would increase ventilator-free days(VFDs)comparedwithamoreactivelyadvancedconventional full enteral nutrition regimen achieving a target target intakeof80%.Thishypothesiswasnot supportedby thestudy findings: there was no difference between trophic feedings vs full enteral feedings in VFDs or any important secondary end points, includingICUstay,organfailure–freedays,28-daymortality, and 60-day mortality. Nonetheless, this study highlights several important practical points. The majority of these patients can be fed nasogastrically; the majority tolerate gastric residual volumes of 400 mL, measured at 6-hour intervals, without high rates of aspiration or increased ventilator-associated pneumonia; and using a protocolized approach for feeding allows clinicians to deliver a greater volume of the target feeding amounts than prior groups have reported. One potentially confounding factor was that the study was initially combined in a factorial design with another study, the OMEGA trial, which randomized patients to receive a supplement containing omega-3 fatty acids, -linolenic acid, and antioxidants until stopped for futility after 272 patients (27%) had been recruited. The results of the trial by Rice et al cannot be used to conclude that trophic feeding is equivalent to full feeding in critically ill patients. This study was not designed or powered as an equivalence study and does not provide definitive data to informcliniciansabouthowmuchnutritionalsupportisenough, how early it should be started, or even if there should be “no nutritionprovision”intheinitialphaseofcritical illness—acase that has been persistently argued and remains to be tested. The effect of nutrition on an end point such as VFDs does not simply depend on dose and duration but on several other factors. These may include a complex interaction of prior nutritional reserves; the effects of any initial or evolving nutritional deficiency; the extent and severity of the underlying illnesses; the processes of recovery interacting with the metabolic signaling and stress from the nutrients; and the burdens imposed by the complications of providing nutritional support. These factors suggest that not all patients may benefit equally. An important challenge is identifying patients at increased nutritional risk.

Fourteen patients with liver cirrhosis of differing severity participated in a one-dimensional chemical shift imaging 31P MRS study of the liver. Patients were divided into two groups according to the severity of their liver disease using Child's classification and the aminopyrine breath test (AB test). Seven normal volunteers without liver disease acted as controls. The phosphomonester (PME) peak in normal subjects was 4.77% (95% confidence interval, CI: 4.11-5.42) of total phosphorus. The PME peak was significantly elevated in both mild cirrhosis [5.80% (95% CI: 5.46-6.14), p = 0.0051, vs normal subjects] and severe cirrhosis [9.64% (95% CI: 8.71-10.57), p = 0.0002, vs normal subjects and p = 0.001, vs mild cirrhosis]. There was a significant negative linear correlation (r = 0.88, p < 0.01) of PME with the percentage dose of 14CO2 excreted over 2 h in the AB test. pH values in patients with mild cirrhosis [7.45 (95% CI: 7.35-7.55)] but not severe cirrhosis [7.36 (95% CI: 7.25-7.47)] were significantly elevated (p = 0.04) compared to normal subjects [7.29 (95% CI: 7.17-7.41)]. Comparison of the peak area of PME at TR = 0.5 s against that using TR = 5.0 s in cirrhotic liver suggested no reduction in T1 of phosphorus metabolites in cirrhosis. A relationship between the severity of liver cirrhosis and a relative increase in PME was demonstrated and this was not due to a reduction of T1. This study highlights the clinical potential of 31P MRS as a non-invasive means of assessing the severity of liver cirrhosis.

There has been little research on smoking cessation after critical illness. Smokers make up a high percentage of patients admitted to intensive care (ICU) and stopping smoking is one message that should be clearly given to recovering patients. The recovery period provides an important opportunity for patients to quit smoking as the period of sedation and ventilation allows patients to start nicotine withdrawal. Smoking cessation advice was included in a 6-week self-help ICU rehabilitation package comprising information and an exercise programme. Recovering ICU patients were randomised to receive either the routine follow-up of ward visits and ICU clinic appointments or routine follow-up plus the ICU rehabilitation package. Twenty out of thirty-one intervention patients and 16/30 control patients were smokers pre-ICU admission. At the 6-month follow-up, previous smokers given the rehabilitation package had a relative risk reduction for smoking of 89% (CI 98%-36%). Smoking cessation after critical illness is aided by the provision of a rehabilitation programme.

INTRODUCTION: Patients recovering from critical illness have been shown to be at risk of developing Post Traumatic Stress disorder (PTSD). This study was to evaluate whether a prospectively collected diary of a patient's intensive care unit (ICU) stay when used during convalescence following critical illness will reduce the development of new onset PTSD. METHODS: Intensive care patients with an ICU stay of more than 72 hours were recruited to a randomised controlled trial examining the effect of a diary outlining the details of the patients ICU stay on the development of acute PTSD. The intervention patients received their ICU diary at 1 month following critical care discharge and the final assessment of the development of acute PTSD was made at 3 months. RESULTS: 352 patients were randomised to the study at 1 month. The incidence of new cases of PTSD was reduced in the intervention group compared to the control patients (5% versus 13%, P = 0.02). CONCLUSIONS: The provision of an ICU diary is effective in aiding psychological recovery and reducing the incidence of new PTSD. RACHEL GROUP in addition to the authors: Denmark, Christensen D, Bogø I, Hansen R, Kjerrumgård H, Mathiasen L, Hyldested C, Toft C, Nordsjaelland Hospital; Bagger C, Larsen MB, Frank de Jong L, Odense University Hospital; Ågård AS, Knudsen K, Hinzel T, Århus University Hospital, Skejby; Italy, Scaramuzza A & Bertacchini S, Ferrara; Norway, Schou Landmark J, Salomonsen A, Tøien K, Walther S, Oslo University Hospital Ulleval; Muri AK, Haukeland University Hospital; Portugal, Neutel E, Gomes E, Cardoso T, Ferreira R, Machado C, Santos C, Pinto S, Hospital Santo António - Centro Hospitalar do Porto, Amaro A, Morujão E, Jerónimo A, Rodrigues T, Carvalho F, Silva A, Morais A Hospital Pedro Hispano; Sweden, Löwenmark U, Etemad W, Rosell E, Sahgrenska University Hospital; Carlson U, Wirbrand Holmquist A, Kungälv Hospital; Åkerman E, Ersson A, Malmö University Hospital; UK, Tobin C, Whiston.